Trimethoprim

Warnings
Precautions

WARNINGS

Serious hypersensitivity reactions have been reported rarely in patients on trimethoprim (trimethoprim (trimethoprim tablet) tablet) therapy. Trimethoprim (trimethoprim (trimethoprim tablet) tablet) has been reported rarely to interfere with hematopoiesis, especially when administered in large doses and/or for prolonged periods.

The presence of clinical signs such as sore throat, fever, pallor or purpura may be early indications of serious blood disorders (see OVERDOSAGE: Chronic). Complete blood counts should be obtained if any of these signs are noted in a patient receiving trimethoprim (trimethoprim (trimethoprim tablet) tablet) and the drug discontinued if a significant reduction in the count of any formed blood element is found.

PRECAUTIONS

General

Trimethoprim (trimethoprim (trimethoprim tablet) tablet) should be given with caution to patients with possible folate deficiency. Folates may be administered concomitantly without interfering with the antibacterial action of trimethoprim.

Trimethoprim (trimethoprim (trimethoprim tablet) tablet) should also be given with caution to patients with impaired renal or hepatic function (see CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION).

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

Long-term studies in animals to evaluate carcinogenic potential have not been conducted with trimethoprim.

Mutagenesis

Trimethoprim (trimethoprim (trimethoprim tablet) tablet) was demonstrated to be nonmutagenic in the Ames assay. In studies at two laboratories, no chromosomal damage was detected in cultured Chinese hamster ovary cells at concentrations approximately 500 times human plasma levels; at concentrations approximately 1000 times human plasma levels in these same cells, a low level of chromosomal damage was induced at one of the laboratories. No chromosomal abnormalities were observed in cultured human leukocytes at concentrations of trimethoprim (trimethoprim (trimethoprim tablet) tablet) up to 20 times human steady-state plasma levels. No chromosomal effects were detected in peripheral lymphocytes of human subjects receiving 320 mg of trimethoprim (trimethoprim (trimethoprim tablet) tablet) in combination with up to 1600 mg of sulfamethoxazole per day for as long as 112 weeks.

Impairment of Fertility

No adverse effects on fertility or general reproductive performance were observed in rats given trimethoprim (trimethoprim (trimethoprim tablet) tablet) in oral dosages as high as 70 mg/kg/day for males and 14 mg/kg/day for females.

Pregnancy

Teratogenic Effects

Pregnancy Category C. Trimethoprim (trimethoprim (trimethoprim tablet) tablet) has been shown to be teratogenic in the rat when given in doses 40 times the human dose. In some rabbit studies, the overall increase in fetal loss (dead and resorbed and malformed conceptuses) was associated with doses six times the human therapeutic dose.

While there are no large, well-controlled studies on the use of trimethoprim (trimethoprim (trimethoprim tablet) tablet) in pregnant women, Brumfitt and Pursell,3 in a retrospective study, reported the outcome of 186 pregnancies during which the mother received either placebo or trimethoprim (trimethoprim (trimethoprim tablet) tablet) in combination with sulfamethoxazole. The incidence of congenital abnormalities was 4.5% (3 of 66) in those who received placebo and 3.3% (4 of 120) in those receiving trimethoprim (trimethoprim (trimethoprim tablet) tablet) and sulfamethoxazole. There were no abnormalities in the 10 children whose mothers received the drug during the first trimester. In a separate survey, Brumfitt and Pursell also found no congenital abnormalities in 35 children whose mothers had received trimethoprim (trimethoprim (trimethoprim tablet) tablet) and sulfamethoxazole at the time of conception or shortly thereafter.

Because trimethoprim may interfere with folic acid metabolism, trimethoprim (trimethoprim (trimethoprim tablet) tablet) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nonteratogenic Effects

The oral administration of trimethoprim (trimethoprim (trimethoprim tablet) tablet) to rats at a dose of 70 mg/kg/day commencing with the last third of gestation and continuing through parturition and lactation caused no deleterious effects on gestation or pup growth and survival.

Nursing Mothers

Trimethoprim is excreted in human milk. Because trimethoprim (trimethoprim (trimethoprim tablet) tablet) may interfere with folic acid metabolism, caution should be exercised when trimethoprim (trimethoprim (trimethoprim tablet) tablet) is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in pediatric patients below the age of 2 months have not been established. The effectiveness of trimethoprim (trimethoprim (trimethoprim tablet) tablet) as a single agent has not been established in pediatric patients under 12 years of age.

Geriatric Use

Clinical studies of trimethoprim (trimethoprim (trimethoprim tablet) tablet) tablets did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience4,5 has not identified differences in response between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.

Case reports of hyperkalemia in elderly patients receiving trimethoprim-sulfamethoxazole have been published.6 Trimethoprim (trimethoprim (trimethoprim tablet) tablet) is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor potassium concentrations and to monitor renal function by calculating creatinine clearance.

REFERENCES

3. Brumfitt W, Pursell R. Trimethoprim (trimethoprim (trimethoprim tablet) tablet) -sulfamethoxazole in the treatment of bacteriuria in women. J Infect Dis. 1973; 128 (suppl):S657-S663.

4. Lacey RW, Simpson MHC, Fawcett C, et al. Comparison of single-dose trimethoprim (trimethoprim (trimethoprim tablet) tablet) with a five-day course for the treatment of urinary tract infections in the elderly. Age and Ageing 10: 179-185, 1981.

5. Ewer TC, Bailey RR, Gilchrist NL, et al. Comparative study of norfloxacin and trimethoprim (trimethoprim (trimethoprim tablet) tablet) for the treatment of elderly patients with urinary tract infection. NZ Med J 101: 537-539, 1988.

6. Marinella MA. Trimethoprim (trimethoprim (trimethoprim tablet) tablet) -induced hyperkalemia: An analysis of reported cases. Gerontology 45: 209-212, 1999.

Last reviewed on RxList: 9/18/2008
This monograph has been modified to include the generic and brand name in many instances.

Warnings
Precautions
A A A

Report Problems to the Food and Drug Administration

 

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.


Women's Health

Find out what women really need.


NIH talks about Ebola on WebMD