Gabapentin

Neurontin is labeled for postherpetic neuralgia in adults and as adjunctive treatment of partial-onset seizures, with or without secondary generalization, in adults and children aged 3 years or older. It is not labeled as seizure monotherapy.

Gralise is labeled for postherpetic neuralgia and has different absorption and dosing. Horizant contains gabapentin enacarbil, a prodrug, and is labeled in adults for moderate-to-severe primary restless legs syndrome and postherpetic neuralgia; it is not recommended for patients who must sleep during the day and remain awake at night.

NICE includes gabapentin among initial options for adult neuropathic pain other than trigeminal neuralgia. Non-postherpetic neuropathic pain is outside the selected Neurontin U.S. label; the guideline is not a blanket indication for every chronic pain condition or sciatica.

For postherpetic neuralgia, studies of 1,800–3,600 mg/day did not demonstrate added benefit above 1,800 mg/day. Higher epilepsy doses have been studied, but they are not the routine recommended maintenance regimen. Renal adjustments can require substantially lower doses.

For hemodialysis, use maintenance dosing based on estimated clearance plus the label’s matched supplemental dose after each 4 hours of dialysis (125–350 mg across the listed regimens). The supplemental dose is not a stand-alone daily regimen; consult the complete table. Renal dosing in children younger than 12 has not been studied.

Take immediate-release Neurontin with or without food; swallow capsules whole with water. Scored 600 mg and 800 mg tablets may be halved: use the unused half for the next dose and discard halves unused for 28 days.

Reduce, discontinue, or replace treatment gradually over at least 1 week; a longer taper may be needed. Abrupt withdrawal can cause seizures and other withdrawal effects.

For adult postherpetic neuralgia, titrate with the evening meal: day 1, 300 mg; day 2, 600 mg; days 3–6, 900 mg; days 7–10, 1,200 mg; days 11–14, 1,500 mg; day 15, 1,800 mg once daily. Swallow whole; do not split, crush, or chew.

At creatinine clearance 30–60 mL/min, start 300 mg daily and titrate to an individualized 600–1,800 mg daily regimen. Do not administer when clearance is below 30 mL/min or during hemodialysis. Do not substitute this schedule for immediate-release dosing.

Take intact extended-release tablets with food. For adult restless legs syndrome with normal renal function: 600 mg at about 5 PM daily. For adult postherpetic neuralgia with normal renal function: 600 mg in the morning for 3 days, then 600 mg twice daily from day 4.

Both regimens require their own renal adjustments. For restless legs syndrome, hemodialysis use is not recommended. For postherpetic neuralgia, the label specifies a post-dialysis regimen. Use section 2.4 for the exact indication-specific titration, maintenance, and taper; do not use the Neurontin renal table.

Gabapentin is not appreciably metabolized. The label reports no hepatic-impairment study; it does not provide a separate hepatic dose-adjustment schedule. Renal function remains central to dosing.

Known hypersensitivity to gabapentin or any product ingredient. Renal impairment requires dose adjustment rather than being an immediate-release absolute contraindication; Gralise has separate renal restrictions.

The selected Neurontin label has no boxed warning. Its respiratory, hypersensitivity, suicidality, and withdrawal warnings remain clinically important.

Common trial events included dizziness, somnolence, and peripheral edema in postherpetic neuralgia; seizure trials also reported ataxia, fatigue, and nystagmus. Pediatric seizure trials reported fever, viral infection, nausea or vomiting, sleepiness, and hostility.

Postmarketing reports include serious skin reactions, rhabdomyolysis, respiratory depression, and withdrawal effects. Their frequencies cannot be reliably estimated from spontaneous reports.

• Opioids and other CNS depressants: additive sedation and breathing risk. Morphine can raise gabapentin exposure; monitor and adjust as clinically needed. Starting or stopping gabapentin can alter hydrocodone exposure and effect.
• Aluminum/magnesium hydroxide antacid: take immediate-release gabapentin at least 2 hours after the antacid.
• Gabapentin has little metabolic interaction with commonly coadministered antiseizure drugs, but pharmacodynamic sedation can still occur.
• Urine protein dipsticks can give false-positive results in the described antiseizure combination setting; use a more specific confirmatory method.

Tell the clinician about alcohol, opioid pain medicines, sleep medicines, and anxiety medicines. FDA recommends low initial doses and monitoring when combined with CNS depressants. Horizant additionally discourages alcohol because it can accelerate release from the extended-release product.

Available observational data have not indicated an increased risk of major birth defects or miscarriage, but study limitations remain and animal developmental toxicity was observed. Individualize treatment with the obstetric and prescribing clinicians. Prolonged exposure with opioids near delivery may increase neonatal withdrawal risk; monitor exposed newborns. The North American Antiepileptic Drug Pregnancy Registry is listed in the label.

Gabapentin enters human milk. The label states that infant effects and effects on milk production are unknown; consider breastfeeding benefits, maternal need, and potential infant risk together.

Adjunctive seizure treatment is established from age 3; pediatric postherpetic-neuralgia treatment and seizure treatment below age 3 are not established. Renal impairment in children younger than 12 has not been studied.

Older adults often have reduced clearance; choose doses by creatinine clearance and monitor sedation, ataxia, edema, and breathing risk.

The precise analgesic and antiseizure mechanisms are unknown. Gabapentin binds the α2δ subunit of voltage-activated calcium channels in vitro; the relationship to therapeutic effects is incompletely defined. Despite structural resemblance to GABA, it does not act by modifying GABA binding, uptake, or degradation.

Absorption

Saturable; bioavailability decreases as the immediate-release dose rises.

Metabolism / elimination

Not appreciably metabolized; excreted unchanged by the kidneys.

Half-life

About 5–7 hours with normal renal function; prolonged in renal impairment.

Dialysis

Hemodialysis removes gabapentin; dose supplementation depends on the regimen.

Gralise has meal-dependent absorption and a later peak than immediate-release gabapentin. Horizant is a prodrug absorbed through different transport pathways and converted to gabapentin; it gives approximately dose-proportional, extended exposure. Equal milligram doses across these products do not establish equivalent exposure or dosing frequency.

• Assess pain relief and function or seizure control against the indication. Reassess tolerability during titration.
• Review creatinine clearance for dosing, especially in older adults, renal disease, or dialysis.
• Monitor sedation, coordination, respiratory symptoms, and concomitant depressants.
• Monitor mood and suicidality during treatment and after discontinuation; track pediatric behavior and school performance.
• Evaluate rash, fever, swollen glands, or other hypersensitivity symptoms promptly; watch for self-escalation or misuse.

• Do not stop or change the dose without a clinician-directed plan.
• Avoid driving or hazardous work until the effect on alertness and coordination is understood.
• Tell the clinician about opioids, sedatives, alcohol, pregnancy, breastfeeding, and kidney or breathing disease.
• Use the correct liquid concentration and a calibrated measuring device. Do not interchange immediate-release, Gralise, and Horizant schedules.
• Seek emergency help for breathing difficulty, inability to awaken, or swelling affecting breathing. Report suicidal thoughts or severe mood changes immediately.
• For overdose, contact U.S. Poison Control at 1-800-222-1222 or obtain emergency assessment.

Other strengths and manufacturers differ. Verify the exact imprint and package with a pharmacist.

Dosage form / strength

Immediate-release capsule · 300 mg

Label distributor

Viatris Specialty LLC

Appearance

Yellow hard gelatin capsule

Imprint

VLE on body · Neurontin / 300 mg on cap

Example package NDC

58151-282-01 · 100 capsules

Neurontin capsules

100, 300, 400 mg

Neurontin tablets

Scored 600, 800 mg

Neurontin oral solution

250 mg/5 mL (50 mg/mL)

Gralise tablets

300, 450, 600, 750, 900 mg; distinct once-daily product

Horizant extended-release tablets

300, 600 mg gabapentin enacarbil; a prodrug

Neurontin capsules and tablets: 25°C (77°F), with excursions 15–30°C (59–86°F). Oral solution: refrigerate at 2–8°C (36–46°F). Discard unused tablet halves after 28 days. Other formulations have their own storage requirements.