MIDAZOLAM 1 mg /Ml Solution

Contents of the leaflet

1. Leaflet accompanying the packaging: patient information
2. Midazolam Accord, 1 mg/ml, solution for injection or infusion
3. Midazolam Accord, 5 mg/ml, solution for injection or infusion
   1. Read the leaflet carefully before the medicine is administered, as it contains important information for the patient.
   2. Table of contents of the leaflet:
4. What Midazolam Accord is and what it is used for
5. Important information before taking Midazolam Accord
   1. When Midazolam Accord should not be administered to the patient
   2. Warnings and precautions
   3. Adults
   4. Children and infants
   5. Midazolam Accord and other medicines
   6. Surgical procedures
   7. Midazolam Accord and alcohol
   8. Pregnancy and breastfeeding
   9. Driving and operating machinery
   10. Midazolam Accord contains sodium
6. How Midazolam Accord will be administered
   1. What dose of midazolam will be administered
   2. Method of administration
   3. Children and infants
   4. Administration of a higher dose of Midazolam Accord than recommended
   5. Discontinuation of Midazolam Accord
7. Possible side effects
   1. If the patient experiences any of the following side effects, they should STOP taking Midazolam Accord and immediately inform their doctor. These may be life-threatening and require urgent treatment.
   2. Other side effects
   3. Immune system disorders
   4. Behavioral effects:
   5. Psychiatric and nervous system disorders
   6. Cardiovascular disorders
   7. Respiratory disorders
   8. Gastrointestinal disorders
   9. Skin and subcutaneous tissue disorders
   10. Muscle disorders
   11. Administration site conditions
   12. Injuries
   13. General disorders
   14. Elderly patients
   15. Patients with severe kidney disease
   16. Reporting side effects
8. How to store Midazolam Accord
9. Contents of the packaging and other information
   1. What Midazolam Accord contains
   2. What Midazolam Accord looks like and contents of the packaging
   3. Marketing authorization holder
   4. Manufacturer/Importer
   5. Date of last revision of the leaflet: July 2024
   6. The following information is intended for healthcare professionals only:

Leaflet accompanying the packaging: patient information

Midazolam Accord, 1 mg/ml, solution for injection or infusion

Midazolam Accord, 5 mg/ml, solution for injection or infusion

Midazolam

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

• 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 symptoms are the same as yours.
• If you experience any side effects, including any not listed in this leaflet, please tell your doctor or nurse. See section 4.

Table of contents of the leaflet:

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

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

Midazolam Accord, 1 mg/ml; 5mg/ml, solution for injection or infusion contains midazolam, which belongs to a group of medicines called benzodiazepines.
This is a short-acting medicine used to induce sedation (a deep state of relaxation, drowsiness or sleep) and to relieve anxiety symptoms and reduce muscle tension.
This medicine is used for:

• inducing shallow sedation (a state of deep relaxation or drowsiness while maintaining consciousness during medical examinations and procedures) in adults and children,
• inducing sedation in adults and children in intensive care units,
• anesthesia in adults, used alone or with other anesthetics,
• premedication, used to induce a state of relaxation, calmness and drowsiness before anesthesia in adults and children.

2. Important information before taking Midazolam Accord

When Midazolam Accord should not be administered to the patient

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

Warnings and precautions

Adults

Before taking the medicine, the patient should inform their doctor or nurse if:

• the patient is over 60 years old,
• the patient has a chronic illness (e.g. chronic respiratory, kidney, liver or heart disease) or is weakened (the patient has an illness that makes them very weak, exhausted and lacking energy);
• the patient has sleep apnea syndrome (pauses in breathing during sleep); such patients will be closely monitored;
• the patient has muscular dystrophy (a nerve-muscle disease characterized by muscle weakness),
• the patient abuses or has abused alcohol in the past. Alcohol can significantly enhance the clinical effect of midazolam, including deep sedation, which can lead to coma or death;
• the patient regularly takes recreational drugs (drugs used for non-medical purposes) or has had problems with drug abuse in the past
• the patient is pregnant or thinks she may be pregnant (see "Pregnancy and breastfeeding").

Children and infants

If it is planned to administer this medicine to a child:

• It is particularly important to inform the doctor or nurse if the child has cardiovascular diseases. The child will then be closely monitored and the dose will be modified accordingly.
• Children should be closely monitored; in the case of infants and children under 6 months of age, this monitoring should include respiratory rate and hemoglobin oxygen saturation.

If any of the above situations apply to the child, the doctor or nurse should be informed.

Midazolam Accord and other medicines

The patient should tell their doctor or nurse about all medicines they have taken recently, as well as any medicines they plan to take, including herbal medicines.
This is very important because taking more than one medicine at a time can enhance or weaken the effect of the medicines taken.
In particular, the doctor or nurse should be informed if the patient is taking any of the following medicines:

• sedatives (used in anxiety states and to facilitate falling asleep),
• sleeping pills,
• hypnotics (inducing a state of calmness and causing drowsiness),
• antidepressant or antipsychotic medicines (used to treat depression or schizophrenia),
• opioid painkillers,
• cough medicines (such as those containing codeine)
• antihistamines (used to treat allergies),
• medicines used to treat fungal infections (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 infection (efavirenz or protease inhibitors such as saquinavir),
• medicines used to treat hepatitis C virus infection (protease inhibitors such as boceprevir and telaprevir),
• a medicine used to treat high cholesterol levels (atorvastatin),
• a medicine used to treat tuberculosis (rifampicin),
• a medicine used to prevent heart attack (ticagrelor),
• St. John's wort,
• 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 any doubts, they should inform their doctor or pharmacist before taking midazolam.

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 the patient has taken midazolam.

Midazolam Accord and alcohol

While taking midazolam, the patient should not drink alcohol, as it can significantly enhance the sedative effect of Midazolam Accord and cause breathing problems.

Pregnancy and breastfeeding

If the patient is pregnant or thinks she may be pregnant or plans to have a child, she should consult her doctor before taking this medicine. The doctor will decide whether this medicine is suitable for her.
Midazolam used in early pregnancy may harm the unborn child. Administration of high doses at the end of pregnancy, during childbirth or cesarean section may cause the mother to be at risk of aspiration, and the newborn to experience heart rhythm disturbances, low muscle tone (hypotonia), sucking problems, low body temperature and breathing difficulties (respiratory depression). With long-term use of the medicine at the end of pregnancy, the child may develop physical dependence, and after birth, withdrawal symptoms may occur.
Midazolam may pass into breast milk, and therefore women should not breastfeed for 24 hours after taking the medicine.

Driving and operating machinery

The mentioned medicine may cause drowsiness, dizziness, memory disturbances, decreased concentration and coordination. These symptoms may affect the performance of tasks that require precision, such as driving vehicles and operating machinery. The patient should not drive vehicles or operate machinery until the effects of the medicine have completely worn off. The doctor will decide when the patient can resume these activities.
Do not drive without knowing how the medicine affects you.
Discuss with your doctor or pharmacist if you are unsure whether you can drive safely while taking this medicine.
Lack of sleep or consumption of alcohol increases the likelihood of weakness, decreased alertness and attention.
After the treatment is completed, the patient should return home accompanied by a responsible adult.

Midazolam Accord contains sodium

This medicinal product contains less than 1 mmol of sodium (23 mg) per ampoule, i.e. the medicine is considered "sodium-free".

3. How Midazolam Accord will be administered

Midazolam should only be administered by experienced doctors or nurses. The medicine should be administered in a healthcare facility (hospital, clinic) equipped with equipment for monitoring and supporting the respiratory and circulatory systems, and by personnel trained in recognizing and treating possible side effects.

What dose of midazolam will be administered

The suitable dose of the medicine for a given patient is determined by the doctor. The doses vary significantly and depend on the planned treatment and the desired level of sedation. The dose size in a specific case depends on the patient's body weight, age, overall health, concomitantly used medicines, reaction to midazolam, and whether the patient will require administration of other medicines during midazolam administration.
If the patient is to receive strong painkillers, they will be administered first, and then midazolam will be administered in an appropriately adjusted dose.

Method of administration

Midazolam Accord can be administered in four different ways:

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

After the treatment is completed, the patient should return home accompanied by a responsible adult.

Children and infants

• In infants and children under 6 months of age, the use of midazolam is only recommended for sedation in intensive care units. The dose of the medicine should be administered gradually intravenously.
• Children aged 12 and under usually receive the medicine intravenously. When the medicine is administered for premedication (to induce relaxation, calmness and drowsiness before anesthesia), it may be administered rectally.

Administration of a higher dose of Midazolam Accord than recommended

The medicine will be administered by a doctor or nurse.
If the patient accidentally overdoses, it may lead to:

• drowsiness,
• clumsiness (lack of coordination) and loss of reflexes,
• speech disturbances (dysarthria)
• eye movement disorders (nystagmus),
• low blood pressure (hypotension),
• breathing difficulties and respiratory and circulatory depression (i.e. slowing or shallowing of breathing and slowing of heart rate) and coma.

Discontinuation of Midazolam Accord

In the case of long-term use of midazolam (for a long time), the patient may:

• develop tolerance to midazolam. The medicine becomes less effective and works weaker.
• experience dependence and withdrawal symptoms (see below).

The doctor will gradually reduce the dose of the medicine to avoid these effects.
During the use of midazolam, the following effects have been observed, especially in children and elderly patients; restlessness, excitement, irritability, involuntary movements, hyperactivity, nervousness, hostility, anger, aggression or violent behavior

If such symptoms occur, the doctor will consider discontinuing midazolam treatment.
Withdrawal symptoms:
Benzodiazepines, such as Midazolam Accord, can cause dependence if used for a long time (e.g. in intensive therapy). This means that if the administration of the medicine is stopped or the dose is reduced too quickly, withdrawal symptoms may occur, including:

• headache
• diarrhea
• muscle pain
• anxiety, tension, restlessness, disorientation, irritability
• insomnia
• mood changes
• hallucinations (seeing and hearing things that are not there)
• seizures.

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

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 taking Midazolam Accord and immediately inform their doctor. These may be life-threatening and require urgent treatment.

• Anaphylactic shock (a life-threatening allergic reaction). Symptoms are sudden rash, itching or hives; swelling of the face, lips, tongue or other parts of the body. There may also be difficulty breathing, wheezing or breathing difficulties, or paleness of the skin, weak and rapid pulse or feeling of loss of consciousness. Additionally, there may be chest pain, which can be a sign of a serious allergic reaction called Kounis syndrome.
• Heart attack (myocardial infarction). Symptoms are chest pain, which may radiate to the neck and arms, and then down to the left arm.
• Breathing difficulties or complications (sometimes causing respiratory arrest)
• Choking and sudden airway obstruction (laryngospasm)

Life-threatening incidents occur more frequently in adults over 60 years of age and in patients with respiratory or cardiac dysfunction, especially if the medicine is injected too quickly or in too high a dose.

Other side effects

Immune system disorders

• general allergic reactions (skin reactions, cardiovascular and respiratory reactions, wheezing)

Behavioral effects:

• restlessness, excitement, irritability, nervousness, anxiety
• hostility, anger, aggression or violent behavior
• excitement
• hyperactivity, changes in libido
• inappropriate behavior

Psychiatric and nervous system disorders

• confusion, disorientation
• emotional and mood disturbances
• involuntary movements
• nightmares, unusual dreams
• hallucinations (seeing and hearing things that are not there)
• psychosis (loss of contact with reality)
• drowsiness and prolonged sedation
• impaired alertness
• dizziness
• headache
• difficulty in coordinating muscle movements
• seizures in premature infants and newborns
• temporary memory loss. The duration of memory loss depends on the duration of treatment and the dose used. Memory loss may occur after treatment is completed. In individual cases, it may persist for a long time.
• drug dependence, abuse
• excitement, restlessness, anger or aggression. Uncontrolled muscle spasms or muscle tremors may also occur. These reactions may occur when the dose of the medicine is too high and (or) when it is injected too quickly. The risk of these symptoms is higher in children and the elderly.

Cardiovascular disorders

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

Respiratory disorders

• shallow breathing
• hiccups

Gastrointestinal disorders

• nausea or vomiting
• constipation
• dry mouth

Skin and subcutaneous tissue disorders

• skin redness (rash)
• itching skin lesions (hives)
• skin itching

Muscle disorders

• muscle spasms and tremors (which cannot be controlled)

Administration site conditions

• redness
• swelling of the skin
• blood clots in blood vessels or pain at the injection site

Injuries

• In elderly patients taking benzodiazepines, an increased risk of falls and fractures has been observed. This risk is higher in elderly patients and those taking other sedative medicines (including alcohol).

General disorders

• fatigue

Elderly patients

The likelihood of life-threatening side effects increases in patients over 60 years of age and in patients with respiratory or cardiac dysfunction, especially if the medicine is injected too quickly or in too high a dose.

Patients with severe kidney disease

In patients with severe kidney disease, there is a higher likelihood of side effects.
If any side effect becomes serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or nurse.

Reporting side effects

If you experience any side effects, including any not listed in this leaflet, please tell your doctor or nurse. Side effects can be reported directly to the regulatory authority 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, you can help provide more information on the safety of this medicine.

5. How to store Midazolam Accord

The storage of the medicine is the responsibility of the doctor or pharmacist. The storage conditions for this medicine are as follows:
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 month.
Store the ampoules in the original packaging to protect from light.
Medicines should not be disposed of via wastewater or household waste. Ask your 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).
Form with a strength of 1 mg/ml
1 ml of the solution for injection contains 1 mg of midazolam (in the form of hydrochloride)
Solution
5 ml
Amount of midazolam
5 mg
Form with a strength of 5 mg/ml
1 ml of the solution for injection contains 5 mg of midazolam (in the form of hydrochloride)
Solution
1 ml
3 ml
10 ml
Amount of midazolam
5 mg
15 mg
50 mg
Other ingredients of the medicine are water for injections, sodium chloride, sodium hydroxide (for pH correction) and hydrochloric acid (for pH correction).

What Midazolam Accord looks like and contents of the packaging

Midazolam Accord, solution for injection or infusion is a clear, colorless to light yellow solution in ampoules made of colorless and transparent glass
Form with a strength of 1 mg/ml is available in a packaging of 10 ampoules, each with a volume of 5 ml.
Form with a strength of 5 mg/ml is available in a packaging of 10 ampoules, each with a volume of 1 ml,
in a packaging of 10 ampoules, each with a volume of 3 ml, in a packaging of 10 ampoules, each with a volume of 10 ml,
and in a packaging of one ampoule with a volume of 10 ml
Ampoules are available in blisters/plastic molds.
Not all pack sizes may be marketed.

Marketing authorization holder

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

Manufacturer/Importer

Accord Healthcare Polska Sp.z o.o.
ul. Lutomierska 50
95-200 Pabianice

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, 50 mg/ml (5%) or 100 mg/ml (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 8°C. Midazolam for injection should not be mixed with any other solution than those mentioned, and in particular should not be dissolved in 6% dextran (with 0.9% sodium chloride solution) in glucose, or mixed with injection solutions with an alkaline reaction. Midazolam precipitates in sodium bicarbonate solutions.
Before administration, the solution should be inspected. Only solutions without visible solid particles should be used.
Shelf life and storage
Midazolam ampoules are for single use only.
Ampoules before opening
Store in the original packaging and protect from light.
Ampoules after dilution
After dilution, the solution retains its chemical and physical stability for 24 hours at room temperature (15-25°C) or for 3 days at a temperature of 8°C.
From a microbiological point of view, the diluted product should be used immediately.
If this is not possible, the responsibility for the storage time and conditions before use rests with the healthcare professional, provided that the storage time does not exceed 24 hours and the temperature is between +2°C and +8°C, unless the dilution is performed under controlled and validated aseptic conditions.
In the case of continuous intravenous infusion, midazolam solution for injection can be diluted to a concentration of 0.015 to 0.15 mg with one of the above-mentioned solutions.
Disposal of leftovers
Any unused product or waste material should be disposed of in accordance with local regulations.