Drug Interaction Report

Methacycline and Methotrexate Injection: Interaction Details

AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature

Methotrexate Injection

Abitrexate® Folex® Jylamvo Mexate® Otrexup Otrexup® Rasuvo Rasuvo®
+

Methacycline

No brand names on record
Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by
Updated Aug 8, 2026
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Interaction severity
Major
Potentially serious — often needs a change or close monitoring.
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.

Of 19 documented Methacycline interactions, 14 are rated major — including this one.
Worried about symptoms right now? Contact your pharmacist or prescriber, or call Poison Control at 1-800-222-1222 (US). Call 911 for an emergency.
Onset
unspecified
Evidence
theoretical
Severity
Major

What happens

Increased methotrexate exposure, an increased risk of methotrexate-related severe adverse reactions, reduced active metabolite formation and possibly reduced methotrexate efficacy

Interaction Deep Dive

Coadministration of methotrexate with highly protein bound drugs like tetracyclines may increase methotrexate exposure, which may increase the risk of methotrexate severe adverse reactions. In some cases, the coadministration of methotrexate with tetracyclines may also subsequently reduce active metabolite formation, which may reduce the clinical effectiveness of methotrexate. If coadministration cannot be avoided, monitor closely for methotrexate adverse reactions1.

Why it happens (mechanism)

Reduced methotrexate absorption; additive hepatotoxicity; protein binding displacement; decreased enterohepatic recycling; suppression of bacterial metabolism

Common questions

Can I take Methacycline and Methotrexate Injection together?

Increased methotrexate exposure, an increased risk of methotrexate-related severe adverse reactions, reduced active metabolite formation and possibly reduced methotrexate efficacy Always confirm with your pharmacist or prescriber before making any change.

How serious is the Methacycline 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 "unspecified". The timing of this interaction is not well characterized.

How strong is the evidence for this interaction?

The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.

Questions for your pharmacist

  • Does my dose of Methacycline 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)

  1. Product Information: JYLAMVO oral solution, methotrexate oral solution. Shorla Oncology Inc (per FDA), Cambridge, MA, 2024. DailyMed
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Beyond drug–drug

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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This information is for education, not a substitute for professional medical advice. Do not start, stop, or change any medication without talking to your pharmacist or prescriber.