Midazolam kalceks

Package leaflet: Information for the user

Midazolam Kalceks, 1 mg/ml, solution for injection / for infusion
Midazolam Kalceks, 5 mg/ml, solution for injection / for infusion
Midazolamum
Please read all of this leaflet carefully before you are given the medicine because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, please ask your doctor or nurse.
• If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the leaflet

1. What Midazolam Kalceks is and what it is used for
2. What you need to know before you are given Midazolam Kalceks
3. How to use Midazolam Kalceks
4. Possible side effects
5. How to store Midazolam Kalceks
6. Contents of the pack and other information

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

Midazolam belongs to a group of medicines called benzodiazepines (sedative medicines). It is a short-acting medicine used to induce sedation (a state of calmness, drowsiness or sleep), relieve anxiety symptoms, and reduce muscle tension. This medicine is used for:

• Inducing mild sedation (a state of calmness or drowsiness while remaining conscious) in adults and children.
• Inducing sedation in adults and children in intensive care units.
• Anaesthesia in adults (used before or during induction of anaesthesia, either alone or in combination with other anaesthetic medicines).
• Used before induction of anaesthesia in children.

2. Important information before receiving Midazolam Kalceks

When not to use Midazolam Kalceks:

• if the patient is allergic to midazolam, other benzodiazepines, or any of the other ingredients of this medicine (listed in section 6),
• if the patient has severe respiratory disorders and is to undergo light sedation.

Warnings and precautions
Before receiving Midazolam Kalceks, speak with your doctor or
nurse if:

• the patient is over 60 years old,
• the patient suffers from chronic or debilitating illness (e.g. chronic diseases of the respiratory, renal, hepatic or cardiovascular systems),
• the patient has muscle weakness (a neuromuscular disorder characterised by reduced muscle strength),
• the patient has previously abused alcohol or drugs,
• the patient is taking other medicines, including those not prescribed by the attending physician (see section “Midazolam Kalceks and other medicines”),
• if the patient has temporary breathing interruptions during sleep,
• the patient is pregnant or suspects she may be pregnant.

Midazolam Kalceks should be administered only in facilities equipped with resuscitation equipment appropriate for the patient's age and body weight. Administration of midazolam may reduce myocardial contractility (the heart muscle's ability to contract) and cause apnoea (respiratory pauses). Serious adverse reactions affecting the cardiovascular and respiratory systems, such as respiratory depression (slowed or shallow breathing), apnoea, respiratory arrest, and (or) circulatory arrest, have been rarely observed. To avoid these events, the medicine should be injected slowly and in the lowest possible dose.
Particular caution should be exercised when administering midazolam to infants and children. Inform the doctor if the child has cardiovascular diseases or respiratory disorders. The child will then be monitored, and the dose adjusted accordingly.
Patients under 6 months of age undergoing sedation in intensive care units are more susceptible to respiratory disturbances; therefore, dosing will be increased very gradually, and respiratory rate and blood oxygen saturation will be monitored.
When midazolam is used for premedication (to induce relaxation, calmness, and drowsiness before administering an anaesthetic), the patient's response will be carefully monitored to ensure appropriate dosing, as sensitivity to the drug varies among individuals. The use of midazolam is not recommended in newborns and children under 6 months of age.
Paradoxical reactions and anterograde amnesia (loss of memory of recent events) have been reported following midazolam administration (see section 4).
Long-term treatment
If midazolam is used for a prolonged period, the patient may develop tolerance (midazolam becomes less effective) or dependence on the drug.
After long-term treatment (e.g. in intensive care units), withdrawal symptoms may occur, such as headache, diarrhoea, muscle pain, anxiety, tension, psychomotor agitation, disorientation, irritability, sleep disturbances, mood changes, hallucinations, and seizures. In severe cases, depersonalisation, numbness and tingling of limbs, hypersensitivity to light, noise, and physical contact may occur. To prevent these adverse effects, the doctor will gradually reduce the dose of the medicine.
Midazolam Kalceks and other medicines
Inform your doctor or nurse about all medicines currently or recently taken by the patient, as well as any medicines the patient plans to take.
This is very important, as taking more than one medicine at the same time may enhance or weaken the effects of the medicines taken.
In particular, inform your doctor or nurse if the patient is taking any of the following medicines:

• anxiolytics (used for anxiety or to help sleep),
• sedatives (inducing a state of calm or causing drowsiness),
• hypnotics (sleeping medicines),
• antidepressants (medicines used to treat depression, e.g. nefazodone),
• opioid analgesics (very strong painkillers, e.g. fentanyl),
• anaesthetics (e.g. propofol),
• certain antihistamines (medicines used to treat allergies),
• antifungal medicines (ketoconazole, voriconazole, fluconazole, itraconazole, posaconazole),
• antibiotics (erythromycin, clarithromycin, telithromycin, roxithromycin),
• blood pressure medicines, calcium channel blockers such as diltiazem, verapamil,
• medicines used to treat HIV (human immunodeficiency virus) infection (efavirenz or saquinavir, lopinavir and other protease inhibitors),
• medicines used to treat hepatitis C virus infection (simeprevir, boceprevir and telaprevir),
• antiepileptic medicines (carbamazepine, phenytoin or valproic acid),
• atorvastatin (used to treat high cholesterol levels),
• rifampicin (used to treat mycobacterial infections, e.g. tuberculosis),
• ticagrelor (used to prevent heart attack),
• aprepitant, netupitant, casopitant (used to prevent nausea and vomiting),
• certain anticancer medicines (e.g. imatinib, lapatinib, idelalisib, vemurafenib),
• everolimus, cyclosporine (used to prevent rejection of transplanted organs),
• propiverine (used for urinary incontinence),
• herbal medicines (e.g. St John's wort, Ginkgo biloba or ginseng).

Concomitant use of midazolam and opioid medicines (strong painkillers, substitution therapy medicines, and some cough medicines) increases the risk of drowsiness, breathing difficulties (respiratory depression), coma, and may be life-threatening. Therefore, concomitant use should only be considered when other treatment options are not feasible.
If your doctor has prescribed midazolam together with opioid medicines, the dose and duration of concomitant treatment should be limited.
Inform your doctor about all opioid medicines being taken and strictly follow the doctor's dosing instructions. It may be helpful to inform friends or family members so they are aware of the above-mentioned symptoms. In case such symptoms occur, contact your doctor immediately.
Surgical procedures
If the patient is to receive an inhaled anaesthetic (one that is inhaled) during surgery or dental treatment, it is important to inform the doctor or dentist that the patient has received Midazolam Kalceks.
Midazolam Kalceks and alcohol
Alcohol may enhance the calming (sedative) effect of midazolam; therefore, the patient should avoid consuming alcohol.
Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor before taking this medicine. The doctor will decide whether the patient should receive the medicine.
If Midazolam Kalceks has been administered to the patient, she should not breastfeed for the next 24 hours. This is because midazolam may pass into human milk.
Driving and operating machinery
Midazolam has a significant effect on the ability to drive and operate machinery.
This medicine may cause drowsiness, memory disturbances, and affect the patient's concentration and coordination. This, in turn, may affect performance of tasks requiring precision, such as driving and operating machinery. After administration of midazolam, the patient should not drive or operate machinery until the medicine's effects have completely subsided. The doctor will decide when the patient may resume these activities. After the procedure, the patient should return home accompanied by a responsible adult.
Inadequate sleep or consumption of alcohol increases the likelihood of reduced alertness and attention.
Midazolam Kalceks contains sodium
Midazolam Kalceks, 1 mg/ml
In a daily dose of up to 6.5 ml, this medicine contains less than 1 mmol (23 mg) of sodium, meaning the medicine is considered "sodium-free". If the administered daily dose is 6.6 ml or more (corresponding to more than 1 mmol of sodium), the following should be considered: The medicine contains 3.5 mg of sodium (main component of table salt) in each ml of solution. This corresponds to 0.18% of the maximum recommended daily dietary sodium intake for adults.
Midazolam Kalceks, 5 mg/ml
In a daily dose of up to 7.3 ml, this medicine contains less than 1 mmol (23 mg sodium), meaning the medicine is considered "sodium-free". If the administered daily dose is 7.4 ml or more (corresponding to more than 1 mmol sodium), the following should be considered: The medicine contains 3.15 mg of sodium (main component of table salt) in each ml of solution. This corresponds to 0.16% of the maximum recommended daily dietary sodium intake for adults.
3. How to use Midazolam Kalceks
This medicine should be administered only by experienced doctors in a facility equipped with equipment for monitoring and supporting the respiratory and circulatory systems, or by trained personnel skilled in recognising and managing possible adverse events.
Dosage and route of administration
The appropriate dose for a given patient is determined by the doctor. Doses vary and depend on the planned treatment and desired level of sedation. The dose depends on body weight, age, general health status, concomitant medicines, response to the medicine, and whether the patient will require administration of other medicines simultaneously.
If the patient is to receive strong analgesics, they will be administered first, followed by Midazolam Kalceks at an appropriately adjusted dose.
This medicine may be injected directly into the patient's vein (intravenously), injected into muscle (intramuscularly), or administered rectally.
Children and infants
In infants and newborns under 6 months of age, midazolam is indicated only for sedation in intensive care units. The medicine should be administered gradually into the vein.
Children aged 12 years and younger usually receive midazolam intravenously. When used for premedication, the medicine may be administered rectally (into the rectum).
Administration of a higher than recommended dose of Midazolam Kalceks
The medicine is administered by a doctor or nurse.
If the patient accidentally receives too much midazolam, this may lead to drowsiness, ataxia (impaired body movement coordination), dysarthria (speech disturbances), nystagmus (involuntary eye movements), loss of reflexes, apnoea (cessation of breathing), hypotension (low blood pressure), respiratory-circulatory depression, and coma. In case of overdose, careful monitoring of vital signs, symptomatic treatment of circulatory-respiratory disturbances, and administration of a benzodiazepine antagonist may be required.
Discontinuation of Midazolam Kalceks
Abrupt discontinuation of treatment may cause withdrawal symptoms such as headache, muscle pain, anxiety, tension, psychomotor agitation, disorientation, mood swings, hallucinations, seizures, insomnia with flashbacks, irritability. The risk of withdrawal symptoms is higher with abrupt discontinuation; therefore, gradual dose reduction is recommended.
If you have any further questions regarding the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible adverse reactions

Like any medicine, this medicine can cause adverse reactions, although not everyone will experience them.
If any of the adverse reactions listed below occur in the patient, you should inform
the doctor immediately. These may be life-threatening reactions and may require urgent treatment:

• Anaphylactic shock (a life-threatening allergic reaction). Symptoms may include sudden rash, itching or raised, itchy rash (urticaria), swelling of the face, lips, tongue or other parts of the body. There may also be shortness of breath, wheezing or difficulty breathing, or pale skin, weak and rapid pulse, or feeling faint. Additionally, chest pain may occur, which could be a symptom of a serious allergic reaction called Kounis syndrome.
• Heart attack (cardiac arrest). Symptoms may include chest pain which may radiate to the neck and arms and down the left arm.
• Breathing difficulties or complications (sometimes leading to respiratory arrest).
• Choking and sudden airway obstruction (laryngospasm).

Life-threatening adverse reactions occur more frequently in adults over 60 years of age and
in patients with breathing difficulties and heart disease, especially if the medicine is injected too quickly
or in too high a dose.
Other adverse reactions:
The following adverse reactions have been reported, but their frequency cannot be estimated from the available data:
Immune system disorders: generalized allergic reactions (skin reactions, cardiac and circulatory reactions, wheezing).
Psychiatric disorders: confusion, disorientation, emotional and mood disturbances, changes in libido.
Paradoxical reactions such as motor restlessness, psychomotor agitation, irritability, nervousness, muscle spasms and tremors, hostility, hallucinations, anger, aggression, anxiety, nightmares, unusual dreams, illusions, psychoses, inappropriate behavior, and other adverse behavioral effects, including episodes of agitation and violent acts, have been observed. These reactions were mainly observed when the medicine was administered too quickly or in too high a dose. The risk of developing these symptoms is higher in children and elderly patients.
Dependence: midazolam may lead to physical dependence, even when used at therapeutic doses. To avoid withdrawal symptoms, including seizures, which may occur after prolonged use of midazolam, the dose should be gradually reduced (see section 2).
Nervous system disorders: drowsiness and prolonged sedation, reduced alertness, lethargy, headache, dizziness, impaired muscle coordination. Temporary memory loss has also been reported. Its duration depends on the dose administered and may also occur after treatment has ended. In isolated cases, memory loss persisted for a prolonged period. Seizures have been observed in premature infants and newborns.
Cardiac disorders: severe adverse reactions such as low blood pressure, slowed heart rate, and blood vessel dilation (e.g., facial and neck flushing, fainting, and headache) have been observed.
Gastrointestinal disorders: nausea, vomiting, constipation, dry mouth.
Skin disorders: skin rash, allergic reaction, itching.
General disorders and administration site conditions: fatigue, redness, skin swelling, blood clots in blood vessels, and pain at the injection site (redness, thrombophlebitis, thrombosis).

In elderly patients taking benzodiazepines, an increased risk of falls and bone fractures has been observed, particularly in elderly individuals who are also taking other sedative medicines (including alcoholic beverages).

There is a higher likelihood of adverse reactions occurring in patients with severe kidney function impairment.

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, you should inform the anaesthesiologist or another doctor. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of 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 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 Kalceks

There are no special storage temperature requirements for this medicinal product.
Store the ampoules in the outer packaging to protect from light.
The medicine should be stored out of sight and reach of children.
After opening the ampoule, the medicinal product should be used immediately.
Chemical and physical in-use stability has been demonstrated for diluted solutions for 24 hours
at 25 °C and for 3 days at 2 °C - 8 °C with the following infusion solutions: 0.9% sodium chloride, 5% and 10% glucose, Ringer's solution and Hartmann's solution.
From a microbiological point of view, the product should be used immediately after dilution. If not used immediately, the responsibility for the storage conditions and duration prior to use lies with the user, provided that the storage period does not exceed 24 hours at a temperature of 2 °C to 8 °C, unless dilution has been carried out under controlled and validated aseptic conditions.
Do not use the medicine after the expiry date stated on the carton and on the ampoule following “Expiry date (EXP)”. The expiry date refers to the last day of the stated month.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Midazolam Kalceks contains

• The active substance is midazolam.

Midazolam Kalceks, 1 mg/ml
1 ml of solution contains 1 mg of midazolam.
One 5 ml ampoule contains 5 mg of midazolam.
Midazolam Kalceks, 5 mg/ml
1 ml of solution contains 5 mg of midazolam.
One 1 ml ampoule contains 5 mg of midazolam.
One 3 ml ampoule contains 15 mg of midazolam.
One 10 ml ampoule contains 50 mg of midazolam.

• The other components are: hydrochloric acid concentrated, sodium chloride, sodium hydroxide (for pH adjustment), water for injections.

What Midazolam Kalceks looks like and contents of the pack
Clear, colourless solution for injection/infusion in ampoules made of colourless type I glass
with one break point OPC, containing 1 ml, 3 ml or 10 ml of solution (for 5 mg/ml)
and 5 ml of solution (for 1 mg/ml).
Pack size: 5 or 10 ampoules.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer/Importer
AS KALCEKS
Krustpils iela 71E
1057 Rīga
Latvia
Tel.: +371 67083320
E-mail: [email protected]

Information intended exclusively for medical professionals:

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

• 0.9% sodium chloride solution
• 5% glucose solution
• 10% glucose solution
• Ringer's solution
• Hartmann's solution

For intravenous infusion administration, the contents of Midazolam Kalceks vials should be diluted
with one of the solutions listed above at a ratio of 15 mg midazolam per 100 to 1,000 mL of
infusion solution.
Midazolam Kalceks solution for injection / for infusion must not be diluted in 6% Macrodex in glucose solution.
Midazolam Kalceks solution for injection / for infusion must not be mixed with alkaline
injection solutions. Midazolam precipitates in solutions containing bicarbonates.
To avoid potential incompatibility, Midazolam Kalceks solution for injection / for infusion must not be mixed with other solutions except those listed above.
Midazolam Kalceks solution for injection / for infusion is intended for single use only.
The solution should be inspected visually prior to administration. Only solutions free from visible particulate matter should be used.

Instructions for opening the ampoule:

1. Position the ampoule so that the coloured dot is at the top. If some of the solution is present in the upper part of the ampoule, gently tap with a finger to ensure all solution collects in the lower part.
2. Use both hands to open: hold the lower part of the ampoule in one hand and snap off the top part with the other hand in the direction away from the coloured dot (see illustrations below).