Trimethoprim 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. 

Trimethoprim produces the predictable adverse effects of an antifolate drug, especially megaloblastic anemia, leukopenia, and granulocytopenia. This can be prevented by the simultaneous administration of folinic acid, 6-8 mg/d. Use of folinic acid to prevent hematologic... 

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. 

TRIMETHOPRIM GANCICLOVIR/ VALGANCICLOVIR Possibly t adverse effects (e.g, myelosuppression) when trimethoprim is co administered with ganciclovir or valgancidovir Small t in bioavailability possible additive toxicity Well tolerated in a study. For patients at risk of additive toxicities, use only if benefits outweigh risks, and monitor FBC closely... 

The frequency and severity of the adverse effects of sulfonamides correspond to those seen with other antibacterial agents (2-5%). Dose-related effects, which tend to be more troublesome than serious, include gastrointestinal symptoms, headache, and drowsiness. Crystalluria can occur, but urinary obstruction is rare. Hematological adverse effects due to folic acid antagonism occur primarily in combination with trimethoprim. Hemolytic anemia occurs in patients with enzyme deficiencies and abnormal hemoglobins. Hypersensitivity... 

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. 

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. 

Concurrent acidosis in patients with trimethoprim-induced hyperkalemia is uncommon, which could be explained if the action of trimethoprim, like that of amiloride, is hmited to the cortical collecting tubule but does not affect the medullary collecting tubule, which has a large capacity to secrete hydrogen ions and may therefore prevent the development of acidosis. Predisposing factors for the rare adverse effect of renal tubular acidosis in this case may have been aldosterone deficiency or resistance, medullary dysfunction of sickle cell anemia, and renal insufficiency. All these factors could contribute to impaired renal handling of secretion of hydrogen ions (72). 

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). 

An early review of newer case reports and placebo-controlled trials involving several hundred patients did not show an increase in fetal abnormalities (176). However, the relative risks of cardiovascular defects and oral clefts in infants whose mothers were exposed to dihydrofolate reductase inhibitors, such as trimethoprim, during the second or third month after the last menstrual period, compared with infants whose mothers had no such exposure, are 3.4 (95% Cl = 1.8, 6.4) and 2.6 (1.1, 6.1) respectively (177). Multivitamin supplements containing folic acid reduced the adverse effects of dihydrofolate reductase inhibitors. There have been two reports of severe spinal malformations in the fetuses of HIV-positive women treated with combination antiretroviral therapy and co-trimoxazole (178). 

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. ... 

Adverse effects on the production of blood cells occur with prolonged use of trimethoprim. 

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