Phenytoin agranulocytosis with

Hypersensitivity reactions include morbilliform rash in 2—5% of patients and occasionally more serious skin reactions, including Stevens-Johnson syndrome. Systemic lupus erythematosus and potentially fatal hepatic necrosis have been reported rarely. Hematological reactions include neutropenia and leucopenia, or more rarely, red-cell aplasia, agranulocytosis, and thrombocytopenia Lymphadenopathy is associated with reduced immunoglobulin A (IgA) production. Hypoprothrombinemia and hemorrhage have occurred in the newborns of mothers who received phenytoin during pregnancy vitamin K is effective treatment or prophylaxis. 

Carbamazepine is metabolized in the liver to carbamtizepine-10, 11-epoxide, an active metabolite that partly contributes to both its anticonvulsant action and neurotoxicity. In contrast to phenytoin. there is u linear increa.se in serum concentration with dosage. Mild neurotoxic effects are common (nau.sea. dizziness, drowsiness, blurred vision and ataxia] and often detemiine the limit of dosage. Agranulocytosis is a rarer idiosyncratic reaction to carbamazepine. 

Severe and life-threatening agranulocytosis in 2 patients and thrombocytopenia in 6 other patients " have been attributed to the concurrent use of phenytoin and cimetidine. Severe skin reactions have also been reported in 3 patients treated with phenytoin, cimetidine, and dexametha-sone after resection of brain tumours, which resolved on discontinuing phenytoin. See also Corticosteroids + Phenytoin , p.l059 for the effects of dexamethasone on phenytoin levels. 

Cimetidine inhibits the activity of the liver enzymes concerned with the metabolism of phenytoin, thus allowing it to accumulate in the body and, in some instances, to reach toxic concentrations. Famotidine, nizatidine and ranitidine normally do not affect these enzymes. Agranulocytosis and thrombocytopenia are relatively rare manifestations of bone marrow depression caused by both phenytoin and the Hj-receptor antagonists. 

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