MIDAZOLAM ACCORD 5 mg/ml INJECTABLE SOLUTION AND PERFUSION SOLUTION

Introduction

Package Leaflet: Information for the User

Midazolam Accord 5 mg/ml Solution for Injection and InfusionEFG

Read all of this leaflet carefully before you are given this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again. If you have any further questions, ask your doctor or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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 Midazolam Accord will be given to you
4. Possible side effects
5. Storage of Midazolam Accord
6. Contents of the pack and other information

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

Midazolam solution for injection and infusion contains midazolam which belongs to a group of medicines known as benzodiazepines.

This is a short-acting medicine used to induce sedation (a state of calm, drowsiness or sleep) and relieve anxiety and muscle tension.

This medicine is used for:

• Conscious sedation (a state of calm or drowsiness in which you remain awake during the medical examination) in adults and children.
• Sedation in intensive care units in adults and children.
• Anesthesia in adults, used alone or with other medicines.
• Pre-medication (medicine used to cause relaxation, calmness and drowsiness before the induction of anesthesia) in adults and children.

2. What you need to know before you are given Midazolam Accord

Do not use Midazolam Accord

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

Do not receive midazolam if any of the above applies to you. If you are not sure, talk to your doctor or nurse before you are given this medicine.

Warnings and precautions

Adults

Before receiving midazolam, tell your doctor or nurse if you:

• Are over 60 years of age.
• Have a long-term illness (such as chronic respiratory problems, kidney or liver failure, or heart disorders). Are debilitated (have an illness that makes you feel very weak, exhausted and without energy).
• Have a condition called "sleep apnea syndrome" (where your breathing stops when you are asleep), so you may be closely monitored.
• Suffer from myasthenia gravis (a neuromuscular disease characterized by muscle weakness).
• Regularly drink large amounts of alcohol or have had problems with alcohol consumption in the past. Alcohol can increase the effects of midazolam, possibly leading to severe sedation that could result in coma or death.
• Regularly take recreational drugs (drugs for non-medical use) or have had problems with drug use in the past.
• Are pregnant or think you may be pregnant.

Children and babies

If your child is going to receive this medicine:

• It is especially important to tell your doctor or nurse if your child has a heart condition. Your child will be closely monitored and the dose will be adjusted especially.
• Children must be closely monitored. For babies and babies under 6 months, this will include monitoring of breathing and oxygen levels.

Talk to the doctor or nurse if any of the above applies to your child.

Using midazolam with other medicines

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

This is especially important because taking more than one medicine at the same time can increase or decrease the effect of the medicines in question.

In particular, tell your doctor or nurse if you are taking any of the following medicines:

• Tranquilizers (to treat anxiety or to help you sleep).
• Hypnotics (medicines that help you sleep).
• Sedatives (make you feel calm or sleepy).
• Antidepressants or antipsychotics (medicines for depression or schizophrenia).
• Narcotic analgesics (very strong medicines to treat pain).
• Cough medicines (such as those containing codeine).
• Antihistamines (used to treat allergic reactions).
• Medicines used to treat fungal infections (such as ketoconazole, voriconazole, fluconazole, itraconazole, posaconazole).
• Macrolide antibiotics (such as erythromycin, clarithromycin or roxithromycin).
• Medicines used to treat high blood pressure and heart disease (such as diltiazem, verapamil and methyldopa).
• Medicines used to treat HIV (efavirenz or protease inhibitors such as saquinavir).
• Medicines for hepatitis C (protease inhibitors such as boceprevir and telaprevir).
• Atorvastatin (used to treat high cholesterol).
• Rifampicin (used to treat mycobacterial infections such as tuberculosis).
• Ticagrelor (used to prevent heart attacks).
• St. John's Wort.
• Carbamazepine (used to treat epilepsy and bipolar disorder).
• Phenytoin (used to treat epilepsy).
• Aprepitant (used to stop feeling nauseous or having nausea).

If you are in any of these cases (or have doubts), consult your doctor or nurse before starting to use Midazolam Accord.

Surgery

If you are going to receive an anesthetic for an operation or for dental treatment (including inhaled anesthetics that you inhale), it is important that you tell your doctor or dentist that you have been using midazolam.

Midazolam Accord with alcohol

Do not drink alcohol if you have been given midazolam. This is because alcohol can increase the sedative effect of midazolam and can cause breathing problems.

Pregnancy and breastfeeding

Tell your doctor if you are pregnant, think you may be pregnant or plan to become pregnant. Your doctor will decide if this medicine is suitable for you.

Midazolam can harm the fetus if given at the beginning of pregnancy. When high doses are given during the last stage of pregnancy, childbirth or cesarean section, there may be a risk of inhalation and your baby may have irregular heartbeats, low muscle tone (hypotonia), difficulty feeding, low body temperature, and difficulty breathing. With prolonged administration during the end of pregnancy, your baby may develop physical dependence and risk of withdrawal symptoms after birth.

• Do not breastfeed for 24 hours after receiving midazolam. This is because midazolam can pass into breast milk.

Driving and using machines

This medicine can cause drowsiness, dizziness, memory loss, or affect your concentration and coordination. This can reduce your performance in tasks that require a specific skill, for example, driving or operating machines. Do not drive a vehicle or operate a machine until you have fully recovered. Your doctor will tell you when you can resume these activities.

Talk to your doctor or pharmacist if you are not sure if it is safe for you to drive while taking this medicine.

Lack of sleep or alcohol consumption can further affect your alertness.

You should always be taken home by a responsible adult after your treatment.

Midazolam Accord contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per ampoule, i.e., it is essentially "sodium-free".

3. How Midazolam Accord will be given to you

Midazolam should only be given by healthcare professionals with experience (doctor or nurse). It should be given in a place (hospital, clinic or operating room) equipped to monitor and maintain the patient's breathing, heart, and circulation (cardiovascular function) and recognize the signs and control the expected side effects of anesthesia.

How much midazolam will be given

Your doctor will decide on a suitable dose for you. The dose you are given will depend on why you are being treated and the type of sedation needed. Your weight, age, state of health, how you respond to midazolam, and whether you need other medicines at the same time will also influence the dose you are given.

If you need strong painkillers, these will be given to you first and then midazolam will be given to you. Your doctor will decide on a suitable dose for you.

How midazolam will be given

Midazolam can be given to you in four different ways:

• By slow injection into a vein (intravenous injection).
• Through a tube in one of your veins (intravenous infusion).
• By injection into a muscle (intramuscular injection).
• By rectal route.

You should always be taken home by a responsible adult after your treatment.

Children and babies

• In children and babies under 6 months of age, midazolam is only recommended for sedation in intensive care units. The dose will be given gradually into a vein.
• In children 12 years or younger, midazolam will normally be given into a vein. When midazolam is used as pre-medication (to give relaxation, calmness, and drowsiness before the anesthetic), it may be given rectally.

If you are given too much Midazolam Accord

Your medicine will be given to you by a doctor or nurse.

If you are accidentally given too much midazolam, you may:

• Feel drowsy.
• Lose your coordination (ataxia) and reflexes.
• Have speech problems (dysarthria).
• Have involuntary eye movements (nystagmus).
• Develop low blood pressure (hypotension).
• Stop breathing (apnea) and suffer from cardiopulmonary depression (slow or stopped breathing and heartbeats) and coma.

Stopping treatment with midazolam

If you receive long-term treatment with midazolam (you are given the medicine for a long time), you may:

Become tolerant to midazolam. The medicine becomes less effective and does not work as well for you.

Become dependent on this medicine and have withdrawal symptoms (see below).

Your doctor will gradually reduce your dose to avoid these effects.

The following effects have been seen with the use of midazolam, particularly in children and elderly patients: restlessness, agitation, irritability, involuntary movements, hyperactivity, nervousness, hostility, delirium, anger, aggression, anxiety, nightmares, hallucinations (seeing and possibly hearing things that are not really there), psychosis (loss of contact with reality), and inappropriate behavior, excitement, and seizures (these reactions are also known as paradoxical reactions, which are opposite results to the expected effects of the medicine). If you experience these, your doctor will consider stopping treatment with midazolam.

Withdrawal symptoms:

Benzodiazepine medicines, such as midazolam, can make you dependent if used for a long time (for example, in intensive care). This means that if you stop treatment suddenly or reduce the dose too quickly, you may have withdrawal symptoms. The symptoms can include:

• Headache, diarrhea, muscle pain.
• Feeling very anxious (anxious), tense, restless, confused, or irritable (irritable) with sleep problems.
• Mood changes.
• Hallucinations (seeing and possibly hearing things that are not there), seizures.

In severe cases of withdrawal, the following may occur: feeling of loss of contact with reality, numbness and tingling of the limbs (e.g., hands and feet), sensitivity to light, noise, and touch.

4. Possible side effects

Like all medicines, Midazolam Accord 1 mg/ml can cause side effects, although not everybody gets them. The following side effects have been seen with this medicine (frequency unknown).

Do not use midazolam and see a doctor urgently if you notice any of the following side effects. These could be life-threatening and may require urgent medical treatment:

• Anaphylactic shock (a life-threatening allergic reaction). The signs will include a sudden rash, itching or hives, swelling of the face, lips, tongue, or other parts of the body. You may also experience difficulty breathing, wheezing, or breathing problems, or pale skin, weak and rapid pulse, or feeling of loss of consciousness. Additionally, you may experience chest pain, which can be a sign of a potentially serious allergic reaction called Kounis syndrome.
• Heart attack (cardiac arrest). The signs may include: chest pain, which may spread to your neck, shoulders, and left arm.
• Breathing problems or complications (sometimes can cause respiratory arrest).
• Suffocation and sudden blockage of the airway (laryngospasm).

The side effects that could be life-threatening are more common in adults over 60 years and those patients who already have breathing difficulties or heart problems, particularly if the injection is given too quickly or at a high dose.

Other possible side effects

Immune system disorders:

Behavioral effects:

• Restlessness, agitation, irritability, nervousness, anxiety.
• Hostility, anger, aggressive excitement, or aggression.
• Changes in hyperactivity in libido.
• Inappropriate behavior.

Mental and nervous system problems:

• Confusion, disorientation, emotional and mood disorders, involuntary movements, nightmares, abnormal dreams.
• Hallucinations (seeing and possibly hearing things that are not really there), psychosis (loss of contact with reality).
• Drowsiness and prolonged sedation reduce alertness.
• Dizziness due to headache.
• Difficulty coordinating muscles.
• Seizures (convulsions) in premature and newborn babies.
• Temporary loss of memory. The duration of this depends on the amount of Midazolam you have been given. You may experience this after your treatment. In isolated cases, this has been prolonged (lasted a long time).
• Drug dependence, abuse.
• Feeling agitated, restless, angry, or aggressive. You may also have muscle spasms or muscle twitches that you cannot control (tremors). These effects are more likely if you have been given a high dose of midazolam or if it has been given too quickly. They are also more likely in children and the elderly.

Heart and circulation problems:

• Low blood pressure. This can make you feel dizzy or lightheaded.
• Slow heart rate.
• Flushing of the face and neck (flushing).
• Fainting.

Breathing problems:

• Shortness of breath.
• Hiccup.

Stomach, intestine, and mouth problems:

• Feeling sick or being sick.
• Constipation.
• Dry mouth.

Skin problems:

• Rash.
• Hives.
• Itching.

Muscle problems:

• Muscle spasms and muscle twitches (muscle twitches that cannot be controlled).

Problems at the injection site:

• Redness of the skin.
• Swelling of the skin.
• Blood clots or pain at the injection site.

Injuries:

• Patients taking benzodiazepine medicines are at risk of falls and fractures. This risk increases in the elderly and those taking other sedatives (including alcohol).

General:

• Fatigue (tiredness).

Elderly patients:

It is more likely that life-threatening side effects will occur in adults over 60 years and those patients who already have breathing difficulties or heart problems, particularly when the injection is given too quickly or at a high dose.

Patient with severe kidney disease:

Patients with severe kidney disease are more likely to experience side effects.

If any of the side effects get serious or troublesome, or if you notice any side effects not mentioned in this leaflet, tell your doctor or nurse.

Reporting of side effects

If you experience any side effects, talk to your doctor or nurse, even if it is possible side effects not listed in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Midazolam Accord

Your doctor or pharmacist is responsible for storing midazolam. The storage details are as follows:

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiration date (CAD) that appears on the box and ampoule. The expiration date is the last day of the month indicated.
• Store the ampoules (small glass bottles) in the original packaging to protect them from light.

• Medicines should not be thrown away through drains or into the trash. Ask your pharmacist how to dispose of packaging and medicines that are no longer needed. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Midazolam Accord5 mg/ml

The active ingredient is midazolam (as midazolam hydrochloride).

Each ml of injectable solution contains 5 mg of midazolam (as midazolam hydrochloride).

Each 3 ml ampoule contains 15 mg of midazolam (as midazolam hydrochloride)

The other components are water for injectables, sodium chloride, sodium hydroxide (to adjust the pH), and concentrated hydrochloric acid (to adjust the pH).

Appearance of the Product and Package Contents

Midazolam Accord 5 mg/ml is a clear, colorless to pale yellow solution, packaged in a transparent glass ampoule.

Midazolam Accord 5 mg/ml is available in packages of 10 ampoules of 1 ml, 10 ampoules of 3 ml, 10 ampoules of 10 ml, and 1 ampoule of 10 ml.

The ampoules are available in a blister/tray package.

Marketing Authorization Holder

Accord Healthcare S.L.U.

World Trade Center

Moll de Barcelona s/n,

Edifici Est, 6ª planta

08039 Barcelona

Spain

Manufacturer

Accord Healthcare Polska Sp.z o.o.,

ul. Lutomierska 50, 95-200 Pabianice,

Poland

Date of Last Revision of this Prospectus:July 2024.

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

This information is intended only for doctors or healthcare professionals:

Preparation of the Solution for Infusion

Midazolam Accord can be diluted with a 0.9% sodium chloride solution, 5% or 10% glucose solution, Ringer's solution, or Hartmann's solution. In the case of continuous intravenous infusion, it can be diluted in the range of 0.015 to 0.15 mg per ml with one of the solutions mentioned above. These solutions remain stable for 24 hours at room temperature and for 3 days at 8°C. Midazolam Accord should not be mixed with any solution other than those listed above. In particular, midazolam should not be diluted with 6% dextran (with 0.9% sodium chloride) in glucose or mixed with an injection of an alkaline compound. Midazolam precipitates in hydrogen carbonate.

The injectable or infusion solution should be visually examined before administration. Only solutions without visible particles will be used.

Validity Period and Storage

Midazolam Accord is designed for single use.

Ampoule before opening

Store in the original packaging to protect it from light.

Ampoule after dilution

Physical-chemical stability has been demonstrated in use conditions for the dilutions for 24 hours at room temperature (15°C-25°C) or for 3 days at 8°C.

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

In the case of continuous intravenous infusion, it can be diluted in the range of 0.015 to 0.15 mg per ml with one of the solutions mentioned above.

Disposal of Waste Products

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