Warning on diabetes drugs, approval of adjuvant flu vaccine

Recalls and warnings

A warning on sodium-glucose cotransporter-2 (SGLT2) inhibitors about the risks of ketoacidosis and serious urinary tract infections. These warnings will be added to the labels of medicines in this class, such as canagliflozin, dapagliflozin, and empagliflozin. In a safety review, the FDA identified 73 cases of ketoacidosis in patients with type 1 or type 2 diabetes treated with SGLT2 inhibitors and 19 cases of life-threatening urosepsis and pyelonephritis that started as urinary tract infections. All 19 patients were hospitalized, and a few required admission to an intensive care unit or dialysis.

A warning of potential contamination of certain lots of baclofen active pharmaceutical ingredient (API) manufactured in China by Taizhou Xinyou Pharmaceutical & Chemical Co. The affected APIs may be at risk for contamination with particulates and should not be used to compound sterile injectable drugs. If patients use or receive injectable drug products compounded with the affected baclofen, especially when administered directly into the spinal column, serious injury may occur.

Approvals

A trivalent vaccine (Fluad) for the prevention of seasonal influenza in people ages 65 years and older. This is the first flu vaccine to contain an adjuvant and is produced from 3 virus strains (2 subtype A and 1 type B). In a trial of 7,082 older participants, the new vaccine and an existing one (Agriflu) induced comparable antibody levels. Safety was evaluated in about 27,000 additional older adults, and no safety concerns were identified. The most common adverse events include injection site pain and tenderness, muscle aches, headache, and fatigue.

A new indication for nivolumab (Opdivo) to treat patients with metastatic renal-cell carcinoma who have received an anti-angiogenic agent. In a study of 821 patients, those treated with nivolumab lived almost 6 months longer than those on everolimus, and 21.5% of them saw shrinkage of their tumors, compared to 3.9%. The most common side effects of the drug for this indication are asthenic conditions, cough, nausea, rash, dyspnea, diarrhea, constipation, decreased appetite, back pain, and arthralgia. Clinicians should also be aware of immune-mediated side effects that can result from the immune system effect of this medication. The drug was previously approved for melanoma and non-small-cell lung cancer.

Alectinib (Alecensa) to treat metastatic anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer after unsuccessful crizotinib (Xalkori) therapy. The oral medication blocks the activity of the ALK protein. In 2 clinical trials, 38% and 44% of participants experienced a partial shrinkage of their lung tumors, an effect that lasted an average of 7.5 months and 11.2 months, respectively. The most common side effects were fatigue, constipation, edema, and myalgia. In the 2 trials, 61% of participants who had measurable brain metastases experienced a complete or partial reduction in their brain tumors that lasted an average of 9.1 months. Serious side effects include liver problems, severe or life-threatening inflammation of the lungs, very slow heartbeats, and severe muscle problems. Treatment may also cause sunburn when patients are exposed to sunlight.

Necitumumab (Portrazza) in combination with 2 forms of chemotherapy to treat metastatic squamous non-small-cell lung cancer. In a clinical study of 1,093 participants who received gemcitabine and cisplatin with or without necitumumab, those taking the drug lived longer on average (11.5 months) compared to those only taking the 2 chemotherapy drugs (9.9 months). The most common side effects were skin rash and hypomagnesemia. The drug has a boxed warning alerting clinicians of its serious risks, including cardiac arrest and sudden death.

Elotuzumab (Empliciti) in combination with 2 other therapies to treat people with multiple myeloma who have received 1 to 3 prior medications. In a study of 646 participants, those taking elotuzumab plus lenalidomide and dexamethasone experienced a delay in the amount of time before their disease worsened (19.4 months) compared to those taking only the latter 2 drugs (14.9 months). In addition, 78.5% of those taking the extra drug saw a complete or partial shrinkage of their tumors, compared to 65.5%. The most common side effects of elotuzumab were fatigue, diarrhea, fever, constipation, cough, peripheral neuropathy, nasopharyngitis, upper respiratory tract infection, decreased appetite, and pneumonia.

Sugammadex (Bridion) injection to reverse the effects of neuromuscular blockade induced by rocuronium bromide and vecuronium bromide used during certain types of surgery. In 3 clinical trials involving 456 patients, treatment groups recovered faster than comparator groups, with most participants recovering within 5 minutes of routine sugammadex use. The most common adverse reactions included vomiting, hypotension, pain, headache, and nausea. Clinicians should be aware of the possibility of a hypersensitivity reaction or anaphylaxis, as well as hemodynamic changes, as cases of marked bradycardia have been observed within minutes of drug administration.

Uridine triacetate (Vistogard) for the emergency treatment of patients who receive an overdose of the chemotherapy agents fluorouracil and capecitabine or who develop early onset, severe toxicities after receiving these treatments. Taken orally, the drug blocks cell damage and cell death and is administered as soon as possible after overdose or within 4 days of severe or life-threatening toxicity. In 2 trials of 135 patients, 97% of overdose patients and 89% of toxicity patients were still alive at 30 days, and 33% of all patients resumed chemotherapy in less than 30 days. The most common side effects were diarrhea, vomiting, and nausea. The drug is not recommended for non-emergency adverse reactions associated with fluorouracil and capecitabine because it may lessen their efficacy.

Recombinant von Willebrand factor (Vonvendi) to treat bleeding episodes in adults diagnosed with von Willebrand disease. Two clinical trials of 69 adult patients with the disease demonstrated that the orphan product was safe and effective for the on-demand treatment and control of bleeding episodes from various sites on the body. The most common adverse reaction was generalized pruritus.

Miscellaneous

A notice that the FDA is eliminating the Risk Evaluation and Mitigation Strategy (REMS) for rosiglitazone-containing type 2 diabetes medicines. These medications are approved as Avandia, Avandamet, Avandaryl, and generics. Drug manufacturers have fulfilled FDA requirements, such as providing training to clinicians about the heart risks of rosiglitazone medications, and the agency has determined that a REMS is no longer necessary to ensure that the benefits of these medicines outweigh their risks.

A voluntary field safety notification for 15 lots of the OmniPod Insulin Management System because of reports of its needle mechanism failing to deploy or demonstrating a delay in deployment. If deployment of the needle mechanism fails, the needle is not inserted, preventing insulin delivery. Affected lots of the product have resulted in 66 medical device reports, including 3 that required medical intervention. The reported incidence of this issue in the affected lots is about 1% to 2%. The company has corrected the manufacturing process and has implemented additional inspection steps. The FDA recommends that consumers using products from the affected lots ensure that the needle mechanism deploys properly.