Trimethoprim-sulfamethoxazole megaloblastic anemia with

Serious adverse effects are rare except in AIDS patients. TMP-SMX can cause the same adverse effects as those associated with sulfonamide administration, including skin rashes, central nervous system (CNS) disturbances, and blood dyscrasias. Blood dyscrasias, hepatotoxicity, and skin rashes are particularly common in patients with AIDS. Most of the adverse effects of this combination are due to the sulfamethoxazole component. Trimethoprim may increase the hematological toxicity of sulfamethoxazole. Long-term use of trimethoprim in persons with borderline foUc acid deficiency, such as alcoholics and the malnourished, may result in megaloblastic anemia, thrombocytopenia, and granulocytopenia. 

Trimethoprim produces the predictable adverse effects of an antifolate drug, especially megaloblastic anemia, leukopenia, and granulocytopenia. The combination trimethoprim-sulfamethoxazole may cause all of the untoward reactions associated with sulfonamides. Nausea and vomiting, drug fever, vasculitis, renal damage, and central nervous system disturbances occasionally occur also. Patients with AIDS and pneumocystis pneumonia have a particularly high frequency of untoward reactions to trimethoprim-sulfamethoxazole, especially fever, rashes, leukopenia, diarrhea, elevations of hepatic aminotransferases, hyperkalemia, and hyponatremia. 

Several drugs (e.g., sulfasalazine, trimethoprim-sulfamethoxazole, and methotrexate) have been reported to cause a fohc acid deficiency megaloblastic anemia. These drugs either interfere with folate absorption or inhibit the dihydrofolate reductase enzyme necessary for conversion of dihydrofolate to its active tetrahydrofolate form (see Chap. 102, on drug-induced blood dyscrasias). 

Antimalarial doses of pyrimethamine alone cause little toxicity except occasional rashes and depression of hematopoiesis. Excessive doses produce a megaloblastic anemia that responds to drug withdrawal or treatment with folinic acid. At high doses, pyrimethamine is teratogenic in animals, and in humans, trimethoprim-sulfamethoxazole therapy is associated with birth defects, but such toxicity has not been studied systematically for pyrimethamine in humans. 

F. Toxicity of Trimethoprim Trimethoprim may cause the predictable adverse effects of an antifolate dmg, including megaloblastic anemia, leukopenia, and granulocytopenia. These effects are usually ameliorated by supplementary folinic acid. The combination of trimethoprim-sulfamethoxazole may cause any of the adverse effects associated with the sulfonamides. AIDS patients given TMP-SMZ have a high incidence of adverse effects, including fever, rashes, leukopenia, and diarrhea. 

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