Drug & supplement interaction

Phenibut + Penicillamine

Penicillamine brand names: Cuprimine, Depen Titratable.

No Known Interaction
Medically reviewed by · Updated July 2026 · Pair last verified Sep 13, 2026
The bottom line No known interaction

We found no known interaction between Phenibut 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

Phenibut 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 Phenibut 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.

Phenibut safety at a glance

Phenibut overall Avoid Phenibut carries a high risk of dependence, dangerous withdrawal, and overdose, and is not approved as a supplement or drug in the U.S.
Pregnancy Avoid There is no safety data in pregnancy and it is a CNS depressant, so it should be avoided.
Breastfeeding Avoid It is unknown whether phenibut passes into breast milk, so it should be avoided while breastfeeding.

Safety guidance is general; always confirm with your pharmacist or doctor for your situation.

Still wondering about combining Penicillamine and Phenibut? 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. Phenibut has documented interactions with 2 drug classes — the most serious being cns depressants (moderate) and pregabalin (lyrica) (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

Phenibut Does Interact With Other Medications

Phenibut has 248 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.

Moderate 248 No known interaction 2,582 (incl. Penicillamine)
Taking anything else?

Check Another of Your Medications Against Phenibut

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

What to actually watch for

No Interaction Found — But Data Suggests Phenibut 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.

  • Kidney problems Worth acting on Additional detail

    Phenibut

    “Orally, phenibut has been associated with withdrawal symptoms, including one case report of rhabdomyolysis and acute kidney injury in a previously healthy 24-year-old male who was also using anabolic steroids. In other case reports, phenibut withdrawal was associated with muscle aches and clonus.”

    Phenibut · Natural Medicines adverse-effect record, reported in muscle breakdown.

    5 sources cited
    1. 96756. Li W, Madhira B. Phenibut (beta-phenyl-gamma-aminobutyric acid) psychosis. Am J Therapeut 2017;24(5):e639-640.
    2. 96751. Brunner E, Levy R. Case report of physiologic phenibut dependence treated with a phenobarbital taper in a patient being treated with buprenorphine. J Addict Med. 2017 May/Jun;11(3):239-40. PubMed
    3. 101108. Hardman MI, Sprung J, Weingarten TN. Acute phenibut withdrawal: A comprehensive literature review and illustrative case report. Bosn J Basic Med Sci. 2019;19(2):125-129. PubMed
    4. 101111. McCabe DJ, Bangh SA, Arens AM, Cole JB. Phenibut exposures and clinical effects reported to a regional poison center. Am J Emerg Med. 2019;37(11):2066-2071. PubMed
    5. 112293. Martin R, Buffenstein I, Cho D, Kiyokawa M. Toxidrome of an Easily Obtainable Nootropic: A Case Report of Phenibut Intoxication and Withdrawal Delirium. J Clin Psychopharmacol 2023. PubMed

    Penicillamine

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

  • Anxiety or restlessness / Nausea reported in 10.5% of FDA reports for Penicillamine Additional detail

    Phenibut

    “Orally, phenibut has been associated with aggression, agitation, altered mental status, anxiety, sedation, hallucinations, insomnia, and coma in case reports and case series. Phenibut is often used concurrently with other addictive substances, including alcohol.

    Observational research and case reports have found that the use of phenibut can lead to the rapid development of tolerance within 3 days, and that use for 3…”

    Phenibut · Natural Medicines adverse-effect record, reported in anxiety.

    6 sources cited
    1. 96748. Downes MA, Berling IL, Mostafa A, Grice J, Roberts MS, Isbister GK. Acute behavioural disturbance associated with phenibut purchased via an internet supplier. Clin Toxicol (Phila). 2015;53(7):636-8. PubMed
    2. 96750. O'Connell CW, Schneir AB, Hwang JQ, Cantrell FL. Phenibut, the appearance of another potentially dangerous product in the United States. Am J Med. 2014 Aug;127(8):e3-4. PubMed
    3. 96753. Owen DR, Wood DM, Archer JR, Dargan PI. Phenibut (4-amino-3-phenyl-butyric acid): Availability, prevalence of use, desired effects, and acute toxicity. Drug Alcohol Rev. 2016 Sep;35(5):591-6. PubMed
    4. 101108. Hardman MI, Sprung J, Weingarten TN. Acute phenibut withdrawal: A comprehensive literature review and illustrative case report. Bosn J Basic Med Sci. 2019;19(2):125-129. PubMed
    5. 101109. Ahuja T, Mgbako O, Katzman C, Grossman A. Phenibut (β-Phenyl-γ-aminobutyric Acid) dependence and management of withdrawal: Emerging nootropics of abuse. Case Rep Psychiatry. 2018;2018:9864285.
    6. 101110. Isoardi KZ, Kulawickrama S, Isbister GK. Severe phenibut poisoning: An adolescent case cluster. J Paediatr Child Health. 2020;56(2):330-331. 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 ›

  • Reduced appetite Additional detail

    Phenibut

    “Orally, phenibut has been associated with nausea and vomiting. Regular phenibut use followed by abrupt discontinuation is associated with withdrawal symptoms, including decreased appetite and nausea.”

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

    3 sources cited
    1. 96753. Owen DR, Wood DM, Archer JR, Dargan PI. Phenibut (4-amino-3-phenyl-butyric acid): Availability, prevalence of use, desired effects, and acute toxicity. Drug Alcohol Rev. 2016 Sep;35(5):591-6. PubMed
    2. 101110. Isoardi KZ, Kulawickrama S, Isbister GK. Severe phenibut poisoning: An adolescent case cluster. J Paediatr Child Health. 2020;56(2):330-331. PubMed
    3. 96754. Magsalin RM, Khan AY. Withdrawal symptoms after internet purchase of phenibut (beta-phenyl-gamma-aminobutyric acid HCl). J Clin Psychopharmacol. 2010 Oct;30(5):648-9.

    Penicillamine

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

  • Vomiting Additional detail

    Phenibut

    Recorded for Phenibut in the same Natural Medicines adverse-effect record shown under Reduced appetite above.

    Penicillamine

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

Reported for Phenibut but not commonly for Penicillamine: confusion, hallucinations, dependence or withdrawal symptoms and severe muscle breakdown.

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

How to take them

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

At least one FDA label for a product containing Penicillamine says to take it on an empty stomach. Most supplements — Phenibut 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 Phenibut 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 Phenibut 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 Phenibut as Part of a Dietary Supplement Product? Check It for Interactions

We hold 41 real supplement products containing Phenibut, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Phenibut. Even though Phenibut 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 Phenibut 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 Phenibut
Top half

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

29 days ago today
Medication Penicillamine
Steady interest

#2,639 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 Phenibut reference on this page ↓
  • Freshness: we automatically re-check this combination every week — this pair was last verified September 13, 2026. The Phenibut and Penicillamine 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 Phenibut

What is Phenibut?

Phenibut
  • Anxiety and stress
  • Insomnia and sleep problems
  • Stress relief
  • Mood and focus
  • Reducing alcohol withdrawal symptoms (unproven)

Phenibut is a synthetic, lab-made central nervous system depressant—not a natural herb—that some people use for anxiety and sleep, but it carries a serious risk of tolerance, dependence, and dangerous withdrawal. It is not an approved medication or dietary supplement in the United States, and we do not recommend its use. Talk to a doctor or pharmacist about safer, proven options for anxiety or sleep.

Synthetic compound (not a plant part) · Powder, capsules, tablets

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

Phenibut: dosing

There is no established safe or standardized dose of phenibut for use as a supplement, and it is not approved as a medicine or supplement in the United States. Products sold online are unregulated, so the actual amount and purity can vary widely and be unpredictable.Because of the real risk of dependence, dangerous withdrawal, and overdose, we do not provide dosing guidance and do not recommend using phenibut. If you already use it regularly, do not stop suddenly—get medical help to taper safely.

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

Read the full Phenibut 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 & Phenibut

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

0Major
248Moderate
0Minor
2,581No known interaction
248 Moderate 2,581 No interaction
Moderate

248 interactions

Showing 60 of 248 moderate interactions — see all 248 on the Phenibut page.

No interaction 2,581 drugs checked — show the list

We also checked Phenibut against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 2,581 medications checked with no known interaction — see the full Phenibut list.

See the full Phenibut interactions page
See every supplement checked against Penicillamine, ranked by severity
Evidence & sources

Phenibut References

The 23 references that drive our Phenibut 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. Downes MA, Berling IL, Mostafa A, Grice J, Roberts MS, Isbister GK. Acute behavioural disturbance associated with phenibut purchased via an internet supplier. Clin Toxicol (Phila). 2015;53(7):636-8. PubMed
  2. Samokhvalov AV, Paton-Gay CL, Balchand K, Rehm J. Phenibut dependence. BMJ Case Rep. 2013 Feb 6;2013. Pii: bcr2012008381.
  3. O'Connell CW, Schneir AB, Hwang JQ, Cantrell FL. Phenibut, the appearance of another potentially dangerous product in the United States. Am J Med. 2014 Aug;127(8):e3-4. PubMed
  4. Brunner E, Levy R. Case report of physiologic phenibut dependence treated with a phenobarbital taper in a patient being treated with buprenorphine. J Addict Med. 2017 May/Jun;11(3):239-40. PubMed
  5. Sankary S, Canino P, Jackson J. Phenibut overdose. AM J Emerg Med. 2017 Mar;35(3):516.e1-516.e2.
  6. Owen DR, Wood DM, Archer JR, Dargan PI. Phenibut (4-amino-3-phenyl-butyric acid): Availability, prevalence of use, desired effects, and acute toxicity. Drug Alcohol Rev. 2016 Sep;35(5):591-6. PubMed
  7. Magsalin RM, Khan AY. Withdrawal symptoms after internet purchase of phenibut (beta-phenyl-gamma-aminobutyric acid HCl). J Clin Psychopharmacol. 2010 Oct;30(5):648-9.
  8. Rod W, Kudryk A, Brunetti L, Sun N, Nguyen M. Phenibut withdrawal management in the setting of concomitant kratom and alcohol dependence. Critical Care Med 2018;46(1):451.
  9. Li W, Madhira B. Phenibut (beta-phenyl-gamma-aminobutyric acid) psychosis. Am J Therapeut 2017;24(5):e639-640.
  10. Joshi Y, Friend S, Jimenez B, Steiger L. Dissociative intoxication and prolonged withdrawal associated with phenibut: a case report. J Clin Psychopharmacol 2017;37(4):478-80. PubMed
  11. Zheng KH, Khan A, Espiridion ED. Phenibut addiction in a patient with substance use disorder. Cureus. 2019;11(7):e5230. PubMed
  12. Hardman MI, Sprung J, Weingarten TN. Acute phenibut withdrawal: A comprehensive literature review and illustrative case report. Bosn J Basic Med Sci. 2019;19(2):125-129. PubMed
  13. Ahuja T, Mgbako O, Katzman C, Grossman A. Phenibut (β-Phenyl-γ-aminobutyric Acid) dependence and management of withdrawal: Emerging nootropics of abuse. Case Rep Psychiatry. 2018;2018:9864285.
  14. Isoardi KZ, Kulawickrama S, Isbister GK. Severe phenibut poisoning: An adolescent case cluster. J Paediatr Child Health. 2020;56(2):330-331. PubMed
  15. McCabe DJ, Bangh SA, Arens AM, Cole JB. Phenibut exposures and clinical effects reported to a regional poison center. Am J Emerg Med. 2019;37(11):2066-2071. 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 Phenibut and Penicillamine Together: Common Questions

Is it safe to take Phenibut with Penicillamine?
We do not list a known interaction between Phenibut 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 Phenibut and Penicillamine have any of the same side effects?
Yes — our sources link each of them separately to 5 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 Phenibut 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 Phenibut 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 Phenibut and Penicillamine combination checked?
Interactions in our licensed database are recorded against drug classes. Penicillamine is filed under 3 classifications, and Phenibut has documented interactions with 2 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 Phenibut interact with any other medications?
Yes. Phenibut has 248 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 — Phenibut 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

Where next

Keep Exploring

Phenibut monograph Uses, safety profile, and every drug interaction in one place Penicillamine drug information The full plain-English guide to this medication Penicillamine supplement interactions Every supplement checked against Penicillamine, ranked by severity Supplement interaction checker Check any supplement or product against your medications Browse medications A–Z Every drug we’ve checked against herbs & supplements References The 23 citations behind this page Ask a pharmacist Free, personal answer from our licensed team

Still Have a Question About Penicillamine and Phenibut?

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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.