Trimethoprim

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Also indexed as:

Proloprim, Trimpex

Trimethoprim is an antibacterial drug used to treat people with urinary tract infections. The combination drug product trimethoprim/sulfamethoxazole (TMP/SMX) is used to treat a wide variety of bacterial infections and some infections due to parasites.

Herbs

Summary of Interactions for Trimethoprim

Depletion or interference	Calcium* Folic acid* Magnesium* Vitamin B12* Vitamin B6* Vitamin K*
Adverse interaction	Potassium
Side effect reduction/prevention	Bifidobacterium longum* Folic acid Lactobacillus acidophilus* Lactobacillus casei* Saccharomyces boulardii* Saccharomyces cerevisiae* Vitamin K*
Supportive interaction	Saccharomyces boulardii*
Reduced drug absorption/bioavailability	None known

An asterisk (*) next to an item in the summary indicates that the interaction is supported only by weak, fragmentary, and/or contradictory scientific evidence.

Interactions with Supplements

Note: Sulfonamides, including sulfamethoxazole, can decrease absorption of calcium, magnesium, and vitamin B12.¹ Since sulfamethoxazole is often prescribed in combination with trimethoprim (e.g., Bactrim® or Septra®), it may be easy to associate this interaction with trimethoprim. However, this interaction is not known to occur with trimethoprim alone.

Folic acid, Vitamin B6, Vitamin K

The use of multivitamin supplements containing folic acid diminishes the occurrence of birth defects associated with trimethoprim. According to one study,² pregnant women who took folic acid-containing multivitamin supplements in addition to their prescription drugs had fewer babies with heart defects and deformities of the upper lip and mouth.

TMP/SMX has been rarely associated with folic acid-deficiency anemia.³ This action may be due to trimethoprim-induced folic acid depletion.⁴ Trimethoprim and TMP/SMX should be used with caution in patients with folic acid deficiency, for which blood tests are available. Folic acid replacement does not interfere with the antibacterial activity of trimethoprim⁵ or TMP/SMX.⁶

Potassium

TMP/SMX has been reported to elevate blood potassium and other constituents of blood (creatine and BUN).^{7, 8} In particular, people with impaired kidney function should be closely monitored by their prescribing doctor for these changes. People taking trimethoprim or TMP/SMX should talk with the prescribing doctor before taking any potassium supplements or potassium-containing products, such as No Salt®, Salt Substitute®, Lite Salt®, and even high-potassium foods (primarily fruit).

Probiotics

A common side effect of antibiotics is diarrhea, which may be caused by the elimination of beneficial bacteria normally found in the colon. Controlled studies have shown that taking probiotic microorganisms-such as Lactobacillus casei, Lactobacillus acidophilus, Bifidobacterium longum, or Saccharomyces boulardii -helps prevent antibiotic-induced diarrhea.⁹

The diarrhea experienced by some people who take antibiotics also might be due to an overgrowth of the bacterium Clostridium difficile, which causes a disease known as pseudomembranous colitis. Controlled studies have shown that supplementation with harmless yeast-such as Saccharomyces boulardii ¹⁰ or Saccharomyces cerevisiae (baker's or brewer's yeast)¹¹ -helps prevent recurrence of this infection. In one study, taking 500 mg of Saccharomyces boulardii twice daily enhanced the effectiveness of the antibiotic vancomycin in preventing recurrent clostridium infection.¹² Therefore, people taking antibiotics who later develop diarrhea might benefit from supplementing with saccharomyces organisms.

Treatment with antibiotics also commonly leads to an overgrowth of yeast (Candida albicans) in the vagina (candida vaginitis) and the intestines (sometimes referred to as "dysbiosis"). Controlled studies have shown that Lactobacillus acidophilus might prevent candida vaginitis.¹³

Vitamin K

Several cases of excessive bleeding have been reported in people who take antibiotics.^{14, 15, 16, 17} This side effect may be the result of reduced vitamin K activity and/or reduced vitamin K production by bacteria in the colon. One study showed that people who had taken broad-spectrum antibiotics had lower liver concentrations of vitamin K2 (menaquinone), though vitamin K1 (phylloquinone) levels remained normal.¹⁸ Several antibiotics appear to exert a strong effect on vitamin K activity, while others may not have any effect. Therefore, one should refer to a specific antibiotic for information on whether it interacts with vitamin K. Doctors of natural medicine sometimes recommend vitamin K supplementation to people taking antibiotics. Additional research is needed to determine whether the amount of vitamin K1 found in some multivitamins is sufficient to prevent antibiotic-induced bleeding. Moreover, most multivitamins do not contain vitamin K.

References

1. Holt GA. Food & Drug Interactions. Chicago: Precept Press, 1998, 248-49, 250-1.
2. Hernández-Díaz S, Werler MM, Walker AM, Mitchell AA. Folic acid antagonists during pregnancy and the risk of birth defects. New Engl J Med 2000;343:1608-14.
3. Sahai J. Urinary tract infections. In Applied Therapeutics: The Clinical Use of Drugs, 6th ed. Vancouver, WA: Applied Therapeutics, 1995, 63-6.
4. Kahn SB, Fein SA, Brodsky I. Effects of trimethoprim on folate metabolism in man. Clin Pharmacol Ther 1968;9:550-60.
5. Threlkeld DS, ed. Systemic Anti-Infectives, Miscellaneous Anti-Infectives, Trimethoprim. In Facts and Comparisons Drug Information. St. Louis, MO: Facts and Comparisons, Aug 1992, 408-a.
6. Sahai J. Urinary tract infections. In Applied Therapeutics: The Clinical Use of Drugs, 6th ed. Vancouver, WA: Applied Therapeutics, 1995, 63-6.
7. Alappan R, Perazella MA, Buller GK. Hyperkalemia in hospitalized patients treated with trimethoprim-sulfamethoxazole. Ann Intern Med 1996;124:316-20.
8. Perazella MA. Drug-induced hyperkalemia: Old culprits and new offenders. Am J Med 2000;109:307-14 [review].
9. Elmer GW, Surawicz CM, McFarland LV. Biotherapeutic agents. A neglected modality for the treatment and prevention of selected intestinal and vaginal infections. JAMA 1996;275:870-6 [review].
10. Elmer GW, Surawicz CM, McFarland LV. Biotherapeutic agents. A neglected modality for the treatment and prevention of selected intestinal and vaginal infections. JAMA 1996;275:870-6 [review].
11. Schellenberg D, Bonington A, Champion CM, et al. Treatment of Clostridium difficile diarrhoea with brewer's yeast. Lancet 1994;343:171-2.
12. Surawicz CM, Elmer GW, Speelman P, et al. Prevention of antibiotic-associated diarrhea by Saccharomyces boulardii: A prospective study. Gastroenterol 1989;96:981-8.
13. Elmer GW, Surawicz CM, McFarland LV. Biotherapeutic agents. A neglected modality for the treatment and prevention of selected intestinal and vaginal infections. JAMA 1996;275:870-6 [review].
14. Suzuki K, Fukushima T, Meguro K, et al. Intracranial hemorrhage in an infant owing to vitamin K deficiency despite prophylaxis. Childs Nerv Syst 1999;15:292-4.
15. Huilgol VR, Markus SL, Vakil NB. Antibiotic-induced iatrogenic hemobilia. Am J Gastroenterol 1997;92:706-7.
16. Bandrowsky T, Vorono AA, Borris TJ, Marcantoni HW. Amoxicllin-related postextraction bleeding in an anticoagulated patient with tranexamic acid rinses. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1996;82:610-2.
17. Kaiser CW, McAuliffe JD, Barth RJ, Lynch JA. Hypoprothrombinemia and hemorrhage in a surgical patient treated with cefotetan. Arch Surg 1991;126:524-5.
18. Conly J, Stein K. Reduction of vitamin K2 concentration in human liver associated with the use of broad spectrum antimicrobials. Clin Invest Med 1994;17:531-9.

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Last Review: 01-21-2009

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The information presented in Aisle7 is for informational purposes only. It is based on scientific studies (human, animal, or in vitro), clinical experience, or traditional usage as cited in each article. The results reported may not necessarily occur in all individuals. For many of the conditions discussed, treatment with prescription or over the counter medication is also available. Consult your doctor, practitioner, and/or pharmacist for any health problem and before using any supplements or before making any changes in prescribed medications. Information expires February 2010.

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