Trimethoprim/Sulfamethoxazole

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Drug Information

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.

Common brand names:

Bactrim DS, Cotrim DS, Septra DS, SMZ-TMP DS

Summary of Interactions with Vitamins, Herbs, & Foods

Types of interactions: Beneficial Adverse Check

Replenish Depleted Nutrients

  • Folic Acid

    The use of multivitamin supplements containing folic acid diminishes the occurrence of birth defects associated with trimethoprim. According to one study, 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.

    The combination drug trimethoprim/sulfamethoxazole (TMP/SMX) has been rarely associated with folic acid-deficiency anemia. This action may be due to trimethoprim-induced folic acid depletion. 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 trimethoprim or TMP/SMX.

  • Potassium

    Tetracycline can interfere with the activity of folic acid, potassium, and vitamin B2, vitamin B6, vitamin B12, vitamin C, and vitamin K. This is generally not a problem when taking tetracycline for two weeks or less. People taking tetracycline for longer than two weeks should ask their doctor about vitamin and mineral supplementation. Taking 500 mg vitamin C simultaneously with tetracycline was shown to increase blood levels of tetracycline in one study. The importance of this interaction is unknown.

    Taking large amounts of niacinamide, a form of vitamin B3, can suppress inflammation in the body. According to numerous preliminary reports, niacinamide, given in combination with tetracycline or minocycline, may be effective against bullous pemphigoid, a benign, autoimmune blistering disease of the skin. Preliminary evidence also suggests a similar beneficial interaction may exist between tetracycline and niacinamide in the treatment of dermatitis herpetiformis.

  • Vitamin B12

    Neomycin can decrease absorption or increase elimination of many nutrients, including calcium, carbohydrates, beta-carotene, fats, folic acid, iron, magnesium, potassium, sodium, and vitamin A, vitamin B12, vitamin D, and vitamin K. Surgery preparation with oral neomycin is unlikely to lead to deficiencies. It makes sense for people taking neomycin for more than a few days to also take a multivitamin-mineral supplement.

  • Vitamin B2

    Tetracycline can interfere with the activity of folic acid, potassium, and vitamin B2, vitamin B6, vitamin B12, vitamin C, and vitamin K. This is generally not a problem when taking tetracycline for two weeks or less. People taking tetracycline for longer than two weeks should ask their doctor about vitamin and mineral supplementation. Taking 500 mg vitamin C simultaneously with tetracycline was shown to increase blood levels of tetracycline in one study. The importance of this interaction is unknown.

  • Vitamin K

    Several cases of excessive bleeding have been reported in people who take antibiotics. 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. 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.

  • Calcium

    Sulfonamides, including sulfamethoxazole, can decrease absorption of calcium, magnesium, and vitamin B12. This is generally not a problem when taking sulfamethoxazole for two weeks or less. People taking sulfamethoxazole for longer than two weeks should ask their doctor about nutrient monitoring and supplementation.

    Note:Since sulfamethoxazole is often prescribed in combination with trimethoprim (for example, in Bactrim or Septra), it may be easy to associate this interaction with trimethoprim. However, this interaction is not known to occur with trimethoprim alone.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Magnesium

    Sulfonamides, including sulfamethoxazole, can decrease absorption of calcium, magnesium, and vitamin B12. This is generally not a problem when taking sulfamethoxazole for two weeks or less. People taking sulfamethoxazole for longer than two weeks should ask their doctor about nutrient monitoring and supplementation.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Vitamin B6

    Sulfonamides, including sulfamethoxazole, can interfere with the activity of folic acid, vitamin B6, and vitamin K. This is generally not a problem when taking sulfamethoxazole for two weeks or less. People taking sulfamethoxazole for longer than two weeks should ask their doctor about nutrient monitoring and supplementation.

    Note:Since sulfamethoxazole is often prescribed in combination with trimethoprim (for example, in Bactrim or Septra), it may be easy to associate this interaction with trimethoprim. However, this interaction is not known to occur with trimethoprim alone.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.

Reduce Side Effects

  • 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.

    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 or Saccharomyces cerevisiae (baker’s or brewer’s yeast)—helps prevent recurrence of this infection.

    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.

  • Vitamin C

    Tooth discoloration is a side effect of minocycline observed primarily in young children, but it may occur in adults as well. Vitamin C supplementation may prevent staining in adults taking minocycline.

  • Brewer’s Yeast

    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.

    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 or Saccharomyces cerevisiae (baker’s or brewer’s yeast)—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. 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.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.

Support Medicine

  • Bromelain

    When taken with amoxicillin, bromelain was shown to increase absorption of amoxicillin in humans. When 80 mg of bromelain was taken together with amoxicillin and tetracycline, blood levels of both drugs increased, though how bromelain acts on drug metabolism remains unknown. An older report found bromelain also increased the actions of other antibiotics, including penicillin, chloramphenicol, and erythromycin, in treating a variety of infections. In that trial, 22 out of 23 people who had previously not responded to these antibiotics did so after adding bromelain taken four times per day.

    Doctors will sometimes prescribe enough bromelain to equal 2,400 gelatin dissolving units (listed as GDU on labels) per day. This amount would equal approximately 3,600 MCU (milk clotting units), another common measure of bromelain activity.

  • Probiotics
    In one study, taking 500 mg of Saccharomyces boulardii twice daily enhanced the effectiveness of the antibiotic vancomycin in preventing recurrent clostridium infection. Therefore, people taking antibiotics who later develop diarrhea might benefit from supplementing with saccharomyces organisms.

Reduces Effectiveness

  • Khat

    Khat (Catha edulis) is an herb found in East Africa and Yemen that has recently been imported into the United States. Studies have shown that chewing khat significantly reduces the absorption of ampicillin, which might reduce the effectiveness of the antibiotic. Therefore, people taking ampicillin should avoid herbal products that contain khat.

  • Magnesium

    Taking calcium, iron, magnesium, or zinc at the same time as minocycline can decrease the absorption of both the drug and the mineral. Therefore, calcium, iron, magnesium, or zinc supplements, if used, should be taken an hour before or after the drug.

  • Zinc

    Taking calcium, iron, magnesium, or zinc at the same time as minocycline can decrease the absorption of both the drug and the mineral. Therefore, calcium, iron, magnesium, or zinc supplements, if used, should be taken an hour before or after the drug.

Potential Negative Interaction

  • Potassium

    The combination drug trimethoprim/sulfamethoxazole (TMP/SMX) has been reported to elevate blood potassium and other constituents of blood (creatine and BUN). 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).

  • PABA

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

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.

Explanation Required 

  • Barberry

    Berberine is a chemical extracted from goldenseal (Hydrastis canadensis), barberry (Berberis vulgaris), and Oregon grape (Berberis aquifolium), which has antibacterial activity. However, one double-blind study found that 100 mg berberine given with tetracycline (a drug closely related to doxycycline) reduced the efficacy of tetracycline in people with cholera. In that trial, berberine may have decreased tetracycline absorption. Another double-blind trial found that berberine neither improved nor interfered with tetracycline effectiveness in cholera patients. Therefore, it remains unclear whether a significant interaction between berberine-containing herbs and doxycycline and related drugs exists.

  • Vitamin K

    Several cases of excessive bleeding have been reported in people who take antibiotics. 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. 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.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
The Drug-Nutrient Interactions table may not include every possible interaction. Taking medicines with meals, on an empty stomach, or with alcohol may influence their effects. For details, refer to the manufacturers’ package information as these are not covered in this table. If you take medications, always discuss the potential risks and benefits of adding a new supplement with your doctor or pharmacist.