Documented interactions for Ambien (zolpidem tartrate). Each entry cites the prescribing information or FDA safety communication it is based on.
| Severity | Interacts with | Class | Concern |
|---|---|---|---|
| Major | Alcohol (ethanol) | CNS depressant | Zolpidem with alcohol: additive CNS depression |
| Major | Alcohol (ethanol) | CNS depressant | Benzodiazepine with alcohol: additive CNS and respiratory depression |
| Major | Other opioids (morphine, fentanyl, methadone, oxycodone, hydromorphone, tramadol) | Opioid | Zolpidem with opioids: additive CNS and respiratory depression |
| Major | Other opioids (morphine, fentanyl, methadone, oxycodone, hydromorphone, tramadol) | Opioid | Opioid with benzodiazepine: risk of profound sedation, respiratory depression, coma, and death |
| Major | Strong CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin, ritonavir, grapefruit juice) | CYP3A4 inhibitor | Strong CYP3A4 inhibitors raise benzodiazepine exposure |
| Moderate | Other CNS depressants (opioids, benzodiazepines, sleep aids, sedating antihistamines, gabapentinoids, muscle relaxants) | CNS depressant | Benzodiazepine with other CNS depressants: additive sedation |
| Moderate | Other Z-drugs (zolpidem, eszopiclone, zaleplon) | Sedative-hypnotic | Zolpidem with other sedatives: additive CNS depression |
| Moderate | Sedating H1 antihistamines (diphenhydramine, hydroxyzine, chlorpheniramine, doxylamine, promethazine) | Sedating antihistamine | Zolpidem with sedating antihistamines: additive CNS depression |
| Moderate | Sedating H1 antihistamines (diphenhydramine, hydroxyzine, chlorpheniramine, doxylamine, promethazine) | Sedating antihistamine | Benzodiazepine with sedating antihistamines: additive sedation |
With: Alcohol (ethanol) CNS depressant
Both agents depress the central nervous system, and alcohol increases zolpidem exposure.
Impaired judgment and motor function, excessive sedation, respiratory depression, coma, and death.
Avoid alcohol with zolpidem.
Basis: Zolpidem tartrate tablets prescribing information, Warnings and Precautions. source
With: Alcohol (ethanol) CNS depressant
Both agents depress the central nervous system and breathing.
Excessive sedation, respiratory depression, and death.
Avoid alcohol during benzodiazepine therapy.
Basis: Benzodiazepine prescribing information, Warnings. source
With: Other opioids (morphine, fentanyl, methadone, oxycodone, hydromorphone, tramadol) Opioid
Additive central nervous system depression and slowed breathing.
Respiratory depression, deep sedation, coma, and death are possible.
Avoid where possible; if used, monitor closely for breathing problems.
Basis: Zolpidem tartrate tablets prescribing information, Drug Interactions. source
With: Other opioids (morphine, fentanyl, methadone, oxycodone, hydromorphone, tramadol) Opioid
Additive depression of the central nervous system and respiratory drive.
FDA requires a boxed warning on benzodiazepines describing this combination. Deep sedation, respiratory arrest, coma, and death have been reported.
Avoid where possible. If used, lowest effective doses for the shortest duration with monitoring.
Basis: FDA Drug Safety Communication (2016); benzodiazepine boxed warning. source
With: Strong CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin, ritonavir, grapefruit juice) CYP3A4 inhibitor
CYP3A4 inhibition slows clearance of benzodiazepines metabolized by this pathway.
Increased sedation; labeling recommends dose reduction for some agents.
Expect the prescriber to reduce the benzodiazepine dose.
Basis: Benzodiazepine prescribing information, Drug Interactions. source
With: Other CNS depressants (opioids, benzodiazepines, sleep aids, sedating antihistamines, gabapentinoids, muscle relaxants) CNS depressant
Additive central nervous system depression.
Excessive sedation, confusion, and impaired coordination.
Review all sedating medications with the prescriber.
Basis: Benzodiazepine prescribing information, Drug Interactions. source
With: Other Z-drugs (zolpidem, eszopiclone, zaleplon) Sedative-hypnotic
Additive sedative effects within the same drug class.
Excessive sedation and impaired coordination.
Only one sedative-hypnotic should be used at a time.
Basis: Zolpidem tartrate tablets prescribing information, Drug Interactions. source
With: Sedating H1 antihistamines (diphenhydramine, hydroxyzine, chlorpheniramine, doxylamine, promethazine) Sedating antihistamine
Sedating H1 antihistamines add to sleep-medication sedation.
Marked drowsiness and impaired coordination.
Avoid combining diphenhydramine or similar antihistamines with zolpidem.
Basis: Zolpidem tartrate tablets prescribing information, Drug Interactions. source
With: Sedating H1 antihistamines (diphenhydramine, hydroxyzine, chlorpheniramine, doxylamine, promethazine) Sedating antihistamine
Additive sedative effects.
Marked drowsiness and impaired coordination.
Avoid combining without prescriber approval.
Basis: Benzodiazepine prescribing information, Drug Interactions. source
We have documented 9 interaction classes for Ambien in our dataset. Usually avoided, or used only with explicit prescriber oversight and close monitoring. The most serious items on this page are marked contraindicated or major.
Alcohol interacts with most of the medications on this site because it adds to sedation and slows breathing. For the specific documented risk, see the relevant entry above. The general rule from labeling is to avoid alcohol.
No. An empty result only means our curated dataset has no matching rule. A pharmacist can run a full interaction screen against every medication and supplement you take.
This site provides educational information only and does not sell, prescribe or dispense medications. Always consult a licensed healthcare provider. This page is not medical advice.