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Sulfamethoxazole/trimethoprim: 7 things you should know

Medically reviewed by Carmen Pope, BPharm. Last updated on March 31, 2023.

1. How it works

  • Sulfamethoxazole/trimethoprim is a fixed combination medicine containing two antibiotics - sulfamethoxazole and trimethoprim.
  • Sulfamethoxazole stops bacteria from making dihydrofolic acid and trimethoprim prevents the formation of tetrahydrofolic acid; both are significant steps in the formation of nucleic acids and proteins essential to many bacteria. The combination of sulfamethoxazole/trimethoprim kills bacteria.
  • Sulfamethoxazole/trimethoprim belongs to the class of medicines known as antibiotics. The sulfamethoxazole component belongs to the class of medicines known as sulfonamides, and the trimethoprim component belongs to the class of medicines known as folic acid inhibitors.

2. Upsides

  • Sulfamethoxazole/trimethoprim is a combination antibiotic used to treat infections such as those affecting the ear, urinary tract, lungs, or gastrointestinal tract.
  • Active against a wide range of susceptible strains of gram-positive and gram-negative bacteria, such as Streptococcus pneumoniae, Escherichia coli, Klebsiella species, Enterobacter species, Haemophilus influenzae, and others.
  • Effective concentrations of both sulfamethoxazole and trimethoprim are reached in the gastrointestinal tract, urinary tract, lungs, mouth, middle ear, and vagina. Both antibiotics also cross the placenta and are excreted in human milk.
  • Bacterial resistance is less likely to develop with the combination of sulfamethoxazole and trimethoprim than if either ingredient (sulfamethoxazole or trimethoprim) is taken alone.
  • Generic sulfamethoxazole/trimethoprim is available.

3. Downsides

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

  • Nausea, vomiting, abdominal pain, diarrhea, mouth or tongue inflammation, weight loss, flatulence, rash, and itchy skin.
  • May not be suitable for some people including those with kidney or liver disease, folate deficiency (the elderly, chronic alcoholics, and people taking anticonvulsants are at risk of folate deficiency), glucose-6-phosphate deficiency, porphyria, severe allergies, thyroid dysfunction, or bronchial asthma. Not suitable for pregnant or breastfeeding women or infants less than two months of age.
  • Elderly people may be more susceptible to the side effects of sulfamethoxazole/trimethoprim.
  • Rarely, severe, sometimes fatal reactions have been reported with the administration of sulfonamide-containing medicines such as sulfamethoxazole/trimethoprim. Reactions have included Stevens-Johnson syndrome (a disorder involving the skin and mucous membranes), liver disease, and blood disorders such as thrombocytopenia (low platelets). Sulfamethoxazole/trimethoprim should be discontinued at the first sign of a skin rash or any other worrying side effect.
  • May lower blood sugar levels in people without diabetes.
  • May interact with several other drugs including thiazides, warfarin, phenytoin, methotrexate, digoxin, and medications for diabetes.

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

4. Bottom Line

Sulfamethoxazole/trimethoprim is an effective combination antibiotic; however, it may not be suitable for those with kidney or liver disease or folate deficiency. The risk of side effects may be higher in the elderly.

5. Tips

  • May be taken with or without food. Swallow tablets with a big glass of water.
  • Take only as directed by your doctor and do not share with anyone else as misuse can encourage the development of drug-resistant bacteria and reduce the effectiveness of sulfamethoxazole/trimethoprim. Sulfamethoxazole/trimethoprim will not treat viral infections, such as a cold or the flu.
  • Discontinue and seek urgent medical advice if a skin rash develops.
  • Complete the full course as prescribed (unless instructed not to do so by your doctor) to reduce the risk of resistant bacteria developing.
  • Should not be used in pregnant or lactating women or babies less than two months old.
  • Seek urgent medical advice if an unexplained cough, shortness of breath, sore throat, fever, muscle or joint pain, paleness or yellowing of the skin, or diarrhea develops.
  • Like other antibiotics, sulfamethoxazole/trimethoprim can change the natural balance of bacteria present in your gut and may cause severe and persistent diarrhea, associated with a bacteria called Clostridium difficile. Contact your doctor if diarrhea develops either during treatment or within a couple of months of ending treatment.
  • Keep well hydrated with fluids to avoid the development of crystals in the urine or kidney stones.

6. Response and effectiveness

  • Sulfamethoxazole/trimethoprim is quickly absorbed with peak levels occurring within one to four hours after oral administration. The antibacterial effects of sulfamethoxazole/trimethoprim persist for at least 12 hours.

7. Interactions

Medicines that interact with sulfamethoxazole/trimethoprim may either decrease its effect, affect how long it works, increase side effects, or have less of an effect when taken with sulfamethoxazole/trimethoprim. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

Common medications that may interact with sulfamethoxazole/trimethoprim include:

  • anticonvulsants such as phenytoin
  • antidepressants, such as amitriptyline, amoxapine, and desipramine
  • cyclosporine
  • digoxin
  • anticoagulants (blood thinners), such as warfarin
  • blood pressure medications, such as captopril or enalapril
  • indomethacin
  • pyrimethamine
  • medications that affect the nervous system, such as amantadine or memantine
  • methotrexate
  • metformin
  • thiazide diuretics
  • other medications that may inhibit or induce CYP2D6 enzymes
  • vaccinations.

Note that this list is not all-inclusive and includes only common medications that may interact with sulfamethoxazole/trimethoprim. You should refer to the prescribing information for sulfamethoxazole/trimethoprim for a complete list of interactions.


Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use sulfamethoxazole/trimethoprim only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Copyright 1996-2023 Revision date: March 30, 2023.