Etomidate

Description

DESCRIPTION Etomidate Injection, USP is a sterile, nonpyrogenic solution. Each milliliter contains etomidate, 2 mg, propylene glycol 35% v/v. The pH is 6.0 (4.0 to 7.0). It is intended for the induction of general anesthesia by intravenous injection. The drug etomidate is chemically identified as (R)-(+)-ethyl-1-(1-phenyethyl)-1H-imidazole-5-carboxylate and has the following structural formula: Molecular Formula: C 14 H 16 N 2 O 2 Molecular Weight: 244.3 chemical structure

What Is Etomidate Used For?

INDICATIONS AND USAGE Etomidate Injection, USP is indicated by intravenous injection for induction of general anesthesia. When considering use of etomidate, the usefulness of its hemodynamic properties (see CLINICAL PHARMACOLOGY ) should be weighed against the high frequency of transient skeletal muscle movements (see ADVERSE REACTIONS ). Intravenous etomidate is also indicated for supplementation of subpotent anesthetic agents, such as nitrous oxide in oxygen, during maintenance of anesthesia for short operative procedures such as dilation and curettage or cervical conization.

Dosage and Administration

DOSAGE AND ADMINISTRATION Do not administer unless solution is clear and container is undamaged. Discard unused portion (see DOSAGE AND ADMINISTRATION ). Etomidate injection is intended for administration only by the intravenous route (see CLINICAL PHARMACOLOGY ). The dose for induction of anesthesia in adult patients and in pediatric patients above the age of ten (10) years will vary between 0.2 mg/kg and 0.6 mg/kg of body weight, and it must be individualized in each case. The usual dose for induction in these patients is 0.3 mg/kg, injected over a period of 30 to 60 seconds. There are inadequate data to make dosage recommendations for induction of anesthesia in patients below the age of ten (10) years; therefore, such use is not recommended. Geriatric patients may require reduced doses of etomidate. Smaller increments of intravenous etomidate may be administered to adult patients during short operative procedures to supplement subpotent anesthetic agents, such as nitrous oxide. The dosage employed under these circumstances, although usually smaller than the original induction dose, must be individualized. There are insufficient data to support this use of etomidate for longer adult procedures or for any procedures in pediatric patients; therefore, such use is not recommended. The use of intravenous fentanyl and other neuroactive drugs employed during the conduct of anesthesia may alter the etomidate dosage requirements. Consult the prescribing information for all other such drugs before using. Premedication: Etomidate injection is compatible with commonly administered pre-anesthetic medications, which may be employed as indicated. See also CLINICAL PHARMACOLOGY , ADVERSE REACTIONS , and dosage recommendations for maintenance of anesthesia. Etomidate anesthesia does not significantly alter the usual dosage requirements of neuromuscular blocking agents employed for endotracheal intubation or other purposes shortly after induction of anesthesia. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. To prevent needle-stick injuries, needles should not be recapped, purposely bent, or broken by hand.

Side Effects (Adverse Reactions)

ADVERSE REACTIONS The most frequent adverse reactions associated with the use of intravenous etomidate are transient venous pain on injection and transient skeletal muscle movements, including myoclonus: 1. Transient venous pain was observed immediately following intravenous injection of etomidate in about 20% of the patients, with considerable difference in the reported incidence (1.2% to 42%). This pain is usually described as mild to moderate in severity but it is occasionally judged disturbing. The observation of venous pain is not associated with a more than usual incidence of thrombosis or thrombophlebitis at the injection site. Pain also appears to be less frequently noted when larger, more proximal arm veins are employed and it appears to be more frequently noted when smaller, more distal, hand or wrist veins are employed. 2. Transient skeletal muscle movements were noted following use of intravenous etomidate in about 32% of the patients, with considerable difference in the reported incidence (22.7% to 63%). Most of these observations were judged mild to moderate in severity but some were judged disturbing. The incidence of disturbing movements was less when 0.1 mg of fentanyl was given immediately before induction. These movements have been classified as myoclonic in the majority of cases (74%), but averting movements (7%), tonic movements (10%), and eye movements (9%) have also been reported. No exact classification is available, but these movements may also be placed into three groups by location: a. Most movements are bilateral. The arms, legs, shoulders, neck, chest wall, trunk and all four extremities have been described in some cases, with one or more of these muscle groups predominating in each individual case. Results of electroencephalographic studies suggest that these muscle movements are a manifestation of disinhibition of cortical activity; cortical electroencephalograms, taken during periods when these muscle movements were observed, have failed to reveal seizure activity. b. Other movements are described as either unilateral or having a predominance of activity of one side over the other. These movements sometimes resemble a localized response to some stimuli, such as venous pain on injection, in the lightly anesthetized patient (averting movements). Any muscle group or groups may be involved, but a predominance of movement of the arm in which the intravenous infusion is started is frequently noted. c. Still other movements probably represent a mixture of the first two types. Skeletal muscle movements appear to be more frequent in patients who also manifest venous pain on injection. OTHER ADVERSE OBSERVATIONS Respiratory System: Hyperventilation, hypoventilation, apnea of short duration (5 to 90 seconds with spontaneous recovery); laryngospasm, hiccup and snoring suggestive of partial upper airway obstruction have been observed in some patients. These conditions were managed by conventional countermeasures. Circulatory System: Hypertension, hypotension, tachycardia, bradycardia and other arrhythmias have occasionally been observed during induction and maintenance of anesthesia. One case of severe hypotension and tachycardia, judged to be anaphylactoid in character, has been reported. Geriatric patients, particularly those with hypertension, may be at increased risk for the development of cardiac depression following etomidate administration (see CLINICAL PHARMACOLOGY ). Gastrointestinal System: Postoperative nausea and/or vomiting following induction of anesthesia with etomidate is probably no more frequent than the general incidence. When etomidate was used for both induction and maintenance of anesthesia in short procedures such as dilation and curettage, or when insufficient analgesia was provided, the incidence of postoperative nausea and/or vomiting was higher than that noted in control patients who received thiopental. T o report SUSPECTED ADVERSE REACTIONS, contact Hikma Pharmaceuticals USA...

Contraindications

CONTRAINDICATIONS Etomidate is contraindicated in patients who have shown hypersensitivity to it.

Pregnancy and Breastfeeding

Pregnancy Risk Summary There are no adequate and well-controlled studies in pregnant women. In animal reproduction studies, fetal deaths and reduced pup survival were noted after intravenous administration of etomidate to pregnant rats at doses 0.17 times the human induction dose of 0.3 mg/kg. Reduced pup survival was noted after intravenous administration of etomidate to pregnant rabbits at 1.6 times the human induction dose. Published studies in pregnant primates demonstrate that the administration of anesthetic and sedation drugs that block NMDA receptors and/or potentiate GABA activity during the period of peak brain development increases neuronal apoptosis in the developing brain of the offspring when used for longer than 3 hours. There are no data on pregnancy exposures in primates corresponding to periods prior to the third trimester in humans. [ See Data ]. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data No malformations or adverse fetal effects were noted in a study in which pregnant rats were intravenously administered 0.31, 1.25, or 5 mg/kg/day etomidate (0.17, 0.68, or 2.7 times the human induction dose of 0.3 mg/kg based on body surface area) during organogenesis (Gestation Days 6-15). Reduced pup survival was noted in all doses tested in a study in which pregnant rabbits were intravenously administered 1.5 or 4.5 mg/kg/day etomidate (1.6 or 4.9 times the human induction dose of 0.3 mg/kg based on body surface area) during organogenesis (Gestation Day 6-18). These doses also produced maternal toxicity (increased mortality). Increased stillborn fetuses and decreased pup survival was noted at all doses tested in...

Nursing Mothers It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when etomidate is administered to a nursing mother.

Overdosage

OVERDOSAGE Overdosage may occur from too rapid or repeated injections. Too rapid injection may be followed by a fall in blood pressure. No adverse cardiovascular or respiratory effects attributable to etomidate overdosage have been reported. In the event of suspected or apparent overdosage, the drug should be discontinued, a patent airway established (intubate, if necessary) or maintained and oxygen administered with assisted ventilation, if necessary.

How Supplied

HOW SUPPLIED Etomidate Injection, USP 2 mg/mL is supplied in single dose containers as follows: Concentration Container Size NDC No. Package Size 2 mg/mL 10 mL 72572- 160 -10 Carton of 10 vials 2 mg/mL 20 mL 72572- 161 -10 Carton of 10 vials Store at 20º to 25ºC (68º to 77ºF) [See USP controlled Room Temperature].