Drug & supplement interaction

Gamma-hydroxybutyrate (ghb) + Nirmatrelvir, Ritonavir

Nirmatrelvir, Ritonavir brand name: Paxlovid.

Moderate Interaction
The bottom line Moderate

Gamma-hydroxybutyrate (ghb) has a moderate interaction with Nirmatrelvir, Ritonavir. Concomitant use of ritonavir and GHB may increase the risk of serious adverse effects.

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

Gamma-hydroxybutyrate (ghb) and Nirmatrelvir, Ritonavir

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

Moderate

RITONAVIR (Norvir)

Concomitant use of ritonavir and GHB may increase the risk of serious adverse effects.
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

Here's the concern with this pair. Paxlovid contains ritonavir, which is a strong blocker of certain liver enzymes. That blocking action is actually the point of ritonavir, it slows the breakdown of the antiviral so it works better. The trouble is that ritonavir can also slow how your body clears GHB, letting GHB pile up to dangerous levels.

There is a real-world report of a near-fatal reaction when someone took even a small amount of GHB along with ritonavir. Because GHB is a powerful nervous-system depressant, too much can cause heavy sedation, slowed or stopped breathing, and coma. This is anecdotal evidence, but the stakes are high. GHB is not a safe supplement to begin with. Please do not combine these, and talk with your pharmacist or doctor about any product you're taking.

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

Gamma-hydroxybutyrate (ghb) Also Interacts With Other Medications

Gamma-hydroxybutyrate (ghb) has 249 major, 20 moderate, 5 minor 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.

Taking anything else?

Check Another of Your Medications Against Gamma-hydroxybutyrate (ghb)

Covers the 2,830 medications we’ve checked against Gamma-hydroxybutyrate (ghb). Pick one to open its full report.

Everything else you take

See Every Supplement That Interacts With Nirmatrelvir, Ritonavir

This page covers Gamma-hydroxybutyrate (ghb) 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 Gamma-hydroxybutyrate (ghb) 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 Gamma-hydroxybutyrate (ghb)
Top half

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

29 days ago today
Medication Nirmatrelvir, Ritonavir
Top 25%

#322 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 Gamma-hydroxybutyrate (ghb)

What is Gamma-hydroxybutyrate (ghb)?

  • Narcolepsy (cataplexy and excessive daytime sleepiness)
  • Sleep aid
  • Misused as a recreational 'party drug'
  • Bodybuilding/muscle building (unproven)
  • Alcohol withdrawal (in some countries)

GHB (gamma-hydroxybutyrate) is a powerful central nervous system depressant that is NOT a safe dietary supplement. In the U.S. it is a controlled substance, and only a tightly regulated prescription form (sodium oxybate) is legal for narcolepsy. Non-prescription GHB can cause coma, breathing failure, and death, and it is also a known 'date-rape' drug — it should not be taken outside of medical supervision.

Read the full Gamma-hydroxybutyrate (ghb) monograph & all interactions
Medication

About Nirmatrelvir and Ritonavir

What Is Nirmatrelvir and Ritonavir Used For?

Brand name: Paxlovid

Paxlovid, which contains nirmatrelvir and ritonavir, treats mild-to-moderate COVID-19 in adults. It is for people at high risk of the illness getting worse, including needing hospitalization or dying.

It is not approved to prevent COVID-19, either before or after exposure to someone who is sick.

See full Nirmatrelvir and Ritonavir drug information
Keep checking

Other Drugs & Gamma-hydroxybutyrate (ghb)

Browse every other medication we’ve checked against Gamma-hydroxybutyrate (ghb) — both the ones with a known interaction and the ones without. Select any drug for the full detail.

249Major
20Moderate
5Minor
2,555No known interaction
Major

249 interactions

Showing 60 of 249 major interactions — see all 249 on the Gamma-hydroxybutyrate (ghb) page.

Moderate

20 interactions

Minor

5 interactions

No interaction 2,555 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

Keep exploring
Pharmacist Counseling Corner

Taking Gamma-hydroxybutyrate (ghb) and Nirmatrelvir, Ritonavir Together: Common Questions

Can you take Gamma-hydroxybutyrate (ghb) 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 Gamma-hydroxybutyrate (ghb) 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

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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.