Neurontin - Warnings & Precautions

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Phenytoin: In a single (400 mg) and multiple dose (400 mg TID) study of Neurontin ® in epileptic patients (N= 8) maintained on phenytoin monotherapy for at least 2 months, gabapentin had no effect on the steady-state trough plasma concentrations of phenytoin and phenytoin had no effect on gabapentin pharmacokinetics.

Carbamazepine:

Steady-state trough plasma carbamazepine and carbamazepine 10, 11 epoxide concentrations were not affected by concomitant gabapentin (400 mg TID; N= 12) administration. Likewise, gabapentin pharmacokinetics were unaltered by carbamazepine administration.

Valproic Acid:

The mean steady-state trough serum valproic acid concentrations prior to and during concomitant gabapentin administration (400 mg TID; N= 17) were not different and neither were gabapentin pharmacokinetic parameters affected by valproic acid.

Phenobarbital:

Estimates of steady-state pharmacokinetic parameters for phenobarbital or gabapentin (300 mg TID; N= 12) are identical whether the drugs are administered alone or together.

Naproxen:

Coadministration (N= 18) of naproxen sodium capsules (250 mg) with Neurontin ® (125 mg) appears to increase the amount of gabapentin absorbed by 12% to 15%. Gabapentin had no effect on naproxen pharmacokinetic parameters. These doses are lower than the therapeutic doses for both drugs. The magnitude of interaction within the recommended dose ranges of either drug is not known.

Hydrocodone:

Coadministration of Neurontin ® (125 to 500 mg; N= 48) decreases hydrocodone (10 mg; N= 50) Cmax and AUC values in a dose-dependent manner relative to administration of hydrocodone alone; Cmax and AUC values are 3% to 4% lower, respectively, after administration of 125 mg Neurontin ® and 21% to 22% lower, respectively, after administration of 500 mg Neurontin ® . The mechanism for this interaction is unknown. Hydrocodone increases gabapentin AUC values by 14%. The magnitude of interaction at other doses is not known.

Morphine:

A literature article reported that when a 60-mg controlled-release morphine capsule was administered 2 hours prior to a 600-mg Neurontin ® capsule (N= 12), mean gabapentin AUC increased by 44% compared to gabapentin administered without morphine (see PRECAUTIONS). Morphine pharmacokinetic parameter values were not affected by administration of Neurontin ® 2 hours after morphine. The magnitude of interaction at other doses is not known.