Gabapentin Enacarbil for Restless Legs Syndrome and Neuropathic Pain

Pharmacological Properties and Mechanism

• The prodrug gabapentin enacarbil is converted to gabapentin, which binds to voltage-gated calcium channels at the α2δ subunit to inhibit neurotransmitter release, providing sustained exposure throughout the day when taken once daily 1

FDA-Approved Indications and Clinical Evidence

• The American Academy of Sleep Medicine (AASM) gives gabapentin enacarbil a strong recommendation as first-line treatment for adults with restless legs syndrome (RLS), ranking it as the #1 pharmacological intervention based on moderate certainty of evidence 2, 3
• Gabapentin enacarbil is FDA-approved for the treatment of moderate to severe primary RLS in adults at a dose of 600 mg once daily, and also approved for the management of postherpetic neuralgia 2

Comparison to Standard Gabapentin and Guideline Recommendations

• The Centers for Disease Control and Prevention (CDC) and AASM guidelines recognize gabapentin enacarbil as distinct from standard gabapentin, with gabapentin enacarbil receiving the strongest recommendation for RLS treatment 2, 4
• The American Academy of Sleep Medicine recommends gabapentin enacarbil as a first-line treatment for RLS, while standard gabapentin remains first-line for neuropathic pain conditions such as diabetic neuropathy and postherpetic neuralgia 1, 4, 5