Etomidate

INDICATIONS AND USAGE Etomidate injection is indicated by intravenous injection for the induction of general anesthesia. When considering use of etomidate injection, 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 injection is also indicated for the 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 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 Injection 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.

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

ADVERSE REACTIONS The most frequent adverse reactions associated with use of intravenous etomidate are transient venous pain on injection and transient skeletal muscle movements, including myoclonus: • 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. • 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: • 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. • 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. • 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. To report SUSPECTED ADVERSE REACTIONS, contact Mylan Pharmaceuticals Inc. at 1-877-446- …

DESCRIPTION Etomidate Injection, USP is a sterile, non-pyrogenic, clear, colorless solution, free from visible particles. Each milliliter contains etomidate USP 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-phenylethyl)-1H-imidazole-5-carboxylate and has the following structural formula: Etomidate USP is a white or almost white powder. Etomidate Chemical Structure

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 overdose 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 Etomidate Injection, USP is a sterile, non-pyrogenic, clear, colorless solution, free from visible particles and is supplied as follows: Etomidate Injection, USP is supplied in the following dosage forms. NDC 51662-1542-1 ETOMIDATE INJECTION, USP 40mg PER 20mL (2mg/mL) 20mL VIAL HF Acquisition Co LLC, DBA HealthFirst Mukilteo, WA 98275 Also supplied in the following manufacture supplied dosage forms Etomidate Injection, USP is a sterile, non-pyrogenic, clear, colorless solution, free from visible particles and is supplied as follows: 20 mg per 10 mL (2 mg / mL) 10 mL Single-Dose Vials in a Carton of 10 NDC 55150-221-10 40 mg per 20 mL (2 mg / mL) 20 mL Single-Dose Vials in a Carton of 10 NDC 55150-222-20 Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. The vial stoppers are not made with natural rubber latex.