Both trimethoprim and sulfamethoxazole interfere with folate: The sulfamethoxazole makes it hard for invading bacteria to manufacture folate, and the trimethoprim makes it hard for bacteria to use the folate. The net effect is to starve the bacteria of this necessary vitamin.

Humans and other mammals are much less affected by these antibiotics than are bacteria, due to the different way we process folate. However, trimethoprim can still interfere to some extent in your body's ability to utilize this essential nutrient. Folate supplementation may be helpful if you take this antibiotic for a long period of time (to prevent urinary tract infections, for example).1

The supplement PABA may make trimethoprim/sulfamethoxazole less effective. If you are being treated with this drug, do not take PABA except on medical advice.2,3

Trimethoprim/sulfamethoxazole might increase levels of potassium in the body.4 Therefore, if you are on long-term treatment with this antibiotic, you should not take potassium supplements except on the advice of a physician.

The herb white willow contains substances very similar to aspirin. On this basis, it might not be advisable to combine white willow with trimethoprim or sulfamethoxazole.

Sulfa drugs can cause increased sensitivity to the sun. Various herbs, including St. John's wort and dong quai, can also cause this problem. Combined treatment with herb and drug might increase the risk further.