Hypnomidato

Hypnomidato is an intravenous induction agent of anaesthesia.

For intravenous administration.

Hypnomidato should be injected slowly by the intravenous route.

The product must only be used by physicians trained in endotracheal intubation. Equipment for artificial respiration must be available.

It is recommended to wear gloves while opening the ampoule. In the case of any accidental dermal exposure, rinse the affected area with water. Avoid use of soap, alcohol and other cleaning materials that may cause chemical or physical abrasions to the skin.

Adults and children:

A dose of 0.3 mg/kg bodyweight given intravenously at induction of anaesthesia, gives sleep lasting from 4 to 5 minutes.

Dosage should be adjusted to the individual patient response and to clinical effects.

In children under 15 years the dosage may need to be increased: a supplementary dose of up to 30% of the normal dose for adults is sometimes necessary to obtain the same depth and duration of sleep as obtained in adults.

Elderly:

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

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

Hypnosis can be prolonged by additional injections of Hypnomidato.

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

Hypnomidato 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.

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

Hypnosis can be prolonged by additional injections of Hypnomidato.

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

Hypnomidato 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.

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.

Induction with Hypnomidato may be accompanied by a slight and transient drop in blood pressure due to a reduction of the peripheral vascular resistance.).).

Convulsions may occur in unpremedicated patients.

Precautions: Hypnomidato by injection should be given slowly (e.g. 10 ml over 30-60 seconds).

Etomidate has a major influence on the ability to drive and use machines. Even though a patient may regain normal alertness 30 to 60 minutes after awakening, it is recommended that patients do not drive or use machines for at least 24 hours after administration of Hypnomidato. Hence, a decision to allow for driving or operating machinery must be a judgment made by the post-anaesthesiology treatment team.

The safety of Hypnomidato was evaluated in 812 subjects who participated in 4 open-label clinical trials of Hypnomidato used for the induction of general anaesthesia. These subjects took at least one dose of Hypnomidato and provided safety data. Based on pooled safety data from these clinical trials, the most commonly reported (>5% incidence) adverse drug reactions (ADRs) were (with % incidence) dyskinesia (10.3) and vein pain (7.6).

Including the above-mentioned ADRs, the following table displays ADRs that have been reported with the use of Hypnomidato from either clinical trial or postmarketing experiences.

The displayed frequency categories use the following convention: Very common (>1/10); common (>1/100 to <1/10); uncommon (>1/1,000 to <1/100); rare (>1/10,000 to <1/1,000); very rare (<1/10,000); and not known (cannot be estimated from the available clinical trial data).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via:

Yellow Card Scheme

Website: www.mhra.gov.uk/yellowcard

Symptoms

Overdosing is likely to result in prolonged anaesthesia with the possibility of respiratory depression and even arrest, in which case adequate respiratory support is mandatory. Hypotension has also been observed. Overdosage may depress cortical secretion. This may be associated with disorientation and delayed awakening.

Treatment

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.

Pharmacotherapeutic group: Other general anesthetics, 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.

Adrenal Suppression

Etomidate when used for the introduction of anaesthesia, produces a decrease in plasma cortisol and aldosterone, which remains suppressed for 6-8 hours. These levels usually return to baseline within 24 hours. Etomidate appears to be a specific and reversible inhibitor of the 11-beta-hydroxylation of adrenal steroid synthesis.

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.

In a reproductive fertility study, results showed no effects on fertility or general pregnancy parameters, and no signs of embryotoxicity or teratogenicity. In standard embryotoxicity and teratology studies, some mortality occurred in the high dose groups (5 mg/kg), however, no embryotoxicity or teratogenicity effects were specifically attributed to the test material. Administration of etomidate during the peri- and post-natal period, resulted in some dose-related maternal mortality and toxicity, and attributed to this, some slight decrease in pup survival in the high dose group (5 mg/kg). No adverse effects were observed on pregnancy rate, litter size, birth weight, or body weight gain, and no offspring abnormalities were noted.

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

None stated.