Drug & supplement interaction

Madagascar Periwinkle + Levoleucovorin

Levoleucovorin brand name: Khapzory.

No Known Interaction
The bottom line No known interaction

We found no known interaction between Madagascar Periwinkle and Levoleucovorin 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

Madagascar Periwinkle and Levoleucovorin

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 Levoleucovorin and Madagascar Periwinkle 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.

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.

Madagascar Periwinkle safety at a glance

Madagascar Periwin... overall Avoid The raw plant contains toxic alkaloids and is not considered safe as a self-care supplement.
Pregnancy Likely Unsafe When used orally. Madagascar periwinkle has abortifacient and teratogenic properties. Read the full pregnancy detail
Breastfeeding Likely Unsafe When used orally; avoid using. Read the full breastfeeding detail

Pregnancy & breastfeeding ratings are from Natural Medicines (Therapeutic Research Center) — the full detail is in the Special populations card below. Safety guidance is general; always confirm with your pharmacist or doctor for your situation.

Still wondering about combining Levoleucovorin and Madagascar Periwinkle? Ask Dr. Brian Staiger, PharmD, BCPS directly ›
Keep it in perspective

Madagascar Periwinkle Does Interact With Other Medications

Madagascar Periwinkle has 87 moderate known drug interactions in our database — Levoleucovorin isn’t one of them. If you take anything else, check it against the full list below.

Taking anything else?

Check Another of Your Medications Against Madagascar Periwinkle

Covers the 2,830 medications we’ve checked against Madagascar Periwinkle. Pick one to open its full report.

What to actually watch for

No Interaction Found — But Data Suggests Madagascar Periwinkle and Levoleucovorin 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. 3 of them are worth acting on rather than waiting out — marked below.

  • A low white blood cell count / A low platelet count Worth acting on reported in 6.8% of FDA reports for Levoleucovorin Additional detail

    Madagascar Periwinkle

    “Orally, Madagascar periwinkle is generally regarded as unsafe for use. Any benefits of therapy may not outweigh the risk of toxicity. Madagascar periwinkle can cause hallucinations, seizures, gastrointestinal upset, hepatotoxicity, and alopecia (17).”

    Madagascar Periwinkle · Natural Medicines adverse-effect record, reported in alopecia.

    4 sources cited
    1. 17. Ellenhorn MJ, et al. Ellenhorn's Medical Toxicology: Diagnoses and Treatment of Human Poisoning. 2nd ed. Baltimore, MD: Williams & Wilkins, 1997.
    2. 6. The Review of Natural Products by Facts and Comparisons. St. Louis, MO: Wolters Kluwer Co., 1999.
    3. 15. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
    4. 100665. Ghosh D, Roy I, Chanda S, Gupta-Bhattacharya S. Allergy to periwinkle pollen (Catharanthus roseus G. Don.). Ann Agric Environ Med. 2007;14(1):39-43.

    “Orally, the vinca alkaloid constituents of Madagascar periwinkle have been reported to cause leukopenia, thrombocytopenia, bleeding, and hyperuricemia (6,15).”

    Madagascar Periwinkle · Natural Medicines adverse-effect record, reported in leukopenia.

    2 sources cited
    1. 6. The Review of Natural Products by Facts and Comparisons. St. Louis, MO: Wolters Kluwer Co., 1999.
    2. 15. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.

    Levoleucovorin

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

  • An allergic reaction Worth acting on Additional detail

    Madagascar Periwinkle

    Recorded for Madagascar Periwinkle in the same Natural Medicines adverse-effect record shown under A low white blood cell count / A low platelet count above.

    Levoleucovorin

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

  • Hair loss Additional detail

    Madagascar Periwinkle

    “Orally, Madagascar periwinkle can cause alopecia (17).”

    Madagascar Periwinkle · Natural Medicines adverse-effect record, reported in alopecia.

    1 source cited
    1. 17. Ellenhorn MJ, et al. Ellenhorn's Medical Toxicology: Diagnoses and Treatment of Human Poisoning. 2nd ed. Baltimore, MD: Williams & Wilkins, 1997.

    Levoleucovorin

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

  • Stomach upset / Vomiting / Nausea reported in 7.8% of FDA reports for Levoleucovorin Additional detail

    Madagascar Periwinkle

    “Orally, Madagascar periwinkle can cause gastrointestinal upset (17). The vinca alkaloid constituents of Madagascar periwinkle have been reported to cause nausea and vomiting (6,15).”

    Madagascar Periwinkle · Natural Medicines adverse-effect record, reported in nausea and vomiting.

    3 sources cited
    1. 17. Ellenhorn MJ, et al. Ellenhorn's Medical Toxicology: Diagnoses and Treatment of Human Poisoning. 2nd ed. Baltimore, MD: Williams & Wilkins, 1997.
    2. 6. The Review of Natural Products by Facts and Comparisons. St. Louis, MO: Wolters Kluwer Co., 1999.
    3. 15. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.

    Levoleucovorin

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

Reported for Madagascar Periwinkle but not commonly for Levoleucovorin: hallucinations, liver problems, dizziness and seizures.

Effects for Levoleucovorin come from the ADVERSE REACTIONS section of its FDA label; effects for Madagascar Periwinkle come from the Natural Medicines adverse-effect record, quoted above. Where a percentage is shown, it is the share of 3,706 voluntary FDA FAERS reports for Levoleucovorin 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.

Special populations

Madagascar Periwinkle in Pregnancy & Breastfeeding

Pregnancy Likely Unsafe

When used orally. Madagascar periwinkle has abortifacient and teratogenic properties.

Lactation Likely Unsafe

When used orally; avoid using.

DISCLAIMER: This tool is intended for informational purposes only, and should not be interpreted as specific medical advice. Patients should consult with a qualified healthcare provider before making decisions about therapies and/or health conditions.© 2026 Therapeutic Research Center

One more smart check

Taking Madagascar Periwinkle as Part of a Dietary Supplement Product? Check It for Interactions

We hold 8 real supplement products containing Madagascar Periwinkle, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Madagascar Periwinkle. Even though Madagascar Periwinkle itself has no known interaction with Levoleucovorin, another ingredient on your label might. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where Madagascar Periwinkle and Levoleucovorin 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 Madagascar Periwinkle
Steady interest

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

29 days ago today
Medication Levoleucovorin
Steady interest

#2,363 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 Madagascar Periwinkle reference on this page ↓
  • Freshness: we automatically re-check this combination every week — this pair was last verified September 20, 2026. The Madagascar Periwinkle and Levoleucovorin records this page draws on were last updated July 11, 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 Madagascar Periwinkle

What is Madagascar Periwinkle?

  • Diabetes (folk use)
  • High blood pressure (traditional use)
  • Sore throat and mouth ailments
  • Wound healing (topical)
  • Source of cancer chemotherapy drugs

Madagascar periwinkle is a flowering plant famous as the natural source of important chemotherapy drugs (vincristine and vinblastine), but the raw plant itself is toxic and not safe to use as a home remedy. While it has a long history in traditional medicine, there is no reliable evidence that taking the whole herb is safe or effective, and it should not be self-administered.

Catharanthus roseus · Apocynaceae · Leaves, roots, and whole aerial parts · Capsules, dried herb, teas, tinctures, and topical extracts (pharmaceutical drugs are made from purified alkaloids)

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

Madagascar Periwinkle: dosing

There is no established safe dose for Madagascar periwinkle as a dietary supplement, and because the plant is toxic, we do not recommend using it for self-care.The medicines made from this plant (such as vincristine and vinblastine) are prescription chemotherapy drugs that must be dosed and administered by trained healthcare providers in a clinical setting. In most cases, the safest choice is to avoid the raw herb entirely.

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

Read the full Madagascar Periwinkle monograph & all interactions
Medication

About Levoleucovorin Injection

What Is Levoleucovorin Injection Used For?

Brand name: Khapzory

Levoleucovorin injection (brands: Fusilev, Khapzory) is used intravenously in three main situations. First, it is given as a "rescue" treatment after high-dose methotrexate chemotherapy in osteosarcoma (bone cancer) — helping to limit the toxic effects methotrexate can have on healthy cells. Second, it is used when methotrexate is not clearing the body fast enough, or when there has been an accidental overdose of methotrexate or similar drugs called folic acid antagonists.

Third, levoleucovorin injection is used alongside the chemotherapy drug 5-fluorouracil (5-FU) for the palliative treatment of advanced metastatic colorectal cancer — meaning it helps make 5-FU work better, though the goal is disease control rather than cure. It is not approved for pernicious anemia or megaloblastic anemias related to vitamin B12 deficiency.

Most-Reported Side Effects for Levoleucovorin

From FAERS, the FDA’s public side-effect reporting system (3,706 reports, all brands). Reports are voluntary and are not proof the drug caused the effect.

Nausea 288 reports
Neutropenia 251 reports
Diarrhea 246 reports
Decreased appetite 187 reports
Vomiting 171 reports
See full Levoleucovorin Injection drug information
Keep checking

Other Drugs & Madagascar Periwinkle

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

0Major
87Moderate
0Minor
2,742No known interaction
Moderate

87 interactions

Showing 60 of 87 moderate interactions — see all 87 on the Madagascar Periwinkle page.

No interaction 2,742 drugs checked — show the list
Evidence & sources

Madagascar Periwinkle References

The 6 references that drive our Madagascar Periwinkle 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. The Review of Natural Products by Facts and Comparisons. St. Louis, MO: Wolters Kluwer Co., 1999.
  2. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
  3. Ellenhorn MJ, et al. Ellenhorn's Medical Toxicology: Diagnoses and Treatment of Human Poisoning. 2nd ed. Baltimore, MD: Williams & Wilkins, 1997.
  4. Brinker F. Herb Contraindications and Drug Interactions. 2nd ed. Sandy, OR: Eclectic Medical Publications, 1998.
  5. Ghosh D, Roy I, Chanda S, Gupta-Bhattacharya S. Allergy to periwinkle pollen (Catharanthus roseus G. Don.). Ann Agric Environ Med. 2007;14(1):39-43.
  6. Oguntibeju OO, Aboua Y, Goboza M. Vindoline-A natural product from catharanthus roseus reduces hyperlipidemia and renal pathophysiology in experimental type 2 diabetes. Biomedicines. 2019 Aug 13;7(3):59. 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 Madagascar Periwinkle and Levoleucovorin Together: Common Questions

Is it safe to take Madagascar Periwinkle with Levoleucovorin?
We do not list a known interaction between Madagascar Periwinkle and Levoleucovorin. 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 Madagascar Periwinkle and Levoleucovorin have any of the same side effects?
Yes — our sources link each of them separately to 7 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.
Does Madagascar Periwinkle interact with any other medications?
Yes. Madagascar Periwinkle has 87 documented drug interactions in our database — Levoleucovorin is simply not one of them. If you take anything else, it is worth checking each one; they are all listed on this page.

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

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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.