Drug Interaction Report

Methotrexate Injection and Procarbazine: Interaction Details

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

Procarbazine

No brand names on record
+

Methotrexate Injection

Abitrexate® Folex® Jylamvo Mexate® Otrexup Otrexup® Rasuvo Rasuvo®
Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by
Updated Aug 8, 2026
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Interaction severity
Moderate
Can be significant — usually manageable with 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 354 documented Methotrexate Injection interactions, 13 are rated moderate — including this one.
Onset
delayed
Evidence
probable
Severity
Moderate

What happens

Renal dysfunction

Interaction Deep Dive

Three cases of renal dysfunction have been reported with concurrent use of procarbazine and high dose methotrexate (2 g/m(2)). After 14 days of procarbazine therapy methotrexate was infused within 48 hours of procarbazine. Renal function began to decline within 24 hours to 48 hours of methotrexate administration1.

Why it happens (mechanism)

Unknown

Literature reports

1 report — tap to read

a) Combined therapy with oral procarbazine 100 mg/m(2) daily and intravenous methotrexate 2 g/m(2) daily resulted in impaired renal function for three patients 1. Renal function was normal prior to drug therapy for all of the patients. Procarbazine was given on days 1 to 14 and the first dose of methotrexate was given within 48 hours after the end of procarbazine therapy. Renal function deteriorated 24 to 48 hours after the methotrexate dose. A delay in administration of the second dose or withdrawal of the methotrexate resulted in normalization of the renal function tests within 3 months. It is unclear from the data presented whether renal impairment occurred secondary to the combination of both agents or from the methotrexate alone and more studies are suggested to better define this interaction. However, as a precautionary measure, a period of 72 hours should elapse between the dosing of these drugs.

Common questions

Can I take Methotrexate Injection and Procarbazine together?

Renal dysfunction Always confirm with your pharmacist or prescriber before making any change.

How serious is the Methotrexate Injection and Procarbazine interaction?

It is rated moderate. Can be significant — usually manageable with 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 Methotrexate Injection or Procarbazine 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 anything you'd monitor while I'm on both?

References (1)

  1. Price P, Thompson H, Bessell EM, et al: Renal impairment following the combined use of high-dose methotrexate and procarbazine. Cancer Chemother Pharmacol 1988; 21:265-267. PubMed
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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.