Mesuximide Phenobarbital

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. 

Sherwin, A. L., Ethosuximide Chnical use, m Antiepileptic Drugs, 4th ed.. Levy, R. H., Mattson, R. H., and Meldrum, B. S., Eds., Raven Press, New York, 1994. Battino, D., Estienne, M., and Avanzini, G., Chnical pharmacokinetics of antiepileptic drugs in paediatric patients. Part 1 Phenobarbital, primidone, valproic acid, ethosuximide and mesuximide, Clin. Pharmacokinet., 29 257-286, 1995. 

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. 

A study in hospitalised patients with petit mal epilepsy found that when mesuximide was given to 8 patients taking phenobarbital and 13 patients taking primidone, the mean serum levels of phenobarbital rose by 38% and 40%, respectively. Dose reductions were needed in 50% and 62% of patients, respectively. It was also found that the concurrent use of phenobarbital increased the serum levels of the active metabolite of mesuximide, A-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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