Zolpidem and alcohol add; zolpidem and opioids add; St John's wort and rifampin subtract
The Ambien label lists both directions: alcohol and other CNS depressants give "possible adverse additive CNS-depressant effects," opioids raise respiratory depression risk, and rifampin or St. John's wort "may decrease effect."
Reasonable evidence with real limitations. how we score evidence
Caveat on this rating: The imipramine and chlorpromazine findings are single-dose volunteer studies, not outcomes in patients. The label gives no figure for how much alcohol changes next-day impairment.
A sleeping pill interacts with the drink taken to help sleep, with the painkiller taken for the back, and with the herbal remedy taken for mood. The label covers all three.
Significant findings
AMBIEN prescribing information (Sanofi, April 2025), Drug Interactions summary: "CNS depressants, including alcohol: Possible adverse additive CNS-depressant effects (5.2, 7.1). Opioids: Concomitant use may increase risk of respiratory depression (5.7, 7.1). Imipramine: Decreased alertness observed (7.1). Chlorpromazine: Impaired alertness and psychomotor performance observed (7.1). CYP3A4 inducers (rifampin or St. John's wort): Combination use may decrease effect (7.2). Ketoconazole: Combination use may increase effect (7.2)."
Section 7.1: "Coadministration of zolpidem with other CNS depressants increases the risk of CNS depression. Concomitant use of zolpidem with these drugs may increase drowsiness and psychomotor impairment, including impaired driving ability." The imipramine and chlorpromazine findings come from single-dose interaction studies in healthy volunteers, which is how the label knows an old antidepressant and an old antipsychotic each worsen next-day alertness with zolpidem.
Section 7.2 on rifampin: "Rifampin, a CYP3A4 inducer, significantly reduced the exposure to and the pharmacodynamic effects of zolpidem. Use of Rifampin in combination with zolpidem may decrease the efficacy of zolpidem and is not recommended." St John's wort is listed under the same mechanism.
The boxed warning on the same label, about complex sleep behaviours such as sleep-driving, is not an interaction warning, but the CNS depressant additivity sits underneath it.
Worth asking
The interaction most people will meet is the first one. If you take zolpidem, the question is not whether one drink is allowed but what the label says happens to alertness and driving the next morning when two depressants overlap. And if a sleeping pill stops working after a new medication or supplement is started, ask the pharmacist whether the new one induces CYP3A4 before the dose is raised.
Source
AMBIEN (zolpidem tartrate) tablets: FDA-approved prescribing information, Drug Interactions 7.1 and 7.2 — Sanofi-Aventis U.S. LLC; US Food and Drug Administration (2025)
Regulator or national health body
How this was scored
- Study design
- Regulatory safety determination
- Funding
- Industry funded
- Published in
- Regulator or national health body
- Sample size
- not recorded
- Preregistered
- not recorded
- Conflicts disclosed
- not recorded
- Independent of proponent
- not recorded
- Retracted
- No
Read the full scoring rubric, including what it can't tell you.
Published September 21, 2026.
Questions
How strong is the evidence behind this?
veisund rates this source "moderate evidence". Reasonable evidence with real limitations. It scores 57 out of 100 on our published rubric. One caveat travels with that badge: The imipramine and chlorpromazine findings are single-dose volunteer studies, not outcomes in patients. The label gives no figure for how much alcohol changes next-day impairment. The score is calculated from recorded facts about the source — study design, funding, publication venue, sample size, preregistration — not typed in by an editor.
What is the source for this?
AMBIEN (zolpidem tartrate) tablets: FDA-approved prescribing information, Drug Interactions 7.1 and 7.2 — Sanofi-Aventis U.S. LLC; US Food and Drug Administration (2025). Published in: Regulator or national health body. The full source is linked on this page so you can read it yourself.
Who paid for this research, and does that matter?
Study design: Regulatory safety determination. Funding: Industry funded. Independence from the proponent is not recorded. Industry sponsorship is one of the most reliably measured biases in medicine, which is why funding carries real weight in the score rather than sitting in a footnote.
Is this medical advice?
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.