Triamterene and Methotrexate Injection: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Triamterene
Methotrexate Injection
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
Bone marrow suppression
Interaction Deep Dive
A case of bone marrow suppression in a 57-year old woman taking triamterene and methotrexate has been reported1. The proposed mechanism was an additive inhibitory effect on dihydrofolate reductase (DHFR). Further case reports or controlled studies are necessary to confirm the extent of this interaction.
Why it happens (mechanism)
Additive effects on folate disposition
Literature reports
1 report — tap to read
a) A case of a 57-year old woman who developed a possible interaction between methotrexate and triamterene has been reported 1. The patient had been taking triamterene-hydrochlorothiazide 50 mg/25 mg per day in addition to atenolol and diclofenac for rheumatoid arthritis and hypertension. Methotrexate 5 mg per week was added to the patient's regimen for active rheumatoid arthritis. After one month of therapy, the patient's hemoglobin count decreased from 10.1 g/dL to 8.0 g/dL and her white cell count was 3.6 x 10(9)/L. The patient developed mouth ulcers, dyspnea, and bruised easily. The patient later developed pancytopenia with renal impairment and was treated for bone marrow suppression. The authors proposed that triamterene may have the ability to inhibit dihydrofolate reductase (DHFR), and that the addition of methotrexate resulted in a synergistic suppression of DHFR. The authors suggested that complete blood count, renal function, and liver function should be monitored carefully whenever methotrexate therapy is initiated.
Common questions
Can I take Triamterene and Methotrexate Injection together?
Bone marrow suppression Always confirm with your pharmacist or prescriber before making any change.
How serious is the Triamterene and Methotrexate Injection interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
Questions for your pharmacist
- Does my dose of Triamterene or Methotrexate Injection need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (1)
- Richmond R, McRorie ER, Ogden DA, et al: Methotrexate and triamterene-a potentially fatal combination?. Ann Rheum Dis 1997; 56:209-210. PubMed
Keep reading about Triamterene
Keep reading about Methotrexate Injection
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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