Lyrica: FDA approves new indication for pregabalin


Pregabalin, an anticonvulsant agent, is now approved by FDA for the management of fibromyalgia.

Key Points

Pregabalin binds with high affinity to the alpha2-delta site in central nervous system tissues. Pregabalin's precise mechanism of action is unknown, but some studies have suggested that pregabalin's ability to bind to the alpha2-delta site may be involved in the agent's antinociceptive and antiseizure effects. Pregabalin was previously approved for the management of neuropathic pain associated with diabetic peripheral neuropathy, for the management of postherpetic neuralgia, and as an adjunctive therapy for adult patients with partial-onset seizures. This agent was approved on June 21, 2007, for the management of fibromyalgia.

Efficacy. The efficacy of pregabalin for the management of fibromyalgia was evaluated in one 14-week, double-blind, placebo-controlled, multicenter study (F1) and in one 6-month, randomized withdrawal study (F2). Both studies enrolled patients with a diagnosis of fibromyalgia based on the American College of Rheumatology criteria. In Study F1, patients were treated with pregabalin 300, 450, or 600 mg/d or placebo. Enrolled patients had a minimum mean baseline pain score ≥4 on an 11-point numeric pain rating scale and a score ≥40 mm on the 100-mm pain visual analog scale (VAS). Patients who responded to placebo during an initial 1-week run-in phase were not randomized into subsequent phases of the trial. Patients randomized to pregabalin demonstrated a superior improvement in Patient Global Impression of Change (PGIC) after 14 weeks versus placebo (pregabalin 300 mg/d, 68.1%; pregabalin 450 mg/d, 77.8%; pregabalin 600 mg/d, 66.1%; placebo, 47.6%). Some patients experienced a decrease in pain as early as Week 1; this decrease persisted throughout the study. In Study F2, pregabalin treatment was titrated during a 6-week, open-label, dose-optimization phase to a total dose of 300, 450, or 600 mg/d. Patients were considered responders if they had ≥50% reduction in pain (VAS) and rated their overall improvement on the PGIC as "much improved" or "very much improved." Responders were then randomized in the double-blind treatment phase to either the dose achieved during the open-label phase or to placebo. Patients were treated for ≤6 months after randomization. Treatment with pregabalin resulted in a longer time to loss of therapeutic response versus treatment with placebo. Additionally, 53% of patients treated with pregabalin continued pregabalin treatment and maintained a therapeutic response to Week 26 of the study versus 33% of patients administered placebo.

Safety. Cases of angioedema have been reported in patients treated with pregabalin, manifested by swelling of the face, mouth, and neck. Rarely, these cases have been life threatening. Patients treated with pregabalin have also experienced hypersensitivity, manifested by skin redness, blisters, hives, rash, dyspnea, and wheezing, shortly after initiation of treatment. Pregabalin treatment may also cause peripheral edema, dizziness and somnolence, weight gain, and blurred vision. Treatment with pregabalin has been associated with creatine kinase elevations and with decreases in platelet count. Pregabalin treatment has also been associated with PR interval prolongation. As with other antiepileptic drugs, pregabalin should be withdrawn gradually (over a minimum of 1 wk) when the drug is being discontinued. The most common adverse events associated with pregabalin therapy for the management of fibromyalgia include dizziness, somnolence, headache, weight gain, blurred vision, dry mouth, constipation, and fatigue.

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