Drug & supplement interaction

Malic Acid + Penicillamine

Penicillamine brand names: Cuprimine, Depen Titratable.

No Known Interaction
The bottom line No known interaction

We found no known interaction between Malic 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

Malic 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 Malic 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.

Malic Acid safety at a glance

Malic Acid overall Use caution Generally well tolerated in food amounts, but supplement safety is not well studied.
Pregnancy Likely Safe When used orally in amounts commonly found in foods. There is insufficient reliable information available about the safety of using malic acid in medicinal amou... Read the full pregnancy detail
Breastfeeding Likely Safe When used orally in amounts commonly found in foods. There is insufficient reliable information available about the safety of using malic acid in medicinal amou... 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 Malic 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. Malic Acid has documented interactions with 1 drug class — the most serious being antihypertensive drugs (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

Malic Acid Does Interact With Other Medications

Malic Acid has 172 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 Malic Acid

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

What to actually watch for

No Interaction Found — But Data Suggests Malic 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. One of them is worth acting on rather than waiting out — marked below.

  • Hives Worth acting on Additional detail

    Malic Acid

    “Topically, malic acid may cause moderate to strong skin irritation and peeling. In patients first patch tested with malic acid, next instructed to avoid foods containing malic or citric acid, and then challenged with foods containing high amounts of malic and citric acid, skin reactions including immediate hives and delayed contact dermatitis occurred.”

    Malic Acid · Natural Medicines adverse-effect record, reported in dermatitis.

    3 sources cited
    1. 26968. Fiume, Z. Final report on the safety assessment of malic acid and sodium malate. Int J Toxicol 2001;20 Suppl 1:47-55. PubMed
    2. 95564. Chiriac A, Brzezinski P. Topical malic acid in combination with citric acid: an option to treat recalcitrant warts. Dermatol Ther. 2015;28(6):336-8. PubMed
    3. 95595. Amended Safety Assessment of Malic Acid and Sodium Malate as Used in Cosmetics. Cosmetic Ingredient Review Expert Panel. Updated May 19, 2017. http://www.cir-safety.org/sites/default/files/malic%20acid.pdf. Accessed January 24, 2018.

    Penicillamine

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

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

    Malic Acid

    “Orally, diarrhea and nausea have been reported for patients taking a specific combination product (Super Malic) containing malic acid1200 mg and magnesium 300 mg twice daily. However, it is unclear if the adverse effect is due to malic acid, since it is known that magnesium can have a laxative effect at this dose.”

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

    1 source cited
    1. 3262. Russell IJ, Michalek JE, Flechas JD, Abraham GE. Treatment of fibromyalgia syndrome with Super Malic: a randomized, double blind, placebo controlled, crossover pilot study. J Rheumatol 1995;22:953-8.

    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

    Malic Acid

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

    Penicillamine

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

Reported for Malic Acid but not commonly for Penicillamine: eye irritation or redness.

Effects for Penicillamine come from the ADVERSE REACTIONS section of its FDA label; effects for Malic 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

Malic Acid in Pregnancy & Breastfeeding

Pregnancy And Lactation Likely Safe

When used orally in amounts commonly found in foods. There is insufficient reliable information available about the safety of using malic acid in medicinal amounts during pregnancy or lactation.

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 — Malic 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 — Malic 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 Malic 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.

Everything else you take

See Every Supplement That Interacts With Penicillamine

This page covers Malic 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 Malic Acid as Part of a Dietary Supplement Product? Check It for Interactions

We hold 678 real supplement products containing Malic Acid, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Malic Acid. Even though Malic 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 Malic 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 Malic Acid
Top 25%

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

29 days ago today
Medication Penicillamine
Steady interest

#2,653 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 Malic Acid reference on this page ↓
  • Freshness: we automatically re-check this combination every week — this pair was last verified September 20, 2026. The Malic 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 Malic Acid

What is Malic Acid?

Malic Acid
  • Fibromyalgia symptoms
  • Muscle pain and fatigue
  • Dry mouth (used in some lozenges)
  • Skin exfoliation (topical)
  • Flavoring and food additive

Malic acid is a natural acid found in apples and other fruits, often combined with magnesium in supplements marketed for fibromyalgia and muscle pain. The evidence for its health benefits is weak and limited, and it is mostly used as a food flavoring. It is generally well tolerated in food amounts, but talk to your pharmacist or doctor before using supplement doses.

Naturally found in fruits like apples; also made synthetically · Tablets, capsules, powders, combination products (often with magnesium), topical skincare products, and as a food additive

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

Malic Acid: dosing

There is no official or standardized dose of malic acid for any health condition. Supplement products vary widely, especially those that combine malic acid with magnesium.The best approach is to follow the directions on the product label and not exceed the recommended amount.

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

Read the full Malic 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 & Malic Acid

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

0Major
172Moderate
0Minor
2,657No known interaction
Moderate

172 interactions

Showing 60 of 172 moderate interactions — see all 172 on the Malic Acid page.

No interaction 2,657 drugs checked — show the list
Evidence & sources

Malic Acid References

The 7 references that drive our Malic 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. Russell IJ, Michalek JE, Flechas JD, Abraham GE. Treatment of fibromyalgia syndrome with Super Malic: a randomized, double blind, placebo controlled, crossover pilot study. J Rheumatol 1995;22:953-8.
  2. Fiume, Z. Final report on the safety assessment of malic acid and sodium malate. Int J Toxicol 2001;20 Suppl 1:47-55. PubMed
  3. Electronic Code of Federal Regulations. Title 21. Part 184 - Direct Food Substances Affirmed as Generally Recognized as Safe. Available at: http://www.ecfr.gov/cgi-bin/text-idx?c=ecfr&sid=786bafc6f6343634fbf79fcdca7061e1&rgn=div5&view=text&node=21:3.0.1.1
  4. Saleem R, Ahmad M, Naz A, et al. Hypotensive and toxicological study of citric acid and other constituents from Tagetes patula roots. Arch Pharm Res 2004;27(10):1037-42.
  5. Chiriac A, Brzezinski P. Topical malic acid in combination with citric acid: an option to treat recalcitrant warts. Dermatol Ther. 2015;28(6):336-8. PubMed
  6. CFR - Code of Federal Regulations Title 21 SUBCHAPTER B. 184.1069 Malic Acid. Food and Drug Administration Department Of Health And Human Services. Updated April 1, 2017. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=184.1069.
  7. Amended Safety Assessment of Malic Acid and Sodium Malate as Used in Cosmetics. Cosmetic Ingredient Review Expert Panel. Updated May 19, 2017. http://www.cir-safety.org/sites/default/files/malic%20acid.pdf. Accessed January 24, 2018.

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 Malic Acid and Penicillamine Together: Common Questions

Is it safe to take Malic Acid with Penicillamine?
We do not list a known interaction between Malic 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 Malic Acid and Penicillamine have any of the same side effects?
Yes — our sources link each of them separately to 4 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 Malic 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 Malic 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 Malic Acid and Penicillamine combination checked?
Interactions in our licensed database are recorded against drug classes. Penicillamine is filed under 3 classifications, and Malic Acid has documented interactions with 1 drug class — 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 Malic Acid interact with any other medications?
Yes. Malic Acid has 172 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 — Malic 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 Malic 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.