Drug & supplement interaction

1,4-butanediol + Penicillamine

Penicillamine brand names: Cuprimine, Depen Titratable.

No Known Interaction
Medically reviewed by · Updated July 2026 · Pair last verified Sep 20, 2026
The bottom line No known interaction

We found no known interaction between 1,4-butanediol 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

1,4-butanediol 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 1,4-butanediol 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.

1,4-butanediol safety at a glance

1,4-butanediol overall Avoid This is a toxic chemical that turns into GHB in the body and can be life-threatening.
Pregnancy Unsafe When used orally. Read the full pregnancy detail
Breastfeeding Unsafe When used orally. 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 1,4-butanediol? 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. 1,4-butanediol has documented interactions with 10 drug classes — the most serious being alcohol (ethanol) (major), cns depressants (major) and narcotic drugs (major) — 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

1,4-butanediol Does Interact With Other Medications

1,4-butanediol has 250 major, 21 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.

Major 250 Moderate 21 No known interaction 2,559 (incl. Penicillamine)
Taking anything else?

Check Another of Your Medications Against 1,4-butanediol

Covers the 2,830 medications we’ve checked against 1,4-butanediol. Pick one to open its full report.

What to actually watch for

No Interaction Found — But Data Suggests 1,4-butanediol 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.

  • Anxiety or restlessness Additional detail

    1,4-butanediol

    “Orally, 1,4-butanediol is metabolized to gamma-hydroxybutyrate (GHB), and its psychoactive effects are primarily due to GHB. 1,4-Butanediol also causes similar CNS toxic effects to GHB, including amnesia, combativeness, confusion, agitation, coma, seizures, and death. After 1,4-butanediol overdoses, sedation gradually increases, consistent with gradual conversion to GHB.”

    1,4-butanediol · Natural Medicines adverse-effect record, reported in anxiety.

    6 sources cited
    1. 102837. Stefani M, Roberts DM. 1,4-Butanediol overdose mimicking toxic alcohol exposure. Clin Toxicol (Phila) 2020;58(3):204-7. doi: 10.1080/15563650.2019.1617419. PubMed
    2. 1318. Smith SW, Zvosec DL. Death and central nervous system depression after ingestion of 1.4-butanediol, a gamma-hydroxybutyrate-related dietary supplement. Ann Emerg Med 2000;36:S85.
    3. 3678. Anon. FDA alert on misuse of consumer products containing GHB, GBL and BD. Food and Drug Administration, Rockville, MD. June 15, 1999.
    4. 3679. Anon. Important message for health professionals: Report serious adverse events associated with dietary supplements containing GBL, GHB or BD. Food and Drug Administration, Rockville, MD. August 25, 1999. Available at: http://vm.cfsan.fda.gov/~dms/mwg
    5. 10640. Zvosec DL, Smith SW, McCutcheon JR, et al. Adverse events, including death, associated with the use of 1,4-butanediol. N Engl J Med. 2001;344:87-94.. PubMed
    6. 37465. Thai, D., Dyer, J. E., Jacob, P., and Haller, C. A. Clinical pharmacology of 1,4-butanediol and gamma-hydroxybutyrate after oral 1,4-butanediol administration to healthy volunteers. Clin.Pharmacol Ther. 2007;81(2):178-184. PubMed

    Penicillamine

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

  • Diarrhea reported in 9.6% of FDA reports for Penicillamine Additional detail

    1,4-butanediol

    “Orally, 1,4-butanediol can cause nausea and vomiting, diarrhea, and fecal incontinence.”

    1,4-butanediol · Natural Medicines adverse-effect record, reported in diarrhea.

    5 sources cited
    1. 1318. Smith SW, Zvosec DL. Death and central nervous system depression after ingestion of 1.4-butanediol, a gamma-hydroxybutyrate-related dietary supplement. Ann Emerg Med 2000;36:S85.
    2. 3678. Anon. FDA alert on misuse of consumer products containing GHB, GBL and BD. Food and Drug Administration, Rockville, MD. June 15, 1999.
    3. 3679. Anon. Important message for health professionals: Report serious adverse events associated with dietary supplements containing GBL, GHB or BD. Food and Drug Administration, Rockville, MD. August 25, 1999. Available at: http://vm.cfsan.fda.gov/~dms/mwg
    4. 10640. Zvosec DL, Smith SW, McCutcheon JR, et al. Adverse events, including death, associated with the use of 1,4-butanediol. N Engl J Med. 2001;344:87-94.. PubMed
    5. 37465. Thai, D., Dyer, J. E., Jacob, P., and Haller, C. A. Clinical pharmacology of 1,4-butanediol and gamma-hydroxybutyrate after oral 1,4-butanediol administration to healthy volunteers. Clin.Pharmacol Ther. 2007;81(2):178-184. 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 ›

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

    1,4-butanediol

    Recorded for 1,4-butanediol in the same Natural Medicines adverse-effect record shown under Anxiety or restlessness above.

    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 ›

Reported for 1,4-butanediol but not commonly for Penicillamine: dependence or withdrawal symptoms, chest pain, hallucinations and a slow heartbeat.

Effects for Penicillamine come from the ADVERSE REACTIONS section of its FDA label; effects for 1,4-butanediol 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

1,4-butanediol in Pregnancy & Breastfeeding

Pregnancy And Lactation Unsafe

When used orally.

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 — 1,4-butanediol Should Not Break It

At least one FDA label for a product containing Penicillamine says to take it on an empty stomach. Most supplements — 1,4-butanediol 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 1,4-butanediol 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 1,4-butanediol 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

How much people look this up

Where 1,4-butanediol 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 1,4-butanediol
Steady interest

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

29 days ago today
Medication Penicillamine
Steady interest

#2,598 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 1,4-butanediol reference on this page ↓
  • Freshness: we automatically re-check this combination every week — this pair was last verified September 20, 2026. The 1,4-butanediol 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 1,4-butanediol

What is 1,4-butanediol?

  • Marketed illegally as a 'recreational' or party substance
  • Falsely sold as a sleep aid
  • Falsely promoted for bodybuilding or muscle growth
  • Industrial solvent and chemical manufacturing

1,4-butanediol is a toxic industrial chemical, not a safe dietary supplement. Once swallowed, the body converts it into GHB, a powerful central nervous system depressant that can cause coma, dangerous breathing problems, addiction, and death. It should never be taken as a supplement or recreational substance.

Synthetic industrial chemical (not a plant) · Liquid solvent (sometimes sold illegally as a 'supplement,' cleaner, or party drug)

An interaction check asks whether these two react with each other — it does not ask whether 1,4-butanediol is a good idea for someone in your situation. Here is what our 1,4-butanediol record says about it on its own.

1,4-butanediol: dosing

There is no established or recommended dose of 1,4-butanediol, because it is not a legitimate supplement or medicine. It should not be taken in any amount.If you have encountered a product that contains or is suspected to contain 1,4-butanediol, do not use it. In the U.S., you can reach Poison Control at 1-800-222-1222.

From our 1,4-butanediol monograph — the full record covers uses, side effects and every documented interaction.

Read the full 1,4-butanediol 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 & 1,4-butanediol

Browse every other medication we’ve checked against 1,4-butanediol — both the ones with a known interaction and the ones without. Select any drug for the full detail.

250Major
21Moderate
0Minor
2,558No known interaction
250 Major 21 Moderate 2,558 No interaction
Major

250 interactions

Showing 60 of 250 major interactions — see all 250 on the 1,4-butanediol page.

Moderate

21 interactions

No interaction 2,558 drugs checked — show the list

We also checked 1,4-butanediol against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 2,558 medications checked with no known interaction — see the full 1,4-butanediol list.

See the full 1,4-butanediol interactions page
See every supplement checked against Penicillamine, ranked by severity
Evidence & sources

1,4-butanediol References

The 20 references that drive our 1,4-butanediol 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. Smith SW, Zvosec DL. Death and central nervous system depression after ingestion of 1.4-butanediol, a gamma-hydroxybutyrate-related dietary supplement. Ann Emerg Med 2000;36:S85.
  2. Anon. Adverse events associated with ingestion of gamma-butyrolactone--Minnesota, New Mexico, and Texas, 1998-1999. MMWR Morb Mortal Wkly Rep 1999;48:137-40.
  3. Harrington RD, Woodward JA, Hooton TM, et al. Life-threatening interactions between HIV-1 protease inhibitors and the illicit drugs MDMA and gamma-hydroxybutyrate. Arch Intern Med 1999;159:2221-4.
  4. Anon. FDA alert on misuse of consumer products containing GHB, GBL and BD. Food and Drug Administration, Rockville, MD. June 15, 1999.
  5. Anon. Important message for health professionals: Report serious adverse events associated with dietary supplements containing GBL, GHB or BD. Food and Drug Administration, Rockville, MD. August 25, 1999. Available at: http://vm.cfsan.fda.gov/~dms/mwg
  6. Anon. Multistate outbreak of poisonings associated with illicit use of gamma hydroxy butyrate. JAMA 1991;265:447-8. DOI
  7. Carotenuto A, De Feo V, Fattorusso E, et al. The flavonoids of Allium ursinum. Phytochem 1996;41:531-6. PubMed
  8. Ferrara SD, Tedeschi L, Frison G, Rossi A. Fatality due to gamma-hydroxybutyric acid (GHB) and heroin intoxication. J Forensic Sci 1995;40:501-4. DOI
  9. Timby N, Eriksson A. Gamma-Hydroxybutyrate-Associated Deaths. Am J Med 2000;108:518. PubMed
  10. Schneir AB, Ly BT, Clark RF. A case of withdrawal from the GHB precursors gamma-butyrolactone and 1,4-butanediol. J Emerg Med 2001;21:31-3.. PubMed
  11. Zvosec DL, Smith SW, McCutcheon JR, et al. Adverse events, including death, associated with the use of 1,4-butanediol. N Engl J Med. 2001;344:87-94.. PubMed
  12. Mason P, Kerns II W. Gamma Hydroxybutyric Acid (GHB) Intoxication. Acad Emerg Med 2002;9:730-39.. DOI
  13. Poldrugo, F., Barker, S., Basa, M., Mallardi, F., and Snead, O. C. Ethanol potentiates the toxic effects of 1,4-butanediol. Alcohol Clin.Exp.Res 1985;9(6):493-497. PubMed
  14. Thai, D., Dyer, J. E., Jacob, P., and Haller, C. A. Clinical pharmacology of 1,4-butanediol and gamma-hydroxybutyrate after oral 1,4-butanediol administration to healthy volunteers. Clin.Pharmacol Ther. 2007;81(2):178-184. PubMed
  15. Boscolo-Berto R, Viel G, Montagnese S, Raduazzo DI, Ferrara SD, Dauvilliers Y. Narcolepsy and effectiveness of gamma-hydroxybutyrate (GHB): a systematic review and meta-analysis of randomized controlled trials. Sleep Med Rev. 2012 Oct;16(5):431-43. 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 1,4-butanediol and Penicillamine Together: Common Questions

Is it safe to take 1,4-butanediol with Penicillamine?
We do not list a known interaction between 1,4-butanediol 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 1,4-butanediol 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 1,4-butanediol 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 1,4-butanediol 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 1,4-butanediol and Penicillamine combination checked?
Interactions in our licensed database are recorded against drug classes. Penicillamine is filed under 3 classifications, and 1,4-butanediol has documented interactions with 10 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 1,4-butanediol interact with any other medications?
Yes. 1,4-butanediol has 271 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 — 1,4-butanediol 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

1,4-butanediol 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 20 citations behind this page Ask a pharmacist Free, personal answer from our licensed team

Still Have a Question About Penicillamine and 1,4-butanediol?

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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.