Med Check: FDA Actions on Xylazine, Austedo XR, and Zuranolone

FDA Aims to Curtail Illegal Importation of Xylazine

The U.S. Food and Drug Administration (FDA) has taken action to restrict the illegal entry of xylazine ingredients and drug products into the country, according to an announcement released in February. Xylazine is a veterinary medication used to sedate large animals such as horses and deer. However, it has increasingly been found in illicit drugs such as illicitly manufactured fentanyl, and xylazine-related overdose deaths have risen in recent years (Psychiatric News, “Xylazine Increasingly Found in Overdose Deaths”).

The FDA’s actions include heightened scrutiny of imports of drugs containing xylazine into the country, and FDA staff may detain shipments if they appear to violate the law. When FDA staff conduct entry reviews of xylazine, they will consider specific evidence offered by importers that the incoming product is properly labeled, not adulterated, and for legitimate veterinary use.

According to the announcement, the FDA and its Office of Criminal Investigations are collaborating with federal, state, and local partners to investigate xylazine-related activities that could be subject to criminal prosecution, including online and in-person conduct. The FDA said it is coordinating with stakeholders in animal health to ensure that drugs containing xylazine are available to veterinarians for legitimate use.

SAMHSA Publishes Advisory About Cannabidiol Products

In February the Substance Abuse and Mental Health Services Administration (SAMHSA) published an advisory about the potential harms, side effects, and unknowns of cannabidiol (CBD).

The advisory covers how CBD is derived and how it differs from delta-9-tetrahydrocannabinol (THC). The advisory also explains that CBD products that are not approved do not have to meet any standards for content or potency (Psychiatric News, “Most OTC Cannabinoid Products Mislabeled”). It notes that the FDA has not approved CBD products to be marketed as food additives or dietary supplements and that the FDA has concluded that a new regulatory pathway is needed for CBD products.

The advisory provides tips and action steps for health professionals, parents, caregivers, and the general public to take regarding education and awareness of the risk of CBD products.

Austedo XR Approved for Treating Tardive Dyskinesia and Huntington’s Chorea

The FDA has approved Austedo XR (deutetrabenazine extended-release tablets) for the treatment of tardive dyskinesia and chorea associated with Huntington’s disease in adults, Teva Pharmaceuticals announced in February. Austedo XR is taken once per day, compared with Austedo, which is taken twice per day. It will be available in three strengths: 6 mg, 12 mg, and 24 mg, and can be taken with or without food. The same total daily dosage can be used when switching between Austedo tablets and Austedo XR tablets.

Austedo XR comes with a boxed warning about depression and suicidality in patients with Huntington’s disease. The warning instructs health professionals who prescribe the medication to monitor patients who take Austedo for the emergence or worsening of depression, suicidality, or changes in behavior. It also instructs health professionals to inform patients, caregivers, and families of the risk of depression and suicidality.

FDA Grants Zuranolone Priority Review for Major Depression and Postpartum Depression

The FDA has granted zuranolone priority review for the treatment of major depressive disorder (MDD) and postpartum depression (PPD), Sage Therapeutics announced in February. Zuranolone is an investigational drug being evaluated as a 14-day, rapid-acting, once-daily, oral treatment in adults with MDD and PPD.

In the WATERFALL trial, 543 adults aged 18 to 64 years with MDD received either 50 mg of zuranolone or placebo daily for 14 days. All patients in the study had a Hamilton Rating Scale for Depression (HAMD-17) total score of at least 24 when they enrolled in the study. By day 15 of the trial, patients who took zuranolone had experienced an average drop of 14.1 points on the HAMD-17, compared with an average drop of 12.3 points in those who took placebo.

In the SKYLARK trial, 195 women with PPD were randomized to take either 50 mg of zuranolone or placebo once per night for 14 days. On Day 15, scores on the 17-item Hamilton Rating Scale for Depression dropped a mean of 15.6 points among women who took zuranolone compared with a mean decrease in score of 11.6 points among women who took placebo.

The FDA’s decision on whether to approve zuranolone for major depressive disorder and postpartum depression is expected by August 5. ■