Phenytoin thrombocytopenia with

A 57-year-old woman developed a diffuse rash and thrombocytopenia with platelets as low as 20,000 per gL on a combination of phenytoin and dexamethasone [137 ]. The combination of these two drugs may worsen phenytoin-induced thrombocytopenia. 

Il.b.l.1. Adverse effects of anti-secretory treatment. Histamine H2 antagonists and proton pump inhibitors are very safe as well as effective treatments. Cimetidine has small effects on hepatic drug metabolism which are only of clinical signiflcance with drugs used in doses close to toxic levels, notably phenytoin, aminophylline and warfarin. Other adverse effects such as headache, rash and thrombocytopenia are rare. 

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. 

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. 

---