Trimethoprim thrombocytopenia 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. 

Severe adverse drug reactions with trimethoprim and co-trimoxazole are rare (12-14). This also applies to children (15). The adverse effects of co-trimoxazole correspond to those expected from a sulfonamide (16). In HIV-infected patients, adverse effects of co-trimox-azole are more frequent and more severe (17-19). Hematological disturbances due to co-trimoxazole include mild anemia, leukopenia, and thrombocytopenia, which may be due to folic acid antagonism. Serious metabolic disturbances that are associated with trimethoprim include hyperkalemia and metabolic acidosis. Trimethoprim can cause hypersensitivity reactions. However, with co-trimoxazole, the sulfonamide is generally believed to be more allergenic (12). Generalized skin reactions predominate. Other effects, such as anaphylactic shock, are extremely rare (20-22). Carcinogenicity due to trimethoprim or co-trimoxazole has not been reported. 

Most hematological adverse effects associated with trimethoprim have been reported with co-trimoxazole. These include macrocytic and megaloblastic anemia, aplastic anemia, neutropenia, hypersegmentation of leukocytes, thrombocytopenia, and pancytopenia (12,61-63,75-79). Sulfonamides alone have not been associated with folate deficiency, but in combination with trimethoprim they can deplete folate stores in patients with preexisting deficiency of folate or vitamin B12 (80). Treatment with co-trimoxazole can impair the function of mobilized autologous peripheral blood stem cells (81). 

Bradley PP, Warden GD, Maxwell JG, Rothstein G. Neutropenia and thrombocytopenia in renal allograft recipients treated with trimethoprim-sulfamethoxazole. Ann Intern Med 1980 93(4) 560-2. 

Trimethoprim (and pyrimethamine) may cause anemia, leukopenia, and thrombocytopenia, most commonly in debilitated or immunosuppressed patients. Hematotoxicity, drug fever, rashes, and severe GI distress are problematic in patients with AIDS. 

Trimethoprim is the only weak base listed (fluoroquinolones and sulfonamides are acidic compounds), and its high lipid solubility at blood pH allows penetration of the drug into prostatic and vaginal fluid to reach levels similar to those in plasma. Leukopenia and thrombocytopenia may occur in folate deficiency when the drug is used alone or in combination with sulfamethoxazole. Fluoroquinolones do not exacerbate symptoms of folic acid deficiency. The answer is (D). 

The observation that haematologieal toxieity often seemed to occur in renal transplant patients given azathioprine and co-trimoxazole, prompted a retrospective survey of the records of 40 patients. It was found that there was no difference in the incidence of thrombocytopenia and neutropenia in those given azathioprine, either alone, or with co-trimoxazole, (trimethoprim 160 to 320 mg and sulfamethoxazole 800 mg to 1.6 g daily) for a short time (6 to 16 days), but a significant increase occurred in the incidence and duration of thrombocytopenia and neutropenia if both drugs were given together for 22 days or more. ... 

Other reports describe a few patients given ciclosporin with co-trimoxazole who developed rises in creatinine levels (interpreted as evidence of nephrotoxicity), " interstitial nephritis, granulocytopenia and thrombocytopenia. Apparent nephrotoxicity has also been seen with trimethoprim and ciclosporin. ... 

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