Recent FDA MedWatch updates on safety and efficacy issues

The following are recent U.S. Food and Drug Administration (FDA) alerts or changes that were made to the package labeling of drugs, based on concerns for patient safety or efficacy:

Long-term Antiplatelet Therapy: Safety Announcement - Preliminary Trial Data Shows Benefits But a Higher Risk of Non-Cardiovascular Death: The FDA is evaluating preliminary data from a clinical trial showing that treatment for 30 months with dual antiplatelet blood-thinning therapy decreased the risk of heart attacks and clot formation in stents, but there was an increased overall risk of death (including non-cardiovascular deaths, primarily cancer and trauma deaths) compared to 12 months of treatment. The FDA believes the benefits of antiplatelet therapy continue to outweigh their potential risks when used for approved uses. They do not recommend that patients should stop taking these drugs because doing so may result in an increased risk of heart attacks, blood clots, strokes, and other major cardiovascular problems. Also, they are advising that healthcare professionals should not change the way they prescribe these drugs at this time.

Tecfidera (dimethyl fumarate) by Biogen Idec: Drug Safety Communication - Case of Rare Brain Infection PML Reported: The FDA is warning that a patient with multiple sclerosis (MS) who was being treated with Tecfidera (dimethyl fumarate) developed a rare and serious brain infection called progressive multifocal leukoencephalopathy (PML), and later died. Tell patients taking Tecfidera to contact you if they develop any symptoms that may be suggestive of PML. Symptoms of PML are diverse, progress over days to weeks, and include the following:

  • Progressive weakness on one side of the body or clumsiness of limbs; disturbance of vision; and changes in thinking, memory and orientation, leading to confusion and personality changes. The progression of deficits can lead to severe disability or death.
  • Stop Tecfidera immediately at the first sign or symptom suggestive of PML and perform an appropriate diagnostic evaluation.
  • Monitor lymphocyte counts in Tecfidera-treated patients according to approved labeling.

Ziprasidone (Marketed as Geodon and Generics): Drug Safety Communication - Rare But Potentially Fatal Skin Reactions: A new warning has been added to the Geodon drug label to describe the serious condition known as Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS). The FDA reviewed information from six patients in whom the signs and symptoms of DRESS appeared between 11 and 30 days after ziprasidone treatment was started. None of these patients died. Patients who have a fever with a rash and/or swollen lymph glands should seek urgent medical care. Health care professionals should immediately stop treatment with ziprasidone if DRESS is suspected.

Prescription and Over-the-Counter (OTC) Pain Medicines: Drug Safety Communication – The FDA reviewed published studies on the potential risks associated with the following three types of pain medicines used during pregnancy:

  • Prescription NSAIDs and the risk of miscarriage in the first half of pregnancy including ibuprofen, naproxen, diclofenac, and celecoxib.
  • Prescription Opioids and the risk of birth defects of the brain, spine, or spinal cord in babies born to women who took these products during the first trimester of pregnancy including oxycodone, hydrocodone, hydromorphone, morphine, and codeine.
  • Acetaminophen in both OTC and prescription products and the risk of attention deficit hyperactivity disorder (ADHD) in children born to women who took this medicine at any time during pregnancy.

The FDA found all of the studies to have potential limitations in their designs where the accumulated studies on a topic sometimes contained conflicting results that prevented them from drawing reliable conclusions. As a result, their recommendations on how pain medicines are used during pregnancy remains the same at this time.

Pregnant women or women considering becoming pregnant should always consult with their health care professional before taking any prescription or OTC medicine to discuss the risks and benefits of pain medicine use. Health care professionals should continue to follow the recommendations in the drug labels when prescribing or recommending pain medicines to pregnant patients. The FDA will continue to monitor and evaluate the use of pain medicines during pregnancy and update the public as new safety information becomes available.

Chantix (varenicline): Drug Safety Communication - FDA Updates Label to Include Potential Alcohol Interaction: The FDA has approved changes to the Chantix label to warn about interactions between alcohol and Chantix resulting in some patients experiencing increased intoxicating effects of alcohol, sometimes associated with aggressive behavior and/or amnesia. In addition, rare accounts of seizures in patients treated with Chantix have been reported.

Treanda (bendamustine hydrochloride) Solution by Teva: FDA Statement - Not Compatible with Closed System Transfer Devices, Adapters, and Syringes Containing Polycarbonate or Acrylonitrile-Butadiene-Styrene: The FDA is warning health care professionals not to use Treanda 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). Most marketed CSTDs contain either polycarbonate or ABS and are not compatible with Treanda Injection (45 mg/0.5 mL or 180 mg/2 mL solution).

N, N-dimethylacetamide (DMA), an ingredient in Treanda Injection (45 mg/0.5 mL or 180 mg/2 mL solution), is incompatible with polycarbonate or ABS. Devices that contain polycarbonate or ABS dissolve when coming into contact with DMA. This can lead to device failure, possible product contamination, and potential serious adverse health consequences, including skin reactions in health care professionals preparing and administering this product and the risk of small blood vessel blockage in patients.

The FDA is requiring label changes for both the solution and the powder formulations of Treanda to reflect safe preparation information.

Over-the-Counter Asthma Products Labeled as Homeopathic: FDA Statement - Consumer Warning About Potential Health Risks: The FDA is warning consumers not to rely on asthma products labeled as homeopathic that are sold over-the-counter (OTC). These products have not been evaluated by the FDA for safety and effectiveness. Many of these products are promoted as "natural," "safe and effective," and include indications that range from treatment for acute asthma symptoms, to temporary relief of minor asthma symptoms. In general, consumers can identify such products by looking for the word "HOMEOPATHIC" or "HOMÅ’OPATHIC" on a product's label and looking for whether the product’s active ingredient(s) are listed in terms of dilution (e.g., "LM1" "6X" or "30C").

There are many prescription asthma treatments approved by the FDA as safe and effective, as well as some products that are marketed OTC in accordance with an FDA monograph. Please advise consumers who think they have asthma or have children with asthma to take an active role in managing their condition by making certain they have appropriate treatments on hand in the event they experience an asthma attack or a worsening of asthma symptoms, and by consulting with a health care provider when needed.

Zyprexa Relprevv (olanzapine pamoate): Drug Safety Communication - FDA Review of Study Sheds Light on Two Deaths Associated with the Injectable Schizophrenia Drug: The FDA has concluded its review to determine the cause of elevated levels of the injectable schizophrenia drug Zyprexa Relprevv (olanzapine pamoate) in two patients who died. On the basis of all of the information reviewed (refer to the Drug Safety Communication for a full data summary), the FDA is not recommending any changes to the current prescribing or use of Zyprexa Relprevv injection at this time. Patients should not stop receiving treatment without first talking to their health care professionals.

Hepatitis C Treatments Containing Sofosbuvir in Combination With Another Direct Acting Antiviral Drug: Drug Safety Communication - Serious Slowing of Heart Rate When Used With Antiarrhythmic Drug Amiodarone: The FDA is warning that symptomatic bradycardia can occur when amiodarone is taken together with either Harvoni (ledipasvir/sofosbuvir) or with Sovaldi (sofosbuvir) taken in combination with another direct acting antiviral such as the investigational drug, daclatasvir or Olysio. The FDA is adding this information to the Harvoni and Sovaldi labels and recommending that health care professionals should not prescribe this combination of medications. In cases where alternative treatment options are unavailable, the FDA recommends heart monitoring in an inpatient hospital setting for the first 48 hours. Subsequently, monitoring in a doctor's office or self-monitoring of the heart rate should be done every day through at least the first 2 weeks of treatment.

Due to the long half-life of amiodarone, patients discontinuing amiodarone just prior to starting Harvoni, or Sovaldi in combination with another direct-acting antiviral should also undergo similar cardiac monitoring as outlined above.

Feraheme (ferumoxytol): Drug Safety Communication – Warnings Strengthened and Prescribing Instructions Changed: All IV iron products carry a risk of potentially life-threatening allergic reactions. Since Feraheme's approval in 2009, serious reactions, including deaths, have occurred despite the proper use of therapies to treat these reactions and emergency resuscitation measures. The FDA evaluated this risk further and has identified ways to reduce the risk of serious allergic reactions with Feraheme:

  • Only administer IV iron products to patients who require IV iron therapy.
  • Do not administer Feraheme to patients with a history of allergic reaction to Feraheme or other IV iron products.
  • Only administer diluted Feraheme as an IV infusion over a minimum of 15 minutes. Feraheme should not be given as an undiluted IV injection.
  • Closely monitor patients for signs and symptoms of serious allergic reactions, including monitoring blood pressure and pulse during Feraheme administration and for at least 30 minutes following each infusion.
  • Carefully consider the potential risks and benefits of Feraheme administration in elderly patients with multiple or serious medical conditions, as these patients may experience more severe reactions.
  • Carefully consider the potential risks and benefits of Feraheme administration in patients with a history of multiple drug allergies. Patients with multiple drug allergies may also be at higher risk.

Flurbiprofen-Containing Topical Pain Medications: FDA Alert - Illnesses and Deaths in Pets Exposed to Prescription Topical Pain Medication: The FDA recommends that people who use topical medications containing flurbiprofen take care to prevent their pets from being exposed to them, even in ways that may seem unlikely to cause problems. Health care providers who prescribe topical pain medications containing flurbiprofen, and pharmacists who fill these prescriptions, should advise patients with pets to take care to prevent exposure of the pet to the medication.

SGLT2 inhibitors: Drug Safety Communication - FDA Warns Medicines May Result in Ketoacidosis: The FDA is investigating whether the SGLT2 inhibitors, canagliflozin, dapagliflozin, and empagliflozin may lead to diabetic ketoacidosis (DKA).

DKA is a subset of ketoacidosis in diabetic patients that usually develops when insulin levels are too low or during prolonged fasting. DKA most commonly occurs in patients with type 1 diabetes and is usually accompanied by high blood sugar levels. These cases were not typical for DKA because the patients had type 2 diabetes and their blood sugar levels were only slightly increased. Factors identified in some reports as having potentially triggered the ketoacidosis included major illness, reduced food and fluid intake, and reduced insulin dose.

Patients should be advised to pay close attention for any signs of ketoacidosis and seek medical attention immediately if they experience symptoms such as difficulty breathing, nausea, vomiting, abdominal pain, confusion, and unusual fatigue or sleepiness. Patients should not stop or change their diabetes medicines without first talking to their prescriber.

Health care professionals should evaluate for the presence of acidosis, including ketoacidosis, in patients experiencing these signs or symptoms; discontinue SGLT2 inhibitors if acidosis is confirmed; and take appropriate measures to correct the acidosis and monitor sugar levels.

Testosterone Products: Drug Safety Communication - FDA Cautions About Using Testosterone Products for Low Testosterone Due to Aging; Requires Labeling Change to Inform of Possible Increased Risk of Heart Attack And Stroke: The FDA is requiring that the manufacturers of all approved prescription testosterone products change their labeling to clarify the approved uses of these medications. The FDA is also requiring the addition of information to the labeling about a possible increased risk of heart attacks and strokes in patients taking testosterone. They caution that prescription testosterone products are approved only for men who have low testosterone levels caused by certain medical conditions. The benefit and safety of these medications have not been established for the treatment of low testosterone levels due to aging, even if a man’s symptoms seem related to low testosterone.

Based on the available evidence from studies and expert input from an FDA Advisory Committee meeting, the FDA has concluded that there is a possible increased cardiovascular risk associated with testosterone use. These studies included aging men treated with testosterone. Some studies reported an increased risk of heart attack, stroke, or death associated with testosterone treatment, while others did not. See the Data Summary section of the FDA Drug Safety Communication for additional details.

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