New concerns about diabetes drugs, migraine patches

Details on the latest safety notices, warnings, and approvals.

Safety notices and warnings

A strengthened warning about the risk of acute kidney injury with canagliflozin (Invokana, Invokamet) and dapagliflozin (Farxiga, Xigduo XR). The FDA has revised the drug label warnings in light of 101 confirmable associated cases of acute kidney injury reported in the past few years. Some patients required hospitalization and dialysis. Clinicians should be aware of the risk factors that may predispose patients to acute kidney injury, which include decreased blood volume, chronic kidney insufficiency, congestive heart failure, and taking certain other medications (e.g., diuretics, angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, and nonsteroidal anti-inflammatory drugs). The FDA also issued an alert that an ongoing clinical trial found an increase in leg and foot amputations, mostly affecting the toes, in patients treated with canagliflozin. The agency continues to investigate and has not determined whether the drug increases the risk of amputations. Clinicians should continue to follow recommendations in the drug labels.

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Photo by Thinkstock

A notice that the FDA is investigating the risk of serious burns and scarring with the use of the sumatriptan iontophoretic transdermal system (Zecuity), a patch for migraines. A large number of patients have reported severe redness, pain, skin discoloration, blistering, and cracked skin where the single-use, battery-powered patch was worn. The manufacturer has temporarily suspended sales, marketing, and distribution of the product to investigate further, and clinicians should discontinue prescribing this drug.

A warning that taking higher-than-recommended doses of loperamide (Imodium) can cause serious heart problems that can lead to death. The majority of reported serious heart problems occurred in people who were intentionally misusing and abusing high doses of the drug in attempts to self-treat opioid withdrawal symptoms or achieve a feeling of euphoria. Some may use other drugs along with loperamide to increase its effects. The FDA continues to evaluate this issue to determine if additional action is needed.


The first buprenorphine implant for the maintenance treatment of opioid dependence (Probuphine). The implant provides a constant, low-level dose of buprenorphine for 6 months in patients who are already stable on low to moderate doses of other forms of the drug. It consists of 4 rods about an inch long that are surgically inserted under the skin on the inside of the upper arm. A clinical trial showed that 63% of treated patients had no evidence of illicit opioid use throughout the 6 months of treatment, similar to the 64% of those who responded to sublingual buprenorphine. The most common side effects include implant-site pain, itching, and redness, as well as headache, depression, constipation, nausea, vomiting, back pain, toothache, and oropharyngeal pain. The implant carries a boxed warning of the risks associated with insertion and removal, such as migration, protrusion, expulsion, and nerve damage. It should be used with counseling and psychosocial support as part of a complete treatment program and can only be prescribed and dispensed by trained clinicians certified with the Probuphine Risk Evaluation and Mitigation Strategy program.

Daclizumab (Zinbryta) to treat adults with relapsing forms of multiple sclerosis. Patients self-administer the long-acting injection once a month. In 1 trial, patients taking the drug had fewer clinical relapses than patients taking interferon, and a second trial showed that those taking the drug had fewer relapses compared to those receiving placebo. Daclizumab has serious safety risks, such as liver injury and immune conditions, and should generally be used only in patients who have had an inadequate response to 2 or more multiple sclerosis drugs. The most common adverse reactions include cold symptoms, upper respiratory tract infection, rash, influenza, dermatitis, throat pain, eczema, enlargement of lymph nodes, depression, rash, and increased alanine aminotransferase levels.

An obesity treatment device (AspireAssist) that uses a surgically placed tube to drain a portion of the stomach contents after every meal. The device is approved for weight loss in patients ages 22 and older who are obese (body mass index of 35 to 55 kg/m2) and have not achieved and maintained weight loss through nonsurgical means. Surgeons insert a tube in the stomach, which is connected to a disk-shaped port valve that lies outside the body, flush against the abdomen. About 20 to 30 minutes after meals, the patient attaches an external tube to the port valve and drains the contents, removing about 30% of the calories consumed. The device automatically stops working after about 5 to 6 weeks of therapy, and patients must return to their clinician in order to continue. In a clinical trial, patients treated with the device and lifestyle therapy lost an average of 12.1% of their total body weight, compared to 3.6% for those receiving only lifestyle therapy. Side effects include occasional indigestion, nausea, vomiting, constipation, and diarrhea. There are also risks associated with the device's endoscopic surgical placement and with the abdominal opening for the port valve.