Drug & supplement interaction

1,4-butanediol + Codeine Phosphate, Pseudoephedrine

Codeine Phosphate, Pseudoephedrine brand names: Nucofed, Kg Fed.

Major Interaction
Medically reviewed by · Updated September 2026
The bottom line Major

Codeine Phosphate, Pseudoephedrine falls into 2 drug categories that 1,4-butanediol can interact with; the most serious is rated major. Theoretically, concomitant use of 1,4-butanediol with CNS depressants may potentiate respiratory and CNS depression.

Read the full interaction report
SeverityMajor
LikelihoodProbable
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

1,4-butanediol and Codeine Phosphate, Pseudoephedrine

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

1,4-butanediol interacts with whole categories of medication. Codeine Phosphate, Pseudoephedrine falls into 2 of those categories, so it can interact with 1,4-butanediol in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Major).

Major

CNS DEPRESSANTS

1 of 2

Why this applies to Codeine Phosphate, Pseudoephedrine

Codeine Phosphate, Pseudoephedrine falls under CNS DEPRESSANTS — the group 1,4-butanediol interacts with.

Theoretically, concomitant use of 1,4-butanediol with CNS depressants may potentiate respiratory and CNS depression.
1,4-Butanediol is metabolized to gamma-hydroxybutyrate (GHB). Concomitant use of CNS depressants with GHB may cause serious CNS and respiratory depression.
Severity Major Likelihood Probable Evidence D

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

First, a real-world heads-up: 1,4-butanediol isn't a true supplement at all. It's a toxic industrial chemical that your body turns into GHB, a strong brain depressant. That matters here because your medicine contains codeine, an opioid that already slows down breathing and dulls the brain.

Stacking two downers like this can add up fast. Together they may cause heavy drowsiness, confusion, very slow or shallow breathing, and in the worst case loss of consciousness or coma. The pseudoephedrine part is a stimulant, but it won't reliably cancel out that danger. The evidence here is mostly anecdotal, but the risk is serious enough that I'd urge you to avoid this combination completely and talk with your doctor or pharmacist.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Anon. Multistate outbreak of poisonings associated with illicit use of gamma hydroxy butyrate. JAMA 1991;265:447-8. DOI
  2. Product information for Xyrem. Jazz Pharmaceuticals, Inc. Palo Alto, CA. March 2022.
Major

NARCOTIC DRUGS

2 of 2

Codeine Phosphate, Pseudoephedrine also falls under NARCOTIC DRUGS.

Theoretically, concomitant use of 1,4-butanediol with narcotic drugs may potentiate respiratory and central nervous system (CNS) depression. 1,4-Butanediol is metabolized to gamma-hydroxybutyrate (GHB).
Concomitant use of narcotic drugs with GHB may cause serious CNS and respiratory depression. In one case report, concurrent use of GHB and heroin was fatal.
Severity Major Likelihood Probable Evidence D

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

I want to be really direct here: 1,4-butanediol is not a supplement at all. It is a toxic industrial chemical that your body turns into GHB, a strong depressant that slows your brain and your breathing. Mixing that with the codeine in Nucofed is genuinely dangerous. Codeine is an opioid that already calms breathing and causes drowsiness, so stacking another CNS depressant on top can deepen sedation, lead to very slow or shallow breathing, unresponsiveness, and in the worst case death. A reported case of GHB combined with another opioid (heroin) was fatal.

The formal evidence is anecdotal and the mechanism is partly theoretical, but the risk is serious and adds up. Please don't take 1,4-butanediol at all, and talk with your pharmacist or doctor right away if you have.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. 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
  2. Anon. Multistate outbreak of poisonings associated with illicit use of gamma hydroxy butyrate. JAMA 1991;265:447-8. DOI
  3. 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
  4. Product information for Xyrem. Jazz Pharmaceuticals, Inc. Palo Alto, CA. March 2022.

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

1,4-butanediol Also Interacts With Other Medications

1,4-butanediol has 249 major, 21 moderate known drug interactions in our database — the Codeine Phosphate, Pseudoephedrine one above is among them. If you take anything else, check it against the full list below.

Major 249 Moderate 21 No known interaction 2,560 (incl. Codeine Phosphate, Pseudoephedrine)
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.

Everything else you take

See Every Supplement That Interacts With Codeine Phosphate, Pseudoephedrine

This page covers 1,4-butanediol only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Codeine Phosphate, Pseudoephedrine page lists 176 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Beer (major), Ephedra (major), Gamma-hydroxybutyrate (ghb) (major) and Kava (major).

By severity: 11 major · 142 moderate · 23 minor.

From our pharmacist’s overview on the Codeine Phosphate, Pseudoephedrine page

“Alcohol is the clearest danger here. Beer and wine both carry a major rating with codeine phosphate and pseudoephedrine (Nucofed, Kg Fed), because alcohol deepens the sedation the codeine half already causes, and that effect is well documented in people.”

Reviewed by 2 · Jul 18, 2026

Open the Codeine Phosphate, Pseudoephedrine interaction page

How much people look this up

Where 1,4-butanediol and Codeine Phosphate, Pseudoephedrine 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

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

29 days ago today
Medication Codeine Phosphate, Pseudoephedrine
Steady interest

#2,602 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 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.

Read the full 1,4-butanediol monograph & all interactions
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.

249Major
21Moderate
0Minor
2,559No known interaction
249 Major 21 Moderate 2,559 No interaction
Major

249 interactions

Showing 60 of 249 major interactions — see all 249 on the 1,4-butanediol page.

Moderate

21 interactions

No interaction 2,559 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 2,559 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 Codeine Phosphate, Pseudoephedrine, ranked by severity
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

Keep exploring
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Pharmacist Counseling Corner

Taking 1,4-butanediol and Codeine Phosphate, Pseudoephedrine Together: Common Questions

Can you take 1,4-butanediol with Codeine Phosphate, Pseudoephedrine?
This is rated a major interaction, so the combination is best avoided unless your doctor or pharmacist has specifically told you otherwise. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 2 interactions listed for 1,4-butanediol and Codeine Phosphate, Pseudoephedrine?
Codeine Phosphate, Pseudoephedrine belongs to more than one drug category, and 1,4-butanediol interacts with each of those categories a little differently. We list every one so nothing is missed — your overall risk is driven by the most serious of them.
How serious is the 1,4-butanediol and Codeine Phosphate, Pseudoephedrine interaction?
We rate it Major. This is a clinically significant combination that is generally best avoided, or used only under the direct supervision of your physician or pharmacist.

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

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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.