Midazolam sun

Package leaflet: Information for the patient

Midazolam SUN, 1 mg/mL, solution for injection/infusion
in ampoule-syringe
Midazolam SUN, 2 mg/mL, solution for injection/infusion
in ampoule-syringe
Midazolamum
For administration to adult patients
Please read this leaflet carefully before using this medicine, because
it contains important information for the patient.

• Keep this leaflet so that you can read it again if necessary.
• If you have any questions, please consult your doctor, pharmacist, or nurse.
• If you experience any adverse reactions, including any adverse reactions not listed in this leaflet, you should inform your doctor, pharmacist, or nurse. See section 4.

Table of contents:

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 pack 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 anesthesia (sedation), as well as to relieve symptoms of anxiety 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 had an allergic reaction to benzodiazepines, such as diazepam or nitrazepam,
• if the patient has severe breathing problems.

If any of the above apply to the patient, Midazolam SUN must not be used. If the patient is unsure whether any of these apply, they should inform their doctor before administration of the medicine.

Warnings and precautions

Administration of midazolam may reduce myocardial contractility (the heart muscle's ability to contract) and cause apnoea (interruptions in breathing). Severe adverse reactions affecting the cardiovascular and respiratory systems, such as respiratory depression (slowed or shallow breathing), apnoea, sudden respiratory arrest, and/or circulatory arrest, have been rarely observed. To avoid these effects, the medicine should be injected slowly and at the lowest possible dose.

Paradoxical reactions and anterograde amnesia (loss of memory for recent events) have been reported following administration of midazolam (see section 4, "Possible side effects").

Adults

Before administering Midazolam SUN, discuss with the doctor if:

• the patient is over 60 years of age,
• the patient has a chronic illness (e.g. chronic respiratory, kidney, liver or heart disease),
• the patient is debilitated (has an illness causing them to feel very weak, exhausted and lacking energy),
• the patient has been diagnosed with sleep apnoea syndrome (interruption of breathing during sleep), in which case close monitoring may be required,
• the patient has muscle weakness (a neuromuscular disorder characterised by reduced muscle strength),
• the patient currently misuses or has previously misused alcohol. Alcohol may enhance the effect of Midazolam SUN, potentially leading to sedation that could result in coma or death,
• the patient regularly takes medicines or has had problems with medication use in the past.

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

Midazolam SUN and other medicines

Tell your doctor, pharmacist or nurse about all medicines the patient is currently taking, including those obtained without a prescription and herbal medicines.

This is very important, as taking several medicines together may increase or reduce their effects.

In particular, inform the doctor or nurse if the patient is taking any of the following medicines:

• sedatives (used for anxiety and to help sleep),
• sleeping pills,
• hypnotics (medicines causing drowsiness or sleep),
• antidepressants (medicines used to treat depression),
• opioid analgesics (strong painkillers),
• antihistamines (medicines used to treat allergies),
• antifungal medicines (such as ketoconazole, voriconazole, fluconazole, itraconazole, posaconazole),
• 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 to lower cholesterol),
• rifampicin (a medicine used to treat mycobacterial infections, e.g. tuberculosis),
• ticagrelor (used to prevent heart attack),
• St John's wort (a herbal remedy).

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

Surgical procedures

If the patient is to receive an anaesthetic before a surgical or dental procedure (including inhaled anaesthetics), it is important to inform the doctor or dentist that the patient has received Midazolam SUN.

Use of Midazolam SUN with alcohol

The patient must not drink alcohol while taking midazolam, as alcohol may greatly enhance the sedative effect of Midazolam SUN and cause breathing problems.

Pregnancy and breastfeeding

If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a baby, she should consult her doctor before using this medicine. The doctor will decide whether this medicine is suitable for her.

Midazolam SUN used during early pregnancy may harm the unborn child. Administration of high doses towards the end of pregnancy, during labour or caesarean section may result in the mother being at risk of aspiration, and in the newborn, disturbances in heart rhythm, hypotonia (reduced muscle tone), feeding difficulties, low body temperature, and respiratory depression (difficulty breathing). With prolonged use towards the end of pregnancy, the baby may develop physical dependence, and withdrawal symptoms may occur after birth.

Midazolam SUN may pass into breast milk; therefore, women should not breastfeed for 24 hours after taking the medicine.

Driving and operating machinery

• Midazolam SUN may cause drowsiness, memory disturbances, reduced concentration, and impaired coordination. These effects may affect performance of tasks requiring precision, such as driving and operating machinery.
• The patient should not drive or operate machinery until full recovery of function. The decision on when the patient may resume these activities should be made by the doctor.
• The patient should not drive while taking this medicine until they know how it affects them.
• Driving while under the influence of this medicine is an offence.
• However, it is not an offence if:
• the medicine was prescribed to treat a medical or dental condition,
• the medicine was taken as directed by the doctor or as stated in the package leaflet,
• the medicine does not impair the ability to drive safely.

If in doubt whether driving while taking this medicine is safe, consult a doctor or pharmacist.

• Lack of sleep or alcohol consumption may also impair concentration.
• After the procedure, the patient should return 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 be administered only by experienced physicians in a healthcare facility (hospital, clinic) equipped with equipment for monitoring and supporting the respiratory, cardiovascular, and circulatory systems, and by personnel trained in recognizing and managing possible adverse reactions.
Dosage in adults
The appropriate dose for each patient is determined by the physician. Doses depend on the planned treatment and requirements for a specific level of sedation. The dose in an individual case depends on the patient's body weight, age, general health status, concomitant medications, response to midazolam, and whether other simultaneously administered drugs may influence the effect of Midazolam SUN.
If the patient is to receive strong analgesic drugs, these will be administered first, followed by midazolam at a dose appropriately 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 intravenous injection (intravenous injection)
• through a special catheter inserted into a vein (intravenous infusion).

After the procedure, the patient should always go home accompanied by a caregiver (an adult person).
Use of a higher than recommended dose of Midazolam SUN
The drug is administered by a physician or nurse. If an accidental overdose occurs, it may lead to:

• drowsiness,
• loss of motor coordination and reflexes,
• dysarthria (speech disturbances),
• nystagmus (involuntary eye movements),
• arterial hypotension (hypotension),
• apnea, respiratory and circulatory depression (slowed or stopped breathing and heart function), and coma.

Discontinuation of Midazolam SUN
In cases of chronic (long-term) use of midazolam, the patient may:

• develop tolerance to midazolam. The drug becomes less effective and works less strongly.
• develop dependence and withdrawal symptoms (see below).

The physician will gradually reduce the dose of the drug to avoid these effects.
The following adverse reactions have been observed during midazolam administration, particularly in elderly patients: motor restlessness, agitation, irritability, involuntary movements, hyperactivity, hostility, hallucinations, anger, aggression, anxiety, nightmares, illusions (seeing and possibly hearing things that are not present), psychoses (loss of contact with reality), inappropriate behavior, excitement, and acts of violence (these are also known as paradoxical reactions, which are effects opposite to those normally expected from the drug). If such symptoms occur, the physician will consider discontinuing treatment with Midazolam SUN.
Withdrawal symptoms:
Benzodiazepines such as Midazolam SUN may cause dependence if used for a long time (e.g., in intensive care units). This means that if administration of the drug is stopped or the dose is reduced too quickly, withdrawal symptoms may occur, including:

• headache,
• diarrhea,
• muscle pain,
• anxiety, tension, psychomotor agitation, disorientation, irritability,
• inability to fall asleep,
• mood changes,
• hallucinations (seeing and hearing things that are not present),
• seizures.

In severe cases of withdrawal, the following may occur: feeling of detachment from reality, numbness and tingling of the extremities (e.g., hands and feet), sensitivity to light, noise, and touch.
If you have any questions regarding the use of this medicine, please consult your doctor, pharmacist, or nurse.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone experiences them.
The adverse reactions listed below occurred with unknown frequency.
If any of the following adverse reactions occur in the patient, administration of Midazolam SUN must be discontinued immediately and the doctor must be informed at once. These may be life-threatening reactions requiring urgent treatment:

• anaphylactic shock (a life-threatening allergic reaction). Symptoms include sudden rash, itching or hives; swelling of the face, lips, tongue or other parts of the body. The patient may also experience shortness of breath, wheezing or difficulty breathing, or pale skin, weak and rapid pulse, or feeling faint. Additionally, chest pain may occur, which could indicate a potentially serious allergic reaction called Kounis syndrome.
• myocardial infarction (cardiac arrest). Symptoms include chest pain which may radiate to the neck, arms and down the left arm.
• breathing difficulties, including complications (sometimes leading to respiratory arrest)
• choking 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 function, particularly if the medicine is injected too rapidly or in high doses.
Other adverse reactions (frequency unknown)
Frequency unknown (cannot be estimated from available data)
Immune system disorders:

• general allergic reactions (skin reactions, cardiac and vascular system reactions, wheezing)

Psychiatric disorders:

• motor restlessness, agitation, irritability
• nervousness, anxiety
• hostility, anger or aggressive behaviour
• excitement
• hyperexcitability
• changes in libido
• inappropriate behaviour

Muscle disorders:

• muscle spasms and muscle tremor (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)

• psychoses (loss of contact with reality)

• drowsiness and prolonged sedation

• reduced attention

• headache

• dizziness

• difficulty in coordinating muscle movements

• transient memory loss (duration depends on the amount of Midazolam SUN received; may occur after treatment. In isolated cases, memory loss was prolonged)

• dependence, drug abuse Cardiac and vascular disorders:

• low blood pressure

• slow heart rate

• flushing of the face and neck (hot flushes), fainting or headache Respiratory system disorders:

• shallow breathing

• hiccups

Gastrointestinal and oral disorders:

• nausea or vomiting
• constipation
• dry mouth

Skin disorders:

• rash
• urticaria (hives)
• itching

Reactions at the site of administration:

• redness
• skin swelling
• thrombosis or pain at the injection site

Injuries:

• patients taking benzodiazepines are at risk of falls and bone fractures. This risk is increased in elderly patients and in patients taking other sedative medicines (including alcohol).

General disorders:

• fatigue (tiredness)

Elderly patients:

• the likelihood of life-threatening adverse reactions increases in patients over 60 years of age and in patients with respiratory insufficiency or impaired cardiac function, particularly if the medicine is administered too rapidly or in high doses.

Patients with severe renal impairment:

• in patients with severe renal impairment, the risk of adverse reactions is higher
• If any adverse reaction worsens or if any adverse reactions not listed in this leaflet occur, the doctor or nurse should be informed.

Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform a doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring of Adverse Drug Reactions, 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
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps provide more information on the safety of the medicine.

5. How to store Midazolam SUN

Keep out of the sight and reach of children.
Do not use Midazolam SUN after the expiry date stated on the carton and
ampoule-syringe following the abbreviation EXP. The expiry date refers to the last day of the stated month.
Store the ampoule-syringe in the outer packaging to protect from light.
The doctor or pharmacist is responsible for the storage of Midazolam SUN and for the proper disposal of any unused remnants.

6. Contents of the package and other information

What Midazolam SUN contains

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

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

What Midazolam SUN looks like and contents of the pack
Midazolam SUN is a clear, colourless and viscous injection/infusion solution.
Midazolam SUN is available in a blister pack containing one pre-filled syringe with 50 mL of injection/infusion solution.

Marketing Authorisation Holder
Sun Pharmaceuticals Industries Europe B.V.
Polarisavenue 87
2132 JH Hoofddorp
The Netherlands

Manufacturer/Importer
Sun Pharmaceuticals Industries Europe B.V.
Polarisavenue 87
2132 JH Hoofddorp
The Netherlands
Terapia S.A.
Strada Fabricii no. 124
400632, Cluj-Napoca
Cluj County
Romania

This medicinal product is authorised for sale in the European Economic Area countries 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

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
Ranbaxy (Poland) Sp. z o.o.
ul. Idzikowskiego 16
00-710 Warsaw, Poland
Tel. +48 22 642 07 75

Information intended exclusively for healthcare professionals:
INFORMATION FOR HEALTHCARE PROFESSIONALS
Please refer to the Summary of Product Characteristics for complete prescribing information.
Dosage and method of administration
Midazolam is a potent substance which should be administered slowly and gradually.
Gradual administration of midazolam is recommended to safely achieve the desired level of sedation depending on clinical needs, patient's health status and age, and concomitant medications. When determining dosage in patients aged 60 years and older, debilitated or chronically ill patients, individual patient-specific risk factors should be taken into account. Standard dosing is provided in the table below.
Additional information is provided below the table.

Sedation in patients in intensive care units
The required level of sedation is achieved by gradually increasing the dose of midazolam, followed by continuous intravenous infusion, depending on clinical needs, the patient's physical condition, age, and concomitant medications.
Adults
Loading dose for intravenous administration:
From 0.03 mg/kg body weight to 0.3 mg/kg body weight of midazolam administered slowly in successive 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 subsequent injections.
In patients with hypovolemia, vasoconstriction, or hypothermia, the loading dose should be reduced or omitted.
If midazolam is administered together with potent analgesic drugs, these should be given first to allow safe adjustment of the sedative effect of midazolam according to the level of sedation caused by the analgesic.
Maintenance dose administered intravenously:
Doses may range from 0.03 mg/kg body weight/hour to 0.2 mg/kg body weight/hour.
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—dose escalation may then be necessary.
If higher doses are required, Midazolam SUN at a concentration of 2 mg/mL should be used.
When initiating midazolam infusion in patients with impaired cardiovascular function, the dose should be gradually increased and the degree of hemodynamic instability monitored, e.g., drop in arterial blood pressure.
These patients are also susceptible to midazolam-induced respiratory depression and require special monitoring of respiratory function and blood oxygen saturation.
Special patient groups
Renal impairment: In patients with severe renal insufficiency (creatinine clearance below 30 mL/min), administration of midazolam may be associated with more pronounced and prolonged sedation, including clinically significant respiratory and cardiovascular depression. In this patient group, midazolam should be administered cautiously, with gradual dose escalation to achieve the desired effect.
In patients with renal failure (creatinine clearance <10 mL/min), the pharmacokinetics of unbound midazolam after a single intravenous dose are similar to those observed in healthy volunteers.
However, during prolonged infusion in patients in intensive care units, the sedative effect in patients with renal failure was more pronounced due to accumulation of 1’-hydroxymidazolam glucuronide.
Hepatic impairment:
Hepatic dysfunction reduces the clearance of intravenously administered midazolam, resulting in prolonged elimination half-life. Therefore, the clinical effect in patients with hepatic impairment may be stronger and prolonged. In such cases, dose reduction of midazolam and monitoring of vital functions may be necessary.
Incompatibilities
Due to lack of compatibility studies with other medicinal products, this medicinal product must not be mixed in the same administration with other products.
The use of polyvinyl chloride (PVC) infusion line extensions should be avoided. If this cannot be avoided, the duration of use of PVC infusion line extensions should be limited to 24 hours.
Special precautions for storage
Store the ampoule-syringe in the outer packaging to protect from light.