Hypnomidate

Package leaflet: Information for the user

Hypnomidate, 2 mg/ml, solution for injection
Etomidatum
Please read all of this leaflet carefully before use, as it contains important information for the patient.

• Keep this leaflet for future reference.
• If you have any questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not share it with others. This medicine may harm others, even if their symptoms are the same.
• If the patient experiences any adverse reactions, including any not listed in this leaflet, inform a doctor, pharmacist, or nurse immediately. See section 4.

Table of contents

1. What Hypnomidate is and what it is used for
2. Important information before using Hypnomidate
3. How to use Hypnomidate
4. Possible side effects
5. How to store Hypnomidate
6. Contents of the pack and other information

1. What Hypnomidate is and what it is used for

The active substance in Hypnomidate is etomidate.
Hypnomidate is indicated for induction of general anaesthesia, as well as for supplemental anaesthesia during local anaesthesia.
Hypnomidate is indicated for short diagnostic procedures or interventions performed under outpatient conditions where rapid recovery of the patient is required.
Hypnomidate is particularly indicated in cardiac surgery and in patients with heart disease.

2. Important information before using Hypnomidate

When not to use Hypnomidate
Do not use this medicine if the patient is allergic to the active substance or to any of the other ingredients of this medicine (listed in section 6).
An allergic reaction may present as: rash, itching, facial and lip swelling, shortness of breath.
All such reactions should be reported immediately to a doctor.

Warnings and precautions
Hypnomidate should be used with caution in patients:

• with adrenal insufficiency, such as patients with sepsis;
• with liver cirrhosis;
• who are receiving neuroleptic drugs, opioids, or sedatives (see below – Hypnomidate and other medicines);
• who are elderly.

Single induction doses of etomidate may lead to transient adrenal insufficiency and reduced serum cortisol concentrations.
Etomidate should be used with caution in critically ill patients, including those with sepsis, as in some studies it has been associated with increased mortality risk in this patient group.
Hypnomidate must be administered only by physicians trained in endotracheal intubation. Resuscitation equipment must be available in case respiratory disturbances or apnea occur.
Initiation of general anesthesia with Hypnomidate may be accompanied by a slight, transient decrease in blood pressure. In weakened patients, the physician should take appropriate corrective measures.
Use of Hypnomidate may be associated with occurrence of spontaneous muscle movements, particularly if premedication (administration of a sedative prior to the anesthetic) has not been given.
Hypnomidate has no analgesic effect; therefore, an appropriate analgesic should be administered 1–2 minutes before injection of Hypnomidate during surgical procedures.

Hypnomidate and other medicines
Inform your doctor or pharmacist about all medicines currently used or recently used, including those obtained without a prescription.
The effect of Hypnomidate may be enhanced by:

• neuroleptic drugs – used in the treatment of psychiatric disorders;
• opioids – pain-relieving medicines, e.g. morphine, fentanyl;
• sedative medicines;
• alcohol.

Hypnomidate may potentiate the effect of:

• antihypertensive medicines (medicines that lower blood pressure).

Pregnancy, breastfeeding and fertility
If the patient is pregnant, breastfeeding, suspects she may be pregnant, or is planning to become pregnant, she should consult a doctor before using this medicine. The doctor will then decide whether to administer Hypnomidate.
Breastfeeding should not be performed during treatment and for 24 hours after administration of Hypnomidate.
Animal fertility studies have not shown that Hypnomidate, when used at recommended doses, affects fertility.

Driving and operating machinery
Hypnomidate has a marked influence on the ability to drive and operate machinery. Operating potentially dangerous machinery or driving vehicles is not recommended within the first 24 hours after administration. The time required to return to normal functioning may vary depending on the duration of the procedure, the total dose administered, and other concomitant medications used. Therefore, the decision to allow the patient to drive or operate machinery must be made by the anesthesiologist.

Hypnomidate contains propylene glycol
Hypnomidate contains propylene glycol, which may cause skin irritation.

3. How to use Hypnomidate

Hypnomidate is intended for administration only by trained medical personnel.
In case of doubt, consult a physician.
How Hypnomidate should be administered:

• intravenously only – by slow injection or infusion;
• may be diluted with physiological saline or glucose solution;

How much Hypnomidate should be administered
The dose is determined by the physician, depending on:

• type of surgical procedure,
• body weight,
• age,
• general health status.

The effective dose inducing sleep is 0.3 mg/kg body weight. Therefore, in adult patients, one ampoule is usually sufficient to induce sleep lasting 4–5 minutes.
Sleep may be prolonged by administering additional doses of Hypnomidate, up to a maximum of 3 ampoules (30 ml).
Elderly patients
In elderly patients, the initial single dose is 0.15–0.2 mg/kg body weight, which will then be individually adjusted according to the patient's response (see section 2. Important information before using Hypnomidate).
Children
In children under 15 years of age, an increased dose may be necessary to achieve the same depth of sleep and duration as in adults. Sometimes, the dose may need to be increased by approximately 30% compared to the standard adult dose.
Administration of a higher than recommended dose of Hypnomidate
In case of etomidate overdose administered as a bolus, sleep becomes deeper and hypotension, adrenal cortical suppression, respiratory depression, or even respiratory arrest may occur. If respiratory arrest occurs, appropriate measures to support breathing must be taken immediately. Disorientation and prolonged emergence may also occur.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
In clinical trials, the most commonly reported adverse reactions were dyskinesia and venous pain.
The adverse reactions listed below (including those mentioned above) have been observed during
administration of Hypnomidate in clinical trials or after marketing authorization.

Very common adverse reactions (may affect at least 1 in 10 patients):

• dyskinesia (movement disorders);
• decreased cortisol levels.

Common adverse reactions (may affect less than 1 in 10 patients):

• myoclonic muscle jerks;
• venous pain, hypotension (low blood pressure);
• apnoea, hyperventilation (accelerated or deepened breathing), stridor;
• vomiting, nausea;
• rash.

Uncommon adverse reactions (may affect less than 1 in 100 patients):

• hypertonia (increased muscle tension), involuntary muscle contractions, nystagmus;
• bradycardia (slow heart rate), extrasystoles, ventricular extrasystoles;
• phlebitis, hypertension (high blood pressure);
• hypoventilation (slowed and weakened breathing), hiccups, cough;
• excessive salivation;
• erythema;
• muscle stiffness;
• injection site pain;
• anaesthesia complications, delayed recovery of consciousness after anaesthesia, inadequate analgesic effect, nausea during procedures.

Adverse reactions with unknown frequency (frequency cannot be estimated from available data):

• hypersensitivity reactions (including anaphylactic shock (sudden circulatory failure), anaphylactic reactions (severe allergic reactions causing breathing difficulties or dizziness), and pseudo-anaphylactic reactions);
• adrenal insufficiency;
• seizures (including generalized tonic-clonic seizures);
• cardiac arrest, complete atrioventricular block;
• shock, thrombophlebitis (deep and superficial);
• respiratory depression, bronchospasm (including fatal cases);
• Stevens-Johnson syndrome (characterized by transient blisters on mucous membranes, mainly in the oral cavity and genital organs, which rupture and form painful erosions making feeding difficult. Fever and joint pain may also occur), urticaria;
• trismus (lockjaw).

Reporting of adverse reactions
If any adverse symptoms occur, including any possible adverse reactions not listed in this leaflet, inform your doctor, pharmacist, or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C, 02-222 Warsaw
Tel.: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions may also be reported to the marketing authorization holder or parallel importer.
Reporting adverse reactions helps provide more information on the safety of this medicine.

5. How to store the medicine Hypnomidate

Store below 25°C.
Keep the medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the stated month.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Contents of the pack and other information

What Hypnomidate contains

• The active substance is etomidate. Hypnomidate ampoules contain 10 ml (20 mg etomidate) of ready-to-use solution (2 mg etomidate per 1 ml of solution).
• Other excipients: propylene glycol and water for injections.

What Hypnomidate looks like and contents of the pack
A 10 ml ampoule containing a sterile, clear, colourless aqueous solution for intravenous injection.
One pack contains 5 ampoules of 10 ml each.
For more detailed information, please contact the responsible party or parallel importer.
Marketing Authorisation Holder in the Czech Republic, country of export, and Manufacturer:
Piramal Critical Care B.V.
Rouboslaan 32, 2252 TR, Voorschoten
The Netherlands
Parallel Importer:
Swiss2Care Sp. z o.o. Sp. k.
ul. Mostowa 38/1
87-100 Toruń
Repackaged in:
CEFEA Sp. z o.o. Sp. k.
ul. Działkowa 56
02-234 Warsaw
Marketing Authorisation Number in the Czech Republic, country of export: 05/160/80-C
Parallel Import Licence Number: 380/22

THE FOLLOWING INFORMATION IS INTENDED FOR PROFESSIONAL

MEDICAL PERSONNEL ONLY
This product must be administered exclusively by physicians trained in endotracheal intubation. When using Hypnomidate, resuscitation equipment must be readily available in case of respiratory depression or apnea.

1. Preparation of the medicinal product for use

Put on protective gloves before opening the ampoule.
Ampoules

1. Hold the ampoule between the thumb and index finger, leaving the neck end free.
2. With the other hand, grasp the neck end, placing the index finger against the tip and the thumb on the colored dot aligned with the colored ring at the end of the ampoule.
3. While keeping the thumb on this spot, firmly snap off the ampoule tip, holding the rest of the ampoule securely with the other hand.

If accidental skin exposure occurs, wash the affected area thoroughly with water. Avoid using soap, alcohol, or other cleansing agents, which may cause chemical or mechanical skin damage.

2. Special warnings and precautions for use

Hypnomidate must be administered intravenously only.
Induction of anesthesia with Hypnomidate may be accompanied by a slight, transient decrease in blood pressure, related to reduced peripheral vascular resistance. In debilitated patients, where hypotension may be hazardous, the following precautionary measures should be taken:

1. The patient should be in the supine position during induction.
2. Secure venous access to ensure adequate circulating blood volume.
3. Hypnomidate should be injected slowly (e.g., 10 ml over 1 minute).
4. If possible, avoid concomitant use of other induction agents.

Resuscitation equipment must be available when administering Hypnomidate, in case of respiratory depression or apnea.
Etomidate doses used for anesthesia induction have been associated with decreased plasma cortisol and aldosterone concentrations. In patients under severe stress, particularly those with adrenal cortical dysfunction, cortisol supplementation should be considered.
A direct consequence of etomidate, when administered as a continuous infusion or in repeated doses, may be prolonged suppression of endogenous cortisol and aldosterone secretion. Therefore, this mode of administration should be avoided.
In such cases, adrenal stimulation with ACTH (adrenocorticotropic hormone) does not yield the desired results.
Etomidate should be used with caution in patients with pre-existing adrenal cortical insufficiency, such as those with sepsis.
The dose of etomidate should be reduced in patients with liver cirrhosis and in those who have already received a neuroleptic, an opioid, or a sedative drug.
Spontaneous muscle movements or myoclonic jerks may occur, especially if premedication has not been administered. These movements are attributed to subcortical disinhibition. They can usually be prevented by administering a small intravenous dose of fentanyl with diazepam 1–2 minutes before induction with Hypnomidate.
During administration of Hypnomidate, myoclonic seizures and injection site pain have been observed, particularly when injected into small veins. This can usually be prevented by administering a small intravenous dose of an appropriate opioid, e.g., fentanyl, 1–2 minutes before induction.
Caution should be exercised when administering Hypnomidate to elderly patients, as it may reduce cardiac output, particularly when doses higher than recommended are used.
Hypnomidate has no analgesic effect; therefore, an appropriate analgesic should be administered during surgical procedures.
Neuroleptics, opioids, sedatives, and alcohol may potentiate the hypnotic effect of etomidate.
Etomidate induction may be accompanied by mild and transient reduction in peripheral resistance, which may enhance the effect of other drugs that lower arterial blood pressure.

Effect of other drugs on etomidate
Concomitant administration of etomidate with alfentanil reduces the terminal half-life of etomidate to 29 minutes. Caution is advised when using etomidate and alfentanil together, as etomidate concentrations may fall below the hypnotic threshold.
The total plasma clearance and volume of distribution of etomidate are reduced by 2 to 3 times without affecting its half-life when administered with intravenous fentanyl. A dose reduction of etomidate may be necessary when co-administered with intravenous fentanyl.

Effect of etomidate on other drugs
Concomitant administration of etomidate and ketamine does not significantly affect the plasma concentrations or pharmacokinetic parameters of ketamine or its main metabolite, norketamine.

3. Overdose

In case of etomidate overdose administered as a bolus, sleep becomes deeper and may be accompanied by hypotension, adrenal cortical suppression, respiratory depression, or even respiratory arrest. In the event of respiratory arrest, appropriate measures to support breathing must be initiated immediately. Disorientation and prolonged emergence may also occur.
In addition to supportive measures (e.g., assisted ventilation), administration of 50 mg–100 mg hydrocortisone (rather than adrenocorticotropic hormone – ACTH) may be necessary.