Drug & supplement interaction

Zinc + Penicillamine

Penicillamine brand names: Cuprimine, Depen Titratable.

Moderate Interaction
The bottom line Moderate

Zinc has a moderate interaction with Penicillamine. Zinc might reduce the levels and clinical effects of penicillamine.

Read the full interaction report
SeverityModerate
LikelihoodProbable
EvidenceB
What do Severity, Likelihood & Evidence mean?
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Interaction report

Zinc and Penicillamine

Here is the interaction we found between these two, with the evidence behind it.

Moderate

PENICILLAMINE (Cuprimine, Depen)

Zinc might reduce the levels and clinical effects of penicillamine.
By forming an insoluble complex with penicillamine, zinc interferes with penicillamine absorption and activity. Zinc supplements reduce the efficacy of low-dose penicillamine (0.5-1 gram/day), but do not seem to affect higher doses (1-2.75 gram/day), provided dosing times are separated. Advise patients to take zinc and penicillamine at least 2 hours apart.
Severity Moderate Likelihood Probable Evidence B

Interaction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the practical issue with these two together: zinc and penicillamine can bind to each other in your stomach and gut, forming a clump your body can't absorb well. When that happens, less penicillamine actually gets into your system, so it may not work as well. For someone taking it for Wilson's disease, cystinuria, or rheumatoid arthritis, weaker absorption could mean copper or cystine isn't being cleared as effectively, or your joint symptoms aren't as well controlled.

The good news is the timing fix is simple. Studies suggest separating the two by at least 2 hours helps a lot, and higher penicillamine doses seem less affected than lower ones. This is fairly well documented, so it's worth doing. Before changing anything, talk with your pharmacist or doctor so your dose and timing are set up right.

References
  1. 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
  2. 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
  3. Mery C, Delrieu F, Ghozlan R, et al. Controlled trial of D-penicillamine in rheumatoid arthritis. Dose effect and the role of zinc. Scand J Rheumatol 1976;5:241-7. PubMed

What These Ratings Mean

Every interaction above is graded three ways — here’s the key to each label.

Severity how clinically significant the interaction is
Major

Clinically significant. Avoid the combination, or use only under close professional supervision.

Moderate

Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.

Minor

Generally not serious. Be aware of it and mention it to your pharmacist.

Likelihood how strong the evidence is that the interaction actually happens in people
  • LikelyWell-controlled human studies have demonstrated the likely existence of this interaction.
  • ProbableInteraction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.
  • PossibleInteraction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.
  • UnlikelyInteraction has been demonstrated in animal or in lab research but has been shown not to occur in humans.
Evidence the quality of the studies behind the rating (graded A–D)
  • AHigh-quality meta-analysis (quantitative systematic review).
  • BCase-control study.
  • CConsensus.
  • DAnecdotal evidence.

These ratings are for information only. Never start, stop, or otherwise change your therapy before speaking with your provider.

Keep it in perspective

Zinc Also Interacts With Other Medications

Zinc has 62 moderate, 4 minor known drug interactions in our database — the Penicillamine one above is 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.

Everything else you take

See Every Supplement That Interacts With Penicillamine

This page covers Zinc 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 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. Your product may carry other ingredients that interact with Penicillamine too, on top of Zinc — and those would not show on this page. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where Zinc 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 Zinc
Top 10

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

29 days ago today
Medication Penicillamine
Steady interest

#2,654 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.

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.

Read the full Zinc 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 & 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
62Moderate
4Minor
2,763No known interaction
Moderate

62 interactions

Showing 60 of 62 moderate interactions — see all 62 on the Zinc page.

Minor

4 interactions

No interaction 2,763 drugs checked — show the list
Sources

Sources & How We Checked

Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.

Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.

Parts of this content are provided by the Therapeutic Research Center, LLC.

DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

© 2021 Therapeutic Research Center, LLC

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Pharmacist Counseling Corner

Taking Zinc and Penicillamine Together: Common Questions

Can you take Zinc with Penicillamine?
There is a moderate interaction, so it may be acceptable with monitoring or timing changes — but check with your pharmacist first. Read the full details on this page and confirm with your pharmacist before combining them.
How serious is the Zinc and Penicillamine interaction?
We rate it Moderate. This combination may require monitoring, a dose adjustment, or separating the times you take each one. Consult your pharmacist before using them together.

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

Still Have a Question About Penicillamine 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.