Flumazenil

Uses

Reversal of benzodiazepine-induced sedation, Benzodiazepine overdose

Flumazenil is also used to associated treatment for these conditions: Sedation caused by benzodiazepine, Anesthesia reversal, Reversal of sedation therapy

How Flumazenil works

Flumazenil, an imidazobenzodiazepine derivative, is a benzodiazepine antagonist. It competitively inhibits the benzodiazepine binding site on the GABA/benzodiazepine receptor complex. Flumazenil is a weak partial agonist in some animal models of activity, but has little or no agonist activity in man.

Dosage

Flumazenil dosage

Intravenous- Reversal of benzodiazepine-induced sedation

• Adult: Anaesth: Initially, 200 mcg over 15 sec. A 2nd dose of 100 mcg can be given if desired degree of consciousness is not obtained w/in 60 sec. May be repeated at 60-sec intervals if necessary. Usual: 300-600 mcg. Max: 1,000 mcg. Intensive care: Initially, 300 mcg over 15 sec. A repeat dose of 100 mcg may be administered if desired degree of consciousness is not obtained w/in 60 sec. May be repeated at 60-sec intervals if necessary. Max: 2,000 mcg. If drowsiness recurs, admin a 2nd bolus inj. Infusion of 100-400 mcg/hr is also useful, adjust according to desired level of sedation.
• Child: >1 yr Initially, 10 mcg/kg (up to 200 mcg) over 15 sec. Repeat at 60-sec intervals if desired level of consciousness is not obtained after 45 sec. Max: 50 mcg/kg or 1,000 mcg, whichever is lower.

Intravenous-

Benzodiazepine overdose

• Adult: Initially, 200 mcg over 30 sec. Additional dose of 300 mcg may be given after 30 sec, followed by 500 mcg at 60-sec intervals if required. Max: 3,000 mcg or 5,000 mcg. Alternatively, infusion may be given at 100-500 mcg/hr, adjusted according to response. Further doses may not be useful if a cumulative dose of up to 5,000 mcg does not produce any response. If symptoms of intoxication recur, may repeat doses at 20-min intervals; repeat doses should not exceed 1,000 mcg/dose (given as 500 mcg/min) and 3,000 mcg/hr.

Side Effects

Dizziness, pain at inj site, increased sweating, headache, abnormal or blurred vision, nausea, vomiting, palpitations, anxiety, fear, transient HTN, flushing, agitation, chills, sensory disturbances.

Toxicity

In clinical studies, most adverse reactions to flumazenil were an extension of the pharmacologic effects of the drug in reversing benzodiazepine effects.

Precaution

Patient with head injury, alcoholism and other drug dependencies, history of panic disorder. Not intended to treat benzodiazepine dependence or withdrawal syndrome. Should only be used until effects of neuromuscular blockade have been fully reversed. Hepatic impairment. Pregnancy and lactation.

Interaction

Antagonises central effects of benzodiazepines and non-benzodiazepine agonists (e.g. zopiclone, triazolopyridazine) by competitive interaction at the receptor.

Food Interaction

• Take separate from meals. Eating during an intravenous infusion of flumazenil increases the elimination of flumazenil, potentially through elevated hepatic blood flow.

Flumazenil Drug Interaction

Moderate: lorazepam, lorazepam, midazolam, midazolamUnknown: aspirin, aspirin, epinephrine, epinephrine, diphenhydramine, diphenhydramine, glucose, glucose, heparin, heparin, furosemide, furosemide, acetaminophen, acetaminophen, valproic acid, valproic acid

Flumazenil Disease Interaction

Major: seizuresModerate: alcoholism, hepatic dysfunction, psychoses

Volume of Distribution

• 0.9 to 1.1 L/kg

Half Life

Initial distribution half-life is 4 to 11 minutes and the terminal half-life is 40 to 80 minutes. Prolongation of the half-life to 1.3 hours in patients with moderate hepatic impairment and 2.4 hours in severely impaired patients. Compared to adults, the elimination half-life in pediatric patients was more variable, averaging 40 minutes (range: 20 to 75 minutes).

Clearance

• 1 L/hr/kg [healthy volunteers receiving a 5-minute infusion of a total of 1 mg]

Elimination Route

Flumazenil is completely (99%) metabolized. Elimination of radiolabeled drug is essentially complete within 72 hours, with 90% to 95% of the radioactivity appearing in urine and 5% to 10% in the feces.

Pregnancy & Breastfeeding use

Category C: Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.

Contraindication

Patient receiving benzodiazepines to control potentially life-threatening conditions (e.g. status epilepticus, raised intracranial pressure). Severe intoxication w/ tricyclic and related antidepressants.

Storage Condition

Store between 20-25°C.

Innovators Monograph

You find simplified version here Flumazenil