Recalls and warnings
New warnings on the entire class of opioid pain medications. Safety risks include potentially harmful interactions with other medications (e.g., serotonergic medicines), adrenal insufficiency, and decreased sex hormone levels. The FDA is requiring changes to the labels of all opioids to include these risks. If serotonin syndrome is suspected, clinicians should discontinue opioid treatment and/or use of the other medicine. In cases of suspected adrenal insufficiency, clinicians should perform diagnostic testing before treating the patient with corticosteroids and weaning him or her off the opioid, if appropriate. In patients presenting with signs or symptoms of decreased sex hormone levels, clinicians should conduct laboratory evaluation. In addition, the FDA is requiring a new boxed warning for immediate-release opioids about the serious risks of misuse, abuse, addiction, overdose, and death.
New drug label warnings on medications that contain saxagliptin and alogliptin, as these drugs may increase the risk of heart failure, particularly in patients with heart or kidney disease. These dipeptidyl peptidase-4 (DPP-4) inhibitors are found in Onglyza (saxagliptin), Kombiglyze XR (saxagliptin and metformin extended release), Nesina (alogliptin), Kazano (alogliptin and metformin), and Oseni (alogliptin and pioglitazone). Clinicians should consider discontinuing saxagliptin and alogliptin in patients who develop heart failure, making sure to monitor their diabetes control. The new warnings hinge on the findings of 2 large clinical trials conducted in patients with heart disease. One trial showed that 3.5% of patients receiving saxagliptin were hospitalized for heart failure, compared to 2.8% of patients receiving placebo. The alogliptin trial showed that 3.9% of patients treated with the drug were hospitalized for heart failure versus 3.3% in the placebo group. Risk factors included a history of heart failure or kidney impairment.
Revised warnings on metformin and reduced kidney function. New label changes will expand metformin's use to patients with mild kidney impairment and some patients with moderate impairment. The FDA is also requiring that labels be revised to recommend using estimated glomerular filtration rate (eGFR) instead of blood creatinine concentration to determine whether a patient can receive metformin. Metformin is now contraindicated in patients with an eGFR below 30 mL/min/1.73 m2 and is not recommended in patients with an eGFR between 30 mL and 45 mL/min/1.73 m2.
A class I recall of the G4 Platinum and G5 Mobile Continuous Glucose Monitoring System Receivers because the audible alarm may not activate in the handheld receiver when hypoglycemia or hyperglycemia is detected. This recall affects 263,520 devices distributed nationwide. Relying on the product for notification of high or low blood glucose could lead to serious adverse events, including death, if the alarm does not sound.
Reslizumab (Cinqair) in combination with other asthma medicines for the maintenance treatment of severe asthma. The drug is approved for patients who have a history of exacerbations despite receiving their current asthma medicines. Administered once every 4 weeks by intravenous infusion, the drug reduces severe asthma attacks by reducing the levels of blood eosinophils. In 4 trials, patients receiving the drug had fewer asthma attacks and a longer time to the first attack than those receiving placebo. The most common side effects were anaphylaxis, cancer, and muscle pain.
The Micra Transcatheter Pacing System, the first leadless pacemaker approved to treat heart rhythm disorders including atrial fibrillation and bradycardia-tachycardia syndrome. The self-contained, inch-long device is implanted into the right ventricle. In a trial of 719 patients implanted with the device, 98% of patients had adequate heart pacing 6 months after implantation. Complications occurred in fewer than 7% of participants and included prolonged hospitalization, deep venous thrombosis, pulmonary embolism, heart injury, device dislocation, and myocardial infarction. The device is contraindicated for patients who have implanted devices that would interfere with the pacemaker, those who are severely obese, those who have an intolerance to its materials or heparin, and those who have veins that are unable to accommodate the 7.8-mm introducer sheath or pacemaker implant.
Infliximab-dyyb (Inflectra), a biosimilar to infliximab, indicated for patients with moderately to severely active Crohn's disease or ulcerative colitis who have had an inadequate response to conventional therapy; patients with moderately to severely active rheumatoid arthritis in combination with methotrexate; patients with active ankylosing spondylitis; patients with active psoriatic arthritis; and patients with chronic severe plaque psoriasis. The most common expected side effects include respiratory infections, headache, coughing, and stomach pain. Symptoms of infusion reactions, which can happen up to 2 hours after an infusion, include fever, chills, chest pain, low blood pressure, high blood pressure, shortness of breath, rash, and itching. A boxed warning includes details about an increased risk of serious infections, such as tuberculosis and bacterial sepsis.
Venetoclax (Venclexta) for the treatment of patients with chronic lymphocytic leukemia who have 17p deletion and have been treated with at least 1 prior therapy. In a trial of 106 patients who took the oral drug every day, beginning with 20 mg and increasing to 400 mg over 5 weeks, 80% of participants experienced complete or partial remission of their cancer. The most common side effects were neutropenia, diarrhea, nausea, anemia, upper respiratory tract infection, thrombocytopenia, and fatigue. Serious complications include pneumonia, neutropenia with fever, fever, autoimmune hemolytic anemia, and tumor lysis syndrome.
Defibrotide sodium (Defitelio) to treat severe hepatic veno-occlusive disease. The drug is the first therapy approved to treat patients with this disease and additional kidney or lung abnormalities after they receive hematopoietic stem-cell transplantation. In 3 studies of 528 patients treated with the drug, 38% to 45% of patients were alive after transplantation, compared to expected survival rates of 21% to 31%. The most common side effects include hypotension, diarrhea, vomiting, nausea, and epistaxis. Serious potential side effects include hemorrhage and allergic reactions, so the drug should not be used in patients who are having bleeding complications or taking blood thinners.
Draft guidance supporting the development of generic versions of approved opioids with abuse-deterrent formulations. The draft includes recommendations about the studies that should be conducted to demonstrate that generic abuse-deterrent formulations are no less abuse-deterrent than their brand-name counterparts. This document is part of the FDA's action plan to create policies with the goal of reversing the opioid epidemic while continuing to provide effective pain relief to patients who need it. The agency seeks input through an open-comment period and will also hold a public meeting later this year to discuss the draft guidance.
A safety alert on CT scans and implantable electronic medical devices, such as insulin pumps, that the presence of these devices should not preclude an appropriate and medically indicated CT scan. Although there have been a small number of reports of adverse events and deaths related to this issue, the FDA maintains that the probability of electronic inference leading to clinically significant adverse events is extremely low. Interference is completely avoided when a medical device is located outside of the CT scanner's primary X-ray beam. If the CT scan will cover the area over the device, the ordering clinician should discuss with the patient whether the device can be safely moved, attached at a different location, or turned off for a period of time. Clinicians should then communicate this information to the facility performing the scan.