nction, the frequency of dosing may need to be adjusted based on calculated creatinine clearance in these patients [see Dosage and Administration (2.3)].
8.6 Renal ImpairmentThe dose of HORIZANT should be adjusted in patients with renal impairment [see Dosage and Administration (2.3), Clinical Pharmacology (12.3)].
9 DRUG ABUSE AND DEPENDENCE
9.1 Controlled SubstanceHORIZANT, a prodrug of gabapentin, is not a scheduled drug.
9.2 AbuseGabapentin does not exhibit affinity for benzodiazepine, opiate (mu, delta, or kappa), or cannabinoid 1 receptor sites. A small number of postmarketing cases report gabapentin misuse and abuse. These individuals were taking higher than recommended doses of gabapentin for unapproved uses. Most of the individuals described in these reports had a history of poly-substance abuse or used gabapentin to relieve symptoms of withdrawal from other substances.
When prescribing products that deliver gabapentin, carefully eva luate patients for a history of drug abuse and observe them for signs and symptoms of gabapentin misuse or abuse (e.g., development of tolerance, self dose escalation, and drug-seeking behavior).
9.3 DependenceThere are rare postmarketing reports of individuals experiencing withdrawal symptoms shortly after discontinuing higher than recommended doses of gabapentin used to treat illnesses for which the drug is not approved. Such symptoms included agitation, disorientation, and confusion after suddenly discontinuing gabapentin that resolved after restarting gabapentin. Most of these individuals had a history of poly-substance abuse or used gabapentin to relieve symptoms of withdrawal from other substances. The dependence and abuse potential of gabapentin has not been eva luated in human studies.
10 OVERDOSAGE
10.1 Human Overdose ExperienceThere have been no reports describing individuals who have taken an overdose of HORIZANT. The highest single dose of gabapentin enacarbil administered to date is 6,000 mg in healthy subjects. At this supratherapeutic dose there were no serious adverse events. The incidence of central nervous system adverse reactions, particularly dizziness and somnolence/sedation, is increased with doses greater than 600 mg daily.
10.2 Overdosage ManagementIn the event of an overdose, the patient should be treated supportively with appropriate monitoring as necessary. Gabapentin derived from gabapentin enacarbil can be removed from plasma by hemodialysis. The mean percentage of gabapentin recovered following hemodialysis in patients with end stage renal disease was 29% (expressed as a proportion of the gabapentin released from HORIZANT).
Further management should be as clinically indicated or as recommended by a poison control center.
11 DESCRIPTION
HORIZANT (gabapentin enacarbil) is a prodrug of gabapentin. Gabapentin enacarbil is described as (1-{[({(1RS)-1-[(2-Methylpropanoyl)oxy]ethoxy}carbonyl)amino]methyl} cyclohexyl) acetic acid. It has a molecular formula of C16H27NO6 and a molecular weight of 329.39. It is a racemate and has the following structural formula:
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 300 mg or 600 mg of gabapentin enacarbil and the following inactive ingredients: colloidal si |
