Anticonvulsants + Stiripentol

Stiripentol causes marked rises in the serum levels of carbamazepine, phenobarbitone and phenytoin. Reduce their dosages to avoid the development of toxicity.

Clinical evidence

A study was undertaken on six epileptic patients taking two or three anticonvulsants (phenytoin, phenobarbitone, carba¬mazepine, pnmidone, nitrazepam) who were additionally given stiripentol (600-2400 mg dally). All five on phenytoin showed a reduction in the phenytoin clearance from 29 5 to 18 5 litre daily while taking 1200 mg stiripentiol daily, and to 6 48 litre daily while on 2400 mg stinpentol. These changes in clearance were reflected in marked rises in the steady-state serum levels of the anticonvulsants for example the serum phenytoin levels of one patient rose from 14 4 mg/1 to 27 4 mg/1 over 30 days while taking stinpentol, despite a halving of his phenytoin dosage. Phenytoin toxicity was seen in two subjects.

The clearance of carbamazepine in one subject fell from 209 to 128 litre daily while on 1200 mg stiripentol daily and to 61 litre daily while on 2400 mg stiripentol daily. Phenobarbitone clearance in two subjects fell from 3 8 and 5 litre daily to 2 3 and 3 4 litre daily while taking 2400 mg stinpentol daily 1 Another study in adults and children confirmed that stiripentol halved the clearance of carbamazepine.

Mechanism

Uncertain It seems probable that stinpentol inhibits the activity of the liver enzymes concerned with the metabolism of these anticonvulsants so that their loss from the body is reduced and their serum levels rise accordingly.

Importance and management

These interactions would seem to be established and of clinical importance. The dosages of phenytoin, pheno-barbitone and carbamazepine should be reduced to avoid the development of elevated serum levels and possible toxicity during concurrent use. In the case of phenytoin halving the dose may not be enough. One study suggests that the carbamazepine dosage should be decreased incrementally over 7-10 days as soon as the stinpentol is started and, regardless of age, the maintenance dose of carbamazepine should be 44 to 87 mg/kg/day to give serum levels of 5-10 /jg/ml.

Generic Neurontin

Generic Neurontin