Midazolam sandoz

Package leaflet: Information for the patient

Midazolam Sandoz, 1 mg/ml, solution for injection or infusion
Midazolam Sandoz, 5 mg/ml, solution for injection or infusion
Midazolamum
Please read all of this leaflet carefully before using this medicine, because it contains important information for you.
Keep this leaflet so that you can read it again if necessary.
If you have any further questions, please consult your doctor, pharmacist, or nurse.
This medicine has been prescribed for a specific person only. Do not pass it on to others.
This medicine may harm other people, even if their symptoms are the same.
If you experience any adverse reactions, including those not listed in this leaflet, tell your doctor, pharmacist, or nurse.
See section 4.

Contents of the leaflet:

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

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

Midazolam Sandoz contains the active substance midazolam and belongs to a group of medicines called benzodiazepines. Midazolam is a short-acting medicine that causes sedation (a state of calmness, drowsiness, or sleep) and relieves anxiety and muscle tension. It has anticonvulsant properties and causes amnesia affecting recent events.
Midazolam Sandoz is used:

• to induce sedation in adults and children during diagnostic or therapeutic procedures
• to induce sedation in adults and children treated in intensive care units
• in anaesthesia of adults (either alone or in combination with other anaesthetic medicines)
• to induce sedation prior to anaesthesia in adults and children

2. Important information before using Midazolam Sandoz

When not to use Midazolam Sandoz
Do not use if:
the patient has hypersensitivity to:

• midazolam or any of the other ingredients of this medicine (listed in section 6)
• other medicines from the benzodiazepine group. The names of their active substances end in "azepam" (e.g. diazepam, nitrazepam)
  the patient has acute or severe respiratory disorders and is to receive Midazolam Sandoz for the purpose of inducing light sedation

If in doubt, consult a doctor or nurse before receiving this medicine.

Warnings and precautions
Midazolam Sandoz should only be administered when appropriate resuscitation equipment suitable for the patient's age and size is available, due to the possibility of life-threatening adverse reactions; see also section 4. Administration of Midazolam Sandoz may depress myocardial contractility and cause apnoea (cessation of breathing). Severe cardiorespiratory adverse reactions may occur, including respiratory depression, apnoea, respiratory arrest, and/or cardiac arrest. To avoid such events, the medicine should be administered slowly and in the lowest possible dose.
If Midazolam Sandoz is administered for premedication, the doctor will closely monitor the patient's response to ensure appropriate dosing, as sensitivity to the drug varies between individuals.
Paradoxical reactions and anterograde amnesia (loss of memory of recent events) have been reported during treatment with Midazolam Sandoz; see section 4.

Long-term use
If Midazolam Sandoz is used for a prolonged period, the patient may develop tolerance (reduced effectiveness of the drug) or dependence.
After long-term treatment (e.g. in an intensive care unit), withdrawal symptoms may occur. To prevent this, the doctor will gradually reduce the dose. Further information is provided in section 3: "Discontinuing Midazolam Sandoz".

Talk to a doctor or nurse before using Midazolam Sandoz if:

• the patient is over 60 years old
  Patients in this age group require lower doses and careful monitoring of vital functions.
• the patient has a chronic illness or is debilitated, for example:
  • has difficulty breathing
    Note: Midazolam Sandoz must not be used in patients with the respiratory disorders described above (see "When not to use Midazolam Sandoz").
  • renal insufficiency
  • hepatic or cardiac dysfunction
    Debilitated or chronically ill patients require lower doses and careful monitoring of vital functions.
• the patient has a certain type of muscle weakness called myasthenia gravis
• the patient has previously abused alcohol or drugs
  Midazolam Sandoz should not be used in patients with a history of such dependence.
• the patient is taking any other medicines, including those prescribed by a doctor (more information in section "Midazolam Sandoz and other medicines")
• the patient has temporary interruptions in breathing during sleep (sleep apnoea)
• the patient is pregnant or suspects she may be pregnant.

Children
Use of Midazolam Sandoz in infants or children requires special caution.
Talk to a doctor or nurse if a child is to receive this medicine and:

• has cardiac or respiratory dysfunction
  The child's condition will be closely monitored and the dose adjusted accordingly.
• is under 6 months of age or is a premature infant
• administration of Midazolam Sandoz in children under 6 months of age is indicated only for sedation in intensive care settings
• gradual dosing and special monitoring of respiration and blood oxygen saturation are required, as patients in this age group are more susceptible to respiratory disturbances.

Midazolam Sandoz and other medicines
Inform the doctor or nurse about all medicines currently taken or recently taken.
Tell the doctor or nurse if the patient is taking any of the following medicines, as they may enhance the effects of Midazolam Sandoz:

• sedatives, hypnotics, muscle relaxants, or medicines used to treat anxiety and psychiatric disorders
• medicines used to aid sleep or in anaesthesia, such as etomidate, ketamine, propofol
• medicines used to treat psychiatric disorders or anxiety, with sedative effects
• medicines used to treat depression
• carbamazepine or phenytoin (medicines that may be given for seizures or epilepsy)
• medicines used to treat severe pain or cough, or used in substitution therapy
• medicines used to treat allergies and sleep disorders (so-called antihistamines)
• medicines used to treat fungal infections, whose active substance names end in "azole", such as ketoconazole, voriconazole, fluconazole, itraconazole, posaconazole
• medicines used to treat bacterial infections, whose active substance names end in "mycin", such as erythromycin, clarithromycin
• diltiazem: a medicine used to treat hypertension and cardiac disorders
• medicines used to treat hypertension that act in the brain
• medicines used to treat HIV infection, whose active substance names end in "navir", such as saquinavir
• medicines used to treat hepatitis C virus infection, whose names end in "previr", such as boceprevir, telaprevir
• atorvastatin: a medicine used to lower cholesterol levels
• rifampicin: a medicine used to treat tuberculosis
• St John's wort (Hypericum perforatum): a herbal medicine used to treat depression
• inhaled anaesthetic agents

Midazolam Sandoz, food, drink and alcohol
Do not drink alcohol while taking Midazolam Sandoz. Alcohol may greatly enhance the sedative effect of this medicine and cause respiratory disturbances.

Pregnancy, breastfeeding and fertility

• Pregnancy
  If the patient is pregnant or suspects she may be pregnant, she should inform her doctor. The doctor will decide whether this medicine is appropriate for her. If the doctor decides to use this medicine late in pregnancy, during delivery or caesarean section, there is a risk of maternal aspiration and of irregular heart rhythm, hypotonia (reduced muscle tone), difficulty sucking, low body temperature, and respiratory depression in the newborn. In infants whose mothers received this medicine for a prolonged period in the last stage of pregnancy, physical dependence and risk of withdrawal symptoms after birth may occur.
• Breastfeeding
  Do not breastfeed for 24 hours after receiving Midazolam Sandoz, as it may pass into breast milk.
• Fertility
  Available data indicate that Midazolam Sandoz does not affect fertility.

Driving and operating machinery

• Do not drive or operate machinery until the effects of the medicine have completely worn off. The doctor should advise the patient when it is safe to resume these activities.
• After receiving this medicine, the patient should always be accompanied by another person when travelling home. Midazolam Sandoz may cause drowsiness, memory loss, or impair concentration and coordination, affecting the ability to perform tasks such as driving or operating machinery.

Midazolam Sandoz contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per ml; therefore, this medicine is considered "sodium-free".

3. How to use Midazolam Sandoz

This medicine should be administered only by an experienced doctor or nurse. It is given in a hospital, clinic, or surgical office equipped with facilities for:

• monitoring and supporting respiration, heart function, and circulation
• diagnosis and appropriate treatment of expected adverse reactions.

Recommended dose:
The doctor determines the dose individually for each patient depending on:

• the indication for treatment
• the type of sedation required
• the patient's age, body weight, and general condition
• concomitant therapy
• the patient's response to Midazolam Sandoz
• the need for simultaneous administration of other medicines

If the patient requires strong pain-relieving medicines, these will be given first, followed by Midazolam Sandoz at an individually adjusted dose.

Route and method of administration

• intravenous administration: by slow injection into a vein
• infusion: by drip into one of the veins
• intramuscular administration: by injection into a muscle
• rectal administration: into the rectum

In children aged 12 years and younger, Midazolam Sandoz is usually administered intravenously. Rectal administration may also be used if sedation prior to anesthesia is required. Please refer to the information under section 2 titled "Children".

Instructions for proper use
Midazolam Sandoz is compatible with the following infusion solutions:

• 0.9% (9 mg/ml) sodium chloride solution
• 5% (50 mg/ml) glucose solution
• 10% (100 mg/ml) glucose solution
• Ringer's solution
• Hartmann's solution

Midazolam Sandoz is not compatible with the following infusion solutions:

• 6% (w/v) dextran solution (in 0.9% sodium chloride solution) in dextrose
• alkaline injection solutions. Midazolam precipitates in solutions containing sodium bicarbonate.

To avoid possible incompatibility, Midazolam Sandoz must not be mixed with other solutions except those listed above.
Midazolam Sandoz ampoules are intended for single use only. Any unused portion of the product must be discarded.
Before administration, inspect the solution in the ampoule. Only use undamaged ampoules and clear solutions that contain no particles and have not changed in colour.

Administration of a higher than recommended dose of Midazolam Sandoz
If the patient experiences any of the following symptoms of overdose, inform the doctor immediately, who will initiate appropriate treatment:

• drowsiness
• difficulty controlling movements or speech
• loss of reflexes
• involuntary eye movements
• low blood pressure (which may cause dizziness or fainting)
• slowed or stopped breathing or heartbeat
• loss of consciousness (coma)

Overdose may require close monitoring of vital functions, symptomatic treatment of cardiovascular and respiratory effects, and administration of a benzodiazepine antagonist.

Discontinuation of Midazolam Sandoz
If Midazolam Sandoz has been administered for a prolonged period:

• it may become less effective and no longer work as expected
• the patient may become dependent on it, and withdrawal symptoms may occur

If treatment is stopped suddenly or if the dose is reduced too quickly, the following withdrawal symptoms may occur:

• headache
• muscle pain
• anxiety
• tension
• motor restlessness
• confusion
• irritability
• difficulty falling asleep
• mood changes
• hallucinations (seeing or hearing things that are not real)
• seizures

The doctor will gradually reduce the dose of the medicine to avoid these withdrawal symptoms.
If you have any further doubts regarding the use of this medicine, consult your doctor or nurse.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
The adverse effects listed below may occur during treatment with this medicine. Their frequency is
unknown (cannot be estimated from available data).
If the patient experiences any of the adverse effects shown in bold,
treatment with Midazolam Sandoz must be DISCONTINUED and the doctor must be informed immediately.
These may be life-threatening reactions requiring urgent treatment.

• Severe allergic reaction (anaphylactic shock) Symptoms include sudden rash, itching or hives; swelling of the face, lips, tongue or other parts of the body. Breathing difficulties, wheezing or trouble breathing, pale skin, weak and rapid pulse, or feeling faint may also occur. Additionally, chest pain may occur, which could be a symptom of a serious allergic reaction called Kounis syndrome.
• Myocardial infarction Symptoms include chest pain, which may radiate to the neck and arms, and then down the left arm.
• Breathing difficulties or complications
• Laryngospasm These life-threatening adverse effects are more likely to occur in patients over 60 years of age or in patients with respiratory or cardiac disorders. They occur mainly after too rapid administration of the medicine or when given in high doses.

Any of the following adverse effects may occur
Nervous system and psychiatric disorders
Reduced alertness
Confusion
Excessive sense of well-being or excitement (euphoria)
Changes in libido
Fatigue, drowsiness and prolonged sedation
Seeing or hearing things that are not there (hallucinations)
Headache
Dizziness
Coordination disturbances
Seizures in preterm infants and newborns
Transient memory loss. The duration of memory loss depends on the length of treatment and the dose administered. It may persist after discontinuation of the medicine, in isolated cases for a prolonged period.
Anxiety, hostility, anger or aggression. Uncontrolled muscle spasms or muscle tremors may also occur. The likelihood of these effects is higher if the patient received a high dose of Midazolam Sandoz or if the medicine was administered too rapidly, as well as in children and elderly patients.
If the patient notices signs of dependence on the medicine or if the medicine becomes less effective and a higher dose is required, this should be reported to the doctor.

Cardiac and circulatory disorders
Slow heart rate
Cardiac arrest
Flushing of the face and neck
Fainting
Low blood pressure (may cause dizziness or lightheadedness)
Formation of blood clots or vein inflammation (thrombophlebitis, thrombosis)

Respiratory disorders
Hiccups
Shortness of breath, breathlessness

Gastrointestinal disorders
Dry mouth
Constipation
Nausea, vomiting

Skin and subcutaneous tissue disorders
Itching
Rash, hives
Redness and pain at the injection site

General disorders and administration site conditions
Allergic reactions, including rash and wheezing
Withdrawal symptoms (see "Discontinuing treatment with Midazolam Sandoz" in section 3)
Falls and bone fractures. The risk is higher if the patient is taking other medicines causing drowsiness (e.g. sedatives or sleeping tablets) or if the patient consumes alcohol concurrently.

Elderly patients
The risk of falls and bone fractures is higher in elderly patients receiving benzodiazepines such as Midazolam Sandoz.
In patients over 60 years of age, the likelihood of experiencing life-threatening adverse effects is increased.

Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, the patient should inform their doctor, pharmacist or nurse. Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions at the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products: Al. Jerozolimskie 181C, 02-222 Warsaw
Tel.: +48 22 49 21 301, Fax: +48 22 49 21 309, Website: https://smz.ezdrowie.gov.pl.
Adverse effects may also be reported to the marketing authorization holder.
Reporting adverse effects helps provide more information on the safety of this medicine.

5. How to store Midazolam Sandoz

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the ampoule and on the outer carton after EXP. The expiry date refers to the last day of the specified month.
Store in the original packaging in order to protect from light.

After opening the ampoule
From a microbiological point of view, the medicine should be used immediately. If not, the responsibility for the duration and conditions of storage prior to use lies with the user.

After dilution
Chemical and physical in-use stability has been demonstrated for 24 hours at room temperature (15–25°C) or for 3 days at +2°C to +8°C.
From a microbiological standpoint, the medicine should be used immediately after dilution. If not, the responsibility for the duration and conditions of storage prior to use lies with the user, provided that the storage period does not exceed 24 hours and the storage temperature is between +2°C and +8°C, unless dilution has been carried out under controlled and validated aseptic conditions.

Ampoules of midazolam are for single use only. Any unused portion or residue must be discarded.
Do not use this medicine if the ampoule is not intact or if the solution contains particles or has changed in colour.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

What Midazolam Sandoz contains
The active substance is midazolam.
Midazolam Sandoz 1 mg/ml
Each 5 ml ampoule of solution for injection or infusion contains 5 mg of midazolam (as midazolam hydrochloride).
Midazolam Sandoz 5 mg/ml
Each 1 ml ampoule of solution for injection or infusion contains 5 mg of midazolam (as midazolam hydrochloride).
Each 3 ml ampoule of solution for injection or infusion contains 15 mg of midazolam (as midazolam hydrochloride).
Each 10 ml ampoule of solution for injection or infusion contains 50 mg of midazolam (as midazolam hydrochloride).
The other ingredients are:
Midazolam Sandoz 1 mg/ml: sodium chloride, hydrochloric acid, water for injections.
Midazolam Sandoz 5 mg/ml: sodium chloride, hydrochloric acid, sodium hydroxide, water for injections.

What Midazolam Sandoz looks like and contents of the pack
This medicine is a clear, light yellow solution in a transparent glass ampoule.
Pack sizes:
Midazolam Sandoz 1 mg/ml
5 x 5 ml
Midazolam Sandoz 5 mg/ml
5 x 1 ml
5 x 3 ml
5 x 10 ml

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Sandoz GmbH
Biochemiestrasse 10
6250 Kundl, Austria

Manufacturers
Salutas Pharma GmbH
Otto-von-Guericke-Allee 1
39179 Barleben, Germany
Sandoz GmbH
Biochemiestrasse 10
6250 Kundl
Austria
EVER Pharma Jena GmbH
Otto-Schott-Straße 15
7745 Jena
Germany
Ever Pharma Jena GmbH
Brüsseler Straße 18
07747 Jena
Germany

For further information about this medicine and its names in other European Economic Area countries, please contact:
Sandoz Polska Sp. z o.o.
ul. Domaniewska 50 C
02-672 Warszawa
tel. 22 209 70 00

Information intended exclusively for medical professionals

Preparation of infusion solution
Midazolam Sandoz can be diluted with 0.9% sodium chloride solution, 5% (50 mg/mL) glucose solution, or 10% (100 mg/mL) glucose solution, Ringer's solution, or Hartmann's solution at a ratio of 15 mg midazolam per 100 to 1000 mL of infusion solution. These solutions remain stable for 24 hours at room temperature and for 3 days at a temperature of +2°C to +8°C.
Do not mix Midazolam Sandoz with other solutions except those listed above.
In particular, do not mix Midazolam Sandoz with 6% (w/v) dextran solution (in 0.9% sodium chloride) in dextrose or with alkaline injection solutions. Midazolam precipitates in solutions containing sodium bicarbonate.
Inspect ampoules and solution before administration. Only use undamaged ampoules and clear solutions free from particulate matter and discoloration.

Shelf life and storage
Midazolam Sandoz ampoules are for single use only.

Ampoules before dilution
Store in the outer packaging to protect from light.

Ampoules after dilution
Chemical and physical stability of diluted solutions has been demonstrated for 24 hours at room temperature (15–25°C) or for 3 days at +2°C to +8°C.
From a microbiological standpoint, the medicinal product should be used immediately after dilution. If not, the responsibility for storage conditions and duration prior to use lies with the user, provided that storage does not exceed 24 hours and the temperature is maintained between +2°C and +8°C, unless dilution has been performed under controlled and validated aseptic conditions.

For continuous intravenous infusion, the solution may be diluted with one of the above-mentioned solutions to achieve a final concentration ranging from 0.015 to 0.15 mg/mL.

Waste disposal
Any unused product or waste material should be disposed of in accordance with local regulations.