PEGANONE- ethotoin tablet
Lundbeck Inc.
DESCRIPTION
PEGANONE (ethotoin tablets, USP) is an oral antiepileptic of the hydantoin series and is chemically identified as 3-ethyl-5-phenyl-2,4-imidazolidinedione.
PEGANONE tablets are available in a dosage strength of 250 mg.
Inactive Ingredients
Acacia, lactose, sodium carboxymethylcellulose, stearic acid and talc.
CLINICAL PHARMACOLOGY
PEGANONE (ethotoin tablets, USP) exerts an antiepileptic effect without causing general central nervous system depression. The mechanism of action is probably very similar to that of phenytoin. The latter drug appears to stabilize rather than to raise the normal seizure threshold, and to prevent the spread of seizure activity rather than to abolish the primary focus of seizure discharges.
Ethotoin is fairly rapidly absorbed; the extent of oral absorption is not known. The drug exhibits saturable metabolism with respect to the formation of N-deethyl and p-hydroxyl-ethotoin, the major metabolites. Where plasma concentrations are below about 8 μg/mL, the elimination half-life of ethotoin is in the range of 3 to 9 hours. A study comparing single doses of 500 mg, 1000 mg, and 1500 mg of PEGANONE (ethotoin tablets, USP) demonstrated that ethotoin, and to a lesser extent 5-phenylhydantoin, a major metabolite, exhibits substantial nonlinear kinetics. The degree of nonlinearity with multiple dosing may be increased over that seen after a single dose, given the likelihood of plasma accumulation based on a reported elimination half-life of 6 to 9 hours and a dosing interval of 4 to 6 hours. Experience suggests that therapeutic plasma concentrations fall in the range of 15 to 50 μg/mL; however, this range is not as extensively documented as those quoted for other antiepileptics.
In laboratory animals, the drug was found effective against electroshock convulsions, and to a lesser extent, against complex partial (psychomotor) and pentylenetetrazol-induced seizures. In mice, the duration of antiepileptic activity was prolonged by hepatic injury but not by bilateral nephrectomy; the drug is apparently biotransformed by the liver.
INDICATIONS AND USAGE
PEGANONE (ethotoin tablets, USP) is indicated for the control of tonic-clonic (grand mal) and complex partial (psychomotor) seizures.
DOSAGE AND ADMINISTRATION
PEGANONE (ethotoin tablets, USP) is administered orally in 4 to 6 divided doses daily. The drug should be taken after food, and doses should be spaced as evenly as practicable. Initial dosage should be conservative. For adults, the initial daily dose should be 1 g or less, with subsequent gradual dosage increases over a period of several days. The optimum dosage must be determined on the basis of individual response. The usual adult maintenance dose is 2 to 3 g daily. Less than 2 g daily has been found ineffective in most adults.
Pediatric dosage depends upon the age and weight of the patient. The initial dose should not exceed 750 mg daily. The usual maintenance dose in children ranges from 500 mg to 1 g daily, although occasionally 2 or (rarely) 3 g daily may be necessary.
If a patient is receiving another antiepileptic drug, it should not be discontinued when PEGANONE therapy is begun. The dosage of the other drug should be reduced gradually as that of PEGANONE is increased. PEGANONE may eventually replace the other drug or the optimal dosage of both antiepileptics may be established.
In tonic-clonic (grand mal) seizures, use of the drug with phenobarbital may be beneficial.
