FDA strengthens kidney warnings for canagliflozin and dapagliflozin
The FDA has strengthened current warnings regarding the risk of acute kidney injury associated with canagliflozin (Invokana, Invokamet) and dapagliflozin (Farxiga, Xigduo XR) treatments for type 2 diabetes mellitus. Based on recent reports, the agency has revised the warnings in the drug labeling to include information about acute kidney injury and made recommendations to minimize risk.
The FDA notes that from March 2013, when canagliflozin was approved, to October 2015, the FDA received reports of 101 confirmable cases of acute kidney injury, some requiring hospitalization and dialysis, with canagliflozin and dapagliflozin use. There may be other cases not reported to the FDA. Prior to starting patients on either of these medications, healthcare providers should consider factors that may predispose patients to acute kidney injury:
* Decreased blood volume
* Chronic kidney insufficiency
* Heart failure
* Taking other medications, such as diuretics, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and nonsteroidal anti-inflammatory drugs.
The FDA recommends that kidney function be assessed before starting canagliflozin or dapagliflozin and should be monitored periodically thereafter. If acute kidney injury occurs, the drugs should be promptly discontinued and the impairment treated.
New drug approved for multiple sclerosis
The FDA approved Biogen's daclizumab (Zinbryta), an interleukin-2 receptor blocking antibody, for the treatment of adults with relapsing forms of multiple sclerosis (MS). It is a long-acting subcutaneous injection self-administered by patients monthly. The effectiveness of Zinbryta was shown in two clinical trials, one comparing it with interferon beta-1a (Avonex), in which patients on Zinbryta had fewer clinical relapses than those taking Avonex. The second trial compared the drug with placebo, and patients taking Zinbryta had fewer relapses compared with those receiving placebo.
Zinbryta should generally be used only in patients who have had an inadequate response to two or more MS drugs, the FDA states, because it has serious safety risks, including liver injury (including life-threatening and fatal events) and immune-mediated disorders (such as noninfectious colitis, skin reactions, and lymphadenopathy). Zinbryta's labeling has a Black Box Warning and is available only via a restricted distribution program under a Risk Evaluation and Mitigation Strategy. Monthly blood tests should be performed prior to each dose and for up to 6 months after the last dose to monitor liver function.
The most common adverse reactions associated with Zinbryta reported by patients in clinical trials comparing it with Avonex include nasopharyngitis, upper respiratory tract infection, rash, influenza, dermatitis, oropharyngeal pain, eczema, and lymphadenopathy. The most common adverse reactions in trials comparing it with placebo included depression, rash, and increased alanine aminotransferase.
Serious heart problems related to loperamide abuse
The FDA warns that taking higher-than-recommended doses of the over-the-counter and prescription diarrhea medication loperamide (Imodium), including through abuse or misuse of the product, can result in serious heart problems that can lead to death. The risk of these problems, including abnormal heart rhythms, may also be increased when high doses of loperamide are taken with several kinds of medications that interact with the drug (http://www.fda.gov/drugs/drugsafety/ucm504617.htm).
Most of the reported serious heart problems occurred in individuals who were intentionally misusing and abusing high doses of loperamide in attempts to self-treat opioid withdrawal symptoms or to achieve a feeling of euphoria, the FDA states.
Serious cardiac adverse events cited by the FDA include QT interval prolongation, torsades de pointes or other ventricular dysrhythmias, syncope, and cardiac arrest. Healthcare professionals should consider loperamide as a possible cause of these unexplained cardiac events and should advise patients that drug interactions with commonly used drugs increase the risk of adverse cardiac events.