Special Alerts

As new information of a critical nature is identified (such as Black Box Warnings) about medications in our database, we publish what we call a Special Alert. These Special Alerts are intended to notify clinicians of important news and warnings.

This information remains on our Special Alerts list for a period of 12 months from its original release date.

The Special Alerts listed below are available immediately to subscribers through Lexicomp Online and through our Mobile App software for smartphones and tablets.

Oxymorphone Hydrochloride (Opana ER) Safety Alert

Endo Pharmaceuticals is voluntarily removing its reformulated Opana ER (oxymorphone hydrochloride) oral tablets from the market in response to the FDA's June 2017 withdrawal request due to risks related to abuse. Data indicate a significant shift in the route of abuse (by crushing, dissolving, and injecting) of Opana ER following the product’s reformulation in 2012, and injection abuse has been associated with an outbreak of HIV and hepatitis C, as well as cases of thrombotic microangiopathy.

Endo plans to work with the FDA for Opana ER's removal and looks to minimize treatment disruption for patients and allow them sufficient time to seek guidance from their health care professionals.

http://endo.com/news-events/press-releases?c=123046&p=irol-newsArticle&ID=2284981.

Narcan Interim Order to Expire

Health Canada is advising health care providers that the Canadian authorized version of Narcan will transition onto the market by July 5, 2017. In July 2016, an Interim Order was issued that permitted the importation, sale, and distribution of Narcan approved in the United States for 1 year. On July 5, 2017, the Interim Order will expire. Product obtained under the Interim Order can continue to be used, but new orders will be for the Canadian-authorized Narcan product. There will be a period of time in which both products will be available.

For further information, visit http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2017/63784a-eng.php.

Influenza New Recommendations

The Centers for Disease Control and Prevention (CDC) is recommending that core requirements for influenza immunization remain the same for the 2017–2018 flu season. The Advisory Committee on Immunization Practices (ACIP) is also recommending that any licensed, recommended, and age-appropriate trivalent or quadrivalent inactivated influenza vaccine (IIV) or recombinant influenza vaccine (RIV) be allowed for pregnant women. The previous recommendation specified use of IIV for pregnant women. ACIP reiterated that the quadrivalent live attenuated influenza nasal spray vaccine (LAIV4) should not be used in any setting during the upcoming flu season. Additional data on LAIV4 are expected in October. Afluria (IIV3) is now indicated for people 5 years and older (previously 9 years and older). ACIP is currently awaiting CDC review of all recommendations. The influenza vaccine strains approved for the 2017–2018 season in the US are:

Trivalent vaccines:

  • A/Michigan/45/2015 (H1N1) pdm09-like virus (updated)
  • A/Hong Kong/4801/2014 (H3N2)-like virus
  • B/Brisbane/60/2008-like virus (Victoria lineage)

Quadrivalent vaccines:

  • The 3 trivalent vaccines, plus B/Phuket/3073/2013-like virus (Yamagata lineage)

Oxymorphone Hydrochloride (Opana ER) Safety Alert

The FDA has requested that Endo Pharmaceuticals’ reformulated Opana ER (oxymorphone hydrochloride) oral tablets be voluntarily removed from the market due to risks related to abuse. Data indicate a significant shift in the route of abuse (by crushing, dissolving, and injecting) of Opana ER following the product's reformulation in 2012, and injection abuse has been associated with an outbreak of HIV and hepatitis C, as well as cases of thrombotic microangiopathy.

If Endo does not voluntarily remove Opana ER from the market, the FDA intends to withdraw approval of the drug. More information may be found at https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm562401.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery.

Gadolinium-Based Contrast Agents for MRI Safety Review

The FDA identified no evidence to date that gadolinium retention in the brain from any of the gadolinium-based contrast agents (GBCAs) for magnetic resonance imaging (MRI) is harmful, including GBCAs associated with higher retention of gadolinium, and therefore, restricting GBCA use is not warranted at this time. All GBCAs may be associated with some gadolinium retention in the brain and other body tissues. The FDA will continue to assess the safety of GBCAs and plan to have a public meeting to discuss this issue in the future. Health care providers should limit GBCA use to circumstances in which additional information provided by the contrast agent is necessary, and assess the necessity of repetitive MRIs with GBCAs. Retention of gadolinium affects only GBCAs, and does not apply to other types of scanning agents used for other imaging procedures, such as those that are iodine-based or radioisotopes.

Further information may be found at https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm559709.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery.

Canagliflozin Safety Alert

Based on new data from 2 large clinical trials, the FDA has concluded that canagliflozin causes an increased risk of leg and foot amputations. New warnings, including a Boxed Warning, will be added to canagliflozin drug labeling to describe this risk.

Before initiating canagliflozin therapy, health care providers should consider factors that may predispose patients to the need for amputations; these factors include a history of prior amputation, peripheral vascular disease, neuropathy, and diabetic foot ulcers. Providers should monitor patients receiving canagliflozin for the signs and symptoms described above and should discontinue canagliflozin if these complications occur. Patients taking canagliflozin should notify their providers immediately if they develop new pain or tenderness, sores or ulcers, or infections in their legs or feet. Patients should not stop taking their diabetes medicine without first consulting their provider.

Further information can be found at https://www.fda.gov/downloads/Drugs/DrugSafety/UCM558427.pdf.

Aranesp Canadian Safety Alert

Health Canada has announced that severe and life-threatening skin reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported in patients treated with darbepoetin alfa (Aranesp). Health care providers are advised to discontinue darbepoetin alfa immediately if a severe skin reaction occurs or SJS/TEN is suspected and to permanently discontinue darbepoetin alfa if SJS/TEN is confirmed. Health Canada is currently working with the manufacturer to include this safety information in the Canadian Product Monograph.

For further information visit http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2017/63198a-eng.php.

Yellow Fever Vaccine Review

Sanofi Pasteur has announced that YF-Vax yellow fever vaccine will be unavailable from mid-2017 to mid-2018 due to delays in the production process. The FDA has approved the importation of Sanofi Pasteur’s Stamari under an investigational new drug program. Stamaril is comparable in safety and efficacy to YF-Vax, but is not licensed in the US and can only be provided to a limited number of clinics. For more information, contact Sanofi Pasteur at 1-800-822-2463.

Further information can be found at https://wwwnc.cdc.gov/travel/news-announcements/yellow-fever-vaccine-access.

Dipeptidylpeptidase-4 (DPP-4) Inhibitors Safety Alert

Health Canada conducted a safety review and found that the use of dipeptidylpeptidase-4 (DPP-4) inhibitors may increase the risk of developing severe joint pain. This review was prompted by adverse events reported to the US FDA Adverse Event Reporting System (FAERS) and found in published literature.

Health Canada is working with manufacturers to update product safety information to include this risk on all DPP-4 inhibitor containing products.

Further information is available at http://www.hc-sc.gc.ca/dhp-mps/medeff/reviews-examens/dipeptidylpeptidase-eng.php.

Anesthetic and Sedation Drugs Safety Alert

The FDA has approved previously announced label changes regarding the use of general anesthetic and sedation medicines in pediatric patients younger than 3 years. A new warning states that exposure to these medicines for long periods of time or over multiple surgeries or procedures may negatively affect brain development in children younger than 3 years. Additional information was also added to the pregnancy and pediatric use sections, describing studies in young animals and pregnant animals that showed that exposure to general anesthetic and sedation drugs for more than 3 hours can cause widespread loss of nerve cells in the developing brain; and that the changes resulted in long-term negative effects on the animals’ behavior or learning.

Health care professionals should continue following their usual practices of patient counseling, including discussing the benefits and risks of surgeries or procedures that require general anesthesia and sedation drugs. The FDA will continue monitoring the use of these drugs in children and will update the public if additional information becomes available. Parents, caregivers, and pregnant women should talk to their health care professionals if they have any questions or concerns about general anesthesia and sedation drugs.

More information may be found at https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm555631.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery.

Iodinated Contrast Media Safety Alert

Health Canada has announced that rare cases of hypothyroidism following iodinated contrast media (ICM) exposure have been reported internationally, particularly in term and preterm infants. No Canadian cases of hypothyroidism related to ICM exposure have been identified to date. In 2015, the US Food and Drug Administration issued a class labeling request to all ICM manufacturers to include information related to rare cases of hypothyroidism reported in infants following the use of ICM products. Health care providers should evaluate and monitor thyroid function in infants exposed to ICM, and if abnormal, continue to monitor until it has normalized. Health Canada is currently working with the ICM manufacturers to update the prescribing information for all ICM products to include this safety information.

Further information may be found at http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2017/63086a-eng.php.

Codeine and tramadol Safety Alert

The FDA has issued a Safety Alert restricting the use of codeine and tramadol in children. Children under 12 years and some adolescents younger than 18 years (especially those with certain genetic factors, obesity, or obstructive sleep apnea and other breathing problems) should not use medicines containing these drugs because of increased medical risks, including slowed or difficult breathing and death. The FDA is also recommending against the use of codeine and tramadol medicines in breastfeeding mothers due to possible harm to their infants, including excess sleepiness, serious breathing problems, or death.

The FDA is requiring several labeling changes to all prescription medicines containing these drugs. Health care professionals should be aware that tramadol and single-ingredient codeine medicines are FDA-approved only for use in adults, and should consider recommending OTC or other FDA-approved prescription medicines for cough and pain management in children younger than 12 years and in adolescents younger than 18 years. The FDA also reminds health care professionals that cough is often secondary to infection and not serious, usually resolving on its own and not requiring treatment.

Further information may be found at https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm554029.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery.

Keytruda Safety Alert

Health Canada is reporting that cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), some with fatal outcomes, have been reported in patients treated with Keytruda (pembrolizumab). Health Canada is working with the manufacturer to update the Canadian product monograph to include this safety information.

Health care providers are advised to counsel patients about the benefits and risks of Keytruda, including the risk and early symptoms of SJS and TEN; to suspend Keytruda treatment and refer for immediate evaluation and treatment for any severe skin reaction or suspected SJS or TEN; and to permanently discontinue Keytruda if SJS or TEN is confirmed.

Further information can be found at http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2017/62670a-eng.php.

Viberzi Safety Alert

The FDA is warning that Allergan’s Viberzi (eluxadoline), indicated to treat irritable bowel syndrome with diarrhea, should not be used in patients who do not have a gallbladder. An FDA review found that these patients have an increased risk of developing serious pancreatitis that could result in hospitalization or death. Pancreatitis symptoms have occurred after 1 to 2 doses in patients who were receiving the recommended dose for those without a gall bladder and who do not consume alcohol. Health care providers should not prescribe Viberzi to patients without a gallbladder and should consider alternative treatment options in these patients. Patients should be instructed to discontinue Viberzi promptly and seek emergency medical care if they experience symptoms of pancreatitis (eg, new or worsening abdominal pain, abdominal pain in the upper right quadrant that radiates to the shoulder or back, abdominal pain with nausea and vomiting). The FDA is working with Allergan to address these safety concerns.

Further information may be found at https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm546771.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery.

Nulojix Shortage Special Alert

Bristol-Myers Squibb projects that the supply of Nulojix (belatacept) in 2017 will not be sufficient to enable new patients to start treatment, and that, effective March 15, 2017, it will not be able to supply Nulojix for new patients. To ensure existing patients continue to receive Nulojix, they must be registered in the Nulojix Distribution Program and receive a unique patient identification number which will be required when placing orders for the drug. McKesson Plasma and Biologics will be the exclusive distributor of Nulojix and may be contacted at 1-877-625-2566 to confirm an existing account and/or establish a purchasing relationship.

Further information may be found at http://www.nulojixhcp.bmscustomerconnect.com/servlet/servlet.FileDownload?file=00Pi000000nzpG5EAI.

Colorectal Stents with Bevacizumab Safety Alert

A Health Canada safety review found limited evidence supporting potential increased risk of bowel rupture when colorectal stents and bevacizumab are used concurrently to treat patients with colon cancer. This review was prompted by published studies reporting an increased risk of bowel rupture in these patients. Health Canada will continue monitoring the safety of both colorectal stents and bevacizumab.

Further information can be found at http://www.hc-sc.gc.ca/dhp-mps/medeff/reviews-examens/stents-endoprotheses-eng.php.

Expiration Dating for Antivenin (Micrurus fulvius): Update

Wyeth Pharmaceuticals no longer manufactures Antivenin (Micrurus fulvius) (Equine Origin), and there is no alternative product licensed in the U.S. for coral snake envenomation. There are currently two lots of Antivenin (Micrurus fulvius) (Equine Origin) available for use: Lot number 4030024, with an expiration date extended through April 30, 2017 and lot number L67530, with an expiration date extended through January 31, 2018.

Institutions should retain any remaining inventory of lot number 4030024 and/or L67530 until the aforementioned expiration date. Clinicians should note that due to supply concerns, Pfizer, Inc supplies product only to direct customers on a replacement or emergency basis. To obtain antivenin, Pfizer, Inc may be reached at 800-666-7248; alternatively, clinicians may contact their local Poison Control Center at 800-222-1222 for assistance in locating antivenin. In the event licensed antivenin cannot be secured, an investigational imported antivenin may be available under an Investigational New Drug (IND) protocol with informed consent; for more information contact a local Poison Control Center at 800-222-1222 or the U.S. Food and Drug Administration (FDA) at 800-835-4709 (business hours) or 301-796-8240 (nonbusiness hours).

Chlorhexidine Safety Review

The FDA is warning that rare but serious allergic reactions have been reported with skin antiseptic products containing chlorhexidine gluconate and is requesting that the manufacturers of nonprescription antiseptic products containing chlorhexidine gluconate add a warning about this risk to their labels. A similar safety review was issued by Health Canada in May 2016. Further information can be found at http://www.hc-sc.gc.ca/dhp-mps/medeff/reviews-examens/chlorhexidine-eng.php.

Health care providers should ask patients if they have ever had an allergic reaction to any antiseptic before recommending or prescribing a chlorhexidine gluconate product. Patients should seek immediate medical attention if they experience symptoms of an allergic reaction when using these products. Alternative antiseptics, such as povidone-iodine, alcohols, benzalkonium chloride, benzethonium chloride, or parachlorometaxylenol, should be considered when any previous allergy to chlorhexidine gluconate is documented or suspected. Patients and consumers should stop using the chlorhexidine gluconate product and seek medical attention immediately if they experience symptoms of a serious allergic reaction.

Further information can be found at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm539575.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery.

Levetiracetam Safety Alert

A Health Canada safety review has found a possible link between the use of levetiracetam and the risk of acute kidney injury. This review was prompted by an article published by the World Health Organization (WHO) suggesting this risk.

The current product information for levetiracetam’s brand name Keppra indicates that acute kidney injury has been reported in patients treated with the drug. Health Canada has requested that other manufacturers of levetiracetam-containing products update their product labeling to include this information.

Further information may be found at http://www.hc-sc.gc.ca/dhp-mps/medeff/reviews-examens/keppra-eng.php.

Isotretinoin Safety Alert

Health Canada has completed a review of the potential risk of erectile dysfunction associated with isotretinoin treatment. Health Canada's review concluded that there may be a link between the use of oral isotretinoin products and the risk of erectile dysfunction, but that the same conclusion cannot be drawn for other drugs in the oral retinoids class. Health Canada has recommended that the product information for all isotretinoin products be made consistent by including erectile dysfunction as an adverse effect.

Further information can be found at http://www.hc-sc.gc.ca/dhp-mps/medeff/reviews-examens/retinoid-eng.php.

Erwinase Safety Alert

To avoid a potential shortage of Erwinase, Health Canada, per the conditions agreed upon by Jazz Pharmaceuticals, is allowing the temporary importation of UK-labeled Erwinase batch CAMR-179G. Particulate matter was observed bound to the stopper and/or present on the lyophilized cake in some vials of Erwinase from batch 179G (lots 179G116, 179G216, 179G316, 179G416, and 179G516). Although affected vials were removed, some remaining vials may still contain particulate matter.

Vials of Erwinase with visible particulate matter should not be administered. If there is no visible particulate matter after reconstitution, health care professionals should use a standard 5-micron filter needle to withdraw the reconstituted product from the vial prior to administration as an additional precaution.

Because there are differences between the currently approved Canadian and UK labeling of Erwinase, health care professionals should refer to the Erwinase Canadian product monograph for prescribing information. A new supply of Erwinase is expected to be delayed until mid-January 2017.

In August and October 2016, particulate matter was also observed in some vials from Erwinase batch CAMR-174 (lot CAMR-174aG116) and Erwinaze batch 178K (lots 178K116, 178K216, 178K316, 178K416, and 178K516), respectively, and similar precautions were taken to prevent a potential shortage.

Further information can be found at http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2016/60014a-eng.php.

Gadolinium-based Contrast Agents Safety Alert

Health Canada has conducted a safety review of gadolinium-based contrast agents (GBCAs) due to evidence of gadolinium accumulation in the brain following multiple contrast-enhanced magnetic resonance imaging (MRI) scans. Clinical evidence indicates gadolinium accumulation in the brain is higher with the use of linear agents than with the use of macrocyclic agents, but it has occurred with both types. Health Canada will be working with Canadian manufacturers to update the labelling of GBCAs to include this new information.

Although no adverse events have been reported or identified in relation to gadolinium accumulation in the brain, Health Canada is advising health care professionals to limit the use of GBCAs to situations where the contrast agent is considered necessary; to use the lowest effective dose; and to weigh the benefits and potential risks before administering repeated doses.

The gadolinium-based contrast agents authorized for sale in Canada include: Dotarem (gadoterate meglumine) - macrocyclic agent; Gadovist (gadobutrol) - macrocyclic agent; Magnevist (gadopentetate dimeglumine) - linear agent; MultiHance (gadobenate dimeglumine) - linear agent; Omniscan (gadodiamide) - linear agent; Optimark (gadoversetamide) - linear agent; Primovist (gadoxetate disodium) - linear agent; and ProHance (gadoteridol) - macrocyclic agent.

Further information may be found at http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2017/61676a-eng.php.

Clozapine REMS Program Delayed

The FDA has announced that the full launch for the Clozapine Risk Evaluation and Mitigation Strategy (REMS) program will not be implemented in 2016 as originally planned due to recent technical and logistical challenges. The Clozapine Product Manufacturers' Group and the FDA are continuing to work to ensure that patients relying on clozapine have continued access to this medication and appropriate management of associated risks. The FDA is planning a phased approach to implement the Clozapine REMS Program in order to carefully balance patient access and to ensure the safe use of clozapine during the transition.

Prescribers and pharmacies that have not certified in the Clozapine REMS Program should use this additional time to certify before the full launch, which includes a fully implemented predispense authorization for pharmacies. In addition, prescribers should submit absolute neutrophil count (ANC) results to the Clozapine REMS Program according to the patient's monitoring frequency (ie, within 7, 15, or 31 days) to ensure that the ANC is current. If prescribers and/or pharmacies are not certified in the Clozapine REMS Program and the ANC in the program is not current after the full launch, the pharmacy's ability to dispense clozapine will be impacted.

Updated information will be sent to prescribers and pharmacies once an implementation date has been confirmed. During this extension, prescribers and pharmacies should continue to adhere to the current Clozapine REMS Program requirements. For additional information about the Clozapine REMS Program, please call the Clozapine REMS Program Contact Center at 844-267-8678 or visit www.clozapinerems.com.

Further information can be found at http://www.fda.gov/Drugs/DrugSafety/ucm467560.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery.

Anesthetic and Sedation Drugs Safety Alert

The FDA is warning that repeated or lengthy use of general anesthetic and sedation drugs during surgeries or procedures in pediatric patients younger than 3 years or in pregnant women during their third trimester may affect the development of children's brains. However, animal and recent human studies suggest that a single, relatively short exposure to general anesthetic and sedation drugs in infants or toddlers is unlikely to have negative effects on behavior or learning. Further research is still needed to fully characterize how early-life anesthetic exposure affects brain development. To better inform the public about this potential risk, the FDA is requiring that warnings be added to the labels of general anesthetic and sedation drugs.

Health care providers should balance the benefits of appropriate anesthesia in pediatric patients and pregnant women against potential risks, especially for procedures that may last longer than 3 hours or if multiple procedures are required in patients under 3 years of age. Providers should discuss the benefits, risks, and appropriate timing of surgery or procedures requiring anesthetic and sedation drugs with parents, caregivers, and pregnant women.

Further information can be found at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm533195.htm.

Jardiance Approved to Reduce Risk of Cardiovascular Death

The FDA has approved an expanded indication for Boehringer Ingelheim’s Jardiance (empagliflozin) to reduce the risk of cardiovascular death in adults with type 2 diabetes mellitus and established cardiovascular disease. Empagliflozin is the first antidiabetic agent approved with an additional indication to reduce the risk of cardiovascular death. The CDC reports that death from cardiovascular disease is 70% higher in adults with diabetes. Patients with diabetes also have a decreased life expectancy, largely due to premature cardiovascular death.

The expanded indication is based on a postmarket clinical study where empagliflozin demonstrated a reduction in the risk of cardiovascular death (compared to a placebo) when added to standard of care therapies for diabetes and atherosclerotic cardiovascular disease.

Further information may be found at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm531517.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery.

SGLT2 inhibitors Safety Alert

Health Canada completed a safety review of sodium-glucose cotransporter-2 (SGLT2) inhibitors and the increased risk of bone mineral loss or bone fractures reported with canagliflozin. The review found evidence of a link between bone-related side effects and canagliflozin, and Health Canada is now working with the manufacturer to update the drug's safety information to reflect these risks. For dapagliflozin, these risks were only identified in patients with renal impairment, a warning already noted in the prescribing information. No evidence of bone-related side effects was found with empagliflozin.

Further information can be found at http://www.hc-sc.gc.ca/dhp-mps/medeff/reviews-examens/sglt2-3-eng.php.

Interferon Beta Products Safety Review

A Health Canada safety review has concluded that there is a very rare risk of pulmonary arterial hypertension associated with the use of interferon beta products for multiple sclerosis after a report from the European Medicines Agency found a possible link. Health Canada has worked with the drug manufacturers to include the risk of pulmonary arterial hypertension in the Canadian product labeling for interferon beta products.

Further information may be found at http://www.hc-sc.gc.ca/dhp-mps/medeff/reviews-examens/interferon-beta2-eng.php.

Tumor Necrosis Factor-Alpha Blockers Safety Alert

Health Canada has reviewed the risk of liver inflammation (autoimmune hepatitis) after 2 cases of serious liver inflammation linked with treatments using tumor necrosis factor (TNF)-alpha blockers were reported. Health Canada's review concluded that there is a possible link between liver inflammation and TNF-alpha blockers. The Canadian product information for Simponi (golimumab) and Cimzia (certolizumab pegol) have been updated to include the risk of liver inflammation (autoimmune hepatitis); the Canadian product information for Humira (adalimumab), Remicade (infliximab), and Enbrel (etanercept) already include this risk.

Further information can be found at http://www.hc-sc.gc.ca/dhp-mps/medeff/reviews-examens/tnf-fnt-2-eng.php.

Testosterone Safety Alert

The US Food and Drug Administration has approved class-wide labeling changes for all prescription testosterone products. A new Warning will alert prescribers to the abuse potential of testosterone and the potential for serious adverse events, especially those related to the heart and mental health. In addition, the Abuse and Dependence and Warnings and Precautions sections have been revised to include information about adverse events reported in association with abuse and dependence of testosterone/anabolic androgenic steroids (AAS) and advising health care providers of the importance of measuring serum testosterone concentration if abuse is suspected.

Healthcare professionals and patients are encouraged to report adverse events related to the use of testosterone products to the FDA's MedWatch Safety Information and Adverse Event Reporting Program. Further information can be found at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm526151.htm.

Atypical Antipsychotics Safety Review

A Health Canada safety review has found evidence supporting a potential link between the use of atypical antipsychotics and the occurrence of urinary retention. This safety review was triggered by new information for Seroquel (quetiapine) that included reports of urinary retention in patients using quetiapine. Health Canada reviewed evidence that also linked this adverse reaction to other atypical antipsychotics available in Canada. Health Canada will be updating the prescribing information for olanzapine to include current information regarding the risk of urinary retention. Health Canada currently considers labeling for this risk adequate for other antipsychotics in the Canadian market.

Further information may be found at http://www.hc-sc.gc.ca/dhp-mps/medeff/reviews-examens/antipsycho3-eng.php.

Faslodex Safety Alert

Health Canada is warning that Faslodex (fulvestrant) can interfere with antibody-based estradiol measurement by immunoassay due to the structural similarity of fulvestrant and estradiol. This can result in falsely elevated estradiol levels, which may lead to misinterpretation of the menopausal status of women and can put patients at risk for unnecessary surgery or endocrine therapy modification. New warnings have been added to the Canadian product monograph for Faslodex advising of this risk.

Health care providers should consider reassessing the menopausal status of Faslodex patients previously tested using antibody-based estradiol assays. Alternative methods for measuring estradiol levels (such as liquid chromatography-mass spectrometry) should be considered in patients receiving Faslodex. When requesting blood tests that include estradiol, providers should indicate if the patient is taking Faslodex. Patients should contact their health care provider for more information.

Further information can be found at http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2016/60590a-eng.php.

Erwinaze Safety Alert

Jazz Pharmaceuticals is alerting health care providers that particulate matter was observed in some vials from batch 178K (lots 178K116, 178K216, 178K316, 178K416, and 178K516) of Erwinaze (asparaginase Erwinia chrysanthemi). Although affected vials were set aside and not released, there remains a possibility that some released vials from this batch may contain particulate matter.

To decrease the potential for adverse events, health care providers should follow these instructions for use of Erwinaze from batch 178K: Prior to reconstitution, carefully inspect each vial. Quarantine any vials in which particulate matter is observed. If particulate matter is not observed in the vial, use a standard 5‐micron filter needle to withdraw the reconstituted product from the vial, then discard this needle and replace it with an appropriate needle prior to administration. The drug should then be administered by intramuscular administration only.

If particulate matter is observed, providers should contact Jazz Pharmaceuticals Medical Information at 1‐800‐520‐5568.

Further information can be found at http://www.fda.gov/downloads/Drugs/DrugSafety/DrugShortages/UCM525379.pdf.

Direct-Acting Antivirals Safety Alert

The FDA is warning about the risk of hepatitis B virus (HBV) reactivation in HBV/hepatitis C virus (HCV) patients with a current or previous HBV infection who are treated with certain direct-acting antiviral (DAA) drugs for HCV. In a few cases, HBV reactivation in patients treated with DAAs resulted in serious liver problems or death; this reactivation usually occurred within 4 to 8 weeks after DAA treatment initiation. As a result, the FDA is requiring that a Boxed Warning regarding the risk of HBV reactivation be added to the drug labels of DAAs, as well as a warning to patient Medication Guides.

Health care providers should screen all patients for evidence of current or prior HBV infection before starting treatment with DAAs, and use blood tests to monitor patients for HBV flare-ups or reactivation during treatment and posttreatment follow-up. Patients should tell their health care providers if they have a history of hepatitis B infection or other liver problems before treatment initiation for hepatitis C. Patients should not stop taking DAAs without first talking to their health care providers, and contact them immediately if they develop fatigue, weakness, loss of appetite, nausea and vomiting, yellow eyes or skin, or light-colored stools, as these may be signs of serious liver problems.

Further information can be found at: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm523690.htm

Safety Alert for Codeine Cough and Cold Medicines

In December of 2015, an FDA advisory committee met to discuss use of codeine in children, while formal recommendations are pending, the majority of the committee voted to have codeine cough preparations contraindicated in patients <18 years of age. The European Medicines Agency (EMA) prohibited the use of codeine to treat cough and cold in children <12 years in April 2015.

Further information can be found at:

http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/Pulmonary-AllergyDrugsAdvisoryCommittee/UCM487401.pdf

http://pediatrics.aappublications.org/content/early/2016/09/15/peds.2016-2396

http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm453379.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery

Health Canada Gabapentin Safety Review

Health Canada’s safety review has found evidence of a link between gabapentin and the risk of respiratory depression. In 2014, the product information for gabapentin was updated to warn about the risk of respiratory depression when it is used with an opioid. While reviewing safety information provided by the manufacturer for this change, Health Canada found cases of respiratory depression in patients treated with gabapentin alone. As a result, the current safety review was performed to assess the possibility of the same concerns in patients using gabapentin alone (when not taken with opioids) and to discover if additional safety measures were needed. Patients at highest risk include those with lung, kidney, and neurological conditions that impact breathing, as well as elderly patients and those taking other medications that cause respiratory depression. Health Canada will work with manufacturers to update the product information to further warn about the risk of serious breathing problems.

Further information may be found at http://www.hc-sc.gc.ca/dhp-mps/medeff/reviews-examens/gabapentin-eng.php.

Soliris and Bexsero Safety Review

A Health Canada safety review of patients treated with Soliris (eculizumab) concluded that there was an increased risk of anemia or hemolysis when they were subsequently vaccinated with Bexsero (multicomponent meningococcal B vaccine [recombinant, adsorbed]). The risk was highest when patients received a dose of Soliris within 2 weeks after being vaccinated with Bexsero. The manufacturer has updated the Canadian product labeling for Soliris to include information regarding the risk of hemolysis with vaccines against Neisseria meningitidis serogroup B, as well as the recommendation that patients being treated with Soliris should only be vaccinated when their disease is controlled and the Soliris concentration in the blood is high.

Further information may be found at http://www.hc-sc.gc.ca/dhp-mps/medeff/reviews-examens/soliris-bexsero-eng.php.

Health Canada Safety Alert: Isotretinoin

Due to the results of a recent study commissioned by Health Canada to evaluate the risk management measures currently in place for isotretinoin, the agency is reinforcing the importance of pregnancy prevention in women taking isotretinoin (Accutane, Clarus, and Epuris). The study identified continued reports of pregnancy among patients using isotretinoin, despite the comprehensive risk management measures in place. Canada has instituted a pregnancy prevention program, which requires a patient's written consent, 2 negative pregnancy tests before starting treatment, monthly tests during treatment and 1 month after stopping, and the use of 2 reliable birth control methods throughout this period. If a patient becomes pregnant while taking isotretinoin, she should stop taking the drug immediately and consult her health care provider.

Further information may be found at http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2016/60096a-eng.php.

Primaxin 500 (Imipenem and Cilastin) Health Canada Safety Alert

The label on the outer packages of Primaxin 500 (imipenem and cilastatin sodium) (lots, 2204290, 2207460, M031928, M032243) and the multi-vial carton of imipenem and cilastatin for injection 500 mg/500 mg (lots 615F001, 615F002) contain incorrect information regarding the final diluted concentration after reconstitution. The labels indicate that the diluted concentration (expressed as imipenem content) is 2.5 mg/mL instead of the actual concentration of 5 mg/mL (when prepared according to the instructions in the package insert). Health care providers should consult the package insert or the Canadian product monograph for the correct reconstitution and dilution instructions. Patients receiving imipenem/cilastatin therapy at home should consult their health care provider to confirm that they are receiving the correct dose of their medication.

Further information may be found at http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2016/60102a-eng.php and http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2016/60098a-eng.php.

Benzodiazepines and Opioid Medicines Safety Alert

An FDA review has found that the combined use of opioid medicines with benzodiazepines or other drugs that depress the CNS resulted in serious adverse reactions, including slowed or difficult breathing and deaths. Based on these findings, the FDA is requiring that new Boxed Warnings be added to the labeling of prescription opioid pain and prescription opioid cough medicines, and benzodiazepines, as well as new or revised patient Medication Guides. The FDA will also continue to evaluate the evidence regarding combined use of benzodiazepines or other CNS depressants with medication-assisted therapy drugs used to treat opioid addiction and dependence, and whether labeling changes will be needed for other CNS depressants. Health care providers should limit prescribing opioid pain medicines with benzodiazepines or other CNS depressants only to patients for whom alternative treatment options are inadequate. If these medicines are prescribed together, the dosages and duration of each drug should be limited to the minimum needed to achieve the desired clinical effect. Patients and caregivers should be warned about the risks of slowed or difficult breathing and/or sedation, and the associated signs and symptoms. The prescribing of opioid cough medicines for patients taking benzodiazepines or other CNS depressants, including alcohol, should also be avoided. Patients taking opioids with benzodiazepines, other CNS depressant medicines, or alcohol, and caregivers of these patients, should seek medical attention immediately if the symptoms of unusual dizziness or lightheadedness, extreme sleepiness, slowed or difficult breathing, or unresponsiveness occur.

Further information may be found at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm518710.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery.

Erwinase for Injection Update

In order to avoid a potential product shortage of Erwinase, Health Canada is allowing previously unreleased Erwinase vials from batch CAMR-174 with UK labeling to be made available for use with a 5-micron filter. However, because small amounts of particulate matter have been observed bound to the stopper of some vials of Erwinase from this batch, each vial should be carefully inspected before reconstitution. If particulate matter is observed anywhere other than on the underside of the stopper (ie, on or in the product), the vial should be discarded. Otherwise, the product may be reconstituted as usual. As an additional precaution, a standard 5-micron filter needle should be used to withdraw the reconstituted product from the vial prior to administration.

Because there are some differences between currently approved Canadian and UK labeling for Erwinase, health care providers should refer to the Erwinase Canadian product monograph for prescribing information. A new supply of Erwinase is expected to be delayed until approximately mid-September 2016.

Further information can be found at http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2016/60014a-eng.php.

Viscous Lidocaine 2% Safety Alert

Health Canada has completed a safety review regarding the potential risk of severe adverse effects such as seizures, severe brain injury, heart problems, and death in pediatric patients administered viscous lidocaine 2%. Although these adverse effects were first reported in the US and had not been seen in Canada, Health Canada has now concluded that there is a link between the use of viscous lidocaine 2% and severe adverse effects in pediatric patients 5 months to 4 years of age.

The current Canadian product information does not recommend using viscous lidocaine 2% for teething pain. For some products, the labeling and dosing instructions do not specify how much time should be left between doses, which could potentially lead to high levels of lidocaine resulting in the severe adverse effects in pediatric patients. Health Canada is working with the manufacturers of viscous lidocaine 2% products to update the Canadian product labeling to include information regarding the potential risk of these severe adverse effects.

Further information can be found at http://www.hc-sc.gc.ca/dhp-mps/medeff/reviews-examens/lidocaine-eng.php.

Revolade Safety Alert

Health Canada is informing the public that cases of severe drug-induced liver injury with Revolade (eltrombopag) have been reported in patients during clinical trials and postmarketing. Recommendations for monitoring liver function prior to and during therapy with Revolade as well as management of patients with abnormal liver function tests during therapy have been added to the Canadian Product Monograph for Revolade.

Further information can be found at http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2016/59916a-eng.php.

Atypical Antipsychotics Safety Alert

Health Canada has completed a safety review related to the risk of sleep apnea with the use of atypical antipsychotics. In a review of 3 studies from the scientific literature and cases reported to Health Canada, sleep apnea was linked to use of atypical antipsychotics; use of concomitant medications and obesity may be contributing factors. Based on the results of their review, Health Canada recommended updating the current product monograph for aripiprazole, asenapine, clozapine, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, and ziprasidone to highlight the risk of sleep apnea.

Further information may be found at http://www.hc-sc.gc.ca/dhp-mps/medeff/reviews-examens/antipsycho2-eng.php.

Adempas Safety Alert

Health Canada is informing the public that the RISE-IIP study, which was to evaluate the efficacy and safety of Adempas (riociguat) in patients with symptomatic pulmonary hypertension associated with idiopathic interstitial pneumonias (PH-IIP), has been terminated early. Interim results of RISE-IIP showed an increased risk of mortality and serious adverse events among patients receiving Adempas compared to those receiving placebo; the available data indicate that the use of Adempas in patients with PH-IIP presents greater risks than benefits. The Adempas Canadian Product Monograph will be updated to contraindicate the use of Adempas in patients with PH-IIP.

Health care providers should not prescribe Adempas for patients with PH-IIP. Adempas should be discontinued in patients with PH-IIP and their clinical status carefully monitored. Patients taking Adempas for PH-IIP should contact their provider immediately about managing their disease. Adempas remains an authorized treatment for adults with the following forms of pulmonary hypertension: chronic thromboembolic pulmonary hypertension (WHO Group 4) and pulmonary arterial hypertension (WHO Group 1).

Further information is available at http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2016/59816a-eng.php.

Antidepressants Safety Alert

Health Canada has completed a safety review related to antidepressant use and the occurrence of angle-closure glaucoma. Based on the results of their review, Health Canada is working with manufacturers of antidepressant products to update the Canadian product information to include a warning of the potential risk for angle-closure glaucoma with antidepressant use. This information is already addressed in US package inserts. The safety review focused on the following 23 antidepressant medications available in Canada: Amitriptyline, bupropion, citalopram, clomipramine, desipramine, desvenlafaxine, doxepin, duloxetine, escitalopram, fluoxetine, fluvoxamine, imipramine, maprotiline, mirtazapine, moclobemide, nortriptyline, paroxetine, phenelzine, sertraline, tranylcypromine, trazodone, trimipramine, and venlafaxine.

Further information may be found at http://www.hc-sc.gc.ca/dhp-mps/medeff/reviews-examens/antidepress-eng.php.

Yondelis Safety Alert

Health Canada has completed a safety review and concluded there is a potential risk of capillary leak syndrome with the use of Yondelis (trabectedin). Health Canada is recommending updates to the Canadian prescribing information to include the potential risk of capillary leak syndrome with the use of Yondelis. At the time of the review, there were no Canadian cases of capillary leak syndrome reported with the use of Yondelis; however, international cases were reported.

Further information may be found at http://www.hc-sc.gc.ca/dhp-mps/medeff/reviews-examens/yondelis-eng.php.

Propecia and Proscar Safety Review: Assessing Potential Seizure Risk

Health Canada conducted a safety review of the potential risk of seizures in patients taking Propecia (finasteride) 1 mg and Proscar (finasteride) 5 mg after cases of seizures were published in the WHO Pharmaceuticals Newsletter. However, findings did not support a link between seizures and finasteride because the information contained in the reports was limited and some patients had other conditions that could cause seizures. At the time of the review, 95 unique cases of seizures associated with finasteride use were found worldwide. Of these, 45 were relevant for this review and further assessed. Ten of the 45 cases were Canadian, with no female cases reported. Health Canada has asked the manufacturers of Propecia and Proscar to continue to provide information on this safety issue.

Further information may be found at http://www.hc-sc.gc.ca/dhp-mps/medeff/reviews-examens/finasteride2-eng.php.

Enbrel Potential Harm to Developing Fetus

After receiving information from a study of a long-term pregnancy registry, Health Canada conducted a safety review to assess potential harm to the developing fetus associated with the use of Enbrel (etanercept) during pregnancy. Health Canada’s review noted that although the use of etanercept during pregnancy was associated with a lower risk of miscarriages, there was a slightly higher risk of birth defects. However, the review could not conclude that etanercept alone was the cause of birth defects. Health Canada will work with the manufacturer to update the product safety information to include information regarding the potential harm to a developing fetus with the use of Enbrel during pregnancy.

Further information may be found at http://www.hc-sc.gc.ca/dhp-mps/medeff/reviews-examens/enbrel2-eng.php.

Kogenate FS/Helixate FS Safety Alert

Health Canada has completed a safety review in response to recent studies that suggested an increased risk of developing inhibitory antibodies to Kogenate FS/Helixate FS as compared to similar medicines used for the treatment of hemophilia A. Patients who develop inhibitory antibodies to Kogenate FS/Helixate FS may be unable to prevent or stop episodes of bleeding despite treatment with these agents. However, Health Canada’s review concluded that this recent evidence does not present a new safety concern and that current Kogenate FS/Helixate FS product information already warns of the risk of inhibitory antibody development. Health Canada will continue to monitor this issue and will take appropriate action when new health risks are identified.

Further information may be found at http://www.hc-sc.gc.ca/dhp-mps/medeff/reviews-examens/kogenate-helixate-eng.php.

Codeine and Hydrocodone Safety Alert

Health Canada has issued a safety alert identifying the need for new warnings and restrictions on prescription codeine and hydrocodone products to improve their safe use in children and adolescents. Life-threatening respiratory depression may occur when these agents are administered at higher than recommended doses. Health care professionals and patients are advised that prescription codeine should not be given to patients under 18 years of age they are having or have recently had a tonsillectomy or adenoidectomy; hydrocodone is no longer recommended in children under the age of six. Health Canada is working with manufacturers to include these new restrictions in the drugs’ prescribing information.

Further information can be found at http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2016/59584a-eng.php.

Fluoroquinolone Antibacterial Drugs Safety Alert

The FDA has approved changes to the labeling of systemic fluoroquinolone antibacterial drugs to include Avelox (moxifloxacin), Cipro and Cipro extended-release (ciprofloxacin), Factive (gemifloxacin), Levaquin (levofloxacin), and ofloxacin. These agents are associated with potentially permanent and disabling adverse effects of the tendons, muscles, joints, nerves, and CNS that may occur together in the same patient. Therefore, in addition to existing warnings for tendinitis, tendon rupture, and worsening of myasthenia gravis, the Boxed Warning of these agents will now include warnings about the risks of peripheral neuropathy, CNS effects, and cardiac, dermatologic, and hypersensitivity reactions.

Health care providers should not prescribe systemic fluoroquinolones to patients who have other treatment options for acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis, and uncomplicated urinary tract infections because the risks outweigh the benefits in these patients. If a patient reports serious side effects, fluoroquinolone treatment should be stopped immediately, and the patient should be switched to a non-fluoroquinolone antibacterial drug to complete the treatment course. Patients should contact their health care provider immediately if they experience any serious side effects while taking a fluoroquinolone (eg, unusual joint or tendon pain, muscle weakness, a “pins and needles” tingling or pricking sensation, numbness in the arms or legs, confusion, hallucinations).

Further information can be found at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm513065.htm.

Blincyto Safety Alert

Health Canada has issued a safety alert concerning cases of life-threatening, sometimes fatal, pancreatitis associated with the use of Blincyto (blinatumomab) in clinical trials and post-marketing settings. Health care providers should consider the diagnosis of pancreatitis in patients taking Blincyto who experience severe upper abdominal pain accompanied by nausea, vomiting, or abdominal tenderness. If pancreatitis is suspected, Blincyto should be either temporarily interrupted or discontinued. The Canadian product monograph for Blincyto has been updated to reflect this new safety information.

Further information can be found at http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2016/59308a-eng.php.

Differin Gel Approved for OTC Acne Treatment

The FDA has approved Differin (adapalene) gel 0.1% for OTC treatment of acne in patients 12 years and older. Differin was previously approved as a prescription-only product and is the first drug in the retinoid pharmacologic category to be available for OTC use.

For more information, visit http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm510362.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery

Contaminated Docusate: Possible Link to Multistate Burkholderia cepacia Infections Safety Review

The CDC and the FDA are investigating a multistate outbreak of Burkholderia cepacia infections, which may be the result of contaminated docusate oral ‎liquid products. The CDC is recommending that health care facilities not use any docusate oral liquid products for patients who are critically ill, ventilated, or immunosuppressed until more information is available.

There is currently no epidemiologic or laboratory evidence to indicate that docusate oral capsules or enemas are affected.

For more information, visit https://www.cdc.gov/hai/outbreaks/b-cepacia/index.html.

ACIP Votes No on LAIV for 2016-2017 Flu Season

The CDC's Advisory Committee on Immunization Practices (ACIP) has voted against the use of MedImmune’s FluMist Quadrivalent (live attenuated influenza vaccine [LAIV]) intranasal spray during the 2016-2017 flu season. Data from 2013-2016 suggest that LAIV had poor or relatively lower vaccine effectiveness. LAIV is currently the only noninjectable flu vaccine available on the market.

ACIP continues to recommend annual influenza vaccination, with either the inactivated influenza vaccine injection or recombinant influenza vaccine injection, for everyone 6 months and older. CDC will be working with manufacturers throughout the summer to ensure there is enough vaccine supply to meet the demand.

Additional information is available at: http://www.cdc.gov/media/releases/2016/s0622-laiv-flu.html.

Drug Reaction/Rash with Eosinophilia and Systemic Symptoms with Uloric

A Health Canada safety review of febuxostat (Uloric) concluded that the data suggest a possible link between Drug Reaction/Rash with Eosinophilia and Systemic Symptoms (DRESS) and febuxostat. The Canadian prescribing information for febuxostat has been updated to include the risk of DRESS. The Canadian prescribing information for febuxostat also states that because many of the patients experiencing serious skin reactions with febuxostat also reported similar skin reactions while using allopurinol, febuxostat should be used with caution in these patients.

Further information may be found at http://www.hc-sc.gc.ca/dhp-mps/medeff/reviews-examens/uloric3-eng.php.

FDA Extends DuoDote Expiration Dates - Update

The FDA is alerting health care providers that additional lots of Meridian Medical Technologies’ DuoDote autoinjectors can be used beyond the manufacturer’s labeled expiration date. The FDA is not requiring or recommending that the identified lots be relabeled with the new use date.

This updates the FDA’s March 2015 alert. More information can be found at: http://www.fda.gov/drugs/drugsafety/ucm376367.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery.

Canagliflozin and Dapagliflozin Safety Alert

The FDA has revised the warnings in the drug labels of canagliflozin (Invokana, Invokamet) and dapagliflozin (Farxiga, Xigduo XR) to include information about the risk of acute kidney injury and recommendations to minimize this risk. Health care professionals should consider factors that may predispose patients to acute kidney injury prior to prescribing canagliflozin or dapagliflozin. Assess kidney function prior to starting canagliflozin or dapagliflozin and monitor periodically thereafter. If acute kidney injury occurs, immediately discontinue the drug and treat the kidney impairment. Patients should seek medical attention immediately if they experience signs and symptoms of acute kidney injury and should not stop taking their medicine without first talking to their health care provider.

Further information can be found at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm506554.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery.

Zecuity Safety Alert: Update

Following an investigation by the FDA about the risk of serious burns and potential permanent scarring associated with the use of Zecuity (sumatriptan iontophoretic transdermal system) migraine patch, Teva Pharmaceuticals has decided to temporarily suspend sales, marketing, and distribution to investigate the cause of burns and scars associated with the patch. Health care providers should discontinue prescribing Zecuity, and patients should stop using any remaining patches and contact their prescribers for an alternative migraine medicine.

Additional information may be found at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm504736.htm.

Influenza Virus Vaccine 2016-2017

The vaccine strains approved for the 2016-2017 season in the United States are as follows: Trivalent influenza vaccines will contain an A/California/7/2009 (H1N1)pdm09-like virus, an A/Hong Kong/4801/2014 (H3N2)-like virus, and a B/Brisbane/60/2008-like virus (B/Victoria lineage). Quadrivalent vaccines will include an additional vaccine virus, a B/Phuket/3073/2013-like virus (B/Yamagata lineage). These strains are similar to the 2015-2016 season vaccine, but patients who received the previous year vaccine still need to be vaccinated due to the limited duration of protection provided. The Advisory Committee on Immunization Practices (ACIP) recommends that health care providers begin offering vaccination as soon as the vaccine becomes available, and if possible, by October. When more than one type of vaccine is appropriate (based on indications and recommendations) and available the ACIP does not have a preferential recommendation for use of one product over another. The ACIP continues to recommend annual vaccination for all persons ≥6 months of age who do not otherwise have contraindications to the vaccine.

For a summary of information, refer to the following CDC website: http://www.cdc.gov/flu/about/season/flu-season-2016-2017.htm

Loperamide Safety Alert

The FDA is warning that the use of higher than recommended doses of nonprescription and prescription loperamide (Imodium), including through abuse or misuse of the product, can cause serious cardiac events that can lead to death. The risk of these cardiac events, including abnormal heart rhythms, may also be increased when high doses of loperamide are taken with other medications that interact with loperamide. The majority of reported cardiac events occurred in individuals intentionally misusing and abusing high doses of loperamide in attempts to self-treat opioid withdrawal symptoms or to achieve a feeling of euphoria.

Health care providers should consider loperamide, in doses higher than recommended, as a possible cause of unexplained cardiac events including QT interval prolongation, torsades de pointes or other ventricular arrhythmias, syncope, and cardiac arrest. Health care providers should also be aware that in cases of abuse, patients have often combined other medications with loperamide in an attempt to increase loperamide absorption and penetration across the blood-brain barrier, inhibit its metabolism, and enhance its euphoric effects. If loperamide toxicity is suspected, the drug should be promptly discontinued and necessary therapy begun; if loperamide ingestion is suspected, blood levels should be measured, which may require specific testing. For cases of torsades de pointes in which drug treatment is ineffective, electrical pacing or cardioversion may be required. Patients with opioid use disorders should be referred for treatment.

Patients should only take loperamide in the dose directed by their health care provider or according to the OTC Drug Facts label. Patients whose diarrhea lasts more than 2 days should stop taking loperamide and contact their health care provider. Patients taking loperamide should seek medical attention immediately if they experience fainting, rapid heartbeat or irregular heart rhythm, or unresponsiveness.

Further information may be found at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm505303.htm.

Tysabri Safety Alert

Health Canada has completed a safety review assessing the potential risk of hemolytic anemia with the use of Tysabri (natalizumab), indicated to treat patients with the relapsing-remitting form of multiple sclerosis (MS). Health Canada has concluded that, overall, the evidence is too limited to support a direct link between Tysabri use and the risk of hemolytic anemia; however, postmarketing cases of anemia reported in MS patients treated with Tysabri suggest a possible role. Following the completion of the safety review, the manufacturer has updated the prescribing information for Tysabri to better reflect this potential risk.

Further information can be found at http://www.hc-sc.gc.ca/dhp-mps/medeff/reviews-examens/tysabri-eng.php.

Denosumab Safety Alert

Health Canada has conducted a safety review following a report from the European Medicines Agency linking denosumab use (Prolia or Xgeva) with hearing loss and deafness. Health Canada’s review concluded that the available information is not sufficient to confirm any additional link between denosumab and hearing loss or deafness at this time. Based on the limited information from the reported cases, the rate of hearing loss in denosumab-exposed patients does not differ from the rate of hearing loss in the general public. Risk of hearing loss or deafness is currently included in Canadian prescribing information for Xgeva (listed as a less common adverse effect for patients with advanced bone cancer), but not in Prolia prescribing information.

Health Canada has asked the manufacturer of Prolia and Xgeva to actively monitor the risk of hearing loss and deafness in patients worldwide and report these to Health Canada. Health Canada will continue to monitor side effect information for Prolia and Xgeva to identify and assess potential harms, and will take appropriate and timely action if and when any new health risks are identified.

Further information can be found at http://www.hc-sc.gc.ca/dhp-mps/medeff/reviews-examens/denosumab-eng.php.

Atarax Safety Review

A Health Canada safety review demonstrated that Atarax (hydroxyzine) has the potential to block hERG channels and other types of cardiac channels, resulting in a potential risk of QT prolongation (QTP) and cardiac arrhythmia events including torsades de pointes. Atarax, along with all generic formulations of hydroxyzine, is now contraindicated in patients with a history of QTP and/or torsades de pointes (including congenital long QT syndromes); history of cardiac arrhythmias; significant electrolyte imbalance (hypokalemia, hypomagnesemia); significant bradycardia; family history of sudden cardiac death and concomitant use of other QT/QTc-prolonging drugs or of CYP3A4/5 inhibitors. Atarax should be used for as short a duration as possible and at the lowest effective dose up to specified maximums. The maximum daily oral dose should be a total of 100 mg in adults given in divided doses, 50 mg in elderly patients given in divided doses (if use cannot be avoided), and 2 mg/kg/day in divided doses in children and adolescents up to 40 kg in weight. In children and adolescents over 40 kg, the maximum daily dose should be the same as for adults.

Patients should stop taking hydroxyzine and contact a health care provider immediately if they experience signs and symptoms of an abnormal heart rate or rhythm such as heart palpitations, dizziness, fainting, or seizures. Before starting treatment with hydroxyzine, patients should speak to their health care provider if they or a family member have had any heart problems, if they are taking other medications, or if they have had low levels of potassium and/or magnesium in their blood. Patients who are already taking hydroxyzine should consult their doctor or pharmacist to confirm they are taking the medication at the correct dose and for the correct duration.

Further information may be found at http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2016/58758a-eng.php.

Nonprescription Aspirin-Containing Antacid Products Safety Review

The FDA is warning consumers about the risk of serious bleeding when using nonprescription aspirin-containing antacid products to treat heartburn, sour stomach, acid indigestion, or upset stomach. Although these products have included label warnings since 2009 about this bleeding risk, the FDA continues to receive reports related to this safety issue. Consumers should read the product labeling when purchasing or taking a nonprescription product to treat heartburn, acid indigestion, or sour or upset stomach, and should consider choosing a product without aspirin to relieve symptoms.

Patients with 1 or more of the following risk factors may have a higher chance of serious bleeding when taking aspirin-containing antacid products: Age 60 years or older; a history of stomach ulcers or bleeding problems; currently taking a blood-thinning or steroid medicine or other medicines containing a nonsteroidal anti-inflammatory drug (eg, ibuprofen, naproxen); drinking 3 or more alcoholic drinks every day; or taking more of these medicines than the amount recommended or for a longer period than recommended.

Further information may be found at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm505190.htm.

Zecuity Safety Alert

The FDA is investigating the risk of serious burns and potential permanent scarring associated with the use of the Zecuity (sumatriptan iontophoretic transdermal system) patch. The FDA’s investigation into the cause and extent of these serious adverse effects was prompted by a large number of patient reports of burns and scars at the application site.

Patients should be advised to immediately remove the Zecuity patch, regardless of how long it has been worn, if they experience moderate to severe pain at the application site. Health care professionals should evaluate the application site and consider alternative formulations of sumatriptan or alternative migraine therapy.

Additional information may be found at http://www.fda.gov/Drugs/DrugSafety/ucm504588.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery.

Ketoconazole Safety Alert

The FDA is warning health care providers to avoid prescribing ketoconazole oral tablets to treat skin and nail fungal infections, which are not approved uses of oral ketoconazole. Oral ketoconazole has a risk of serious liver damage, adrenal gland problems, and potentially harmful drug-drug interactions, all of which outweigh any benefit in the treatment of skin and nail fungal infections. In 2013, the FDA approved changes to the oral ketoconazole tablet labeling to reflect these serious risks and removed indications for treatment of skin and nail fungal infections. However, an FDA safety review found that oral ketoconazole continues to be prescribed for these conditions. Since the 2013 labeling change, one patient death due to liver failure associated with oral ketoconazole prescribed to treat a fungal infection of the nails has been reported to the FDA.

Health care providers should use ketoconazole tablets only to treat serious systemic fungal infections when no other antifungal therapies are available. Skin and nail fungal infections in otherwise healthy individuals are not life-threatening, and therefore the risks associated with oral ketoconazole outweigh the benefits. Patients should discuss the risks and benefits of available therapies with their health care provider prior to using any medicine to treat skin and nail fungal infections. Patients taking ketoconazole tablets should seek immediate medical attention if they experience any signs or symptoms of liver problems, including loss of appetite, nausea, vomiting, or abdominal discomfort; yellowing of the skin or the whites of the eyes (jaundice); unusual darkening of the urine or lightening of the stools; or right upper abdomen pain and discomfort.

Topical ketoconazole has not been associated with liver damage, adrenal problems, or drug-drug interactions when applied to the skin or nails

Further information can be found at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm502073.htm.

Canagliflozin Safety Alert

The FDA is alerting the public about interim safety results from an ongoing clinical trial that found an increase in leg and foot amputations (mostly affecting the toes) in patients treated with canagliflozin (Invokana, Invokamet). The FDA has not yet determined whether canagliflozin increases the risk of leg and foot amputations and is still investigating this new safety issue. Patients taking canagliflozin or canagliflozin-containing products should not stop or change their diabetes medicine without first discussing with their health care provider. Health care providers should follow recommendations in the canagliflozin product labeling and monitor patients for new pain, tenderness, sores, ulcers, and/or infections on the legs or feet.

Further information can be found at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm501565.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery.

SGLT2 Inhibitors Safety Review

Health Canada conducted a safety review following a recent US Food and Drug Administration notice concerning cases of diabetic ketoacidosis in patients taking sodium-glucose contransporter-2 (SGLT2) inhibitors (canagliflozin [Invokana], dapagliflozin [Forxiga], empagliflozin [Jardiance]). The review concluded that SGLT2 inhibitors may increase the risk of diabetic ketoacidosis in patients using these medications for treatment of type 2 diabetes. Health Canada has currently received 5 reports of diabetic ketoacidosis in patients taking canagliflozin (Invokana) and is recommending that manufacturers update the product information to better describe symptoms of diabetic ketoacidosis.

Further information can be found at http://www.hc-sc.gc.ca/dhp-mps/medeff/reviews-examens/sglt2-2-eng.php.

Fluoroquinolone Safety Alert

An FDA safety review has shown that fluoroquinolones when used systemically can cause disabling and potentially permanent serious adverse effects in patients with sinusitis, bronchitis, and uncomplicated urinary tract infections. The FDA is advising that the serious adverse effects associated with fluoroquinolone antibacterial drugs generally outweigh the benefits for patients with these conditions. Fluoroquinolones should only be used in patients who do not have alternative treatment options.

The FDA is requiring all systemic (ie, oral, injectable) fluoroquinolone antibacterial drugs to include this new safety information in drug labels and patient Medication Guides. Patients should contact health care professionals if they develop any serious adverse effects, which can include tendon, joint and muscle pain, a “pins and needles” tingling or pricking sensation, confusion, and hallucinations. Health care professionals should immediately stop systemic fluoroquinolone treatment if a patient reports serious adverse effects, and switch to a non-fluoroquinolone antibacterial drug to complete the patient’s treatment course.

Further information can be found at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm500665.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery.

Eylea Safety Review

Health Canada has evaluated the risk of adverse reactions in areas of the body other than the eye associated with Eylea (aflibercept) injection after newly published literature suggested that the body takes a longer time to remove Eylea from the bloodstream compared with removal time of a similar product used for the same condition. The safety review concluded that despite the presence of low levels of Eylea systemically, the risk of adverse reactions did not differ from that of the similar product. Health Canada continues to monitor the safety of Eylea and encourages health care providers to report any adverse reactions related to its use.

Further information can be found at http://www.hc-sc.gc.ca/dhp-mps/medeff/reviews-examens/eylea-eng.php.

Olanzapine Safety Alert

The FDA is warning that olanzapine can cause a rare but serious skin reaction known as drug reaction with eosinophilia and systemic symptoms (DRESS). DRESS may consist of a cutaneous reaction (eg, rash or exfoliative dermatitis) along with eosinophilia, fever, lymphadenopathy and systemic complications such as hepatitis, myocarditis, pericarditis, pancreatitis, nephritis, and pneumonitis and has a mortality rate of up to 10%. The FDA is adding a new warning to the drug labeling for all olanzapine-containing products that describes this severe condition.

Patients taking olanzapine-containing products who develop a fever with a rash and swollen lymph glands, or swelling in the face, should seek medical care immediately as these symptoms are commonly seen together in DRESS. Health care providers should immediately stop treatment with olanzapine if DRESS is suspected. Although there is currently no specific treatment, DRESS can be managed through early recognition of the syndrome, discontinuation of the offending agent, and supportive care. Treatment with systemic corticosteroids should be considered in cases with extensive organ involvement.

Further information can be found at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm500123.htm.

Proton Pump Inhibitors - Potential Risk of Clostridium difficile

Health Canada has conducted a review on the potential risk of Clostridium difficile infection with proton pump inhibitors that concluded evidence was too limited to establish that the use of proton pump inhibitors causes C. difficile infection. Currently, the Canadian prescribing information for all proton pump inhibitors reflects the observation that patients using these drugs are slightly more likely to develop C. difficile infections. The labeling will be updated to include additional information on the various risk factors of C. difficile infection and to encourage optimal use of proton pump inhibitors.

Further information can be found at http://www.hc-sc.gc.ca/dhp-mps/medeff/reviews-examens/ppi-ipp-eng.php.

BCR-ABL Tyrosine Kinase Inhibitors — Risk of Hepatitis B Reactivation Safety Alert

Health Canada is notifying health care professionals of a recent review showing that hepatitis B virus (HBV) reactivation can occur in chronic HBV carriers after they receive BCR-ABL tyrosine kinase inhibitors (TKIs), which include imatinib (Gleevec), nilotinib (Tasigna), bosutinib (Bosulif), dasatinib (Sprycel), and ponatinib (Iclusig). Some cases of HBV reactivation have resulted in acute hepatic failure or fulminant hepatitis leading to liver transplantation or death. It is recommended that patients be tested for HBV infection prior to initiation of treatment with BCR-ABL TKIs; experts in liver disease and in the treatment of HBV be consulted promptly before initiating treatment in chronic HBV carriers (including those with active disease) and in patients who test positive for HBV infection during treatment; and patients who are carriers of HBV requiring treatment with BCR-ABL TKIs be closely monitored for signs and symptoms of active HBV infection throughout therapy and for several months following termination of therapy. The Canadian prescribing and consumer information for BCR-ABL TKIs will be updated to reflect this new safety information.

Further information can be found at http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2016/58222a-eng.php.

Aripiprazole Safety Alert

The FDA is warning the public that compulsive or uncontrollable urges to gamble, binge eat, shop, and have sex have been reported with the use of the antipsychotic drug aripiprazole (Abilify, Abilify Maintena, Aristada, and generics). The uncontrollable urges were reported to have stopped when the medicine was discontinued or the dose was reduced. These impulse-control problems are rare, but they can affect anyone who is taking the medicine, and they may result in harm to the patient and others if not recognized. As a result, the FDA is adding new warnings about all of these compulsive behaviors to the drug labels and patient Medication Guides for all aripiprazole products.

Health care providers should make patients and caregivers aware of the risk of these uncontrollable urges when prescribing aripiprazole, and specifically ask patients about any new or increasing urges while they are being treated with aripiprazole. Patients at higher risk for impulse-control problems should be closely monitored for new or worsening uncontrollable urges; these include those with a personal or family history of obsessive-compulsive disorder, impulse-control disorder, bipolar disorder, and impulsive personality, as well as alcoholism, drug abuse, or other addictive behaviors. The dose may need to be reduced or the medicine stopped if such urges develop.

Patients and caregivers should be alert for uncontrollable and excessive urges and behaviors with the use of aripiprazole. To prevent or limit possible harm, patients and caregivers should talk with a health care provider as soon as possible if any uncontrollable urges develop. Patients should not suddenly stop taking aripiprazole without first talking to their health care provider.

Further information may be found at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm498823.htm.

Brintellix Brand Name Change

The FDA has approved a brand name change for the antidepressant Brintellix (vortioxetine) to decrease the risk of prescribing and dispensing errors resulting from confusion with the blood-thinning medicine Brilinta (ticagrelor). The new brand name of the drug will be Trintellix, and it is expected to be available in June 2016. No other changes will be made to the label or packaging, and the medicine is the same.

Because of the delay associated with manufacturing bottles with the new brand name, health care providers and patients may continue to see bottles labeled with the brand name Brintellix during the transition period. Providers should carefully check to ensure they have prescribed or dispensed the correct medicine. Prescribers can reduce the risk of confusion by including the generic name of the medication they are ordering, in addition to the brand name and indication for use. Patients should be sure they have received the correct medicine. Trintellix tablets will be identical to Brintellix tablets. Patients with questions or concerns should talk to their health care provider or pharmacist.

Further information can be found at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm498607.htm.

Clozapine Safety Review

The US Food and Drug Administration (FDA) has alerted pharmacists and other health care providers of updates regarding the clozapine Risk Evaluation and Mitigation Strategy (REMS) program rollout. As part of the new REMS program, patients taking clozapine need to have their absolute neutrophil count (ANC) regularly monitored, as the drug may decrease the number of neutrophils in the blood and leave patients prone to infections. Due to implementation challenges identified following the approval of the Clozapine REMS Program in September 2015, the FDA extended the deadlines for certification of prescribers and pharmacies to help ensure that health care professionals had sufficient time to complete this process and to ensure patient access to clozapine was maintained. Prior to the approval of the Clozapine REMS Program, individual clozapine manufacturers operated separate patient registries.

The FDA is continuing to work with clozapine manufacturers to develop a timeline for the program’s full implementation, including pre-dispense authorization and prescriber and pharmacy certification requirements, which will be completed in a phased approach beginning in May 2016. The goal is to have the Clozapine REMS Program fully operational by the end of 2016, at which time prescribers and pharmacies will need to be certified in order to prescribe and dispense clozapine.

Further information can be found at http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm497790.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery.

Yervoy Safety Review

After conducting a safety review, Health Canada concluded that there is a potential risk of drug reaction with eosinophilia and systemic symptoms (DRESS) with Yervoy (ipilimumab), and has worked with the manufacturer to update prescribing information to include information about this potential risk. There were no Canadian case reports of DRESS with the use of Yervoy, but a search in the World Health Organization’s Adverse Drug Reaction database found 3 reports of DRESS with the use of Yervoy, and the manufacturer shared a report from the Global Safety Database that included cases of DRESS possibly caused by Yervoy.

Further information is available at http://www.hc-sc.gc.ca/dhp-mps/medeff/reviews-examens/yervoy2-eng.php.

Perjeta Health Canada Safety Alert

Health Canada has carried out a safety review into the potential risk of Stevens-Johnson syndrome, identified during a routine review of information received from the manufacturer, with the use of Genentech’s Perjeta (pertuzumab). The review concluded that the evidence was too limited to support a link between the use of Perjeta and the risk of Stevens-Johnson syndrome. However, Health Canada has asked the manufacturer to continue to actively monitor for this risk worldwide and to report new cases of Stevens-Johnson syndrome with Perjeta use.

Additional information is available at http://www.hc-sc.gc.ca/dhp-mps/medeff/reviews-examens/perjeta-eng.php.

Opioid Pain Medicine Safety Alert

The US Food and Drug Administration (FDA) is warning the public about several safety issues associated with the entire class of opioid pain medicines. These risks are: Potentially harmful interactions with numerous other medications, leading to serotonin syndrome; problems in which the adrenal glands do not produce adequate amounts of cortisol; and decreased sex hormone levels, possibly leading to reduced interest in sex, impotence, or infertility.

The FDA is requiring class-wide safety labeling changes for all opioid pain medications warning of these risks. In addition to these labeling changes, the FDA is requiring a new boxed warning in the labeling of immediate-release opioids about the serious risks of misuse, abuse, addiction, overdose, and death, as well an updated indication clarifying that, because of these risks, immediate-release opioids should be reserved for pain severe enough to require opioid treatment and for which alternative treatment options are inadequate or not tolerated.

If serotonin syndrome is suspected, health care providers should discontinue opioid treatment and/or use of other contributing medications. If adrenal insufficiency is suspected, health care providers should perform diagnostic testing and initiate treatment with corticosteroids and wean the patient off of the opioid, if appropriate; if the opioid can be discontinued, follow-up assessment of adrenal function should be performed to determine if treatment with corticosteroids can be discontinued. If the patient has signs or symptoms of decreased sex hormone levels, health care providers should conduct a laboratory evaluation.

Further information can be found at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm491715.htm.

Idelalisib (Zydelig) Safety Alert

The FDA is alerting health care providers about reports of an increased rate of adverse events (including deaths) in clinical trials with idelalisib when used in combination with other cancer medicines. The manufacturer, Gilead Sciences, has confirmed that they are halting 6 clinical trials with idelalisib in patients with chronic lymphocytic leukemia, small lymphocytic lymphoma, and indolent non-Hodgkin lymphomas. The FDA is reviewing the findings of the clinical trials and will communicate new information as necessary.

Health care providers should be aware that idelalisib is not approved for previously untreated chronic lymphocytic leukemia. Idelalisib is currently FDA-approved for the treatment of relapsed chronic lymphocytic leukemia (in combination with rituximab), in patients for whom rituximab alone would be considered appropriate due to other comorbidities; for relapsed follicular B-cell non-Hodgkin lymphoma in patients who have received at least 2 prior systemic therapies; and for relapsed small lymphocytic lymphoma in patients who have received at least 2 prior systemic therapies.

The FDA urges health care providers and patients to report adverse events involving idelalisib to the FDA MedWatch program.

Further information may be found at http://www.fda.gov/Drugs/DrugSafety/ucm490618.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery

Imatinib and Risk of Kidney Function Decline Safety Review

A Health Canada safety review concluded there was sufficient evidence to consider a potential link between Novartis' Gleevec (imatinib) and a decline in kidney function during long-term treatment. Health Canada reviewed 30 reports of decreased or abnormal kidney function linked with imatinib and Novartis found an additional 63 reports worldwide of decreased kidney function linked with imatinib. To reduce this risk, Health Canada is working with Novartis to include the following safety information in the product monograph: Long-term treatment with Gleevec may result in decline in renal function. Patients treated with imatinib in clinical studies had a decrease over time in estimated glomerular filtration rate (eGFR). Monitoring for renal function should be undertaken before initiating therapy and periodically thereafter.

Further information can be found at: http://www.hc-sc.gc.ca/dhp-mps/medeff/reviews-examens/gleevec-eng.php.

Influenza Health Advisory

The Centers for Disease Control and Prevention (CDC) is informing the public of recent reports of severe influenza illness as influenza activity increases across the country. Health care providers are reminded to treat suspected influenza in high-risk outpatients, in those with progressive disease, and in all hospitalized patients with antiviral medications (ie, oral oseltamivir, inhaled zanamivir, or intravenous peramivir) as soon as possible (ideally within 48 hours of symptom onset), regardless of negative rapid influenza diagnostic test (RIDT) results and without waiting for reverse transcription-polymerase chain reaction (RT-PCR) testing results. Although clinical results are most effective when antiviral treatment is administered early, treatment may also be beneficial when started up to 4 to 5 days after symptom onset in hospitalized patients.

The advisory was prompted by recent reports to the CDC of severe respiratory illness among young- to middle-aged adults with H1N1pdm09 influenza virus infection, the predominant strain in recent weeks. Some of these patients required intensive care unit (ICU) admission, and fatalities have been reported. Most of these patients were reportedly unvaccinated, and some reportedly tested negative for influenza by RIDT, with their influenza diagnosis made later using molecular assays.

Health care providers should continue to vaccinate patients for as long as influenza viruses are circulating, and should promptly start antiviral treatment of severely ill and high-risk patients if influenza is suspected or confirmed.

Patients at a higher risk for influenza complications include: Children younger than 2 years; adults 65 years and older; persons with chronic pulmonary (including asthma), cardiovascular (except hypertension alone), renal, hepatic, hematological (including sickle cell disease), metabolic disorders (including diabetes mellitus), or neurologic and neurodevelopment conditions (including disorders of the brain, spinal cord, peripheral nerve, and muscle such as cerebral palsy, epilepsy [seizure disorders], stroke, intellectual disability [mental retardation], moderate to severe developmental delay, muscular dystrophy, or spinal cord injury); persons with immunosuppression, including that caused by medications or by HIV infection; women who are pregnant or postpartum (within 2 weeks after delivery); persons younger than 19 years who are receiving long-term aspirin therapy; American Indians and Alaska Natives; persons who are morbidly obese (ie, body-mass index is equal to or greater than 40); and residents of nursing homes and other chronic-care facilities.

Further information can be found at http://emergency.cdc.gov/han/han00387.asp.

Tarceva Maintenance Treatment Alert

Health Canada has notified health care professionals that based on a recent study, IUNO (B025460), the benefit-risk of Tarceva (erlotinib) as maintenance treatment in patients with advanced non–small cell lung cancer (NSCLC) whose tumors do not have an epidermal growth factor receptor (EGFR)–activating mutation is negative. The IUNO study compared the primary endpoint of overall survival using maintenance Tarceva therapy with Tarceva administered at the time of disease progression in patients with advanced NSCLC whose tumors did not harbor an EGFR-activating mutation (exon 19 deletion or exon 21 L858R mutation). Overall survival rate was not superior to that of patients randomized to receive maintenance Tarceva. The role of Tarceva as maintenance therapy in patients whose tumors do harbor an EGFR-activating mutation with locally advanced or metastatic NSCLC will be assessed by Health Canada. Health Canada, in collaboration with Hoffmann-La Roche Limited, will revise the Canadian prescribing and consumer information for Tarceva to reflect these updated data.

For additional information, refer to http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2016/56720a-eng.php.

CellCept and Myfortic Teratogenicity Alert

Health Canada has notified health care providers that mycophenolate is a confirmed human teratogen, and increases the risk of spontaneous abortions and congenital malformations following exposure during pregnancy. Health Canada, in conjunction with Hoffmann-La Roche Limited and Novartis Pharmaceuticals Canada, is working to add new contraindications to the CellCept (mycophenolate mofetil) and Myfortic (mycophenolate sodium) Canadian Product Monographs in order to strengthen safety information. Prior to therapy with any mycophenolate-containing product, women of childbearing potential must have 2 negative serum or urine pregnancy tests; the second test should be performed 8 to 10 days after the initial test and immediately before treatment initiation. Repeat pregnancy tests should be performed during routine follow-up visits. Women of childbearing potential should use 2 reliable forms of contraception simultaneously, including at least 1 highly effective method before and during therapy and for 6 weeks following mycophenolate discontinuation. Sexually-active men (including reproductively competent and vasectomized men) should use condoms during treatment and for at least 90 days after mycophenolate cessation. Men should not donate sperm/semen during therapy or for at least 90 days following mycophenolate discontinuation. Female partners of male patients should use highly effective contraception during treatment and for a total of 90 days after the patient’s last dose of any mycophenolate-containing product.

All patients should be informed not to donate blood during treatment or for at least 6 weeks following discontinuation of any mycophenolate-containing product. Health care providers should ensure that women and men taking mycophenolate products understand the risk of harm to the fetus, the need for effective contraception, and the need to immediately consult a physician if there is a possibility of pregnancy.

For additional information, refer to http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2016/56690a-eng.php.

Noxafil Oral Formulations Dosing Errors

The FDA is cautioning that differences in dosing regimens between the 2 oral formulations (oral suspension and delayed-release tablet) of Merck’s Noxafil (posaconazole) have resulted in dosing errors. The drug labels have been revised to indicate that the 2 oral formulations cannot be directly substituted for each other but require a change in dose. Direct mg-for-mg substitution of the 2 formulations can result in drug levels that are lower or higher than needed to effectively treat certain fungal infections. Since the approval of Noxafil delayed-release tablets in November 2013, the FDA has received 11 reports of the wrong oral formulations being prescribed and/or dispensed to patients. One case resulted in death, and another case resulted in hospitalization. Prescribers should specify the dosage form, strength, and frequency on all Noxafil prescriptions. Pharmacists should request clarification from prescribers when the dosage form, strength, or frequency is not specified. Patients should consult their health care provider before they switch from one oral formulation to the other.

Further information can be found at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm479782.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery.

Zelboraf Warning for Risk of Radiation Sensitization or Radiation Recall Reactions

Health Canada has notified health care providers and the public that Zelboraf (vemurafenib) has the potential risk causing radiation sensitization and radiation recall reactions in patients treated with radiation prior to, during, or following Zelboraf treatment. Health Canada, in collaboration with Hoffmann-La Roche Limited, has updated the Canadian prescribing and consumer information for Zelboraf to reflect this safety risk. Zelboraf is indicated for the treatment of patients with unresectable or metastatic melanoma with BRAF V600 mutation, as detected by a validated test. It is recommended that Zelboraf not be used concomitantly with radiation therapy, unless the potential benefit justifies the potential risk to the patient.

Any case of radiation sensitization or radiation recall or other serious or unexpected side effects in patients receiving Zelboraf should be reported to Hoffmann-La Roche Limited or Health Canada by calling 1-888-762-4388 or 1-866-234-2345.

Further information can be found at http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2015/56368a-eng.php.

Rosiglitazone-Containing Diabetes Medicines Safety Alert

The FDA is eliminating the Risk Evaluation and Mitigation Strategy (REMS) for rosiglitazone-containing type 2 diabetes medicines, which are approved as Avandia, Avandamet, Avandaryl, and generics. The REMS is no longer necessary to ensure that the benefits of rosiglitazone medicines outweigh their risks.

Further information may be found at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm477601.htm.

OTC Acne Products With Benzoyl Peroxide and Salicylic Acid Safety Review

Health Canada is advising that the use of OTC acne products applied to the skin containing benzoyl peroxide or salicylic acid may cause rare, but serious, allergic reactions (eg, anaphylactic reaction; itchy hives with swelling of the face, eyes, lips, mouth, or throat; difficulty breathing; throat tightness or hoarseness; fainting). Health Canada has completed a safety review and has concluded that there is evidence supporting a link between the use of OTC acne products containing either benzoyl peroxide or salicylic acid and more serious allergic reactions, and as a result, manufacturers will be requested to revise the labeling to include these changes:

  • Instructions for sensitivity testing to help determine whether a new user of an acne product may be sensitive or allergic to the product;
  • Updated warnings relating to possible skin reactions and allergic reactions, and what consumers should do; and
  • A warning that the product should not be used if someone is allergic to any of the ingredients of the product, including benzoyl peroxide or salicylic acid.

Patients who use OTC topical acne products containing benzoyl peroxide or salicylic acid should read and follow the safety instructions and seek medical attention if they develop an allergic reaction.

Further information is available at http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2015/56268a-eng.php.

SGLT2 Inhibitors Label Warnings

An FDA safety review has resulted in new warnings to the labels of all sodium-glucose cotransporter-2 (SGLT2) inhibitors about the risks of ketoacidosis and serious urinary tract infections, which could result in hospitalization. This safety review, following the FDA Drug Safety Communication in May 2015 about the risk of ketoacidosis with SGLT2 inhibitors, identified 73 cases of ketoacidosis in patients with type 1 or type 2 diabetes treated with SGLT2 inhibitors from March 2013 to May 2015. In addition, 19 cases of life-threatening blood infections (urosepsis) and kidney infections (pyelonephritis) that started as urinary tract infections with the SGLT2 inhibitors were reported from March 2013 through October 2014. Health care providers should assess for ketoacidosis and urinary tract infections in patients with suggestive symptoms, and discontinue the drug and institute treatment promptly if ketoacidosis is suspected.

Further information can be found at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm475553.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery.

Phosphate Injection Shortage and Import of Glycophos (Sodium Glycerophosphate Pentahydrate)

The U.S. Food and Drug Administration (FDA) previously allowed the import of Glycophos (sodium glycerophosphate pentahydrate) from a Fresenius Kabi plant in Norway to alleviate the phosphate injection shortage. According to the FDA drug shortages website, the sodium phosphate shortage has been resolved. However, some Glycophos product may remain available in the marketplace. Unlike other phosphate products available in the US, sodium glycerophosphate pentahydrate is an organic phosphate product and varies from other phosphate products in terms of concentration, dosing, and preservative content; use caution when switching between products.

Compatibility Issue with Primene and Trace Elements

Health Canada and Baxter are informing health care providers that the use of a final filter is required to administer Primene 10% solution that has been compounded with trace elements. During investigations, visible particulate matter was observed on the inlet side of an inline filter when Primene 10% was admixed with trace elements in 2-in-1 or 3-in-1 parenteral nutrition solutions. Compliance with USP limits for particulate matter was only achieved after filtration. The precipitate may result from interaction between hydrogen sulfide (from degradation of cysteine during sterilization of Primene) and copper ions in the trace elements solution. Infusion of a precipitate may lead to serious adverse effects including phlebitis, thrombophlebitis, thrombosis, and major organ dysfunction.

Health care providers should adopt the following recommendations when using Primene 10% solution that has been compounded with trace elements:

  • Use a 0.22-micron filter for 2-in-1 (amino acids and carbohydrates) parenteral nutrition solutions. Piggyback lipids for infusion to the patient below the filter (Y-site).
  • Use a 1.2-micron filter for 3-in-1 (lipid, amino acids, and carbohydrates) parenteral nutrition solutions, as the addition of lipids requires a larger filter.
  • Perform visual inspections for cloudiness or precipitation of the TPN solution, infusion set, catheter, and in-line filter after compounding, prior to administration and periodically during administration.
  • If discoloration or precipitation is noted in the filter, it is not necessary to stop the infusion. Where medically relevant, perform blood levels of copper (or other trace elements).

Further information is available at http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2015/55942a-eng.php.

Iodine-Containing Contrast Agents Safety Alert

The FDA is advising that rare cases of underactive thyroid have been reported in infants following the use of iodinated contrast media (ICM) for x-rays and other medical imaging procedures. In all reported cases (N = 10), the infants were either premature or had other serious underlying medical conditions. Available evidence suggests that this effect is usually temporary, resolves without treatment, and does not result in any lasting effects. The affected infants typically did not show any visible signs of underactive thyroid.

The FDA has approved changes to the labels of all ICM products (http://www.fda.gov/Drugs/DrugSafety/ucm472782.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery) to include information about these cases. No changes to current prescribing, administration, or monitoring practices are recommended. Manufacturers of ICM products have been required to conduct a study to investigate this safety issue further.

Parents and caregivers should contact their infant’s health care provider for additional information or if they have questions or concerns about their infant receiving an ICM product. Health care providers should continue to follow the label recommendations for ICM products and exercise their clinical judgment to determine if testing for underactive thyroid is necessary.

Further information may be found at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm472995.htm.

Hepatitis C Treatments Safety Alert: Updated

The FDA and Health Canada are warning health care providers that hepatitis C treatments dasabuvir/ombitasvir/paritaprevir/ritonavir (Viekira Pak [US brand name]/Holkira Pak [Canadian brand name]) and ombitasvir/paritaprevir/ritonavir (Technivie) can cause serious hepatic injury mostly in patients with underlying advanced hepatic disease. The FDA and Health Canada are requiring the manufacturer of these drugs to include warnings about serious hepatotoxicity to the drug labels.

Health care professionals should closely monitor for signs and symptoms of worsening liver disease such as ascites, hepatic encephalopathy, variceal hemorrhage, and/or increases in direct bilirubin in the blood.

Further information may be found at:

US: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm468757.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery

Canada: http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2015/55800a-eng.php

Clopidogrel Safety Alert

An FDA review of the blood-thinning medication clopidogrel (Plavix) has determined that long-term use (12 months or longer) does not increase or decrease overall risk of death in patients with, or at risk for, heart disease. The FDA evaluation of the Dual Antiplatelet Therapy (DAPT) trial and several other clinical trials does not suggest that clopidogrel increases the risk of cancer or death from cancer. The FDA performed meta-analyses of other long-term clinical trials to assess the effects of clopidogrel on death rates (from all causes); the results indicate that long-term dual antiplatelet therapy (clopidogrel and aspirin) does not appear to change the overall risk of death, compared to short-term use (6 months or less) of clopidogrel and aspirin or aspirin alone.

Patients should not stop taking clopidogrel or other antiplatelet medicines because stopping therapy may result in an increased risk of heart attacks and blood clots. Health care professionals should consider the benefits and risks of available antiplatelet medicines prior to initiating treatment.

Further information can be found at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm471531.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery.

Abilify Safety Alert

Health Canada is notifying health care providers that labeling for Abilify and Abilify Maintena (aripiprazole) have been updated to note an increased risk of impulsive behaviors including pathological gambling and hypersexuality. The findings are the result of a Health Canada safety review that identified 18 international cases of pathological gambling and 6 international cases of hypersexuality described in published scientific literature. In most cases, the behaviors ceased or improved when treatment was stopped or when the dose was reduced, suggesting a direct link between the drug and the adverse reaction. The reports involved male and female patients ranging from 19 to 64 years of age.

Patients should be alert for unusual impulse-related behaviors (including uncontrollable impulse to gamble, unusual sexual thoughts, fantasies, desires or behaviors, or any other uncontrollable behaviors found to be stressful) and report them to their health care provider. Patients with a history of a gambling disorder may be at an increased risk of pathological gambling and should be monitored closely.

Further information may be found at http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2015/55668a-eng.php.

Vincristine Sulfate Safety Alert

Health Canada is notifying health care providers that certain lots of Hospira’s vincristine sulfate 1 mg/mL injection (DIN 02183013: 2 mL vial, list #7077A001; 5 mL vial, list #7082A001) have incorrect or outdated safety information on the inner/outer labels and package insert, which may increase the risk to patients and may result in significant patient harm requiring medical intervention. These warnings include:

  • Vincristine should only be administered by the intravenous (IV) route. Administration of vincristine by any other route can be fatal.
  • Syringes containing this product should be labeled “Warning - for IV use only.”
  • Extemporaneously prepared syringes containing this product must be packaged in an overwrap which is labeled “Do not remove covering until moment of injection. For IV use only - fatal if given by other routes.”
  • Contraindication of vincristine in patients with demyelinating Charcot-Marie-Tooth syndrome.
  • Potential risk of acute shortness of breath when vincristine is coadministered with mitomycin-C and GI toxicities including necrosis with administration of vincristine.

Health care providers are requested to consult with the approved Canadian product monograph for vincristine sulfate 1 mg/mL for the most updated information. Consumers with questions should contact their health care provider for more information.

Entacapone: No Increased Cardiovascular Risk Safety Review

An FDA safety review has found no clear evidence of an increased risk of heart attack, stroke, or other cardiovascular events associated with the use of entacapone for the treatment of Parkinson disease. Recommendations for using Comtan (entacapone) and Stalevo (combination of entacapone, carbidopa, and levodopa) will remain the same in the product labeling. In August 2010, the FDA alerted patients and health care providers about a possible increased risk for cardiovascular events and death with Stalevo. Carbidopa and levodopa have been used extensively and have not been shown to have an increased cardiovascular risk.

Additional information is available at http://www.fda.gov/Drugs/DrugSafety/ucm468803.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery.

Kayexalate Safety Alert

The FDA is requiring the manufacturer of Kayexalate (sodium polystyrene sulfonate) to conduct drug interactions studies to investigate the potential of Kayexalate to bind to other oral medications, which could affect the concomitant medication’s absorption and, therefore, efficacy. Kayexalate labeling describes its potential to decrease absorption of lithium and thyroxine; however, extensive drug-drug interaction studies with Kayexalate have not been performed. To reduce the potential risk of Kayexalate to bind to other oral medications, prescribers and patients should consider separating Kayexalate dosing from other oral medications by at least 6 hours.

Further information may be found at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm468720.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery.

Gilenya Safety Alert

Health Canada is informing Canadians that Gilenya (fingolimod) product labeling has been updated with new safety information to include the risk of skin cancer, as well as progressive multifocal leukoencephalopathy (PML). Cases of PML, a rare infection caused by the John Cunningham virus, have been reported with Gilenya use including in patients who were not currently taking and had not previously taken other medications that suppress or change the immune system. Gilenya labeling currently includes information regarding the possible risk of lymphoma, and warnings about how this drug reduces the body’s ability to fight infection. Gilenya is indicated for the treatment of relapsing-remitting multiple sclerosis to reduce the frequency of attacks (relapses) and delay the progression of physical disability.

Further information can be found at http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2015/55160a-eng.php.

Avycaz Safety Alert

The FDA is warning health care providers about the risk for dosing errors with Avycaz (ceftazidime and avibactam) injection due to confusion about the drug strength displayed on the vial and carton labels. Avycaz was initially approved with the vial and carton labels displaying the individual strengths of the two active ingredients (ie, 2 gram/0.5 gram); however, the product is dosed based on the sum of the active ingredients (ie, 2.5 gram). The FDA has revised the labels to indicate that each vial contains Avycaz 2.5 gram, equivalent to ceftazidime 2 gram and avibactam 0.5 gram.

Further information may be found at: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm463595.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery.

Tramadol Safety Alert – Risks associated with off-label use in pediatric patients

The US Food and Drug Administration (FDA) is investigating the use of tramadol in children 17 years and younger because of the rare, but serious, risk of slowed or difficult breathing. The risk may be increased in children treated with tramadol for pain following tonsillectomy and/or adenoidectomy and/or who are ultrarapid metabolizers of the drug. Adverse events were reported in one child following a single dose of tramadol.

Tramadol is not FDA approved for use in children; however, data show it is being used “off-label” in the pediatric population. Health care providers should consider alternative FDA-approved pain medications for children and should instruct parents and caregivers of children taking tramadol who notice any signs of slow or shallow breathing, difficult or noisy breathing, confusion, or unusual sleepiness to discontinue the drug immediately and seek medical attention.

Further information can be found at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm463499.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery.

Humalog KwikPen New Strength

Health Canada has recently authorized Humalog (insulin lispro) KwikPen 200 units/mL. Humalog 200 units/mL solution for injection should only be administered using the supplied Humalog 200 units/mL KwikPen. There are currently 2 insulin KwikPen types available (100 units/mL and 200 units/mL). When switching between one concentration of Humalog KwikPen and the other, it is important to understand that the dose counter window on each of the 2 insulin KwikPen types indicates the number of units of insulin to be injected. The KwikPen automatically delivers the correct volume of insulin so conversion of dose between devices is not needed. Unnecessary dose conversions or transfer of the higher concentration insulin lispro 200 units/mL from the Humalog 200 units/mL KwikPen to a different insulin delivery system (syringe or infusion pump) may lead to under- or over-dosing, resulting in severely low or high blood sugar. Health Canada is communicating this important safety information to health care providers and to the public through its MedEffect Canada website.

Further information can be found at http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2015/54974a-eng.php.

Pyrimethamine Availability Alert

As of June 2015, pyrimethamine is no longer available in retail pharmacies in the United States and is only available through a special pharmacy program (http://www.daraprimdirect.com/how-to-prescribe). If there is a delay in procuring pyrimethamine, refer to appropriate guidelines for alternative drug regimens for treatment and/or prophylaxis of Toxoplasma encephalitis, Pneumocystis pneumonia, and Isospora infection. For patients with suspected or documented toxoplasmosis who do not have a history of sulfa allergy, trimethoprim-sulfamethoxazole should be used in place of pyrimethamine-containing regimens until pyrimethamine is available.

Further information may be found at https://aidsinfo.nih.gov/e-news/archive/2015/9/11.

Invokana and Invokamet Safety Alert

The FDA has strengthened the warning for the type 2 diabetes medicines Invokana and Invokamet (canagliflozin) related to the increased risk of bone fractures, and added new information about decreased bone mineral density to the product labeling. The FDA has added a new WARNING AND PRECAUTION and revised the ADVERSE REACTIONS section of the Invokana and Invokamet drug labels to address these safety concerns.

Health care professionals should consider factors that contribute to fracture risk prior to initiating canagliflozin. Patients should talk to their health care professionals about factors that may increase their risk for bone fracture. Patients should not stop or change their diabetes medicine without first talking to their health care professional.

Additional information for health care professionals:

-Bone fractures have been seen in patients taking the type 2 diabetes medicine canagliflozin.

- Fractures can occur as early as 12 weeks after starting canagliflozin.

- Canagliflozin has also been linked to decreases in bone mineral density at the hip and lower spine.

- Consider factors that contribute to fracture risk prior to initiating canagliflozin.

- Counsel patients about factors that may contribute to bone fracture risk.

Further information can be found at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm461876.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery.

Treanda Label Changes

In March 2015, the US FDA warned health care providers not to use Teva's Treanda solution for injection (45 mg/0.5 mL or 180 mg/2 mL solution) with closed system transfer devices (CSTD), adapters, and syringes containing polycarbonate or acrylonitrile-butadiene-styrene (ABS). N, N-dimethylacetamide, an ingredient in Treanda solution for injection, is incompatible with polycarbonate or ABS and causes the device to dissolve. The FDA is now providing a list of compatible devices and intravenous (IV) administration sets for use with Treanda injection based on testing performed by Teva from February through June 2015. These restrictions do not apply to Treanda lyophilized powder for injection. Therefore, solutions reconstituted from the lyophilized powder should not be mixed with the solution formulation. The FDA required label changes for both the solution and powder formulations to reflect safe preparation information.

Further information and a list of compatible products can be found at http://www.fda.gov/Drugs/DrugSafety/ucm437469.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery.

Type 2 Diabetes DPP-4 Inhibitors May Cause Severe Joint Pain

The FDA has issued a warning that the type 2 diabetes medications sitagliptin, saxagliptin, linagliptin, and alogliptin may cause joint pain that can be severe and disabling. Thirty-three cases of severe arthralgia were reported between 2006 and 2013. The time of onset of symptoms following initiation varied from 1 day to years, but in a majority of cases the pain appeared within a month of initiation. Symptoms resolved with discontinuation of the medication, although some patients had recurrence of symptoms when the medication was reinitiated or another DPP-4 (dipeptidyl peptidase-4) inhibitor was used. Patients taking DPP-4 inhibitors should contact their health care providers immediately if they experience severe and persistent joint pain. Patients should not stop taking DPP-4 inhibitors without first discussing it with their health care providers.

Further information can be found at http://www.fda.gov/Drugs/DrugSafety/ucm459579.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery.

Picato Safety Alert

The FDA issued a warning about reports of severe allergic reactions and herpes zoster (shingles) associated with the use of Picato (ingenol mebutate) gel. Cases involving severe eye injuries and skin reactions have been reported with use of Picato; however, some cases were associated with the gel not being used according to the instructions on the label. The FDA is requiring changes to the label to warn about these new safety risks and to provide additional instructions on the safe and appropriate application of the product.

Patients should not use Picatogel on an area of skin larger than, or for a longer period than, is instructed in the label. Patients should avoid applying the gel in, near, and around the mouth, lips, and eye area. Accidental transfer of Picato gel from the hands - even after washing - has occurred, including through application of makeup and insertion of contact lenses. Applying Picato gel in a manner other than that recommended in the product label has been associated with severe skin reactions and eye injuries.

Patients who experience a severe allergic reaction should stop use and seek immediate medical attention. Patients should also stop using the product and contact their health care provider if they develop hives, itching, or severe skin rash. If accidental eye exposure occurs, flush the eyes thoroughly with water and seek medical care.

Further information may be found at http://www.fda.gov/Safety/MedWatch/SafetyInformation...

Concomitant Use of Repaglinide and Clopidogrel Contraindicated in Canadian Labeling: Update

Novo Nordisk Canada and Health Canada have reviewed new safety information determining that coadministration of repaglinide and clopidogrel may lead to a significant decrease in blood glucose levels. Clopidogrel, a CYP2C8 inhibitor, may inhibit the metabolism of repaglinide, potentially increasing its systemic exposure and the risk of hypoglycemia. Health Canada has announced that a contraindication for concomitant use of these drugs has been added to the repaglinide Canadian product monograph and is being added to the clopidogrel product monograph.

Further information can be found at http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2015/54454a-eng.php.

Brintellix and Brilinta Name Confusion: Update

The FDA has issued a warning that name confusion between the antidepressant Brintellix (vortioxetine) and the antiplatelet medication Brilinta (ticagrelor) has resulted in the wrong medication being prescribed or dispensed. The FDA has determined that the main reason for the confusion between these two medications is the similarity of their brand names. Health care professionals can reduce the risk of name confusion by including the generic name of the medication, in addition to the brand name, and the indication for use when prescribing these medications.

Further information may be found at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm456569.htm

Gadolinium-Based Contrast Agents Safety Alert: Update

The FDA is investigating the risk of brain deposits following repeated use of gadolinium-based contrast agents (GBCAs) for magnetic resonance imaging (MRI). Recent publications have reported that deposits of GBCAs remain in the brains of some patients who undergo 4 or more contrast MRI scans, long after the last administration. It is unknown whether these gadolinium deposits are harmful or can lead to adverse health effects. To reduce the potential for gadolinium accumulation, health care providers should consider using GBCA only when the contrast is clinically necessary. This issue only affects GBCAs and does not apply to other types of scanning agents used for other imaging procedures. The FDA is not requiring manufacturers to make changes to the labels of GBCA products.

Further information can be found at: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm456012.htm

Pulmonary Hypertension in Infants and Newborns: Update

The FDA has issued a warning that pulmonary hypertension, a serious lung condition, has been reported in infants and newborns treated with Proglycem (diazoxide) for low blood glucose concentrations. In all cases, the pulmonary hypertension resolved or improved after diazoxide was discontinued. Health care professionals should closely monitor patients receiving diazoxide, especially those with risk factors for pulmonary hypertension (eg, meconium aspiration syndrome, respiratory distress syndrome, transient tachypnea of the newborn, pneumonia, sepsis, congenital diaphragmatic hernia, and congenital heart disease). Therapy should be discontinued if pulmonary hypertension is identified. The FDA is continuing to investigate this safety issue and will determine whether changes are needed in the Proglycem prescribing information.

Further information may be found at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm455125.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery.

Safety Alert for Codeine Cough and Cold Medicines: Update

The FDA is currently investigating the safety of using codeine-containing medicines to treat coughs and colds in children younger than 18 years. In April 2015, the European Medicines Agency (EMA) prohibited the use of codeine to treat cough and cold in children younger than 12 years and recommended against its use in children and adolescents between 12 and 18 years of age with breathing problems.

The FDA will continue to evaluate this safety issue and will consider the EMA recommendations.

Further information can be found at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm453379.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery.

Unapproved Prescription Otic Products Safety Concern: Update

The FDA has announced its intention to take enforcement action against companies that manufacture and/or distribute certain unapproved prescription otic products labeled to relieve ear pain, infection, and inflammation. Unapproved prescription ear drops containing the following ingredients are covered by this action: benzocaine; benzocaine and antipyrine; benzocaine, antipyrine, and zinc acetate; benzocaine, chloroxylenol, and hydrocortisone; chloroxylenol and pramoxine; and chloroxylenol, pramoxine, and hydrocortisone. The product labels do not state that they lack FDA approval, and health care providers may be unaware of their unapproved status. The FDA has informed the companies that the manufacturing of unapproved prescription otic products must stop. Consumers who believe they are using these products should contact their health care provider to discuss alternatives.

Further information can be found at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm453430.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery.

Safety Alert for Daytrana Patch: Update

The FDA is warning that permanent loss of skin color may occur with use of the Daytrana (methylphenidate) patch. The FDA has added a new warning to the drug label to describe this skin condition, known as chemical leukoderma. Cases reported to the FDA and described in the medical literature reported a decrease in or loss of skin color, in most cases limited to areas around where the patch application site was rotated. A small number of patients reported skin color changes in areas when the patch was not applied. Time to onset of leukoderma after initiating treatment with Daytrana ranged from 2 months to 4 years; in all reported cases the decrease in skin color was permanent. The FDA recommends that health care providers consider alternative treatments for patients who experience skin color changes.

Further information can be found at http://www.fda.gov/Drugs/DrugSafety/ucm452244.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery.

Safety Alert for Injectable Soft Tissue Fillers: Update

The FDA has reviewed information that suggests unintentional injection of soft tissue fillers into facial blood vessels can result in blocked blood vessels and restricted blood supply to tissues. This may cause vision impairment, blindness, stroke, and damage and/or death of the skin and underlying facial structures.

Reports of blood vessel blockage have been reported more often in certain injection locations, including the skin between the eyebrows and nose, in and around the nose and forehead, and around the eyes. The FDA is working with product manufacturers to update labeling to include additional warnings, precautions, and other statements regarding the risk of unintentional injection into blood vessels.

Further information can be found at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm448439.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery.

Ketoacidosis Warning with SGLT2 Inhibitors: Update

The FDA is warning that sodium-glucose transporter-2 (SGLT2) inhibitors used to treat type 2 diabetes, canagliflozin, dapagliflozin, and empagliflozin (alone or in combination products), may lead to ketoacidosis. Patients experiencing signs or symptoms of ketoacidosis (eg, difficulty breathing, nausea, vomiting, abdominal pain, confusion, unusual fatigue or sleepiness) should be evaluated and SGLT2 inhibitors should be discontinued if acidosis is confirmed. The blood glucose levels in reported cases were only slightly increased compared to those typically observed in diabetic ketoacidosis. Major illness, reduced food and fluid intake, and reduced insulin dose may contribute to ketoacidosis in patients on SGLT2 inhibitors.

Further information can be found at http://www.fda.gov/Drugs/DrugSafety/ucm446845.htm.

Safety Alert for Zerbaxa Dosing: Update

The FDA is warning health care providers about the risk of dosing errors with Zerbaxa (ceftolozane and tazobactam) injection due to confusion about the drug strength displayed on the vial and carton labeling. The vial label was initially approved with a strength reflecting each individual active ingredient (eg, ceftolozane 1 g/tazobactam 0.5 g), but the product is dosed based on the sum of these ingredients (eg, 1.5 g). To prevent medication errors, the strength on the drug labeling has been revised to reflect the sum of the 2 active ingredients. Zerbaxa vials will now list a strength of 1.5 g, equivalent to ceftolozane 1 g and tazobactam 0.5 g.

Further information is available at: http://www.fda.gov/Drugs/DrugSafety/ucm445919.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery.

Expiration Dating for Antivenin (Micrurus fulvius): Update

Wyeth Pharmaceuticals no longer manufactures Antivenin (Micrurus fulvius) (Equine Origin), and there is no alternative product licensed in the U.S. for coral snake envenomation. There is currently one lot of Antivenin (Micrurus fulvius) (Equine Origin) available for use: Lot number 4030024, with an expiration date extended through April 30, 2016.

Institutions should retain any remaining inventory of lot number 4030024 until the aforementioned expiration date. Clinicians should note that due to supply concerns, Pfizer, Inc supplies product only to direct customers on a replacement or emergency basis. To obtain antivenin, Pfizer, Inc may be reached at 800-666-7248; alternatively, clinicians may contact their local Poison Control Center at 800-222-1222 for assistance in locating antivenin. In the event licensed antivenin cannot be secured, an investigational imported antivenin may be available under an Investigational New Drug (IND) protocol with informed consent; for more information contact a local Poison Control Center at 800-222-1222 or the U.S. Food and Drug Administration (FDA) at 800-835-4709 (business hours) or 301-796-8240 (nonbusiness hours).

FDA Extends DuoDote Expiration Dates - Update

The FDA is alerting health care providers that additional lots of Meridian Medical Technologies’ DuoDote autoinjectors can be used for up to 2 years beyond the manufacturer’s labeled expiration date. The FDA is not requiring or recommending that the identified lots be relabeled with the new use date.

This updates the FDA’s May 2014 alert, which notified health care providers of a 2-year extension of the labeled expiration date of certain lots of DuoDote autoinjectors. More information can be found here http://www.fda.gov/drugs/drugsafety/ucm376367.htm?source=gov...

Compatibility Issue with Primene and Trace Elements

Baxter, in consultation with Health Canada, is informing health care providers of the potential for formation of a precipitate following addition of trace elements to Primene 10% solution, a result of a suspected interaction between trace elements and cysteine. Formation of this precipitate may result in insufficient levels of cysteine and trace elements in total parenteral nutrition (TPN) solutions. TPN and other solutions containing trace elements compounded with Primene should be administered to the patient using a 0.22 micron filter. Deficiencies of cysteine or trace elements can lead to serious health consequences. Infusion of a precipitate may lead to serious adverse effects including phlebitis, thrombophlebitis, thrombosis, and major organ dysfunction.

Further information can be found at http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2015/53019a-eng.php.

Priapism Risk with Methylphenidate Products

Purdue Pharma, Janssen, and Novartis Pharma Canada, in consultation with Health Canada, are informing health care providers of important safety information related to priapism that has been very rarely reported in patients, including children, taking methylphenidate products.

Further information can be found at http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2015/53011a-eng.php.

Updated Safety Labeling for Feraheme

The FDA has approved new labeling for Amag Pharmaceuticals? Feraheme (ferumoxytol) injection to include a Boxed Warning regarding the risk of serious, potentially fatal allergic reactions, as well as a new contraindication advising against the use of Feraheme in patients who have had an allergic reaction to any intravenous iron replacement product. Feraheme is indicated for the treatment of iron deficiency anemia in adults with chronic kidney disease.

Further information is available at http://www.fda.gov/Drugs/DrugSafety/ucm440138.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery.

Updated Labeling for Multidose Diabetes Pens

The FDA has approved labeling changes to Gilead Sciences' Harvoni (ledipasvir/sofosbuvir) and Sovaldi (sofosbuvir) to include postmarketing information regarding serious and life-threatening cases of symptomatic bradycardia. Symptomatic bradycardia has been reported with Harvoni in combination with amiodarone, or Sovaldi in combination with amiodarone and another direct-acting antiviral (eg, simeprevir). Harvoni is indicated for the treatment of chronic hepatitis C genotype 1 infection in adults; Sovaldi is indicated for the treatment of genotype 1, 2, 3, or 4 chronic hepatitis C infection in adults in combination with ribavirin or with peginterferon alfa and ribavirin. Bradycardia may occur within hours to days, but has been reported up to 2 weeks after initiating treatment. Administration of amiodarone with Harvoni or Sovaldi (in combination with another direct acting antiviral drug [eg, simeprevir]) is not recommended.

Further information can be found at http://www.fda.gov/Drugs/DrugSafety/ucm439484.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery.

Risperidone Dementia Indication Updated

Health Canada and Janssen are informing health care professionals of important updates regarding the use of risperidone for severe dementia. Use of risperidone for dementia has been limited to severe dementia of the Alzheimer type for short-term management of aggression or psychotic symptoms. This recommendation is based on evaluation of safety information related to all antipsychotic drugs that demonstrated a higher risk of cerebrovascular adverse events in patients with mixed or vascular dementia, compared with those with dementia of the Alzheimer type.

Further information can be found at http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2015/43797a-eng.php.

Dimethyl Fumarate Associated with Risk of Progressive Multifocal Leukoencephalopathy

Biogen Idec Canada, in consultation with Health Canada, is informing health care providers of important new safety information regarding the potential risk of progressive multifocal leukoencephalopathy (PML) with dimethyl fumarate. A fatal case of PML has been reported in a patient who developed severe and prolonged lymphopenia while receiving dimethyl fumarate. The product monograph will be updated to include the risk of PML and additional recommendations on lymphocyte monitoring.

Further information can be found at http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2015/43625a-eng.php.

Domperidone Associated with Serious Ventricular Arrhythmias or Sudden Cardiac Death

Apotex Incorporated, Dominion Pharmacal, Jamp Pharma Corporation, Marcan Pharmaceuticals Inc, Mylan Pharmaceuticals ULC, Pharmascience Inc, Pro Doc Limitée, Ranbaxy Pharmaceuticals Inc, Sanis Health Inc, Sivem Pharmaceuticals ULC, Teva Canada Limited, and Ratiopharm Inc, in consultation with Health Canada, are informing health care providers of new safety information regarding an increased risk of serious ventricular arrhythmias or sudden cardiac death in association with domperidone. The warning is based on epidemiological studies and recent postmarketing survey findings.

The product monograph has been revised to reflect a new recommended maximum daily dose, new restrictions of use, and stronger warnings.

Further information can be found at http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2015/43423a-eng.php

FDA Reviews Possible Risks of Pain Medicine Use During Pregnancy

Following recent reports questioning the safety of prescription and over-the-counter (OTC) pain medication when used during pregnancy, the FDA has evaluated research studies involving nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, and acetaminophen and has determined that the studies are too limited to make any recommendations. However, the FDA is warning that the use of pain medication during pregnancy should be carefully considered and pregnant women should always consult with their health care providers before taking any prescription or OTC medication. Women taking pain medication who are considering becoming pregnant should consult with their health care providers to discuss the risks and benefits associated with the use of these drugs. Health care providers are encouraged to continue following the recommendations in the drug labels when prescribing pain medication to pregnant patients.

Further information can be found at http://www.fda.gov/Safety/MedWatch/SafetyInformation...

Metoclopramide Associated with Extrapyramidal Symptoms in Children

Sandoz Canada, Apotex, Omega Laboratories Limited, and Pendopharm Division of Pharmascience, in consultation with Health Canada, is informing health care providers of important new prescribing information regarding the potential risk of extrapyramidal symptoms (EPS) in children treated with metoclopramide at the recommended dose. Metoclopramide should not be used in children less than 1 year of age as they appear to be at higher risk of EPS. Metoclopramide should not be used in children greater than 1 year of age unless treatment is clearly necessary. The product monograph has been recently revised to reflect the new recommendations.

Further information can be found at http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2015/43167a-eng.php.

Ziprasidone Associated with Rare, Potentially Fatal Skin Reactions

The FDA is warning that ziprasidone (Geodon) is associated with a condition known as drug reaction with eosinophilia and systemic symptoms (DRESS). DRESS is a rare but serious skin reaction that can progress to organ involvement. In general, DRESS is characterized by skin rash, systemic symptoms (malaise, fever, lymphedema), organ involvement (liver, kidney, lungs), and abnormal laboratory values (leukocytosis with eosinophilia, atypical lymphocytosis, increases in ALT). In case reports, DRESS appeared between 11 and 30 days after treatment with ziprasidone was initiated. A new warning for DRESS has been added to Geodon product labeling. Ziprasidone is indicated for the treatment of bipolar disorder and schizophrenia.

Further information can be found at http://www.fda.gov/Drugs/DrugSafety/ucm426391.htm.

Dietary Supplements Containing Live Bacteria or Yeast and Risk of Invasive Fungal Disease

The FDA is warning health care providers of the risks associated with the use of dietary supplements containing live bacteria or yeast in immunocompromised patients. A premature infant administered a dietary supplement, Solgar's ABC Dophilus Powder, as part of in-hospital course of treatment, developed GI mucormycosis caused by the mold Rhizopus oryzae and died. The mold was found to be present as a contaminant in an unopened container of the ABC Dophilus Powder, which is formulated to contain 3 species of live bacteria.

The FDA advises health care providers to use dietary supplements containing live bacteria or yeast in immunocompromised patients with caution. Health care providers should be aware that these products are not subject to FDA premarket safety and effectiveness review and approval or to the manufacturing and testing standards for products regulated as drugs by FDA. FDA encourages health care providers who use dietary supplements containing live bacteria or yeast as drugs (eg, to treat, mitigate, cure, or prevent a disease or condition) to submit an Investigational New Drug Application for FDA review.

Further information is available at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlerts...

CDC Advisory for 2014-2015 Influenza Season

Influenza A (H3N2) viruses have been most frequently reported this season in the United States and have been detected in almost all states. During past seasons when influenza A (H3N2) viruses were dominant, higher overall and age-specific hospitalization rates and increased mortality were observed, especially among older people, very young children, and people with certain chronic medical conditions, compared with seasons during which influenza A (H1N1) or influenza B viruses were dominant.

Data indicate that 48% of the influenza A (H3N2) viruses collected and analyzed in the U.S. from October 1 through November 22, 2014, were antigenically like the 2014 to 2015 influenza A (H3N2) vaccine component, but that 52% were antigenically different (drifted) from the H3N2 vaccine virus. In past seasons during which predominant circulating influenza viruses have been antigenically different, decreased vaccine effectiveness has been observed. However, vaccination has been found to provide some protection against drifted viruses. Because of the detection of these drifted influenza A (H3N2) viruses, the Centers for Disease Control and Prevention (CDC) is emphasizing the importance of the use of neuraminidase inhibitor antiviral medications when indicated for treatment and prevention of influenza, as an adjunct to vaccination.

Two prescription antiviral medications recommended for treatment or prevention of influenza are Tamiflu (oseltamivir) and Relenza (zanamivir). Evidence from past influenza seasons and the 2009 H1N1 pandemic has shown that treatment with neuraminidase inhibitors has clinical and public health benefit in reducing severe outcomes of influenza and, when indicated, should be initiated as soon as possible after illness onset. The CDC recommends that clinicians encourage all patients 6 months and older who have not yet received an influenza vaccine this season to be vaccinated against influenza and that patients with influenza-like illness who are at high risk for influenza complications seek care promptly to determine if treatment with influenza antiviral medications is warranted.

Updated Administration Recommendations for Feraheme Announced by Health Canada

Health Canada is informing health care providers of pending labeling changes for Takeda's Feraheme (ferumoxytol), regarding its administration. To reduce the risk of serious hypersensitivity reactions, Health Canada recommends that Feraheme only be administered as an intravenous (IV) infusion in 50 to 250 mL of normal saline or dextrose 5% water over a minimum of 15 minutes; administration by direct IV injection of the undiluted product is no longer recommended. Patients should be closely monitored for signs and symptoms of hypersensitivity reactions, including monitoring blood pressure and pulse during and for at least 30 minutes following each infusion.

Further labeling changes include a contraindication in patients with any known history of drug allergy and warnings regarding potentially more severe outcomes in elderly patients (> 65 years of age) or patients with multiple comorbidities who experience a serious hypersensitivity reaction due to Feraheme. It is also recommended that patients be placed in a reclined or semireclined position during infusion and for at least 30 minutes thereafter.

Further information is available at http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2014/42607a-eng.php.

Updated Safety and Dosing Information for Imovane

Sanofi-aventis Canada, in consultation with Health Canada, is informing health care providers of new dosing instructions for Imovane (zopiclone) due to the risk of next-day CNS impairment. The recommended starting dose has been reduced to 3.75 mg. The prescribed dose should not exceed 5 mg in elderly patients, patients with hepatic or renal impairment, or those currently treated with potent CYP3A4 inhibitors. Patients should be instructed to wait for at least 12 hours after dosing before driving or engaging in other activities requiring full mental alertness.

Expiration Dating for Antivenin (Micrurus fulvius): Update

Wyeth Pharmaceuticals no longer manufactures Antivenin (Micrurus fulvius) (Equine Origin), and there is no alternative product licensed in the U.S. for coral snake envenomation. There is currently one lot of Antivenin (Micrurus fulvius) (Equine Origin) available for use: Lot number 4030024, with an expiration date extended through April 30, 2015. Lot number 4030026 expired October 31, 2014, with no further extension of the expiration date.

Institutions should retain any remaining inventory of lot number 4030024 until the aforementioned expiration date. Clinicians should note that due to supply concerns, Pfizer, Inc supplies product only to direct customers on a replacement or emergency basis. To obtain antivenin, Pfizer, Inc may be reached at 800-666-7248; alternatively, clinicians may contact their local Poison Control Center at 800-222-1222 for assistance in locating antivenin. In the event licensed antivenin cannot be secured, an investigational imported antivenin may be available under an Investigational New Drug (IND) protocol with informed consent; for more information contact a local Poison Control Center at 800-222-1222 or the U.S. Food and Drug Administration (FDA) at 800-835-4709 (business hours) or 301-796-8240 (nonbusiness hours).

Updated Safety Information for Reminyl ER Capsules

Janssen Inc, in consultation with Health Canada, is informing health care providers of new safety information regarding the risk of serious skin reactions (Stevens Johnson syndrome, acute generalized exanthematous pustulosis, and erythema multiforme) associated with the use of Reminyl ER and the generic versions of galantamine. Patients should be instructed to inform their health care provider immediately if they notice any skin reaction; galantamine should be discontinued at the first appearance of skin rash. Reminyl ER is indicated for the symptomatic treatment of patients with mild to moderate dementia of the Alzheimer type.

Further information is available at http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2014/42235a-eng.php

FDA Extends Expiration Dates for Certain Meridian Autoinjectors

The FDA is alerting health care providers and emergency responders that certain lots of AtroPen (atropine), CANA (diazepam), morphine sulfate, and pralidoxime chloride autoinjectors manufactured by Meridian Medical Technologies can be used for up to 1 year beyond the labeled expiration date, which should help mitigate potential shortages of these drugs. To ensure patient safety, products should be stored under the manufacturer's labeled storage conditions.

Additional information may be found at http://www.fda.gov/Drugs/DrugSafety/ucm376367.htm.

Canadian Labeling Updated for Immunoglobulin Products

Health Canada is updating prescribing information for all immunoglobulin products with strengthened warnings on the rare but serious risk of thrombosis. Thrombosis has been reported in patients with and without risk factors and can occur regardless of immunoglobulin dose or route of administration.

Updated Safety and Dosing Information for Diclofenac Tablets and Suppositories

Novartis Pharma Canada, Pfizer Canada, and Health Canada are informing health care providers of new safety and dosing information for diclofenac tablets and suppositories (eg, Voltaren/Voltaren SR, Voltaren Rapide, Arthrotec) because of an increased risk of myocardial infarction or stroke, especially at high doses (150 mg/day). Treatment with diclofenac tablets and suppositories is not recommended in patients with a history of, or risk factors for, cardiac disease, stroke, or uncontrolled hypertension. The recommended maximum daily dose for diclofenac tablets and suppositories has also been decreased to 100 mg/day. Diclofenac is a nonsteroidal anti-inflammatory drug used to relieve pain and inflammation.

Further information is available at http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2014/41703a-eng.php.

Updated Safety Information for Xolair

The FDA has reviewed safety studies that suggest a slightly increased risk of serious cardiovascular and cerebrovascular adverse events in patients being treated with Xolair (omalizumab). The review found no difference in the rates of cancer between patients treated with Xolair and those not treated with Xolair, but a potential cancer risk cannot be ruled out due to study limitations.

Further information is available at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm416408.htm.

Influenza Virus Vaccine 2014–2015

The vaccine strains approved for the 2014-2015 season in the United States are as follows: Trivalent influenza vaccines will contain an A/California/7/2009 (H1N1)-like virus, an A/Texas/50/2012 (H3N2)-like virus, and a B/Massachusetts/2/2012-like virus. Quadrivalent vaccines will include an additional vaccine virus, a B/Brisbane/60/2008-like virus. These are identical to the 2013-2014 season vaccine, but patients who received the previous year vaccine still need to be vaccinated due to the limited duration of protection provided. The Advisory Committee on Immunization Practices (ACIP) recommends that health care providers begin offering vaccination as soon as the vaccine becomes available, and if possible, by October. Several types of influenza virus vaccine will be available for this season including a trivalent inactivated influenza vaccine (IIV3), quadrivalent inactivated influenza vaccine (IIV4), trivalent recombinant influenza vaccine (RIV3), and a quadrivalent live-attenuated influenza vaccine (LAIV4). When more than one type of vaccine is appropriate (based on indications and recommendations) and available the ACIP does not have a preferential recommendation for use of one product over another. The ACIP continues to recommend annual vaccination for all persons =6 months of age.

For a summary of information, refer to the following CDC website: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6332a3.htm

Risk of Contamination with Amsacrine (AMSA PD Injection)

ERFA Canada 2012 Inc and Health Canada are informing health care professionals of a potential, but very low, risk of infection with the product AMSA PD Inj 50 mg/mL (amsacrine injection). A recall has not been implemented because the risk of contamination is minimal. Contamination risk may be further minimized by the use of Sartorius sterile filters (Minisart SRP [PTFE] 0.2 micrometer, 15 mm) prior to transferring AMSA PD Inj 50 mg/mL to the diluents. These filters will be provided by ERFA Canada 2012 Inc. Health care professionals should monitor their patients treated with AMSA PD Inj 50 mg/mL for any signs or symptoms of infection.

AMSA PD is indicated for the induction of remission in acute adult leukemia refractory to conventional therapy.

Further information is available at http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2014/41245a-eng.php.

Rescheduling of Hydrocodone Combination Products From Schedule III to Schedule II

The U.S. Drug Enforcement Agency (DEA) announced that hydrocodone combination products will be placed into Schedule II of the Controlled Substances Act (CSA) effective October 6, 2014. All single ingredient hydrocodone products (eg, Zohydro ER) are already in Schedule II of the CSA and are not impacted by this action.

More information is available at https://www.federalregister.gov/articles/2014/08/22/2014-19922/schedules-of-controlled-substances-rescheduling-of-hydrocodone-combination-products-from-schedule.

Updated Safety Information for Arzerra

GlaxoSmithKline Inc and Health Canada are informing health care professionals of updates to safety information regarding infusion reactions related to Arzerra (ofatumumab), indicated for the treatment of chronic lymphocytic leukemia (CLL). A severe infusion reaction resulting in death was reported in a patient with CLL given Arzerra. Prescribing information for Arzerra is being revised to include information regarding the potential for fatal infusion reactions.

More information can be found at http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2014/40853a-eng.php.

NuvaRing Safety Information

New usage restrictions for NuvaRing (etonogestrel/ethinyl estradiol slow-release vaginal ring), prescribed for birth control, have been released by Merck Canada in collaboration with Health Canada. NuvaRing should not be used by women who smoke and are older than 35 years of age, or who have more than 1 or a serious form of the following: Heart problems, high blood pressure, blood tests indicating abnormal levels of fats or substances that control blood clotting, diabetes, or limited ability to move around for a long time after an operation. NuvaRing should also not be used by women who experience migraine headaches with vision problems, or constant stomach pains caused by pancreas problems along with high levels of fat in the blood.

More information can be found at http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2014/40841a-eng.php.

Temporary Importation of Zinc Injectable 1 mg/mL Solution

Due to a critical shortage of zinc injection in the U.S., the FDA is coordinating with Laboratoire Aguettant to increase the availability of these products. Laboratoire Aguettant has initiated temporary importation of the non-FDA approved drug zinc injectable 1 mg/mL (zinc gluconate trihydrate) solution for infusion (lot T-7506C, expiration date February 2, 2015; lot T-7519C, expiration date March 3, 2015) through its U.S. distributor Baxter Healthcare Corporation. This product is manufactured at an FDA-inspected facility in France and displays the original French product labels. A product comparison table with French prescribing information translated into English is included in the link below. Zinc injectable 1 mg/mL (zinc gluconate trihydrate) solution for infusion is meant to be used in the same way as U.S. marketed drugs, with notation to a difference in maximum potential aluminum content.

More information can be found at http://www.fda.gov/downloads/Drugs/DrugSafety/DrugShortages/UCM373067.pdf.

Updated Feraheme Safety Information

Takeda Canada Inc and Health Canada are informing health care professionals that Feraheme (ferumoxytol) intravenous solution should not be used in patients who are allergic to other iron products given by injection or infusion, or in patients with multiple drug allergies. Life-threatening and sometimes fatal allergic reactions have occurred with the use of Feraheme; because of this, it should only be given in settings where appropriate therapies for the treatment of severe allergic reactions are immediately available.

Further information can be found at http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2014/40507a-eng.php.

Black Widow Spider Antivenin Expanded Expiration Date

Merck is extending the expiration date of one packaged lot (H019984) of antivenin (Latrodectus mactans), commonly referred to as black widow spider antivenin (BWSA), until January 3, 2015. The labeled expiration date is March 31, 2014. Lot number 0672105 of antivenin, included in this packaged lot, may be used until its expiration date of January 3, 2015.

Do not use the expired diluent packaged within lot number H019984. The expiration for the sterile diluent, lot number 0671078, supplied with this lot has not been extended. Instead, reconstitute the antivenin with 2.5 mL of sterile water for injection.

Do not discard any antivenin from lot number 0672105; keep available for use until January 3, 2015. For questions, call the Merck National Service Center at 1-800-672-6372.

New Boxed Warning for Lidocaine Viscous

The FDA is requiring a Boxed Warning for lidocaine topical 2% (viscous) solution alerting health care providers and caregivers against its use in treating teething pain in infants and children, which may cause serious harm, including death. When too much viscous lidocaine is given to infants and young children, or if they accidentally swallow too much, seizures, severe brain injury, and cardiac problems may result.

Reports of serious adverse events (including death) in infants and young children 5 months to 3.5 years of age given lidocaine 2% viscous solution for mouth pain (including pain due to teething and stomatitis), or with accidental ingestion, have been reviewed by the FDA.

The American Academy of Pediatrics recommends managing teething pain with a chilled (not frozen) teething ring or gently rubbing/massaging with the caregiver's finger. The FDA recommends against using topical OTC medications for teething pain as some products may cause harm.

Further information can be found at http://www.fda.gov/Safety/MedWatch/SafetyInformation/....

Warning of Hypersensitivity Reactions for OTC Acne Products

The FDA is warning that certain over-the-counter (OTC) topical acne products marketed under various brand names may cause rare but serious and potentially life-threatening allergic reactions or severe irritation. Consumers should stop using their topical OTC acne product if they develop hives or itching and should stop using the product and seek emergency medical attention immediately if they experience hypersensitivity reactions such as throat tightness; difficulty breathing; feeling faint; or swelling of the eyes, face, lips, or tongue. The hypersensitivity reactions may occur within minutes to a day or longer after product use and differ from local skin irritation (redness, burning, dryness, itching, peeling or slight swelling) that may occur at the site of product application. It cannot be determined if the serious hypersensitivity reactions were triggered by the active ingredients in the acne products (benzoyl peroxide or salicylic acid), the inactive ingredients, or by a combination of both. The FDA is monitoring and evaluating this safety issue and will work with manufacturers regarding any future label changes that would address the risk of severe hypersensitivity reactions.

Before using a topical OTC acne drug product for the first time, consumers should apply a small amount to 1 or 2 small affected areas for 3 days to make sure they do not develop hypersensitivity symptoms.

Further information is available at: http://www.fda.gov/Drugs/DrugSafety/ucm400923.htm

Cardiovascular Risks with Olmesartan for Diabetics Not Conclusive

The FDA has completed its safety review of olmesartan and has found no clear evidence of increased cardiovascular risks associated with olmesartan in diabetic patients. After evaluating the study that prompted the review (the Randomized Olmesartan and Diabetes Microalbuminuria Prevention trial), additional studies, and a large study in Medicare patients, the FDA believes the benefits of olmesartan in patients with high blood pressure continue to outweigh potential risks. Patients should not stop taking olmesartan or any blood pressure medication without first discussing it with their health care provider. Recommendations for olmesartan use remain the same, although the FDA will require information regarding some of the studies to be included in the prescribing information.

Further information is available at http://www.fda.gov/Safety/MedWatch/SafetyInformation/....

Treatment with Docetaxel Products May Cause Symptoms of Alcohol Intoxication

The FDA is warning health care providers and patients that docetaxel injection products contain ethanol, which may cause patients to experience symptoms of alcohol intoxication during and after treatment. The FDA is revising the labels of all docetaxel drug products to warn about this risk. Health care providers should consider the alcohol content of docetaxel products when prescribing or administering the drug to patients, particularly in those whom alcohol intake should be avoided or minimized and when using it in conjunction with other medications. Patients should avoid driving, operating machinery, or performing other activities that are dangerous for one to two hours after docetaxel infusion.

Further information is available at: http://www.fda.gov/Drugs/DrugSafety/ucm401752.htm

New Dosing for Zofran in Elderly Patients

Health Canada and GlaxoSmithKline are informing health care providers and patients of new dosing and administration restrictions for intravenous (I.V.) Zofran (ondansetron) to mitigate the risk of QT prolongation in patients older than 65 years of age. In these patients, the risk of QT prolongation is expected to be greater with faster infusion rates and larger doses. In patients 75 years and older, the initial I.V. dose must not exceed 8 mg; in patients younger than 75 years, the initial I.V. dose must not exceed 16 mg. Subsequent doses must not exceed 8 mg and may be given 4 to 8 hours after the initial dose. All I.V. doses must be diluted in 50 to 100 mL of saline or other compatible fluid and must be infused over no less than 15 minutes.

Further information is available at http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2014/39943a-eng.php.

Risk of Anaphylaxis and Toxic Epidermal Necrolysis With Terazol

Health Canada and Janssen are informing health care providers and patients that anaphylaxis and toxic epidermal necrolysis (TEN) have been reported rarely with Terazol 7 vaginal cream 0.4% and Terazol 3 Dual-Pak vaginal cream 0.8%/vaginal ovules 80 mg (terconazole); patients should be instructed to discontinue use of the product if signs or symptoms of serious allergic reactions occur and to call their doctor or pharmacist immediately.

Further information is available at http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2014/39915a-eng.php.

Campath Withdrawn From Market to be Relaunched as Lemtrada: Update

Sanofi withdrew its leukemia therapy Campath (alemtuzumab) from the U.S. market in September 2012 to prepare for a relaunch (under the name Lemtrada) at a lower dose to treat relapsing-remitting multiple sclerosis (MS). Genzyme, a Sanofi company, had originally anticipated Lemtrada might be launched in 2013. However, the FDA issued a Complete Response Letter to Genzyme in December 2013, indicating Lemtrada is not ready for approval. Genzyme has resubmitted its supplemental Biologics License Application (sBLA) for Lemtrada in May 2014 and expects FDA action on the sBLA in the fourth quarter.

Campath remains accessible (free of charge) through the Campath Distribution Program for the treatment of B-cell chronic lymphocytic leukemia and select unlabeled uses.

For additional information, please refer to the following:

http://news.genzyme.com/press-release/genzymes-lemtrada-resubmission-accepted-review-fda

http://news.genzyme.com/press-release/genzyme-receives-complete-response-letter-fda-lemtrada-alemtuzumab-application

http://www.campath.com

Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Reported with Vectibix

Health Canada and Amgen Canada are informing health care providers that Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported rarely with Vectibix (panitumumab) use; health care providers should monitor patients for dermatologic and soft tissue signs or symptoms, and should also consider withholding or discontinuing Vectibix in patients with severe or life-threatening and inflammatory or infectious complications.

Further information is available at http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2014/39581a-eng.php

FDA Lowers Recommended Eszopiclone (Lunesta) Dose

The FDA is requiring the starting dose of Lunesta (eszopiclone) oral tablets, indicated for the treatment of insomnia, to be lowered to 1 mg at bedtime. The change was prompted after a study found that the previously recommended dose of 3 mg can cause impairment to driving skills, memory, and coordination lasting more than 11 hours after dosing. The 1 mg starting dose is recommended for women and men because they are both equally susceptible. If needed, the dose can be increased to 2 or 3 mg, but higher doses are more likely to result in next-day impairment. Patients taking a 3 mg dose should be cautioned against driving and other activities that require complete mental alertness the day after use.

For more information, see http://www.fda.gov/downloads/Drugs/DrugSafety/UCM397277.pdf

FDA Extends DuoDote Expiration Dates - Update

The FDA is alerting health care providers that additional lots of Meridian Medical Technologies' DuoDote autoinjectors can be used for up to 2 years beyond the manufacturer's labeled expiration date. The FDA is not requiring or recommending that the identified lots be relabeled with the new use date.

This updates the FDA's March 2014 alert, which notified health care providers of a 2-year extension of the labeled expiration date of certain lots of DuoDote autoinjectors. More information can be found here http://www.fda.gov/drugs/drugsafety/ucm376367.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery

Serotonin Blocking Drugs and Risk of Serotonin Syndrome

Health Canada has completed a safety review on the serotonin blocking drugs dolasetron (Anzemet), granisetron (Kytril), ondansetron (Zofran), and palonosetron (Aloxi), indicated for treating nausea and vomiting due to cancer therapy, and have identified a potential risk of serotonin syndrome with their use. The review by Health Canada was prompted by a 2012 article in the World Health Organization (WHO) Pharmaceuticals Newsletter indicating that ondansetron, when used concomitantly with other serotonergic agents, may lead to the development of serotonin syndrome in susceptible patients. In the Health Canada review, literature and a number of reports, including international reports and two Canadian case reports, were identified.

Serotonin syndrome occurs when serotonin, a chemical normally found in the body, accumulates to high levels. Symptoms of serotonin syndrome may include agitation, confusion, fast heartbeat, muscle twitching or stiffness, fever, loss of consciousness, or coma. If untreated, serotonin syndrome can be fatal.

Health Canada has requested that manufacturers update the Canadian product monograph. Aloxi, Kytril, and Zofran now contain the new safety information; Anzemet has recently been withdrawn from the Canadian market by the manufacturer.

Nitroglycerin in Dextrose 5% Injection Shortage and Import of Nitronal (glyceryl trinitrate)

The U.S. Food and Drug Administration (FDA) is temporarily allowing the import of Nitronal (glyceryl trinitrate) through Arbor Pharmaceuticals from G. Pohl Boskamp GmbH & Co. KG (Pohl-Boskamp), Germany to alleviate the nitroglycerin in dextrose 5% shortage. Nitronal is different from other injectable nitroglycerin products in the United States. Nitronal is available in 25 mL ampuls and 50 mL vials at a concentration of 1 mg/mL which may be diluted to obtain similar concentrations to the FDA-approved products. To place an order, please contact Arbor Pharmaceuticals, LLC at 1-866-516-4950, extension 0 (Monday - Friday 9:00 am to 5:00 pm Eastern Daylight Time), or email GMB-SPS-ARBOR@cordlogistics.com.

FDA Recommends Acetaminophen 325 mg or Less Per Dosage Unit: Update

In follow-up to the January 2014 MedWatch Safety Alert, FDA is reminding health care providers to discontinue prescribing and dispensing prescription combination drug products that contain more than acetaminophen 325 mg per tablet, capsule, or other dosage unit. These products are no longer considered safe by FDA.

Although these products were voluntarily withdrawn by the manufacturers at FDA's request, some prescription combination drug products containing more than acetaminophen 325 mg per dosage unit may remain available. Pharmacists are encouraged to return these products to the wholesaler or manufacturer; wholesalers are requested to remove product codes for all prescription combination drug products containing more than acetaminophen 325 mg per dosage unit from ordering systems and return products to manufacturers.

The FDA recommends that a pharmacist who receives a prescription for a combination product with more than acetaminophen 325 mg per dosage unit should contact the prescriber to discuss a product with a lower dose of acetaminophen.

For additional information, please refer to the following:
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm381650.htm

Epidural Corticosteroid Injection May Cause Neurologic Complications

The FDA is warning that epidural injection of corticosteroids, such as methylprednisolone, hydrocortisone, triamcinolone, betamethasone, and dexamethasone, may result in rare but serious adverse events, including loss of vision, stroke, paralysis, and death. The injections are administered to treat neck and back pain, as well as radiating pain in the arms and legs. The safety and effectiveness of epidural corticosteroid administration have not been established; this use is not FDA-approved. The FDA is requiring the addition of a Warning to the drug labels of injectable corticosteroids describing these risks.

Patients should discuss the benefits and risks of epidural corticosteroid injections with their health care providers, along with the benefits and risks associated with other possible treatments.

For additional information, please refer to the following:
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm394530.htm

Extension of Expiration Dating for Antivenin (Micrurus fulvius): Update

Wyeth Pharmaceuticals (a subsidiary of Pfizer, Inc) has announced that the expiration date of one lot of antivenin, lot number 4030024, has been extended through April 30, 2015. Wyeth Pharmaceuticals no longer manufactures Antivenin (Micrurus fulvius) (Equine Origin), and there is no alternative product licensed in the U.S. for coral snake envenomation. There are currently 2 lots of Antivenin (Micrurus fulvius) (Equine Origin) available for use including lot number 4030024 and lot number 4030026, with an expiration date of October 31, 2014.

Institutions should retain any remaining inventory of either lot number 4030024 or 4030026 until the aforementioned expiration dates. Clinicians should note that due to supply concerns, Pfizer, Inc supplies product only to direct customers on a replacement or emergency basis. To obtain antivenin, Pfizer, Inc may be reached at 800-666-7248; alternatively, clinicians may contact their local Poison Control Center at 800-222-1222 for assistance in locating antivenin. In the event licensed antivenin cannot be secured, an investigational imported antivenin may be available under an Investigational New Drug (IND) protocol with informed consent; for more information contact a local Poison Control Center at 800-222-1222 or the U.S. Food and Drug Administration (FDA) at 800-835-4709 (business hours) or 301-796-8240 (nonbusiness hours).

Safety Alert for Neupogen and Neulasta - Canada

Amgen Canada Inc, and Health Canada are informing health care professionals of the risk of capillary leak syndrome (CLS) associated with the use of granulocyte colony stimulating factors Neupogen (filgrastim) and Neulasta (pegfilgrastim). CLS has been reported in patients undergoing chemotherapy who were receiving Neupogen or Neulasta, as well as in donors undergoing peripheral blood progenitor cell mobilization who were receiving Neupogen. CLS can cause circulatory shock and may be fatal. It is associated with hypotension, hemoconcentration, generalized edema and hypoalbuminemia, and episodes can vary in frequency and severity. Patients should be advised to contact their health care provider if they develop symptoms of CLS. Neupogen or Neulasta should be discontinued if CLS is suspected and patients should be closely monitored.

For additional information, please refer to the following:
http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2014/38893a-eng.php

Campath Withdrawn From Market to be Relaunched as Lemtrada: Update

Sanofi withdrew its leukemia therapy Campath (alemtuzumab) from the U.S. market in September 2012 to prepare for a relaunch (under the name Lemtrada) at a lower dose to treat relapsing-remitting multiple sclerosis (MS). Genzyme, a Sanofi company, had originally anticipated Lemtrada might be launched in 2013. However, the FDA issued a Complete Response Letter to Genzyme in December 2013, indicating Lemtrada is not ready for approval. In April 2014, Genzyme announced plans to resubmit its supplemental Biologics License Application (sBLA) for Lemtrada to the FDA during the second quarter.

Campath remains accessible (free of charge) through the Campath Distribution Program for the treatment of B-cell chronic lymphocytic leukemia and select unlabeled uses.

For additional information, please refer to the following:
http://news.genzyme.com/press-release/genzyme-receives-complete-response-letter-fda-lemtrada-alemtuzumab-application
http://news.genzyme.com/press-release/genzyme-resubmit-lemtradatm-application-fda-review
http://www.campath.com

Liver Problems Reported with Zelboraf – Canadian

Health Canada and Roche Canada are informing patients that liver problems, including severe problems, have been reported with Zelboraf (vemurafenib) use; health care providers should monitor patients for signs of liver problems by utilizing appropriate blood tests before starting Zelboraf therapy and monthly, or as appropriate, while taking Zelboraf. Patients should contact their health care provider immediately if they notice yellowing skin or the whites of the eyes; tiredness; dark or brown urine; severe itching; nausea or vomiting; or loss of appetite

Further information may be found at
http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2014/38869a-eng.php.

Revatio Safety Alert

The FDA is clarifying the strength of a warning statement communicated previously in the Revatio (sildenafil) product labeling regarding its use in children with pulmonary arterial hypertension (PAH). Revatio is approved only to treat PAH in adults, not in children. However, health care providers must consider whether the benefits of treatment with Revatio are likely to outweigh its potential risks for each patient. After increased mortality was observed with high Revatio doses in pediatric patients in a long-term clinical trial, the FDA revised labeling for Revatio in August 2012 to say that its use, especially long-term use, is not recommended in children. However, situations may exist in which the benefit-risk profile of Revatio may make its use, with close monitoring, acceptable in individual children, for example, when other treatment options are limited.

For more information, refer to
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm391152.htm.

Remeron and Remeron RD Associated With QT Prolongation/Torsades de Pointes

Health Canada is informing customers of new warnings for Remeron and Remeron RD (mirtazapine) regarding postmarketing cases of QT prolongation and torsades de pointes reported with the use of mirtazapine. Most cases occurred in association with drug overdose or in patients with risk factors for QT prolongation, including concomitant use of QT-prolonging medications. Serious outcomes including torsades de pointes and death have been reported with mirtazapine overdose.

More information can be found at
http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2014/38709a-eng.php.

Black Widow Spider Antivenin Expanded Expiration Date

Merck is extending the expiration date of one packaged lot (H019984) of antivenin (Latrodectus mactans), commonly referred to as black widow spider antivenin (BWSA), until July 8, 2014. The labeled expiration date is March 31, 2014. Lot number 0672105 of antivenin, included in this packaged lot, may be used until its expiration date of July 8, 2014.

Do not use the expired diluent packaged within lot number H019984. The expiration for the sterile diluent, lot number 0671078, supplied with this lot has not been extended. Instead, reconstitute the antivenin with 2.5 mL of sterile water for injection.

Do not discard any antivenin from lot number 0672105; keep available for use until July 8, 2014. For questions, call the Merck National Service Center at 1-800-672-6372.

Further information is available at:
http://www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/ucm390808.htm.

Safety Alert for Imuran and Purinethol – Canada

Health Canada and manufacturers Triton Pharma Inc., and Teva Canada Ltd., are informing health care providers that cases of hepatosplenic T-cell lymphoma (HSTCL) have been reported in patients with inflammatory bowel disease (IBD) treated with Imuran (azathioprine) or Purinethol (mercaptopurine). Labeling for these drugs has been updated to include information about the associated risk of HSTCL.

Imuran is indicated for the treatment of rheumatoid arthritis in adults and to help prevent kidney transplant rejection; Purinethol is indicated for the treatment of certain kinds of leukemia. Neither drug is indicated for the treatment of IBD.

Further information is available at:
http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2014/38693a-eng.php.

Safety Alert for Effexor XR 150 mg and Venlafaxine HCl 150 mg Extended-Release Capsules

Pfizer Inc is voluntarily recalling particular lots of venlafaxine 150 mg extended-release capsules due to the possible presence of Tikosyn (dofetilide) 0.25 mg capsules within the same package. Accidental ingestion of dofetilide in patients taking venlafaxine could lead to serious (some potentially fatal) adverse effects, including QT prolongation.

Affected lots of venlafaxine 150 mg extended-release capsules include:

Effexor XR (venlafaxine HCl) 150 mg extended-release capsules: Lots V130140 and V130142

Greenstone LLC-branded Venlafaxine HCl 150 mg extended-release capsules: Lot V130014

Pharmacists should immediately quarantine, discontinue distribution of, and return all recalled lots of these products, as well as notify any of their customers to whom they distributed the products. Patients with affected product should notify their health care providers and/or return the product to their pharmacies.

Customers are being notified by UPS next day mail, and Pfizer is arranging for the return of all recalled products. Patients with questions regarding the return of product should contact Stericycle at 1-888-345-0481 (Monday through Friday, 8 AM to 5 PM ET). Patients with questions regarding this recall can contact Pfizer Medical Information at 1-800-438-1985 (Monday through Thursday, 9 AM to 8 PM ET or Friday, 9 AM to 5 PM ET).

For more information, refer to:
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm388352.htm.

Safety Alert for Doribax

The FDA has concluded that Doribax (doripenem) carries an increased risk of death and lower clinical cure rates compared with use of Primaxim (imipenem and cilastatin) for injection when used to treat ventilator-associated pneumonia. Based on an FDA analysis of data from a 3-year clinical trial that was prematurely stopped in 2011 due to these safety concerns, the FDA approved changes to the Doribax prescribing information which now includes a new warning about this unapproved use. Doribax is not approved to treat any type of pneumonia.

Health care providers should consider whether the benefits of Doribax treatment are likely to exceed its potential risks in patients who develop ventilator-associated pneumonia. Doribax is still considered safe and effective for its FDA-approved indications.

For more information, refer to:
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm388328.htm.

Meningococcal Disease Outbreak: Update

Novartis is providing serogroup B meningococcal vaccine (Bexsero) to the University of California Santa Barbara (UCSB) as part of a vaccination program to protect against meningitis B outbreaks. In December, the FDA approved the use of Bexsero under an Investigational New Drug application in response to a meningitis B outbreak at Princeton University. More than 5000 students were vaccinated at Princeton University, and 20,000 students will be offered vaccination at UCSB. Novartis is pursuing a license that would make Bexsero available in the United States. Currently, Bexsero is only approved for use in Europe, Canada, and Australia.

Meningococcal disease is caused by multiple serogroups of Neisseria meningitidis. These bacteria can cause serious infections including meningococcal meningitis and meningococcal septicemia. There are 5 main serogroups ("strains") of meningococcal bacteria: A, B, C, Y, and W. In the U.S., serogroups B, C, and Y cause the majority of the disease. Meningococcal vaccines in routine use in the U.S. include meningococcal polysaccharide vaccine (Menomune) and meningococcal conjugate vaccine (Menactra, Menveo, and MenHibrix). These vaccines help provide immunity for the following serogroups: A, C, W-135, and Y. There are currently no approved vaccines in the U.S. to provide immunity for serogroup B. The serogroup B meningococcal vaccine provided to Princeton University and UCSB is expected to cover 91% of circulating serogroup B meningococcus strains that cause disease in the U.S. and protect against the exact strain, ST409, causing the outbreak at the universities.

For more information, refer to the following websites:
http://www.cdc.gov/meningococcal/outbreaks/ucsb.html.
http://www.cdc.gov/meningococcal/outbreaks/princeton.html
http://www.novartis.com/newsroom/media-releases/en/2014/1763969.shtml

Safety Alert for Saxagliptin and Metformin

The FDA has requested clinical trial data from the manufacturer of saxagliptin to investigate a possible association with heart failure. A study published in the New England Journal of Medicine reported an increased rate of hospitalization for heart failure with use of saxagliptin (marketed as Onglyza and Kombiglyze XR) compared with an inactive treatment. The study did not find increased rates of death or other major cardiovascular risks, including heart attack or stroke, in patients who received saxagliptin. The manufacturer is expected to submit the trial data to the FDA by early March 2014, after which a thorough analysis and report of the findings will be conducted.

Patients should not discontinue saxagliptin treatment and should speak with their health care providers about any questions or concerns. Health care providers should continue to follow the prescribing recommendations in the drug labels.

For additional information, please refer to http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm385471.htm.

Campath Withdrawn From Market to be Relaunched as Lemtrada: Update

Sanofi withdrew its leukemia therapy Campath (alemtuzumab) from the U.S. market in September 2012 to prepare for a relaunch (under the name Lemtrada) at a lower dose to treat relapsing-remitting multiple sclerosis (MS). Genzyme, a Sanofi company, had originally anticipated Lemtrada might be launched in 2013. However, the FDA issued a Complete Response Letter to Genzyme in December 2013, indicating Lemtrada is not ready for approval.

Campath remains accessible (free of charge) through the Campath Distribution Program for the treatment of B-cell chronic lymphocytic leukemia and select unlabeled uses.

For additional information, please refer to http://news.genzyme.com/press-release/genzyme-receives-complete-response-letter-fda-lemtrada-alemtuzumab-application or http://www.campath.com.

New Safety Information for Cosopt

Merck Canada Inc., in consultation with Health Canada, is informing health care professionals and patients of the potential risk of eye injury (cuts, scratches) that can occur due to a change in the design of the unit dose pipette for Cosopt Preservative-Free Ophthalmic Solution. Health Canada is aware of nine reports of eye injury that may be associated with the use of the newly designed fin-tipped pipette in which plastic is left in place after the tab is twisted off. Therefore, it is important that the tip or fins of the pipette do NOT touch the eye or surrounding area of the eye. Merck Canada Inc. is working to introduce to the market a new revised pipette design later in 2014. In the interim, the manufacturer has introduced a warning sticker on the outer carton and updated the instructions in the product information.

Any case of eye injury or adverse reactions/product complaints in patients receiving Cosopt Preservative-Free should be reported to Merck Canada Inc. or Health Canada. Medication errors can also be reported to the Institute for Safe Medication Practices (ISMP) Canada through the Canadian Medication Incident Reporting and Prevention System.

Further information may be found at http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2014/37909a-eng.php

New Safety Information for Lithium

Health Canada is informing health care professionals and patients of new safety information and treatment recommendations regarding lithium and the risk of hypercalcemia sometimes associated with hyperparathyroidism.

Product labeling for lithium already includes a warning of the risk of hypercalcemia with or without hyperparathyroidism. Health Canada is currently working with manufacturers to update product labels for lithium to include new warnings regarding the risk of hypercalcemia and hyperparathyroidism, as well as the need to consider calcium monitoring before initiating lithium, after 6 months on therapy, and annually during long-term therapy.

Additional information is available at http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2014/37933a-eng.php

Testosterone Product Safety Alert

The FDA is investigating the risk of stroke, heart attack, and death in men taking FDA-approved testosterone products. The FDA is evaluating information from 2 separate studies that suggest an increased risk of cardiovascular events among groups of men prescribed testosterone therapy, although the agency has not concluded that these products increase the risk of stroke, heart attack, or death. Testosterone products are indicated for replacement therapy in conditions associated with a deficiency or absence of endogenous testosterone. Patients should not stop taking prescribed testosterone products without first discussing any questions or concerns with their health care providers. Health care providers should consider whether the benefits of FDA-approved testosterone treatment are likely to exceed the potential risk of treatment. The FDA will communicate final conclusions and recommendations when the evaluation is complete.

Additional information is available at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm384225.htm

Health Canada Evaluating Emergency Contraception Effectiveness Data

Health Canada is evaluating the effectiveness of emergency contraception-containing levonorgestrel, also known as the "morning after pill," after receiving new data that suggests the contraceptive may be less effective in women with higher body weights. Recently in Europe, the product labeling for Norlevo was updated with clinical trial information suggesting the contraceptive may be less effective in women ≥75 kg and not effective in women >80 kg.

Health Canada is also considering whether labeling changes will be needed for all levonorgestrel emergency contraceptive products to better reflect the patient population in which these products are effective.

Further information is available at http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2014/37771a-eng.php

Important Safety Information for Arzerra

GlaxoSmithKline, in conjunction with Health Canada, has issued notice to health care professionals that the ofatumumab (Arzerra) Canadian product monograph has been updated with new recommendations for screening, monitoring, and the management of hepatitis B reactivation in patients treated with ofatumumab. New recommendations include screening all patients for HBV infection prior to treatment; not treating patients who have active HBV infection with Arzerra; monitoring patients for clinical and laboratory signs of hepatitis or HBV reactivation during treatment and for several months after treatment; and immediately discontinuing Arzerra in patients who develop reactivation of HBV.

For more information, see http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2014/37705a-eng.php

Sodium Chloride 0.9% Safety Alert

Due to increased demand, it has been difficult for hospitals to obtain sodium chloride 0.9% injection in liter bags. Because of the shortage, some hospitals have been administering sodium chloride for irrigation 0.9% as an alternative to the injection. However, this item does not meet the same specifications of the sterile injection and should not be used; sterility requirements and limits on particulate matter differ between these 2 products.

Iclusig Available in the United States

Ariad Pharmaceuticals announced the commercial availability of Iclusig (ponatinib) in the United States. Iclusig is indicated for the treatment of adult patients with refractory chronic myeloid leukemia and Philadelphia chromosome–positive acute lymphoblastic leukemia. Ariad began shipping Iclusig to Biologics, Inc, its exclusive specialty pharmacy, which is now filling prescriptions and distributing the medication.

On October 31, 2013, the FDA requested and Ariad agreed to voluntarily suspend marketing of Iclusig. The FDA's request resulted from an investigation which revealed a steady increase in the number of serious vascular occlusion events identified through continued safety monitoring. This observation represented a significant change in the safety profile of Iclusig, as the proportion of patients on the drug experiencing vascular occlusion events (eg, blood clots and severe narrowing of blood vessels) was significantly greater than the proportion reported at the time of its approval in December 2012.

The FDA approved revised prescribing information for Iclusig in the United States, as well a communications Risk Evaluation and Mitigation Strategy (REMS) that allowed for the immediate resumption of its marketing and commercial distribution. The updates include a revised indication statement and boxed warning, updated safety information, and recommendations regarding dosing considerations for prescribers.

Additional information is available at http://www.fda.gov/Drugs/DrugSafety/ucm379554.htm and http://meetinglibrary.asco.org/content/109745-132

Effient Associated With Increased Risk of Serious Bleeding

Eli Lilly Canada, in collaboration with Health Canada, warns that Effient (prasugrel) is associated with an increased risk of serious bleeding in patients with unstable angina (UA) or non-ST–segment elevation myocardial infarction (NSTEMI) undergoing percutaneous coronary intervention (PCI). Effient is an antiplatelet agent indicated for the prevention of atherothrombotic events in patients with acute coronary syndromes.

In a clinical trial involving NSTEMI patients, prasugrel loading dose (30 mg) given 2-48 hours (average 4 hours) prior to diagnostic coronary angiography followed by prasugrel 30 mg at the time of PCI increased the risk of major and minor periprocedural bleeding compared with the full approved prasugrel loading dose (60 mg) at the time of PCI.

When coronary angiography is performed in UA/NSTEMI patients within 48 hours after admission, the full approved loading dose of prasugrel (60 mg) should generally be given at the time of PCI in order to minimize the risk of bleeding, followed by a 10 mg maintenance dose.

The Canadian product monograph for Effient has recently been revised to include this new safety finding. A copy of the most current monograph can be found on the Health Canada website and on the Eli Lilly Canada website.

Any cases of serious or unexpected adverse reactions in patients receiving Effient should be reported to Eli Lilly Canada or Health Canada.

For additional information, please refer to http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2014/37615a-eng.php

FDA Recommends Acetaminophen 325 mg or Less Per Dosage Unit

The FDA is recommending that health care providers discontinue prescribing and dispensing prescription combination drug products that contain more than acetaminophen 325 mg per tablet, capsule, or other dosage unit. There are no available data to show that taking more than acetaminophen 325 mg per dosage unit provides additional benefit that outweighs the added risks for liver injury. Limiting the amount of acetaminophen per dosage unit will reduce the risk of severe liver injury from inadvertent acetaminophen overdose, which can lead to liver failure, liver transplant, and death.

Over half of manufacturers voluntarily complied with the initial FDA request in January 2011 to limit the amount of acetaminophen to no more than 325 mg in each dosage unit; however, some prescription combination drug products containing more than acetaminophen 325 mg per dosage unit remain available. The FDA intends to institute proceedings to withdraw approval of prescription combination drug products with more than acetaminophen 325 mg per dosage unit that remain on the market in the near future.

The FDA recommends that a pharmacist who receives a prescription for a combination product with more than acetaminophen 325 mg per dosage unit should contact the prescriber to discuss a product with a lower dose of acetaminophen.

Additional information can be found at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm381650.htm

Safety Alert for Jevtana

Sanofi-Aventis Canada, in consultation with Health Canada, has issued notice to health care professionals regarding the risk for medication errors leading to overdose in the preparation of Jevtana (cabazitaxel) and the importance of ensuring that the entire content of the diluent (5.67 mL) is added to the concentrate vial during reconstitution. Failure to properly reconstitute the concentrate vial with the entire amount of diluent may lead to a higher dosage of Jevtana being administered and increased risk of toxicity (eg, bone marrow suppression, gastrointestinal effects). Reconstitution errors leading to overdose with Jevtana have been reported in Europe, resulting in doses 15% to 20% higher than the prescribed dose. No cases of reconstitution errors have been reported in Canada.

Further information is available at http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2014/37453a-eng.php

Sodium Phosphate Overdose Warning

The FDA has issued a warning regarding rare but potentially serious adverse effects (including death) that may occur when exceeding recommended doses of over-the-counter (OTC) sodium phosphate preparations to treat constipation. Severe dehydration and alterations in serum electrolytes (eg, calcium, sodium, phosphate) leading to adverse effects on organs (eg, kidney, heart) have been reported, mostly when single maximum doses were exceeded or when more than 1 dose was taken per day. Patients should be advised to adhere to the product labeling and not exceed maximum recommended doses. Health care providers should use caution when recommending doses for oral sodium phosphate preparations for children less than 5 years of age. Rectal preparations should never be administered to children less than 2 years of age.

Further information may be found at http://www.fda.gov/Drugs/DrugSafety/ucm380757.htm

New Dosage Recommendations for Sublinox

Meda Valeant Pharma Canada Inc., in consultation with Health Canada, has revised the initial dose of Sublinox (zolpidem tartrate) to 5 mg for women and either 5 or 10 mg for men. The total dose of Sublinox should not exceed 10 mg once daily immediately before bedtime with at least 7 to 8 hours remaining before the planned time of awakening. In some patients, the higher morning blood levels following use of the 10 mg dose increase the risk of next-day impairment of driving and other activities that require full alertness. The recommended initial doses for women and men reflect the lower rate of clearance and higher blood levels of zolpidem in women compared with men. In all patients, the lowest effective dose should be used. The recommended dose of Sublinox in elderly patients is 5 mg regardless of gender.

Health care providers should also advise patients taking Sublinox about the risk of next-day impairment for activities that require complete mental alertness. In particular, the following points should be mentioned: the impairment risk is increased if dosing instructions are not carefully followed; a patient should not drive or engage in hazardous activities requiring complete alertness until they know how the drug affects them the next day; and even if a patient took Sublinox as instructed and does not feel drowsy in the morning, the patient still must wait at least 8 hours after taking a dose before driving or engaging in other activities requiring full mental alertness.

For additional information, please refer to http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2014/37415a-eng.php