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Trimethoprim/Sulfamethoxazole

Also indexed as: Bactrim®, Cotrim®, Co-Trimoxazole, Septra®, SMX/TMP, TMP/SMX, Uroplus®

The antibiotic combination of trimethoprim and sulfamethoxazole (TMP/SMX) is used to treat a wide variety of bacterial infections and some infections due to parasites. Bactrim®, Cotrim®, and Septra® are brand names for products containing identical amounts of TMP/SMX. Bactrim® DS and Septra® DS contain twice as much TMP and SMX as Bactrim® and Septra®.

Interactions with Dietary Supplements

Folic acid
TMP/SMX has, on rare occasions, been associated with anemia due to folic acid deficiency.1 This effect may be due to trimethoprim.2 TMP/SMX should be used with caution in patients with folic acid deficiency, for which a blood test is available. Folic acid replacement does not interfere with the antibacterial activity of TMP/SMX.3 People with AIDS-related pneumonia given TMP/SMX had a worse survival rate when folinic acid, an activated form of folic acid, was added.4

PABA (para-aminobenzoic acid)
PABA may interfere with the action of sulfamethoxazole. It should not be taken together with trimethoprim/sulfamethoxazole.

Potassium
TMP/SMX has been reported to increase blood potassium to levels above the normal range in some patients, particularly those with impaired kidney function.5 People who have been prescribed TMP/SMX should ask their doctor whether they should avoid potassium supplements, potassium-containing salt substitutes (No Salt®, Morton Salt Substitute®, and others), and 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.6

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 boulardii7 or Saccharomyces cerevisiae (baker’s or brewer’s yeast)8 —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.9 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.10

Vitamin K
Several cases of excessive bleeding have been reported in people who take antibiotics.11 12 13 14 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.15 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.

Summary of Interactions for Trimethoprim/Sulfamethoxazole

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

For the convenience of the reader, the information in the summary is categorized as follows: “Depletion or interference” indicates the drug may deplete or interfere with the absorption or function of the supplement or herb. “Adverse interaction” indicates that the supplement or herb used together with the drug may result in undesirable effects. “Side effect reduction/prevention” indicates the supplement or herb may reduce the likelihood and/or severity of a potential side effect caused by the drug. “Supportive interaction” indicates the supplement or herb may support or aid the function of the drug. “Reduced drug absorption/bioavailability” indicates that the supplement or herb may decrease the absorption and/or activity of the drug in the body. An asterisk (*) next to an item in the summary indicates that the interaction is supported only by weak, fragmentary, and/or contradictory scientific evidence.

References:

1. Young LY, Koda-Kimble MA, eds. Applied Therapeutics: The Clinical Use of Drugs. Vancouver, WA: Applied Therapeutics, 1988, 911.

2. Kahn SB, Fein SA, Brodsky I. Effects of trimethoprim on folate metabolism in man. Clin Pharmacol Ther 1968;9:550–60.

3. Young LY, Koda-Kimble MA, eds. Applied Therapeutics: The Clinical Use of Drugs. Vancouver, WA: Applied Therapeutics, 1988, 911.

4. Safrin S, Lee BL, Sande MA. Adjunctive folinic acid with trimethoprim-sulfamethoxazole for pneumocystis carinii pneumonia in AIDS patients is associated with an increased risk of therapeutic failure and death. J Infect Dis 1994;170:912–7.

5. Alappan R, Perazella MA, Buller GK. Hyperkalemia in hospitalized patients treated with trimethoprim-sulfamethoxazole. Ann Intern Med 1996;124:316–20.

6. 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].

7. 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].

8. Schellenberg D, Bonington A, Champion CM, et al. Treatment of Clostridium difficile diarrhoea with brewer’s yeast. Lancet 1994;343:171–2.

9. Surawicz CM, Elmer GW, Speelman P, et al. Prevention of antibiotic-associated diarrhea by Saccharomyces boulardii: A prospective study. Gastroenterol 1989;96:981–8.

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. 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.

12. Huilgol VR, Markus SL, Vakil NB. Antibiotic-induced iatrogenic hemobilia. Am J Gastroenterol 1997;92:706–7.

13. 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.

14. Kaiser CW, McAuliffe JD, Barth RJ, Lynch JA. Hypoprothrombinemia and hemorrhage in a surgical patient treated with cefotetan. Arch Surg 1991;126:524–5.

15. 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.