HORIZANT
Clinical safety rating: caution
Comprehensive clinical and safety monograph for HORIZANT (HORIZANT).
Gabapentin enacarbil is a prodrug of gabapentin, which binds to the alpha2-delta subunit of voltage-gated calcium channels in the central nervous system, reducing the release of excitatory neurotransmitters such as glutamate, norepinephrine, and substance P. This modulation decreases neuronal excitability and pain signaling.
| Metabolism | Hydrolyzed by non-specific esterases (primarily in enterocytes and hepatocytes) to gabapentin; gabapentin is not significantly metabolized and is excreted renally unchanged. Minor metabolism via gabapentin lactam formation. |
| Excretion | Renal: 90-95% unchanged in urine. Fecal/biliary: minimal (≤3%). |
| Half-life | 5-7 hours; in patients with CrCl <30 mL/min, half-life is prolonged with clinical need for dose adjustment. |
| Protein binding | ≤3%, primarily albumin. |
| Volume of Distribution | 0.9-1.3 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Oral: 90-100% (well absorbed, minimal first-pass effect). |
| Onset of Action | Oral: 1-2 hours; peak effects at 3-4 hours. |
| Duration of Action | 4-6 hours; clinical duration may be extended in renal impairment. |
600 mg orally once daily, taken in the morning with or without food.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | For CrCl 30-59 mL/min: 300 mg once daily; for CrCl 15-29 mL/min: 300 mg every other day; for CrCl <15 mL/min or on hemodialysis: not recommended. |
| Liver impairment | No dose adjustment required for mild-to-moderate hepatic impairment (Child-Pugh A or B); not studied in severe impairment (Child-Pugh C). |
| Pediatric use | Not approved for use in pediatric patients under 18 years of age. |
| Geriatric use | Select dose based on renal function; monitor for dizziness, somnolence, and falls; consider lower starting dose if renal impairment exists. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for HORIZANT (HORIZANT).
| Breastfeeding | Gabapentin is excreted into human milk. The milk-to-plasma concentration ratio of gabapentin is approximately 1.0. Infant exposure is estimated to be 1-2% of the maternal weight-adjusted dose. Effects on the nursing infant are unknown; caution is advised. Monitor infant for sedation and poor feeding. |
| Teratogenic Risk | Pregnancy Category C. In animal studies, gabapentin enacarbil (active ingredient of HORIZANT) caused developmental toxicity including skeletal malformations and reduced fetal weight at doses similar to human exposure. There are no adequate and well-controlled studies in pregnant women. First trimester: Potential risk based on animal data; second and third trimesters: Unknown risk; use only if maternal benefit outweighs fetal risk. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to gabapentin enacarbil or any component of the formulation
| Precautions | Central nervous system depression (dizziness, somnolence), syncope, suicidal behavior and ideation, respiratory depression (especially with concomitant CNS depressants or in patients with respiratory compromise), hypersensitivity reactions (including drug reaction with eosinophilia and systemic symptoms), increased seizure frequency if withdrawn abruptly, driving impairment, renal impairment (dose adjustment required), and carcinogenicity (pancreatic acinar cell tumors in animal studies; clinical significance unknown). |
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| Fetal Monitoring | Monitor maternal renal function, blood pressure, and signs of CNS depression. Fetal monitoring includes ultrasound for growth and development if exposure occurs during pregnancy. No specific fetal monitoring recommended beyond standard obstetric care. |
| Fertility Effects | In animal studies, no adverse effects on fertility were observed at doses up to 3 times the maximum human dose. No human data available; potential effect on male or female fertility is unknown. |