Doxepin and Midazolam interaction

Doxepin and Midazolam: both prescribing labels flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.

Major

Do not combine without a prescriber's guidance. The label language below is the strongest FDA uses.

What the FDA labels say

From the Midazolam (Midazolam in Sodium Chloride) label · effective 2025-07-31

Major

WARNING: PERSONNEL AND EQUIPMENT FOR MONITORING AND RESUSCITATION, AND RISKS FROM CONCOMITANT USE WITH OPIOID ANALGESICS AND OTHER SEDATIVE-HYPNOTICS Personnel and Equipment for Monitoring and ResuscitationOnly personnel trained in the administration of procedural sedation, and not involved in the conduct of the diagnostic or therapeutic procedure, should administer…

Boxed warningby drug classView label on DailyMed
Major

Risks from Concomitant Use with Opioids, Other Sedative Hypnotics, or Other Central Nervous System Depressants Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death.

Warnings and precautionsby drug classView label on DailyMed
Major

Opioid Analgesics and Other Sedative Hypnotics : Risk of respiratory depression is increased ( 7.1 )

Drug interactionsby drug classView label on DailyMed
Major

Opioid Analgesics and Other Sedative Hypnotics The concomitant use of benzodiazepines and opioids increases the risk of respiratory depression because of actions at different receptor sites in the CNS that control respiration.

Drug interactionsby drug classView label on DailyMed
Moderate

Because intravenous midazolam can depress respiration [see Clinical Pharmacology (12)] , especially when used concomitantly with opioid agonists and other sedatives [see Dosage and Administration (2)] , it should be used for sedation/anxiolysis/amnesia only in the presence of personnel skilled in early detection of hypoventilation, maintaining a patent airway,…

Warnings and precautionsby drug classView label on DailyMed

From the Doxepin (Silenor) label · effective 2026-04-21

Moderate

Potential additive effects when used in combination with CNS depressants or sedating antihistamines.

Warnings and precautionsby drug classView label on DailyMed
Moderate

Although behaviors such as "sleep-driving" may occur with hypnotics alone at therapeutic doses, the use of alcohol and other CNS depressants with hypnotics appears to increase the risk of such behaviors, as does the use of hypnotics at doses exceeding the maximum recommended dose.

Warnings and precautionsby drug classView label on DailyMed
Moderate

When taken with SILENOR, the sedative effects of alcoholic beverages, sedating antihistamines, and other CNS depressants may be potentiated [s ee Warnings and Precautions (5.2) and Drug Interactions (7.3 , 7.4) ].

Warnings and precautionsby drug classView label on DailyMed
Moderate

Patients should be cautioned about potential additive effects of SILENOR used in combination with CNS depressants or sedating antihistamines [s ee Warnings and Precautions (5.2) and Drug Interactions (7.4) ].

Warnings and precautionsby drug classView label on DailyMed
Moderate

Alcohol: Sedative effects may be increased with doxepin.

Drug interactionsby drug classView label on DailyMed

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Not medical advice. Interaction Checker quotes FDA label text and NIH fact sheets. Whether an interaction matters for you depends on doses, timing, kidney and liver function, and other conditions. Confirm with a pharmacist or prescriber.