Medication·Interactions & depletion·Reviewed June 9, 2026
Trimethoprim-Sulfamethoxazole interactions.
Trimethoprim-Sulfamethoxazole has 4 documented interactions in the NutriStack database. Prolonged use is also associated with lower Folate. The full interaction list, depletion table, and replacement suggestions are below. None of this is a substitute for your prescriber's advice.
Trimethoprim-Sulfamethoxazole at a glance.
A quick, data-grounded summary. The full tables are below.
Trimethoprim-Sulfamethoxazole has 4 documented interactions in the NutriStack database. Prolonged use is also associated with lower Folate. The full interaction list, depletion table, and replacement suggestions are below. None of this is a substitute for your prescriber's advice.
Substances that interact with trimethoprim-sulfamethoxazole.
Every supplement and medication in the NutriStack database with a documented interaction with this drug, highest-severity first. Open any pair for the mechanism and sources.
| Substance | Interaction | What happens |
|---|---|---|
| Methylfolate | Caution | Trimethoprim inhibits dihydrofolate reductase and can cause folate deficiency with prolonged use, particularly in people with marginal folate... details → |
| Potassium | Caution | Trimethoprim blocks the epithelial sodium channel (ENaC) in the distal nephron, acting similarly to potassium-sparing diuretics like amiloride.... details → |
| Vitamin B9 | Caution | Trimethoprim is a folate antagonist that can lower host folate stores during prolonged therapy, particularly in patients with marginal folate... details → |
| Probiotics | Synergy | Probiotic supplementation during trimethoprim-sulfamethoxazole therapy reduces antibiotic-associated diarrhea and helps preserve gut microbiome... details → |
What trimethoprim-sulfamethoxazole can deplete.
Nutrients this medication is associated with lowering over time, with the mechanism, a suggested replacement where one applies, and the biomarker to monitor. Discuss any replacement with your prescriber first.
| Nutrient | Severity | How it happens | Replace with | Monitor |
|---|---|---|---|---|
| Folate | Moderate | Trimethoprim inhibits dihydrofolate reductase and sulfamethoxazole adds antifolate pressure, which can lower functional folate status in susceptible... | Folic Acid | CBC + serum folate or RBC folate |
The full trimethoprim-sulfamethoxazole profile.
Uses, typical dosing, side effects, and the cited evidence for this medication.
Common trimethoprim-sulfamethoxazole questions.
Quick answers drawn from the tables above.
What interacts with Trimethoprim-Sulfamethoxazole?
In the NutriStack database, Trimethoprim-Sulfamethoxazole has 4 documented interactions. The most notable include Methylfolate, Potassium, Vitamin B9, and Probiotics. Check any specific combination before taking it and confirm with your prescriber.
Does Trimethoprim-Sulfamethoxazole deplete any nutrients?
Trimethoprim-Sulfamethoxazole is associated with lowering Folate with prolonged use. Useful biomarkers to monitor include CBC + serum folate or RBC folate. Ask your prescriber before adding any replacement supplement.
Is it safe to take Methylfolate with Trimethoprim-Sulfamethoxazole?
NutriStack classifies the Methylfolate and Trimethoprim-Sulfamethoxazole pairing as caution: Trimethoprim inhibits dihydrofolate reductase and can cause folate deficiency with prolonged use, particularly in people with marginal folate status, pregnancy, or... Methylfolate supplementation is generally safe during trimethoprim-sulfamethoxazole therapy and is recommended for prolonged courses, pregnancy, or... Always confirm with your prescriber.
Check your whole stack
See how trimethoprim-sulfamethoxazole fits your supplements.
NutriStack screens your full routine for interactions and depletions, and updates the moment you change it.