MIDAZOLAM 1 mg /Ml Solution

Contents of the leaflet

1. Leaflet attached to the packaging: patient information
2. Midazolam SUN, 1 mg/mL, solution for injection/infusion
   1. Midazolam SUN, 2 mg/mL, solution for injection/infusion in a pre-filled syringe
   2. It is essential to carefully read the contents of the leaflet before using the medicine, as it contains important information for the patient.
   3. Table of contents of the leaflet:
3. What Midazolam SUN is and what it is used for
4. Important information before using Midazolam SUN
   1. When not to use Midazolam SUN
   2. Warnings and precautions
   3. Adults
   4. Midazolam SUN and other medicines
   5. Surgical procedures
   6. Using Midazolam SUN with alcohol
   7. Pregnancy and breastfeeding
   8. Driving and operating machinery
   9. Midazolam SUN contains sodium
5. How to use Midazolam SUN
   1. Dosage for adults
   2. Children
   3. Method of administration
   4. Using a higher dose of Midazolam SUN than recommended
   5. Stopping the use of Midazolam SUN
6. Possible side effects
   1. If the patient experiences any of the following side effects, they should stop using Midazolam SUN and immediately inform their doctor. These may be life-threatening and require urgent treatment:
   2. Other side effects (frequency unknown)
   3. Frequency unknown (cannot be estimated from available data)
   4. Immune system disorders:
   5. Psychiatric disorders:
   6. Muscle disorders
   7. Nervous system disorders
   8. Cardiovascular disorders:
   9. Respiratory disorders:
   10. Gastrointestinal and oral disorders:
   11. Skin disorders:
   12. Administration site conditions:
   13. Injuries:
   14. General disorders:
   15. Reporting side effects
7. How to store Midazolam SUN
8. Contents of the packaging and other information
   1. What Midazolam SUN contains
   2. What Midazolam SUN looks like and contents of the packaging
   3. Marketing authorization holder
   4. Manufacturer/Importer
   5. This medicinal product is authorized in the Member States of the European Economic Area under the following names:
   6. France
   7. Spain
   8. Germany
   9. Poland
   10. Romania
   11. United Kingdom
   12. Italy
   13. To obtain more detailed information about this medicine, the patient should contact the local representative of the marketing authorization holder:
   14. INFORMATION FOR HEALTHCARE PROFESSIONALS
   15. It is essential to read the Summary of Product Characteristics to obtain full information on prescribing the medicine.
   16. Dosage and method of administration
   17. Adults
   18. Intravenous loading dose:
   19. Intravenous maintenance dose:
   20. Special patient groups
   21. Renal impairment:
   22. Hepatic impairment:
   23. Incompatibilities
   24. Special precautions for storage

Leaflet attached to the packaging: patient information

Midazolam SUN, 1 mg/mL, solution for injection/infusion

In a pre-filled syringe

Midazolam SUN, 2 mg/mL, solution for injection/infusion in a pre-filled syringe

Midazolam
For administration to adult patients

It is essential to carefully read the contents of the leaflet before using the medicine, as it contains important information for the patient.

• The leaflet should be kept in case it needs to be read again.
• In case of any doubts, the patient should consult a doctor, pharmacist, or nurse.
• If the patient experiences any adverse reactions, including any adverse reactions not listed in this leaflet, they should inform their doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet:

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

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

Midazolam SUN belongs to a group of medicines called benzodiazepines. It is a short-acting medicine used to induce deep sedation and sleep (sedation), as well as to relieve anxiety symptoms and reduce muscle tension.
The medicine is used for sedation in adult patients in intensive care units.

2. Important information before using Midazolam SUN

When not to use Midazolam SUN

• if the patient is allergic 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.

If any of the above information applies to the patient, Midazolam SUN should not be used. If the patient is unsure whether this information applies to them, they should inform their doctor before taking the medicine.

Warnings and precautions

Administering midazolam may lower heart muscle contractility (the ability of the heart muscle to contract) and cause apnea (pauses in breathing). Rarely, severe adverse reactions related to the cardiovascular and respiratory systems have been observed, such as respiratory depression (slowing or shallowing of breathing), apnea, sudden cessation of breathing and/or circulation. To avoid these reactions, the medicine should be injected slowly and in the smallest possible dose.
Paradoxical reactions and anterograde amnesia (loss of memory for recent events) have been reported after midazolam administration (see section 4 "Possible side effects").

Adults

Before administering Midazolam SUN, the patient should discuss the following with their doctor:

• if the patient is over 60 years old,
• if the patient has a chronic illness (e.g., chronic respiratory, kidney, liver, or heart disease),
• if the patient is weakened (has a disease that makes them feel very weak, exhausted, and lacking energy),
• if the patient has been diagnosed with "sleep apnea syndrome" (cessation of breathing during sleep), and may therefore be closely monitored,
• if the patient has muscle weakness (a neuromuscular disease characterized by muscle weakness),
• if the patient has a history of alcohol abuse. Alcohol may enhance the effect of Midazolam SUN, potentially leading to sedation that can cause coma or death.
• if the patient regularly takes other medicines or has had problems with taking medicines in the past. If any of the above situations apply to the patient or if they have any doubts, they should inform their doctor or nurse before using Midazolam SUN.

Midazolam SUN and other medicines

The patient should inform their doctor, pharmacist, or nurse about all medicines they are currently taking, as well as any medicines they plan to take, including those available without a prescription and herbal remedies.
This is very important because taking several medicines at the same time can increase or decrease their effects.
In particular, the patient should inform their doctor or nurse if they are taking any of the following medicines:

• sedatives (used to treat anxiety and to facilitate sleep),
• sleeping pills,
• hypnotics (inducing a state of calm or sleepiness),
• antidepressants (medicines used to treat depression),
• narcotic painkillers (strongly acting painkillers),
• antihistamines (medicines used to treat allergies),
• medicines used to treat fungal infections (ketokonazole, vorikonazole, fluconazole, itraconazole, posakonazole),
• macrolide antibiotics (such as erythromycin or clarithromycin),
• diltiazem (a medicine used to treat high blood pressure),
• medicines used to treat HIV infection called protease inhibitors (such as saquinavir),
• medicines used to treat hepatitis C virus infection (protease inhibitors, such as boceprevir and telaprevir),
• atorvastatin (a medicine that lowers cholesterol levels),
• rifampicin (a medicine used to treat tuberculosis),
• tikagrelor (used to prevent heart attack),
• St. John's Wort (a herbal medicine). If any of the above situations apply to the patient or if they have any doubts, they should inform their doctor or nurse before using Midazolam SUN.

Surgical procedures

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

Using Midazolam SUN with alcohol

During treatment with midazolam, the patient should not drink alcohol, as it may significantly enhance the sedative effect of Midazolam SUN and cause breathing problems.

Pregnancy and breastfeeding

If the patient is pregnant or breastfeeding, thinks they may be pregnant, or plans to have a child, they should consult their doctor before using this medicine. The doctor will decide whether the medicine is suitable for them.
Midazolam SUN used in early pregnancy may harm the unborn child.
Administering 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, hypotonia (low muscle tone), feeding problems, low body temperature, and respiratory depression (breathing difficulties). In the case of prolonged use at the end of pregnancy, the child may develop physical dependence, and after birth, withdrawal symptoms may occur.
Midazolam SUN may pass into breast milk, and therefore, women should not breastfeed for 24 hours after taking the medicine.

Driving and operating machinery

• Midazolam SUN may cause drowsiness, memory disturbances, decreased concentration, and coordination. These symptoms may affect the performance of tasks that require precision, such as driving and operating machinery.
• The patient should not drive or operate machinery until they have fully recovered. The doctor will decide when the patient can resume these activities.
• The patient should not drive while taking this medicine until they know how it affects them.
• Driving while the medicine affects the ability to drive is an offense.
• It will not be an offense if:
• The medicine was prescribed to treat a medical or dental problem.
• The patient took the medicine as directed by the doctor or according to the information provided with the medicine.
• The medicine does not affect the ability to drive safely.

In case of doubts about the safety of driving while taking this medicine, the patient should consult their doctor or pharmacist.

• Lack of sleep or alcohol consumption may also impair concentration.
• After the procedure, the patient should always go home accompanied by an adult caregiver.

Midazolam SUN contains sodium

This medicinal product contains 157.36 mg of sodium (the main component of table salt) in each pre-filled syringe.
This is equivalent to 7.9% of the maximum daily sodium intake for an adult.

3. How to use Midazolam SUN

Midazolam should only be administered by experienced doctors in a healthcare facility (hospital, clinic) equipped with equipment for monitoring and supporting respiratory, cardiac, and circulatory functions, as well as by personnel trained in recognizing and treating possible adverse reactions.

Dosage for adults

The appropriate dose of the medicine for a given patient is determined by the doctor. The doses depend on the planned treatment and the required level of sedation and sleep (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 other concomitantly administered medicines will affect the product Midazolam SUN.
If the patient is to receive strong painkillers, they will be administered first, and then midazolam will be administered in a dose adjusted to the patient.

Children

Midazolam SUN is not recommended for use in children due to the total amount of midazolam contained in the pre-filled syringe.

Method of administration

Midazolam SUN can be administered in two different ways:

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

After the procedure, the patient should always go home accompanied by an adult caregiver.

Using a higher dose of Midazolam SUN than recommended

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

• drowsiness,
• loss of coordination and reflexes,
• dyarthria (speech disturbances)
• nystagmus (involuntary eye movements),
• hypotension (low blood pressure),
• apnea, respiratory and circulatory depression (slowing or cessation of breathing and heart function) and coma.

Stopping the use of Midazolam SUN

In the case of prolonged 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 reactions.
During treatment with midazolam, the following adverse reactions have been observed, especially in elderly patients: restlessness, agitation, irritability, involuntary movements, hyperactivity, hostility, aggression, anxiety, nightmares, hallucinations (seeing and possibly hearing things that are not there), psychosis (loss of contact with reality), inappropriate behavior, excitement, and violent acts (these are also known as paradoxical reactions, which are the opposite of the expected effects of the medicine). If such symptoms occur, the doctor will consider discontinuing treatment with Midazolam SUN.
Withdrawal symptoms:
Benzodiazepines, such as Midazolam SUN, can cause dependence if used for a long time (e.g., in intensive care units). This means that if the patient's treatment is stopped or the dose is reduced too quickly, withdrawal symptoms may occur, including:

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

In severe cases of withdrawal, the patient may experience a feeling of loss of contact with reality, numbness and tingling of limbs (e.g., hands and feet), sensitivity to light, noise, and touch.
If the patient has any questions about the use of this medicine, they should consult their doctor, pharmacist, or nurse.

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 SUN 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. The patient may also experience difficulty breathing, wheezing, or breathing 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 potentially serious allergic reaction called Kounis syndrome.
• heart attack (cardiac arrest). Symptoms are chest pain that may radiate to the neck, arms, and down to the left arm.
• breathing difficulties, including complications (sometimes causing cessation of breathing)
• choking and sudden airway obstruction (laryngospasm).

Life-threatening side effects occur more frequently in patients over 60 years old, patients with respiratory failure, or impaired heart muscle function, especially if the medicine is injected too quickly or in large doses.

Other side effects (frequency unknown)

Frequency unknown (cannot be estimated from available data)

Immune system disorders:

• general allergic reactions (skin reactions, cardiovascular and blood disorders, wheezing)

Psychiatric disorders:

• restlessness, agitation, irritability
• nervousness, anxiety
• hostility, anger, or aggressive behavior
• excitement
• hyperactivity
• libido changes
• inappropriate behavior

Muscle disorders

• muscle spasms and muscle tremors (uncontrolled muscle shaking)

Nervous system disorders

• -confusion, disorientation
• -emotional and mood disturbances, involuntary movements
• -nightmares, unusual dreams
• -hallucinations (seeing and possibly hearing things that are not there)
• -psychosis (loss of contact with reality)
• -drowsiness and prolonged sedation
• -limited attention
• -headache
• -dizziness
• -difficulty with muscle coordination
• -temporary memory loss (the duration depends on the amount of Midazolam SUN administered; it may occur after treatment. In individual cases, memory loss was prolonged)

Dependence and abuse of the medicine may occur.

Cardiovascular disorders:

• low blood pressure
• slow heart rate
• flushing of the face and neck (hot flashes), fainting, or headache

Respiratory disorders:

• shallow breathing
• hiccups

Gastrointestinal and oral disorders:

• nausea or vomiting
• constipation
• dry mouth

Skin disorders:

• rash,
• hives (papular rash),
• itching

Administration site conditions:

• redness
• swelling of the skin
• thrombophlebitis or pain at the injection site

Injuries:

• patients taking benzodiazepine medicines are at risk of falls and bone fractures. This risk increases in older people and those taking other sedative medicines (including alcohol).

General disorders:

• fatigue (tiredness)

Elderly patients:

• the likelihood of life-threatening side effects increases in patients over 60 years old and in patients with respiratory failure or impaired heart muscle function, especially if the medicine is injected too quickly or in large doses.

Patients with severe renal impairment:

• in patients with severe renal impairment, the risk of side effects is higher
• if any of the side effects worsen or if any side effects not listed in the leaflet occur, the patient should inform their doctor or nurse.

Reporting side effects

If side effects occur, including any side effects not listed in this leaflet, the patient should inform their doctor or pharmacist. Side effects can be reported directly to the Department of Adverse Reaction Monitoring 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.
Reporting side effects will help gather more information on the safety of the medicine.

5. How to store Midazolam SUN

Store in a place out of sight and reach of children.
Do not use Midazolam SUN after the expiry date stated on the carton and pre-filled syringe after the "EXP" deadline. The expiry date refers to the last day of the specified month.
Store the pre-filled syringe in the outer packaging to protect it from light.
The doctor or pharmacist is responsible for storing Midazolam SUN and for the proper disposal of any unused remains.

6. Contents of the packaging and other information

What Midazolam SUN contains

• The active substance of the medicine is midazolam. Midazolam SUN, 1 mg/mL: Each mL of the solution for injection/infusion contains 1 mg of midazolam. Each pre-filled syringe with a capacity of 50 mL contains 50 mg of midazolam.

Midazolam SUN, 2 mg/mL:
Each mL of the solution for injection/infusion contains 2 mg of midazolam.
Each pre-filled syringe with a capacity of 50 mL contains 100 mg of midazolam.
Other ingredients of the medicine are: sodium chloride, 0.5% hydrochloric acid (to adjust pH), and sodium hydroxide (to adjust pH), water for injections.

What Midazolam SUN looks like and contents of the packaging

Midazolam SUN is a clear, colorless, and viscous solution for injection/infusion.
Midazolam SUN is available in a blister pack containing one pre-filled syringe with 50 mL of solution for injection/infusion.

Marketing authorization holder

Sun Pharmaceuticals Industries Europe B.V.
Polarisavenue 87
2132 JH Hoofddorp
Netherlands

Manufacturer/Importer

Sun Pharmaceuticals Industries Europe B.V.
Polarisavenue 87
2132 JH Hoofddorp
Netherlands
Terapia S.A.
Strada Fabricii nr. 124
400632, Cluj-Napoca
Cluj County
Romania

This medicinal product is authorized in the Member States of the European Economic Area under the following names:

France

Midazolam SUN

Spain

Midazolam SUN

Germany

Midazolam SUN

Poland

Midazolam SUN

Romania

Midazolam SUN

United Kingdom

Midazolam

Italy

Midazolam SUN

To obtain more detailed information about this medicine, the patient should contact the local representative of the marketing authorization holder:

Ranbaxy (Poland) Sp. z o. o.
ul. Idzikowskiego 16
00-710 Warsaw, Poland
Phone: +48 22 642 07 75
Date of last revision of the leaflet: 09.08.2023
Information intended only for healthcare professionals:

INFORMATION FOR HEALTHCARE PROFESSIONALS

It is essential to read the Summary of Product Characteristics to obtain full information on prescribing the medicine.

Dosage and method of administration

Midazolam is a potent substance that should be administered slowly and gradually.
It is recommended to administer midazolam gradually to safely achieve the desired level of sedation, depending on the patient's clinical needs, health status, and age, as well as other concomitantly administered medicines. When determining the dose for patients over 60 years old, weakened, or chronically ill, the doctor should consider the specific risk factors for each patient. Standard dosing is provided in the table. Additional information is provided below the table.
Sedation in intensive care unit patients
The required level of sedation is achieved by gradually increasing the dose of midazolam and then administering the medicine in a continuous intravenous infusion, depending on clinical needs, the patient's physical condition, age, and concomitantly administered medicines.

Adults

Intravenous loading dose:

From 0.03 mg/kg to 0.3 mg/kg of midazolam administered slowly, in consecutive injections.
Each dose of 1 mg to 2.5 mg should be administered over a period of 20 to 30 seconds, with a 2-minute interval between consecutive injections.
In patients with hypovolemia, vasoconstriction, or hypothermia, the loading dose should be reduced or omitted.
If midazolam is administered with potent analgesics, these should be administered first to safely adjust the sedative effect of midazolam according to the level of sedation caused by the analgesic.

Intravenous maintenance dose:

Doses may range from 0.03 mg/kg/h to 0.2 mg/kg/h.
In patients with hypovolemia, vasoconstriction, or hypothermia, the maintenance dose should be reduced. The level of sedation should be regularly assessed.
During prolonged sedation, tolerance may develop, and it may be necessary to increase the dose.
If higher doses are required, Midazolam SUN 2 mg/mL should be used.
When starting an infusion with midazolam in patients with impaired cardiovascular function, the dose should be gradually increased, and the patient's hemodynamic instability should be monitored, e.g., a decrease in blood pressure.

Such patients are also prone to midazolam-induced respiratory depression and require close monitoring of their respiratory function and oxygen saturation.

Special patient groups

Renal impairment:

In patients with severe renal impairment (creatinine clearance below 30 mL/min), midazolam administration may be accompanied by more pronounced and prolonged sedation, including potentially clinically significant respiratory and cardiovascular depression. In this patient group, midazolam should be dosed cautiously and gradually increased to achieve the desired effect.
In patients with renal impairment (creatinine clearance <10 ml min), the pharmacokinetics of unbound midazolam after a single intravenous dose is similar to that observed in healthy volunteers. however, during prolonged infusion intensive care unit patients, sedative effect was more pronounced patients with renal impairment due accumulation 1'-hydroxymidazolam glucuronide.< p>

Hepatic impairment:

Hepatic impairment reduces the clearance of midazolam administered intravenously, resulting in an increased terminal half-life. Therefore, the clinical effect in patients with hepatic impairment may be stronger and prolonged. In such cases, it may be necessary to reduce the dose of midazolam and monitor the patient's vital functions.

Incompatibilities

Due to the lack of compatibility studies for this medicinal product with other pharmaceutical products, it should not be mixed with them in the same administration.
The use of extension tubes for infusion pumps made of polyvinyl chloride (PVC) should be avoided. If this cannot be avoided, the use of PVC extension tubes for infusion pumps should be limited to 24 hours.

Special precautions for storage

The pre-filled syringe should be stored in the outer packaging to protect it from light.