Drug Interaction Report

Meperidine and Istradefylline: Interaction Details

A pharmacist-reviewed analysis of the Meperidine and Istradefylline 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

Meperidine

Demerol
+

Istradefylline

Nourianz Nourianz®
Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by
Dr. Brian Staiger, PharmD, BCPS
Updated Aug 8, 2026
Editorial policy · Data sources
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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 66 documented Meperidine interactions, 59 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 meperidine exposure and risk of increased or prolonged opioid effects

Interaction Deep Dive

Concomitant use of meperidine and any CYP3A4 inhibitor may increase exposure of meperidine, and may lead to prolonged opioid effects, including respiratory depression, particularly when an inhibitor is added after a stable dosage of meperidine is achieved. Plasma concentrations of the active metabolite normeperidine may be increased by ritonavir (CYP3A4 inhibitor). If use of a CYP3A4 inhibitor is necessary in a patient receiving meperidine, consider reducing the dose of meperidine and monitor for sedation and respiratory depression frequently. When discontinuing a CYP3A4 inhibitor in a patient receiving meperidine therapy, consider a meperidine dose increase and monitor for signs of opioid withdrawal12.

Why it happens (mechanism)

Inhibition of CYP3A4-mediated metabolism of meperidine

Literature reports

1 report — tap to read

a) Plasma concentrations of the active metabolite normeperidine may be increased by ritonavir (CYP3A4 inhibitor) 12.

Common questions

Can I take Meperidine and Istradefylline together?

Increased meperidine exposure and risk of increased or prolonged opioid effects Always confirm with your pharmacist or prescriber before making any change.

How serious is the Meperidine and Istradefylline 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 Meperidine or Istradefylline 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 (2)

  1. Product Information: MEPERGAN intramuscular, intravenous injection, meperidine HCl, promethazine HCl intramuscular, intravenous injection. West-Ward Pharmaceuticals Corp (per FDA), Eatontown, NJ, 2023.
  2. Product Information: DEMEROL(R) oral tablets, oral solution, meperidine HCl oral tablets, oral solution. Validus Pharmaceuticals LLC (per FDA), Parsippany, NJ, 2023. DailyMed
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Meperidine

Keep reading about Meperidine

All Meperidine interactions (66)
Also serious with: Linezolid Injection Palonosetron Injection Nalbuphine Injection Aripiprazole Injection
Istradefylline

Keep reading about Istradefylline

All Istradefylline interactions (87) Istradefylline drug information
Also serious with: Ensitrelvir Colchicine Morphine Injection Itraconazole
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:

Meperidine + 1,4-butanediol Activated Charcoal Beer Gamma-hydroxybutyrate (ghb) Kava L-tryptophan Lithium Wine + 147 more
Istradefylline + Activated Charcoal Grapefruit St. John's Wort Acacia Rigidula Adrafinil African Wild Potato American Elder Astaxanthin + 130 more

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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.