Pregabalin has become the first drug to win approval by the Food and Drug Administration for the management of fibromyalgia.
The FDA based the approval on two double-blind, controlled trials of approximately 1,800 patients. Data from the studies have shown that patients with fibromyalgia “have decreased pain after taking [pregabalin], but, the mechanism by which [pregabalin] produces such an effect is unknown,” according to an agency-issued statement.
In the clinical trials of patients with fibromyalgia, those on pregabalin (Lyrica) had “rapid and sustained improvements in pain,” compared with those on placebo, and “reported feeling better and improvements in physical function,” according to a statement issued by Pfizer, which manufactures pregabalin. The same statement explains that the drug's mechanism of action for fibromyalgia is not known, but states that patients with fibromyalgia may be more sensitive than normal to stimuli that are not usually painful, and that pregabalin may reduce the degree of pain experienced by patients with fibromyalgia by binding to a specific protein within “overexcited nerve cells.”
The approval “marks an important advance, and provides a reason for optimism for the many patients who will receive pain relief” with pregabalin, Dr. Steven Galson, the director of the FDA's Center for Drug Evaluation and Research said in the FDA statement. He added, however, that consumers should understand that some patients in trials did not benefit from the drug, and that “we still have more progress to make for treatment of this disorder.”
The two studies enrolled patients diagnosed with fibromyalgia using American College of Rheumatology (ACR) criteria, which are a history of widespread pain for 3 months and pain present at 11 or more of the 18 specific tender point sites, according to the revised prescribing information for pregabalin. The two studies–a 14-week double-blind placebo-controlled study and a 6-month randomized withdrawal study–found that treatment was associated with a reduction in pain by visual analog scale and improvements based on a patient global assessment and on the Fibromyalgia Impact Questionnaire.
In the 14-week study, some patients experienced reductions in pain during the first week of treatment, which continued throughout the study. Nearly 70% of those on a total daily dose of 300 mg of pregabalin, and 78% of those on a total daily dose of 450 mg experienced any improvement on the patient global impression of change scale, compared with 48% of those on placebo. The total daily dose of 600 mg was not more effective than the lower doses, and there was evidence of dose-related side effects.
The daily dose should be administered in two divided doses per day, starting at a total daily dose of 150 mg/day, which may be increased to 300 mg/day, within 1 week; the maximum dose is 450 mg/day, according to the prescribing information.
The most common side effects in the trials were mild to moderate dizziness and sleepiness, blurred vision, weight gain, dry mouth, and swelling of the hands and feet also were also reported. Side effects appeared to be dose related, according to the FDA. Patients should talk to their physicians or other health care providers about whether pregabalin–which can impair motor function, concentration, and attention–can affect their ability to drive, the FDA advised. Pfizer has agreed to conduct a study of pregabalin in children and another in women who are breast-feeding.
Pregabalin, a centrally acting drug, was first approved in 2004 for the management of neuropathic pain associated with diabetic peripheral neuropathy and postherpetic neuralgia, and for the adjunctive therapy for adult patients with partial onset seizures. It is taken orally in capsule form.