Adverse Effects and Drug Interactions

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. Tri-methoprim may increase the hematological toxicity of sulfamethoxazole. Long-term use of trimethoprim in persons with borderline folic acid deficiency, such as alcoholics and the malnourished, may result in megaloblastic anemia, thrombocytopenia, and granulocytopenia.

Trimethoprim has been reported to decrease the therapeutic effect of cyclosporine with a concomitant increased risk of nephrotoxicity. Increased levels of dapsone, warfarin, methotrexate, zidovudine, and sul-fonylureas may occur when given together with tri-methoprim; dosages of these drugs should be modified and the patient monitored accordingly.

Because both drugs may interfere with folic acid metabolism, their use during pregnancy is usually con-traindicated by the potential for effects on the fetus, such as the development of neural tube defects associated with folate deficiency. The use of trimethoprim is contraindicated in patients with blood dyscrasias, hepatic damage, and renal impairment.


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