Metamizole kalceks

Package leaflet: Information for the user

Metamizole Kalceks, 500 mg/ml, solution for injection
Metamizolum natricum monohydricum
Metamizole Kalceks may cause abnormally low white blood cell count (agranulocytosis),
which may lead to severe and life-threatening infections (see section 4).
The drug should be discontinued and immediate medical advice sought if any of the
following symptoms occur: fever, chills, sore throat, painful ulcers in the nose,
mouth or throat, or in the genital or anal area.
If agranulocytosis has ever occurred in the patient during treatment with metamizole or
similar drugs, this medication must never be used again in the future (see section 2).
Please read this leaflet carefully before using this medicine, as it contains
important information for the patient.

• Keep this leaflet for future reference.
• If you have any questions, consult your doctor, pharmacist or nurse.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm other people, even if their symptoms are the same.
• If the patient experiences any adverse reactions, including any not listed in this leaflet, inform your doctor, pharmacist or nurse. See section 4.

Contents of the leaflet

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

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

Metamizole Kalceks contains the active substance metamizole, which is a medicine with
analgesic, antipyretic and spasmolytic properties.
Metamizole Kalceks is used in the treatment of:

• acute, severe or prolonged pain;
• fever when other treatment methods are ineffective.

2. Information before using Metamizole Kalceks

When not to use Metamizole Kalceks

• if the patient is allergic to metamizole or other related substances (e.g. phenazone, propyphenazone, phenylbutazone, oxyphenbutazone) or to any of the excipients listed in section 6;
• if the patient has previously experienced a significant decrease in the number of white blood cells called granulocytes, caused by metamizole or other similar drugs known as pyrazolones or pyrazolidines;
• if the patient has hypotension or circulatory disorders;
• if the patient has bone marrow dysfunction or a disease affecting the production or function of blood cells;
• if the patient has asthma or has ever had an allergic reaction to painkillers (salicylates, paracetamol or other analgesics such as: diclofenac, ibuprofen, indomethacin or naproxen), manifested by urticaria or facial swelling and mucosal oedema of the respiratory or gastrointestinal tract;
• if the patient has severe liver disease – porphyria (risk of porphyria attack);
• if the patient has congenital glucose-6-phosphate dehydrogenase deficiency (risk of haemolysis);
• in pregnant women during the third trimester.

Warnings and precautions
Before starting treatment with Metamizole Kalceks, discuss this with your doctor, pharmacist or nurse.
Exercise particular caution when using Metamizole Kalceks:

• If fever, chills, sore throat or oral mucosal ulcers occur, consult a doctor immediately. These symptoms may indicate neutropenia (reduced number of white blood cells – neutrophils).
• If any symptoms suggesting blood disorders occur (e.g. general weakness, infection, persistent fever, bruising, bleeding, pallor), seek immediate medical advice. These symptoms may be due to pancytopenia (reduction in all types of blood cells).
• If the patient has asthma or atopy (a type of allergy). In such cases, there is an increased risk of anaphylactic shock (a life-threatening allergic reaction) (see section When not to use Metamizole Kalceks).
• If any of the following conditions are present, due to increased risk of severe anaphylactoid reactions after metamizole:
• bronchial asthma with concomitant rhinitis;
• chronic or persistent urticaria;
• alcohol intolerance, i.e. in patients who react to even small amounts of alcohol with sneezing, tearing and facial flushing;
• hypersensitivity to dyes (e.g. tartrazine) or preservatives (e.g. benzoates).
• If the patient has hypotension, fluid loss, unstable fluid volume, early-stage circulatory disturbances, or high fever. There is an increased risk of severe hypotension (related to a drop in blood pressure). The doctor will carefully consider initiating treatment with Metamizole Kalceks, and if the drug is used, it will be administered under strict supervision. Appropriate measures must be taken to minimize the risk of severe hypotension. Administration of metamizole may cause these reactions even in the absence of the above-mentioned conditions. These reactions appear to be dose-dependent. The doctor will carefully evaluate the indication for using a single dose of metamizole exceeding 1 g.
• If the patient has severe coronary artery disease or significant cerebral vessel stenosis. In these cases, it is absolutely essential to avoid hypotension, and therefore metamizole may only be administered under strict circulatory monitoring.
• If the patient has kidney or liver disease. High doses of metamizole should not be used in these cases due to reduced elimination of the drug.

Low white blood cell count (agranulocytosis)
Metamizole Kalceks may cause agranulocytosis, i.e. a very low number of a type of white blood cells called granulocytes, which play an important role in fighting infections (see section 4). Treatment with metamizole must be discontinued and medical advice sought immediately if any of the following symptoms occur, as they may indicate possible agranulocytosis: chills, fever, sore throat and painful ulcers of the mucous membranes, especially in the mouth, nose and throat, or in the genital or anal area.
The doctor will order laboratory tests to check the patient's blood cell count.
If metamizole is taken for fever, some symptoms of developing agranulocytosis may remain unnoticed. Similarly, symptoms may also be masked if the patient is receiving antibiotics.
Agranulocytosis may develop at any time during treatment with Metamizole Kalceks, and even shortly after discontinuation of metamizole.
Agranulocytosis may occur even if metamizole was previously administered without complications.

Severe skin reactions
Severe skin reactions have been reported with metamizole treatment, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS syndrome). If any of these symptoms associated with severe skin reactions listed in section 4 occur, discontinue metamizole and seek immediate medical help.
If the patient has ever experienced severe skin reactions, Metamizole Kalceks must never be used again in the future (see section 4).

Liver-related disorders
Cases of hepatitis have been reported in patients taking metamizole, with symptoms appearing from several days to several months after starting treatment.
Treatment with Metamizole Kalceks should be discontinued and a doctor consulted if the patient develops liver-related symptoms such as: malaise (nausea or vomiting), fever, fatigue, loss of appetite, dark urine, pale stools, jaundice (yellowing of the skin or whites of the eyes), itching, rash or upper abdominal pain. The doctor will check the patient's liver function.
The patient should not take Metamizole Kalceks if they have previously used any medicinal products containing metamizole and experienced liver-related adverse effects.

Metamizole Kalceks and other medicines
Inform your doctor about all medicines currently or recently taken, as well as any medicines planned for future use. This is particularly important if the patient is taking:

• bupropion, a medicine used to treat depression or to aid smoking cessation;
• efavirenz, a medicine used to treat HIV infection (AIDS);
• methadone, a medicine used in the treatment of addiction to illegal narcotics (so-called opioids);
• valproate, a medicine used to treat epilepsy or bipolar affective disorder;
• tacrolimus, a medicine used to prevent organ rejection in transplant patients;
• sertraline, a medicine used to treat depression;
• cyclosporine, an immunosuppressive medicine.

When Metamizole Kalceks is administered concomitantly with any of the medicines listed above, the patient's health status should be monitored.
Concomitant administration of Metamizole Kalceks and methotrexate (an immunosuppressive medicine) may enhance methotrexate's side effects on blood cell formation (haematopoiesis, haematotoxicity), especially in elderly patients. Concomitant use of these medicines should be avoided.
Caution is advised when administering this medicine together with acetylsalicylic acid used for prevention of myocardial infarction.

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 a doctor before using this medicine.

Pregnancy
Available data on the use of metamizole during the first three months of pregnancy are limited, but do not indicate harmful effects on the embryo. In selected cases, if no other treatment options are available, after consultation with a doctor or pharmacist, the patient may receive single doses of metamizole during the first and second trimesters, provided that the benefits and risks of taking the medicine are carefully considered. In principle, administration of metamizole during the first and second trimesters is not recommended.
Metamizole Kalceks must not be taken during the last three months of pregnancy due to increased risk of complications for both mother and child (bleeding, premature closure of an important blood vessel, the so-called ductus arteriosus Botalli, in the unborn child, which normally closes only after birth).

Breastfeeding
Metamizole metabolites pass into breast milk in significant amounts, and risk to the breastfed infant cannot be excluded. Therefore, repeated use of metamizole should be particularly avoided during breastfeeding.
After a single dose of metamizole, mothers should be advised to express and discard breast milk for 48 hours after administration of the drug.

Driving and operating machinery
At the recommended dosage, this medicine does not affect the ability to drive or operate machinery. When higher than recommended doses are used, especially in combination with alcohol, driving and operating machinery should be avoided, as reaction time and concentration may be impaired.

Metamizole Kalceks contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per daily dose up to 0.7 ml, meaning the medicine is considered "sodium-free". For a daily dose of 0.8 ml or more (corresponding to more than 1 mmol of sodium), note: This medicine contains 32.71 mg of sodium (main component of table salt) per ml of solution. This corresponds to 1.64% of the maximum recommended daily dietary sodium intake for adults.

3. How to use Metamizole Kalceks

This medicine should always be used according to the instructions given by the doctor or pharmacist. In case of doubt, consult a doctor or pharmacist.
The dosage and method of administration depend on the desired analgesic effect and the patient's health condition.
The dose depends on the severity of pain or fever and on the individual's response to Metamizole Kalceks.
A clear effect of the medicine can be expected approximately 30 minutes after administration. The duration of action usually lasts about 4 hours.
Metamizole Kalceks is administered as an intravenous or intramuscular injection. After administration, the patient should remain lying down and under medical supervision to ensure appropriate monitoring of health status.
If the effect of a single dose is insufficient or if the analgesic effect wears off, the doctor may administer another dose, provided that the total amount of medicine taken by the patient within 24 hours does not exceed the maximum daily dose.

Adults and adolescents aged 15 years or older
For adults and adolescents aged 15 years or older (with body weight exceeding 53 kg), a single dose of 1–2 ml may be administered intravenously or intramuscularly; if necessary, the single dose may be increased up to a maximum of 5 ml (corresponding to 2500 mg of Metamizole Kalceks). The maximum daily dose is 8 ml; if necessary, the daily dose may be increased up to a maximum of 10 ml (corresponding to 5000 mg of Metamizole Kalceks).

Infants and children
The following dosage schedule should be followed for single intravenous or intramuscular doses:

Elderly individuals and patients in poor general health or with kidney function disorders
In elderly individuals, debilitated patients, and patients with impaired kidney function, the dose should be reduced due to the possibility of prolonged elimination of metamizole metabolites.

Patients with impaired kidney or liver function
Due to reduced elimination rate in patients with impaired kidney or liver function, repeated administration of high doses should be avoided. In short-term use, dose reduction is not required. There is no experience regarding long-term use.

Use in children
Dosage – see table above.
The usual dose for the treatment of fever in children is 10 mg per kg of body weight.

Use of a higher than recommended dose of Metamizole Kalceks
After acute overdose, symptoms such as nausea, vomiting, abdominal pain, impaired kidney function or acute kidney failure, nervous system disturbances (dizziness, drowsiness, coma, convulsions), hypotension, and cardiac arrhythmias may occur. Very high doses may cause harmless red discoloration of urine.

If you have any further doubts regarding the use of this medicinal product, consult a physician, pharmacist, or nurse.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
Immediately discontinue treatment and seek medical attention from a doctor or hospital if any of the
following adverse reactions occur. These symptoms may indicate
agranulocytosis (reduction or complete absence of one type of white blood cells) (rare –
less than 1 in 1,000 patients):

• fever (persistent or recurring)
• chills
• sore throat
• difficulty swallowing
• oral ulcers or mucosal lesions in the nose, genital organs, or rectum
  Agranulocytosis is unpredictable and may occur even if no adverse reactions were observed during previous use of metamizole. Agranulocytosis can be life-threatening and may lead to death (see Warnings and precautions). In patients receiving antibiotics, symptoms of agranulocytosis may be mild. Erythrocyte sedimentation rate increases significantly, while lymph node enlargement is moderate or absent.

Severe skin reactions
Discontinue metamizole and immediately seek medical help if the patient experiences any of the following severe adverse reactions (frequency unknown – cannot be estimated from available data):

• red, flat lesions on the trunk in a target-like shape or circular lesions, often with blisters in the center, skin peeling, and ulcers in the mouth, throat, nose, genital organs, or eyes. Such serious skin eruptions may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome, toxic epidermal necrolysis);
• widespread rash, high fever, and enlarged lymph nodes (DRESS syndrome or drug hypersensitivity syndrome).

Discontinue taking Metamizole Kalceks and immediately seek medical help if any of the following symptoms occur:

• malaise (nausea or vomiting), fever, fatigue, loss of appetite, dark urine, pale stools, yellowing of the skin or whites of the eyes, itching, rash, or upper abdominal pain. These may be symptoms of liver damage. See also section 2 "Warnings and precautions".

Consult a doctor if any of the following adverse reactions occur or if you have any other problems related to the medicine.
Rare (less than 1 in 1,000 patients):

• aplastic anaemia (reduced number of red blood cells)
• leukopenia (reduced number of white blood cells)
• pancytopenia (reduced number of all blood cells)
• thrombocytopenia (reduced number of platelets) (increased tendency to bleed, presence of small reddish-brown spots (petechiae) on the skin and mucous membranes)
• allergic reactions (anaphylactic or anaphylactoid)
• anaphylactic shock (potentially fatal)
  These symptoms may occur during injection or several hours (most commonly within one hour) after administration of the medicine. They may occur even if previous repeated use of metamizole was not associated with any adverse reactions. Moderately severe allergic reactions typically present as skin lesions and mucosal changes (itching, burning, redness, urticaria, swelling), breathing difficulties, or less commonly gastrointestinal symptoms. In more severe cases, symptoms may become generalized and include: severe angioedema (swelling of the face, lips, tongue, and throat, which may lead to difficulty swallowing and breathing), severe bronchospasm, dyspnoea, cardiac arrhythmias, low blood pressure, and anaphylactic shock. In patients with bronchial asthma, these symptoms may present as bronchospasm.
• rash

Very rare (less than 1 in 10,000 patients):

• reversible renal failure with reduced (oliguria) or nearly complete cessation (anuria) of urine output, or acute renal failure with proteinuria (protein in urine).

Frequency not known (cannot be estimated from available data):

• Kounis syndrome (allergic myocardial infarction)
• transient, rarely critical, isolated drop in blood pressure without further signs of hypersensitivity reaction. Rapid intravenous injection of the medicine may increase the risk of such a reaction
• interstitial nephritis
• pain at the injection site
• phlebitis
• hepatitis, jaundice, elevated liver enzymes in blood.

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. 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 to provide more information on the safety of the medicine.

5. How to store Metamizole Kalceks

Keep in the original packaging to protect from light. Do not freeze.
After opening the ampoule: the medicinal product should be used immediately.
Shelf-life after dilution
Chemical and physical in-use stability has been demonstrated for 6 hours at 25°C after dilution with 0.9% sodium chloride solution or Ringer's solution.
Chemical and physical in-use stability has been demonstrated for 20 minutes at 25°C after dilution with 5% glucose solution.
From a microbiological point of view, if the method of dilution does not exclude the risk of microbiological contamination, the product should be used immediately. If not used immediately, the user is responsible for the storage duration and conditions.
Keep the medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after: Expiry (EXP) and on the ampoule after: EXP. The expiry date refers to the last day of the stated month.
Medicines should not be disposed of via the sewage system. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Contents of the pack and other information

What Metamizole Kalceks contains

• The active substance is metamizole sodium monohydrate.

1 ml of solution contains 500 mg of metamizole sodium monohydrate.
1 ampoule (2 ml) contains 1000 mg of metamizole sodium monohydrate.
1 ampoule (5 ml) contains 2500 mg of metamizole sodium monohydrate.

• Other ingredients: hydrochloric acid 1 M (for pH adjustment), water for injections.

What Metamizole Kalceks looks like and contents of the pack
Injection solution.
A clear, almost colourless to brownish-yellow solution, practically free from particles.
2 or 5 ml of solution in an ampoule made of amber glass.
5 ampoules are packed in a tray. 1, 2 or 20 trays are placed in a cardboard box.
Pack sizes: 5, 10 or 100 ampoules of 2 ml and 5, 10 or 100 ampoules of 5 ml.
Not all pack sizes may be marketed.

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

Manufacturer/Importer
Akciju sabiedrība “Kalceks”
Krustpils iela 71E
Rīga, LV-1057
Latvia

This medicinal product is authorised in the European Economic Area countries under the following names:
Czech Republic Metamizole Kalceks
Austria, Germany Metamizol Kalceks 500 mg/ml Injektionslösung
Bulgaria Metamizole Kalceks 500 mg/ml инжекционен разтвор
Croatia Metamizolnatrij hidrat Kalceks 500 mg/ml otopina za injekciju
Lithuania Metamizole sodium Kalceks 500 mg/ml injekcinis tirpalas
Poland Metamizole Kalceks
Romania Metamizol Kalceks 500 mg/ml soluție injectabilă
Slovakia Metamizole Kalceks 500 mg/ml injekčný roztok
Slovenia Natrijev metamizolat Kalceks 500 mg/ml raztopina za injiciranje
Spain Metamizol Kalceks 500 mg/ml solución inyectable EFG
Hungary Metamizole Kalceks 500 mg/ml oldatos injekció

For information about this medicine, please contact the Marketing Authorisation Holder.

Information intended exclusively for healthcare professionals:

Parenteral administration of the drug is associated with a high risk of anaphylactic or
anaphylactoid reactions.
It is essential to ensure that the drug injection is discontinued at the first signs of an
anaphylactic or anaphylactoid reaction and that the risk of isolated hypotensive reactions is
minimized. During parenteral administration, the patient should be in a lying position and under
close medical supervision. Additionally, to prevent hypotensive reactions, intravenous
administration should be performed very slowly, at a rate not exceeding 1 ml (500 mg of metamizole) per minute.
The injection solution may be diluted using 5% glucose solution, 0.9% sodium chloride solution, or Ringer's solution. Due to possible pharmaceutical incompatibilities, metamizole solution should not be administered together with other injectable drugs.