METAMIZOLE 500 mg /Ml Solution

Contents of the leaflet

1. Package Leaflet: Information for the User
2. Metamizole Kabi, 500 mg/mL, Solution for Injection
   1. Metamizole Kabi may cause a severely decreased number of white blood cells (agranulocytosis), which can lead to severe and life-threatening infections (see section 4).
   2. Stop taking the medicine and contact your doctor immediately if you experience any of the following symptoms: fever, chills, sore throat, painful mouth ulcers, or ulcers in the genital or anal area.
   3. If the patient has ever had agranulocytosis while taking metamizole or similar medicines, they should never take this medicine again (see section 2).
   4. Read the leaflet carefully before taking the medicine, as it contains important information for the patient.
   5. Table of Contents of the Leaflet
3. What is Metamizole Kabi and what is it used for
4. Important information before taking Metamizole Kabi
   1. When not to take Metamizole Kabi:
   2. Warnings and precautions
   3. Metamizole Kabi and other medicines
   4. Metamizole Kabi and alcohol
   5. Pregnancy, breastfeeding, and fertility
   6. Driving and using machines
5. How to take Metamizole Kabi
   1. Overdose of Metamizole Kabi
   2. Missed dose of Metamizole Kabi
6. Possible side effects
   1. Other side effects:
   2. Reporting side effects
7. How to store Metamizole Kabi
8. Contents of the pack and other information
   1. What Metamizole Kabi contains
   2. What Metamizole Kabi looks like and contents of the pack
   3. Marketing authorization holder
   4. Manufacturer
   5. Date of last revision of the leaflet: ------------------------------------------------------------------------------------------------------------------------
   6. Information intended for healthcare professionals only:

Package Leaflet: Information for the User

Metamizole Kabi, 500 mg/mL, Solution for Injection

Metamizole Sodium Monohydrate

Metamizole Kabi may cause a severely decreased number of white blood cells (agranulocytosis), which can lead to severe and life-threatening infections (see section 4).

Stop taking the medicine and contact your doctor immediately if you experience any of the following symptoms: fever, chills, sore throat, painful mouth ulcers, or ulcers in the genital or anal area.

If the patient has ever had agranulocytosis while taking metamizole or similar medicines, they should never take this medicine again (see section 2).

Read the leaflet carefully before taking the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or nurse. See section 4.

Table of Contents of the Leaflet

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

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

The active substance of Metamizole Kabi is metamizole. Metamizole is a pyrazolone derivative with strong analgesic, antipyretic, and spasmolytic effects, but weak anti-inflammatory effects.
Indications for use:
Pain of various origins with high intensity.
Fever, when other treatment methods are ineffective.
Metamizole Kabi should only be used when oral administration is not indicated.

2. Important information before taking Metamizole Kabi

When not to take Metamizole Kabi:

• if the patient has a history of significantly decreased white blood cell count (granulocytopenia) caused by metamizole or other similar medicines (pyrazolones or pyrazolidines);
• if the patient has bone marrow disorders or diseases that affect blood cell production or function;
• if the patient is allergic to metamizole, other pyrazolone derivatives, or pyrazolidines (such as propyphenazone, phenazone, or phenylbutazone), or any of the other ingredients of this medicine (listed in section 6);
• if the patient has analgesic asthma or intolerance to painkillers, manifested by urticaria, angioedema, or anaphylactoid reactions 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 liver or kidney dysfunction;
• if the patient has acute porphyria (a hereditary disorder of red blood cell production);
• if the patient has a congenital deficiency of glucose-6-phosphate dehydrogenase (a condition that causes red blood cell breakdown);
• 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 risks of side effects or when other treatment methods are not available or not suitable.
Taking Metamizole Kabi is associated with an increased risk of rare but life-threatening side effects, such as agranulocytosis or severe allergic reactions - anaphylactic shock (see also section 4).
Agranulocytosis
Metamizole Kabi may cause agranulocytosis, a very low number of a type of white blood cell called granulocytes, which play an important role in fighting infections (see section 4).
Stop taking metamizole and contact your doctor immediately if you experience any of the following symptoms, as they may indicate possible agranulocytosis: chills, fever, sore throat, and painful mouth ulcers, especially in the mouth, nose, and throat, or in the genital or anal area. Your doctor will order a blood test to check your 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 taking antibiotics.
Agranulocytosis can develop at any time during treatment with Metamizole Kabi, even after a short period of treatment.
Agranulocytosis can occur even if metamizole was previously taken without complications.
Anaphylactic and anaphylactoid reactions
Very rarely, after intravenous administration of Metamizole Kabi, severe allergic reactions (anaphylactic) may occur. They can lead to life-threatening hypotension, coma, and even death.
Tell your doctor if:

• you have analgesic asthma or intolerance to painkillers, manifested by urticaria, angioedema, especially if accompanied by nasal polyposis and sinusitis;
• you have bronchial asthma, especially if accompanied by sinusitis and nasal polyps;
• you have chronic urticaria;
• you are intolerant to alcohol (manifested by rhinitis, tearing, and facial flushing in response to even small amounts of alcohol; this may indicate undiagnosed analgesic asthma);
• you are allergic (hypersensitive) to dyes (e.g., tartrazine) or preservatives (e.g., benzoates);
• you have atopic diseases.

If you experience symptoms of anaphylactic or anaphylactoid reactions, such as shortness of breath, tongue swelling, angioedema, rash, or urticaria, stop taking the medicine and seek medical help immediately, as it can be life-threatening.
Patient who have had an anaphylactic or other immunological reaction to metamizole are also at risk of a similar reaction to other pyrazolones and pyrazolidines and 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), have been reported with metamizole treatment.
If you experience any of the following severe skin reactions, stop taking metamizole and seek medical help immediately:
­
red, flat spots on the torso, target-like, or round, often with blisters in the center, peeling skin, mouth ulcers, throat, nose, genitals, and eye irritation. The occurrence of such serious skin rashes may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome, toxic epidermal necrolysis);
­
widespread rash, high fever, and swollen lymph nodes (DRESS or hypersensitivity syndrome).

Metamizole Kabi contains sodium.
This medicine contains 32.7 mg of sodium (the main component of common salt) per mL of solution.
This corresponds to 1.64% of the maximum recommended daily intake of sodium in the diet for adults.

Metamizole Kabi and other medicines

Tell your doctor or nurse about all medicines you are taking, have recently taken, or might take.
In particular, tell your doctor about the following medicines:

• anticoagulants (coumarin derivatives);
• oral antidiabetic medicines;
• cyclosporine (used in transplant patients);
• enzyme inducers (e.g., glutethimide, used in sleep disorders);
• chlorpromazine (used in the treatment of schizophrenia);
• oleandomycin (an antibiotic used to treat infections);
• captopril (used to treat high blood pressure);
• methotrexate (used to treat cancer);
• bupropion (used to treat depression or as an aid to smoking cessation);
• efavirenz (used to treat HIV infection (AIDS));
• methadone (used to treat opioid dependence);
• valproate (used to treat epilepsy or bipolar disorder);
• tacrolimus (used to prevent organ rejection in transplant patients);
• sertraline (used to treat depression).

Metamizole may reduce the effect of acetylsalicylic acid on platelets. Be cautious when taking this medicine and acetylsalicylic acid, used to prevent heart attack.

Metamizole Kabi and alcohol

Do not drink alcohol while taking this medicine.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before taking this medicine.
Pregnancy
There is limited data on the use of metamizole during the first 3 months of pregnancy, but it does not indicate a harmful effect on the fetus. In selected cases, if there are no other treatment options, after consulting a doctor or pharmacist, a pregnant woman may take a single dose of metamizole in the first and second trimester, provided that the benefits and risks of taking the medicine are carefully considered. As a rule, metamizole should not be taken during the first and second trimester.
Do not take Metamizole Kabi during the last three months of pregnancy due to the increased risk of complications in the mother and child (bleeding, premature closure of the ductus arteriosus in the unborn child, which normally closes after birth).
Breastfeeding
Metamizole metabolites pass into breast milk in significant amounts, and the risk to the breastfed child cannot be excluded. Therefore, it is recommended to avoid repeated use of metamizole during breastfeeding. In the case of a single dose of metamizole, it is recommended that mothers discard breast milk for 48 hours after administration.
Fertility
There is no data on the effect of metamizole on fertility.

Driving and using machines

Metamizole Kabi may cause drowsiness, fatigue, and low blood pressure (manifested by dizziness, dizziness, palpitations, blurred vision). Do not drive, operate machinery, or perform tasks that require attention if you experience any of these symptoms.

3. How to take Metamizole Kabi

The dose depends on the severity of the pain or fever and the individual's response to Metamizole Kabi.
Metamizole Kabi is administered by intravenous or intramuscular injection.
If a single dose is not sufficiently effective or if the analgesic effect weakens over time, your doctor may administer another dose, not exceeding the maximum daily dose specified below.
Adults and adolescents over 15 years
Adults and adolescents over 15 years (with a body weight over 53 kg) can be given 1-2 mL as a single dose intravenously or intramuscularly; if necessary, the single dose can be increased to a maximum of 5 mL (corresponding to 2500 mg of metamizole). The maximum daily dose is 8 mL; if necessary, the daily dose can be increased to a maximum of 10 mL (corresponding to 5000 mg of metamizole).
Infants and children
Follow the dosing schedule below for single intravenous or intramuscular doses:

Elderly and patients in poor general health or with renal impairment
In elderly patients, weakened patients, and patients with impaired renal function, the dose should be reduced due to the possibility of prolonged elimination of metamizole metabolites.
Patient with renal or hepatic impairment
Due to reduced elimination in patients with renal or hepatic impairment, it is recommended to avoid repeated administration of high doses. In the case of short-term use, dose reduction is not required. There is no experience with long-term use.

Overdose of Metamizole Kabi

In case of overdose, the following symptoms may occur: nausea, vomiting, stomach irritation, abdominal pain, dry mouth, fatigue, rash, low blood pressure (sometimes leading to shock), weakness, headache, fever, and urticaria.
In case of acute overdose, the following symptoms may also occur: renal impairment, including acute renal failure (e.g., interstitial nephritis), central nervous system symptoms (dizziness, drowsiness, coma, seizures), and increased heart rate.
If you have taken more than the recommended dose of the medicine or if you think you have taken too much, tell your doctor immediately.

Missed dose of Metamizole Kabi

Do not take a double dose to make up for a missed dose.
If you have any further questions on the use of this medicine, ask your doctor or nurse.

4. Possible side effects

Like all medicines, Metamizole Kabi can cause side effects, although not everybody gets them.
Stop taking Metamizole Kabi and seek medical help immediately if you experience any of the following symptoms:

• 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 pain in the upper abdomen. These may be symptoms of liver damage. See also section 2 Warnings and precautions.

Tell your doctor immediately if you experience any of the following side effects:
Rare (may affect up to 1 in 1,000 people):
­
allergic reactions (anaphylactic or anaphylactoid), anaphylactic shock (with possible fatal outcome). These reactions can occur during or within a few hours of administration. They usually occur within an hour of administration. Less severe allergic reactions occur in the form of skin or mucous membrane changes (e.g., itching, burning, redness, urticaria, and angioedema) or, less frequently, gastrointestinal disorders.
In severe cases, general reactions may occur, including severe angioedema (facial, lip, tongue, or throat swelling, causing difficulty swallowing and breathing), severe bronchospasm, dyspnea, arrhythmias, and hypotension, which can lead to anaphylactic shock, with possible fatal outcome.
Very rare (may affect up to 1 in 10,000 people):
­
agranulocytosis, manifested by: fever, chills, sore throat, difficulty swallowing, mouth ulcers, and mucous membrane damage (e.g., nose, genitals, and anus), lymph node enlargement (very rare).
Agranulocytosis can occur unexpectedly, even in patients who have previously taken this medicine without complications. Agranulocytosis is a life-threatening side effect and can lead to death (see also Warnings and precautions).
Frequency not known (cannot be estimated from the available data):
Severe skin reactions
Stop taking metamizole and seek medical help immediately if you experience any of the following severe side effects:
­
red, flat spots on the torso, target-like, or round, often with blisters in the center, peeling skin, mouth ulcers, throat, nose, genitals, and eye irritation. The occurrence of such serious skin rashes may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome, toxic epidermal necrolysis);
­
widespread rash, high fever, and swollen lymph nodes (DRESS or hypersensitivity syndrome).

Other side effects:

Common (may affect up to 1 in 10 people):

• rash.

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

• leukopenia (decreased white blood cell count).

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

• thrombocytopenia (decreased platelet count).

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

• hemolytic anemia (decreased red blood cell count, causing pale or yellowish skin, weakness, or shortness of breath);
• aplastic anemia and pancytopenia (severe decrease in all types of blood cells, causing bleeding, bruising, or infection);
• low blood pressure (see also Warnings and precautions); rapid intravenous administration may increase the risk of this reaction;
• nausea or vomiting;
• stomach irritation;
• dry mouth;
• acute renal failure, interstitial nephritis (kidney disease, in which there is inflammation in the spaces between the renal tubules);
• excessive sweating;
• drowsiness;
• fatigue;
• headache;
• common bullous pemphigoid (a skin disorder with fragile, easily rupturing blisters on the skin or mucous membranes, which can cause a general reaction);
• hepatitis, jaundice, and elevated liver enzymes in the blood.

During treatment with Metamizole Kabi, bronchospasm or porphyria may occur.
During intravenous administration of Metamizole Kabi, pain and reactions at the injection site may occur.

Reporting side effects

If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Drug Safety, Urząd Rejestracji Produktów Leczniczych, Wyrobów Medycznych i Produktów Biobójczych
Al. Jerozolimskie 181C
02-222 Warszawa
tel.: +48 22 49 21 301
fax: +48 22 49 21 309
website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder.
Reporting side effects will help to gather more information on the safety of this medicine.

5. How to store Metamizole Kabi

Do not store above 25°C.
Store in the original package to protect from light. Do not store in the refrigerator or freeze.
Keep the medicine out of the 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 month stated.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Metamizole Kabi contains

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

What Metamizole Kabi looks like and contents of the pack

Metamizole Kabi is a clear, almost colorless to yellowish-brown solution, without visible particles.
Metamizole Kabi is available in orange glass ampoules containing 2 mL or 5 mL of solution.
Pack sizes:
5 ampoules of 2 mL in a carton
10 ampoules of 2 mL in a carton
5 ampoules of 5 mL in a carton
10 ampoules of 5 mL in a carton
Not all pack sizes may be marketed.

Marketing authorization 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
To obtain more detailed information on this medicine, contact the marketing authorization holder:
Fresenius Kabi Polska Sp. z o.o.
Al. Jerozolimskie 134
02-305 Warszawa
tel.: +48 22 345 67 89

Date of last revision of the leaflet: ------------------------------------------------------------------------------------------------------------------------

Information intended for healthcare professionals only:

Due to the risk of severe side effects, metamizole should be administered intravenously under close medical supervision and with immediate access to medical care.
Administration and precautions
Administration should be carried out under close medical supervision.
The need to administer a dose of metamizole higher than recommended above in section 3 should be carefully considered, as the risk of dangerous hypotension is likely to increase with the dose.
Intravenous administration
To minimize the risk of anaphylactic shock and hypotensive reactions during intravenous administration, the following precautions should be taken:

• before administration, the solution should be warmed to body temperature;
• intravenous injection should be performed very slowly (500 mg/min);
• the medicine should be administered after dilution in a ratio of 1:10, using one of the following solutions: 0.9% sodium chloride solution, Ringer's solution with lactate, 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 solutions.

Mixing with tramadol
It has been shown that Metamizole Kabi can be mixed with injection solutions containing tramadol 50 mg/mL and excipients: water for injections and sodium acetate.
The mixture of tramadol and metamizole should be prepared in a ratio of 1:10, after dilution in the above-mentioned solutions, i.e., for example, 2 mL of Metamizole Kabi (500 mg/mL) is mixed with 2 mL of a medicine containing tramadol (50 mg/mL), and then the mixture is diluted in 20 mL of 0.9% sodium chloride solution or Ringer's solution with lactate, or 5% glucose solution.
The prepared mixture of metamizole and tramadol may have a yellowish color.
Do not mix Metamizole Kabi with other medicines in the same syringe, except for those mentioned above.
The patient's supine position and constant monitoring of blood pressure, heart rate, and respiratory rate facilitate early detection of anaphylactic and anaphylactoid reactions 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.
For microbiological reasons, the product should be used immediately. If not used immediately, the responsibility for the storage time and conditions before use lies with the user.
Duration of treatment
The duration of treatment depends on the type and severity of the disease. In the case of long-term treatment with Metamizole Kabi, the doctor will decide on the necessary tests.