Metamizole kabi

Package leaflet: Information for the user

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

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

Table of contents of the leaflet

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

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

The active substance in Metamizole Kabi is metamizole. Metamizole is a pyrazolone derivative
with strong analgesic, antipyretic and spasmolytic effects, but weak anti-inflammatory activity.
Indications:
Severe pain of various origins.
Fever when other treatment methods are ineffective.
Metamizole Kabi should only be used when oral administration is not appropriate.

2. Important information before using Metamizole Kabi

When not to use Metamizole Kabi:

• 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 bone marrow dysfunction or a condition affecting the production or function of blood cells;
• if the patient is allergic to metamizole, other pyrazolone or pyrazolidine derivatives such as propyphenazone, phenazone or phenylbutazone, or any of the other ingredients of this medicine (listed in section 6);
• if the patient has analgesic-induced asthma syndrome or intolerance to painkillers manifested by urticaria, angioedema, i.e. patients who react with bronchospasm or another anaphylactoid reaction to salicylates, paracetamol or other non-opioid analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs), such as: diclofenac, ibuprofen, indomethacin or naproxen;
• if the patient has severe impairment of liver and/or kidney function;
• if the patient has acute hepatic porphyria (a hereditary disorder in red blood cell formation);
• if the patient has congenital glucose-6-phosphate dehydrogenase deficiency (a disorder causing breakdown of red blood cells);
• if the patient is in the last three months of pregnancy.

Warnings and precautions
Metamizole Kabi should only be used when the benefits of treatment outweigh the potential risk of adverse reactions or when other treatment methods are unavailable or inappropriate.
The use of Metamizole Kabi is associated with an increased risk of rare but life-threatening adverse reactions, such as agranulocytosis or severe allergic reaction – anaphylactic shock (see also section 4).
Low white blood cell count (agranulocytosis)
Metamizole Kabi may cause agranulocytosis, i.e. a very low number of a certain type of white blood cells called granulocytes, which play an important role in fighting infections (see section 4).
Treatment with metamizole should 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 mucosal ulcers, 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 used 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 Kabi, and even shortly after discontinuation of metamizole.
Agranulocytosis may occur even if metamizole was previously administered without complications.
Anaphylactic and anaphylactoid reactions
Very rarely, severe allergic (anaphylactic) reactions may occur after intravenous administration of Metamizole Kabi. These may lead to shock with life-threatening low blood pressure, coma, and even death.
Before using the medicine, tell the doctor if:

• the patient has analgesic-induced asthma syndrome or intolerance to painkillers manifested by urticaria, angioedema, particularly if associated with nasal polyposis and sinusitis;
• the patient has bronchial asthma, especially when associated with sinusitis and nasal polyps;
• the patient has chronic urticaria;
• the patient is intolerant to alcohol (manifested by catarrh, tearing eyes and facial flushing even after small amounts of alcohol; this may indicate previously undiagnosed analgesic-induced asthma);
• the patient has an allergy (hypersensitivity) to dyes (e.g. tartrazine) or preservatives (e.g. benzoates);
• the patient suffers from atopic diseases.

If symptoms of anaphylactic or anaphylactoid reactions occur, such as dyspnoea, tongue swelling, angioedema, rash or urticaria, the drug should be discontinued immediately and medical help sought, as there is a risk to life.
Patients who have experienced an anaphylactic or other immunological reaction to metamizole are also at risk of a similar reaction to other pyrazolones and pyrazolidines, as well as non-opioid analgesics.
Severe skin reactions
Severe skin reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), have been reported in association with metamizole treatment. If any of these symptoms related to severe skin reactions listed in section 4 occur in the patient, metamizole treatment should be discontinued and immediate medical help sought.
If the patient has ever experienced severe skin reactions, Metamizole Kabi should never be used again in the future (see section 4).
Low blood pressure
In some cases, low blood pressure (hypotension) may occur during treatment with Metamizole Kabi (see also section 4).
This reaction is dose-dependent and may occur:

• if the drug is administered intravenously too rapidly;
• in patients with hypotension, reduced fluid-electrolyte volume, dehydration, or circulatory failure (e.g. patients with myocardial infarction or multiple trauma);
• in patients with high fever.

Before administering Metamizole Kabi, tell the doctor if the patient has:

• heart disease;
• cerebral vasoconstriction;
• kidney or liver disease.

The use of Metamizole Kabi is associated with the occurrence of acute attacks of porphyria. Metamizole Kabi must not be used in patients with porphyria (see When not to use Metamizole Kabi).
During treatment with Metamizole Kabi, cases of haemolytic and aplastic anaemia have been observed (see section 4).
Do not mix Metamizole Kabi with other medicines in the same syringe, except with tramadol-containing solutions (50 mg/mL).
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 Kabi should be discontinued and medical advice sought if the patient experiences 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 Kabi if they have previously taken any medicines containing metamizole and experienced liver-related problems.
Metamizole Kabi contains sodium
This medicine contains 32.7 mg of sodium (a main component of table salt) in each mL of solution.
This corresponds to 1.64% of the maximum recommended daily sodium intake in the diet of adults.
Metamizole Kabi and other medicines
Tell the doctor or nurse about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take.
In particular, inform the doctor if the patient is taking the following medicines:

• anticoagulants (coumarin derivatives);
• oral antidiabetic drugs;
• cyclosporine (used in transplant patients);
• enzyme-inducing drugs (e.g. glutethimide, used for sleep disorders);
• chlorpromazine (used, among others, in the treatment of schizophrenia);
• oleandomycin (an antibiotic used to treat infections);
• captopril (used to treat hypertension);
• methotrexate (used in the treatment of cancer);
• bupropion (used to treat depression or as an aid in smoking cessation);
• efavirenz (used to treat HIV infection (AIDS));
• methadone (used to treat addiction to illegal opioids);
• valproate (used to treat epilepsy or bipolar affective disorder);
• tacrolimus (used to prevent organ rejection in transplant patients);
• sertraline (used to treat depression).

Metamizole may reduce the antiplatelet effect of acetylsalicylic acid. Caution should be exercised when administering this drug together with acetylsalicylic acid used for the prevention of myocardial infarction.
Metamizole Kabi and alcohol
Do not drink alcohol while taking this medicine.
Pregnancy, breastfeeding and effects on fertility
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 take single doses of metamizole during the first and second trimesters, provided that the benefits and risks of treatment are carefully considered. In principle, the use of metamizole during the first and second trimesters is not recommended.
Metamizole Kabi must not be taken during the last three months of pregnancy due to an increased risk of complications for mother and child (bleeding, premature closure of a vital blood vessel, the so-called ductus arteriosus Botalli, in the unborn child, which normally closes only after birth).
Breastfeeding
Metamizole metabolites pass into human milk in significant amounts, and the 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.
Fertility
There is no data available on the effect of metamizole on fertility.
Driving and operating machinery
Metamizole Kabi may cause drowsiness, fatigue and low blood pressure (manifested by a feeling of emptiness in the head, dizziness, palpitations, blurred vision). Do not drive, operate machinery or perform tasks requiring attention if any of the above symptoms occur.

3. How to use Metamizole Kabi

The dose depends on the severity of pain or fever and the individual's response to Metamizole Kabi.
Metamizole Kabi is administered as intravenous or intramuscular injections.
If a single dose is insufficiently effective or if the analgesic effect diminishes over time,
the physician may administer another dose, without exceeding the maximum daily dose
specified below.

Adults and adolescents aged 15 years and above
For adults and adolescents aged 15 years and above (with body weight exceeding 53 kg), a single dose of 1–2 mL may be given intravenously or intramuscularly; if necessary, the single dose may be increased up to a maximum of 5 mL (corresponding to 2500 mg of metamizole). 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).

Infants and children
The dosing schedule given below should be followed for single intravenous or intramuscular doses:

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

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

Use of a higher than recommended dose of Metamizole Kabi
If a higher than recommended dose of the medicinal product is administered, nausea, vomiting, gastric irritation, abdominal pain, dryness of the mouth, fatigue, rash, low blood pressure (sometimes leading to shock), weakness, headache, fever, and urticaria may occur.

In case of acute overdose, renal dysfunction may also occur, including acute renal failure (e.g. due to interstitial nephritis), symptoms from the central nervous system (dizziness, drowsiness, coma, convulsions), and increased heart rate.

If a higher than recommended dose has been administered or if you feel that you have received more than the recommended dose, you should immediately inform your doctor.

Missed dose of Metamizole Kabi
Do not take a double dose to make up for a missed dose.

If you have any further questions concerning the use of this medicinal product, consult your doctor or nurse.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
You must stop using Metamizole Kabi and seek immediate medical help if any of the following symptoms occur:

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

You should immediately inform your doctor if any of the following adverse effects occur:
Rare (may affect up to 1 in 1,000 patients):
­ Allergic reactions (anaphylactic or anaphylactoid), anaphylactic shock (which may be fatal). These reactions may occur during injection or within a few hours after administration. They usually occur within one hour of administration. Milder allergic reactions may present as skin or mucosal changes (e.g. itching, burning, redness, urticaria, and swelling) or, less frequently, gastrointestinal disturbances.
In severe cases, systemic reactions may occur, including severe angioedema (swelling of the face, lips, tongue, or throat causing difficulty in swallowing and breathing), severe bronchospasm, dyspnoea, cardiac arrhythmias, and arterial hypotension, which may lead to anaphylactic shock, potentially fatal.
Very rare (may affect up to 1 in 10,000 patients):
­ Agranulocytosis presenting as: fever, chills, sore throat, difficulty swallowing, oral ulcers, and mucosal lesions (e.g. in the nose, genital organs, and rectum), lymphadenopathy (very rare).
Agranulocytopenia may occur unexpectedly even in patients who previously used this medicine without complications. Agranulocytosis is a life-threatening adverse effect and may lead to death (see also Warnings and precautions).
Frequency unknown (cannot be estimated from available data):
Severe skin reactions
Metamizole must be discontinued and immediate medical help sought if any of the following severe adverse effects occur:
­ Reddish, flat lesions on the trunk in the shape of a target or circular, often with blisters in the center, skin peeling, ulcers in the mouth, throat, nose, genital organs, and around the eyes. Such serious skin rashes 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).
Other adverse effects:
Common (may affect up to 1 in 10 patients):

• Rash.

Rare (may affect up to 1 in 1,000 patients):

• Leukopenia (reduced number of white blood cells).

Very rare (may affect up to 1 in 10,000 patients):

• Thrombocytopenia (reduced number of blood platelets).

Frequency unknown (frequency cannot be estimated from available data):

• Haemolytic anaemia (reduced number of red blood cells, causing pale or yellowish skin, weakness, or shortness of breath);
• Aplastic anaemia and pancytopenia (marked reduction in all types of blood cells, leading to bleeding, bruising, petechiae, or infection);
• Low blood pressure (see also Warnings and precautions); rapid intravenous administration may increase the risk of this reaction;
• Nausea or vomiting;
• Gastric irritation;
• Dryness of the mouth;
• Acute renal failure, interstitial nephritis (a kidney disease in which inflammation occurs in the spaces between the renal tubules);
• Excessive sweating;
• Drowsiness;
• Fatigue;
• Headache;
• Bullous pemphigoid (a skin disorder characterized by flaccid, easily ruptured blisters on the skin or mucous membranes, which may cause systemic reaction);
• Hepatitis, jaundice, elevated liver enzymes in blood.

Bronchospasm or porphyria may occur during treatment with Metamizole Kabi.
Pain and reactions at the injection site may occur during administration of Metamizole Kabi injection.
Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, you should inform your doctor, pharmacist, or nurse. Adverse effects 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 effects can also be reported to the marketing authorization holder.
Reporting adverse effects helps to provide more information on the safety of the medicine.

5. How to store Metamizole Kabi

Do not store above 25°C.
Store in the original packaging to protect from light. Do not store in the refrigerator or freeze.
Keep the medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the carton after: EXP. The expiry date refers to the last day of the stated month.
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 Metamizole Kabi contains

• The active substance is metamizole sodium. Each mL of injection solution contains 500 mg of anhydrous metamizole sodium. Each ampoule (2 mL) contains 1000 mg of monohydrate metamizole sodium. Each ampoule (5 mL) contains 2500 mg of monohydrate metamizole sodium.
• Other ingredients: hydrochloric acid (for pH adjustment), water for injections.

What Metamizole Kabi looks like and contents of the pack
Metamizole Kabi is a clear solution, almost colourless to brownish-yellow, without visible solid particles.
Metamizole Kabi is available in amber glass ampoules containing 2 mL or 5 mL of solution.
Pack sizes:
5 ampoules of 2 mL in a cardboard pack
10 ampoules of 2 mL in a cardboard pack
5 ampoules of 5 mL in a cardboard pack
10 ampoules of 5 mL in a cardboard pack
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Fresenius Kabi Polska Sp. z o.o.
Al. Jerozolimskie 134
02-305 Warszawa
Manufacturer
Labesfal - Laboratórios Almiro, S.A.
Zona Industrial do Lagedo
3465-157 Santiago de Besteiros
Portugal

For further information about this medicinal product, please contact the Marketing Authorisation Holder:
Fresenius Kabi Polska Sp. z o.o.
Al. Jerozolimskie 134
02-305 Warszawa
tel.: +48 22 345 67 89

Information intended exclusively for healthcare professionals:

Due to the risk of severe adverse reactions, metamizole should be administered intravenously only under strict medical supervision and with immediate access to emergency medical treatment if required.

Route of administration and precautions

Administration of the drug must be performed under strict medical supervision.

The need for administering a dose of metamizole higher than the recommended dose specified in section 3 above should be carefully considered, as the risk of dangerous drop in arterial blood pressure is likely to increase with higher doses.

Intravenous administration

To reduce the risk of anaphylactic shock and hypotensive reactions during intravenous administration, the following precautions should be observed:

• Warm the solution to body temperature before administration;
• Intravenous injection must be performed very slowly (500 mg/min);
• The drug should be prepared at a 1:10 weight ratio, diluted in one of the following solutions: 0.9% sodium chloride solution, Ringer's lactate solution, or 5% glucose solution. Therefore, the contents of a 2 mL ampoule should be diluted in 20 mL, and the contents of a 5 mL ampoule in 50 mL of one of the above-mentioned solutions.

Mixing with tramadol

It has been demonstrated that Metamizole Kabi can be mixed with injection solutions containing tramadol 50 mg/mL and the excipients: water for injections and sodium acetate.

The tramadol and metamizole mixture should be prepared at a 1:10 weight ratio, diluted in one of the solutions listed above; for example, 2 mL of Metamizole Kabi (concentration 500 mg/mL) is mixed with 2 mL of a tramadol-containing solution (concentration 50 mg/mL), and the mixture is then diluted in 20 mL of 0.9% sodium chloride solution, Ringer's lactate solution, or 5% glucose solution.

The ready-to-use diluted mixture of metamizole and tramadol may have a yellowish color.

Do not mix Metamizole Kabi with other medicinal products in the same syringe, except those mentioned above.

Having the patient in a lying position and continuous monitoring of blood pressure, heart rate, and respiratory rate facilitate early detection of anaphylactic, anaphylactoid, and hypotensive reactions.

Shelf-life after first opening

Metamizole Kabi should be used immediately after opening.

Shelf-life after dilution

Metamizole Kabi should be used immediately after dilution.

From a microbiological standpoint, the product should be used immediately. If not used immediately, the responsibility for storage conditions and duration prior to use lies with the user.

Duration of treatment

The duration of treatment depends on the type and severity of the disease. In cases of prolonged treatment with Metamizole Kabi, the physician will decide whether appropriate tests should be performed.