Hypnomidate

Package leaflet: Information for the user

Warning! Keep the leaflet! Information on the immediate packaging in a foreign language.
Hypnomidate, 2 mg/ml, solution for injection
Etomidatum
Please read the entire leaflet carefully before using the medicine, as it contains
important information for the patient.

• Keep this leaflet so that you can read it again if necessary.
• If you have any questions, consult your doctor or pharmacist.
• If you experience any adverse reactions, including any adverse reactions not listed in this leaflet, tell your doctor or pharmacist. 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 in local anaesthesia.
Hypnomidate is indicated for short diagnostic procedures or procedures performed under outpatient conditions where rapid awakening 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 Hypnomidate if the patient is allergic to the active substance or to any of the other ingredients of this medicine (listed in section 6).
If in any doubt whether the above information applies to the patient, consult a doctor or nurse before administering Hypnomidate.

Warnings and precautions
Before starting treatment with Hypnomidate, discuss with a doctor or nurse if:

• the patient has liver disease;
• the patient has low blood pressure, e.g. due to weakness;
• the patient has adrenal insufficiency.

Hypnomidate should be used with caution in patients:

• with adrenal cortex insufficiency, such as in patients with sepsis (severe blood infection);
• with liver cirrhosis or who are taking medicines used in the treatment of certain psychiatric disorders (neuroleptics), strong painkillers (opioids), or sedatives. The dose of etomidate should be reduced.
• of advanced age.

Single induction doses of etomidate may lead to transient adrenal insufficiency and reduced serum cortisol concentration.
Etomidate should be used with caution in critically ill patients, including patients with sepsis, as in some studies this has been associated with an increased risk of death in this patient group.
Hypnomidate should only be administered by a physician trained in endotracheal intubation. Equipment for resuscitation should be available in case respiratory disturbances or apnea occur.
Induction of general anesthesia with Hypnomidate may be accompanied by slight, transient reduction in blood pressure. In weakened patients, the physician will take appropriate preventive measures.
Administration of Hypnomidate may cause spontaneous muscle movements, particularly if premedication (administration of a sedative before the anesthetic) has not been given.
Hypnomidate has no analgesic effect; therefore, during a surgical procedure, an appropriate analgesic should be administered 1–2 minutes before Hypnomidate.

Hypnomidate and other medicines
Inform the doctor or nurse about all medicines currently taken or taken recently by the patient, as well as medicines available without prescription.
The effect of Hypnomidate may be enhanced by:

• neuroleptic medicines (used in the treatment of psychiatric disorders);
• opioids (strong painkillers, e.g. morphine, fentanyl);
• medicines with sedative effect;
• alcohol.

Hypnomidate may enhance the effect of:

• medicines that reduce arterial blood pressure.

Caution is recommended when administering etomidate with alfentanil or fentanyl given intravenously.

Pregnancy, breastfeeding and fertility
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult a doctor before using this medicine.

Pregnancy
Hypnomidate should not be used in pregnant women unless the potential benefits of treatment for the mother outweigh the risks to the fetus. The physician will decide whether to use Hypnomidate.
If the patient suspects she may be pregnant, she should inform the doctor. Some animal studies have shown harmful effects on offspring development.

Breastfeeding
Hypnomidate passes into human milk. Breastfeeding should be avoided during treatment and for 24 hours after administration of Hypnomidate.

Driving and operating machinery
Hypnomidate has a marked effect on the ability to drive and operate machinery.
Operating machinery or driving vehicles is not allowed for 24 hours after administration of this medicine. The time required to return to normal functioning may vary depending on the duration of the procedure, the total dose administered, and other medicines used. Therefore, the anesthesiologist will decide when the patient may resume driving and operating machinery.

Hypnomidate contains propylene glycol
This medicine contains 3626 mg of propylene glycol in 10 ml.
Before administering the medicine to a child under 5 years of age, consult a doctor or pharmacist, especially if the child is taking other medicines containing propylene glycol or alcohol.
Pregnant or breastfeeding women should not take this medicine without a doctor's recommendation. The doctor may decide to perform additional tests in such patients.
Patients with impaired liver or kidney function should not take this medicine without a doctor's recommendation. The doctor may decide to perform additional tests in such patients.

3. How to use Hypnomidate

Hypnomidate is intended for administration only by a physician trained in
endotracheal intubation procedures.
If you have any doubts, please consult a physician.
How Hypnomidate should be administered

• intravenously only – administered as a slow injection;
• Hypnomidate has no analgesic effect; therefore, the patient will receive an appropriate analgesic prior to administration of Hypnomidate.

How much Hypnomidate should be administered
The physician will determine the dose based on:

• type of surgical procedure
• body weight
• age
• general health condition.

The effective dose inducing anesthesia is 0.3 mg/kg body weight. In adult patients, one vial is usually sufficient to induce anesthesia lasting 4–5 minutes.
Anesthesia may be prolonged by administering additional doses of Hypnomidate, but not exceeding a total of 3 vials (30 ml).
Elderly patients
For elderly patients, an initial single dose of 0.15–0.2 mg/kg body weight should be administered, which will then be individually adjusted according to the patient's response (see section 2).
Children and adolescents
In children under 15 years of age, it may be necessary to increase the dose to achieve the same depth and duration of anesthesia as in adults. Occasionally, the dose may need to be increased by approximately 30% above the standard adult dose.
Administration of a higher than recommended dose of Hypnomidate
In case of etomidate overdose administered as a bolus, anesthesia 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 experiences them.
In clinical trials, the most commonly reported adverse reactions were dyskinesia and venous pain.

The adverse reactions listed below (including those mentioned above) were observed during clinical trials or after marketing authorization of the medicine Hypnomidate.

Very common adverse reactions (may affect more than 1 in 10 people):

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

Common adverse reactions (may affect up to 1 in 10 people):

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

Uncommon adverse reactions (may affect up to 1 in 100 people):

• hypertonia (increased muscle tone), 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 rigidity;
• 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 (severe allergic reactions causing breathing difficulties or dizziness) and anaphylactoid reactions;
• adrenal insufficiency;
• seizures (including generalized tonic-clonic seizures);
• cardiac arrest, complete atrioventricular block;
• shock, thrombophlebitis (deep and superficial veins);
• 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, joint pain, and urticaria may also occur);
• trismus (lockjaw).

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can also be reported directly to the Department of Monitoring of Adverse Drug Reactions, 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 .
Reporting adverse reactions helps to provide more information on the safety of this medicine.

5. How to store Hypnomidate

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.
Store below 25°C.
For single use only. After opening the ampoule, any unused portion of the medicine must be discarded.
Medicines must not be disposed of via the sewage system or in household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the packaging and other information

What Hypnomidate contains

• The active substance is etomidate. One ampoule contains 20 mg of etomidate.
• Other ingredients are: propylene glycol and water for injections.

What Hypnomidate looks like and contents of the pack
Hypnomidate is a sterile, clear, colourless aqueous solution for intravenous injection.
Ampoule of 10 ml in a cardboard box.
Pack size: 5 ampoules of 10 ml.
For more detailed information, please contact the marketing authorisation holder or the parallel importer.
Marketing authorisation holder in the Czech Republic, country of export:
Piramal Critical Care B.V., Rouboslaan 32, 2252 TR, Voorschoten, The Netherlands
Manufacturer:
Piramal Critical Care B.V., Rouboslaan 32, 2252 TR, Voorschoten, The Netherlands
Parallel importer:
InPharm Sp. z o.o.
ul. Strumykowa 28/11
03-138 Warsaw
Repackaged in:
InPharm Sp. z o.o. Services sp. k.
ul. Chełmżyńska 249
04-458 Warsaw
Marketing authorisation number in the Czech Republic, country of export: 05/160/80-C
Parallel import authorisation number: 219/20

Information intended exclusively for healthcare professionals:

This medicinal product must be administered only by physicians trained in endotracheal intubation. During administration of Hypnomidate, resuscitation equipment must be readily available in case of respiratory depression or apnea.

Preparation of the medicinal product for administration
Put on protective gloves before opening the ampoule.

Ampoules

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

If the skin is accidentally exposed to the medicinal product, wash the affected area thoroughly with water.
Do not use soap, alcohol, or other cleansing agents, as they may cause chemical or mechanical skin damage.
Any unused medicinal product or waste material must be disposed of in accordance with local regulations. Do not retain any unused portion of the medicinal product for subsequent administration.

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 due to reduced peripheral vascular resistance. In weakened patients, in whom hypotension may be dangerous, the following precautions should be taken:

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

Resuscitation equipment must be readily available during administration of Hypnomidate in case of respiratory depression or apnea.
Etomidate doses used for induction of anesthesia have been shown to reduce plasma cortisol and aldosterone concentrations. In patients under severe stress, particularly those with adrenal cortical dysfunction, cortisol supplementation should be considered.

Prolonged suppression of endogenous cortisol and aldosterone secretion may occur as a direct consequence of etomidate administration via continuous infusion or repeated dosing. Therefore, such administration routes should be avoided.
In these cases, adrenal stimulation with ACTH (adrenocorticotropic hormone) does not produce the desired response.

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 hepatic cirrhosis and in those who have already received a neuroleptic, an opioid, or a sedative agent.

Spontaneous movements of muscles or muscle groups may occur, particularly if premedication has not been administered. These movements are attributed to subcortical disinhibition. They can usually be prevented by intravenous administration of a small dose of fentanyl with diazepam 1–2 minutes before induction with Hypnomidate.

Myoclonic jerks and injection site pain have been observed during administration of Hypnomidate, especially when injected into small veins. These effects can usually be prevented by intravenous administration of a small dose of an appropriate opioid, such as fentanyl, 1–2 minutes prior to 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, sedative agents, 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 medicinal products 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 simultaneously, 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 concomitantly with intravenous fentanyl. A dose reduction of etomidate may be necessary when administered together with intravenous fentanyl.

Effect of etomidate on other medicinal products
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, sedation 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 respiration 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 (but not adrenocorticotropic hormone – ACTH) may be necessary. General supportive measures and close monitoring are recommended.