Serum phenytoin levels can rise if progabide is used concurrently. A reduction in the dosage of phenytoin may be required. A rise in serum phenobarbitone levels has been seen. Changes in the serum levels of other anticonvulsants (carbamazepine, sodium valproate, clonazepam) caused by progabide and their effects on serum progabide levels appear to be small.
Clinical evidence, mechanism, importance and management
Marked increases in serum phenytoin levels have been seen in a few patients given progabide concurrently. In one study in epileptic patients, 17 out of 26 needed a reduction in the dosage of phenytoin to keep the levels within + 25% of the serum levels before progabide was given, and this occurred within 4-10 weeks of starting concurrent treatment. Most of the patients needing a dosage reduction showed a maximum increase of 40% or more. In contrast only small changes were seen in another study. Yet another described a small increase in the clearance of progabide in the presence of phenytoin.
Information about other anticonvulsants is limited, but progabide is reported not to change carbamazepine or sodium valproate serum levels, nor to affect clonazepam levels significantly, while a small increase in serum phenobarbitone levels has been seen. An increase m carba-mazepme-epoxide levels has been reported. Some reduction in serum progabide levels is reported with sodium valproate.
The possibility that the dosage of phenytoin and phenobarbitone may need to be reduced should be borne in mind if progabide is used concurrently. The significance of the increased levels of carbamazepme-epoxide is uncertain.