Drug & supplement interaction

Perillyl Alcohol + Methotrexate

Methotrexate brand names: Rheumatrex, Otrexup, Rasuvo, Reditrex.

No Known Interaction
Medically reviewed by · Updated July 2026 · Pair last verified Sep 13, 2026
The bottom line No known interaction

We found no known interaction between Perillyl Alcohol and Methotrexate in our sources. Absence of a documented interaction is not the same as proven safety, and does not guarantee one does not exist. Do not start, stop, or change a medication or supplement based on this page; confirm with your pharmacist or doctor first. Additionally, although there is no interaction, the two are separately associated with some of the same side effects, which would make a new symptom harder to attribute to one or the other.

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Interaction report

Perillyl Alcohol and Methotrexate

We checked these two against our interaction database. Here is what we found.

No Known Interaction Found

We did not find a documented interaction between Methotrexate and Perillyl Alcohol in our sources. This does not guarantee that the combination is completely free of risk — there is often limited research on supplements and herbal products, especially around drug interactions.

Worth understanding: our licensed dataset holds no drug-interaction record for Perillyl Alcohol at all — not against Methotrexate, and not against any other medication we track. This verdict therefore rests on the absence of any recorded data, not on research that looked at this combination and found nothing. We cannot rule an interaction out.

If you decide to take both, the practical routine is simple: add one new thing at a time and note the date you started it. If the combination is going to disagree with you, it usually shows in the first days to a couple of weeks — and a start date turns “I’ve been feeling off” into something a pharmacist can actually work with. Do not stop a prescribed medicine on your own.

Always talk with your pharmacist or doctor before making changes to your medications or supplements, particularly if you take several medications or have an ongoing health condition.

Perillyl Alcohol safety at a glance

Perillyl Alcohol overall Use caution It is mostly an investigational compound with limited human safety data outside clinical trials.
Pregnancy Avoid There is not enough safety information, so it is best avoided during pregnancy.
Breastfeeding Avoid Safety while breastfeeding is unknown, so avoid use.

Safety guidance is general; always confirm with your pharmacist or doctor for your situation.

Still wondering about combining Methotrexate and Perillyl Alcohol? Ask Dr. Brian Staiger, PharmD, BCPS directly ›
What to actually watch for

No Interaction Found — But Data Suggests Perillyl Alcohol and Methotrexate May Share Several of the Same Side Effects

This is not an interaction. Neither one changes how your body handles the other, and nothing here says they react together. What our sources do show is that each has separately been linked to the effects below — so taking both can make those effects more likely to turn up, and harder to pin on one or the other if they do. One of them is worth acting on rather than waiting out — marked below.

  • Pancreatitis Worth acting on Additional detail

    Perillyl Alcohol

    “Orally, perillyl alcohol can cause adverse effects including gastrointestinal upset, reflux, nausea, diarrhea or constipation, fatigue, and headache. In high doses, perillyl alcohol has been associated with single reports of acute pancreatitis, increased bilirubin, increased white blood cell count, and hypokalemia.

    Topically, perillyl alcohol has been rarely reported to cause a mild rash or tenderness.”

    Perillyl Alcohol · Natural Medicines adverse-effect record, reported in cluster headache.

    6 sources cited
    1. 15274. Bailey HH, Wilding G, Tutsch KD, et al. A phase I trial of perillyl alcohol administered four times daily for 14 days out of 28 days. Cancer Chemother Pharmacol 2004;54:368-76. PubMed
    2. 15277. Stearns V, Coop A, Singh B, et al. A pilot surrogate end point biomarker trial of perillyl alcohol in breast neoplasia. Clin Cancer Res 2004;10:7583-91. PubMed
    3. 15279. Morgan-Meadows S, Dubey S, Gould M, et al. Phase I trial of perillyl alcohol administered four times daily continuously. Cancer Chemother Pharmacol 2003;52:361-6. PubMed
    4. 15284. Liu G, Oettel K, Bailey H, et al. Phase II trial of perillyl alcohol (NSC 641066) administered daily in patients with metastatic androgen independent prostate cancer. Invest New Drugs 2003;21:367-72. PubMed
    5. 58047. Ripple, G. H., Gould, M. N., Arzoomanian, R. Z., Alberti, D., Feierabend, C., Simon, K., Binger, K., Tutsch, K. D., Pomplun, M., Wahamaki, A., Marnocha, R., Wilding, G., and Bailey, H. H. Phase I clinical and pharmacokinetic study of perillyl alcohol adm
    6. 58132. Ripple GH, Gould MN, Stewart JA, and et al. Phase I clinical trial of perillyl alcohol administered daily. Clin Cancer Res 1998;4(5):1159-1164.

    “Orally, perillyl alcohol can cause gastrointestinal upset, reflux, nausea, vomiting, lack of appetite, bloating, belting, heartburn, diarrhea, or constipation. Some side effects appear to be dose related. Higher doses are more likely to cause gastrointestinal upset such as reflux.”

    Perillyl Alcohol · Natural Medicines adverse-effect record, reported in constipation.

    6 sources cited
    1. 15274. Bailey HH, Wilding G, Tutsch KD, et al. A phase I trial of perillyl alcohol administered four times daily for 14 days out of 28 days. Cancer Chemother Pharmacol 2004;54:368-76. PubMed
    2. 15277. Stearns V, Coop A, Singh B, et al. A pilot surrogate end point biomarker trial of perillyl alcohol in breast neoplasia. Clin Cancer Res 2004;10:7583-91. PubMed
    3. 15279. Morgan-Meadows S, Dubey S, Gould M, et al. Phase I trial of perillyl alcohol administered four times daily continuously. Cancer Chemother Pharmacol 2003;52:361-6. PubMed
    4. 15284. Liu G, Oettel K, Bailey H, et al. Phase II trial of perillyl alcohol (NSC 641066) administered daily in patients with metastatic androgen independent prostate cancer. Invest New Drugs 2003;21:367-72. PubMed
    5. 58047. Ripple, G. H., Gould, M. N., Arzoomanian, R. Z., Alberti, D., Feierabend, C., Simon, K., Binger, K., Tutsch, K. D., Pomplun, M., Wahamaki, A., Marnocha, R., Wilding, G., and Bailey, H. H. Phase I clinical and pharmacokinetic study of perillyl alcohol adm
    6. 58132. Ripple GH, Gould MN, Stewart JA, and et al. Phase I clinical trial of perillyl alcohol administered daily. Clin Cancer Res 1998;4(5):1159-1164.

    Methotrexate

    Listed in the ADVERSE REACTIONS section of the FDA label for Methotrexate. Read the label on DailyMed ›

  • Reduced appetite / Vomiting Additional detail

    Perillyl Alcohol

    Recorded for Perillyl Alcohol in the same Natural Medicines adverse-effect record shown under Pancreatitis above.

    Methotrexate

    Listed in the ADVERSE REACTIONS section of the FDA label for Methotrexate. Read the label on DailyMed ›

  • Stomach upset / Nausea / Diarrhea reported in 5.9% of FDA reports for Methotrexate Additional detail

    Perillyl Alcohol

    Recorded for Perillyl Alcohol in the same Natural Medicines adverse-effect record shown under Pancreatitis above.

    Methotrexate

    Listed in the ADVERSE REACTIONS section of the FDA label for Methotrexate, and in voluntary FDA adverse-event reports. Read the label on DailyMed ›

  • Tiredness / Headache reported in 6.7% of FDA reports for Methotrexate Additional detail

    Perillyl Alcohol

    “Orally, perillyl alcohol in high doses (at least 1.2 grams/m2 four times daily) can cause significant adverse effects including fatigue and headache. Intranasally, perillyl alcohol has been associated with headaches.”

    Perillyl Alcohol · Natural Medicines adverse-effect record, reported in cluster headache.

    5 sources cited
    1. 15274. Bailey HH, Wilding G, Tutsch KD, et al. A phase I trial of perillyl alcohol administered four times daily for 14 days out of 28 days. Cancer Chemother Pharmacol 2004;54:368-76. PubMed
    2. 15277. Stearns V, Coop A, Singh B, et al. A pilot surrogate end point biomarker trial of perillyl alcohol in breast neoplasia. Clin Cancer Res 2004;10:7583-91. PubMed
    3. 15284. Liu G, Oettel K, Bailey H, et al. Phase II trial of perillyl alcohol (NSC 641066) administered daily in patients with metastatic androgen independent prostate cancer. Invest New Drugs 2003;21:367-72. PubMed
    4. 98639. Bailey HH, Attia S, Love RR, et al. Phase II trial of daily oral perillyl alcohol (NSC 641066) in treatment-refractory metastatic breast cancer. Cancer Chemother Pharmacol. 2008;62(1):149-57. PubMed
    5. 106535. Schönthal AH, Peereboom DM, Wagle N, et al. Phase I trial of intranasal NEO100, highly purified perillyl alcohol, in adult patients with recurrent glioblastoma. Neurooncol Adv 2021;3(1):vdab005. PubMed

    Methotrexate

    Listed in the ADVERSE REACTIONS section of the FDA label for Methotrexate, and in voluntary FDA adverse-event reports. Read the label on DailyMed ›

  • Itching Additional detail

    Perillyl Alcohol

    “Intranasally, perillyl alcohol has been associated with nasal soreness or itching, runny nose, and skin irritation.”

    Perillyl Alcohol · Natural Medicines adverse-effect record, reported in skin irritation.

    1 source cited
    1. 106535. Schönthal AH, Peereboom DM, Wagle N, et al. Phase I trial of intranasal NEO100, highly purified perillyl alcohol, in adult patients with recurrent glioblastoma. Neurooncol Adv 2021;3(1):vdab005. PubMed

    Methotrexate

    Listed in the ADVERSE REACTIONS section of the FDA label for Methotrexate. Read the label on DailyMed ›

  • A skin rash Additional detail

    Perillyl Alcohol

    Recorded for Perillyl Alcohol in the same Natural Medicines adverse-effect record shown under Pancreatitis above.

    Methotrexate

    Listed in the ADVERSE REACTIONS section of the FDA label for Methotrexate. Read the label on DailyMed ›

Reported for Perillyl Alcohol but not commonly for Methotrexate: low potassium, yellowing of the skin or eyes, constipation and a stuffy or runny nose.

Effects for Methotrexate come from the ADVERSE REACTIONS section of its FDA label; effects for Perillyl Alcohol come from the Natural Medicines adverse-effect record, quoted above. Where a percentage is shown, it is the share of 489,806 voluntary FDA FAERS reports for Methotrexate that mention that effect — a reporting proportion, not an incidence rate and not evidence the drug caused it. Wording is matched across sources by our own clinical vocabulary, so treat this as a prompt to pay attention, not a diagnosis.

Overlapping uses

What Methotrexate Is Prescribed For, and What Perillyl Alcohol Has Been Studied For

These two come up together because they touch the same health topic — not because they do the same job. Methotrexate is a prescription medicine with approved uses on its FDA label. Perillyl Alcohol is a supplement: what follows is what researchers have looked at it for, and how strong that evidence is.

Methotrexate is prescribed for: Methotrexate treats a wide range of serious conditions. In cancer care, it is used for acute lymphoblastic leukemia, non-Hodgkin lymphoma, osteosarcoma, breast cancer, head and neck cancer, and gestational trophoblastic neoplasia (a rare tumor related to pregnancy). It is also used to prevent and treat meningeal leukemia (cancer affecting the lining of the brain and spinal cord). Outside of cancer, methotrexate is prescribed for adults with rheumatoid arthritis (RA), children with polyarticular juvenile idiopathic arthritis (a form of childhood arthritis), and adults with severe psoriasis that hasn't responded well to other treatments.

Perillyl Alcohol has been studied for:

  • Breast cancer studied, not established Perillyl Alcohol has been studied for this. Natural Medicines rates the evidence: Insufficient Reliable Evidence To Rate Read what the research shows

    Perillyl Alcohol for breast cancer

    Preliminary clinical research shows that taking perillyl alcohol 1200-1500 mg/m2 orally four times daily does not improve survival in women with advanced treatment-refractory breast cancer. Adverse effects limited the planned duration of the study.

    1 source cited
    1. 98639. Bailey HH, Attia S, Love RR, et al. Phase II trial of daily oral perillyl alcohol (NSC 641066) in treatment-refractory metastatic breast cancer. Cancer Chemother Pharmacol. 2008;62(1):149-57. PubMed

Effectiveness ratings and the research summaries above are the verbatim record from the Natural Medicines database, which grades evidence from “Effective” down to “Insufficient Reliable Evidence To Rate”. A rating below the top of that scale means researchers have looked at it — not that it works, and never that it can stand in for a prescribed medicine. Do not stop or replace Methotrexate on your own; if you are taking Perillyl Alcohol for the same health topic, tell your prescriber, especially if the medicine is being adjusted to a target.

From our Q&A

Questions About Perillyl Alcohol or Methotrexate

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Perillyl Alcohol or Methotrexate, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Methotrexate

This page covers Perillyl Alcohol only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Methotrexate page lists 82 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Apple (major), Beer (major), Grapefruit (major) and Siberian Cocklebur (major).

By severity: 7 major · 60 moderate · 15 minor.

From our pharmacist’s overview on the Methotrexate page

“The liver is where methotrexate and supplements clash most. Methotrexate (Rheumatrex, Otrexup, Rasuvo), used for rheumatoid arthritis, psoriasis, and certain cancers, can strain the liver on its own, and 38 of the 82 interacting ingredients on this list add liver risk of their own, alcohol included, which makes this a list to approach…”

Reviewed by 2 · Jul 18, 2026

Open the Methotrexate interaction page

How much people look this up

Where Perillyl Alcohol and Methotrexate Sit Against Everything Else

Out of every supplement and medication people look up on HelloPharmacist, here is where these two land this week — and which way each has been moving.

Supplement Perillyl Alcohol
Steady interest

#1,375 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Methotrexate
Top 5%

#44 of 2,830 medications looked up here in the last 7 days

29 days ago today

Position among everything looked up on this site, not a measure of how commonly either one is used or how important it is. A supplement can climb this list because of a news story. It counts every request to the page, automated ones included, and nothing here identifies anyone.

Where does our data come from?
  • Source: the Natural Medicines (TRC Healthcare) clinical database — the evidence-graded professional reference for herb & supplement interactions.
  • Citation library: 103,510 references behind our interaction content, 65,311 of them resolved to verified PubMed/DOI sources. See every Perillyl Alcohol reference on this page ↓
  • Freshness: we automatically re-check this combination every week — this pair was last verified September 13, 2026. The Perillyl Alcohol and Methotrexate records this page draws on were last updated July 10, 2026.
  • What “no known interaction” means: no documented interaction in the sources above — not a guarantee of safety. Supplements are studied far less than prescription drugs, so we say exactly what the evidence supports, and nothing more.
Data structure & sourcing designed and verified by .
Supplement

About Perillyl Alcohol

What is Perillyl Alcohol?

  • Cancer research (investigational)
  • Antioxidant interest
  • General wellness supplement
  • Aromatherapy-related products

Perillyl alcohol is a natural compound found in the essential oils of plants like mint, lavender, and citrus, and it has mainly been studied as an experimental anti-cancer agent rather than as an everyday supplement. The evidence in people is limited and still under investigation, so it should not be used to treat or prevent any disease without medical supervision. Talk to your pharmacist or doctor before trying it.

Naturally found in the essential oils of plants such as lavender, peppermint, sage, cherries, and citrus fruits; often produced from limonene · Capsules, oral liquid, and (in research settings) intranasal preparations

An interaction check asks whether these two react with each other — it does not ask whether Perillyl Alcohol is a good idea for someone in your situation. Here is what our Perillyl Alcohol record says about it on its own.

Perillyl Alcohol: dosing

There is no established standard supplement dose of perillyl alcohol for the general public. The doses used in research were chosen for clinical trials and were given under close medical supervision, so they do not apply to over-the-counter use.If you choose to use a product that contains perillyl alcohol, follow the directions on the product label and do not exceed them.

From our Perillyl Alcohol monograph — the full record covers uses, side effects and every documented interaction.

Read the full Perillyl Alcohol monograph & all interactions
Medication

About Methotrexate

What Is Methotrexate Used For?

Brand names: Rheumatrex, Otrexup, Rasuvo, Reditrex

Methotrexate treats a wide range of serious conditions. In cancer care, it is used for acute lymphoblastic leukemia, non-Hodgkin lymphoma, osteosarcoma, breast cancer, head and neck cancer, and gestational trophoblastic neoplasia (a rare tumor related to pregnancy). It is also used to prevent and treat meningeal leukemia (cancer affecting the lining of the brain and spinal cord).

Outside of cancer, methotrexate is prescribed for adults with rheumatoid arthritis (RA), children with polyarticular juvenile idiopathic arthritis (a form of childhood arthritis), and adults with severe psoriasis that hasn't responded well to other treatments.

Most-Reported Side Effects for Methotrexate

From FAERS, the FDA’s public side-effect reporting system (489,806 reports, all brands). Reports are voluntary and are not proof the drug caused the effect.

Rheumatoid arthritis 42,798 reports
Arthralgia 40,830 reports
Fatigue 33,049 reports
Nausea 28,999 reports
Joint swelling 25,026 reports
See full Methotrexate drug information
Keep checking

Other Drugs & Perillyl Alcohol

Browse every other medication we’ve checked against Perillyl Alcohol — both the ones with a known interaction and the ones without. Select any drug for the full detail.

0Major
0Moderate
0Minor
2,829No known interaction
2,829 No interaction
No interaction 2,829 drugs checked — show the list

We also checked Perillyl Alcohol against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 2,829 medications checked with no known interaction — see the full Perillyl Alcohol list.

See the full Perillyl Alcohol interactions page
See every supplement checked against Methotrexate, ranked by severity
Evidence & sources

Perillyl Alcohol References

The 18 references that drive our Perillyl Alcohol monograph and interaction data, from the evidence-graded Natural Medicines (TRC Healthcare) database. Citations with a link open the study on PubMed or the publisher’s site.

  1. Bailey HH, Wilding G, Tutsch KD, et al. A phase I trial of perillyl alcohol administered four times daily for 14 days out of 28 days. Cancer Chemother Pharmacol 2004;54:368-76. PubMed
  2. Stearns V, Coop A, Singh B, et al. A pilot surrogate end point biomarker trial of perillyl alcohol in breast neoplasia. Clin Cancer Res 2004;10:7583-91. PubMed
  3. Morgan-Meadows S, Dubey S, Gould M, et al. Phase I trial of perillyl alcohol administered four times daily continuously. Cancer Chemother Pharmacol 2003;52:361-6. PubMed
  4. Liu G, Oettel K, Bailey H, et al. Phase II trial of perillyl alcohol (NSC 641066) administered daily in patients with metastatic androgen independent prostate cancer. Invest New Drugs 2003;21:367-72. PubMed
  5. Granath J, Ingvarsson S, von Thiele U, Lundberg U. Stress management: a randomized study of cognitive behavioural therapy and yoga. Cogn Behav Ther 2006;35:3-10. PubMed
  6. Ripple, G. H., Gould, M. N., Arzoomanian, R. Z., Alberti, D., Feierabend, C., Simon, K., Binger, K., Tutsch, K. D., Pomplun, M., Wahamaki, A., Marnocha, R., Wilding, G., and Bailey, H. H. Phase I clinical and pharmacokinetic study of perillyl alcohol adm
  7. Ripple GH, Gould MN, Stewart JA, and et al. Phase I clinical trial of perillyl alcohol administered daily. Clin Cancer Res 1998;4(5):1159-1164.
  8. Hudes, G. R., Szarka, C. E., Adams, A., Ranganathan, S., McCauley, R. A., Weiner, L. M., Langer, C. J., Litwin, S., Yeslow, G., Halberr, T., Qian, M., and Gallo, J. M. Phase I pharmacokinetic trial of perillyl alcohol (NSC 641066) in patients with refract
  9. Bailey, H. H., Levy, D., Harris, L. S., Schink, J. C., Foss, F., Beatty, P., and Wadler, S. A phase II trial of daily perillyl alcohol in patients with advanced ovarian cancer: Eastern Cooperative Oncology Group Study E2E96. Gynecol.Oncol. 2002;85(3):464- PubMed
  10. Murren, J. R., Pizzorno, G., DiStasio, S. A., McKeon, A., Peccerillo, K., Gollerkari, A., McMurray, W., Burtness, B. A., Rutherford, T., Li, X., Ho, P. T., and Sartorelli, A. Phase I study of perillyl alcohol in patients with refractory malignancies. Canc PubMed
  11. Azzoli, C. G., Miller, V. A., Ng, K. K., Krug, L. M., Spriggs, D. R., Tong, W. P., Riedel, E. R., and Kris, M. G. A phase I trial of perillyl alcohol in patients with advanced solid tumors. Cancer Chemother.Pharmacol. 2003;51(6):493-498. PubMed
  12. Meadows, S. M., Mulkerin, D., Berlin, J., Bailey, H., Kolesar, J., Warren, D., and Thomas, J. P. Phase II trial of perillyl alcohol in patients with metastatic colorectal cancer. Int J Gastrointest.Cancer 2002;32(2-3):125-128. PubMed
  13. Stratton SP, Alberts DS, Einspahr JG, et al. A phase 2a study of topical perillyl alcohol cream for chemoprevention of skin cancer. Cancer Prev Res (Phila). 2010;3(2):160-9. PubMed
  14. da Fonseca CO, Linden R, Futuro D, Gattass CR, Quirico-Santos T. Ras pathway activation in gliomas: a strategic target for intranasal administration of perillyl alcohol. Arch Immunol Ther Exp (Warsz). 2008;56(4):267-76. PubMed
  15. Stratton SP, Saboda KL, Myrdal PB, et al. Phase 1 study of topical perillyl alcohol cream for chemoprevention of skin cancer. Nutr Cancer. 2008;60(3):325-30. PubMed

Medication overviews come from MedlinePlus (NIH); supplement label data from the NIH Dietary Supplement Label Database. Content is written and reviewed by licensed HelloPharmacist pharmacists — see our data sources and editorial standards.

Pharmacist Counseling Corner

Taking Perillyl Alcohol and Methotrexate Together: Common Questions

Is it safe to take Perillyl Alcohol with Methotrexate?
We do not list a known interaction between Perillyl Alcohol and Methotrexate. That does not guarantee the combination is risk-free, so confirm with your pharmacist or doctor — especially if you take other medications or have a health condition.
Do Perillyl Alcohol and Methotrexate have any of the same side effects?
Yes — our sources link each of them separately to 10 of the same effects. That is not an interaction: neither changes how your body handles the other. It does mean that if one of those effects turns up, it can be harder to tell which one is behind it. They are listed on this page with the source behind each.
Are Perillyl Alcohol and Methotrexate used for the same thing?
They overlap in purpose, which usually means the real question is whether you need both rather than whether they are safe together. This page lists the shared uses and how strong the evidence is for Perillyl Alcohol in each. That is a conversation for your prescriber, especially if Methotrexate is being adjusted to a target.
Does Methotrexate interact with any supplements?
Yes. Methotrexate has documented interactions with 82 supplements in our database — Perillyl Alcohol is not one of them. The Methotrexate interaction page linked on this page lists every one, ranked by severity.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Where next

Keep Exploring

Perillyl Alcohol monograph Uses, safety profile, and every drug interaction in one place Methotrexate drug information The full plain-English guide to this medication Methotrexate supplement interactions Every supplement checked against Methotrexate, ranked by severity Supplement interaction checker Check any supplement or product against your medications Browse medications A–Z Every drug we’ve checked against herbs & supplements References The 18 citations behind this page Ask a pharmacist Free, personal answer from our licensed team

Still Have a Question About Methotrexate and Perillyl Alcohol?

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This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.