From the Guidelines
Gabapentin enacarbil is recommended over gabapentin for the treatment of restless legs syndrome (RLS) due to its improved bioavailability and absorption, leading to more consistent blood levels and potentially better adherence and symptom control, as supported by a strong recommendation with moderate certainty of evidence from the American Academy of Sleep Medicine 1. Gabapentin enacarbil and gabapentin are related medications with important differences. Gabapentin is the original medication, commonly prescribed for neuropathic pain, epilepsy, and certain anxiety disorders, typically dosed multiple times daily (300-1200mg three times daily) due to its shorter half-life and variable absorption.
- Key differences between gabapentin enacarbil and gabapentin include:
- Improved bioavailability and absorption of gabapentin enacarbil
- Once or twice-daily dosing of gabapentin enacarbil (typically 600mg once or twice daily) compared to multiple daily doses of gabapentin
- FDA approval of gabapentin enacarbil for restless legs syndrome and postherpetic neuralgia, while regular gabapentin has broader approved and off-label uses
- The improved pharmacokinetic profile of gabapentin enacarbil may result in better adherence and more consistent symptom control, as noted in the American Academy of Sleep Medicine clinical practice guideline 1.
- Both medications share similar overall side effect profiles, including dizziness, somnolence, and peripheral edema, but the improved absorption of gabapentin enacarbil may lead to fewer gastrointestinal side effects for some patients.
- The cost of gabapentin enacarbil is generally higher than generic gabapentin, which may influence prescription choices depending on insurance coverage and patient needs, although the guideline recommends its use over no gabapentin enacarbil despite this consideration 1.
From the Research
Comparison of Gabapentin Enacarbil and Gabapentin
- Gabapentin enacarbil is a prodrug of gabapentin, with different pharmacokinetics and a more predictable absorption rate 2.
- Studies have shown that gabapentin enacarbil is effective in treating moderate to severe primary restless legs syndrome (RLS) symptoms, with significant improvements in International Restless Legs Scale (IRLS) total score and Clinical Global Impression-Improvement (CGI-I) response 3, 4, 5.
- Gabapentin enacarbil has been compared to other RLS treatments, including dopamine agonists such as pramipexole and ropinirole, and has shown similar efficacy in alleviating RLS symptoms 2, 6.
- The safety profile of gabapentin enacarbil is generally well-tolerated, with common adverse events including somnolence and dizziness 4, 5.
Efficacy of Gabapentin Enacarbil
- Gabapentin enacarbil has been shown to be effective in treating RLS symptoms, including subjective symptoms and sleep disturbances 3, 5.
- The 600 mg once-daily dosage of gabapentin enacarbil has been approved by the US Food and Drug Administration for the treatment of moderate to severe primary RLS 3.
- Higher doses of gabapentin enacarbil (1200 mg or higher) may be more effective in treating severe sleep disturbances associated with RLS, but are also associated with higher rates of adverse events 3, 4.
Safety and Tolerability
- Gabapentin enacarbil has been shown to be generally well-tolerated, with common adverse events including somnolence and dizziness 4, 5.
- The safety profile of gabapentin enacarbil is consistent with that of gabapentin, but with a more predictable absorption rate and lower inter-patient variability in bioavailability 2.
- Gabapentin enacarbil may be associated with a lower risk of nausea and discontinuations due to adverse events compared to other RLS treatments, such as pramipexole and ropinirole 6.