Doxepin and Flumazenil interaction
Doxepin and Flumazenil: both prescribing labels flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.
Do not combine without a prescriber's guidance. The label language below is the strongest FDA uses.
What the FDA labels say
From the Flumazenil label · effective 2025-09-23
THESE ARE MOST FREQUENT IN PATIENTS WHO HAVE BEEN ON BENZODIAZEPINES FOR LONG-TERM SEDATION OR IN OVERDOSE CASES WHERE PATIENTS ARE SHOWING SIGNS OF SERIOUS CYCLIC ANTIDEPRESSANT OVERDOSE.
…Flumazenil is contraindicated: in patients with a known hypersensitivity to flumazenil or benzodiazepines. in patients who have been given a benzodiazepine for control of a potentially life-threatening condition (e.g., control of intracranial pressure or status epilepticus). in patients who are showing signs of serious cyclic antidepressant overdose (see WARNINGS ).
Possible risk factors for seizures include: concurrent major sedative-hypnotic drug withdrawal, recent therapy with repeated doses of parenteral benzodiazepines, myoclonic jerking or seizure activity prior to flumazenil administration in overdose cases, or concurrent cyclic antidepressant poisoning.
In such cases flumazenil should be withheld and the patient should be allowed to remain sedated (with ventilatory and circulatory support as needed) until the signs of antidepressant toxicity have subsided.
Particular caution is necessary when using flumazenil in cases of mixed drug overdosage since the toxic effects (such as convulsions and cardiac dysrhythmias) of other drugs taken in overdose (especially cyclic antidepressants) may emerge with the reversal of the benzodiazepine effect by flumazenil (see WARNINGS ).
From the Doxepin (Silenor) label · effective 2026-04-21
Potential additive effects when used in combination with CNS depressants or sedating antihistamines.
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.
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) ].
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) ].
Alcohol: Sedative effects may be increased with doxepin.
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Open in the checkerNot 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.