Adverse drug reactions trimethoprim

Sulphonamides, amongst the first successful chemotherapeutic agents, now have their place in medicine mainly in combination with trimethoprim. Because of the risks of adverse drug reactions associated with their use, this is generally restricted to specific indications where other therapeutic agents have clearly inferior efficacy. Many sulphonamide compounds have been withdrawn from the market. Their individual names are standardised in the UK to begin with sulfa-. ... 

Antonen JA, Markula KP, Pertovaara MI, Pasternack AI. Adverse drug reactions in Sjogren s syndrome. Frequent allergic reactions and a specific trimethoprim-associated systemic reaction. Scand J Rheumatol 1999 28(3) 157-9. 

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. 

PCP = Pneumocystis carinii pneumonia AIDS = acquired immunodeficiency syndrome ADR adverse drug reaction TMP-SMX = trimethoprim sulfamethoxazole. 

Cribb AE, Lee BL, Trepanier LA, et al. Adverse reactions to sulphonamide and sulphonamide-trimethoprim antimicrobials clinical syndromes and pathogenesis. Adverse Drug React Toxicol Rev 1996 15 9-50. 

Trimethoprim-sulfamethoxazole is used frequently for preventive or active treatment of Pneumocystis carinii pneumonia in patients with the AIDS. Adverse reactions to trimethoprim-sulfamethoxazole have been observed to occur much more frequently in these patients compared with those without AIDS. Adverse effects to trimethoprim-sulfamethoxazole occur in 50% to 80% of AIDS patients compared with 10% of other immunocompromised patients. Trimethoprim-sulfamethoxazole was associated with an adverse-event rate of 26.3 per 100 person-years and hypersensitivity events at 22 per 100 person-years. Adverse-event rate was related to lower CD4+ cell count. When the CD4+ cell count was less than 100/mm , the adverse drug event rate was 31 per 100 person-years. ... 

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. 

Pentamidine is a well-established alternative therapy for pulmonary and extrapulmonary disease caused by P jiroveci. The drug has somewhat lower efficacy and greater toxicity than trimethoprim-sulfamethoxazole. The standard dosage is 3 mg/kg/d intravenously for 21 days. Significant adverse reactions are common, and with multiple regimens now available to treat P jiroveci infection, pentamidine is best reserved for patients with severe disease who cannot tolerate or fail other drugs. 

Drugs that inhibit folate metabolism increase the likelihood of serious adverse reactions to methotrexate, particularly hematological toxicity. The additional risk of myelosuppression and subsequent severe pancytopenia has been particularly exemplified by the combination of methotrexate and co-trimoxazole (trimethoprim plus sulfamethoxazole) (133). This should also be taken into account in patients taking trimethoprim alone (SEDA-22, 418). 

Drug-related adverse events are rare with nitrofurantoin and occur in fewer patients than with co-trimoxazole or trimethoprim, for example (1-3). The frequency of certain adverse reactions varies in different geographical areas (4,5). Lung reactions are more prevalent in Scandinavia and South Africa than in the UK, whereas polyneuropathies or gastrointestinal reactions are more frequent in the UK than in Sweden. These discrepancies are unexplained. 

Dapsone in combination with trimethoprim is also used for the treatment of mild to moderate first episodes of TCP, or alone for PCP prophylaxis [115, 198]. The most frequent adverse events are dose related metheglobinemia and hemolytic anemia. Since multi-drug therapy began to be used in leprosy patients, an increasing number of a rare, idiosyncratic reaction with multiorgan involvement... 

Uncertain, but a reasonable surmise can be made. Pyrimethamine and trimethoprim are both folate antagonists and both selectively inhibit the actions of the enzyme dihydrofolate reductase, which is concerned with the eventual synthesis of the nucleic acids needed for the production of new cells. The sulfonamides inhibit another part of the same synthetic chain. The adverse reactions seen would seem to reflect a gross reduction of the normal folate metabolism caused by the combined actions of both drugs. Megaloblastic anaemia and pancytopenia are among the adverse reactions of pyrimethamine and, more rarely, of co-trimoxazole taken alone. 

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