Gabapentin

NEURONTIN ® is indicated for: • Management of postherpetic neuralgia in adults • 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 NEURONTIN is indicated for: • Postherpetic neuralgia in adults. • 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 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.

• Postherpetic Neuralgia o Dose can be titrated up as needed to a dose of 1800 mg/day o Day 1: Single 300 mg dose o Day 2: 600 mg/day (i.e., 300 mg two times a day) o Day 3: 900 mg/day (i.e., 300 mg three times a day) • Epilepsy with Partial Onset Seizures o 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 o 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 • Dose should be adjusted in patients with reduced renal function

NEURONTIN is contraindicated in patients who have demonstrated hypersensitivity to the drug or its ingredients. Known hypersensitivity to gabapentin or its ingredients

• Drug Reaction with Eosinophilia and Systemic Symptoms (Multiorgan hypersensitivity): Discontinue if alternative etiology is not established. • Anaphylaxis and Angioedema: Discontinue and evaluate patient immediately. • Driving Impairment, Somnolence/Sedation and Dizziness: Warn patients not to drive until they have gained sufficient experience to assess whether their ability to drive or operate heavy machinery will be impaired. • Suicidal Behavior and Ideation: Monitor for suicidal thoughts/behavior. • Abrupt or rapid discontinuation may increase the risk for seizures. Withdrawal symptoms, or suicidal behavior and ideation have been observed after discontinuation. • Respiratory Depression: May occur with NEURONTIN when used with concomitant central nervous system (CNS) depressants, including opioids, or in the setting of underlying respiratory impairment.

The following serious adverse reactions are discussed in greater detail in other sections: • Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity • Anaphylaxis and Angioedema • Somnolence/Sedation and Dizziness • Suicidal Behavior and Ideation • Increased Risk of Seizures and Other Adverse Reactions with Abrupt or Rapid Discontinuation • Status Epilepticus • Respiratory Depression • Neuropsychiatric Adverse Reactions (Pediatric Patients 3 to 12 Years of Age) Most common adverse reactions (incidence ≥8% and at least twice that for placebo) were: • Postherpetic neuralgia: Dizziness, somnolence, and peripheral edema. • Epilepsy in patients >12 years of age: Somnolence, dizziness, ataxia, fatigue, and nystagmus. • Epilepsy in patients 3 to 12 years of age: Viral infection, fever, nausea and/or vomiting, somnolence, and hostility

Concentrations increased by morphine, may need dose adjustment Opioids Respiratory depression and sedation, sometimes resulting in death, have been reported following coadministration of gabapentin with opioids (e.g., morphine, hydrocodone, oxycodone, buprenorphine). Hydrocodone Coadministration of NEURONTIN with hydrocodone decreases hydrocodone exposure. The potential for alteration in hydrocodone exposure and effect should be considered when NEURONTIN is started or discontinued in a patient taking hydrocodone. Morphine When gabapentin is administered with morphine, patients should be observed for signs of CNS depression, such as somnolence, sedation and respiratory depression.

Store NEURONTIN Tablets and Capsules at 25°C (77°F), excursions permitted between 15°C to 30°C (59°F to 86°F). Store NEURONTIN Oral Solution refrigerated, 2°C to 8°C (36°F to 46°F).