Drug & supplement interaction

1,4-butanediol + Nirmatrelvir, Ritonavir

Nirmatrelvir, Ritonavir brand name: Paxlovid.

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

1,4-butanediol has a moderate interaction with Nirmatrelvir, Ritonavir. Concomitant use of 1,4-butanediol with ritonavir may potentiate adverse effects.

Read the full interaction report
SeverityModerate
LikelihoodPossible
EvidenceD
What do Severity, Likelihood & Evidence mean?
Know someone taking this? Share
Facebook Post Reddit Email
On this page
Interaction report

1,4-butanediol and Nirmatrelvir, Ritonavir

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

Moderate

RITONAVIR (Norvir)

Concomitant use of 1,4-butanediol with ritonavir may potentiate adverse effects.
1,4-Butanediol is metabolized to gamma-hydroxybutyrate (GHB). Concomitant use of a small dose of GHB with the antiretroviral drugs ritonavir and saquinavir reportedly caused a near-fatal reaction, likely due to inhibition of GHB metabolism.
Severity Moderate Likelihood Possible Evidence D

Interaction 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.

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

First, the most important thing: 1,4-butanediol is not a real supplement. It is a toxic industrial chemical that your body turns into GHB, a powerful nervous system depressant. On its own it can cause deep sedation, dangerously slow breathing, coma, and death, so it should never be swallowed in the first place.

On top of that, the ritonavir piece of Paxlovid is a strong booster that blocks certain liver enzymes. That same blocking effect can slow how your body clears GHB, letting it pile up. There's a real-world report of a near-fatal reaction when someone combined GHB with ritonavir. So the danger of the GHB (heavy sedation, stopped breathing) could be made much worse. The evidence here is anecdotal, but the risk is serious. Please talk with your pharmacist or doctor.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. 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.

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 250 major, 20 moderate known drug interactions in our database — the Nirmatrelvir, Ritonavir one above is one of them. If you take anything else, check it against the full list below.

Major 250 Moderate 20 No known interaction 2,560 (incl. Nirmatrelvir, Ritonavir)
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 Nirmatrelvir, Ritonavir

This page covers 1,4-butanediol only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Nirmatrelvir, Ritonavir 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), Grapefruit (major), Siberian Cocklebur (major) and St. John's Wort (major).

By severity: 6 major · 134 moderate · 36 minor.

From our pharmacist’s overview on the Nirmatrelvir, Ritonavir page

“Paxlovid (nirmatrelvir and ritonavir) deserves genuine care around supplements, mostly because its ritonavir component strongly blocks the liver enzyme CYP3A4. The bulk of this list is made up of ingredients that enzyme normally clears, so their levels can climb unpredictably during the five-day course.”

Reviewed by 2 · Jul 18, 2026

Open the Nirmatrelvir, Ritonavir interaction page

How much people look this up

Where 1,4-butanediol and Nirmatrelvir, Ritonavir 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
Top half

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

29 days ago today
Medication Nirmatrelvir, Ritonavir
Top 10%

#244 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
Medication

About Nirmatrelvir and Ritonavir

What Is Nirmatrelvir and Ritonavir Used For?

Brand name: Paxlovid

Paxlovid is approved to treat mild-to-moderate COVID-19 in adults who are at high risk of progressing to severe disease — meaning hospitalization or death. It is intended for people who already have symptoms and a confirmed COVID-19 diagnosis.

Paxlovid is not approved to prevent COVID-19 before or after exposure. It is a treatment, not a preventive medication.

See full Nirmatrelvir and Ritonavir 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
20Moderate
0Minor
2,559No known interaction
250 Major 20 Moderate 2,559 No interaction
Major

250 interactions

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

Moderate

20 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 Nirmatrelvir, Ritonavir, 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
1,4-butanediol monograph › Uses, safety, and every drug interaction in one place Nirmatrelvir, Ritonavir supplement interactions › Every supplement checked against Nirmatrelvir, Ritonavir, ranked by severity Nirmatrelvir and Ritonavir drug information › The full plain-English guide to this medication Supplement interaction checker › Check any supplement or product against your medications Browse medications A–Z › Every drug we've checked against herbs & supplements Ask a pharmacist › Free, personal answer from our licensed team
Pharmacist Counseling Corner

Taking 1,4-butanediol and Nirmatrelvir, Ritonavir Together: Common Questions

Can you take 1,4-butanediol with Nirmatrelvir, Ritonavir?
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 1,4-butanediol and Nirmatrelvir, Ritonavir 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 Nirmatrelvir, Ritonavir and 1,4-butanediol?

Our pharmacists answer your medication & supplement questions — free.

Ask a pharmacist

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.