GRALISE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for GRALISE (GRALISE).
Gabapentin is a structural analogue of GABA, but it does not bind to GABA-A or GABA-B receptors. It is thought to exert its antiepileptic and analgesic effects by binding to the alpha-2-delta subunit of voltage-gated calcium channels, inhibiting calcium influx and reducing neurotransmitter release.
| Metabolism | Gabapentin is not significantly metabolized in humans. It is excreted unchanged in the urine. |
| Excretion | Renal elimination: >95% of absorbed dose excreted unchanged in urine. |
| Half-life | Terminal half-life: 5-7 hours in patients with normal renal function; prolonged in renal impairment (up to 32 hours in ESRD). |
| Protein binding | <3% bound to plasma proteins. |
| Volume of Distribution | Vd: 0.5-0.7 L/kg, indicating distribution into total body water. |
| Bioavailability | Oral: 80-90% (relative to immediate-release gabapentin); food slightly increases rate and extent of absorption. |
| Onset of Action | Oral: Peak plasma concentrations achieved 2-3 hours after dosing; clinical effect on neuropathic pain may be evident within 1-2 weeks of therapeutic dosing. |
| Duration of Action | Dosing interval typically every 8 hours; sustained effect over 24 hours with thrice-daily regimen; longer dosing interval in renal impairment. |
Administer orally once daily with evening meal: start at 300 mg on day 1, 600 mg on day 2, then 900 mg on days 3-6, then 1200 mg on days 7-10, then 1500 mg on days 11-14, then 1800 mg daily thereafter. For postherpetic neuralgia, titrate up to 1800 mg orally once daily with evening meal.
| Dosage form | TABLET |
| Renal impairment | For CrCl 30-59 mL/min: reduce dose by 50% of target maximum. For CrCl 15-29 mL/min: reduce dose by 75% of target maximum. For CrCl <15 mL/min: reduce dose by 90% of target maximum. Administer after hemodialysis on dialysis days. |
| Liver impairment | No specific dose adjustment recommended for hepatic impairment based on Child-Pugh score; use caution in severe impairment. |
| Pediatric use | Not approved for use in pediatric patients; safety and efficacy not established. |
| Geriatric use | Initiate at lower doses due to age-related renal impairment; consider dose adjustment based on creatinine clearance. Use the same titration schedule but do not exceed maximum dose of 1800 mg/day; monitor for dizziness, somnolence, and falls. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for GRALISE (GRALISE).
| Breastfeeding | Gabapentin is excreted into breast milk with a milk-to-plasma ratio (M/P) of approximately 1.0. Peak milk concentrations occur 2 hours after maternal dose. Infant exposure via breast milk is estimated at 1–4 mg/kg/day (5–15% of maternal weight-adjusted dose). Monitor infant for sedation, poor feeding, and hypotonia. Benefits of breastfeeding may outweigh risks in certain circumstances; risk-benefit assessment is recommended. |
| Teratogenic Risk | GRALISE (gabapentin) is classified as FDA Pregnancy Category C. First trimester: Animal studies show fetal developmental toxicity (skeletal and visceral anomalies) at doses below human therapeutic levels. Second/third trimester: Risk of neonatal withdrawal (jitteriness, irritability, hypotonia) and possible altered neurodevelopment. Data from pregnancy registries suggest increased risk of major congenital malformations (especially cardiac) and preterm birth, but causal attribution remains uncertain. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
["Hypersensitivity to gabapentin or any component of the formulation"]
| Precautions | ["Increased risk of suicidal thoughts or behavior","Respiratory depression, especially in patients with respiratory risk factors or concomitant CNS depressants","Dizziness and somnolence may impair ability to drive or operate machinery","Abrupt discontinuation may precipitate withdrawal symptoms","Anaphylaxis and angioedema","Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)","Cognitive and motor impairment","Increased seizure frequency if withdrawn abruptly in patients with epilepsy","Pancreatitis","Hematologic effects (e.g., leukopenia)"] |
Loading safety data…
| Fetal Monitoring | Monitor maternal gabapentin serum levels if toxicity suspected. Fetal surveillance: Targeted ultrasound for structural anomalies (especially cardiac) if exposure in first trimester. Neonatal monitoring: Observe for withdrawal symptoms (tremors, irritability, feeding difficulties) and respiratory depression for 48 hours post-delivery. Consider therapeutic drug monitoring during pregnancy due to altered pharmacokinetics. |
| Fertility Effects | In animal studies, high-dose gabapentin caused reversible effects on spermatogenesis (decreased testicular weight, sperm count) in male rats, and prolonged estrous cycle in female rats. Human data are limited; no significant impact on fertility has been reported, but potential for hormonal changes exists. Patients should be counseled regarding possible effects. |