Introduction
Neurontin (gabapentin) is an anticonvulsant medication originally developed for the treatment of epilepsy. It is a structural analog of gamma-aminobutyric acid (GABA) but possesses a distinct mechanism of action from traditional GABAergic drugs. Over time, its therapeutic applications have expanded to include neuropathic pain conditions and other off-label uses.
Mechanism of Action
Gabapentin's exact mechanism remains incompletely understood. It does not directly interact with GABA receptors or significantly affect GABA uptake or metabolism. Instead, it binds to the α2δ-1 subunit of voltage-gated calcium channels in the central nervous system. This binding modulates calcium influx, reducing the release of excitatory neurotransmitters including glutamate, norepinephrine, and substance P. The drug also increases GABA synthesis and may influence NMDA receptor activity.
Indications
FDA-approved indications:- Postherpetic neuralgia
- Adjunctive therapy for partial seizures with and without secondary generalization in patients ≥3 years
- Neuropathic pain (diabetic neuropathy, radiculopathy)
- Fibromyalgia
- Restless legs syndrome
- Migraine prophylaxis
- Anxiety disorders
- Alcohol withdrawal syndrome
Dosage and Administration
Adults:- Epilepsy: Initial dose 300 mg three times daily; may titrate up to 1800-3600 mg/day
- Postherpetic neuralgia: Initial dose 300 mg on day 1, 300 mg twice daily on day 2, 300 mg three times daily on day 3; may increase to 1800-3600 mg/day
- CrCl ≥60 mL/min: 300-1200 mg three times daily
- CrCl 30-59 mL/min: 200-700 mg twice daily
- CrCl 15-29 mL/min: 200-700 mg once daily
- CrCl <15 mL/min: 100-300 mg once daily
- Take with or without food
- For patients requiring titration, gradual dose escalation over several days improves tolerability
- Do not crush or chew extended-release formulations
Pharmacokinetics
- Absorption: Bioavailability approximately 60% at 300 mg TID dosing; decreases with increasing doses due to saturable L-amino acid transport system
- Distribution: Volume of distribution 0.6-0.8 L/kg; not significantly protein bound
- Metabolism: Not significantly metabolized in humans; no hepatic cytochrome P450 involvement
- Elimination: Excreted unchanged primarily renally; elimination half-life 5-7 hours in normal renal function
- Special populations: Renal impairment significantly prolongs elimination; hemodialysis removes gabapentin
Contraindications
- Hypersensitivity to gabapentin or any component of the formulation
- Concomitant use with other gabapentinoids without specific clinical indication
Warnings and Precautions
Boxed Warning:- Increased risk of suicidal thoughts and behavior in patients taking antiepileptic drugs
- CNS depression: May impair mental and physical abilities; caution when operating machinery
- Respiratory depression: Risk increased with concomitant opioid use
- Withdrawal syndrome: Abrupt discontinuation may precipitate seizures or withdrawal symptoms
- Drug reaction with eosinophilia and systemic symptoms (DRESS)
- Anaphylaxis and angioedema
- Driving impairment: May cause dizziness, somnolence, and visual changes
Drug Interactions
- CNS depressants: Enhanced sedative effects with alcohol, opioids, benzodiazepines
- Antacids: Aluminum/magnesium-containing antacids reduce absorption by 20%; separate administration by至少2 hours
- Opioids: Increased risk of respiratory depression and CNS depression
- Morphine: Increased gabapentin concentrations
- Hydrocodone: Increased hydrocodone concentrations
Adverse Effects
Common (≥5%):- Dizziness (28%)
- Somnolence (21%)
- Peripheral edema (8%)
- Fatigue (11%)
- Ataxia (8%)
- Nystagmus (8%)
- Suicidal ideation and behavior
- Respiratory depression
- Severe dermatologic reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis)
- Angioedema
- Withdrawal seizures
- DRESS syndrome
Monitoring Parameters
- Efficacy: Seizure frequency, pain scores, functional assessment
- Safety: Mental status changes, mood alterations, suicidal ideation
- Renal function: Serum creatinine at baseline and periodically
- Neurological: Ataxia, dizziness, sedation
- Other: Weight gain, peripheral edema, visual changes
- Therapeutic drug monitoring: Not routinely indicated due to poor correlation between plasma concentrations and efficacy
Patient Education
- Take medication exactly as prescribed; do not stop abruptly
- May cause dizziness, drowsiness, or vision changes; avoid driving or hazardous activities until effects are known
- Do not consume alcohol while taking gabapentin
- Report any mood changes, depression, or suicidal thoughts immediately
- Notify healthcare provider if pregnancy is planned or suspected
- Keep all follow-up appointments for monitoring
- Be aware of potential withdrawal symptoms if discontinuing
- Inform all healthcare providers about gabapentin use, especially before surgery
References
1. FDA Prescribing Information: Neurontin (gabapentin). 2017 2. Backonja M, et al. Gabapentin for the symptomatic treatment of painful neuropathy in patients with diabetes mellitus. JAMA. 1998;280(21):1831-1836 3. Rowbotham M, et al. Gabapentin for the treatment of postherpetic neuralgia. JAMA. 1998;280(21):1837-1842 4. Patsalos PN, et al. Antiepileptic drugs—best practice guidelines for therapeutic drug monitoring. Therapeutic Drug Monitoring. 2008;30(1):1-13 5. Goodman CW, Brett AS. Gabapentin and Pregabalin for Pain. JAMA. 2017;318(17):1728 6. Bockbrader HN, et al. Clinical pharmacokinetics of gabapentin. Drugs. 2010;70(1):65-80 7. Johansen ME. Gabapentinoid Use in the United States 2002 Through 2015. JAMA Intern Med. 2018;178(2):292-294
This monograph is for educational purposes only and does not replace professional medical advice. Always consult with a healthcare provider for personalized medical recommendations.