Fentanyl Kalceks 50 micrograms/ml solution for injection EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Fentanilo Kalceks 50 micrograms/ml injectable solution EFG

fentanyl

Read the entire leaflet carefully before you start using this medicine, as it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor or nurse.
• This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it could harm them.
• If you experience any adverse effects, consult your doctor or nurse, even if these effects are not listed in this leaflet. See section 4.

Leaflet contents

1. What Fentanilo Kalceks is and what it is used for
2. What you need to know before you are given Fentanilo Kalceks
3. How Fentanilo Kalceks is administered
4. Possible side effects
5. How to store Fentanilo Kalceks
6. Contents of the pack and other information

1. What Fentanilo Kalceks is and what it is used for

Fentanilo Kalceks 50 microgramos/ml, solution for injection, is a liquid that is injected. Fentanilo is the active substance that relieves pain and is responsible for the effect of this medicine. Fentanilo belongs to a group of strong narcotic painkillers, also known as opioid analgesics.

This medicine will be administered during surgery to ensure you do not feel pain.

2. What you need to know before Fentanilo Kalceks is administered to you

Do not be given Fentanilo Kalceks

• if you are allergic to fentanyl or to any of the other ingredients of this medicine (listed in section 6). Also, if you are hypersensitive to other strong opioid analgesics (narcotics), you should not receive this medicine.
• if your lungs do not function normally (without mechanical ventilation).

Warnings and precautions

After administration of this medicine, your breathing may become excessively slow or weak. It is important that you inform your doctor immediately if this happens. Since this may also occur during the postoperative period, you will be under observation during this time.

Before Fentanilo Kalceks is administered to you, consult your doctor or nurse if:

• you have liver, kidney, or thyroid insufficiency;
• you have lung or respiratory disease;
• you consume alcohol or drugs;
• you have any muscle disorders (myasthenia gravis);
• you are taking certain medications for depression (see “Other medicines and Fentanilo Kalceks”);
• you are elderly or debilitated, or if you are a child (see section 3);
• you or a family member has ever abused or been dependent on alcohol, prescription medicines, or illegal drugs (“addiction”);
• you are a smoker;
• you have ever had problems with your mood (depression, anxiety, or a personality disorder), or if you have been treated by a psychiatrist for another mental illness.

Inform your doctor if any of these warnings apply to you. Close medical monitoring may be necessary when this medicine is administered. A dose adjustment may also be required.

Repeated use of opioid analgesics may cause the medicine to lose effectiveness (you may become tolerant to it). It may also lead to dependence and abuse, which could result in a potentially fatal overdose. If you are concerned about the possibility of becoming dependent on Fentanilo Kalceks, it is important to consult your doctor.

If treatment is discontinued, withdrawal symptoms may occur. Inform your doctor or nurse if you think this is happening to you (see also section 4. Possible side effects).

Children

There is no experience with the use of this medicine in children under 2 years of age. Therefore, administration of this medicine is not recommended in children under 2 years.

Other medicines and Fentanilo Kalceks

Inform your doctor or nurse if you are taking, have recently taken, or might need to take any other medicines, including those obtained without a prescription.

This is especially important for the medicines listed below, as it may be necessary to adjust the dose of this or other medicines, or closer monitoring may be required.

Inform your doctor if you are taking or have recently taken:

• certain medicines for treating depression:

• selective serotonin reuptake inhibitors (SSRIs);

• serotonin-norepinephrine reuptake inhibitors (SNRIs);

• monoamine oxidase inhibitors (MAOIs).

If used together, these may cause changes in mood (e.g., agitation, hallucinations [perceiving things that are not there], coma), body temperature above 38°C, rapid heartbeat, unstable blood pressure, hyperactive reflexes, muscle rigidity, lack of coordination, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Your doctor will determine whether this medicine is suitable for you.

If you are taking an MAO inhibitor, your doctor will discontinue treatment with these medicines at least 2 weeks before administering this medicine, whenever possible.

• long-term use of strong analgesics;
• certain analgesics for neuropathic pain (gabapentin and pregabalin);
• medicines for treating psychosis or Parkinson’s disease;
• sleeping pills;
• tranquilizers;
• antiepileptic medicines (e.g., carbamazepine or phenytoin);
• medicines for reducing anxiety;
• medicines for certain mental illnesses;
• medicines for fungal infections (e.g., fluconazole or voriconazole);
• ritonavir (a medicine for treating HIV infection). If you are given a single dose of fentanyl, your doctor will be especially vigilant and may prescribe a lower dose for prolonged use.

Fentanilo Kalceks with alcohol

Inform your doctor if you are using or have recently used alcohol or drugs.

Alcohol may increase certain effects of this medicine. This medicine may also influence the effect of alcohol. For these reasons, do not drink alcohol before receiving this medicine or on the day after administration.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

Pregnancy

There is insufficient knowledge about whether the use of this medicine is harmful during pregnancy. The use of fentanyl is not recommended during childbirth, including cesarean section, as it may cause respiratory problems in the newborn.

Breastfeeding

The active substance of this medicine passes into breast milk. Therefore, breastfeeding is not recommended during the first 24 hours after administration of this medicine. Do not use breast milk expressed within 24 hours after administration of this medicine. Talk to your doctor.

Driving and using machines

Do not drive a car or operate any vehicle, and do not use machines or tools for at least 24 hours after receiving this medicine, as this medicine may affect your alertness and ability to drive. Your doctor will decide when you can drive again or operate dangerous machinery after receiving this medicine.

Use in athletes

Athletes are advised that this medicine contains a component that may result in a positive analytical finding in doping controls.

Fentanilo Kalceks contains sodium

This medicine contains less than 23 mg of sodium (1 mmol) per 2 ml vial; this is essentially “sodium-free”.

This medicine contains 35.41 mg of sodium (main component of cooking/table salt) per 10 ml vial. This corresponds to 1.78% of the maximum recommended daily dietary intake of sodium for an adult.

3. How Fentanilo Kalceks is administered

This medicine is administered by injection into a vein.

Dosage

It is important that you receive the correct amount of this medicine. The dose may vary depending on age, body weight, physical condition, underlying diseases, concomitant medications, and the type of anaesthesia and surgical procedure. Your doctor will determine the correct dose for you.

Adults

Typically, 4–12 ml of this medicine is administered just before the surgical procedure. If considered necessary by the doctor, an additional dose may be given later.

Elderly and debilitated patients

The dose administered to elderly patients (65 years of age or older) or debilitated patients just before surgery is lower than that indicated for other adults. If considered necessary by the doctor, an additional dose may be given later.

Children aged 2 years and older

The dose administered to children just before surgery depends on the child's weight. If considered necessary by the doctor, an additional dose may be given later.

Adolescents aged 12 to 17 years receive the same dose as adults.

Children under 2 years of age

There is no experience with the use of this medicine in children under 2 years of age. Therefore, administration of this medicine is not recommended in this age group.

Patients with renal problems

The doctor may decide to reduce the dose administered to patients with renal problems.

Obese patients

The dose administered to obese patients just before surgery may be lower than that indicated for other adults. If considered necessary by the doctor, an additional dose may be given later.

If you use more Fentanilo Kalceks than you should

Since this medicine will be administered by a healthcare professional, it is unlikely that you will receive too much. However, inform your doctor or nurse immediately if you experience shallow or slow breathing, or if your breathing stops temporarily.

An overdose may result in brain disorder (known as toxic leukoencephalopathy).

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service at 91 562 04 20, indicating the medicine and the amount ingested.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.

Some adverse effects may be serious. If you experience any of the side effects listed below, your doctor must decide whether your treatment should be stopped immediately:

Frequency not known (cannot be estimated from available data):

• anaphylactic shock (a severe allergic reaction to certain substances, in which the following occur as a result of sudden and severe dilation of blood vessels: sudden drop in blood pressure, pallor, restlessness, weak and rapid pulse, moist skin, and loss of consciousness);
• serotonin syndrome (a syndrome characterized by features such as restlessness, hallucinations, coma, palpitations, unstable blood pressure, elevated body temperature, increased response to stimuli, poor coordination, rigidity, nausea, vomiting, and diarrhea).

Other side effects. Inform your doctor or nurse if any of these adverse effects worsen:

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

• nausea, vomiting;
• muscle rigidity.

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

• involuntary movements, drowsiness, dizziness;
• visual disturbances;
• slow heart rate, fast heart rate, heart rhythm disorders;
• decreased blood pressure, increased blood pressure, vein pain;
• spasms of the vocal cords, difficulty breathing due to spasms of the muscles in the airways, shallow or interrupted breathing;
• allergic skin inflammation;
• postoperative confusion, nervous system disturbances due to anesthesia.

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

• agitation or euphoric mood;
• headache;
• superficial vein inflammation, fluctuations in blood pressure;
• hyperventilation, hiccups;
• difficulty swallowing;
• chills, low body temperature;
• respiratory problems due to anesthesia, postoperative agitation, complications resulting from the surgical procedure.

Frequency not known (cannot be estimated from available data):

• hypersensitivity (including itchy rash and widespread hives (urticaria); hypersensitivity to the medicine's components may cause a severe reaction in which blood vessels suddenly widen, causing low blood pressure and a rapid but weak heartbeat, manifesting as pallor, restlessness, and moist skin);
• delirium (symptoms may include a combination of agitation, restlessness, disorientation, confusion, fear, seeing or hearing things that are not really there, sleep disturbances, nightmares);
• seizures, loss of consciousness, sudden muscle contractions (myoclonus);
• cardiac arrest;
• decreased strength, depth, or frequency of breathing;
• itching;
• withdrawal syndrome symptoms (may manifest as the appearance of the following side effects: nausea, vomiting, diarrhea, anxiety, chills, tremor, and sweating).

Cases of serotonin syndrome have been reported when fentanyl was used together with certain medicines for depression (see section "Other medicines and Fentanilo Kalceks").

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor or nurse, even if they are adverse effects not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicines: www.notificaRAM.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Fentanilo Kalceks Storage

Keep this medicine out of sight and reach of children.

Store in the original packaging to protect from light. Do not freeze.

Do not use this medicine after the expiry date stated on the outer packaging or on the ampoule following EXP. The expiry date refers to the last day of the month indicated.

Medicines must not be disposed of via wastewater or household waste. If you have any doubts, ask your pharmacist how to dispose of medicines and packaging no longer required. This will help protect the environment.

6. Contents of the pack and other information

Composition of Fentanilo Kalceks

• The active substance is fentanyl (as fentanyl citrate).

Each ml of solution contains 50 micrograms of fentanyl (as fentanyl citrate).

Each 2 ml ampoule contains 100 micrograms of fentanyl (as fentanyl citrate).

Each 10 ml ampoule contains 500 micrograms of fentanyl (as fentanyl citrate).

• The other components are sodium chloride, sodium hydroxide (for pH adjustment), water for injections. This medicine does not contain preservatives.

Appearance of Fentanilo Kalceks and contents of the pack

Clear, colourless, injectable solution free from visible particles.

10 glass ampoules of 2 ml
10 glass ampoules of 10 ml

Only certain pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

AS KALCEKS
Krustpils iela 71E, Riga, LV-1057, Latvia
Tel.: +371 67083320
E-mail: [email protected]

For further information about this medicine, please contact the local representative of the Marketing Authorisation Holder

EVER Pharma Therapeutics Spain SL
Toledo 170,
28005 Madrid
Spain

This medicine is authorised in the member states of the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:

Netherlands Fentanyl Kalceks 0.05 mg/ml solution for injection
Austria Fentanyl Kalceks 50 microgramm/ml Injektionslösung
Bulgaria Fentanyl Kalceks 50 ??????????/ml ??????????? ???????
Croatia Fentanil Kalceks
Denmark Fentanyl Kalceks
Estonia Fentanyl Kalceks
Finland Fentanyl Kalceks
Germany Fentanyl Kalceks 50 Mikrogramm/ml Injektionslösung
Greece FENTANYL/KALCEKS
Hungary Fentanyl Kalceks 50 mikrogramm/ml oldatos injekció
Ireland Fentanyl 50 micrograms/ml solution for injection
Italy Fentanil Kalceks
Norway Fentanyl Kalceks
Romania Fentanil Kalceks 50 micrograme/ml solutie injectabila
Slovakia Fentanyl Kalceks 50 mikrogramov/ml injekcný roztok
Slovenia Fentanil Kalceks 50 mikrogramov/ml raztopina za injiciranje
Spain Fentanilo Kalceks 50 microgramos/ml solución inyectable EFG
Sweden Fentanyl Kalceks
United Kingdom (Northern Ireland) Fentanyl 50 micrograms/ml solution for injection

Date of the most recent revision of this leaflet: March 2024

Detailed and up-to-date information on this medicine is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS) http://www.aemps.gob.es/.

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This information is intended for healthcare professionals only:

Refer to the Summary of Product Characteristics or Technical Data Sheet for a complete description and further information.

Therapeutic indications

Fentanilo Kalceks 50 micrograms/ml is an analgesic and anaesthetic:

• for use as an opioid analgesic adjunct in general or local anaesthesia;
• for administration with a neuroleptic.

Posology and method of administration

Fentanilo Kalceks 50 micrograms/ml must only be administered in a setting where airway control is possible and by professionals capable of monitoring the airway (see Summary of Product Characteristics section 4.4).

The dose of Fentanilo Kalceks 50 micrograms/ml must be individually determined according to age, body weight, physical condition, underlying pathological condition, use of other drugs, and type of surgical procedure and anaesthesia.

Adults

For induction of anaesthesia, intravenous doses of 200 to 600 micrograms (2.8 to 8.5 micrograms/kg), corresponding to 4–12 ml, are usually administered. Doses exceeding 200 micrograms should only be given with ventilation support. Additional intravenous doses of 50 to 200 micrograms (0.7 to 2.8 micrograms/kg), corresponding to 1–4 ml, may be administered every 30 to 45 minutes to maintain analgesia.

Paediatric population

Adolescents aged 12 to 17 years

Follow the adult dose recommendations.

Children aged 2 to 11 years

For induction of anaesthesia in children, a dose of 1.25–2.5 micrograms/kg or 0.25–0.5 ml per 10 kg of body weight is generally recommended. For maintenance of analgesia, additional intravenous doses of 0.25 ml per 10 kg may be administered every 30–45 minutes.

Children under 2 years of age

There is no experience with fentanyl use in children under 2 years of age.

Use in children

In children with spontaneous respiration, analgesic techniques should only be used as part of an anaesthetic technique or administered as part of a sedation/analgesia regimen by experienced personnel in a setting that allows management of sudden muscle rigidity (requiring intubation) or apnoea (requiring ventilation) (see Summary of Product Characteristics section 4.4).

Use in the elderly

As with other opioids, the initial dose for elderly patients (>65 years) and debilitated patients should be reduced. The effect of the initial dose should be taken into account when determining additional doses.

Use in patients with renal impairment

In patients with renal impairment, a reduction in the dose of Fentanilo Kalceks 50 micrograms/ml should be considered, and these patients should be carefully monitored for signs of fentanyl toxicity (see Summary of Product Characteristics section 5.2).

Use in obese patients

In obese patients, there is a risk of overdose if the dose is calculated based on total body weight. The dose for obese patients (BMI >30 kg/m²) should be calculated based on estimated lean body mass rather than total body weight. Any subsequent dose adjustments should be made cautiously based on response (see Summary of Product Characteristics section 5.2).

Method of administration

Administer by slow intravenous injection (over 1–2 minutes).

Contraindications

• Hypersensitivity to the active substance or to any of the excipients listed in section 6, or to other opioids.
• Respiratory insufficiency without mechanical ventilation, due to the specific respiratory depressant effect of morphine-like drugs.

Special warnings and precautions for use

• Fentanyl must only be administered in a setting where airway control is possible and by professionals capable of monitoring the airway.
• As with all potent opioids, fentanyl may cause dose-dependent respiratory depression. After administration of doses exceeding 200 micrograms of fentanyl (4 ml), significant respiratory depression will occur. This pharmacological effect can be reversed by naloxone, a specific opioid antagonist. Repeated doses of the antagonist may occasionally be required, as respiratory depression may last longer than the action of these antagonists. Deep analgesia is accompanied by manifest respiratory depression, which may persist or recur in the postoperative period. Therefore, it is important that patients remain under appropriate monitoring. Resuscitation equipment and opioid antagonists must be immediately available. Hyperventilation during anaesthesia may alter the patient's response to CO2, thereby affecting respiration in the postoperative period.
• Muscle rigidity may occur, which may lead to respiratory depression. The incidence can be reduced by slow intravenous injection (which is usually sufficient for low doses). The reaction can be managed with mechanical ventilation, premedication with a benzodiazepine, and, if necessary, administration of muscle relaxants.
• Anaphylactic reaction may occur when fentanyl is administered.
• Non-epileptic myoclonic movements may occur.
• Bradycardia and cardiac failure may occur if the patient receives insufficient anticholinergic medication or when this medicine is combined with non-vagolytic muscle relaxants. Bradycardia can be treated with atropine.
• Opioids may cause hypotension, especially in patients with hypovolaemia. Appropriate measures should be taken to maintain stable blood pressure.
• Rapid (bolus) injection of opioid should be avoided. In patients with impaired cerebral distensibility, the transient reduction in mean arterial pressure has sometimes been associated with a short-term reduction in cerebral blood flow.
• Patients receiving chronic opioid therapy or those with opioid addiction may require higher doses.
• Dose reduction is recommended in elderly or debilitated patients. In cases of uncontrolled hypothyroidism, pulmonary disease, respiratory insufficiency or alcoholism, opioid dosage should be carefully adjusted, as well as in patients with hepatic impairment due to possible altered metabolism. Patients with renal impairment should be carefully monitored for any signs of fentanyl toxicity. The volume of distribution of fentanyl may vary as a result of dialysis, which may affect plasma concentrations. These patients should undergo prolonged postoperative observation.
• If this medicine is administered together with neuroleptics, the healthcare professional must be familiar with the specific properties of each drug, particularly differences in duration of action. The risk of hypotension is higher when this combination is used. Neuroleptics may cause extrapyramidal symptoms, which can be counteracted with antiparkinsonian agents, although combining these may increase the risk of tardive dyskinesia.
• As with other opioids, due to anticholinergic effects, fentanyl administration may cause increased pressure in the biliary tract and, occasionally, spasms of the sphincter of Oddi may be observed.
• In patients with myasthenia gravis, the use of certain anticholinergics and neuromuscular blockers should be carefully considered before and during the administration of a general anaesthesia regimen including intravenous fentanyl.
• Caution is required when administering this medicine concomitantly with drugs affecting serotonergic neurotransmitter systems.

Concomitant use of serotonergic drugs, such as SSRIs and serotonin-norepinephrine reuptake inhibitors (SNRIs), and drugs affecting serotonin metabolism (including monoamine oxidase inhibitors [MAOIs]), may result in a potentially life-threatening serotonin syndrome. This may occur even at recommended doses.

Serotonin syndrome may include changes in mental status (e.g., agitation, hallucinations, or coma), autonomic instability (e.g., tachycardia, labile blood pressure, or hyperthermia), neuromuscular abnormalities (e.g., hyperreflexia, lack of coordination, or rigidity), and/or gastrointestinal symptoms (e.g., nausea, vomiting, or diarrhoea).

If serotonin syndrome is suspected, rapid discontinuation of treatment with this medicine should be considered.

Tolerance and opioid use disorder (abuse and dependence)

Tolerance, physical and psychological dependence may occur after repeated administration of opioids.

Repeated use of opioids may lead to opioid use disorder (OUD). Intentional abuse or misuse of opioids may cause overdose and/or death. The risk of developing OUD increases in patients with personal or family history (parents or siblings) of substance use disorders (including alcohol use disorder), in active smokers, or in patients with personal history of other mental health disorders (e.g., major depression, anxiety, and personality disorders).

Withdrawal syndrome

Repeated administration at short intervals over prolonged periods may lead to the development of a withdrawal syndrome after discontinuation of treatment, which may manifest as the following adverse effects: nausea, vomiting, diarrhoea, anxiety, chills, tremors, and sweating.

Paediatric population

In children with spontaneous respiration, analgesic techniques should only be used as part of an anaesthetic technique or administered as part of a sedation/analgesia regimen by experienced personnel in a setting that allows management of sudden muscle rigidity (requiring intubation) or apnoea (requiring ventilation).

Use in athletes

This medicine contains fentanyl, which may result in a positive doping test.

Excipients

This medicine contains:

7.08 mg of sodium, less than 23 mg of sodium (1 mmol) per 2 ml ampoule, which is essentially "sodium-free".

35.41 mg of sodium per 10 ml ampoule, equivalent to 1.78% of the maximum daily intake recommended by the WHO of 2 g of sodium for an adult.

Interaction with other medicines and other forms of interaction

Effect of other medicines on fentanyl

MAO inhibitors and other serotonergic drugs

Concomitant administration of fentanyl with MAO inhibitors may cause paroxysmal stimulation of the CNS and hypertension. Concomitant use should be avoided, and if possible, treatment with MAO inhibitors should be discontinued at least 2 weeks before initiating therapy with this medicine.

Concomitant use of fentanyl with serotonergic drugs, such as SSRIs and SNRIs, and with monoamine oxidase inhibitors (MAOIs) may increase the risk of developing a potentially life-threatening serotonin syndrome.

If concomitant use of this medicine with SSRIs, SNRIs or MAOIs is unavoidable, patients should be monitored for symptoms of serotonin syndrome during coadministration.

The use of barbiturates, benzodiazepines, neuroleptics, halogenated gases, gabapentinoids (gabapentin and pregabalin), and other non-selective CNS depressants (including alcohol) may potentiate the respiratory depression caused by opioids. If patients have received CNS depressants, the required dose of fentanyl will be lower than usual.

Fentanyl, a high-clearance active substance, is rapidly and extensively metabolised by CYP3A4. Itraconazole (a potent CYP3A4 inhibitor) administered orally at 200 mg/day for four days did not exert a significant effect on the pharmacokinetics of intravenous fentanyl. Oral administration of ritonavir (one of the most potent CYP3A4 inhibitors) reduced the clearance of intravenously administered fentanyl by two-thirds. However, maximum plasma concentrations were not affected after administration of a single intravenous dose of fentanyl.

Co-administration of fluconazole or voriconazole with fentanyl may increase fentanyl exposure by approximately 25% to 40%. Close monitoring of patients and dose adjustment of fentanyl as necessary are required during combined use of fluconazole or voriconazole and fentanyl.

Special attention and patient observation are required when using potent CYP3A4 inhibitors such as ritonavir concomitantly with a single oral dose of fentanyl. With continuous administration, it may be necessary to reduce the fentanyl dose to avoid accumulation, which in certain cases increases the risk of prolonged or delayed respiratory depression.

Cytochrome P450 3A4 (CYP3A4) inducers

An injection of fentanyl administered together with potent CYP3A4 inducers (e.g., carbamazepine or phenytoin) may decrease fentanyl plasma concentrations, thereby reducing its efficacy. Patients should be closely monitored for signs of reduced analgesic effect if fentanyl is used with a strong CYP3A4 inducer. Increasing the fentanyl dose may also be considered if necessary.

Effects of fentanyl on other medicines

Concomitant use of other drugs with central nervous system depressant effects, such as opioids, sedatives, hypnotics, general anaesthetics, phenothiazines, tranquilisers, muscle relaxants, sedating antihistamines, and alcoholic beverages, may produce additive depressant effects and may lead to hypoventilation, hypotension, and profound sedation or coma. Therefore, the use of fentanyl with any of the above-mentioned medicines requires special attention and patient monitoring.

With concomitant use of fentanyl, plasma concentrations of etomidate increased considerably (by a factor of 2–3). During simultaneous use, total plasma clearance and volume of distribution of etomidate decrease by a factor of 2 to 3, without any change in half-life.

Concomitant administration of fentanyl and intravenous midazolam results in an increased terminal plasma half-life and decreased plasma elimination of midazolam. Exposure to midazolam increases by approximately 50%. The mechanism of interaction is competitive inhibition of CYP3A4 (see Summary of Product Characteristics section 5.2). When midazolam is administered together with fentanyl, the midazolam dose may need to be reduced.

Incompatibilities

This medicine must not be mixed with other medicines.

Special precautions for disposal and other handling

For single use only. If only partially used, discard the remaining solution.

Protect fingers when opening an ampoule.

After first opening: the medicine should be used immediately.

Instructions for opening the ampoule:

1. Hold the ampoule with the coloured dot facing upwards. If any solution remains in the upper part of the ampoule, gently tap with the finger to allow all solution to flow down to the bottom.
2. Use both hands to open it: while holding the lower part of the ampoule with one hand, use the other hand to break the top part of the ampoule in the direction opposite to the coloured dot (see images below).

Disposal of unused medicine and all materials that have come into contact with it should be carried out in accordance with local regulations.