Mixed drug overdosage-

particular caution is necessary when using flumazenil in cases of mixed drug overdosage; toxic effects(eg. convulsions, cardiac dysrhythmias) of other drugs taken in over dose(especially cyclic antidepressants) may emerge with reversal of benzodiazepine effect by flumazenil.

Reversal of benzodiapene sedation-

Deaths have occured in patients who received flumazenil. The majority of deaths occured in patients with serious underlying disease or in patients who had ingested large amounts of non-benzodiazepine drugs. Nausea, vomiting, hiccups. Dizziness, agitation, dry mouth, palpitations, insomnia,dyspnea, hyperventilation. Body as a whole- headache, injection at site pain, increased sweating, injection at site reaction(thrombohelbitis, skin abnormality, rash) fatigue, (asthenia, malaise) rigors,shivering. Cardiovascular- cutaneous vasodilation( sweating, flushing, hort flushes) arrhythmia (atrial , nodal, ventricular extrasystoles) bradycardia, tachycardia, hypertension,chest pain. GI- nausea, vomiting, hiccups CNS- dizziness, vertigo, ataxia,agitation, anxiety nervousness, dry mouth, tremors, palpiations, insomnia, dyspnea, hyperventilation, emotional lability, abnormal crying, depersonalization, euphoria, increased tears, depression, dysphoria, paronia, confusion, difficulty in concentrating, delirium, convulsions, somnolence, speech disorder,dysphonia, thick tongue Special senses- abnormal vision, visual defect, diplopia, blurred vision, paresthesia, sensationl abnomal, hyperacusis, tinnitus

Hypersens to flumazenil or benzodoazepine Special precautions: Monitoring- monitor patients for resedation, respiratory depression. Use with caution in intensive care unit.

Return of sedation- Resedation is least likely in cases where flumazenil is administered to reverse a low dose of a short-acting benzodiazepine (10mg midzolam ). It is most likely in cases where a single or cumulative dose of a benzodiazepine has been given in the course of a long procedure along with neuromuscular blocking agents and multiple anesthetic agents.

Intensive care Unit (ICU)- use with caution in ICU because of the increased risk of unrecognized benzodiazepine depedence in such settings. Flumazenil may produce convulsions in patients physically dependent on benzodiazepines Overdose situations- flumazenil is intended as an adjunct to, not a substitute for, proper management of airway, assisted breathing,circulatory access and support , internal decontamination by lavage and charcoal ,and adequate clinical evaluation.

Head injury- use with caution in patients withnhead injury as flumazenil may be capable of precipitating convulsions or altering cerebral flow in patients receiving benzodiazepines.

Neuromuscular blocking agents- do not use flumazenil until th reffects of neuromuscular blockade has been fully reversed Psychiatric patients- flumezenil may provoke panic attacks in patients with a history of panic disorder.

Drug and alcohol dependent- use with caution in patients with alcoholism and other drugs dependencies due to the increased frequency of benzodiazepine tolerance and dependence observed in these patient populations.

Tolerance to benzodiazepines- flumazenil may cause benzodiazepine withdrawal symptoms in individuals who have been taking benzodiazepine long enough to have some degree of tolerance.

Pain on injection- to minimise the likeliihood of pain at the injection site,administer flumazenil through free flowing IV infusion into a large vein.

Respiratory disease- appropiate ventilatory support is the primary treatment for patients with serious lung diseases who experience serious respiratory depression due to benzodiazepines rather than the administration of flumazenil.

Ambulatory patients- becausee of the increased risk of adverse reactions in patients who have taking benzodiazepines on a regular basis it is particularly important to carefully query about benzodioazepine, alcohol and sedative use as part of the history prior to any procedure in which flumazenil is planned.

Drug abuse and depenendence- Flumazenil has benzodiazepine -like structure but does not act as a benzodiazepine against in man and is not a controlled substance.

Warnings- Seizures- the use of flumzenil has been associated with the occurrence of seizures.These are most frequent in patients who have been on benzzodiazepines for a long- term sedation or in overdose cases where the patients are showing signs of serious cyclic antidepressant overdose.

Hypoventilation- monitor patients who have received flumazenil for the revesal of benzodiapine effects (after conscious sedation or general anesthesia) for resedation, respiratory depression or other resudual benzodiapine effects for an appropiate period ( up to 120 minutes ) based on the dose of effect of the benzodiapine employed.

Hepatic function impairment- while the dose of flumazenil used for initial reversal of benzodiazepine effects is not affected, reduce the size and frequency of repeat doses of the drug in liver disease.

Elderly- the pharmacokinetics of flumazenil have been studied in elderly and are not significantly different than younger patients.

Pregnancy- use during pregnancy only if potential benefits justify potential risks to the fetus

Lactation- excercise caution when deciding to administer flumazenil to a nursing woman.

Children- flumazenil is not recommended for use in children.

Approved by FDA in December 1991

Indication:

Reversal of benzodiazepine sedation

Dosage:

For IV use only. Individualise dose and administer flumazenil through a freely running IV infusion.

Overdosage-

Large IV doses oof flumazenil when administred to healthy volunteers inthe absence of benzodiazepine agonist,produced no serious adverse reactions. Reversal with excessive high dose of flumazenil may produce anxiety, agitation, increased muscle tone,hyperesthesia and possibly convulsions Convulsions have treated with barbiturates ,benzodiazepines, and phynetoin, generally with prompt resolution of the seizures.

1. Flumazenil does not consistently reverse amnesia. Patients cannot be expected to remember information told to them in the post-procedure peroid.

2. Advise patients not engage inany activities requiring complete alertness.

3. Not to take any alcohol or non-prescribtion drugs for 18 to 24 hrs after flumazenil administartion.

Pregnancy:

Use during pregnanacy only if needed.

Lactation:

Excercise caution while administering flumazenil to a nursing woman

Children-

Flumazenil is not recommended for use in children.