Horizant (gabapentin enacarbil) - 2 indications

Scroll down for information on each indication:

• the treatment of restless legs syndrome; approved April 2011
• the management of postherpetic neuralgia; approved June 2012

General Information

Horizant is an extended-release formulation of gabapentin enacarbil, a prodrug of gabapentin. The precise mechanism by which gabapentin is efficacious in restless legs syndrome (RLS) and postherpetic neuralgia (PHN) is unknown. 

Horizant is specifically indicated for the following:

• the treatment of moderate-to-severe primary RLS in adults
• for the management of PHN in adults

Horizant is supplied as an extended release tablet for oral administration. Tablets should be swallowed whole and should not be cut, crushed, or chewed. Tablets should be taken with food. Scroll down to see the recommended dosing/administration for each indication.

Mechanism of Action

Horizant is an extended-release formulation of gabapentin enacarbil, a prodrug of gabapentin. The precise mechanism by which gabapentin is efficacious in restless legs syndrome (RLS) and postherpetic neuralgia (PHN) is unknown. Gabapentin is structurally related to the neurotransmitter gamma-aminobutyric acid (GABA) but has no effect on GABA binding, uptake, or degradation.

Side Effects

Adverse effects associated with the use of Horizant for RLS may include, but are not limited to, the following:

• somnolence/sedation
• dizziness

Adverse effects associated with the use of Horizant for PHN may include, but are not limited to, the following:

• dizziness
• somnolence
• headache

Indication 1 - restless legs syndrome

approved April 2011

Dosing/Administration

The recommended dosage for Horizant is 600 mg once daily at about 5 PM. If the dose is not taken at the recommended time, the next dose should be taken the following day as prescribed.

Clinical Trial Results

The FDA approval of Horizant for RLS was based on two 12-week clinical studies in approximately 400 adults with RLS. The subjects were required to have a total score of ≥15 on the International Restless Legs Syndrome (IRLS) Rating Scale at baseline. In Study 1 the subjects received the 1,200mg of Horizant or placebo taken once daily at about 5 PM with food. In Study 2 the subjects received 600 mg of Horizant, 1,200 mg of Horizant or placebo taken once daily at about 5 PM with food. Efficacy was evaluated using the IRLS Rating Scale and Clinical Global Impression of Improvement (CGI-I) score. Statistically significant differences (P<0.05) between the treatment groups receiving 600 and 1,200 mg of Horizant and the group receiving placebo were observed at Week 12 for both the mean change from baseline in the IRLS Scale total score and the proportion of responders (much improved) or (very much improved) on the CGI-I Scale.

Indication 2 - the management of postherpetic neuralgia

approved June 2012

Dosing/Administration

The recommended dosage of Horizant is 600 mg twice daily. Horizant should be initiated at a dose of 600 mg in the morning for 3 days of therapy, then increased to 600 mg twice daily (1,200 mg/day) on day four. If the dose is not taken at the recommended time, skip this dose, and the next dose should be taken at the time of the next scheduled dose.

Clinical Trial Results

The FDA approval of Horizant for PHN was based on the results of one 12-week clinical trial. The multicenter, randomized, double-blind, parallel-group, placebo-controlled study evaluated the efficacy, safety, and dose response of 3 maintenance doses of Horizant (1,200, 2,400, and 3,600 mg/day, with 107, 82, and 87 adult subjects in each dosing group, respectively). Placebo was administered to 95 subjects. Subjects were required to have a minimum baseline 24-hour average Pain Intensity Numerical Rating Scale (PI-NRS) intensity score of at least 4.0 on the 11-point numerical PI-NRS. Following a 1-week baseline period during which subjects were screened for eligibility, subjects completed a 1-week up-titration period followed by a 12 week maintenance treatment period, and then a 1-week down-titration period. Treatment with Horizant statistically significantly improved the mean pain score and increased the proportion of subjects with at least a 50% reduction in pain score from baseline at all doses tested. A benefit over placebo was observed for all 3 doses of the drug as early as Week 1 and maintained to the end of treatment.