Indications| Complete or partial reversal of the central sedative effects of benzodiazepines. It is therefore used in anesthesia and intensive care in the following indications:Anesthesia: Termination of general anesthesia induced and maintained with benzodiazepines in in-patients. Reversal of benzodiazepine sedation in short diagnostic and therapeutic procedures in both in-patients and out-patients. Intensive Care and Management of Unconsciousness of Unknown Origin: Anexate provides diagnosis of benzodiazepine intoxication or rules out such intoxication.
For specific reversal of the central effects of benzodiazepines in drug overdose (return to spontaneous respiration and consciousness in order to render intubation unnecessary or allow extubation). | Dosage| Anexate is recommended for IV use only and should be administered by an anesthesiologist or experienced physician. Anexate is compatible with 5% dextrose in water, lactated Ringer’s and normal saline solutions. If Anexate is drawn into a syringe or mixed with any of these solutions, it should be discarded after 24 hours (see Stability under Cautions for Usage).
Dosage should be titrated for the intended effect. Since the duration of action of some benzodiazepines may exceed that of Anexate, repeated doses may be required if sedation recurs following awakening. Anesthesia: Recommended Initial Dose: 0. 2 mg administered IV over 15 sec. If the desired degree of consciousness is not obtained within 60 sec, a second dose (0. 1 mg) can be injected and this may be repeated at 60-sec intervals where necessary, up to a total dose of 1 mg. The usual dose is 0. 3-0.
6 mg, but individual requirements may vary considerably, depending on the dose and duration of effect of the benzodiazepine administered and patient characteristics. Intensive Care and Management of Unconsciousness of Unknown Origin: Recommended Initial Dose: 0. 3 mg IV. If the desired level of consciousness is not obtained within 60 sec, Anexate may be injected repeatedly until the patient awakes or up to a total dose of 2 mg. If drowsiness recurs, Anexate may be administered as ? 1 bolus IV doses as stated previously or as an IV infusion of 0. 1-0. 4 mg/hr.
The rate of infusion should be individually adjusted to the desired level of arousal. If a significant improvement in consciousness or respiratory function is not obtained after repeated doses of Anexate, a nonbenzodiazepine etiology must be assumed. In the intensive care unit, in patients treated with high doses of benzodiazepines and/or for long periods of time, the individually titrated injections of Anexate, slowly administered, should not produce withdrawal syndromes. If unexpected symptoms occur, diazepam or midazolam could be carefully titrated IV according to patient’s response (see Precautions).
Children >1 year: Reversal of Conscious Sedation Induced with Benzodiazepines: Recommended Initial Dose: 0. 01 mg/kg (up to 0. 2 mg) administered IV over 15 sec. If the desired level of consciousness is not obtained after waiting an additional 45 sec, further injections of 0. 01 mg/kg (up to 0. 2 mg) can be administered and repeated at 60-sec intervals where necessary (up to a maximum of 4 additional times) to a maximum total dose of 0. 05 mg/kg or 1 mg, whichever is lower. The dose should be individualized based on patient’s response.
| Overdosage| There is very limited experience of acute overdose in humans with Anexate. There is no specific antidote for overdose with Anexate. Treatment of an overdose with Anexate should consist of general supportive measures including monitoring of vital signs and observation of the clinical status of patient. Even when given at doses exceeding those recommended, no symptoms of overdosage were observed. For withdrawal symptoms attributable to the agonist (see Dosage & Administration). | Contraindications| Patients with known hypersensitivity to Anexate.
Patients who have been given a benzodiazepine for control of a potentially life-threatening condition (eg, control of intracranial pressure or status epilepticus). | Special Precautions| Particular caution is necessary when using Anexate in cases of mixed-drug overdose since the toxic effects (eg, convulsions and cardiac dysrhythmias) of other drugs taken in overdose (especially cyclic antidepressants) may emerge with the reversal of benzodiazepine effects by Anexate. The use of Anexate is not recommended in epileptic patients who have been receiving benzodiazepine treatment for a prolonged period.
Although Anexate exerts a slight intrinsic anticonvulsant effect, its abrupt suppression of the protective effect of a benzodiazepine agonist can give rise to convulsions in epileptic patients. Patients who have received Anexate for the reversal of benzodiazepine effects should be monitored for resedation, respiratory depression or other residual benzodiazepine effects for an appropriate period based on the dose and duration of effect of the benzodiazepine employed. When Anexate is used with neuromuscular blocking agents, it should not be injected until the effects of neuromuscular blockade have been fully reversed.
Anexate should be used with caution in patients with head injury as it may be capable of precipitating convulsions or altering cerebral blood flow in patients receiving benzodiazepines. Rapid injection of Anexate should be avoided in patients with high dose and/or long-term exposure to benzodiazepines ending at any time within the weeks preceding Anexate administration as it may produce withdrawal symptoms, including agitation, anxiety, emotional lability as well as mild confusion and sensory distortions (see Dosage & Administration).
Anexate is not recommended either as a treatment for benzodiazepine dependence or for the management of protracted benzodiazepine abstinence syndromes. Effects on the Ability to Drive or Operate Machinery: Patients should be warned against engaging in hazardous activities requiring complete mental alertness (eg, operating dangerous machinery or driving a motor vehicle) during the first 24 hrs after administration, since the effect of the originally ingested or administered benzodiazepine (eg, sedation) may occur.
Carcinogenicity, Mutagenicity & Impairment of Fertility: In vitro and animal studies using high doses of Anexate have not shown evidence of mutagenicity, teratogenicity or impairment of fertility. Use in pregnancy & lactation: The safety of Anexate in human pregnancy has not been established. Therefore, the benefits of drug therapy during pregnancy should be weighed against possible risks to the fetus. Parenteral administration of Anexate in emergencies is not contraindicated during lactation.
Use in children: Anexate should be used with caution for the reversal of conscious sedation in children <1 year, for the management of overdose in children, for resuscitation of the newborn and for reversal of the sedative effects of benzodiazepines used for induction of general anesthesia in children, as experience is limited (see Dosage & Administration). | Adverse Drug Reactions| Anexate is well tolerated in adults and children. In adults, Anexate is well tolerated even at doses exceeding those recommended.
Complaints eg, feelings of anxiety, palpitations and fear have been infrequently observed after rapid injection of Anexate. These undesirable effects usually do not necessitate special treatment. Seizures have been reported in patients known to suffer from epilepsy or severe hepatic impairment, particularly after long-term treatment with benzodiazepines or in cases of mixed-drug overdose. In cases of mixed-drug overdose, particularly with cyclic antidepressants, toxic effects (eg, convulsions and cardiac dysrhythmias) may emerge with the reversal of benzodiazepines effects by Anexate.
Withdrawal symptoms may occur following rapid injection of Anexate in patients with long-term exposure to benzodiazepines ending at any time within the weeks preceding Anexate administration. Anexate has been reported to provoke panic attacks in patients with a history of panic disorders. Click to view ADR Monitoring Website| Drug Interactions| Anexate blocks the central effects of benzodiazepines by competitive interaction at the receptor level. The effects of nonbenzodiazepine agonists at benzodiazepine receptors eg, zopiclone, triazolopyridazines and others, are also blocked by Anexate.
The pharmacokinetics of benzodiazepine agonists are unaltered in the presence of Anexate and vice versa. There is no pharmacokinetic interaction between ethanol and flumazenil. View more drug interactions with Anexate| Pregnancy Category (US FDA)| | | | | | | | | | | | | 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.
| Caution For Usage| Stability: When Anexate is drawn into a syringe or diluted with normal saline or 5% dextrose, it should be discarded after 24 hrs (see Dosage & Administration). | Mechanism of Action| Benzodiazepine Antagonist. ATC code: V03AB25. Pharmacology: Pharmacodynamics: Mechanism of Action: Anexate, an imidazobenzodiazepine, is a benzodiazepine antagonist. It competitively inhibits agents that act via benzodiazepine receptors, specifically blocking their central nervous effects. In animal experiments, the effects of compounds showing affinity for benzodiazepine receptors were blocked.
In healthy volunteers, IV Anexate has been shown to antagonize the sedation, amnesia and psychomotor impairment produced by benzodiazepine agonists. Hypnotic-sedative benzodiazepine effects are rapidly reversed after IV injection (1-2 min) and may then reappear gradually within the next few hours, depending on the t? and dose ratio of the agonist and antagonist. Anexate may possess some weak intrinsic agonistic (eg, anticonvulsant) activity. In animals pre-treated with high doses of benzodiazepines over several weeks, Anexate elicited symptoms of benzodiazepine withdrawal, including seizures.
A similar effect was seen in adult human subjects. Pharmacokinetics: Absorption:The pharmacokinetics of flumazenil are dose-proportional within and above the therapeutic range (up to 100 mg). Distribution: Flumazenil, a weak lipophilic base, is about 50% bound to plasma proteins. Albumin accounts for 2/3 of plasma protein-binding. Flumazenil is extensively distributed in the extravascular space. Plasma concentrations of flumazenil decrease with a t? of 4-11 min during the distribution phase. The volume of distribution at steady state is 0. 9-1. 1 L/kg. Metabolism: Flumazenil is extensively metabolized in the liver.
The carboxylic acid metabolite is the main metabolite in plasma (free form) and urine (free form and its glucuronide). This main metabolite shows no benzodiazepine agonist or antagonist activity in pharmacological tests. Elimination: Flumazenil is almost completely (99%) eliminated by nonrenal routes. Practically no unchanged flumazenil is excreted in the urine, suggesting complete metabolic degradation of the drug. Elimination of radiolabelled drug is essentially complete within 72 hrs, with 90-95% of the radioactivity appearing in urine and 5-10% in the feces.
Elimination is rapid, as shown by a short elimination t?of 40-80 min. The total plasma clearance of flumazenil is 0. 8-1 L/hr/kg and can be attributed almost entirely to hepatic clearance. Ingestion of food during an IV infusion of flumazenil results in a 50% increase in clearance, most likely due to the increased hepatic blood flow that accompanies a meal. Special Populations:
In patients with impaired liver function, the elimination t? of flumazenil is longer and the total body clearance lower than in healthy subjects. The pharmacokinetics of flumazenil are not significantly affected in the elderly, by gender, hemodialysis or renal failure.
The elimination t? in children >1 year is more variable than in adults, averaging 40 min and generally ranging from 20-75 min. Clearance and volume of distribution, normalized for body weight, are in the same range as is seen in adults. | MIMS Class| Antidotes, Detoxifying Agents & Drugs Used in Substance Dependence| ATC Classification| V03AB25 – flumazenil ; Belongs to the class of antidotes. Used in the management of hypnotics and sedatives overdose. | Poison Schedule| Rx| Presentation/Packing| Inj 0. 5 mg/5 mL x 5’s. | | Why it is prescribed (Indications) :
This medication is a benzodiazepine antagonist, prescribed for reversing drowsiness, sedation and other effects caused by benzodiazepine. It is also used for hepatic encephalopathy (confusion, altered level of consciousness and coma as a result of liver failure). When it is not to be taken (Contraindications): Contraindicated in patients with hypersensitivity, who have been given benzodiazepine for control of a potentially life-threatening condition, who have experienced with serious side effects due to overdose of depression medications.
Pregnancy Category 😐 A| B| C| D| X| | Category C :Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks. When it is to be taken : Adult: IV- The recommended dose is 200 I? g every 1i?? 2 minutes until the effect is seen, to a maximum of 3 mg per hour. How it should be taken :
It comes as a solution for injection, to be administered by a healthcare provider into the vein. Special Instruction : * Caution should be exercised in patients with history of seizures, panic attacks, alcohol or drug dependency, breathing disorders, heart disease, liver disease, head injury, allergies, elderly, children, during pregnancy and breastfeeding. * Patient may develop with increased risk of epilepsy, respiratory depression, if it so consult with your doctor. * It may cause lightheadedness, dizziness or drowsiness, do not drive a car or operate machinery while taking this medication. Side Effects :
Most frequent- Dizziness, injection site pain, increased sweating, headache and abnormal or blurred vision. Body as a Whole- Fatigue, weakness, uneasiness and injection site pain. Heart- Dilation of blood vessels, flushing, palpitations and hot flushes. Gastrointestinal- Nausea, vomiting and dry mouth. Central Nervous System- Agitation, anxiety, nervousness, tremor, sleeplessness, and emotional lability. Respiratory- Difficulty in breathing. | Other Precautions : *
Avoid alcohol consumption. Storage Conditions : Store it at controlled room temperature (25A°Read more:Flumazenil (Anexate) Drug Information – Indications, Dosage, Side Effects and Precautions | Medindiahttp://www. medindia. net/doctors/drug_information/flumazenil. htm#ixzz1qrfgFjLF Flumazenil (also known as flumazepil, code name Ro 15-1788, trade names Anexate,Lanexat, Mazicon, Romazicon) is a benzodiazepine antagonist available for injection only, and the only benzodiazepine receptor antagonist on the market today.
Indications| Listed in Dosage. | Dosage| PO Vit K deficiency due to drugs or malabsorption 10-40 mg/day. Over-anticoagulation Up to 5 mg.
IV Over-anticoagulation 0. 5-5 mg. Click to view phytomenadione Dosage by Indications| Administration| May be taken with or without food. | Contraindications| Hypersensitivity. | Special Precautions| Increased risk of severe haemolytic anaemia in neonates after large doses; severe hepatic impairment; pregnancy. Premature neonates weighing <2. 5 kg. | Adverse Drug Reactions| Anaphylaxis, dyspnoea, cyanosis, pain, swelling, phloebitis at the Inj site, diaphoresis, dizziness, hypotension (rare), allergic reactions after SC and IM inj.
| Drug Interactions| Decreased effect of oral anticoagulants. | Pregnancy Category (US FDA)| | | | | | | | | | | | | 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. | Mechanism of Action|
For details of the mechanism of action, pharmacology and pharmacokinetics and toxicology …click to view phytomenadione| MIMS Class| Haemostatics| ATC Classification| B02BA01 – Phytomenadione ; Belongs to the class of vitamin K. Used in the treatment of hemorrhage. | Medications containing hydrocortisone: hydrocortisone systemic Brand names: Cortef, Solu-Cortef, GENERIC NAME: isosorbide dinitrate BRAND NAMES:
Isordil Titradose, Dilatrate-SR, Isochron GD-035-PHS-EMS: Drug Profile for Dexamethasone Sodium Phosphate GENERIC NAME: DEXAMETHASONE SODIUM PHOSPHATE BRAND NAME: Decadron CLASS: synthetic adrenocorticoid/glucocorticoid with a predominance of glucocorticoid action, anti-inflammatory Mechanism of Action:
Improves lung function and myocardial performance: stabilization of lysosomal and cell membranes, inhibition of compliment-induced granulocyte aggregation, rightward shift in oxygen-hemoglobin dissociation curve, inhibition of prostaglandin and leukotriene production, increase in surfactant production, decrease in pulmonary edema, relaxation of bronchospasm. Indications and Field Use: Reactive airway disease: Acute exacerbation of bronchial asthma Anaphylaxis Cerebral edema (non-traumatic) Contraindications:
Systemic fungal infections Hypersensitivity to any component of dexamethasone, including sulfites Preterm infants Adverse Reactions: Sodium retention, fluid retention, potassium loss, hypokalemic alkalosis, hypertension, convulsions, hyperglycemia, myocardial rupture following recent myocardial infarction NOTES ON ADMINISTRATION Incompatibilities/Drug Interactions: Dexamethasone is not compatible with benadryl or versed in IV tubing. Adult Dosage: Reactive Airway Disease, Anaphylaxis 8-24 mg Cerebral Edema 1-5 mg/kg Page 1 of 2 1/21/05 GD-035-PHS-EMS:
Drug Profile for Dexamethasone Sodium Phosphate Pediatric Dosage: Reactive Airway Disease, Anaphylaxis 0. 25-0. 5 mg/kg Cerebral Edema 0. 5-1. 5 mg/kg Routes of Administration: IV bolus, IM Onset of Action: 4-8 hours Peak Effects: 6-12 hours Duration of Action: 24-72 hours Dosage Forms/Packaging: 20 mg/5 mL, 100 mg/25 mL, 120 mg/5 mL Arizona Drug Box Supply Range: PARAMEDIC: 2-4 120 mg/5 mL and 2-4 20 mg/5 mL INTERMEDIATE: 2-4 120 mg/5 mL and 2-4 20 mg/5 mL.