Med Check

FDA to Remove Some Warnings From Chantix, Zyban Labels

The Food and Drug Administration (FDA) announced this past December that it will remove the boxed warning related to serious mental health side effects from the smoking cessation medication Chantix (varenicline). The language describing the serious mental health side effects seen in patients quitting smoking will also be removed from the boxed warning in the Zyban (bupropion) label. The announcement was made after a large clinical trial found such risks were lower than previously suspected.

The trial to evaluate the neuropsychiatric safety of the medications in patients with and without a history of psychiatric disorders included over 8,000 patients in 16 countries. The study participants were randomly assigned to take Chantix (1 mg twice daily), Zyban (150 mg twice daily), nicotine replacement therapy (NRT), or placebo for 12 weeks, followed by a non-treatment phase of 12 weeks.

Clinically significant neuropsychiatric adverse events occurred at a similar frequency across treatment arms in patients without psychiatric diagnoses (3.1 percent to 3.5 percent in the treatment groups versus 4.1 percent in placebo group). There was a higher incidence of neuropsychiatric adverse events in patients with psychiatric diagnoses who took Chantix and Zyban (11.8 percent to 12.2 percent versus 9.5 percent). The results of the trial also confirmed that Chantix and Zyban were superior to placebo in promoting smoking abstinence regardless of a person’s mental health history.

Because the active ingredient in Zyban is in the antidepressant class, the label carries the class boxed warning for suicidality and antidepressants. This language will remain in a boxed warning for Zyban and other bupropion products.

FDA Delays Initial Launch of Clozapine REMS Program

Clozapine prescribers and pharmacies who have yet to complete certification in the Clozapine REMS Program will have more time to complete the task, after the FDA announced in December 2016 that it was postponing the full program launch.

The Clozapine REMS program is part of an effort announced by the FDA in September 2015 to improve the monitoring and management of patients taking clozapine.

“The Clozapine Product Manufacturer’s Group and the U.S. Food and Drug Administration are continuing to work to ensure that patients relying on clozapine are able to maintain access to this medication, while also ensuring that the risks associated with it are appropriately managed,” the FDA said in a statement.

During this extension, prescribers and pharmacies should continue to adhere to the Clozapine REMS Program requirements. A complete list of these requirements can be accessed here.

Bristol-Myers Squibb to Pay $19.5M For Off-Label Promotion of Abilify

Bristol-Myers Squibb Co. has agreed to pay $19.5 million to settle multistate allegations that it improperly promoted the antipsychotic Abilify, New York Attorney General Eric Schneiderman announced in December 2016.

The deal with 42 states and the District of Columbia resolves claims that the company marketed Abilify for children and elderly patients with dementia and Alzheimer’s disease, when neither use was approved by the FDA. According to the attorney general, the company also violated state consumer protection laws by misrepresenting the risks of Abilify, including weight gain and metabolic side effects.

Bristol-Myers Squibb has denied any wrongdoing.

FDA to Consider Abilify Maintena for Treatment of Bipolar I Disorder

The FDA has indicated that it will review an application to expand the Abilify Maintena label to include maintenance treatment for adults with bipolar I disorder, H. Lundeck A/S and Otsuka Pharmaceuticals announced in November 2016. According to the companies, the agency is expected to make a decision regarding the label expansion by late July 2017.

Abilify Maintena is an extended-released release injectable atypical antipsychotic that was first approved in the United States in 2013 for the treatment of schizophrenia in adults.

Merck’s BACE1 Inhibitor Reduces Amyloid Production

In November 2016, Merck published data from a phase 1 trial showing that verubecestat, a small-molecule inhibitor of β-site amyloid precursor protein cleaving enzyme 1 (BACE1), slowed beta-amyloid production in healthy volunteers and people with Alzheimer’s disease. BACE1 is involved in stimulating production of beta-amyloid protein, a hallmark of Alzheimer’s disease.

For the study, 32 participants were randomized to receive one of three daily doses of verubecestat (12 mg, 40 mg, or 60 mg) or placebo for seven days. Samples of cerebral spinal fluid were collected over 36 hours via a lumbar catheter and analyzed for levels of amyloid β 40 (Aβ40), amyloid β 42 (Aβ42), and soluble amyloid precursor protein β (sAPPβ) as biomarkers of BACE1 activity.

According to a Merck release, “Verubecestat at doses of 12, 40, and 60 mg caused a dose-dependent and sustained reduction in the levels of Aβ40 from baseline in the CSF, a measure of BACE1 activity, of 57, 79, and 84 percent, respectively.”

The medication was generally well tolerated, with headache, nasal congestion, and dizziness reported.

Merck is exploring whether 12 mg and 40 mg daily doses of verubecestat can slow the progression of cognitive decline in patients with mild-to-moderate AD in a phase 2/3 clinical trial series (the EPOCH study) and the onset of AD in patients with prodromal AD in a phase 3 trial (the APECS study). ■