Drug & supplement interaction

Zinc + Leucovorin Calcium

Leucovorin Calcium brand name: Wellcovorin.

No Known Interaction
The bottom line No known interaction

We found no known interaction between Zinc and Leucovorin Calcium 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

Zinc and Leucovorin Calcium

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 Leucovorin Calcium and Zinc 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.

Zinc safety at a glance

Zinc overall Use caution Generally safe in recommended amounts, but high doses can be harmful.
Pregnancy Likely Safe When used orally and appropriately. Zinc is safe in amounts that do not exceed the tolerable upper intake level (UL) of 34 mg daily during pregnancy in those 14... Read the full pregnancy detail
Breastfeeding Likely Safe When used orally and appropriately. Zinc is safe in amounts that do not exceed the tolerable upper intake level (UL) of 34 mg daily during lactation in those 14... 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 Leucovorin Calcium and Zinc? Ask Dr. Brian Staiger, PharmD, BCPS directly ›
How we checked

Why No Interaction Is Listed for Leucovorin Calcium

Interactions in our licensed database are recorded against drug classes, not just single drug names. Leucovorin Calcium is filed under a single classification — oral drugs. Zinc has documented interactions with 10 drug classes — the most serious being bictegravir/emtricitabine/tenofovir alafenamide (biktarvy) (moderate), cephalexin (keflex) (moderate) and cisplatin (platinol-aq) (moderate) — and none of Leucovorin Calcium’s classifications are among them.

Classification data comes from our licensed Natural Medicines dataset. A medication can belong to classes beyond those recorded there, so this describes how the check was run — it is not a safety guarantee.

Keep it in perspective

Zinc Does Interact With Other Medications

Zinc has 63 moderate, 4 minor known drug interactions in our database — Leucovorin Calcium 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 Zinc

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

What to actually watch for

No Interaction Found — But Data Suggests Zinc and Leucovorin Calcium 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. 2 of them are worth acting on rather than waiting out — marked below.

  • A low white blood cell count Worth acting on reported in 5.8% of FDA reports for Leucovorin Calcium Additional detail

    Zinc

    “There is concern that high daily doses of zinc, above the tolerable upper intake level (UL) of 40 mg per day, might increase the risk of copper deficiency, potentially leading to anemia and leukopenia. To prevent copper deficiency, some clinicians give a small dose of copper when zinc is used in high doses, long-term.”

    Zinc · Natural Medicines adverse-effect record, reported in anemia.

    3 sources cited
    1. 7135. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, DC: National Academy Press, 2002.
    2. 112473. Magham K, Han J, Eilbert W, Bunney EB. Severe copper deficiency anemia caused by zinc supplement use. Am J Emerg Med 2023;72:222. PubMed
    3. 7303. Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss. AREDS report no. 8. Arch Oph

    “Daily doses of 300 mg of supplemental zinc for 6 weeks appear to impair immune response. A case of erythematosus-like syndrome, including symptoms such as fever, leg ulcers, and rash, has been reported following intake of effervescent tablets (Solvezink) containing zinc 45 mg. In another case, severe neutropenia was reported after taking supplemental zinc 900 mg daily for an unknown duration.”

    Zinc · Natural Medicines adverse-effect record, reported in myasthenia gravis.

    3 sources cited
    1. 7135. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, DC: National Academy Press, 2002.
    2. 87506. Fjellner, B. Drug-induced lupus erythematosus aggravated by oral zinc therapy. Acta Derm.Venereol. 1979;59(4):368-370. DOI
    3. 112473. Magham K, Han J, Eilbert W, Bunney EB. Severe copper deficiency anemia caused by zinc supplement use. Am J Emerg Med 2023;72:222. PubMed

    Leucovorin Calcium

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

  • Kidney problems Worth acting on Additional detail

    Zinc

    “Orally, zinc is well tolerated in doses below the tolerable upper intake level (UL), which is 40 mg daily for adults. Topically, zinc is well tolerated.

    Most Common Adverse Effects:

    Orally: Abdominal cramps, diarrhea, metallic taste, nausea and vomiting (dose-related).

    Topically: Burning, discoloration, itching, stinging, and tingling when applied to irritated tissue.

    Intranasally: Bad taste, dry mouth, headache, irr…”

    Zinc · Natural Medicines adverse-effect record, reported in anemia.

    Leucovorin Calcium

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

  • Mouth irritation or sores Additional detail

    Zinc

    “Orally, zinc can cause nausea, vomiting, a metallic or objectionable taste in the mouth, abdominal cramping, indigestion, heartburn, dry mouth, and mouth irritation. When used orally in amounts above the tolerable upper intake level, zinc may cause irritation and corrosion of the gastrointestinal tract, watery diarrhea, epigastric pain, and severe vomiting.

    Intranasally, zinc can cause bad taste, dry mouth, and burni…”

    Zinc · Natural Medicines adverse-effect record, reported in diarrhea.

    6 sources cited
    1. 338. Smith DS, Helzner EC, Nuttall CE Jr, et al. Failure of zinc gluconate in treatment of acute upper respiratory tract infections. Antimicrob Agents Chemother 1989;33:646-8. PubMed
    2. 2663. Chan S, Gerson B, Subramaniam S. The role of copper, molybdenum, selenium, and zinc in nutrition and health. Clin Lab Med 1998;18:673-85. DOI
    3. 2681. Fosmire GJ. Zinc toxicity. Am J Clin Nutr 1990;51:225-7.
    4. 6592. Wray D. A double-blind trial of systemic zinc sulfate in recurrent aphthous stomatitis. Oral Surg Oral Med Oral Pathol 1982;53:469-72. PubMed
    5. 6700. Douglas RM, Miles HB, Moore BW, et al. Failure of effervescent zinc acetate lozenges to alter the course of upper respiratory tract infections in Australian adults. Antimicrob Agents Chemother 1987;31:1263-5. PubMed
    6. 18216. Science M, Johnstone J, Roth DE, et al. Zinc for the treatment of the common cold: a systematic review and meta-analysis of randomized controlled trials. CMAJ 2012;184:E551-61. PubMed

    Leucovorin Calcium

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

  • Diarrhea / Vomiting / Nausea reported in 9.5% of FDA reports for Leucovorin Calcium Additional detail

    Zinc

    Recorded for Zinc in the same Natural Medicines adverse-effect record shown under Kidney problems above.

    Leucovorin Calcium

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

  • Tiredness reported in 4.6% of FDA reports for Leucovorin Calcium Additional detail

    Zinc

    “Zinc-containing denture adhesives can cause toxicity if used more frequently than recommended for several years. Case reports describe hyperzincemia, low copper levels, blood dyscrasias, and neurological problems, including sensory disturbances, numbness, tingling, limb weakness, and difficulty walking in patients applying denture adhesive multiple times daily for several years.”

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

    6 sources cited
    1. 17092. Health Canada / GlaxoSmithKline Consumer Healthcare. Association of long-term, excessive use of zinc-containing Poli-Grip products with myeloneuropathy and blood dyscrasias. February 18, 2010. Available at: http://hc-sc.gc.ca/dhp-mps/alt_formats/pdf/medef
    2. 17093. GlaxoSmithKline Consumer Advisory. GlaxoSmithKline (GSK) warns about a potential health risk associated with long-term, excessive use of GSK's zinc-containing denture adhesives Super Polygrip Original, Ultra Fresh and Extra Care. February 18, 2010. Availa
    3. 90205. Crown LA, May JA. Zinc toxicity: denture adhesives, bone marrow failure and polyneuropathy. Tenn Med. 2012 Feb;105(2):39-40, 42.
    4. 90233. Zittel S, Ufer F, Gerloff C, Münchau A, Rosenkranz M. Severe myelopathy after denture cream use--is copper deficiency or excess zinc the cause? Clin Neurol Neurosurg. 2014 Jun;121:17-8. PubMed
    5. 8628. Turner RB. Ineffectiveness of intranasal zinc gluconate for prevention of experimental rhinovirus colds. Clin Infect Dis 2001;33:1865-70. PubMed
    6. 87534. Bosch, F. and Jimenez, E. Post-marketing surveillance of zinc acexamate in peptic ulcer treatment. Clin Trials J 1990;27:301-312.

    “Occupational inhalation of zinc oxide fumes can cause metal fume fever with symptoms including fatigue, chills, fever, myalgias, cough, dyspnea, leukocytosis, thirst, metallic taste, and salivation.”

    Zinc · Natural Medicines adverse-effect record, reported in cough.

    1 source cited
    1. 331. Barceloux DG. Zinc. J Toxicol Clin Toxicol 1999;37:279-92.

    Leucovorin Calcium

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

  • A skin rash Additional detail

    Zinc

    “Topically, zinc can cause burning, stinging, itching, and tingling when applied to inflamed tissue. Zinc oxide can be deposited in the submucosal tissue and cause dark discoloration of the skin. This can occur with prolonged topical application to intact skin, application to eroded or ulcerated skin, or penetrating traumatic exposure, and also parenteral administration.

    In rare cases, oral zinc has resulted in worsen…”

    Zinc · Natural Medicines adverse-effect record, reported in acne.

    6 sources cited
    1. 6911. Ewing CI, Gibbs AC, Ashcroft C, David TJ. Failure of oral zinc supplementation in atopic eczema. Eur J Clin Nutr 1991;45:507-10.
    2. 8623. Godfrey HR, Godfrey NJ, Godfrey JC, Riley D. A randomized clinical trial on the treatment of oral herpes with topical zinc oxide/glycine. Altern Ther Health Med 2001;7:49-56.
    3. 87297. Cochran, R. J., Tucker, S. B., and Flannigan, S. A. Topical zinc therapy for acne vulgaris. Int.J Dermatol. 1985;24(3):188-190. DOI
    4. 8618. Greenberg JE, Lynn M, Kirsner RS, et al. Mucocutaneous pigmented macule as a result of zinc deposition. J Cutan Pathol 2002;29:613-5. PubMed
    5. 104056. Yee BE, Richards P, Sui JY, Marsch AF. Serum zinc levels and efficacy of zinc treatment in acne vulgaris: A systematic review and meta-analysis. Dermatol Ther. 2020:e14252. PubMed
    6. 6592. Wray D. A double-blind trial of systemic zinc sulfate in recurrent aphthous stomatitis. Oral Surg Oral Med Oral Pathol 1982;53:469-72. PubMed

    Leucovorin Calcium

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

Reported for Zinc but not commonly for Leucovorin Calcium: stomach pain, unsteadiness, a change in taste and stomach upset.

Effects for Leucovorin Calcium come from the ADVERSE REACTIONS section of its FDA label; effects for Zinc come from the Natural Medicines adverse-effect record, quoted above. Where a percentage is shown, it is the share of 19,003 voluntary FDA FAERS reports for Leucovorin Calcium 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

Zinc in Pregnancy & Breastfeeding

Pregnancy Likely Safe

When used orally and appropriately. Zinc is safe in amounts that do not exceed the tolerable upper intake level (UL) of 34 mg daily during pregnancy in those 14-18 years of age and 40 mg daily in those 19-50 years of age.

Pregnancy Likely Unsafe

When used orally in doses exceeding the UL.

Lactation Likely Safe

When used orally and appropriately. Zinc is safe in amounts that do not exceed the tolerable upper intake level (UL) of 34 mg daily during lactation in those 14-18 years of age, and 40 mg daily for those 19-50 years of age.

Lactation Possibly Unsafe

When used orally in doses exceeding the UL. Higher doses can cause zinc-induced copper deficiency in nursing infants.

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

Everything else you take

See Every Supplement That Interacts With Leucovorin Calcium

This page covers Zinc only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Leucovorin Calcium page lists 17 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Coffee Charcoal (moderate), European Mandrake (moderate), Glucomannan (moderate) and Guar Gum (moderate).

By severity: 1 major · 7 moderate · 9 minor.

Open the Leucovorin Calcium interaction page

One more smart check

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

We hold 26,692 real supplement products containing Zinc, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Zinc. Even though Zinc itself has no known interaction with Leucovorin Calcium, 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 Zinc and Leucovorin Calcium 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 Zinc
Top 10

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

29 days ago today
Medication Leucovorin Calcium
Top 25%

#694 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 Zinc reference on this page ↓
  • Freshness: we automatically re-check this combination every week — this pair was last verified September 13, 2026. The Zinc and Leucovorin Calcium 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 Zinc

What is Zinc?

Zinc
  • Zinc deficiency
  • Immune support
  • Cold symptoms
  • Acne
  • Wound healing

Zinc is an essential mineral that your body needs for immune function, wound healing, taste, and smell. Most people get enough from food, but supplements can help correct or prevent a deficiency. Taking too much zinc for too long can cause harm, so check with a pharmacist or doctor before using high-dose supplements.

Not applicable (an essential mineral) · Tablets, capsules, lozenges, liquid, and topical creams

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

Zinc: dosing

The right amount of zinc depends on your age, sex, health, and the reason you are taking it. A standardized supplement dose is not established for most uses, and different products contain different amounts and forms of zinc.For general nutrition, many people meet their needs through food and a standard multivitamin. Avoid taking high doses long-term on your own.

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

Read the full Zinc monograph & all interactions
Medication

About Leucovorin

What Is Leucovorin Used For?

Brand name: Wellcovorin

Leucovorin is used to reduce the harmful effects of methotrexate when the body is slow to clear it, and to counteract accidental overdoses of drugs that block folic acid (called folic acid antagonists or DHFR inhibitors). It is also used to treat cerebral folate transport deficiency (FOLR1-CFTD), a rare genetic condition that prevents the brain from receiving enough folate.

The injectable forms — including leucovorin calcium injection and Vykoura — are additionally approved for rescue after high-dose methotrexate therapy, for treatment of megaloblastic anemia (a type of anemia caused by low folic acid) when oral treatment isn't possible, and for use alongside fluorouracil in treating metastatic colorectal cancer. Leucovorin calcium injection is specifically indicated for rescue after high-dose methotrexate in osteosarcoma.

Most-Reported Side Effects for Leucovorin Calcium

From FAERS, the FDA’s public side-effect reporting system (19,003 reports, all brands). Reports are voluntary and are not proof the drug caused the effect.

Diarrhea 1,799 reports
Nausea 1,388 reports
Vomiting 1,135 reports
Neutropenia 1,094 reports
Fever 1,011 reports
See full Leucovorin drug information
Keep checking

Other Drugs & Zinc

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

0Major
63Moderate
4Minor
2,762No known interaction
Moderate

63 interactions

Showing 60 of 63 moderate interactions — see all 63 on the Zinc page.

Minor

4 interactions

No interaction 2,762 drugs checked — show the list
Evidence & sources

Zinc References

The 88 references that drive our Zinc 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. Barceloux DG. Zinc. J Toxicol Clin Toxicol 1999;37:279-92.
  2. Eby GA, Davis DR, Halcomb WW. Reduction in duration of common colds by zinc gluconate lozenges in a double-blind study. Antimicrob Agents Chemother 1984;25:20-4. DOI
  3. Smith DS, Helzner EC, Nuttall CE Jr, et al. Failure of zinc gluconate in treatment of acute upper respiratory tract infections. Antimicrob Agents Chemother 1989;33:646-8. PubMed
  4. Blondeau JM. Expanded activity and utility of the new fluoroquinolones: a review. Clin Ther 1999;21:3-40. PubMed
  5. Reyes AJ, Olhaberry JV, Leary WP, et al. Urinary zinc excretion, diuretics, zinc deficiency and some side-effects of diuretics. S Afr Med J 1983;64:936-41.
  6. Kugelmas M. Preliminary observation: oral zinc sulfate replacement is effective in treating muscle cramps in cirrhotic patients. J Am Coll Nutr 2000;19:13-5. PubMed
  7. Hebel SK, ed. Drug Facts and Comparisons. 52nd ed. St. Louis: Facts and Comparisons, 1998.
  8. Chan S, Gerson B, Subramaniam S. The role of copper, molybdenum, selenium, and zinc in nutrition and health. Clin Lab Med 1998;18:673-85. DOI
  9. Brewer GJ, Yuzbasiyan-Gurkan V, Johnson V, et al. Treatment of Wilson's disease with zinc: XI. Interaction with other anticopper agents. J Am Coll Nutr 1993;12:26-30. PubMed
  10. Fosmire GJ. Zinc toxicity. Am J Clin Nutr 1990;51:225-7.
  11. Lomaestro BM, Bailie GR. Absorption interactions with fluoroquinolones. 1995 update. Drug Saf 1995;12:314-33. PubMed
  12. Hansten PD, Horn JR. Drug Interactions Analysis and Management. Vancouver, WA: Applied Therapeutics Inc., 1997 and updates.
  13. Seelig MS. Auto-immune complications of D-penicillamine - A possible result of zinc and magnesium depletion and of pyridoxine inactivation. J Am Coll Nutr 1982;1:207-14. PubMed
  14. Neuvonen PJ. Interactions with the absorption of tetracyclines. Drugs 1976;11:45-54.. PubMed
  15. Hirt M, Nobel S, Barron E. Zinc nasal gel for the treatment of common cold symptoms: A double-blind, placebo-controlled trial. Ear Nose Throat J 2000;79:778-82.. DOI

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 Zinc and Leucovorin Calcium Together: Common Questions

Is it safe to take Zinc with Leucovorin Calcium?
We do not list a known interaction between Zinc and Leucovorin Calcium. 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 Zinc and Leucovorin Calcium have any of the same side effects?
Yes — our sources link each of them separately to 8 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.
How was the Zinc and Leucovorin Calcium combination checked?
Interactions in our licensed database are recorded against drug classes. Leucovorin Calcium is filed under 1 classification, and Zinc has documented interactions with 10 drug classes — none of Leucovorin Calcium's classifications are among them. A medication can belong to classes beyond those recorded in our dataset, so this describes how the check was run rather than guaranteeing safety.
Does Zinc interact with any other medications?
Yes. Zinc has 67 documented drug interactions in our database — Leucovorin Calcium is simply not one of them. If you take anything else, it is worth checking each one; they are all listed on this page.
Does Leucovorin Calcium interact with any supplements?
Yes. Leucovorin Calcium has documented interactions with 17 supplements in our database — Zinc is not one of them. The Leucovorin Calcium interaction page linked on this page lists every one, ranked by severity.

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

Still Have a Question About Leucovorin Calcium and Zinc?

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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.