Med Check

On October 25, the Food and Drug Administration (FDA) approved the first single-entity extended-release (ER) formulation of hydrocodone bitartrate (Zohydro ER) for management of severe pain that requires daily around-the-clock treatment.

Safety and efficacy findings for Zohydro ER were based on clinical trials including more than 1,600 participants with chronic and severe pain. Those given Zohydro ER reported a significant improvement in chronic pain compared with those receiving placebo. The most common side effects reported were constipation, nausea, drowsiness, headache, dizziness, dry mouth, and itching.

The FDA warns that “because of the greater risks of overdose and death with ER/LA opioid formulations, Zohydro ER should be reserved for use in patients for whom alternative treatment options are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. Zohydro ER is not approved for as-needed pain relief.”

The approved labeling for Zohydro ER is the first to conform to the updated labeling requirements for all extended-release/long-acting opioid analgesics that were announced by the FDA this summer. The new hydrocodone formulation is classified as a Schedule II substance under the Controlled Substance Act—indicating that it can only be dispensed by prescription and cannot be refilled.

Zohydro ER is manufactured by Zogenix Inc.

Two years ago, the U.S. Supreme Court ruled that generic drugs—unlike branded drugs—were not required to have updated safety labels, even after discovery of new side effects associated with the medications.

Last month, the FDA proposed a rule that will challenge the 2011 Supreme Court ruling in that it will require makers of generic drugs to quickly update their warning labels with new safety information for doctors and patients.

“More than 80 percent of prescriptions filled in the U.S. are for generics. . . . This proposal will help ensure that health care professionals and consumers have access to the latest safety information for the medications they use,” said Janet Woodcock, M.D., director of the FDA’s Center for Drug Evaluation and Research.

The proposed mandate means that generic-drug manufacturers would face the same kind of liability over product labeling as brand-name companies do and would lose the shield given them by the Supreme Court ruling.

Displeased with the FDA’s proposal, the Generic Pharmaceutical Association (GPhA) said in statement that “the Supreme Court has repeatedly held that generic pharmaceutical manufacturers must duplicate the language on the brand pharmaceutical manufacturer’s labels. . . . Multiple versions of critical safety information would lead to unnecessary confusion and uncertainty for prescribers and other health care professionals, with harmful consequences for patients.” The GPhA plans to advocate against the new proposal.

Lundbeck and Otsuka have announced the continuation of their development program for the Alzheimer’s disease (AD) drug Lu AE58054 (Lu).

The program, which will consist of four phase 3 clinical trials, will include about 3,000 patients with mild-to-moderate AD who will receive ranging doses of Lu in combination with donepezil to assess the effectiveness of Lu as an adjunctive therapy to acetylcholinesterase inhibitors.

Results from phase 2 trials, presented at the Alzheimer’s Association International Conference in July, showed Lu and donepezil to be effective in improving cognitive function in patients over a six-month period compared with placebo.

Lu is a selective serotonin receptor 6 (5-HT6) antagonist with a proposed mechanism of action that is different from that of currently available AD medications, which target beta-amyloid and tau-associated mechanisms.

The FDA announced October 31 that it is implementing strategies to further enhance the government’s efforts to prevent and reduce medication shortages—a significant public-health threat that can delay critical care for patients.

Since President Obama’s 2011 executive order to reduce such shortages, the number of new shortages decreased by more than 50 percent from 2011 through 2012. The FDA plans to further reduce these numbers by improving its approach to addressing the underlying causes of these shortages and requiring all manufacturers of certain critical drugs to notify the FDA of any interruption in manufacturing likely to disrupt drug supply.

“Early notification is a critical tool that helps mitigate or prevent looming shortages,” said Janet Woodcock, M.D., director of the FDA’s Center for Drug Evaluation and Research. “The FDA continues to take all steps it can within its authority, but the FDA alone cannot solve shortages. Success depends upon a commitment from all stakeholders.”

Currently there are seven psychiatric drugs on the shortage list including lorazepam injection, prochlorperazine injection, methylin chewable tablets, various forms of methylphenidate hydrochloride, and various forms of fluphenazine hydrochloride.

Previous studies investigating nicotine-replacement therapy in methadone-maintained (MMT) opiate-dependent smokers have shown low quitting rates. Researchers from Brown University investigated whether varenicline—the key ingredient in the smoking-cessation drug Chantix—could be successful in treating this difficult-to-treat population.

In more than 300 MMT opiate-dependent smokers, the researchers evaluated the efficacy of varenicline compared with placebo and nicotine replacement therapy (NRT) over six months.

Results showed that varenicline was 50 percent less effective in achieving smoking cessation than was NRT. There was no significant difference in abstinence rates for varenicline versus placebo.

Michael Stein, M.D, a professor of medicine and health services at Brown University, told Psychiatric News that quit rates across all tested medication options—which now include varenicline—have been low for MMT smokers. Stein concluded that future studies should focus on “novel behavioral interventions combined with medication” to achieve smoking cessation in this population.

Stein M., Caviness C., Kurth M.: “Varenicline for Smoking Cessation Among Methadone-Maintained Smokers: A Randomized Clinical Trial.” 2013. Drug Alcohol Depend. December 1. http://www.sciencedirect.com/science/article/pii/S0376871613002706.

Researchers from the Scripps Research Institute conducted a study showing that gabapentin, an anticonvulsant medication, may serve as a potential therapy to alleviate alcoholism.

The study—funded by the National Institute on Alcohol Abuse and Alcoholism—included evaluations of 150 alcohol-dependent patients who received moderate to high doses of gabapentin or placebo.

After 12-weeks of treatment, 43 percent of the patients who received the drug were able to refrain from heavy drinking days, compared with 23 percent in the placebo group. In addition, the gabapentin group was four times more likely to stop drinking altogether than those given placebo. The medication appeared to be well tolerated with few side effects and alcohol withdrawal symptoms.

Researchers concluded that because of gabapentin’s demonstrated ability to reduce drinking days and relapse-related symptoms, it can serve as a treatment option for alcohol dependence in primary care settings.

Mason B., Quello S., Goodell V., et. al.: “Gabapentin Treatment for Alcohol Dependence: A Randomized Clinical Trial.” 2013. JAMA Intern Med. Nov 4. [Epub ahead of print] http://www.ncbi.nlm.nih.gov/pubmed/24190578. ■