Megaloblastic anemia drugs associated with

TABLE 102—5. Drugs Associated with Megaloblastic Anemia... 

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. 

It is incumbent on health professionals to avoid toxic drugs whenever possible. Antibiotics associated with CNS toxicities, usually when not dose-adjusted for renal function, include penicillins, cephalosporins, quinolones, and imipenem. Hematologic toxicities generally are manifested with prolonged use of nafcillin (neutropenia), piperacillin (platelet dysfunction), cefotetan (hypoprothrombinemia), chloramphenicol (bone marrow suppression, both idiosyncratic and dose-related toxicity), and trimethoprim (megaloblastic anemia). Reversible nephrotoxicity classically is associated with aminoglycosides... 

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. 

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