MIDAZOLAM ACCORD 1 mg/ml INJECTABLE SOLUTION AND PERFUSION IN PRE-FILLED SYRINGE

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

You should not be given Midazolam Accord if:

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

You should not be given 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

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

• Are over 60 years old.
• Have a long-term illness, such as chronic respiratory problems or kidney, liver or heart problems.
• Have an illness that makes you feel very weak, tired and lacking in energy.
• Have a condition called myasthenia graviswhere your muscles are weak.
• Suffer from "sleep apnoea syndrome" (where your breathing stops when you are asleep), 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 breast-feeding').

If you are in any of these situations (or are unsure), talk to your doctor before you start using this medicine.

If your child (≥ 12 years of age) is going to be given this medicine:

• Tell your doctor or nurse if your child (≥ 12 years of age) is in any of the above situations.
• In particular, tell your doctor or nurse if your child has heart or breathing problems.

Other medicines and Midazolam Accord

Tell your doctor or nurse if you are taking or have recently taken any other medicines, including those obtained without a prescription and herbal medicines. This is because midazolam can affect the way other medicines work. Similarly, other medicines can affect the way midazolam works.

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

• Antidepressants or antipsychotics (medicines for depression or schizophrenia).
• Sleeping tablets (hypnotics).
• Sedatives (make you feel calm or sleepy).
• Tranquillisers (to treat anxiety or to help you sleep).
• Carbamazepine or phenytoin (used to treat fits 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 ketoconazol, voriconazol, fluconazol, itraconazol, posaconazol).
• Strong painkillers (narcotic analgesics) for pain relief.
• Atorvastatin (used to treat high cholesterol).
• Antihistamines (used to treat allergic reactions).
• St John’s Wort (a herbal medicine 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 heart attack)
• Carbamazepine (used to treat epilepsy and bipolar disorder)
• Phenytoin (used to treat epilepsy)
• Aprepitant (used to prevent feeling sick)

If you are in any of these situations (or are unsure), talk to your doctor or nurse before you start using this medicine.

Surgical procedures

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

Midazolam Accord with alcohol

Do not drink alcohol if you have been given midazolam. This is because you may feel very sleepy and have problems breathing.

Pregnancy and breast-feeding

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

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

Midazolam Accord may harm your baby when used at the start of pregnancy. When high doses are used at the end of pregnancy, during delivery or caesarean section, there is a risk of inhalation and your baby may have an irregular heartbeat, low muscle tone (hypotonia), feeding difficulties, low body temperature and breathing difficulties. With prolonged use at the end of pregnancy, your baby may become physically dependent and have a risk of withdrawal symptoms after birth.

Driving and using machines

• After you have been given midazolam, do not drive or use tools or machines until your doctor tells you that you can.
• This is because midazolam can make you feel sleepy or forgetful. It can also affect your concentration and co-ordination. This can affect your ability to drive or use tools and machines.
• You should be taken home by an adult after treatment.

Midazolam Accord contains sodium

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

3. How Midazolam Accord is used

This medicine should only be given by a doctor or nurse with experience in a place that is properly equipped for monitoring and treatment of side effects. This place may be a hospital, clinic or doctor’s surgery. In particular, your breathing, heart and circulation will be monitored.

This medicine is not recommended for the treatment of children under 12 years of age.

How Midazolam Accord will be given to you

Midazolam will be given 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 given to you

The dose varies from person to person. Your doctor will decide 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 medicine, your response to treatment and whether you are given other medicines at the same time.

After you have been given Midazolam Accord

After treatment, you should go home accompanied by an adult who can take care of you. This is because midazolam can make you feel sleepy or forgetful. It can also affect your concentration and co-ordination.

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

If you are given too much Midazolam Accord

This medicine will be given to you by a doctor or nurse. This means that it is unlikely that you will be given too much midazolam. However, if you are given too much by mistake, you may notice the following:

• Feeling sleepy and losing your co-ordination (ataxia) and reflexes.
• Having problems speaking (dysarthria) and having uncontrolled eye movements (nystagmus).
• Having low blood pressure (hypotension). This can make you feel dizzy or faint.
• Stopping breathing (apnoea) and having slow heart beats and breathing (cardiorespiratory depression) and being unconscious (coma).

In case of overdose or accidental ingestion, contact your doctor or pharmacist or call the Toxicological Information Service, telephone: 91 562 04 20, indicating the medicine and the amount taken.

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

If you are given midazolam for a long time, the following may happen:

• You may become used to the medicine.
• You may become physically dependent on the medicine and have withdrawal symptoms when you stop using it (see “If you stop using Midazolam Accord” in section 3).

If you stop using Midazolam Accord

If you have been given midazolam for a long time, for example in intensive care, you may have withdrawal symptoms when you stop using midazolam. These symptoms may be:

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

Your doctor will reduce your dose gradually. This will help you to avoid these withdrawal symptoms.

4. Possible side effects

Like all medicines, Midazolam Accord can cause side effects, although not everybody gets them. The following side effects have been reported (frequency not known, cannot be estimated from the available data).

Stop using Midazolam Accord and contact your doctor immediately if you experience any of the following side effects. They can be life-threatening and you may need urgent medical treatment:

• Severe allergic reaction (anaphylactic shock). Symptoms can include skin rash, itching or hives (urticaria), swelling of the face, lips, tongue or other parts of the body (angioedema). You may also have difficulty breathing, wheezing or coughing, or pale skin, weak and fast 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). Symptoms can include chest pain that can spread to your neck and shoulders and down your arm.
• Breathing problems, sometimes causing breathing to stop.
• Muscle spasm of the glottis, causing asphyxia.

Potentially life-threatening side effects are more likely in adults over 60 years of age, and in people who already have breathing or heart problems. These side effects are also more likely if the injection is given too quickly or in high doses.

Other possible side effects

Nervous system and psychiatric disorders:

• Decreased alertness
• Confusion
• Feeling extremely happy or excited (euphoria),
• Changes in sexual behaviour
• Feeling tired, sleepy or sedated for a long time
• Seeing or possibly hearing things that do not exist (hallucinations)
• Headache
• Feeling dizzy
• Difficulty co-ordinating your muscles
• Convulsions in premature and newborn babies
• Temporary loss of memory. The length of time this can last depends on the amount of midazolam given. Occasionally it can last for a long time
• Agitation, restlessness, irritability, uncontrolled movements (including muscle tremors), hyperactivity, nervousness, hostility, anger, aggression. You may also experience muscle spasms or uncontrolled shaking of your muscles. These effects have been seen more frequently when high doses of midazolam have been given or when the injection has been given quickly. These effects are more likely in children and the elderly

Cardiac and vascular disorders:

• Fainting.
• Decreased heart rate.
• Flushing of the face and neck (rubor).
• Low blood pressure. This can make you feel dizzy or faint.

Respiratory, thoracic and mediastinal disorders:

• Hiccup.
• Shortness of breath

Gastrointestinal disorders:

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

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 wheezing.
• Withdrawal symptoms (see “If you stop using Midazolam Accord” in section 3).
• Falls and bone fractures: The risk is higher if you are also taking other medicines that cause sedation (e.g. painkillers or sleeping medicines), or if you drink alcohol.

Use in elderly patients:

• Elderly patients who take benzodiazepines, such as midazolam, have a higher risk of falls and bone fractures in adults over 60 years of age.
• Potentially life-threatening side effects are more likely in adults over 60 years of age.

Unexpected reactions:

With midazolam, unexpected (paradoxical) reactions have occurred such as restlessness, agitation, irritability, uncontrolled movements (including muscle tremors), hyperactivity, nervousness, hostility, anger, aggression. You may also experience muscle spasms or uncontrolled shaking of your muscles. These effects can occur with high doses and/or when the injection is given quickly. These effects are more frequent in children and the elderly.

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaRAM.es/. By reporting side 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 carton after “EXP”. The expiry date refers to the last day of the month shown.
• This medicine does not require any special storage conditions. Store in the original packaging to protect from light.
• This medicine is for single use only and any remaining solution should be discarded. Do not use this medicine if it has been spilled in the container, the solution is not clear, it contains visible particles or there are signs of discolouration of the solution.
• Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Container Content and Additional Information

Composition of Midazolam Accord

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

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

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

Appearance and Container Content of the Product

Midazolam Accord is a clear, 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, 6ª planta

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 Last Revision of this Prospectus:July 2024

Detailed information on this medicinal product 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 healthcare professionals:

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

Preparation of the Solution for Perfusion

This medicinal product may 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 perfusion, 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 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 (w/v) in glucose or mixed with an alkaline compound injection. Midazolam precipitates in hydrogen carbonate.

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

The dose of Midazolam Accord must be carefully calculated for each patient. Only a portion of the medicinal product 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 reach the required volume, discarding any excess before injection in the case of intramuscular or intravenous bolus injection.

Shelf Life and Storage

Midazolam Accord is designed for single use.Discard any excess content. The use of this medicinal product 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

Physical and chemical stability of the dilutions 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 point of view, the product must be used immediately. If not used immediately, the storage times and 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 perfusion, 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 Unused Medicinal Products

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