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Flumazenil

Also known as: Flumazenil

Benzodiazepine Antagonist

Route: Intravenous

3 interactions on record⛔ Black Box Warning

Flumazenil has 3 known drug interactions based on U.S. FDA drug labeling data. 1 are classified as major interactions requiring close medical supervision. Notable interactions include combinations with Cyclic Antidepressants, Zopiclone. Patients taking Flumazenil should inform their healthcare provider of all current medications — including over-the-counter drugs and supplements — to avoid potentially harmful combinations. Data sourced from OpenFDA and the NIH National Library of Medicine.

Total: 3
Major: 1
Moderate: 1

Major (1)

Flumazenil + Cyclic Antidepressants— Toxic effects such as convulsions and cardiac dysrhythmias may emerge with reversal of benzodiazepine effect by flumazen…

Moderate (1)

Flumazenil + Zopiclone— Central effects are blocked by flumazenil through competitive interaction at benzodiazepine receptors.

Flumazenil + Cyclic Antidepressants⚠️Major

Toxic effects such as convulsions and cardiac dysrhythmias may emerge with reversal of benzodiazepine effect by flumazenil in cases of mixed drug overdosage.

Flumazenil + Zopiclone🟡Moderate

Central effects are blocked by flumazenil through competitive interaction at benzodiazepine receptors.

Flumazenil + Nalmefene Hydrochlorideℹ️Unknown

Preclinical studies show both drugs can induce seizures in animals. Coadministration produced fewer seizures than expected, suggesting no adverse interaction likely, but seizure risk remains a potential concern.

⛔ FDA Black Box Warning

THE USE OF FLUMAZENIL HAS BEEN ASSOCIATED WITH THE OCCURRENCE OF SEIZURES. 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. PRACTITIONERS SHOULD INDIVIDUALIZE THE DOSAGE OF FLUMAZENIL AND BE PREPARED TO MANAGE SEIZURES.

Contraindications

CONTRAINDICATIONS 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 ).

Pregnancy & Breastfeeding

Pregnancy Pregnancy Category C: There are no adequate and well-controlled studies of the use of flumazenil in pregnant women. Flumazenil should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Teratogenic Effects: Flumazenil has been studied for teratogenicity in rats and rabbits following oral treatments of up to 150 mg/kg/day. The treatments during the major organogenesis were on days 6 to 15 of gestation in the rat and days 6 to 18 of gestation in the rabbit. No teratogenic effects were observed in rats or rabbits at 150 mg/kg; the dose, based on the available data on the area under the plasma concentration-time curve (AUC) represented 120x to 600x the human exposure from a maximum recommended intravenous dose of 5 mg in humans. In rabbits, embryocidal effects (as evidenced by increased preimplantation and postimplantation losses) were observed at 50 mg/kg or 200x the human exposure from a maximum recommended intravenous dose of 5 mg. The no-effect dose of 15 mg/kg in rabbits represents 60x the human exposure. Nonteratogenic Effects: An animal reproduction study was conducted in rats at oral dosages of 5, 25, and 125 mg/kg/day of flumazenil. Pup survival was decreased during the lactating period, pup liver weight at weaning was increased for the high-dose group (125 mg/kg/day) and incisor eruption and ear opening in the offspring were delayed; the delay in ear opening was associated with a delay in the appearance of the auditory startle response. No treatment-related adverse effects were noted for the other dose groups. Based on the available data from AUC, the effect level (125 mg/kg) represents 120x the human exposure from 5 mg, the maximum recommended intravenous dose in humans. The no-effect level represents 24x the human exposure from an intravenous dose of 5 mg. Pregnancy Category C: There are no adequate and well-controlled studies of the use of flumazenil in pregnant women. Flumazenil should be used during

Data sourced from U.S. FDA drug labeling via openFDA and the NIH National Library of Medicine, supplemented with a small number of well-established interactions from curated clinical references. For informational purposes only. Always consult your pharmacist or physician.