Gabapentin Enacarbil Extended-Release Tablets

The following adverse reactions are described in more detail in the WARNINGS AND PRECAUTIONS section of the label:

• Somnolence/sedation and dizziness [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.

In all controlled and uncontrolled trials across various patient populations, more than 2,300 patients have received HORIZANT orally in daily doses ranging from 600 to 3,600 mg.

The exposure to HORIZANT in 1,201 patients with RLS included 613 exposed for at least 6 months and 371 exposed for at least 1 year. HORIZANT in the treatment of RLS was studied primarily in placebo-controlled trials (n = 642), and in longterm follow-up studies. The population with RLS ranged from 18 to 82 years of age, with 60% being female and 95% being Caucasian.

The safety of HORIZANT in doses ranging from 600 to 2,400 mg has been evaluated in 515 patients with RLS in 3 double-blind, placebo-controlled, 12-week clinical trials. The 600-mg dose was studied in 2 of the 3 studies. Eleven out of 163 (7%) patients treated with 600 mg of HORIZANT discontinued treatment due to adverse reactions compared with 10 of the 245 (4%) patients who received placebo.

The most commonly observed adverse reactions ( ≥ 5% and at least 2 times the rate of placebo) in these trials for the 600-mg dose of HORIZANT were somnolence/sedation and dizziness (see Table 4). Table 4 lists treatment-emergent adverse reactions that occurred in ≥ 2% of patients with RLS treated with HORIZANT and numerically greater than placebo.

Table 4: Incidence of Adverse Reactions in 12-Week RLS Studies Reported in ≥ 2% of Patients Treated With 600 or 1,200 mg of HORIZANT and Numerically Greater Than Placebo

Adverse reactions reported in these three 12-week studies in < 2% of patients treated with 600 mg of HORIZANT and numerically greater than placebo were balance disorder, blurred vision, disorientation, feeling drunk, lethargy, and vertigo.

The following adverse reactions were dose-related: somnolence/sedation, dizziness, feeling drunk, libido decreased, depression, headache, peripheral edema, and vertigo.

The exposure to HORIZANT in 417 patients with PHN included 207 patients exposed for at least 3 months. Overall, the mean age of patients in the PHN studies ranged from 61 to 64 years of age across dose groups; the majority of patients were male (45% to 61%) and Caucasian (80% to 98%).

The safety of HORIZANT in doses ranging from 1,200 to 3,600 mg has been evaluated in 417 patients with PHN in 3 clinical studies. The principal efficacy study evaluating the efficacy and safety of HORIZANT in the management of PHN was a 12-week, double-blind, multicenter study comparing 1,200 mg/day, 2,400 mg/day and 3,600 mg/day to placebo. Six out of 107 (6%) patients treated with 1,200 mg of HORIZANT discontinued treatment due to adverse events compared with 12 of the 95 (13%) patients who received placebo.

The most commonly observed adverse reactions ( ≥ 10% and greater than placebo) in this trial for the 1,200 mg dose of HORIZANT were dizziness, somnolence, and headache (see Table 5). Table 5 lists treatment-emergent adverse reactions that occurred in ≥ 2% of patients with PHN treated with HORIZANT 1,200 mg/day and numerically greater than placebo.

Table 5: Incidence of Adverse Reactions (in At Least 2% of Patients Treated With 1,200 mg/day of HORIZANT and Numerically Greater Than the Placebo Rate) Reported in All Patients in the 12-Week PHN Study

The following adverse reactions were also reported as ≥ 2% at 2,400 mg/day and/or 3,600 mg/day and appeared to be dose-related but were < 2% at 1,200 mg/day: balance disorder, confusional state, depression, dry mouth, flatulence, increased appetite, irritability, and vertigo. Dizziness, somnolence, fatigue, and insomnia appeared to show a dose relationship.

Adverse Events Associated With Gabapentin

The following adverse events have been reported in patients receiving gabapentin, either in clinical trials or postmarketing: breast enlargement, gynecomastia, and elevated creatine kinase.

Read the entire FDA prescribing information for Horizant (Gabapentin Enacarbil Extended-Release Tablets)