HORIZANT® (gabapentin enacarbil) Extended

Gabapentin enacarbil is a white to off-white crystalline solid with a melting onset of approximately 64°C and a solubility of 0.5 mg/mL in water and 10.2 mg/mL in phosphate buffer (pH 6.3).

HORIZANT is administered orally. Each HORIZANT Extended-Release Tablet contains 600 mg of gabapentin enacarbil and the following inactive ingredients: colloidal silicon dioxide, dibasic calcium phosphate dihydrate, glyceryl behenate, magnesium stearate, sodium lauryl sulfate, and talc.

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. Gabapentin enacarbil and gabapentin have been tested in radioligand binding assays, and neither exhibited affinity for a number of other common receptor, ion channel, or transporter proteins.

In vitro studies have shown that gabapentin binds with high affinity to the a2d subunit of voltage-activated calcium channels; however, the relationship of this binding to the therapeutic effects of gabapentin enacarbil in RLS is unknown.

USE IN SPECIFIC POPULATIONS
Pregnancy: based on animal data, may cause fetal harm.
Renal impairment: Dosage adjustments necessary. HORIZANT is not recommended for use in patients with creatinine clearance (CrCl) <30 mL/min or in patients on hemodialysis.

None.

• Driving impairment: Warn patients not to drive until they have gained sufficient experience with HORIZANT to assess whether it will impair their ability to drive.
• Somnolence/sedation and dizziness: May impair the patient’s ability to operate complex machinery.
• HORIZANT is not interchangeable with other gabapentin products.
• Suicidal thoughts or behaviors: Monitor for suicidal thoughts or behaviors.

To report SUSPECTED ADVERSE REACTIONS, contact GlaxoSmithKline at 1-888-825-5249 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

Restless Legs Syndrome
The recommended dosage for HORIZANT is 600 mg once daily taken with food at about 5 PM. A daily dose of 1,200 mg provided no additional benefit compared with the 600-mg dose, but caused an increase in adverse reactions.

If the dose is not taken at the recommended time, the next dose should be taken the following day as prescribed.

Tablets should be swallowed whole and should not be cut, crushed, or chewed.

Renal Impairment and Hemodialysis
In patients with compromised renal function (creatinine clearance [CrCl] 30 to 59 mL/min), 600 mg of HORIZANT should be administered on Day 1, Day 3, and every day thereafter.

In patients with stable renal function, CrCl can be estimated using the equation of Cockcroft and Gault:

for males: CrCl = (140-age)(weight) / [(72)(SCr)]

for females: CrCl = (0.85)(140-age)(weight) / [(72)(SCr)]

where age is in years, weight is in kilograms, and SCr is serum creatinine in mg/dL.

HORIZANT is not recommended for use in patients with a CrCl <30 mL/min or on hemodialysis because the dose cannot be reduced below 600 mg.

HORIZANT Extended-Release Tablets, 600 mg, are white to off-white, oval-shaped tablets debossed with “GS LFG”. HORIZANT Extended-Release Tablets may contain occasional black/grey spots.

NDC 0173-0806-01: Bottles of 30

Store at 25°C (77°F); excursions permitted 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Protect from moisture. Do not remove desiccants. Dispense in original bottle.

for:
GlaxoSmithKline
Research Triangle Park, NC 27709

Licensed from:
XenoPort, Inc.
Santa Clara, CA 95051
©2011, GlaxoSmithKline. All rights reserved.

April 2011