Midazolam accord

Patient Information Leaflet

Midazolam Accord, 1 mg/ml, solution for injection/infusion in pre-filled syringe
Midazolamum
Please read all of this leaflet carefully before this medicine is administered, because it
contains important information for you.

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

Leaflet Contents:

1. What Midazolam Accord is and what it is used for
2. What you need to know before Midazolam Accord is administered
3. How Midazolam Accord is administered
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

Midazolam Accord contains the active substance midazolam, which belongs to a group of medicines called benzodiazepines.
Midazolam Accord is a fast-acting medicine used to induce drowsiness or sleep, relieve anxiety, and reduce muscle tension.
Midazolam Accord is used in adults:

• as part of general anaesthesia to induce or maintain sleep.

Midazolam Accord is also used in adults and children (aged 12 years and older):

• to induce sedation – a calm and drowsy state – during treatment in intensive care units;
• to induce mild sedation – a calm and drowsy state while maintaining consciousness – before and during medical procedures and examinations;
• to induce a calm and drowsy state prior to anaesthesia.

2. Important information before using Midazolam Accord

When not to use Midazolam Accord

• if the patient has a known allergy (hypersensitivity) to midazolam or any of the other ingredients of this medicine listed in section 6,
• if the patient has a known allergy to medicines of the benzodiazepine group, such as diazepam or nitrazepam,
• if the patient has serious breathing problems and is to undergo light sedation.

If any of the above apply, Midazolam Accord must not be administered. If
the patient is unsure, they should inform the doctor or nurse before the medicine is given.

Warnings and precautions

Before administration, inform the doctor or nurse if:

• the patient is over 60 years of age;
• the patient has chronic illness, including chronic respiratory, kidney, liver, or heart disease;
• the patient has an illness causing them to be very weak, exhausted, and lacking energy;
• the patient has muscle weakness characterized by reduced muscular strength;
• the patient has sleep apnoea syndrome (cessation of breathing during sleep); such patients will be monitored particularly closely;
• the patient currently misuses or has previously misused alcohol;
• the patient currently misuses or has previously misused drugs;
• the patient is pregnant or suspects she may be pregnant (see section "Pregnancy and breastfeeding").

If any of the above apply (or if the patient is unsure), they should
inform the doctor or nurse before receiving Midazolam Accord.

If Midazolam Accord is to be administered to a child aged 12 years or older:

• inform the doctor or nurse if any of the above apply to the child (aged 12 years or older);
• in particular, inform the doctor or nurse if the child has heart or breathing problems.

Midazolam Accord and other medicines

Tell the doctor or nurse about all medicines the patient is currently taking or has recently taken, including over-the-counter medicines and herbal remedies.
Concomitant use of Midazolam Accord with other medicines may affect their action.
In particular, inform the doctor or nurse if the patient is taking any of the following medicines:

• antidepressants or antipsychotics (medicines used to treat depression or schizophrenia),
• sleeping medicines,
• sedatives (medicines that cause drowsiness and calmness),
• tranquilizers (medicines used for anxiety and to help sleep),
• carbamazepine or phenytoin (used for seizures or convulsions),
• rifampicin (used to treat tuberculosis),
• medicines used to treat HIV infection called protease inhibitors (such as saquinavir),
• macrolide antibiotics (such as erythromycin or clarithromycin),
• antifungal medicines (ketoconazole, voriconazole, fluconazole, itraconazole, posaconazole),
• opioid analgesics (very strong painkillers),
• atorvastatin (used to treat high cholesterol levels),
• antihistamines (medicines used to treat allergies),
• St John's wort (a herbal remedy used to treat depression),
• cough medicines (such as those containing codeine),
• medicines used to treat high blood pressure known as calcium channel blockers and heart conditions (such as diltiazem, verapamil, and methyldopa),
• medicines used to treat hepatitis C virus infection (protease inhibitors such as boceprevir and telaprevir),
• ticagrelor (a medicine used to prevent heart attack),
• carbamazepine (used to treat epilepsy and bipolar disorder),
• phenytoin (used to treat epilepsy),
• aprepitant (used to prevent nausea or vomiting).

If any of the above situations apply or if the patient has any doubts, they should
inform the doctor or nurse before using Midazolam Accord.

Surgical procedures

If the patient is to receive an anaesthetic before surgery or dental treatment (including inhaled anaesthetics), it is important to inform the doctor or dentist that the patient has received Midazolam Accord.

Midazolam Accord and alcohol

The patient must not drink alcohol while receiving Midazolam Accord, as alcohol may increase drowsiness and cause breathing problems.

Pregnancy and breastfeeding

• If the patient is pregnant or suspects she may be pregnant, she should inform the doctor before receiving Midazolam Accord. The doctor will decide whether this medicine is suitable.
• Women should not breastfeed for 24 hours after taking Midazolam Accord, as it may pass into breast milk.

Midazolam Accord used during early pregnancy may harm the unborn child.
Administration of high doses towards the end of pregnancy, during labour or caesarean section, may cause the mother to be at risk of aspiration, and the newborn to experience cardiac arrhythmia, reduced muscle tone (hypotonia), sucking difficulties, low body temperature, and breathing difficulties (respiratory depression). With prolonged use of the medicine towards the end of pregnancy, the child may develop physical dependence, and withdrawal symptoms may occur after birth.

Driving and operating machinery

• After receiving Midazolam Accord, the patient must not drive or operate machinery until the doctor decides otherwise.
• Midazolam Accord may cause drowsiness, memory disturbances, reduced concentration, and impaired coordination. These effects may affect the ability to drive and operate machinery.
• After treatment, the patient should return home accompanied by an adult caregiver.

Midazolam Accord contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per dose, i.e. this medicine is considered "sodium-free".

3. How to use Midazolam Accord

Midazolam should only be administered by a doctor or nurse in a healthcare facility (hospital, clinic) equipped with monitoring equipment, particularly for the respiratory, cardiac and circulatory systems, as well as for the treatment of potential adverse reactions.
Midazolam Accord is not recommended for use in infants and children under 12 years of age.
Method of administration
Midazolam Accord can be administered in the following ways:

• by slow injection into a vein (intravenous injection),
• through a special catheter inserted into a vein (intravenous infusion),
• by injection into a muscle (intramuscular injection),
• rectally.

Dosage and route of administration
The dose of Midazolam Accord may vary for each patient. The appropriate dose for a given patient is determined by the doctor. The dose depends on the patient's age, body weight, and general health status. It also depends on the intended purpose of treatment, the patient's response to therapy, and whether other medications are being administered concurrently.
After administration of Midazolam Accord
After the procedure, the patient should return home accompanied by an adult caregiver, as Midazolam Accord may cause drowsiness, memory disturbances, reduced concentration, and impaired coordination.
Overdose of Midazolam Accord
The medicine will be administered by a doctor or nurse, which means the likelihood of an overdose is low. However, if accidental overdose occurs, it may lead to:

• drowsiness and loss of motor coordination (ataxia) and reflexes,
• speech disturbances (dysarthria) and involuntary eye movements (nystagmus),
• low blood pressure (hypotension) – which may cause dizziness or feeling faint,
• apnea and respiratory-circulatory depression (slowing or stopping of breathing and heart function) and loss of consciousness (coma).

Use of Midazolam Accord for prolonged sedation in patients
receiving intensive medical care
When Midazolam Accord is used for a prolonged period, the following may occur:

• reduced effectiveness of the medicine,
• patient dependence on the medicine and withdrawal symptoms after discontinuation (see below).

Discontinuation of Midazolam Accord
When Midazolam Accord has been used for a prolonged period, for example in an intensive care unit, discontinuation of the medicine may result in withdrawal symptoms including:

• mood changes,
• seizures,
• headaches,
• diarrhoea,
• muscle pain,
• inability to sleep (insomnia),
• anxiety, tension, psychomotor agitation, disorientation, irritability,
• hallucinations (seeing or hearing things that are not there).

The doctor will gradually reduce the dose of the medicine to avoid the occurrence of these effects.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
The adverse reactions listed below occurred with unknown frequency.
If any of the following adverse reactions occur in the patient, Midazolam Accord must be discontinued immediately and the doctor must be informed without delay.
These may be life-threatening reactions requiring immediate treatment.

• Severe allergic reaction (anaphylactic shock). Symptoms include sudden rash, itching or hives; swelling of the face, lips, tongue or other parts of the body. There may also be shortness of breath,
  wheezing or difficulty breathing, or pale skin, weak and rapid pulse, or
  feeling faint. Additionally, chest pain may occur, which could be a sign of a serious allergic reaction known as Kounis syndrome.

• Heart attack (cardiac arrest). Symptoms include chest pain that may radiate to the neck and arms, and then down to the left arm.

• Breathing difficulties, sometimes leading to respiratory arrest.

• Shortness of breath and sudden airway obstruction (laryngospasm).

Life-threatening adverse reactions occur more frequently in patients over 60 years of age,
in patients with respiratory insufficiency or impaired cardiac muscle function, particularly
if the medicine is injected too rapidly or in high doses.

Other adverse reactions

Psychiatric and nervous system disorders

• reduced alertness,
• confusion,
• excessive feeling of happiness or excitement (euphoria),
• changes in libido,
• feeling of fatigue, drowsiness, prolonged sedation,
• seeing and hearing things that are not there (hallucinations),
• headache,
• dizziness,
• difficulty with muscle coordination,
• seizures in premature infants and newborns,
• temporary memory loss. The duration of memory loss depends on the amount of Midazolam Accord received. In individual cases, it may persist for a long time.
• Agitation, restlessness, anger or aggressive behaviour. Muscle spasms and uncontrolled muscle tremors may also occur. These disorders are more likely after administration of a high dose of Midazolam Accord or if the medicine is administered too quickly. This is also more likely in children and elderly individuals.

Cardiovascular disorders

• fainting (syncope),
• slowed heart rate,
• redness of the face and neck,
• low blood pressure, which may cause dizziness or lightheadedness.

Respiratory disorders

• hiccups,
• shallow breathing.

Gastrointestinal disorders

• dryness of the mouth,
• constipation,
• nausea, vomiting.

Skin and subcutaneous tissue disorders

• itching,
• rash, including raised rash (urticaria),
• redness, pain, blood clots or swelling of the skin at the injection site.

General disorders

• allergic reactions, including skin rash and wheezing,
• withdrawal symptoms (see section 3.),
• increased risk of falls and bone fractures. This risk is greater if the patient is also taking medicines that cause drowsiness (e.g. sedatives or hypnotics) or consuming alcohol.

Elderly patients

• In adult patients over 60 years of age taking benzodiazepines such as Midazolam Accord, an increased risk of falls and bone fractures has been observed.
• The likelihood of life-threatening adverse reactions increases in adult patients over 60 years of age.

Unexpected symptoms

• During administration of midazolam, unexpected (paradoxical) reactions have occurred, such as motor restlessness, psychomotor agitation, irritability, involuntary movements (including muscle tremors), hyperactivity, nervousness, hostility, delusions, anger, aggression, anxiety, nightmares, hallucinations (seeing and hearing things that do not exist), psychoses (loss of contact with reality), and inappropriate behaviour, episodic agitation and acts of violence. These reactions may occur after administration of too high a dose of the medicine and/or too rapid injection. The risk of these symptoms is higher in children and elderly individuals.

Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform your doctor or nurse. Adverse reactions can be reported directly to the Marketing Authorisation Holder or to the Department of Monitoring Adverse Drug Reactions at the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C, 02-222 Warsaw
Tel: +48 22 49 21 301, Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the Marketing Authorisation Holder.
Reporting adverse reactions helps provide more information on the safety of the medicine.

5. How to store Midazolam Accord

• Keep out of the sight and reach of children.
• Do not use Midazolam Accord after the expiry date stated on the carton and ampoule after EXP. The expiry date refers to the last day of the stated month.
• No special temperature requirements for storage. Store in the outer packaging to protect from light.
• For single use only. Any unused portion of the medicinal product must be discarded. Do not use Midazolam Accord if the container is leaking, or if the solution is discoloured, cloudy, or contains visible particles.
• Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the package and other information

What Midazolam Accord contains

• The active substance is midazolam (in the form of hydrochloride).
• The other components are sodium chloride, sodium hydroxide (for pH adjustment), concentrated hydrochloric acid (for dissolution and pH adjustment), and water for injections.

Each ml of 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.
What Midazolam Accord looks like and contents of the pack
Midazolam Accord is a clear, colourless to pale yellow solution, free from foreign particles, contained in pre-filled syringes made of colourless glass.
Midazolam Accord is available in packaging containing 1 pre-filled syringe.
Marketing Authorisation Holder
Accord Healthcare Polska Sp. z o.o.
Taśmowa 7 Street
02-677 Warsaw
Tel: + 48 22 577 28 00
Manufacturer/Importer
Accord Healthcare Polska Sp. z o.o.
Lutomierska 50 Street
95-200 Pabianice
LABORATORI FUNDACIÓ DAU
C/ C, 12-14 Pol. Ind. Zona Franca
08040 Barcelona
Spain

The following information is intended solely for medical or healthcare personnel:

Preparation of infusion solution
Midazolam for injection can 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 solution may be diluted to concentrations between 0.015 and 0.15 mg/mL using one of the solutions listed above.
These solutions remain stable for 24 hours at room temperature and for 3 days at 8°C. Midazolam for injection must not be mixed with any solution other than those listed above; in particular, it must not be dissolved in 6% w/v dextran (in 0.9% sodium chloride solution) in glucose, nor mixed with alkaline injection solutions. Midazolam precipitates in sodium bicarbonate solutions.
Before administration, inspect the solution visually. Only solutions without visible solid particles may be used.

The dose of Midazolam Accord must be precisely calculated for each individual patient. Only a portion of the vial content may be required; therefore, care must be taken to ensure accurate dosing according to the patient's body weight.
When the amount of drug to be injected needs to be adjusted according to the patient's body weight, calibrated syringe-vials should be used to achieve the required volume, with excess volume removed prior to intravenous or intramuscular injection.

Shelf life and storage
Midazolam Accord is intended for single use only. Any unused portion of the product must be discarded. Repeated use of the product, either in the same or different patients, is not recommended.

Unopened vials
Store in the outer packaging to protect from light.

Diluted solutions
The diluted solution maintains its chemical and physical stability for 24 hours at room temperature (15–25°C) or for 3 days at +2°C to +8°C.
From a microbiological standpoint, the product should be used immediately after dilution. If not used immediately, the responsibility for storage conditions and duration prior to use lies with the user, provided that storage does not exceed 24 hours and the temperature is maintained between +2°C and +8°C, unless dilution has been performed under controlled and validated aseptic conditions.

For continuous intravenous infusion, midazolam injection solution may be diluted to concentrations between 0.015 and 0.150 mg/mL with one of the solutions listed above.

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