Med Check: Guidance on Drug Labeling; Lumateperone; Melatonin; Sunosi; Vyleesi

FDA Issues Draft Guidance on Drug Labeling for Abuse, Dependence

In July the Food and Drug Administration (FDA) published draft guidance to assist drug manufacturers in writing the “Drug Abuse and Dependence” section of a medication’s labeling.

In a statement, Acting Commissioner of Food and Drugs Norman E. Sharpless, M.D., and Director of the Center for Drug Evaluation and Research Janet Woodcock, M.D., said that the guidance “will help ensure that information in product labeling on abuse, misuse, addiction, physical dependence, and tolerance is clear, concise, useful, and informative.”

They added that the guidance provides recommendations on how to present information about applicable drug products consistently within and across drug classes and recommends that terminology such as “abuse,” “misuse,” “addiction,” “physical dependence,” and “tolerance” be defined in the labeling to ensure common understanding.

The FDA is accepting electronic or written comments on the draft guidance before it begins work on the final version. Those interested in providing comments should do so by September 3. Instructions for submitting comments are posted here.

Phase 3 Trials of Lumateperone Yield Mixed Results

Lumateperone, an investigational serotonin 5-HT2A receptor antagonist by Intra-Cellular Therapies, improved symptoms in patients with bipolar disorder compared with placebo in one phase 3 clinical trial, but not in another, the company announced in July.

The first trial included 381 patients who were assigned to take lumateperone (42 mg) or placebo once daily.  After six weeks, patients who took lumateperone achieved a greater improvement in symptoms from baseline than those who took placebo, as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS). In addition, lumateperone 42 mg improved symptoms compared with placebo on the MADRS total score in a subgroup analyses of patients with bipolar I and patients with bipolar II disorder. In the second trial, 554 patients were randomized to lumateperone (28 mg or 42 mg) or placebo. Neither dose of lumateperone met the primary endpoint of statistical separation from placebo as measured by change from baseline on the MADRS total score. The company noted in a press release that there was a high placebo response in this trial.

A third trial, still underway, is evaluating lumateperone as an adjunctive therapy to lithium or valproate for the treatment of bipolar disorder. Last December the company announced that the FDA had accepted for review its New Drug Application for lumateperone as a treatment for schizophrenia.

Melatonin May Improve Hospital-Related Insomnia

A study in the Journal of Pharmacy Practice suggests that melatonin may be as effective as zolpidem for treating hospital-related insomnia.

Researchers used the Verran and Snyder-Halpern Sleep Scale to evaluate sleep in 100 hospitalized patients who received either melatonin or zolpidem as a sleep aid the night before. None of the patients had acute psychological issues or a history of substance abuse.

There were no significant differences in patient perceptions of effectiveness or in adverse events between the two groups. The only adverse events reported in both groups were grogginess and headache.

The study, “Comparison of Melatonin and Zolpidem for Sleep in an Academic Community Hospital: An Analysis of Patient Perception and Inpatient Outcomes,” is posted here.

Sunosi Now Available for Improving Wakefulness

Jazz Pharmaceuticals’ Sunosi (solriamfetol), approved by the FDA in March for improving wakefulness in adults with excessive daytime sleepiness associated with narcolepsy or obstructive sleep apnea, became available last month. Sunosi is a once-daily, dual-acting dopamine and norepinephrine reuptake inhibitor available in 75 mg and 150 mg tablets.

The Drug Enforcement Agency in June classified Sunosi as a Schedule IV drug because it can be a target for people who abuse prescription medications or use street drugs.

In 12-week clinical studies, approximately 68% to 74% of participants who took the 75 mg dose and 78% to 90% of participants who took the 150 mg dose reported improvement in their overall clinical condition, as assessed by the Patient Global Impression of Change scale. The most common adverse reactions were headache, nausea, decreased appetite, and anxiety.

Vyleesi Wins Approval for Female Sexual Disorder

The FDA in June approved Palatin Technologies Inc.’s Vyleesi (bremelanotide) to treat premenopausal women for acquired, generalized hypoactive sexual desire disorder (HSDD). HSDD (classified as female sexual interest/arousal disorder in DSM-5) is characterized by low sexual desire that causes distress and cannot be explained by a comorbid physical or psychiatric illness, the side effects of substance use or medications, or severe relationship problems. Acquired HSDD means a woman has previously experienced sexual desire (low desire has not been a lifelong problem).

The approval of Vyleesi was supported by two, 24-week, randomized clinical studies involving 1,247 premenopausal women with HSDD. In both trials, Vyleesi was more effective than placebo at improving patient- reported sexual desire and reducing emotional distress.

To achieve the desired effects of Vyleesi, women are advised to inject the medication into their abdomen or thigh at least 45 minutes before anticipated sexual activity. Vyleesi is not approved to enhance sexual performance, and women should not use more than one dose every 24 hours or more than eight doses per month, according to the FDA statement. ■