Neurontin (gabapentin) - 2 indications

Scroll down for information on each indication:

• adjunctive therapy to treat partial seizures with and without secondary generalization in adults w/ epilepsy; approval expanded to include pediatric patients three years of age and older; approved March 2000, October 2000
• the treatment of Post-herpetic neuralgia (PHN); approved May 2002

General Information

Neurontin (gabapentin) is an anticonvulsant.

Neurotin is specifically indicated for the following:

• adjunctive therapy in the treatment of partial onset seizures, with and without secondary generalization, in adults and pediatric patients 3 years and older with epilepsy
• the management of postherpetic neuralgia in adults

Neurontin is supplied as capsules, tablets and as an oral solution. Scroll down for specific dosing recommendations for each indication.

Mechanism of Action

The precise mechanisms by which gabapentin produces its analgesic and antiepileptic actions are unknown. Gabapentin is structurally related to the neurotransmitter gamma-aminobutyric acid (GABA) but has no effect on GABA binding, uptake, or degradation. In vitro studies have shown that gabapentin binds with high-affinity to the α2δ subunit of voltage-activated calcium channels; however, the relationship of this binding to the therapeutic effects of gabapentin is unknown.

Side Effects

Adverse effects associated with the use of Neurontin for postherpetic neuralgia may include, but are not limited to, the following:

• dizziness
• somnolence
• peripheral edema

Adverse effects associated with the use of Neurontin for epilepsy in patients >12 years of age may include, but are not limited to, the following:

• somnolence
• dizziness
• ataxia
• fatigue
• nystagmus

Adverse effects associated with the use of Neurontin for epilepsy in patients 3 to 12 years of age may include, but are not limited to, the following:

• viral infection
• fever
• nausea and/or vomiting
• somnolence
• hostility

Indication 1 -adjunctive therapy to treat partial seizures in adults and pediatrics >3 years of age

approved March and October 2000

Dosing/Administration

• Patients 12 years of age and older: starting dose is 300 mg three times daily; may be titrated up to 600 mg three times daily
• Patients 3 to 11 years of age: starting dose range is 10 to 15 mg/kg/day, given in three divided doses; recommended dose in patients 3 to 4 years of age is 40 mg/kg/day, given in three divided doses; the recommended dose in patients 5 to 11 years of age is 25 to 35 mg/kg/day, given in three divided doses. The recommended dose is reached by upward titration over a period of approximately 3 days.

Clinical Trial Results

The effectiveness of Neurontin Capsules as adjunctive therapy was established in three multicenter placebo-controlled, double-blind, parallel-group trials in 705 adults with refractory partial seizures. Effectiveness was assessed primarily on the basis of the percent of patients with a 50% or greater reduction in seizure frequency from baseline to treatment (the "responder rate") and a derived measure called response ratio.

One study compared Neurontin 1200 mg/day TID with placebo. The responder rate was 23% in the Neurontin group and 9% in the placebo group; the difference between groups was statistically significant. A second study compared primarily 1200 mg/day TID Neurontin with placebo, with additional Neurontin dosage groups (600 mg/day, 1800 mg/day) also studied for information regarding dose response. The responder rate was higher in the Neurontin 1200 mg/day group (16%) than in the placebo group (8%), but the difference was not statistically significant. The responder rate at 600 mg was also not significantly higher than in the placebo, but the rate in the 1800 mg group was statistically superior to the placebo rate. A third study compared Neurontin 900 mg/day TID and placebo. A statistically significant difference in responder rate was seen in the Neurontin 900 mg/day group (22%) compared to that in the placebo group (10%). 

A fourth study in pediatric patients age 3 to 12 years compared 25 –35 mg/kg/day Neurontin (N=118) with placebo (N=127). For all partial seizures in the intent-to-treat population, the response ratio was statistically significantly better for the Neurontin group (-0.146) than for the placebo group (-0.079). For the same population, the responder rate for Neurontin (21%) was not significantly different from placebo (18%).

A study in pediatric patients age 1 month to 3 years compared 40 mg/kg/day Neurontin (N=38) with placebo (N=38) in patients who were receiving at least one marketed antiepileptic drug and had at least one partial seizure during the screening period (within 2 weeks prior to baseline). Patients had up to 48 hours of baseline and up to 72 hours of double-blind video EEG monitoring to record and count the occurrence of seizures. There were no statistically significant differences between treatments in either the response ratio or responder rate.

Indication 2 - Post-herpetic neuralgia (PHN)

approved May 2002

Dosing/Administration

Dose can be titrated up as needed to a dose of 1800 mg/day

• Day 1: Single 300 mg dose
• Day 2: 600 mg/day (i.e., 300 mg two times a day)
• Day 3: 900 mg/day (i.e., 300 mg three times a day)

Clinical Trial Results

The approval of Neurontin was supported by a multi-center trial involving 229 subjects with PHN. Results showed that subjects suffering from PHN experienced a statistically significant reduction in average daily pain after treatment with Neurontin. Almost twice as many subjects treated with Neurontin (16%) were pain-free versus those treated with placebo (8.8%) at the end of the trial. The study also showed that those receiving Neurontin experienced improvement in sleep and overall quality of life.