Cimetidine thrombocytopenia with

McDaniel JL, Stein JJ (1979) Thrombocytopenia with cimetidine therapy. N Engl J Med 300 864... 

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. 

Cimetidine may infrequently cause diarrhea, nausea, vomiting, or mental confusion. A rare association with granulocytopenia, thrombocytopenia, and pancytopenia has been reported. Gynecomastia has been demonstrated in patients receiving either high-dose or... 

The main varieties of adverse effects attributed to cimetidine relate to its antiandrogenic properties and its actions in sufficient concentrations on the central nervous system. There is also a spectrum of drug interactions, mainly attributable to inhibition of hepatic CYP isoforms, but they only have clinical consequences under special circumstances. Occasional adverse effects, which are generally minor, include bradycardia and conduction defects, thrombocytopenia, neutropenia, interstitial nephritis, mild hepatic dysfunction, and headache. Intestinal infection due to loss of the gastric acid barrier also occurs, and myalgia, fever, monoamine oxidase-Uke interactions, and neuropathies have been well documented occasionally. Allergic reactions, such as bronchospasm, have rarely been described. Anaphylaxis with recurrence on rechallenge is on record, as are asthma and skin effects. 

Thrombocytopenia has been attributed to cimetidine, with recurrence on rechallenge, and neutropenia has also been documented as an occasional adverse effect, possibly related to inhibition of granulocyte colony growth (SEDA-10, 325). These effects appear to occur with aU H2 receptor antagonists in an incidence roughly proportional to their sales. Exceptionally, thrombocytopenia and leukopenia have occurred together (SEDA-17, 417). In one case of pancytopenia there was cimetidine dose-related inhibition of normal human CFU-GM colon formation (SEDA-16, 422). 

Famotidine is a histamine H2 receptor antagonist. It does not affect drug metabolism and it has been claimed to be free of the antiandrogenic effect of cimetidine however in one woman who accidentally took double doses of the drug for some months it did cause hyperprolactinemia and breast engorgement (SEDA-18, 372). In other ways it bears a very close resemblance to cimetidine for example, headache and confusion with intravenous use are reported, as are thrombocytopenia and pancytopenia (SEDA-15, 395). 

Although it is hard to make a direct comparison between famotidine and cimetidine, since the former has been less extensively used, it is possible that the hematological problems occur more often with famotidine there have been frequent well-documented reports of both thrombocytopenia and neutropenia, sometimes severe (SEDA-17, 417). 

Ranitidine is generally well tolerated in therapeutic doses. Ranitidine has less central nervous system (CNS) penetration, endocrine effects, and cardiovascular effects than cimetidine. Reported CNS effects associated with ranitidine include hallucinations, depression, delirium, headaches, dystonia, and choreoathetosis. Cardiac arrest during infusion, bradycardia, and progressive AV block with syncope have been reported in association with ranitidine. Abnormal liver enzymes, interstitial nephritis, parotitis, leukopenia, granulocytopenia, thrombocytopenia, pancytopenia, eosinophilia, vasculitis, dermatitis, toxic epidermal necrolysis, sexual impotence, gynecomastia, and polymyositis have also been reported in association with ranitidine therapy. 

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. 

Reports are inconsistent. Cimetidine and famotidine have been reported to increase cielosporin levels, whereas in other studies cimetidine, famotidine and ranitidine have been reported to not affect cielosporin levels. Both cimetidine and ranitidine have been reported to cause an increase in serum creatinine levels, in some but not all studies, but this may possibly not be a reliable indicator of increased nephrotoxicity. Isolated cases of thrombocytopenia and hepatotoxicity have been reported with ranitidine and cielosporin. 

Harpey JP, Caille B, Moulias R, Goust JM (1972) Drug allergy and lupus-like syndrome (with special reference to d-penicillamine). In Dash CH, Jones HEH (eds) Mechanisms in drug allergy. Churchill Livingstone, Edinburgh London, pp 51-57 Idvall J (1979) Cimetidine-associated thrombocytopenia. Lancet 2 159... 

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