Hypnomidate^® 2 mg/ml Injection

Each ml of Hypnomidate contains etomidate 2 mg.

Solution for injection.

Hypnomidate is an intravenous induction agent of anaesthesia.

For intravenous administration.

Adults and children:

A dose of 0.3 mg/kg given intravenously at induction of anaesthesia, gives sleep lasting from 6 to 10 minutes.

Elderly:

A dose of 0.15-0.2 mg/kg bodyweight should be given and the dose should be further adjusted according to effects. (see Section 4.4 Special Warnings and Precautions for Use).

Since Hypnomidate has no analgesic action, appropriate analgesics should be used in procedures involving painful stimuli.

Do not exceed a total dose of 30 ml (3 ampoules).

Hypnomidate should only be given by slow intravenous injection.

Hypnomidate may be diluted with sodium chloride infusion BP or dextrose infusion BP but it is not compatible with compound sodium lactate infusion BP (Hartmann's solution). Combinations with pancuronium bromide may show a very slight opalescence; for this reason the two should not be mixed together.

Hypnomidate is contraindicated in patients with known hypersensitivity to etomidate.

Warnings: In patients with liver cirrhosis, or in those who have already received neuroleptic, opiate or sedative agents, the dose of etomidate should be reduced.

When Hypnomidate is used, resuscitation equipment should be readily available to manage apnoea. In cases of adrenocortical gland dysfunction and during very long surgical procedures, a prophylactic cortisol supplement may be required (for example 50 to 100 mg hydrocortisone).

Reduced serum cortisol levels, unresponsive to ACTH injections, have been reported in some patients during induction of anaesthesia but particularly during maintenance of anaesthesia with etomidate; for this reason etomidate should not be used for maintenance. However, when etomidate is used for induction, the post-operative rise in serum cortisol which has been observed after thiopentone induction is delayed for approximately 3-6 hours.

Hypnomidate should not be administered to patients with evidence or suggestion of reduced adrenal cortical function.

Hypnomidate should be used with caution in elderly patients, since the potential exists for decreases in cardiac output, which have been reported with doses greater than recommended (see Section 4.2 Posology and Method of Administration for recommended dose in the elderly).

Convulsions may occur in unpremedicated patients.

Precautions: Hypnomidate by injection should be given slowly.

Sedative drugs potentiate the hypnotic effect of Hypnomidate.

Hypnomidate is pharmacologically compatible with the muscle relaxants, premedicant drugs and inhalation anaesthetics in current clinical use.

Hypnomidate has no primary effect on fertility, nor primary embryotoxic or teratogenic effects. At maternally toxic doses in rats, decreased survival was noted. Safety in human pregnancy has not been established. As with other drugs, the possible risks should be weighed against the potential benefits before the drug is administered during pregnancy. Hypnomidate may cross the placental barrier during obstetric anaesthesia.

Lactation: It is not known whether etomidate is excreted in human milk. However, caution should be exercised when Hypnomidate is administered to a nursing mother.

Not applicable, but no effects likely. After very short surgical procedures (up to 15 minutes) the patient regains normal alertness 30 to 60 minutes after waking. After long operations, normal alertness is regained after 4 to 24 hours, depending on the duration of the operation.

The use of narcotic analgesics or diazepam as premedication and during surgery will reduce the uncontrolled spontaneous muscle movements shown by some patients after Hypnomidate administration.

Pain can occur after injection into the small veins of the dorsum of the hand. Use of larger veins or an intravenous application of a small dose of fentanyl 1-2 minutes before induction reduces pain on injection. In a small number of patients, thrombophlebitis has been reported.

Nausea and/or vomiting may occur although these are mainly as a result of concurrent use of opiates. Coughing, hiccough and/or shivering may also be experienced. Allergic reactions, including rare cases of bronchospasm and anaphylactoid reactions, have been reported. Rare cases of laryngospasm, cardiac arrhythmias and convulsions have also been reported.

A slight and transient drop in blood pressure may occur due to a reduction of the peripheral vascular resistance. In vulnerable patients, special care should be exercised to minimise this effect.

Respiratory depression and apnoea may occur.

Overdosing is likely to result in prolonged anaesthesia with the possibility of respiratory depression and even arrest. Hypotension has also been observed. General supportive measures and close observation are recommended. In addition, administration of 50 -100 mg hydrocortisone (not ACTH) may be required for depression of cortisol secretion.

ATC code N01AX07

Etomidate is a short acting intravenous hypnotic which is rapidly inactivated by enzyme metabolism so that it does not give rise to a hangover effect. It does not release histamine, and has no effect on liver function. In vitro studies have shown etomidate to be an inhibitor of microsomal enzymes. Limited in vivo studies have demonstrated only minimal inhibition of hepatic metabolism.

Profile in Plasma

After intravenous administration, the time-course of the etomidate plasma levels can be described by a three-compartment model reflecting distribution, metabolism, and elimination processes. Plasma concentrations decrease rapidly for about 30 minutes and then more slowly; traces are still detectable after about 6 hours. Metabolites, chiefly of hydrolysis, are more slowly excreted.

Distribution

Etomidate is approximately 76.5% bound to plasma proteins. Etomidate is rapidly distributed to the brain and other tissues. Its volume of distribution is about 4.5 L/kg.

Metabolism and Elimination

Etomidate is metabolized in the liver. After 24 hours, 75% of the administered dose of etomidate has been eliminated in the urine primarily as metabolites. Only 2% of etomidate is excreted unchanged via the urine. The terminal half-life of about 3 to 5 hours reflects the slow distribution of etomidate from the deep peripheral compartment.

No relevant information other than that contained elsewhere in the Summary of Product Characteristics.

Propylene glycol

Water for injections

1N sodium hydroxide*

1N hydrochloric acid*

* for occasional pH adjustment only

Combinations with pancuronium bromide may show a very slight opalescence; for this reason the two should not be mixed together.

5 years.

Store at room temperature.

Colourless glass ampoule, PhEur Type I, containing 10 ml Hypnomidate, in packs of 5 and 10 ampoules.

Not all pack sizes may be marketed

None stated.

Janssen-Cilag Limited

50-100 Holmers Farm Way

High Wycombe

Buckinghamshire

HP12 4EG

UK

PL 0242/0019

27 October 1978/20 March 2004

17 March 2009