Flumazenil and Protriptyline interaction

Flumazenil and Protriptyline: 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 Flumazenil label · effective 2025-09-23

Major

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.

Boxed warningby drug classView label on DailyMed
Major

…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 ).

Contraindicationsby drug classView label on DailyMed
Moderate

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.

Warningsby drug classView label on DailyMed
Moderate

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.

Warningsby drug classView label on DailyMed
Moderate

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 ).

Drug interactionsby drug classView label on DailyMed

From the Protriptyline (Protriptyline Hydrochloride) label · effective 2023-07-25

Moderate

Protriptyline may enhance the response to alcohol and the effects of barbiturates and other CNS depressants.

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.