The U.S. Food and Drug Administration (FDA) has approved pregabalin (Lyrica™) for the treatment of fibromyalgia, a disorder characterized by pain, fatigue and sleep problems. The approval was supported by two double-blind, controlled clinical trials, involving about 1,800 patients, with doses of 300 milligrams or 450 milligrams per day.
The most common side effects of Lyrica include mild-to-moderate dizziness and sleepiness. Blurred vision, weight gain, dry mouth, and swelling of the hands and feet also were reported in clinical trials. The side effects appeared to be dose-related. Lyrica can impair motor function and cause problems with concentration and attention. FDA advises that patients talk to their doctor or other health care professional about whether use of Lyrica may impair their ability to drive.

Pfizer has agreed to perform a study of the drug in children with fibromyalgia and a study in breastfeeding women.

In the UK pregabalin is licensed for the following:

• The treatment of peripheral and central neuropathic pain in adults.
• As adjunctive therapy in adults with partial seizures with or without secondary generalisation.
• The treatment of Generalised Anxiety Disorder (GAD) in adults

Link: http://www.fda.gov/bbs/topics/NEWS/2007/NEW01656.html

Source: FDA

In briefing documents released ahead of the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee review panel's meeting this week, Agency staff have expressed their concern over "increased frequencies of psychiatric adverse effects" including suicide and seizures linked to rimonabant, which, if approved, will be sold as Zimulti in the US.

The FDA has delayed a final decision on whether to approve rimonabant for obesity in the US several times amid concerns about depression and a high drop-out rate in clinical trials. The FDA Advisory Committee is due to meet this week; briefing documents compiled by the FDA and Sanofi for the meeting are now available on the FDA website (see link).

The FDA briefing notes that: ‘Among the most significant adverse events throughout the Phase III programme were those in the primary System Organ Class (SOC) psychiatric disorders, specifically depressive events, anxiety, psychomotor agitation, and sleep disorders’. More specifically:

• In the pooled RIO studies, for subjects receiving the same treatment during the whole study, 26% of rimonabant 20mg treated subjects vs. 14% of placebo treated subjects experienced a psychiatric symptom reported as an adverse event. Specifically, 9% of rimonabant 20-mg treated subjects vs. 5% of placebo treated subjects reported symptoms of depression (depressed mood; depression; depressive symptom; or major depression).

• The relative risk for psychiatric adverse events in the rimonabant 20 mg vs. placebo groups ranged from 1.5 to 2.5 in the four RIO studies. When considered in aggregate, the overall relative risk for psychiatric adverse events in the rimonabant 20 mg vs. placebo group was 1.9 (1.5, 2.3).

As a result, Sanofi is proposing that rimonabant "should not be initiated in patients with uncontrolled psychiatric illness such as a major depression" and notes that "there is limited data" in patients taking antidepressants in combination with its drug, "therefore the use of rimonabant is not recommended in these patients".

Link: http://www.fda.gov/ohrms/dockets/ac/07/briefing/2007-4306b1-fda-backgrounder.pdf (PDF)