Drug Interaction Report

Cyclophosphamide and St John's Wort: Interaction Details

A pharmacist-reviewed analysis of the Cyclophosphamide and St John's Wort 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

St John's Wort

No brand names on record
+

Cyclophosphamide

Cytoxan® Frindovyx
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 88 documented Cyclophosphamide interactions, 47 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
delayed
Evidence
probable
Severity
Major

What happens

Reduced cyclophosphamide effectiveness

Interaction Deep Dive

This interaction has not been reported clinically, it is based on the interaction of St. John's Wort with other drugs metabolized through the same pathway1. The activation pathway of cyclophosphamide involves CYP2D6, CYP2C9 and CYP3A4 isoenzymes. CYP3A4 also catalyzes the inactivation of cyclophosphamide to dechloroethylcyclophosphamide 2. Several case reports of decreased drug concentration and/or effectiveness have been reported when St. John's Wort was taken with drugs metabolized by CYP3A4 345. St. John's Wort has been shown to induce cytochrome P450 3A4, 1A2, 2D6, and 2E1 67 in human subjects.

Why it happens (mechanism)

Induction of cytochrome P450 3A4 and 2D6 by St. John's Wort

Common questions

Can I take Cyclophosphamide and St John's Wort together?

Reduced cyclophosphamide effectiveness Always confirm with your pharmacist or prescriber before making any change.

How serious is the Cyclophosphamide and St John's Wort 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 Cyclophosphamide or St John's Wort 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 (7)

  1. Anon: Risk of drug interactions with St. John's Wort. JAMA 2000; 283(13):1679. DOI
  2. Boddy AV & Yule SM: Metabolism and pharmacokinetics of oxazaphosphorines. Clin Pharmacokinet 2000; 38(4):291-304. PubMed
  3. Bolley R, Zulke C, Kammerl M, et al: Tacrolimus-induced nephrotoxicity unmasked by induction of the CYP3A4 system with St. John's Wort. Transplantation 2002; 73(6):1009. DOI
  4. Piscitelli S, Burstein A, Chaitt D, et al: Indinavir concentrations and St. John's Wort. Lancet 2000; 355:547-548. PubMed
  5. Ruschitzka F, Meier P, Turina M, et al: Acute heart transplant rejection due to St. John's Wort. Lancet 2000; 355:548-549.
  6. Gurley BJ, Gardner SF, Hubbard MA, et al: Cytochrome P450 phenotypic ratios for predicting herb-drug interactions in humans. Clin Pharmacol Ther 2002; 72(3):276-287. PubMed
  7. Roby CA, Anderson GD, Kantor E, et al: St. John's Wort: effect on CYP3A4 activity. Clin Pharmacol Ther 2000; 67:451-457. DOI
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St John's Wort

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Cyclophosphamide

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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:

Cyclophosphamide + Activated Charcoal Beer Grapefruit Siberian Cocklebur St. John's Wort Wine Acacia Rigidula Acerola + 212 more

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.