Patient Information Leaflet

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

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

• Keep this leaflet, as 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 or pharmacist or nurse, even if they are not listed in this leaflet. See section 4.

This medicationcontains midazolam which belongs to a group of medicines known as benzodiazepines.

This medication acts quickly and makes you feel sleepy or fall asleep. It will also calm and relax your muscles.

This medication is used in adults:

• As a general anesthetic to induce sleep or to keep them asleep.

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

• To calm them and make them feel sleepy if they are in the Intensive Care Unit. This is called “sedation”.
• Before and during a medical procedure in which they will be awake. Midazolam calms them and makes them feel sleepy. This is called “conscious sedation”.
• To calm them and make them feel sleepy before anesthesia.

You should 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 difficultiesandare to be given conscious sedation..

You should not receive midazolam if you are in any of the above situations. If you are unsure, speak with your doctor or nurse before they administer this medicine.

Warnings and precautions

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

• Are over 60 years old.
• 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 calledmyasthenia gravisin which your muscles are weak.
• Suffer from "sleep apnea" (in which breathing stops when you are asleep), so 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 you are in any of these situations (or 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 other medicines, including those bought without a prescription and herbal medicines..This is because midazolam may affect how other medicines work. In the same way, other medicines may modify 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).
• Hypnotics (help you sleep).
• Sedatives (make you feel calm or sleepy).
• Tranquilizers (to treat anxiety or to 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).
• Opioid analgesics (very strong painkillers).
• Atorvastatin (used to treat high cholesterol).
• Antihistamines (used to treat allergic reactions).
• St. John's Wort (a medicinal plant used to treat depression).
• Medicines for cough (such as those containing codeine).Medicines used to treat high blood pressure and heart conditions called calcium channel blockers (such as diltiazem, verapamil and metildopa)
• Medicines used to treat 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 or being sick)

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

Surgical procedures

If you are to receive an anesthetic for surgery or dental treatment (including inhaled anesthetics that you breathe in), it is essential 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 make you very sleepy and cause breathing problems.

Pregnancy and breastfeeding

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

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

Midazolam Accord may harm the fetus when used at the beginning of pregnancy. When high doses are given at the end of pregnancy, delivery or cesarean section, there may be a risk of inhalation and your baby may experience irregular heart rate, low muscle tone (hypotonia), feeding difficulties, low body temperature and breathing difficulties. With prolonged administration at the end of pregnancy, your baby may develop physical dependence and risk of withdrawal symptoms after birth.

Driving and operating machinery

• After you have been given midazolam, do not drive vehicles or use tools or machines until your doctor tells you when you can do so.
• This is because midazolam may make you feel sleepy or forgetful. It may also affect your concentration and coordination. This may affect your ability to drive or use tools and machines.
• You should 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, that is essentially "sodium-free".

This medication must be administered only by a doctor or nurse with experience in a properly equipped place for monitoring and treatment of adverse effects. This place can be a hospital, a clinic or a medical office. Specifically, your breathing, heart and circulation will be monitored.

This medication is not recommended for the treatment of children under 12 years old.

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 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 on the most suitable dose for you. It will depend on your age, weight and physical condition. It will also depend on why you need the medication, your response to treatment and if you will be administered other medications concurrently.

After the administration of Midazolam Accord

After treatment, you must go home accompanied by an adult who can take care of you. This is because midazolam can make you feel drowsy or forget things. It can also affect your concentration and coordination.

If you have been treated with midazolam for a long time, for example in intensive care, your body may start to get used to the medication. This means that the effect may not be the same.

If you receive more Midazolam Accord than you should

This medication must be administered by a doctor or nurse. This means that it is unlikely that you will be administered too much midazolam by mistake. However, if you are administered too much by mistake, you will notice the following:

• You will feel drowsy and lose your coordination (ataxia) and reflexes.
• You will have problems speaking (dysarthria) and have unusual eye movements (nystagmus).
• You will develop low blood pressure (hypotension). This can make you feel dizzy or vertiginous.
• You will stop breathing (apnea) and suffer from cardiac and respiratory depression (slow or stopped breathing and heart rate and unconsciousness (coma).

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicological Information Service, phone: 91 562 04 20, indicating the medication and the amount ingested.

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

If you are administered midazolam for a long period of time, the following may occur:

• You may start to have less effect.
• You may develop dependence on the medication and experience withdrawal symptoms when you stop using it (see "If you interrupt treatment with midazolam").

If you interrupt treatment with Midazolam Accord

If you have been treated with midazolam for a long time, for example in intensive care, you may experience withdrawal symptoms when you stop receiving midazolam. These symptoms may be:

• Mood changes,
• Seizures,
• Headache,
• Diarrhea
• Muscle pain,
• Difficulty sleeping (insomnia),
• Feeling very worried (anxious), tense, restless, confused or irritable,
• Seeing and possibly hearing things that do not exist (hallucinations),

Your doctor will gradually reduce your dose.This will help you not to have those withdrawal symptoms.

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

Stop taking Midazolam Accord and seek medical attention immediately if you experience any of the following side effects. They may be potentially fatal and may require urgent medical treatment:

• Severe allergic reaction (anaphylactic shock). Symptoms may include skin rash, itching, or hives (exanthema), swelling of the face, lips, tongue, or other parts of the body (angioedema).You may also experience shortness of breath, making sounds while breathing, or difficulty breathing, or pale skin, weak and rapid pulse, or feeling loss of consciousness. Additionally, you may experience chest pain, which may be a sign of a potentially severe allergic reaction called Kounis syndrome.
• Heart attack (cardiac arrest). Symptoms may include chest pain that may extend to the neck and shoulders and along the arm.
• Respiratory problems, sometimes causing respiratory arrest.
• Spasm of the glottis, causing asphyxia.

The potentially fatal side effects are more likely to occur in adults over 60 years old, and in people who already have respiratory or heart problems. These side effects are also more likely to occur if the injection is administered too quickly or a high dose is given.

Other possible side effects

Neurological and psychiatric disorders:

• Decreased alertness
• Confusion
• Feeling excessively happy or excited (euphoria),
• Changes in sexual behavior
• Feeling tired, sleepy, or sedated for a long time
• Seeing or possibly hearing things that do not exist (hallucinations)
• Headache
• Feeling dizzy
• Difficulty coordinating muscles
• Convulsions in premature babies and newborns
• Temporary loss of memory. The duration may depend on the amount ofmidazolam administered. Occasionally, it may last for a long period of time
• Agitation, restlessness, hostility, anger, or aggression. You may also experience muscle spasms or uncontrollable tremors of your muscles. These effects have been observed more frequently when high doses of midazolam are administered or when it is administered quickly. These effects are more likely to occur in children and older adults

Cardiovascular and vascular disorders:

• Fainting.
• Decreased heart rate.
• Redness of the face and neck (flushing).
• Low blood pressure. This may make you feel dizzy or lightheaded.

Respiratory, thoracic, and mediastinal disorders:

• Hiccup.
• Shortness of breath

Gastrointestinal disorders:

• Dry mouth.
• Constipation.
• Sensation of nausea or vomiting.

Skin and subcutaneous tissue disorders:

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

General disorders:

• Allergic reactions, including skin rash and breathing sounds.
• Withdrawal symptoms (see "If you interrupt treatment with midazolam" in section 3).
• Falls and bone fractures: The risk is higher if you are taking other sedating medications (such as tranquilizers or sleep medications) at the same time, or if you are drinking alcohol.

Use in elderly patients:

• Older adults taking medications from the benzodiazepine group, such as midazolam, have a higher risk of falls and bone fractures in adults over 60 years old.
• The potentially fatal side effects are more likely to occur in adults over 60 years old.

Unexpected reactions:

Unexpected reactions (paradoxical) such as restlessness, agitation, irritability, involuntary movements (including muscle tremors), hyperactivity, nervousness, hostility, delirium, anger, aggression, anxiety, nightmares, hallucinations (seeing or possibly hearing things that really do not exist), psychosis (loss of contact with reality), and inappropriate behavior, excitement, and aggression have been reported with midazolam. These reactions may occur with high doses and/or when the injection is administered quickly. These reactions are more frequent in children and the elderly.

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a side effect that does not appear in this leaflet. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use: www.notificaRAM.es/. By reporting side effects, you can contribute to providing more information on the safety of this medication.

• Keep this medication out of the sight and reach of children.
• Do not use this medication after the expiration date that appears on the packaging after “CAD” or “EXP”. The expiration date is the last day of the month indicated.
• This medication does not require any special storage temperature. Store in the original packaging to protect it from light.
• This medication is for single use only and any excess solution must be discarded. Do not use this medication if it has been spilled into the container, the solution is not transparent, has visible particles, or shows signs of discoloration of the solution.
• Medications should not be thrown down the drains or in the trash. Ask your pharmacist how to dispose of the packaging and medications that you no longer need. This will help protect the environment.

Midazolam Accord Composition

• The active ingredient is midazolam (as midazolam hydrochloride).
• The other components are sodium chloride, sodium hydroxide (for pH adjustment), concentrated hydrochloric acid (as a solubilizer and for pH adjustment) and water for injection.

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

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

Product Appearance and Packaging Contents

Midazolam Accord is a transparent, colorless to pale yellow solution, free of particles, packaged in a transparent glass pre-filled syringe.

Midazolam Accord is available in packs of 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 Responsible

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

Last Review Date of this Leaflet:July 2024

The detailed information of this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) http://www.aemps.gob.es/

This information is intended solely for medical professionals or healthcare professionals:

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

Preparation of the infusion solution

This medicine 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, Midazolam Accord can be diluted in the range of 0.015 to 0.15 mg per ml with one of the above-mentioned solutions.

These solutions remain stable for 24 hours at room temperature, and for 3 days at 2-8°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 solution (with 0.9% sodium chloride) in glucose or mixed with an injection of an alkaline compound. Midazolam precipitates in hydrogen carbonate.

The injectable solution should be visually inspected before administration. Only solutions without visible particles should be used.

The dose of Midazolam Accord should be calculated carefully for each patient. Only a part of the medicine may be required. Please pay attention to the accuracy of the required dose for each patient based on their body weight.

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

Shelf Life and Storage

Midazolam Accord has been designed for single use.Dispose of any excess content. 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 it from light.

After Dilution

Physical and chemical stability has been demonstrated in conditions of use for 24 hours at room temperature (15°C-25°C) or for 3 days at 2-8°C.

From a microbiological point of view, the product should be used immediately. If not used immediately, the storage times in conditions of use and the conditions prior to use will be the responsibility of the user and will generally not be more than 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, Midazolam Accord can be diluted in the range of 0.015 to 0.15 mg per ml with one of the above-mentioned solutions.

Disposal of Waste Products

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