Midazolam Accord

Leaflet accompanying the packaging: patient information

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

Midazolam

Read the leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet, so you can read it again if you need to.
• If you have any doubts, consult your doctor or nurse.
• If the patient experiences any side effects, including those not listed in this leaflet, they should inform their doctor or nurse. See section 4.

Table of contents of the leaflet:

• 1. What is Midazolam Accord and what is it used for
• 2. Important information before using Midazolam Accord
• 3. How to use Midazolam Accord
• 4. Possible side effects
• 5. How to store Midazolam Accord
• 6. Contents of the packaging and other information

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

Midazolam Accord contains midazolam, which belongs to a group of medicines called benzodiazepines.
Midazolam Accord is a fast-acting medicine used to induce a feeling of sleepiness or sedation and to relieve anxiety symptoms and reduce muscle tension.
Midazolam Accord is used in adults:

• in general anesthesia to induce or maintain sleep.

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

• to induce sedation - a state of calmness and sleepiness during treatment in the intensive care unit;
• to induce shallow sedation - a state of calmness and sleepiness with preserved consciousness before and during medical examinations and procedures,
• to induce a state of calmness and sleepiness before inducing anesthesia.

2. Important information before using Midazolam Accord

When not to use Midazolam Accord

If any of the above applies to the patient, Midazolam Accord should not be administered. If the patient is unsure, they should inform their doctor or nurse before taking the medicine.

Warnings and precautions

Before administering the medicine, the doctor or nurse should be informed if:

• the patient is over 60 years old;
• the patient has a chronic illness, suffers from chronic respiratory, kidney, liver, or heart disease;
• the patient has a disease that causes them to be very weak, exhausted, and lacking energy;
• the patient has muscle weakness characterized by decreased muscle strength;
• the patient has sleep apnea syndrome (pauses in breathing during sleep); such patients will be closely monitored;
• the patient abuses or has abused alcohol in the past;
• the patient abuses or has abused drugs in the past;
• the patient is pregnant or suspects she may be pregnant (see "Pregnancy and breastfeeding").

If any of the above applies to the patient (or if the patient is unsure), they should inform their doctor or nurse before taking Midazolam Accord.
If it is planned to administer this medicine to a child aged 12 or older:

• the doctor or nurse should be informed if any of the above applies to the child (aged 12 or older);
• in particular, the doctor or nurse should be informed if the child has heart or breathing problems.

Midazolam Accord and other medicines

The doctor or nurse should be informed about all medicines the patient is currently taking or has recently taken. This includes medicines bought without a prescription and herbal medicines.
Taking Midazolam Accord with other medicines may affect their action.
In particular, the doctor or nurse should be informed if the patient is taking any of the following medicines:

• antidepressant or antipsychotic medicines (used to treat depression or schizophrenia),
• sleeping medicines,
• sedatives (used to calm and induce sleep),
• anxiolytics (used to treat anxiety and facilitate sleep),
• carbamazepine or phenytoin (used to treat seizures or epilepsy),
• rifampicin (used to treat tuberculosis),
• medicines used to treat HIV infection, known as protease inhibitors (such as saquinavir),
• macrolide antibiotics (such as erythromycin or clarithromycin),
• medicines used to treat fungal infections (ketoconazole, voriconazole, fluconazole, itraconazole, posaconazole),
• opioid painkillers (very strong painkillers),
• atorvastatin (used to treat high cholesterol),
• antihistamines (used to treat allergies),
• St. John's Wort (a herbal medicine used to treat depression),
• cough medicines (such as those containing codeine),
• medicines used to treat high blood pressure and heart disease, such as calcium channel blockers (e.g., diltiazem, verapamil, and methyldopa),
• medicines used to treat hepatitis C infection (protease inhibitors such as boceprevir and telaprevir),
• tikagrelor (a medicine used to prevent heart attacks),
• 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 to the patient or if they have doubts, they should inform their doctor or nurse before using Midazolam Accord.

Surgical procedures

If the patient is to be given an anesthetic before surgery or dental treatment (including inhaled anesthetics), it is essential to inform the doctor or dentist that they have taken Midazolam Accord.

Midazolam Accord and alcohol

While taking Midazolam Accord, the patient should not drink alcohol, as it may enhance the feeling of sleepiness and cause breathing problems.

Pregnancy and breastfeeding

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

Midazolam Accord used in early pregnancy may harm the unborn child.
Administering high doses at the end of pregnancy, during delivery, or cesarean section may cause the risk of inhalation, and in the newborn, heart rhythm disturbances, low muscle tone (hypotonia), feeding problems, low body temperature, and breathing difficulties (respiratory depression). With prolonged use of the medicine at the end of pregnancy, the child may develop physical dependence, and after birth, withdrawal symptoms may occur.

Driving and operating machinery

• After taking Midazolam Accord, the patient should not drive or operate machinery until their doctor decides it is safe to do so.
• Midazolam Accord may cause sleepiness, memory disturbances, decreased concentration, and coordination. These effects may impair the ability to drive or operate machinery.
• After treatment, the patient should go home accompanied by an adult caregiver.

Midazolam Accord contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per dose, which means the 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, and for the treatment of possible side effects.
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 tube inserted into a vein (intravenous infusion),
• by injection into a muscle (intramuscular injection),
• rectally.

Dosage and administration route

The dose of Midazolam Accord may vary for each patient. The appropriate dose of the medicine for a given patient is determined by the doctor. The dose size depends on the patient's age, body weight, and overall health. It also depends on the purpose of the medicine and the patient's response to treatment, as well as whether other medicines are being administered at the same time.

After administering Midazolam Accord

After the procedure, the patient should go home accompanied by an adult caregiver, as Midazolam Accord may cause sleepiness, memory disturbances, decreased concentration, and coordination.

Using a higher dose of Midazolam Accord than recommended

The medicine will be administered by a doctor or nurse, which means there is a low probability of using too high a dose. However, if the patient accidentally overdoses, it may lead to:

• sleepiness and loss of coordination (ataxia) and reflexes,
• speech disturbances (dysarthria) and involuntary eye movements (nystagmus),
• low blood pressure (hypotension) - which may cause dizziness or fainting,
• breathing difficulties and respiratory and circulatory depression (slowdown or cessation of breathing and heart function) and loss of consciousness (coma).

Using Midazolam Accord for long-term sedation in patients in the intensive care unit

In the case of long-term use of Midazolam Accord, the following may occur:

• decreased efficacy of the medicine,
• patient dependence on the medicine and withdrawal symptoms after stopping its use (see below).

Stopping the use of Midazolam Accord

In the case of long-term use of Midazolam Accord, for example, in the intensive care unit, after stopping the administration of the medicine, withdrawal symptoms may occur, including:

• mood changes,
• seizures,
• headaches,
• diarrhea,
• muscle pain,
• insomnia,
• anxiety, tension, restlessness, disorientation, irritability,
• hallucinations (seeing and 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 side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The following side effects have occurred with an unknown frequency.

If the patient experiences any of the following side effects, they should

STOP using Midazolam Accord and immediately inform their doctor.

These may be life-threatening side effects and require immediate treatment.

• Severe allergic reaction (anaphylactic shock). Symptoms are sudden rash, itching, or hives; swelling of the face, lips, tongue, or other parts of the body. It is also possible to experience breathing difficulties, wheezing, or respiratory problems, or pale skin, weak and rapid pulse, or a feeling of loss of consciousness. Additionally, there may be chest pain, which can be a sign of a severe allergic reaction called Kounis syndrome.

Chest pain, which may radiate to the neck and arms, and then down to the left arm.

• Heart attack (cardiac arrest). Symptoms are chest pain, which 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 side effects occur more frequently in patients over 60 years old, in patients with respiratory or cardiac dysfunction, especially if the medicine is injected too quickly or in high doses.

Other side effects

Psychiatric and nervous system disorders

• impaired alertness,
• confusion,
• excessive feelings of happiness or excitement (euphoria)
• changes in libido,
• feeling of fatigue, sleepiness, 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 administered. In individual cases, it may last for a long time.
• Agitation, restlessness, anger, or aggressive behavior. There may also be muscle spasms and involuntary muscle twitching. These disorders are more likely to occur after administration of a high dose of Midazolam Accord or if the medicine is injected too quickly. This is also more likely in children and the elderly.

Cardiovascular disorders

• fainting,
• slow heart rate,
• flushing of the face and neck,
• low blood pressure, which may cause dizziness or fainting.

Respiratory disorders

• hiccups,
• shallow breathing.

Gastrointestinal disorders

• dry mouth,
• constipation,
• nausea, vomiting.

Skin and subcutaneous tissue disorders

• itching,
• rash, including papular rash (hives),
• redness, pain, thrombophlebitis, 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 higher if the patient is also taking medicines that cause sleepiness (e.g., sedatives or sleeping pills) or alcohol.

Elderly

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

Unexpected symptoms

• During the use of midazolam, unexpected (paradoxical) reactions have occurred, such as restlessness, excitement, irritability, involuntary movements (including muscle twitching), overstimulation, nervousness, hostility, delusions, anger, aggression, restlessness, nightmares, hallucinations (seeing and hearing things that do not exist), psychosis (loss of contact with reality), and inappropriate behavior, fits of excitement, and violent acts. These reactions are more likely to occur after administration of a high dose of the medicine and/or if the medicine is injected too quickly. The risk of these symptoms is higher in children and the elderly.

Reporting side effects

If side effects occur, including those not listed in this leaflet, the patient should inform their doctor or nurse. Side effects can be reported directly to the marketing authorization holder or to the Department of Drug Safety Monitoring of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products
Al. Jerozolimskie 181C, 02-222 Warsaw
Phone: +48 22 49 21 301, Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder.
By reporting side effects, more information can be collected on the safety of the medicine.

5. How to store Midazolam Accord

• Store out of sight and reach of children.
• Do not use Midazolam Accord after the expiry date stated on the carton and ampoule after the abbreviation EXP. The expiry date refers to the last day of the specified month.
• No special storage temperature instructions. Store in the outer packaging to protect from light.
• For single use only. Any unused medicine should be discarded. It is not recommended to use the medicine for multiple administrations to one or different patients.
• Medicines should not be disposed of via wastewater or household waste. The patient should ask their pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the packaging and other information

What Midazolam Accord contains

• The active substance of the medicine is midazolam (in the form of hydrochloride).
• The other ingredients of the medicine are sodium chloride, sodium hydroxide (to adjust pH), hydrochloric acid (to dissolve and adjust pH), and water for injections.

Each ml of the solution contains midazolam hydrochloride equivalent to 1 mg of midazolam.
Each pre-filled syringe with a capacity of 5 ml contains midazolam hydrochloride equivalent to 5 mg of midazolam.

What Midazolam Accord looks like and what the packaging contains

Midazolam Accord is a clear, colorless to pale yellow solution, free from foreign particles, in pre-filled syringes made of colorless glass.
Midazolam Accord is available in packaging containing 1 pre-filled syringe.

Marketing authorization holder

Accord Healthcare Polska Sp. z o.o.
Taśmowa 7
02-677 Warsaw
Phone: +48 22 577 28 00

Manufacturer/Importer

Accord Healthcare Polska Sp. z o.o.
Lutomierska 50
95-200 Pabianice
LABORATORI FUNDACIÓ DAU
C/ C, 12-14 Pol. Ind. Zona Franca
08040 Barcelona
Spain

Date of last revision of the leaflet: July 2024

The following information is intended for healthcare professionals only:

Preparation of the infusion solution
Midazolam for injection can be diluted in 0.9% sodium chloride solution, 5% or 10% glucose solution, Ringer's solution, or Hartmann's solution. In the case of continuous intravenous infusion, the midazolam solution can be diluted to a concentration of 0.015 to 0.15 mg per ml, using one of the above-mentioned solutions.
These solutions remain stable for 24 hours at room temperature and for 3 days at a temperature of 2°C to 8°C.
From a microbiological point of view, the product should be used immediately after dilution. If the product is not used immediately, the responsibility for the storage time and conditions before use lies with the person administering the medicine, provided that the storage time does not exceed 24 hours and the temperature is between 2°C and 8°C, unless the dilution was performed under controlled and validated aseptic conditions.
In the case of continuous intravenous infusion, midazolam injection solution can be diluted to a concentration of 0.015 to 0.150 mg with one of the above-mentioned solutions.
Disposal of residues
Any unused product or waste should be disposed of in accordance with local regulations.

The dose of Midazolam Accord must be precisely calculated for each patient. Only part of the medicine may be required, so attention should be paid to the accuracy of the dose needed by the patient, depending on their body weight.

When the amount of medicine to be injected requires adjustment based on the patient's body weight, calibrated pre-filled syringes should be used to achieve the required volume, removing any excess before injection in the case of rapid intravenous or intramuscular injection.

Intramuscular injection.
Shelf life and storage

Midazolam Accord is intended for single use only. Any unused product should be discarded. It is not recommended to use the medicine for multiple administrations to one or different patients.

Ampoules before opening
Store in the outer packaging to protect from light.
Ampoules after dilution
The solution remains chemically and physically stable after dilution for 24 hours at room temperature (15-25°C) or for 3 days at a temperature of 2°C to 8°C.
From a microbiological point of view, the product should be used immediately after dilution. If the product is not used immediately, the responsibility for the storage time and conditions before use lies with the person administering the medicine, provided that the storage time does not exceed 24 hours and the temperature is between 2°C and 8°C, unless the dilution was performed under controlled and validated aseptic conditions.
In the case of continuous intravenous infusion, midazolam injection solution can be diluted to a concentration of 0.015 to 0.150 mg with one of the above-mentioned solutions.
Disposal of residues
Any unused product or waste should be disposed of in accordance with local regulations.