Recommended Dosage of Horizant (Gabapentin Enacarbil) for RLS/PLMD
The FDA-approved and guideline-recommended dose of Horizant (gabapentin enacarbil) for moderate-to-severe restless legs syndrome in adults is 600 mg once daily, taken at approximately 5 PM with food. 1
Standard Dosing Protocol
Take 600 mg once daily at approximately 5 PM with food - this timing and food requirement are critical for optimal absorption and symptom control during evening hours when RLS symptoms typically worsen. 1
The 600 mg dose was specifically approved by the FDA because higher doses (1200 mg) provided no additional benefits in the primary endpoints while causing significantly higher rates of adverse events, particularly somnolence and dizziness. 2, 3
Pre-Treatment Requirements Before Starting Horizant
Before initiating gabapentin enacarbil, you must address these critical factors that can significantly impact treatment success:
Check iron studies (morning fasting ferritin and transferrin saturation) - supplement if ferritin ≤75 ng/mL or transferrin saturation <20%, as correcting iron deficiency may reduce or eliminate the need for pharmacotherapy. 1
Review and discontinue exacerbating medications including antihistamines, serotonergic agents (SSRIs, SNRIs), antidopaminergics (antipsychotics), alcohol, and caffeine. 1
Screen for untreated obstructive sleep apnea, as it can worsen RLS symptoms and increase risk of adverse effects from gabapentin enacarbil. 1
Key Advantages Over Dopamine Agonists
Gabapentin enacarbil does not cause augmentation - the paradoxical worsening of symptoms with earlier onset, increased intensity, and anatomic spread that occurs with dopamine agonists like pramipexole and ropinirole. 1, 4
The American Academy of Sleep Medicine now strongly recommends alpha-2-delta ligands (including gabapentin enacarbil) as first-line therapy over dopaminergic agents, representing a major shift from older 2009 guidelines. 4, 5
Expected Outcomes and Tolerability
In 12-week placebo-controlled trials, gabapentin enacarbil 600 mg significantly improved RLS symptom scores, pain scores, sleep quality, and mood outcomes compared to placebo. 6, 7
The most common adverse events are somnolence (21-24%) and dizziness (14-19%), which are typically mild to moderate in severity. 8
Responses are sustained in longer-term trials up to 52 weeks, with lower relapse rates compared to placebo. 6
No reports of augmentation or QT-interval prolongation have been documented with gabapentin enacarbil. 6
Critical Dosing Caveat
While some research suggests 1200 mg may provide additional benefits for severe sleep disturbances associated with RLS 2, the FDA-approved dose remains 600 mg once daily because the risk-benefit ratio favors the lower dose for the general RLS population. 1, 3 Higher doses should only be considered in consultation with sleep medicine specialists for refractory cases.
Special Population Considerations
Pregnancy: Consider pregnancy-specific safety profiles when treating RLS in pregnant women, as gabapentin enacarbil data in pregnancy are limited. 1
Renal impairment: Dose adjustment is required for patients with reduced creatinine clearance, though specific dosing for PLMD in renal disease is not well-established. 4