Drug & supplement interaction

Folic Acid + Penicillamine

Penicillamine brand names: Cuprimine, Depen Titratable.

No Known Interaction
The bottom line No known interaction

We found no known interaction between Folic Acid and Penicillamine 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 label for Penicillamine states a food rule worth keeping to, and 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

Folic Acid and Penicillamine

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 Penicillamine and Folic Acid 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.

Folic Acid safety at a glance

Folic Acid overall Generally safe Generally safe at recommended doses for most adults.
Pregnancy Likely Safe When used orally and appropriately. Folic acid 300-400 mcg is commonly used during pregnancy for prevention of neural tube defects. Miscarriage rates and negati... Read the full pregnancy detail
Breastfeeding Likely Safe When used orally and appropriately. Folic acid 300-400 mcg is commonly used during pregnancy for prevention of neural tube defects. Miscarriage rates and negati... 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 Penicillamine and Folic Acid? Ask Dr. Brian Staiger, PharmD, BCPS directly ›
How we checked

Why No Interaction Is Listed for Penicillamine

Interactions in our licensed database are recorded against drug classes, not just single drug names. Penicillamine is filed under 3 classifications — including nephrotoxic drugs, oral drugs. Folic Acid has documented interactions with 7 drug classes — the most serious being 5-fluorouracil (moderate), capecitabine (xeloda) (moderate) and methotrexate (trexall, others) (moderate) — and none of Penicillamine’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

Folic Acid Does Interact With Other Medications

Folic Acid has 40 moderate known drug interactions in our database — Penicillamine 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 Folic Acid

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

What to actually watch for

No Interaction Found — But Data Suggests Folic Acid and Penicillamine 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.

  • Wheezing Worth acting on Additional detail

    Folic Acid

    “Folic acid use in late pregnancy has been associated with an increased risk of persistent and childhood asthma at 3.5 years in population research. When taken pre-pregnancy or early in pregnancy, population research has not found an association with increased risk of asthma or allergies in childhood.”

    Folic Acid · Natural Medicines adverse-effect record, reported in allergic rhinitis (hay fever).

    4 sources cited
    1. 50380. Whitrow, M. J., Moore, V. M., Rumbold, A. R., and Davies, M. J. Effect of supplemental folic acid in pregnancy on childhood asthma: a prospective birth cohort study. Am J Epidemiol. 12-15-2009;170(12):1486-1493. PubMed
    2. 90799. Crider KS, Cordero AM, Qi YP, Mulinare J, Dowling NF, Berry RJ. Prenatal folic acid and risk of asthma in children: a systematic review and meta-analysis. Am J Clin Nutr. 2013;98(5):1272-81. PubMed
    3. 103979. Liu J, Li Z, Ye R, Liu J, Ren A. Periconceptional folic acid supplementation and risk of parent-reported asthma in children at 4-6 years of age. ERJ Open Res. 2020;6(1):00250-2019. PubMed
    4. 50328. Haberg, S. E., London, S. J., Stigum, H., Nafstad, P., and Nystad, W. Folic acid supplements in pregnancy and early childhood respiratory health. Arch Dis.Child 2009;94(3):180-184. PubMed

    Penicillamine

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

  • Anemia Worth acting on Additional detail

    Folic Acid

    “Orally, folic acid 15 mg daily can sometimes cause altered sleep patterns, vivid dreaming, irritability, excitability, hyperactivity, confusion, and impaired judgment (15). Large doses of folic acid can also precipitate or exacerbate neuropathy in people deficient in vitamin B12.”

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

    3 sources cited
    1. 15. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
    2. 6243. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline (2000). Washington, DC: National Academy Press, 2000. Available at: http://b
    3. 13068. Morris MC, Evans DA, Bienias JL, et al. Dietary folate and vitamin B12 intake and cognitive decline among community-dwelling older persons. Arch Neurol 2005;62:641-5. PubMed

    Penicillamine

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

  • Liver problems Worth acting on Additional detail

    Folic Acid

    Recorded for Folic Acid in the same Natural Medicines adverse-effect record shown under Wheezing above.

    Penicillamine

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

  • A change in taste / Diarrhea / Nausea reported in 10.5% of FDA reports for Penicillamine Additional detail

    Folic Acid

    “Orally, folic acid 5 mg daily can cause abdominal cramps and diarrhea. Folic acid 15 mg daily can sometimes cause nausea, abdominal distention, flatulence, and bitter taste in the mouth (15). In children aged 6-30 months at risk of malnourishment, taking a nutritional supplement (Nutriset Ltd) enriched in folic acid 75-150 mcg daily, with or without vitamin B 12 0.9-1.8 mcg daily, for 6 months increases the likelihoo…”

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

    3 sources cited
    1. 7225. Sandoval M, Charbonnet RM, Okuhama NN, et al. Cat's claw inhibits TNFalpha production and scavenges free radicals: role in cytoprotection. Free Radic Biol Med 2000;29:71-78.
    2. 15. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
    3. 90391. Taneja S, Strand TA, Kumar T, et al. Folic acid and vitamin B-12 supplementation and common infections in 6-30-mo-old children in India: a randomized placebo-controlled trial. Am J Clin Nutr 2013;98(3):731-7. PubMed

    Penicillamine

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

  • A skin rash Additional detail

    Folic Acid

    “Orally, folic acid 1-5 mg daily can cause rash. Folic acid 15 mg daily can sometimes cause allergic skin reactions (15).”

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

    4 sources cited
    1. 7225. Sandoval M, Charbonnet RM, Okuhama NN, et al. Cat's claw inhibits TNFalpha production and scavenges free radicals: role in cytoprotection. Free Radic Biol Med 2000;29:71-78.
    2. 90375. Fonseca VA, Lavery LA, Thethi TK, et al. Metanx in type 2 diabetes with peripheral neuropathy: A randomized trial. Am J Med 2013;126(2):141-9. PubMed
    3. 91319. Van Der Woude DA, De Vries J, Van Wijk EM, Verzijl JM, Pijnenborg JM. A randomized controlled trial examining the addition of folic acid to iron supplementation in the treatment of postpartum anemia. Int J Gynaecol Obstet. 2014;126(2):101-5. PubMed
    4. 15. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.

    Penicillamine

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

  • Vomiting Additional detail

    Folic Acid

    “Liver dysfunction, with jaundice and very high liver enzymes, occurred in a 30-year-old pregnant patient with severe nausea and vomiting taking a folic acid supplement (Folic acid, Nature Made) 400 mcg daily.”

    Folic Acid · Natural Medicines adverse-effect record, reported in nausea and vomiting.

    1 source cited
    1. 91309. Matsubara S, Imai K, Murayama K, Higashizawa T. Severe liver dysfunction during nausea and vomiting of pregnancy: folic acid supplement as a suggested culprit. J Obstet Gynaecol. 2012;32(7):701-2. PubMed

    Penicillamine

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

Reported for Folic Acid but not commonly for Penicillamine: trouble sleeping, an allergic reaction, a severe allergic reaction and stomach pain.

Effects for Penicillamine come from the ADVERSE REACTIONS section of its FDA label; effects for Folic Acid come from the Natural Medicines adverse-effect record, quoted above. Where a percentage is shown, it is the share of 917 voluntary FDA FAERS reports for Penicillamine 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

Folic Acid in Pregnancy & Breastfeeding

Pregnancy And Lactation Likely Safe

When used orally and appropriately. Folic acid 300-400 mcg is commonly used during pregnancy for prevention of neural tube defects. Miscarriage rates and negative impacts on fetal growth have not been shown to increase with peri-conception supplemental folic acid intakes of 4 mg per day. However, other research shows that taking more than 5 mg per day during pregnancy may reduce development of cognitive, emotional, and motor skills in infants. Also, the tolerable upper intake level (UL) of folic acid for pregnant or lactating women is 800 mcg daily for those 14-18 years of age and 1000 mcg daily for those 19 years and older.

Pregnancy And Lactation Possibly Safe

When L-5-methyltetrahydrofolate (L-5-MTHF), the reduced form of folate, is used orally and appropriately, short-term. L-5-MTHF has been used with apparent safety at a dose of 416 mcg daily for 16 weeks during lactation. Compared to folic acid, this form seems to further increase the folate concentration of red blood cells, but not breast milk.

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

How to take them

Some Penicillamine Products Have a Food Rule — Folic Acid Should Not Break It

At least one FDA label for a product containing Penicillamine says to take it on an empty stomach. Most supplements — Folic Acid included — are taken with a meal, so the easy mistake is swallowing both together at breakfast. Where that rule applies, keep Penicillamine on its own and move Folic Acid to a meal later in the day.

This may not be true of your version. Food instructions belong to the product, not the ingredient: two Penicillamine products can carry different directions, and extended-release forms often differ from immediate-release ones. The label we read is quoted below — check the directions on your own box or bottle, or ask your pharmacist, for how to take the exact product you were given.

DOSAGE AND ADMINISTRATION In all patients receiving penicillamine, it is important that CUPRIMINE be given on an empty stomach, at least one hour before meals or two hours after meals, and at least one hour apart from any other drug, food, or milk.

From the Dosage and Administration section of the FDA label we read for Penicillamine — where that label names a specific product, the instruction is that product's. Read the label on DailyMed ›

A food rule is not an interaction — it is about how much of the medicine you absorb. The directions that came with your own product, and your pharmacist, outrank anything on this page.

From our Q&A

Questions About Folic Acid or Penicillamine

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Folic Acid or Penicillamine, 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 Penicillamine

This page covers Folic Acid only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Penicillamine page lists 26 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Asarabacca (major), Siberian Cocklebur (major), Aristolochia (moderate) and Coffee Charcoal (moderate).

By severity: 3 major · 13 moderate · 10 minor.

From our pharmacist’s overview on the Penicillamine page

“People take penicillamine (Cuprimine, Depen) for demanding conditions, Wilson's disease, rheumatoid arthritis, cystinuria, and its 26 supplement interactions are not a list to skim, three of them rated major. Seventeen ingredients can keep an oral dose from being fully absorbed, activated charcoal chief among them, and six more can str…”

Reviewed by 2 · Jul 18, 2026

Open the Penicillamine interaction page

One more smart check

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

We hold 92 real supplement products containing Folic Acid, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Folic Acid. Even though Folic Acid itself has no known interaction with Penicillamine, 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 Folic Acid and Penicillamine 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 Folic Acid
Top 25%

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

29 days ago today
Medication Penicillamine
Steady interest

#2,400 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 Folic Acid reference on this page ↓
  • Freshness: we automatically re-check this combination every week — this pair was last verified September 20, 2026. The Folic Acid and Penicillamine 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 Folic Acid

What is Folic Acid?

  • Preventing neural tube birth defects
  • Treating or preventing folate deficiency
  • Supporting pregnancy health
  • Certain types of anemia
  • Heart and blood vessel health

Folic acid is the man-made form of vitamin B9 and is one of the most well-studied supplements, especially for preventing serious birth defects when taken before and during early pregnancy. It is widely available, inexpensive, and generally safe at recommended doses, but you should still check with your pharmacist or doctor about the right amount for you.

Synthetic vitamin (not a plant part); natural folate is found in many foods · Tablets, capsules, softgels, multivitamins, prenatal vitamins, fortified foods

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

Folic Acid: dosing

People being treated for a deficiency may need higher amounts under medical supervision. Do not guess at high doses on your own — check with a healthcare professional, especially if you have anemia or are over 50.

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

Read the full Folic Acid monograph & all interactions
Medication

About Penicillamine

What Is Penicillamine Used For?

Brand names: Cuprimine, Depen Titratable

Penicillamine is used for three distinct conditions. It treats Wilson's disease — a rare genetic disorder in which the body accumulates dangerous levels of copper — by binding to the excess copper and helping the body remove it. It also treats cystinuria, a condition where the amino acid cystine builds up and forms painful kidney stones, by converting cystine into a more soluble form that the body can excrete more easily.

For patients with severe, active rheumatoid arthritis who have not responded adequately to conventional therapies, penicillamine (available as Aagylur, Cuprimine, Depen, and other products) may be used to help suppress disease activity and reduce joint pain, tenderness, and swelling.

See full Penicillamine drug information
Keep checking

Other Drugs & Folic Acid

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

0Major
40Moderate
0Minor
2,789No known interaction
Moderate

40 interactions

No interaction 2,789 drugs checked — show the list
Evidence & sources

Folic Acid References

The 56 references that drive our Folic Acid 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. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
  2. Duhra P. Treatment of gastrointestinal symptoms associated with methotrexate therapy for psoriasis. J Am Acad Dermatol 1993;28:466-9. PubMed
  3. Morgan SL, Baggott JE, Vaughn WH, et al. Supplementation with folic acid during methotrexate therapy for rheumatoid arthritis. A double-blind, placebo-controlled trial. Ann Intern Med 1994;121:833-41. PubMed
  4. Froscher W, Maier V, Laage M, et al. Folate deficiency, anticonvulsant drugs, and psychiatric morbidity. Clin Neuropharmacol 1995;18:165-82. PubMed
  5. Lewis DP, Van Dyke DC, Willhite LA, et al. Phenytoin-folic acid interaction. Ann Pharmacother 1995;29:726-35. PubMed
  6. Berg MJ, Stumbo PJ, Chenard CA, et al. Folic acid improves phenytoin pharmacokinetics. J Am Diet Assoc 1995;95:352-6. PubMed
  7. Berg MJ, Fincham RW, Ebert BE, et al. Phenytoin pharmacokinetics: Before and after folic acid administration. Epilepsia 1992;33:712-20. PubMed
  8. Shafer RB, Nuttall FQ. Calcium and folic acid absorption in patients taking anticonvulsant drugs. J Clin Endocrinol Metab 1975;41:1125-9. PubMed
  9. Leeb BF, Witzmann G, Ogris E, et al. Folic acid and cyanocobalamin levels in serum and erythrocytes during low-dose methotrexate therapy of rheumatoid arthritis and psoriatic arthritis patients. Clin Exp Rheumatol 1995;13:459-63.
  10. Morgan SL, Baggott JE, Lee JY, Alarcón GS. Folic acid supplementation prevents deficient blood folate levels and hyperhomocysteinemia during longterm, low dose methotrexate therapy for rheumatoid arthritis: implications for cardiovascular disease preventi
  11. Dijkmans BA. Folate supplementation and methotrexate. Br J Rheumatol 1995;34:1172-4. PubMed
  12. Segal S, Kaminski S. Drug-nutrient interactions. American Druggist 1996 Jul;42-8.
  13. Lambie DG, Johnson RH. Drugs and folate metabolism. Drugs 1985;30:145-55. PubMed
  14. Amer College of Rheumatology ad hoc committee on clinical guidelines. Guidelines for monitoring drug therapy in rheumatoid arthritis. Arthritis Rheum 1996;39:723-31. DOI
  15. Suitor CW, Bailey LB. Dietary folate equivalents: interpretation and application. J Am Diet Assoc 2000;100:88-94. 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 Folic Acid and Penicillamine Together: Common Questions

Is it safe to take Folic Acid with Penicillamine?
We do not list a known interaction between Folic Acid and Penicillamine. 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 Folic Acid and Penicillamine 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.
Should I take Folic Acid and Penicillamine at the same time of day?
At least one FDA label for a product containing Penicillamine says to take it on an empty stomach, and supplements are usually taken with a meal — so taking them together at breakfast is the easy mistake. Where that applies, keep Penicillamine on its own and move Folic Acid to a meal later in the day. Food instructions belong to the product rather than the ingredient, so check the directions on your own box. This is about absorption, not an interaction.
How was the Folic Acid and Penicillamine combination checked?
Interactions in our licensed database are recorded against drug classes. Penicillamine is filed under 3 classifications, and Folic Acid has documented interactions with 7 drug classes — none of Penicillamine'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 Folic Acid interact with any other medications?
Yes. Folic Acid has 40 documented drug interactions in our database — Penicillamine 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 Penicillamine interact with any supplements?
Yes. Penicillamine has documented interactions with 26 supplements in our database — Folic Acid is not one of them. The Penicillamine 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 Penicillamine and Folic Acid?

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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.