Midazolam Accord

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 given, 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.

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 given
• 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, 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 with preserved 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 relaxation, calmness, and drowsiness before anesthesia in adults and children.

2. Important information before taking Midazolam Accord

When Midazolam Accord should not be given to the patient

• if the patient has been diagnosed with an allergy (hypersensitivity) to midazolam or any of the other ingredients of this medicine listed in section 6,
• if the patient has been diagnosed with an allergy to benzodiazepine medicines, such as diazepam or nitrazepam,
• if the patient has severe breathing difficulties and is to undergo shallow sedation.

If any of the above applies to the patient, midazolam should not be given. If the patient is unsure, they should tell 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 or thinks they may be pregnant (see "Pregnancy and breastfeeding").

Children and infants

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

• It is especially 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 or 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 sleep),
• sleeping pills,
• hypnotics (inducing a state of calm 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 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 they have taken midazolam.

Midazolam Accord and alcohol

During treatment with 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 they may be pregnant or plans to have a child, they should consult their doctor before taking this medicine. The doctor will decide if this medicine is suitable for them.
Midazolam used in early pregnancy may harm the unborn child. Administration of high doses at the end of pregnancy, during delivery, or cesarean section may cause the mother to be at risk of aspiration, and the newborn may experience heart rhythm disturbances, low muscle tone (hypotonia), sucking 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.
Midazolam may pass into breast milk, and therefore, women should not breastfeed for 24 hours after taking the medicine.

Driving and using machines

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

Midazolam Accord contains sodium

This medicinal product contains less than 1 mmol of sodium (23 mg) per ampoule, which means it is essentially "sodium-free".

3. How Midazolam Accord will be given

Midazolam should only be given by experienced doctors or nurses. The medicine should be given in a healthcare facility (hospital, clinic) equipped with equipment for monitoring and supporting respiratory and cardiovascular functions and by personnel trained to recognize and treat possible side effects.

How much midazolam will be given

The appropriate dose of the medicine for the patient will be 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 particular case depends on the patient's body weight, age, overall health, concomitantly used medicines, reaction to midazolam, and whether the patient will require other medicines during midazolam administration.
If the patient is to receive strong painkillers, they will be given first, and then midazolam will be given in an appropriately adjusted dose.

Method of administration

Midazolam Accord can be given 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 treatment, the patient should be accompanied home by a responsible adult.

Children and infants

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

Overdose of Midazolam Accord

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

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

Stopping Midazolam Accord treatment

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 treatment with midazolam, the following effects have been observed, especially in children and elderly patients; restlessness, agitation, irritability, involuntary movements, hyperactivity, nervousness, hostility, anger, aggression, excitement, changes in libido, inappropriate behavior

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 tell their doctor immediately. 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 shortness of breath, or pale 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 side effects are more common in adults over 60 years of age and in patients with respiratory or cardiac impairment, 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, agitation, 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 do not exist)
• psychosis (loss of contact with reality)
• drowsiness and prolonged sedation
• impaired alertness
• dizziness
• headache
• difficulty 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. Amnesia may occur after treatment has ended. In individual cases, it may persist for a long time.
• drug dependence, abuse
• agitation, restlessness, anger, or aggression. Uncontrolled muscle spasms or tremors may also occur. These reactions may occur when the medicine is given in too high a dose and (or) when it is injected too quickly. The risk of these effects 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)
• itchy skin changes (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, there is an increased risk of falls and fractures. 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 impairment, 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 risk 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 side effects occur, including any not listed in this leaflet, the patient should tell 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
Jerozolimskie Avenue 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

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. 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 pack and other information

What Midazolam Accord contains

The active substance of the medicine is midazolam (as hydrochloride).
1 mg/ml strength
1 ml of solution for injection contains 1 mg of midazolam (as hydrochloride)
Solution
5 ml
Amount of midazolam
5 mg
5 mg/ml strength
1 ml of solution for injection contains 5 mg of midazolam (as 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 adjustment), and concentrated hydrochloric acid (for pH adjustment).

What Midazolam Accord looks like and contents of the pack

Midazolam Accord, solution for injection or infusion, is a clear, colorless to pale yellow solution in ampoules made of clear and colorless glass
The 1 mg/ml strength is available in packs of 10 ampoules of 5 ml each.
The 5 mg/ml strength is available in packs of 10 ampoules of 1 ml each, in packs of 10 ampoules of 3 ml each, in packs of 10 ampoules of 10 ml each, and in packs of 1 ampoule 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.
Taśmowa Street 7
02-677 Warsaw
Phone: +48 22 577 28 00

Manufacturer/Importer

Accord Healthcare Polska Sp.z o.o.
Lutomierska Street 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 8°C. Midazolam for injection should not be mixed with any other solution than those mentioned, and in particular, it 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 particles should be used.
Shelf life and storage
Ampoules of midazolam 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 8°C.
From a microbiological point of view, the diluted product should be used immediately.
If not, 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 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 should be disposed of in accordance with local regulations.