Neurontin (gabapentin) is an anticonvulsant and neuropathic pain agent indicated for the management of postherpetic neuralgia and as adjunctive therapy in the treatment of partial onset seizures with and without secondary generalization in patients 3 years of age and older. Its mechanism of action, while not fully elucidated, is distinct from other antiepileptic drugs, as it is believed to bind to the alpha-2-delta subunit of voltage-gated calcium channels in the central nervous system. This action modulates the release of several excitatory neurotransmitters, resulting in its therapeutic effects on neuronal excitability and pain signaling pathways. This profile provides a comprehensive overview for healthcare professionals regarding its appropriate clinical application.

Features

• Active Pharmaceutical Ingredient: Gabapentin.
• Available Formulations: Film-coated tablets (600 mg, 800 mg), capsules (100 mg, 300 mg, 400 mg), and an oral solution (250 mg/5 mL).
• Pharmacologic Class: Anticonvulsant, Analog of the neurotransmitter gamma-aminobutyric acid (GABA).
• Mechanism of Action: Binds to the alpha-2-delta subunit of voltage-dependent calcium channels, reducing the release of excitatory neurotransmitters.
• Bioavailability: Is dose-dependent and not proportional to dose increase; decreases with higher single doses (e.g., 60% for 300 mg, 35% for 1600 mg).
• Elimination Half-life: Approximately 5 to 7 hours in patients with normal renal function.
• Primary Route of Elimination: Renal excretion, unchanged.

Benefits

• Provides effective management of neuropathic pain conditions, particularly postherpetic neuralgia, improving patient quality of life.
• Offers adjunctive control for partial seizures, reducing seizure frequency in both adult and pediatric populations.
• Exhibits a favorable pharmacokinetic profile with no hepatic metabolism, minimizing risk of drug interactions mediated by the cytochrome P450 enzyme system.
• Allows for flexible dosing titration, enabling clinicians to tailor therapy to individual patient response and tolerability.
• Presents a generally well-tolerated side effect profile when initiated and titrated appropriately.

Common use

Neurontin is primarily prescribed for two key indications. First, for the management of neuropathic pain associated with postherpetic neuralgia in adults. Second, as adjunctive therapy (added to other antiepileptic drugs) in the treatment of partial onset seizures with and without secondary generalization in adults and pediatric patients 3 years and older. It is also used off-label for a variety of other conditions, including other neuropathic pain syndromes (e.g., diabetic neuropathy), restless legs syndrome, and certain anxiety disorders, based on clinical evidence and practitioner judgment. Its use is always contingent upon a thorough patient assessment and diagnosis.

Dosage and direction

Dosing must be individualized based on therapeutic response and patient tolerability. For postherpetic neuralgia in adults, therapy may be initiated with a single 300 mg dose on Day 1, 600 mg/day (300 mg two times daily) on Day 2, and 900 mg/day (300 mg three times daily) on Day 3. The dose can subsequently be titrated up as needed for pain relief to a daily dose of 1800 mg (divided into three daily doses). Doses up to 3600 mg/day have been studied, but no additional benefit was demonstrated, and a higher incidence of adverse reactions was observed.

For epilepsy, the effective dose is 900 to 1800 mg/day in three divided doses. Titration to an effective dose can occur rapidly, over three days, using a three-times-daily schedule. The initial dose is 300 mg three times daily on Day 1, which can be increased to 300 mg four times daily on Day 2, and 600 mg four times daily on Day 3.

Crucially, for all patients, Neurontin must be taken with particular attention to dosing frequency. The prescribed daily dose should be administered in three divided doses, with no more than 12 hours between doses, to maintain consistent serum levels. The tablets should be swallowed whole with plenty of water. Dosage adjustment is required in patients with impaired renal function, calculated based on creatinine clearance (CrCl).

Precautions

Patients should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, or any unusual changes in mood or behavior. Antiepileptic drugs, including Neurontin, increase the risk of suicidal thoughts or behavior. Patients, their caregivers, and families should be advised of this risk and advised to be alert for the emergence or worsening of these symptoms. Caution is advised when driving or operating complex machinery until the patient’s experience with the drug is established, as Neurontin can cause dizziness, somnolence, and other CNS effects. Abrupt withdrawal of anticonvulsant therapy may precipitate status epilepticus; therefore, gradual withdrawal over a minimum of one week is recommended. Patients with a history of substance abuse should be closely monitored.

Contraindications

Neurontin is contraindicated in patients with a known hypersensitivity to gabapentin or any of the inactive ingredients in the formulations.

Possible side effect

The most commonly observed adverse reactions (≥5% and twice the rate of placebo) associated with the use of Neurontin in adults are:

• Dizziness
• Somnolence (sleepiness)
• Peripheral edema (swelling of the extremities)
• Asthenia (weakness)
• Ataxia (lack of coordination)
• Fatigue
• Nystagmus (involuntary eye movement)
• Tremor
• Blurred vision
• Diplopia (double vision)
• Dry mouth Other reported side effects include weight gain, dysarthria (slurred speech), and amnesia. Most adverse events are mild to moderate and dose-related.

Drug interaction

Gabapentin is not metabolized in the liver and does not induce or inhibit hepatic cytochrome P450 enzymes, limiting its potential for pharmacokinetic interactions. However, pharmacodynamic interactions are possible. Antacids containing aluminum and magnesium can reduce the bioavailability of gabapentin by approximately 20%. It is recommended to administer gabontin at least 2 hours following antacid intake. Coadministration with other CNS depressants (e.g., opioids, benzodiazepines, barbiturates, alcohol) may potentiate sedation, dizziness, and respiratory depression. Morphine coadministration increases gabapentin AUC and may require gabapentin dose adjustment. Hydrocodone coadministration increases gabapentin AUC.

Missed dose

If a dose is missed, it should be taken as soon as it is remembered. However, if it is almost time for the next scheduled dose, the missed dose should be skipped, and the regular dosing schedule resumed. Patients should be instructed not to take a double dose to make up for a missed one.

Overdose

Overdose has been reported with symptoms including double vision, slurred speech, drowsiness, lethargy, and diarrhea. Fatal cases have been reported in combination with other CNS depressants, notably opioids. In the event of a suspected overdose, supportive care should be initiated, including maintaining an adequate airway and ventilation. Hemodialysis is an effective means of removing gabapentin from the bloodstream and may be indicated in significant overdose, especially in patients with renal impairment. The value of gastric lavage or emesis is variable.

Storage

Store Neurontin capsules and tablets at room temperature, 20°C to 25°C (68°F to 77°F), in their original container to protect from moisture. The oral solution should be stored at 2°C to 8°C (36°F to 46°F) and discarded after 56 days if not used. Keep all medications out of the reach of children and pets.

Disclaimer

This information is intended for educational purposes and as a summary for healthcare professionals. It is not exhaustive and does not replace the full Prescribing Information. The prescribing physician remains responsible for determining the appropriate dosage and therapy for each individual patient, considering their specific clinical situation, contraindications, and potential adverse effects. Patients must be directed to consult their healthcare provider for any questions regarding their medical condition or treatment.

Reviews

• Clinical Efficacy in PHN: “In multiple randomized, double-blind, placebo-controlled trials, gabapentin demonstrated statistically significant and clinically meaningful reductions in pain scores for patients with postherpetic neuralgia. It is a well-established first-line option in our treatment algorithm.” – Neurologist, Pain Management Specialist
• Adjunctive Seizure Control: “As an add-on therapy for refractory partial seizures, Neurontin provides a useful tool. Its lack of significant drug interactions is a major advantage in polypharmacy patients. Titration is key to managing initial side effects like dizziness.” – Epileptologist
• Tolerability Profile: “While generally well-tolerated, the side effects of somnolence and dizziness are very real and can impact patient adherence. A slow, upward titration from a low dose is the best strategy to improve tolerability and allow patients to persist with therapy.” – Clinical Pharmacist
• Practical Considerations: “The requirement for TID dosing can be a barrier for some patients, and the dose-dependent absorption is a unique pharmacokinetic feature we must account for. The renal dosing adjustments are straightforward but absolutely critical to prevent toxicity.” – Nephrologist