Midazolam Accord 1 mg/ml solution for injection and infusion in pre-filled syringe

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Midazolam Accord 1 mg/ml solution for injection and infusion in pre-filled syringe

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

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or nurse.
• If you experience any side effects, talk to your doctor, pharmacist, or nurse, including any side effects not listed in this leaflet. See section 4.

Contents of the leaflet

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

1. What Midazolam Accord is and what it is used for

This medicine contains midazolam, which belongs to a group of medicines known as benzodiazepines.

This medicine acts quickly and makes you feel sleepy or causes you to fall asleep. It also calms you and relaxes your muscles.

This medicine is used in adults:

• As a general anaesthetic to induce sleep or to keep you asleep.

This medicine is also used in adults and children (≥ 12 years of age):

• To calm you and make you feel sleepy if you are in the Intensive Care Unit. This is called "sedation".
• Before and during a medical procedure in which you will remain awake. Midazolam calms you and makes you feel sleepy. This is called "conscious sedation".
• To calm you and make you feel sleepy before anaesthesia.

2. What you need to know before Midazolam Accord is administered to you

Do not be given Midazolam Accord if:

• You are allergic (hypersensitive) to midazolam, or to any of the other components of this medicine (listed in section 6).
• You are allergic to other benzodiazepines, such as diazepam or nitrazepam.
• You have severe breathing difficulties and you are going to undergo conscious sedation.

You must not receive midazolam if any of the above situations apply. If you are unsure, speak with your doctor or nurse before this medicine is administered.

Warnings and precautions

Check with your doctor or nurse before receiving this medicine if you:

• Are over 60 years of age.
• Have a long-term illness, for example, chronic respiratory problems or kidney, liver, or heart problems.
• Have a condition that makes you feel very weak, exhausted, and lacking in energy.
• Have a condition called myasthenia gravis, in which your muscles are weak.
• Suffer from "sleep apnoea syndrome" (in which breathing stops while you are asleep), in which case you may be closely monitored.
• Have ever had problems with alcohol.
• Have ever had problems with drugs.
• Are pregnant or think you may be pregnant (see 'Pregnancy and breastfeeding').

If any of these situations apply to you (or if you are unsure), consult your doctor before starting to use this medicine.

If your child (≥ 12 years) is to start receiving this medicine:

• Inform your doctor or nurse if your child (≥ 12 years) is in any of the above situations.
• Specifically, inform your doctor or nurse if your child has heart or respiratory problems.

Other medicines and Midazolam Accord

Inform your doctor or nurse if you are using or have recently used any other medicines, including those obtained without a prescription and herbal remedies. This is because midazolam may affect how other medicines work. Likewise, other medicines may alter the effect of midazolam.

Specifically, inform your doctor or nurse if you are taking any of the following medicines:

• Antidepressants or antipsychotics (medicines for depression or schizophrenia).
• Hypnotic medicines (help you sleep).
• Sedatives (make you feel calm or drowsy).
• Tranquillizers (to treat anxiety or help you sleep).
• Carbamazepine or phenytoin (used to treat seizures or convulsions).
• Rifampicin (used to treat tuberculosis).
• Medicines used to treat HIV called "protease inhibitors" (such as saquinavir).
• Antibiotics called "macrolides" (such as erythromycin or clarithromycin).
• Medicines used to treat fungal infections (such as ketoconazole, voriconazole, fluconazole, itraconazole, posaconazole).
• Narcotic analgesics (strong painkillers used to treat pain).
• Atorvastatin (used to treat high cholesterol).
• Antihistamines (used to treat allergic reactions).
• St. John’s Wort (a herbal remedy used for depression).
• Cough medicines (such as those containing codeine).
• Medicines used to treat high blood pressure and heart conditions called calcium channel blockers (such as diltiazem, verapamil, and methyldopa).
• Medicines for hepatitis C (protease inhibitors such as boceprevir and telaprevir).
• Ticagrelor (used to prevent myocardial infarction).
• Carbamazepine (used to treat epilepsy and bipolar disorder).
• Phenytoin (used to treat epilepsy).
• Aprepitant (used to prevent feeling sick or vomiting).

If you are in any of these situations (or have any doubts), consult your doctor or nurse before starting to use this medicine.

Surgical procedures

If you are to be given an anaesthetic for surgery or for dental treatment (including inhaled anaesthetics that you breathe in), it is important that you inform your doctor or dentist that you have been given Midazolam Accord.

Midazolam Accord and alcohol

Do not drink alcohol if you have been given midazolam. This is because it may cause excessive drowsiness and breathing problems.

Pregnancy and breastfeeding

Before receiving midazolam, tell your doctor if you are pregnant or think you might be pregnant. Your doctor will decide whether this medicine is suitable for you.

After you have been given midazolam, you must not breastfeed your baby for 24 hours. This is because Midazolam Accord may pass into breast milk.

Midazolam can harm the fetus when used during early pregnancy. When high doses are administered late in pregnancy, during labour or caesarean section, there is a risk of aspiration and your baby may experience irregular heart rate, low muscle tone (hypotonia), feeding difficulties, low body temperature, and breathing difficulties. With prolonged administration late in pregnancy, your baby may develop physical dependence and risk withdrawal symptoms after birth.

Driving and using machines

• After receiving midazolam, you must not drive or operate tools or machinery until your doctor tells you when you may do so.
• This is because midazolam may make you feel drowsy or forgetful. It may also affect your concentration and coordination. This could impair your ability to drive or use tools and machinery.
• You must be accompanied home by an adult after treatment.

Midazolam Accord contains sodium

This medicine contains less than 23 mg of sodium (1 mmol) per pre-filled syringe, i.e. essentially "sodium-free".

3. How to use Midazolam Accord

This medicine must be administered only by a physician or nurse experienced in its use, and only in a properly equipped setting for monitoring and treatment of adverse effects. This may be a hospital, clinic, or medical office. Specifically, your breathing, heart, and circulation will be monitored.

This medicine is not recommended for use in children under 12 years of age.

How Midazolam Accord will be administered to you

Midazolam will be administered to you in one of the following ways:

• Slow injection into a vein (intravenous injection),
• Through a cannula placed in one of your veins (intravenous infusion),
• Injection into a muscle (intramuscular injection).

How much Midazolam Accord will be administered to you

The dose varies from patient to patient. Your doctor will decide the most appropriate dose for you. It will depend on your age, weight, and physical condition. It also depends on why you need the medicine, your response to treatment, and whether you are receiving other medicines at the same time.

After administration of Midazolam Accord

After treatment, you must go home accompanied by an adult who can take care of you. This is because midazolam may make you feel sleepy or cause memory loss. It may also affect your concentration and coordination.

If you have been receiving midazolam for a prolonged period, for example in intensive care, your body may begin to get used to the medicine. This means that its effect may not be the same over time.

If you receive more Midazolam Accord than you should

This medicine is administered by a healthcare professional, so it is unlikely that you will receive an overdose. However, if too much midazolam is accidentally administered, you may experience:

• Drowsiness and loss of coordination (ataxia) and reflexes,
• Difficulty speaking (dysarthria) and unusual eye movements (nystagmus),
• Low blood pressure (hypotension), which may cause dizziness or vertigo,
• Cessation of breathing (apnea) and cardiorespiratory depression (slow or stopped breathing and heartbeat), and unconsciousness (coma).

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

Long-term use of Midazolam Accord for sedation in intensive care

If you receive midazolam for a prolonged period, the following may occur:

• The medicine may gradually become less effective,
• You may develop dependence on the medicine and experience withdrawal symptoms when you stop taking it (see “If you stop treatment with midazolam”).

If you stop treatment with Midazolam Accord

If you have received midazolam for a long time, for example in intensive care, you may experience withdrawal symptoms when treatment is discontinued. These symptoms may include:

• Mood changes,
• Seizures,
• Headache,
• Diarrhea,
• Muscle pain,
• Sleep disturbances (insomnia),
• Feeling very anxious, tense, restless, confused, or irritable,
• Seeing and possibly hearing things that are not real (hallucinations).

Your doctor will gradually reduce your dose. This will help prevent withdrawal symptoms.

4. Possible adverse effects

Like all medicines, Midazolam Accord can cause adverse effects, although not everyone experiences them. The following adverse effects have been reported (frequency unknown, cannot be estimated from available data).

Stop taking Midazolam Accord and seek immediate medical attention if you experience any of the following adverse effects. These may be potentially life-threatening and may require urgent medical treatment:

• Severe allergic reaction (anaphylactic shock). Symptoms may include rash, itching or skin eruption (hives), swelling of the face, lips, tongue, or other parts of the body (angioedema). You may also experience shortness of breath, noisy breathing or difficulty breathing, pale skin, weak and rapid pulse, or feeling faint. Additionally, you may experience chest pain, which could be a sign of a potentially serious allergic reaction known as Kounis syndrome.
• Heart attack (cardiac arrest). Symptoms may include chest pain that may spread to the neck, shoulders, and down the arm.
• Breathing problems, sometimes leading to respiratory arrest.
• Muscle spasm of the glottis, causing suffocation.

Potentially life-threatening adverse effects are more likely in individuals over 60 years of age and in those who already have pre-existing respiratory or heart conditions. These adverse effects are also more likely if the injection is administered too quickly or if a high dose is given.

Other possible adverse effects

Nervous system and psychiatric disorders:

• Reduced alertness
• Confusion
• Feeling excessively happy or excited (euphoria)
• Changes in sexual behavior
• Feeling tired, drowsy, or sedated for a prolonged period
• Seeing or possibly hearing things that are not real (hallucinations)
• Headache
• Dizziness
• Difficulty coordinating muscles
• Seizures in premature infants and newborns
• Temporary memory loss. The duration depends on the amount of midazolam administered. Occasionally, this may last for a long period of time
• Agitation, restlessness, hostility, angry reactions, or aggressiveness. You may also experience muscle spasms or uncontrollable muscle tremors. These effects have been observed more frequently when high doses of midazolam are administered or when the drug is given rapidly. These effects are more likely to occur in children and elderly individuals

Cardiac and vascular disorders:

• Fainting
• Decreased heart rate
• Flushing of the face and neck (redness)
• Low blood pressure. This may cause dizziness or vertigo

Respiratory, thoracic, and mediastinal disorders:

• Hiccups
• Shortness of breath

Gastrointestinal disorders:

• Dry mouth
• Constipation
• Nausea or vomiting

Skin and subcutaneous tissue disorders:

• Itching
• Skin rash, including hives (urticaria)
• Redness, pain, blood clots, or inflammation of the skin at the injection site

General disorders:

• Allergic reactions including skin rash and breathing noises
• Withdrawal symptoms (see “If you stop treatment with midazolam” in section 3)
• Falls and bone fractures: The risk is higher if you are also taking other medications that cause sedation (e.g., tranquilizers or sleep medicines), or if you consume alcohol

Use in elderly patients:

• Elderly patients taking benzodiazepines such as midazolam have an increased risk of falls and bone fractures, particularly in individuals over 60 years of age.
• Potentially life-threatening adverse effects are more likely in adults over 60 years of age.

Unexpected reactions:

Unexpected (paradoxical) reactions with midazolam include restlessness, agitation, irritability, involuntary movements (including muscle tremor), hyperactivity, nervousness, hostility, delirium, anger, aggressiveness, anxiety, nightmares, hallucinations (seeing or possibly hearing things that are not real), psychosis (loss of contact with reality), and inappropriate behavior, excitement, and aggression. These reactions may occur with high doses and/or when the injection is administered rapidly. These reactions are more frequent in children and elderly individuals.

Reporting of adverse effects

If you experience any adverse effects, consult your doctor or pharmacist, even if they are 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. Storage of Midazolam Accord

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date which is stated on the packaging after “CAD” or “EXP”. The expiry date refers to the last day of the month indicated.
• This medicine does not require any special storage temperature. Store in the original packaging to protect from light.
• This medicine is for single use only and any unused solution must be discarded. Do not use this medicine if the container is leaking, if the solution is not clear, if it contains visible particles, or if there are signs of discoloration of the solution.
• Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging that you no longer need. This will help protect the environment.

6. Contents of the container and other information

Composition of Midazolam Accord

• The active substance is midazolam (as midazolam hydrochloride).
• The other components are sodium chloride, sodium hydroxide (to adjust pH), concentrated hydrochloric acid (as a solubilizer and to adjust pH), and water for injections.

Each ml of injectable solution contains midazolam hydrochloride, equivalent to 1 mg of midazolam.

Each 5 ml pre-filled syringe contains midazolam hydrochloride, equivalent to 5 mg of midazolam.

Appearance of the product and contents of the container

Midazolam Accord is a clear, colourless to pale yellow solution, free from particles, contained in a transparent glass pre-filled syringe.

Midazolam Accord is available in packs containing 1 pre-filled syringe.

Marketing Authorization Holder

Accord Healthcare S.L.U.

World Trade Center

Moll de Barcelona s/n,

Edifici Est, 6th floor

08039 Barcelona, Spain

Manufacturer

Accord Healthcare Polska Sp. z o.o.,

ul. Lutomierska 50, 95-200 Pabianice, Poland

or

Laboratori Fundació Dau

C/ C, 12-14 Pol. Ind.

Zona Franca, Barcelona, 08040, Spain

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

Detailed information on this medicinal product is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS) http://www.aemps.gob.es/

This information is intended only for healthcare professionals:

Midazolam Accord 1 mg/ml solution for injection and infusion in pre-filled syringe

Preparation of the infusion solution

This medicine may be diluted with 0.9% sodium chloride solution, 5% or 10% glucose solution, Ringer's solution, or Hartmann's solution. For continuous intravenous infusion, Midazolam Accord may be diluted in the range of 0.015 to 0.15 mg per ml with one of the solutions listed above.

These diluted solutions remain physically and chemically stable for 24 hours at room temperature and for 3 days at 8°C. Midazolam Accord must not be mixed with any solution other than those listed above. In particular, midazolam must not be diluted with 6% dextran p/v (with 0.9% sodium chloride) in glucose or mixed with an alkaline compound injection. Midazolam precipitates in bicarbonate.

The injectable solution must be visually inspected before administration. Only solutions free from visible particles should be used.

The dose of Midazolam Accord must be carefully calculated for each individual patient. Only part of the medicinal product may be required. Please pay attention to the accuracy of the dose required for each patient based on body weight.

When the amount of drug to be injected needs to be adjusted according to the patient's body weight, use the graduated pre-filled syringe to achieve the required volume, discarding the excess before injection in case of intramuscular or intravenous bolus administration.

Shelf life and storage

Midazolam Accord is intended for single use only. Any unused portion must be discarded. The use of this medicine for multiple administrations in the same or different patients is not recommended.

Before opening

Store in the original packaging to protect from light.

After dilution

Physicochemical stability of the diluted solutions has been demonstrated under conditions of use for 24 hours at room temperature (15°C–25°C) or for 3 days at 2–8°C.

From a microbiological standpoint, the product should be used immediately. If not used immediately, the duration and conditions of storage prior to use are the responsibility of the user and should generally not exceed 24 hours at 2–8°C, unless dilution has taken place under controlled and validated aseptic conditions.

For continuous intravenous infusion, Midazolam Accord may be diluted in the range of 0.015 to 0.15 mg per ml with one of the solutions listed above.

Disposal of waste products

Any unused medicine or waste material must be disposed of in accordance with local regulations.