Drowsiness primidone

The dose-related adverse effects of primidone are similar to those of its metabolite, phenobarbital, except that drowsiness occurs early in treatment and may be prominent if the initial dose is too large. Gradual increments are indicated when starting the drug in either children or adults. 

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 is probably as effective as carbamazepine and phenytoin in the treatment of tonic-clonic and partial seizures, but it i,s much more sedative. Tolerance occurs with prolonged use and sudden withdrawal may precipitate status epilcpticus. Side-effects include cerebellar symptoms (e.g, sedation, iitaxia. nystagmus), drowsiness in adults and liyperkinc.sia in children. Primidone is metabolized to active anticonvulsant metabolites, one of which is phenobarbital. 

An established interaction. If felbamate is added to established treatment with phenobarbital or primidone, particularly in patients already taking substmtial doses, monitor well for any evidence of increased adverse effects (drowsiness, lethargy, anorexia, ataxia) and reduce the dosages of the phenobarbital or primidone if necessary. 

Another child who had been treated with valproate for several years was prescribed isoniazid for the treatment of tuberculosis. At the same time, seizures recurred, and the valproate was stopped and primidone 750 mg daily started. Seven months later seizures persisted, and she was admitted to hospital. Liver enzyme values were normal. Valproate 300 mg daily increased to 600 mg daily was added, and within 2 days she was vomiting and drowsy. After 5 days she had increased liver enzymes and her prothrombin time had fallen, so the valproate was stopped. Valproate levels were 81 micrograms/mL. It was speculated that the CNS effects and hepatic impairment were due to an interaction between the valproate and isoniazid. ... 

Comparative studies In an open prospective comparison of valproate and primidone in 136 patients with partial epilepsy unresponsive to carbamazepine significantly more of those who took valproate (51%) achieved a greater than 50% seizure reduction than those who took primidone (34%) [231 ]. One patient withdrew from valproate because of dizziness and three because of nausea. Of those who took primidone, three withdrew because of dizziness, three patients because of drowsiness, and one because of gastrointestinal complaints. Adverse effects in other patients were mild and gradually disappeared during treatment. 

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