Trimethoprim-sulfamethoxazole adverse effects

Trimethoprim (Trimpex) interferes with the ability of bacteria to metabolize folinic acid, thereby exerting bacteriostatic activity. Trimethoprim is used for UTIs that are caused by susceptible microorganisms. Trimethoprim administration may result in rash, pruritus, epigastric distress, nausea, and vomiting. When trimethoprim is combined with sulfamethoxazole (Septra), the adverse effects associated with a sulfonamide may also occur. The adverse reactions seen with other anti-infectives, such as ampicillin, the sulfonamides, and cephalosporins, are given in their appropriate chapters. 

Co-trimoxazole is a combination of trimethoprim and the sulfonamide sulfamethoxazole. Since THF synthesis is inhibited at two successive steps, the antibacterial effect of co-trimoxazole is better than that of the individual components. Resistant pathogens are infrequent a bactericidal effect may occur. Adverse effects correspond to those of the components. 

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. 

The most common adverse effects of lamivudine seen at doses used to treat HBV are mild they include headache, malaise, fatigue, fever, insomnia, diarrhea, and upper respiratory infections. Elevated alanine aminotransferase (ALT), serum lipase, and creatine kinase may also occur. The safety and efficacy of lamivudine in patients with decompensated liver disease have not been established. Dosage adjustment is required in individuals with renal impairment. Coadministration of trimethoprim-sulfamethoxazole decreases the renal clearance of lamivudine. 

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. 

Potential adverse effects are headache, dizziness, insomnia, fatigue, and gastrointestinal discomfort, although these are typically mild. Lamivudine s bioavailability increases when it is -administered with trimethoprim-sulfamethoxazole. Lamivudine and zalcitabine may inhibit the intracellular phosphorylation of one another therefore, their concurrent use should be avoided if possible. Short-term safety of lamivudine has been demonstrated for both mother and infant. 

Atovaquone is an alternative therapy for P jiroveci infection, although its efficacy is lower than that of trimethoprim-sulfamethoxazole. Standard dosing is 750 mg taken with food twice daily for 21 days. Adverse effects include fever, rash, nausea, vomiting, diarrhea, headache, and insomnia. Serious adverse effects appear to be minimal, although experience with the drug remains limited. Atovaquone has also been effective in small numbers of immunocompromised patients with toxoplasmosis unresponsive to other agents, although its role in this disease is not yet defined. 

Doxycycline is commonly used for moderate to severe acne vulgaris. It is more effective and produces less resistance than tetracycline. The initial dose is 100 or 200 mg daily, followed by 50 mg daily as a maintenance dose after improvement is seen. Doxycycline maybe given with food, but it is more effective when taken 30 minutes before meals. / Minocycline is also commonly used for moderate to severe acne vulgaris. It is more effective than tetracycline. It is dosed similar to doxycycline (100 mg/day or 50 mg twice daily) and on an indefinite basis in selected patients. Minocycline has the most reported adverse effects of the tetracyclines, some of which may be serious. Trimethoprim-sulfamethoxazole (or trimethoprim alone) is a second-line oral agent that may be used for patients who do not tolerate tetracyclines and erythromycin or in cases of resistance to these antibiotics. The adult dose is usually 800 mg sulfamethoxazole and 160 mg trimethoprim twice daily. Clindamycin use is limited by diarrhea and the risk of pseudomembranous colitis. 

Woody RC, Brewster MA. Adverse effects of trimethoprim-sulfamethoxazole in a child with dihydropteridine reductase deficiency. Dev Med Child Neurol 1990 32(7) 639 2. 

The administration of DMSO is accompanied by few problems and is relatively safe. However, concentrations higher than 10% administered i.v. may cause intravascular hemolysis, diarrhea, muscle tremors and colic. Ocular toxicity and teratogenicity have been reported in laboratory animals treated with DMSO. In addition, the cutaneous absorption of DMSO may cause sedation, dizziness, headache or nausea in certain individuals. Because of these potential adverse effects, users, especially pregnant women, should take care to avoid contact when applying DMSO. Another major concern is the ability of DMSO to translocate other chemicals (Brayton 1986). Despite this, the i.v. administration of DMSO does not increase the CSF concentrations of trimethoprim or sulfamethoxazole (Green et al 1990). 

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. ... 

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. 

In one study 15 patients with tuberculosis, who had taken rifampicin 450 mg daily for at least 15 days, were given co-trimoxazole (trimethoprim 320 mg and sulfamethoxazole 800 mg 12-hourly) for 5 to 10 days. Rifampicin levels were measured at 5 time points over 6 hours before and during co-trimoxazole treatment. At 4 and 6 hours, rifampicin levels were significantly higher (27% and 56%, respectively) during co-trimoxazole treatment, but peak levels were only increased by about 18%. Concurrent use did not result in any increase in adverse effects over the study period. ... 

The incidence of side effects is higli Lower-dose oral therapy with 800 mg sulfamethoxazole plus 160 mg trimethoprim (given twice daily) has been used successjully in AIDS patients with less severe pneumonia (P02 >70 mm Hg). Prophylaxis with 800 mg sulfamethoxazole and 160 mg trimethoprim once daily or three times a week is effective in preventing pneumonia caused by this organism in patients with AIDS. Adverse reactions are less frequent with the lower prophylactic doses of trimethoprimr-sulfamethoxazole. The most common problems are rash, fever, leukopenia, and hepatitis. 

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