Flumazenil
/api/v1/drug/flumazenilMechanism of action
Sourced from openFDAMechanism-of-action classes: GABA A Antagonists; GABA B Antagonists.
Indications
Sourced from openFDA- Adult Patients Flumazenil Injection, USP is indicated for the complete or partial reversal of the sedative effects of benzodiazepines in cases where general anesthesia has been induced and/or maintained with benzodiazepines, where sedation has been produced with benzodiazepines for diagnostic and therapeutic procedures, and for the management of benzodiazepine overdose. Pediatric Patients (aged 1 to 17) Flumazenil Injection, USP is indicated for the reversal of conscious sedation induced with benzodiazepines (see PRECAUTIONS: Pediatric Use ).
Contraindications
Sourced from openFDA- 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).contraindicated
Dosage & administration
Sourced from openFDAFlumazenil injection is recommended for intravenous use only. It is compatible with 5% dextrose in water, lactated Ringer’s and normal saline solutions. If flumazenil injection is drawn into a syringe or mixed with any of these solutions, it should be discarded after 24 hours. For optimum sterility, flumazenil injection should remain in the vial until just before use. As with all parenteral drug products, flumazenil injection should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. To minimize the likelihood of pain at the injection site, flumazenil injection should be administered through a freely running intravenous infusion into a large vein. Reversal of Conscious Sedation Adult Patients For the reversal of the sedative effects of benzodiazepines administered for conscious sedation, the recommended initial dose of flumazenil injection is 0.2 mg (2 mL) administered intravenously over 15 seconds. If the desired level of consciousness is not obtained after waiting an additional 45 seconds, a second dose of 0.2 mg (2 mL) can be injected and repeated at 60-second intervals where necessary (up to a maximum of 4 additional times) to a maximum total dose of 1 mg (10 mL). The dosage should be individualized based on the patient’s response, with most patients responding to doses of 0.6 mg to 1 mg (see INDIVIDUALIZATION OF DOSAGE ). In the event of resedation, repeated doses may be administered at 20-minute intervals as needed.
Warnings & precautions
Sourced from openFDARisk of Seizures The reversal of benzodiazepine effects may be associated with the onset of seizures in certain high-risk populations. 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. Flumazenil is not recommended in cases of serious cyclic antidepressant poisoning, as manifested by motor abnormalities (twitching, rigidity, focal seizure), dysrhythmia (wide QRS, ventricular dysrhythmia, heart block), anticholinergic signs (mydriasis, dry mucosa, hypoperistalsis), and cardiovascular collapse at presentation. 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. Treatment with flumazenil has no known benefit to the seriously ill mixed-overdose patient other than reversing sedation and should not be used in cases where seizures (from any cause) are likely. Most convulsions associated with flumazenil administration require treatment and have been successfully managed with benzodiazepines, phenytoin or barbiturates. Because of the presence of flumazenil, higher than usual doses of benzodiazepines may be required.
Adverse reactions
Sourced from openFDASerious Adverse Reactions Deaths have occurred in patients who received flumazenil in a variety of clinical settings. The majority of deaths occurred in patients with serious underlying disease or in patients who had ingested large amounts of non-benzodiazepine drugs (usually cyclic antidepressants), as part of an overdose. Serious adverse events have occurred in all clinical settings, and convulsions are the most common serious adverse events reported. Flumazenil administration has been associated with the onset of convulsions in patients with severe hepatic impairment and in patients who are relying on benzodiazepine effects to control seizures, are physically dependent on benzodiazepines, or who have ingested large doses of other drugs (mixed-drug overdose) (see WARNINGS ). Two of the 446 patients who received flumazenil in controlled clinical trials for the management of a benzodiazepine overdose had cardiac dysrhythmias (1 ventricular tachycardia,1 junctional tachycardia). Adverse Events in Clinical Studies The following adverse reactions were considered to be related to flumazenil administration (both alone and for the reversal of benzodiazepine effects) and were reported in studies involving 1875 individuals who received flumazenil in controlled trials. Adverse events most frequently associated with flumazenil alone were limited to dizziness, injection site pain, increased sweating, headache, and abnormal or blurred vision (3% to 9%).
Overdosage
Sourced from openFDAThere is limited experience of acute overdosage with flumazenil. There is no specific antidote for overdose with flumazenil. Treatment of an overdose with flumazenil injection should consist of general supportive measures including monitoring of vital signs and observation of the clinical status of the patient. Intravenous bolus administration of doses ranging from 2.5 to 100 mg (exceeding those recommended) of flumazenil, when administered to healthy normal volunteers in the absence of a benzodiazepine agonist, produced no serious adverse reactions, severe signs or symptoms, or clinically significant laboratory test abnormalities. In clinical studies, most adverse reactions to flumazenil were an extension of the pharmacologic effects of the drug in reversing benzodiazepine effects. Reversal with an excessively high dose of flumazenil injection may produce anxiety, agitation, increased muscle tone, hyperesthesia and possibly convulsions. Convulsions have been treated with barbiturates, benzodiazepines and phenytoin, generally with prompt resolution of the seizures (see WARNINGS ).
Approval history
Sourced from openFDA- Oct 12, 2004ANDAANDA076755Baxter Hlthcare Corp
- Oct 12, 2004ANDAANDA076955Fresenius Kabi Usa
- Mar 23, 2009ANDAANDA078527Hikma Farmaceutica
FAERS reports
- 1Intentional Overdose10312%
- 2Drug Ineffective9011%
- 3Toxicity To Various Agents8911%
- 4Coma708.4%
- 5Off Label Use698.3%
- 6Intentional Product Misuse617.3%
- 7Drug Dependence576.9%
- 8Depressed Level Of Consciousness566.7%
- 9Hypotension556.6%
- 10Product Use Issue556.6%
- 11Seizure475.6%
- 12Drug Withdrawal Convulsions445.3%
- 13Somnolence425.0%
- 14Overdose414.9%
- 15Suicide Attempt334.0%
Literature
Recent PubMed references pinned to Flumazenil as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.
- Prolonged and fluctuating consciousness after mixed overdose: navigating the complexities of polypharmacy, hepatic impairment and flumazenil use.BMJ case reports · 2026 · Truong V, Chandrasekara HPMID 42215065DOI 10.1136/bcr-2025-270601
- Adverse events associated with the use of flumazenil in the Emergency Department.Medicina clinica · 2026 · Ruiz Ramos J, García Peláez M, Castellanos Clemente Y, et al.PMID 41534387DOI 10.1016/j.medcli.2025.107312
- Routine flumazenil administration confounds emergence time comparisons between remimazolam and propofol: a methodological concern.BMC anesthesiology · 2025 · Cui H, Zeng Q, Zhang Y, et al.PMID 41444866DOI 10.1186/s12871-025-03552-7
- Improving MRI-Negative Epilepsy Localization: Synergy of Dual-Probe PET/MR (18F-FDG/11C-FMZ).Journal of visualized experiments : JoVE · 2025 · Pei Y, Wang Z, Wu X, et al.PMID 41428614DOI 10.3791/69386
- Stereotactic Functional Neurosurgery Combining Sedation and Awake Procedures Using Remimazolam Besylate and Flumazenil: A Technical Note.Neurologia medico-chirurgica · 2025 · Yamamoto K, Higuchi H, Fukui K, et al.PMID 40803842DOI 10.2176/jns-nmc.2025-0011
- Effects of Remimazolam-Propofol with Flumazenil Reversal on the Emergence Time and Hemodynamics of Patients Undergoing Laparoscopic Partial Hepatectomy: A Prospective Randomized Controlled Trial.Drug design, development and therapy · 2025 · Feng Y, Jia JM, Cheng YX, et al.PMID 40786246DOI 10.2147/DDDT.S531034
- Comparison of remimazolam-flumazenil versus propofol on delayed emergence from anaesthesia in major spine surgery: protocol for a multicentre, single-blinded, randomised controlled trial.BMJ open · 2025 · Sun J, Luo W, Wen L, et al.PMID 40780711DOI 10.1136/bmjopen-2024-097541
- Low risk of adverse events associated with flumazenil administration: a retrospective poison center analysis of acutely poisoned patients.Clinical toxicology (Philadelphia, Pa.) · 2025 · Vohra V, Darling A, Welch R, et al.PMID 40586943DOI 10.1080/15563650.2025.2516130
Clinical trials
The 10 most recently updated of 54 ClinicalTrials.gov registrations naming Flumazenil as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.
- Flumazenil for Benzodiazepine Reversal in Electroconvulsive TherapyRecruiting · Interventional · 145 enrolled · Anders JørgensenNCT07619092updated 2026-06-01
- Remimazolam TIVA-Flumazenil Antagonism in Short-duration ENT SurgeriesCompleted · Observational · 511 enrolled · Tongji HospitalNCT07389798updated 2026-05-11
- The Effect of Reversal of Remimazolam Sedation With Flumazenil on Cognitive Function in Patients Undergoing Hip Arthroplasty Under Spinal AnesthesiaNot yet recruiting · Phase 4 · Interventional · 150 enrolled · Medical University of GdanskNCT07277881updated 2026-01-06
- Comparison of Emergence Agitation Between Remimazolam With Flumazenil and Propofol-based Total Intravenous Anesthesia in Patients Undergoing Nasal SurgeryNot yet recruiting · Interventional · 204 enrolled · Seoul National University HospitalNCT07265050updated 2025-12-04
- Effects of Flumazenil on Recovery After Total Intravenous Anesthesia With RemimazolamRecruiting · Interventional · 24 enrolled · Pusan National University Yangsan HospitalNCT05939674updated 2025-09-12
- Effects of Music During Atrial Fibrillation Ablation Under Conscious SedationRecruiting · Interventional · 120 enrolled · Shaoxing People's HospitalNCT06953752updated 2025-07-10
- Total Intravenous Anesthesia for Rigid Bronchoscopy Using RemimazolamWithdrawn · Interventional · 0 enrolled · Samsung Medical CenterNCT05835713updated 2025-03-30
- PET with [18F]Flumazenil As an Index of Neurodegeneration in MSCompleted · Interventional · 45 enrolled · Institut National de la Santé Et de la Recherche Médicale, FranceNCT03825601updated 2025-03-05
- Sleep/Wake State Assessment with Non-invasive EarbudsCompleted · Interventional · 8 enrolled · Emory UniversityNCT05066009updated 2025-02-11
- Rapid Reversal of CNS-Depressant Drug Effect Prior to Brain Death DeterminationWithdrawn · Early phase 1 · Interventional · 0 enrolled · Prisma Health-MidlandsNCT03743805updated 2024-10-31
Frequently asked questions
- How does Flumazenil work?
- Mechanism-of-action classes: GABA A Antagonists; GABA B Antagonists.
- What is Flumazenil used for?
- According to FDA labeling, Flumazenil carries indications including: Adult Patients Flumazenil Injection, USP is indicated for the complete or partial reversal of the sedative effects of benzodiazepines in cases where general anesthesia has been induced and/or maintained with benzodiazepines, where sedation has been produced with benzodiazepines for diagnostic and therapeutic procedures, and for the management of benzodiazepine overdose. Pediatric Patients (aged 1 to 17) Flumazenil Injection, USP is indicated for the reversal of conscious sedation induced with benzodiazepines (see PRECAUTIONS: Pediatric Use ).. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.
- What class of drug is Flumazenil?
- Flumazenil is classified as Antidotes, Benzodiazepine Antagonist, GABA A Antagonists, GABA B Antagonists, Decreased GABA Activity.
- What are the contraindications for Flumazenil?
- Flumazenil labeling lists contraindications including: 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).. Always consult the full prescribing information and a clinician.
flumazenil is illustrative MVP content compiled from public sources. pharmacopeia is for educational and informational use only and is not a substitute for professional medical advice.