Med Check

The long-acting formulation of olanzapine pamoate (Zyprexa Relprevv) for intramuscular injection has been linked to two “unexplained deaths,” the Food and Drug Administration (FDA) announced in a safety alert June 18. The drug is indicated for treatment of schizophrenia in adults, with a recommended dosing schedule of once every two or four weeks. Because of known risks for delirium and severe sedation, even coma requiring intubation and resuscitation, the use of this product is restricted to health care professionals and facilities registered in a special program. All patients receiving the injection are required to remain under observation for three hours after every injection before they are allowed to leave accompanied, according to the prescribing information.

The two deaths occurred three to four days after an olanzapine injection. Both “were found to have very high olanzapine blood levels after death,” according to the FDA. In clinical trials that led to the drug’s approval, the same phenomenon of rapidly and greatly elevated olanzapine concentration in the blood stream had been documented and considered a possible cause for the severe sedation. The FDA says in the alert that it is “continuing to evaluate these deaths.” The alert is posted at http://www.fda.gov/drugs/drugsafety/ucm356971.htm, and prescribing information for Zyprexa Relprevv is posted at http://pi.lilly.com/us/zyprexa_relprevv.pdf.

Two large pharmaceutical companies, Roche and AstraZeneca, announced June 26 a plan to share biochemistry data on molecules in each company’s drug-development pools in the hope of designing and discovering molecules with a better chance to become viable drug candidates. An external company specializing in molecular analysis will manage this collaboration.

Paroxetine, a selective serotonin reuptake inhibitor, was approved by the FDA June 28 for treating moderate to severe hot-flash symptoms associated with menopause. The 7.5 mg formulation of paroxetine will be marketed by Noven Therapeutics under the brand name Brisdelle. Two randomized, double-blind, placebo-controlled clinical trials had been conducted in more than 1,000 postmenopausal women suffering from seven to eight hot flashes a day or 50 to 60 a week. After 12 weeks or 24 weeks of treatment, patients on paroxetine reported greater reduction in hot flashes than patients on placebo.

Rivastigmine transdermal patch has been approved by the FDA for treatment of severe Alzheimer’s disease (AD), Novartis announced June 27. The patch was previously approved for only mild and moderate AD. This approval was based on a randomized, double-blind, 24-week study in which the high-dose patch (13.3 mg/24 hour) was compared with the low-dose patch (4.6 mg/24 hour) in patients with severe AD. The improvement on cognition and daily-function assessments in the high-dose group was statistically significantly greater than that for the low-dose group. In the clinical trial, adverse drug reactions were more common in the high-dose group.

Merck’s new insomnia drug, suvorexant, has received a green light from the FDA at the doses of 10 mg to 20 mg but not 30 mg and 40 mg, the company announced July 1. In a complete response letter, the agency agreed that the efficacy of the drug is established, but it did not approve the higher doses out of safety concerns. Suvorexant is an orexin receptor antagonist, a class of molecules that are separate from currently available drugs used to treat insomnia. Orexin, also known as hypocretin, is a neuropeptide associated with the regulation of wakefulness. In May, an advisory committee voted 13-3 in favor of approving suvorexant at doses of up to 20 mg. The votes on the higher doses were mixed, with eight against, seven for, and one abstention.

A combination of buprenorphine and naloxone in sublingual tablet (brand name Zubsolv) has been approved by the FDA for the maintenance treatment of opioid dependence, the manufacturer Orexo US, announced July 5. The product will compete with Suboxone sublingual film, marketed by Reckitt Benkiser Pharmaceuticals, which contains the same active drugs. Like Suboxone, Zubsolv is a C3 controlled substance. The approval is based on a provision in the Federal Food, Drug, and Cosmetic Act known as 505(b)(2), a company spokesperson told Psychiatric News. The provision allows a new drug application to be approved on data published in medical literature or the agency’s finding of safety and/or effectiveness of a previously approved drug product. ■