Horizant (Gabapentin Enacarbil) Dosing for RLS and PHN
For moderate to severe Restless Legs Syndrome (RLS), Horizant (gabapentin enacarbil) should be administered at 600 mg once daily with food at about 5 PM. 1, 2, 3
Dosing for Restless Legs Syndrome (RLS)
Recommended Dosing
- Initial and maintenance dose: 600 mg once daily with food at approximately 5 PM
- The 600 mg dose is FDA-approved as it provides optimal benefit with fewer adverse events compared to higher doses 2
- Take with food to enhance absorption and bioavailability
Alternative Dosing Considerations
- While clinical trials have evaluated doses up to 1,200 mg/day, the 600 mg dose is preferred due to:
- Similar efficacy to higher doses for subjective RLS symptoms
- Lower rates of adverse events like somnolence and dizziness 2
- For patients with severe sleep disturbances associated with RLS, some evidence suggests 1,200 mg/day may provide additional benefits 2
Dosing for Postherpetic Neuralgia (PHN)
- For PHN, Horizant is typically dosed at 1,800 mg daily, taken once daily with the evening meal 4, 5
- This extended-release formulation allows for once-daily dosing compared to immediate-release gabapentin which requires three divided doses 4
Efficacy Evidence
- Multiple clinical trials demonstrate that gabapentin enacarbil significantly improves:
- Long-term efficacy has been demonstrated in 36-week and 52-week extension studies 3, 5
Safety and Adverse Effects
- Most common adverse events: somnolence/sedation and dizziness 3, 5
- Most adverse events are mild to moderate in severity
- Notable advantages over dopaminergic agents for RLS:
- No reports of augmentation (worsening of symptoms over time)
- No QT-interval prolongation 3
- The American Academy of Sleep Medicine recommends alpha-2-delta ligands like gabapentin as first-line options for RLS due to favorable long-term safety profiles 6
Special Populations
- Dose adjustment may be necessary for patients with renal impairment
- For patients with CKD or ESRD, standard gabapentin (not enacarbil) with dose adjustment is recommended 6
Clinical Pearls
- Horizant should be taken with food to enhance absorption
- The timing of the dose (around 5 PM) is important for RLS management to ensure peak plasma levels coincide with typical symptom onset in the evening
- Unlike immediate-release gabapentin, the extended-release formulation of Horizant allows for once-daily dosing, improving convenience and potentially adherence 4
- Discontinuation should be gradual over at least one week to minimize withdrawal symptoms
Gabapentin enacarbil represents an important non-dopaminergic option for RLS treatment with sustained efficacy and favorable tolerability compared to dopamine agonists which carry risks of augmentation with long-term use 6, 3.