Manufacturer:

GlaxoSmithKline Pharmaceuticals

Active Ingredient(s):

Gabapentin enacarbil 600mg; extended-release tablets.

Indication(s):

Treatment of moderate-to-severe ­primary restless legs syndrome (RLS) in adults.

Pharmacology:

Gabapentin enacarbil is a prodrug of gabapentin and, accordingly, its therapeutic effects in RLS are attributable to gabapentin. The precise mechanism by which gabapentin is ­efficacious in RLS is unknown. Gabapentin is structurally related to the neurotransmitter gamma-aminobutyric acid (GABA) but has no effect on GABA binding, uptake, or degradation. In vitro studies have shown that gabapentin binds with high affinity to the α2δ subunit of voltage-activated calcium channels; however, the relationship of this binding to the effects of gabapentin enacarbil in RLS is unknown.

Clinical Trials:

The effectiveness of Horizant in the treatment of moderate-to-severe primary RLS was demonstrated in two 12-week clinical studies in adults diagnosed with RLS using the International Restless Legs Syndrome Study Group diagnostic criteria. Patients with RLS secondary to other conditions (eg, pregnancy, renal failure, iron deficiency anemia) were excluded. In Study 1, patients were randomized to receive Horizant 1200mg or placebo taken once daily at about 5pm with food. In Study 2, patients were randomized to receive Horizant 600mg, Horizant 1200mg, or placebo taken once daily at about 5pm with food.

Efficacy was evaluated using the IRLS Rating Scale and Clinical Global Impression of Improvement (CGI-I) scores. The IRLS Rating Scale contains 10 items designed to assess the severity of sensory and motor symptoms, sleep disturbance, daytime somnolence/sedation, and impact on activities of daily living and mood associated with RLS. The range of scores is 0 to 40, with 0 being absence of RLS symptoms and 40 the most severe symptoms. The change from baseline in the IRLS Rating Scale at Week 12 and the proportion of responders on the CGI-I Scale defined as a rating of “much improved” or “very much improved” at Week 12 were co-­primary outcomes in these studies.

Statistically significant differences between the treatment groups receiving 600mg and 1200mg 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 (Study 1: Horizant 1200mg: –13.2, placebo: –8.8; Study 2: Horizant 600mg: –13.8, Horizant 1200mg: –13, placebo: –9.8) and the proportion of responders (“much improved” or “very much improved”) on the CGI-I Scale (Study 1: Horizant 1200mg: 76%, placebo: 39%; Study 2: Horizant 600mg: 73%, Horizant 1200mg: 77%, placebo: 45%).

Legal Classification:

Rx

Adults:

Swallow whole. Take with food. 600mg once daily at about 5pm (no additional benefit seen with 1200mg dose). If dose is not taken at recommended time, next dose should be taken the following day. Renal impairment: CrCl 30–59mL/min: 600mg on Day 1, Day 3, and every day thereafter. CrCl<30mL/min or on hemodialysis: not recommended.

Children:

Not recommended.

Warnings/Precautions:

Not interchangeable with other gabapentin products. Not recommended for patients who are required to sleep during the day and remain awake at night. May cause significant driving impairment; do not drive until impairment is assessed. Epilepsy. Monitor for worsening of depression, suicidal thoughts/behavior, and unusual changes in mood/behavior. Pregnancy (Cat. C). Nursing mothers: not recommended.

Adverse Reaction(s):

Somnolence/sedation, dizziness, balance disorder, blurred vision, disorientation, feeling drunk, lethargy, vertigo.

How Supplied:

Tabs—30

Last Updated:

7/21/2011