Med Check: Allergan's Migraine Treatment, GI Warning for Clozapine, Alkermes' Treatment, Reyvow, Bumetanide

Allergan’s Migraine Treatment Approved

In December the Food and Drug Administration (FDA) approved Ubrelvy (ubrogepant tablets), Allergan’s treatment for migraine with or without aura in adults. Ubrelvy is the first drug in the class of oral calcitonin gene-related peptide receptor antagonists approved for the acute treatment of migraine. The approved doses are 50 mg or 100 mg taken orally.

Ubrelvy was shown to be effective in treating migraine in two randomized, double-blind, placebo-controlled trials—ACHIEVE I and ACHIEVE II. In these studies, 1,439 adult patients with a history of migraine, with and without aura, received either 50 mg or 100 mg of Ubrelvy or placebo while experiencing a migraine. In both studies, more participants in the treatment groups were free from pain two hours later than in the placebo groups. Compared with the placebo groups, more participants in the treatment groups were also free from migraine symptoms such as nausea, sensitivity to light, and sensitivity to sound.

FDA Strengthens GI Warning for Clozapine

In January the FDA strengthened an existing warning that constipation caused by the antipsychotic clozapine may lead to serious bowel complications that may be fatal if not treated promptly. The agency said that the risk increases at higher doses and when clozapine is used with other medications known to cause constipation.

The strengthened warning came after the FDA reviewed reports filed from 2006 to 2016 about patients who took clozapine and experienced constipation that progressed to serious complications. The agency identified 10 reports involving constipation that resulted in hospitalization, surgery, and five deaths. The total daily dose of clozapine in these cases ranged from 200 mg to 600 mg, and the time to onset of serious bowel events ranged from three days to six months. The adverse events included “death of the colon wall or part of the intestine, blockage of blood flow to the intestines, and abdominal distention leading to bowel obstruction,” according to the FDA website.

The FDA requires that the prescribing information for all clozapine products include the new warning and updates about the risk. The agency also recommended that health professionals evaluate bowel function in patients before prescribing clozapine and askpatients about their bowel movements throughout treatment.

FDA to Review Alkermes’ Treatment for Schizophrenia, Bipolar I Disorder

Alkermes earlier this year announced that the FDA has accepted for review a New Drug Application for ALKS 3831 (olanzapine/samidorphan) for treating schizophrenia. The application also includes an indication for manic or mixed episodes associated with bipolar I disorder either as a monotherapy or adjunct to lithium or valproate and for maintenance treatment of bipolar I disorder.

ALKS 3831 is a once-daily, oral atypical antipsychotic medication designed to provide the efficacy of olanzapine while lessening the risk of weight gain that is normally associated with olanzapine. The proposed fixed dosage strengths for ALKS 3831 include 10 mg of samidorphan coformulated with 5 mg, 10 mg, 15 mg, or 20 mg of olanzapine.

To support its application, Alkermes submitted data from the ENLIGHTEN clinical development program. The ENLIGHTEN-1 study compared outcomes in patients with schizophrenia who received ALKS 3831 with those who received placebo over four weeks. The ENLIGHTEN-2 study assessed weight gain in patients with schizophrenia who took ALKS 3831 compared with those who took olanzapine over six months.

Reyvow Now Available for Migraine

Patients who experience migraines now have a new option for relief: Last month manufacturer Eli Lilly and Co. announced the medication Reyvow (lasmiditan) is now available in pharmacies. The medication is a serotonin 5-HT1F receptor agonist. It is available in two doses, 50 mg and 100 mg tablets.

The FDA approved Reyvow last October. The approval was based in part on two randomized, double-blind, placebo-controlled trials involving 3,177 adult patients. A significantly greater percentage of patients who received Reyvow during a migraine attack reported the pain and migraine symptoms including nausea and light sensitivity resolved within two hours of treatment compared with those who received placebo.

The most common side effects reported by patients included dizziness, fatigue, tingling or numbing sensations on the skin, sedation (sleepiness or drowsiness), nausea and/or vomiting, and muscle weakness

Bumetanide Shows Promise for Reducing Autism Symptoms

A study in Translational Psychiatry suggests that the diuretic bumetanide may improve symptoms of autism in children. In a three-month trial led by researchers at Shanghai Jiao Tong University School of Medicine in China and colleagues, 81 children aged three to six years with autism spectrum disorder received either two 0.5 mg tablets of bumetanide a day or no treatment.

Compared with the control group, at three months the patients in the bumetanide group experienced less severe symptoms as shown by improved scores on the Childhood Autism Rating Scale. This scale measures a child’s behavior, characteristics, and abilities against the expected developmental growth of a typical peer. Children in the bumetanide group also showed greater improvements on the Clinical Global Impressions Scale, which rates the severity of symptoms.

The study is posted here. ■