Primidone Isoniazid

Drugs that may affect primidone include acetazolamide, carbamazepine, hydantoins, isoniazid, nicotinamide, and succinimides. 

Certain concomitantly administered drugs may interfere with the effectiveness of the oral contraceptives or lead to an increased incidence of breakthrough bleeding. These include rifampin, isoniazid, ampiciUin, neomycin, penicillin V, chloramphenicol, sulfonamides, nitrofurantoin, phenytoin, barbiturates, primidone, analgesics, and phenothiazines. 

Increased effects (P450 3A4 inhibitors) cimetidine, danazol, diltiazem, erythromycin, troleandomycin, clarithromycin, fluoxetine, isoniazid, niacinamide, nicotinamide, propoxyphene, ketoconazole, itraconazole, verapamil,and valproate Decreased effects (P450 3A4 inducers) cisplatin, doxorubicin, felbamate, rifampin, phenobarbital, phenytoin, primidone, theophylline... 

Carbamazepine, cholestyramine, dexamethasone, isoniazid, nafcillin, octreotide, phenobarbital, phenytoin, primidone, rifampin, sulfadimidine, sulfinpyrazone, ticlopidine Increase concentrations of CNIs... 

Cerebellar symptoms such as tremor can be troubling and difficult to control. Medications that may be helpful include propranolol, primidone, and isoniazid. 

Primidone Isoniazid Deer, metabolism of primidone Chlorpromazine Deer, chlorpromazine... 

Transient elevations of the serum transaminases occur in 12% to 15% of patients receiving isoniazid and usually occur within the first 8 to 12 weeks of therapy. Overt hep ato toxicity, however, occurs in only 1% of cases. Risk factors for hepatotoxicity include patient age, preexisting liver disease, excessive alcohol intake, pregnancy, and the postpartum state. Isoniazid also may result in neurotoxicity, most frequently presenting as peripheral neuropathy or, in overdose, as seizures and coma. Patients with pyridox-ine deficiency, such as pregnant women, alcoholics, children, and the malnourished, are at increased risk. Isoniazid may inhibit the metabolism of phenytoin, carbamazepine, primidone, and warfarin." Patients who are being treated with these agents should be monitored closely, and appropriate dose adjustments should be made when necessary. 

A single case report describes elevated serum primidone levels and reduced phenobarbital levels when primidone was given with isoniazid. 

A patient taking primidone had raised serum primidone levels and reduced serum phenobarbital levels. This was attributed to the concurrent use of isoniazid, which inhibited the metabolism of the primidone by the liver. The half-life of primidone rose from 8.7 to 14 hours while taking isoniazid and steady-state primidone levels rose by 83%. The importance of this interaction is uncertain but prescribers should bear this interaction in mind in case of an unexpected response to primidone. 

Sutton G, Kupfeibeig HJ Isoniazid as an inhibitor of primidone metabolism. Neurology (1975) 25,1179-81... 

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. ... 

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