Mesuximide Phenytoin

Ethosuximide and mesuximide are succinimides. Ethosuximide is the agent of first choice for the management of absence (petit mal) seizures. It inhibits low-threshold Ca" " currents in the thalamus. As it may precipitate grand mal seizures it is frequently given together with a barbiturate or with phenytoin to prevent that. Its plasma concentrations do not closely correlate with the therapeutic effects. 

Of 26 patients with complex partial seizures refractory to phenytoin, carbamazepine, phenobarbital, or primidone, mesuximide produced a 50% or greater reduction in seizure frequency in eight after 8 weeks, and five of those continued to benefit after 3-34 months (1). Drowsiness, gastrointestinal disturbances, hiccups, irritability, and headache were the common adverse effects. 

Phenobarbital, phenytoin, and possibly felbamate increase the levels of the active metabolite of mesuximide, IV-desmethylmesux-imide. Mesuximide increases the serum levels of phenobarbital and phenytoin, and decreases the levels of lamotrigine, and to a lesser extent, valproate. 

Mesuximide was given to 17 patients taking phenytoin, which resulted in a 78% rise in the phenytoin serum levels requiring dose reductions in about 30% of the patients. It was also found that the concurrent use of phenytoin increased the serum levels of the active metabolite of mesuximide, V-desmethylmesuximide. ... 

It has been suggested that phenobarbital, phenytoin and felbamate compete with mesuximide for the same metabolic mechanisms (hydroxyla-tion) in the liver. As a result each one is metabolised more slowly and therefore their levels increase. Mesuximide appears to increase the clearance of valproate, and lamotrigine (which is principally via glucuronida-tion). 

Information about these interactions is limited. Nevertheless, concurrent use should be monitored. Anticipate the need to reduce the dose of phenytoin, phenobarbital or primidone if mesuximide is given. The dose of lamotrigine may need to be increased if mesuximide is given. There is also some evidence that the dose of valproate may need to be increased. 

The activity of mesuximide is thought to be due to its active metabolite, A-desmethylmesuximide. Therefore, it has been suggested that levels of this metabolite should also be monitored. Anticipate the need to reduce the dose of mesuximide if felbamate is added. Other antiepileptics such as phenobarbital and phenytoin may also increase levels of A-desmethylm-esuximide. ... 

Rambeck B, Pharmacological interactions of mesuximide with phenobarbital and phenytoin in hospitalized epileptic patients. Epilepsia (1979) 20,147-56,... 

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