Rare diseases
Investigational molecules
Locations
Flumazenil is a chemical substance classified as a benzodiazepine receptor antagonist. Its Anatomical Therapeutic Chemical (ATC) code is V03AB25, placing it among antidotes and other substances used to counteract the effects of medicines.[5] The substance is a white to off-white crystalline compound that is insoluble in water but slightly soluble in acidic aqueous solutions.[4] Flumazenil is already authorised as a medicine, with authorisation records in France and Germany held by Cheplapharm Arzneimittel GmbH and B. Braun Melsungen AG. It is known under the trade names Anexate and flumazenil B. Braun, among others.[1]
Flumazenil works by blocking the benzodiazepine recognition site on the GABA/benzodiazepine receptor complex in the central nervous system. It competitively inhibits the activity of benzodiazepines at this site, reversing their sedative effects.[4] Flumazenil has been shown to reverse sedation, impairment of recall, psychomotor impairment and ventilatory depression produced by benzodiazepines in healthy human volunteers. The duration and degree of reversal are related to the dose and plasma concentrations of flumazenil. Doses of approximately 0.1 mg to 0.2 mg produce partial antagonism, while higher doses of 0.4 to 1 mg usually produce complete antagonism in patients who have received the usual sedating doses.[4] Flumazenil does not reverse the effects of opioids, ethanol, barbiturates or general anesthetics, because these act on the brain through mechanisms other than the benzodiazepine receptor.[4]
Flumazenil is available as a sterile solution for injection and as a solution for injection or infusion. It is given by intravenous administration.[5] The product information describes a concentration of 0.1 mg of flumazenil per millilitre, with each 5 ml ampoule containing 500 micrograms of flumazenil.[4][5] In the registered clinical trials, flumazenil is given as an injection or intravenous administration. The trial in depression uses a 1.00 mg dose given by injection, while the pediatric study uses a dose of 0.05 mg per kilogram given by injection.[2][3]
Three clinical trials of flumazenil are registered in the EU Clinical Trials Information System, all with the status Authorised. The largest is a Phase 3 randomised controlled trial of 145 participants with depression, studying whether flumazenil given after electroconvulsive therapy reduces cognitive side-effects while preserving clinical efficacy. Its primary outcome is objective cognitive function.[2] A Phase 3 trial in general anesthesia with 10 healthy volunteers measures the time to the return of spontaneous breathing after rapid sequence emergence from general anaesthesia.[1] A low-intervention trial in pediatric emergence delirium has one participant and measures the occurrence of postoperative delirium until discharge from the recovery room, using a score of 10 or more points as indicative of delirium.[3]
In animals pretreated with high doses of benzodiazepines over several weeks, flumazenil elicited symptoms of benzodiazepine withdrawal, including seizures. A similar effect was seen in adult human subjects.[4] The product information does not list further side effects in the sources provided.
Each condition opens its own overview and trial list
Recruiting trials first
Tell us about your condition – we search every trial in Europe and connect you with the right site.
