Label change for pioglitazone-containing medications

Recalls and warnings

A label change for pioglitazone-containing medications (Actos, Actoplus Met, Actoplus Met XR, Duetact, Oseni) regarding the drug's association with risk of bladder cancer. Although labels of these drugs have warned about this risk since 2011, the FDA has approved updated labels that will describe the additional studies it recently reviewed. The agency recommends against using the diabetes drug in patients with active bladder cancer and urges clinicians to carefully consider risks and benefits before using it in patients with a history of bladder cancer.

Removal of warnings on the risk of serious mental health side effects from two smoking cessation medications. The black box warning label will be removed from varenicline (Chantix), and the boxed warning for bupropion (Zyban) will be updated. The FDA has determined that the risks of serious side effects on mood, behavior, or thinking are lower than previously suspected, based on its review of a large clinical trial the agency required the drug companies to conduct. The risk of mental health side effects still exists, especially in patients currently or formerly treated for mental illnesses, but most people who experienced these side effects did not have serious consequences (e.g., hospitalization).

Approvals

A new indication for empagliflozin (Jardiance) to reduce the risk of cardiovascular death in adult patients with type 2 diabetes mellitus and cardiovascular disease. In a postmarketing clinical trial of more than 7,000 patients with type 2 diabetes and cardiovascular disease, the drug reduced the risk of cardiovascular death compared to placebo when added to standard-of-care therapies for diabetes and atherosclerotic cardiovascular disease. The most common side effects of empagliflozin are urinary tract infections and female genital infections, and it can also cause such conditions as dehydration, hypotension, acute kidney injury, increased cholesterol, and ketoacidosis.

Rucaparib (Rubraca) to treat advanced ovarian cancer. The drug is indicated for women who have been treated with two or more types of chemotherapy and whose tumors have a deleterious BRCA mutation, as identified by FoundationFocus CDxBRCA, an FDA-approved companion diagnostic test. The safety and efficacy of the orphan drug, which received accelerated approval, were shown in two single-arm clinical trials involving 106 participants. In the trials, 54% of those who received the drug experienced complete or partial shrinkage of their tumors, a response rate that lasted a median of 9.2 months. Common side effects include nausea, fatigue, vomiting, anemia, abdominal pain, dysgeusia, constipation, decreased appetite, diarrhea, thrombocytopenia, and dyspnea. Serious risks include myelodysplastic syndrome, acute myeloid leukemia, and fetal harm.

Crisaborole (Eucrisa) ointment to treat mild to moderate atopic dermatitis. Patients topically apply the phosphodiesterase-4 inhibitor twice daily. In two placebo-controlled trials with a total of 1,522 participants ages 2 to 79, those receiving the ointment achieved greater response with clear or almost clear skin after 28 days of treatment. Serious side effects include hypersensitivity reactions, and the ointment is contraindicated in patients who have had a hypersensitivity reaction to its active ingredient, crisaborole. The most common side effect is pain (e.g., burning, stinging) at the application site.

Autologous cultured chondrocytes on porcine collagen membrane (Maci) for the repair of symptomatic, full-thickness cartilage defects of the knee in adult patients. This is the first FDA-approved product that applies the process of tissue engineering to grow cells on scaffolds using healthy cartilage tissue from the knee. Safety and long-term efficacy were shown in a two-year clinical trial of 144 patients. The most common side effects were joint pain, common cold-like symptoms, headache, and back pain.

Miscellaneous

An alert for physicians caring for pregnant women meeting the CDC's clinical and/or epidemiological criteria for Zika virus that false-positive results have been reported with the ZIKV Detect test. The results were reported by Laboratory Corporation of America (LabCorp). The serological IgM test remains useful in ruling out Zika exposure, but the FDA urges physicians to wait for confirmatory testing of presumptive or possible positive results, which may take a week to a month, before making patient management decisions. To facilitate prioritization of confirmatory testing by the CDC or qualified laboratories, notify the laboratory of the patient's pregnancy. The FDA has not yet determined if the reported false positives are related to the test or to the testing facility.