Pfizer Inc (NEW YORK, NY) announced that the US FDA approved Lyrica® (pregabalin) capsules CV for the management of fibromyalgia, one of the most common chronic, widespread pain conditions in the US. Lyrica, which received a priority review, is the first FDA-approved medicine for the condition in adults. Pfizer has agreed to perform a study of the drug in children with fibromyalgia and a study in breastfeeding women.

The effectiveness of Lyrica in treating fibromyalgia was established in two randomized, placebo-controlled trials of approximately 1800 people, which demonstrated that doses of 300 to 450 mg per day reduced pain and improved physical function in fibromyalgia patients, when compared with placebo. In addition, symptoms of fibromyalgia worsened when Lyrica was withdrawn.

The most commonly occurring side effects for patients taking Lyrica were dizziness, somnolence, dry mouth, edema, blurred vision, weight gain, constipation, euphoric mood, balance disorder, increased appetite, and abnormal thinking (primarily difficulty with concentration/attention). A higher proportion of patients treated with Lyrica (7%) than patients treated with placebo (2%) reported blurred vision, which resolved with continued dosing in a majority of cases. More frequent assessment should be considered for patients who are routinely monitored for ocular conditions. Lyrica may cause allergic reactions, such as angioedema and hypersensitivity. If patients have had a drug or alcohol problem, they may be more likely to misuse Lyrica.

In addition to this new indication in the US, Lyrica is approved 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. Lyrica has been prescribed to more than 5 million patients worldwide.

Fibromyalgia is thought to result from neurological changes in how patients perceive pain, specifically a heightened sensitivity to stimuli that are not normally painful. Pregabalin binds with high affinity to the alpha2-delta site (an auxiliary subunit of voltage-gated calcium channels) in central nervous system tissues. Although the pregabalin's mechanism of action is unknown, results with genetically modified mice and compounds structurally related to pregabalin (such as gabapentin) suggest that binding to the alpha2-delta subunit may be involved in pregabalin's antinociceptive and antiseizure effects in animal models. In vitro, pregabalin reduces the calcium dependent release of several neurotransmitters, possibly by modulation of calcium channel function.

Although pregabalin is a structural derivative of the inhibitory neurotransmitter γ-aminobutyric acid (GABA), it does not bind directly to GABAA, GABAB, or benzodiazepine receptors, nor augment GABAA responses in cultured neurons, alter rat brain GABA concentration, or have acute effects on GABA uptake or degradation. However, prolonged application of pregabalin in cultured neurons increases the density of GABA transporter protein and increases functional GABA transport. Pregabalin does not block sodium channels or alter cyclooxygenase enzyme activity. It is inactive at opiate, serotonin, and dopamine receptors and does not inhibit dopamine, serotonin, or noradrenaline reuptake.

—J. McCloskey