Drug Interaction Report

Simeprevir and Methotrexate Injection: Interaction Details

Name: Simeprevir and Methotrexate Injection Interaction
Creator: Dr. Brian Staiger, PharmD, BCPS

A pharmacist-reviewed analysis of the Simeprevir and Methotrexate Injection interaction: the documented clinical effects, severity rating, onset, mechanism, and management considerations, with cited references throughout.

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

Simeprevir

Olysio®

Methotrexate Injection

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

Medically reviewed by

Dr. Brian Staiger, PharmD, BCPS

Updated Aug 8, 2026

Editorial policy · Data sources

Interaction severity

Major

Potentially serious — often needs a change or close monitoring.

Minor

Moderate

Major

Contraindicated

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 47 documented Simeprevir interactions, 42 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 exposure of OATP1B1/3 substrate

Interaction Deep Dive

Coadministration of simeprevir (an OATP1B1/3 inhibitor) and an OATP1B1/3 substrate may result in increased exposure of the OATP1B1/3 substrate¹.

Why it happens (mechanism)

Inhibition of OATP1B1/3-mediated efflux transport by simeprevir

Common questions

Can I take Simeprevir and Methotrexate Injection together?

Increased exposure of OATP1B1/3 substrate Always confirm with your pharmacist or prescriber before making any change.

How serious is the Simeprevir 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 Simeprevir 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)

Product Information: OLYSIO(R) oral capsules, simeprevir oral capsules. Janssen Therapeutics (per manufacturer), Titusville, NJ, 2014.

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Simeprevir

Keep reading about Simeprevir

All Simeprevir interactions (47) Simeprevir drug information

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Methotrexate Injection

Keep reading about Methotrexate Injection

All Methotrexate Injection interactions (354) Methotrexate Injection drug information

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About our interaction database: depth, not breadth

HelloPharmacist doesn't license one of the big commercial interaction databases, so what you'll find here is not a complete list of every known drug interaction. Instead, each entry is researched, analyzed, and written up individually — documented from the published literature, reviewed by a pharmacist, and cited so you can check every source yourself.

If a combination isn't listed here, it means we haven't documented it yet — never that it's safe. For screening a full medication list, we recommend pairing this site with a comprehensive tool like the Drugs.com Interaction Checker and, most importantly, a review by your own pharmacist. For a deep, plain-English, fully sourced explanation of a specific documented interaction — that's exactly what we built this for.

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.