Pireoxing

Leaflet accompanying the packaging: information for the user

Pyreoxing, 500 mg/ml, solution for injection

Metamizole sodium

You should carefully read the contents of the leaflet before using the medicine, as it contains important information for the patient.

• You should keep this leaflet, so that you can read it again if you need to.
• If you have any doubts, you should consult a doctor or pharmacist.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should tell their doctor or pharmacist. See section 4.

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

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

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

Table of contents of the leaflet

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

1. What is Pyreoxing and what is it used for

Pyreoxing is a non-addictive medicine with analgesic (pain-relieving), antipyretic (fever-reducing), and spasmolytic (muscle-relaxing) effects.
It is used to relieve severe acute pain and fever when other treatment methods are ineffective. The medicine in the form of a solution for injection should only be used when oral administration is not indicated.
The route of administration in the form of intravenous injection allows for extremely strong analgesic effects in various conditions, making it possible to control pain that would otherwise only respond to opioid-containing products. Unlike opioids, Pyreoxing does not cause addiction or respiratory depression, even at high doses. The medicine does not disrupt intestinal peristalsis or labor contractions.
It is used to treat severe, sudden, or persistent pain and fever that do not respond to other treatment methods.
The active substance of Pyreoxing is metamizole.

2. Important information before using Pyreoxing

When not to use Pyreoxing

• If the patient is allergic to metamizole or any of the other ingredients of this medicine (listed in section 6) or to other similar active substances (e.g., phenazone, propyphenazone, phenylbutazone, oxyphenbutazone).
• If the patient has blood disorders or a disease that affects the production or function of blood cells.
• If the patient has a history of significantly reduced white blood cell count (granulocytopenia) caused by metamizole or other similar medicines called pyrazolones or pyrazolidines.
• If the patient has asthma or allergic reactions to painkillers (salicylates, paracetamol, or other painkillers, e.g., diclofenac, ibuprofen, indomethacin, naproxen), such as hives or angioedema (swelling of the face and mucous membranes of the respiratory, gastrointestinal, or genital tract).
• If the patient has severe liver disease, such as porphyria (risk of porphyria attack).
• If the patient has a congenital deficiency of glucose-6-phosphate dehydrogenase (risk of hemolysis).
• During the last three months of pregnancy.
• If the patient has low blood pressure or circulation problems.

Warnings and precautions

Before starting to use Pyreoxing, you should discuss it with your doctor or pharmacist:

• In case of fever, chills, sore throat, or ulcers in the mouth, you should stop the treatment and contact your doctor immediately. These symptoms may be related to neutropenia (a very low number of granulocytes). This reaction is very rare, may be severe, and can be life-threatening. It is not dose-dependent and can occur at any time during treatment. If neutropenia occurs (1500 granulocytes per microliter of blood or less), you should stop the treatment immediately.
• In case of any symptoms indicating blood disorders (e.g., general weakness, infection, persistent fever, bruising, bleeding, pallor), you should consult your doctor immediately. These symptoms may be caused by pancytopenia (a decrease in the number of all types of blood cells).
• If the patient has asthma or atopy (a type of allergy), there is an increased risk of anaphylactic shock (a life-threatening allergic reaction) after administering metamizole, especially when given as an injection.
• If the patient has any of the following conditions, due to the increased risk of severe anaphylactoid reactions after administering metamizole:
• asthma and concurrent mucosal inflammation;
• prolonged and (or) chronic hives;
• alcohol intolerance, manifested by sneezing, tearing, and significant facial flushing after consuming even small amounts of alcoholic beverages;
• hypersensitivity to dyes (e.g., tartrazine) or preservatives (e.g., benzoates).
• If the patient has low blood pressure or is dehydrated, has unstable fluid volume, early-stage circulatory failure, or high fever. In such cases, there is an increased risk of severe hypotensive reactions (reactions related to a drop in blood pressure). Therefore, in such cases, the administration of metamizole should be carefully considered, and if the decision to use it is made, close medical supervision is necessary. Preventive measures should be taken to reduce the risk of hypotensive reactions. Administration of metamizole may cause hypotensive reactions unrelated to the above conditions. These reactions seem to be dose-dependent, and their occurrence is more likely after injection.

In order to reduce the risk of hypotensive reactions, it is necessary to implement preventive measures.

• If the patient has severe coronary artery disease or significant narrowing of the blood vessels supplying blood to the brain. In such cases, it is absolutely necessary to avoid lowering blood pressure, so metamizole should only be administered after careful monitoring of cardiovascular function has been initiated.
• If the patient has kidney or liver disease. In such cases, large doses of metamizole should not be administered, as its elimination is reduced.
• If the patient has previously taken a medicine containing metamizole and had liver problems.

Liver problems
Patients taking metamizole have experienced cases of liver inflammation, whose symptoms appeared within a few days to several months after starting treatment. You should stop using Pyreoxing and contact your doctor if you experience symptoms of liver dysfunction, such as nausea or vomiting, fever, fatigue, loss of appetite, dark urine, light-colored stools, yellowing of the skin or whites of the eyes, itching, rash, or pain in the upper abdomen. The doctor will check the patient's liver function.
You should not use Pyreoxing if you have previously taken a medicine containing metamizole and had liver problems.
Severe skin reactions
Severe skin reactions, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS), have been reported in association with metamizole treatment. If you experience any of these symptoms, you should stop using metamizole and seek medical attention immediately.
If you have ever experienced severe skin reactions, you should never restart treatment with Pyreoxing (see section 4).
Agranulocytosis (severely low number of white blood cells)
Pyreoxing may cause agranulocytosis, a severely low number of a certain type of white blood cell called granulocytes, which play an important role in fighting infections (see section 4). You should 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 ulcers of the mucous membranes, especially in the mouth, nose, and throat, or in the genital or anal area. The doctor will order a laboratory test 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 taking antibiotics.
Agranulocytosis may develop at any time during treatment with Pyreoxing and even for a short time after stopping metamizole.
Agranulocytosis may occur even if metamizole was previously taken without complications.

Pyreoxing and other medicines

You should tell your doctor or pharmacist about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take.
Metamizole may weaken the effect of some medicines:

• bupropion, a medicine used to treat depression or to help quit smoking;
• efavirenz, a medicine used to treat HIV/AIDS infection;
• methadone, a medicine used to treat opioid addiction;
• valproate, a medicine used to treat epilepsy or bipolar disorder;
• tacrolimus, a medicine used to prevent transplant rejection in patients who have undergone organ transplantation;
• sertraline, a medicine used to treat depression;
• cyclosporine, a medicine that suppresses the immune system.

The doctor should carefully monitor whether the patient is taking metamizole at the same time as any of the above medicines.
Adding metamizole to methotrexate (an immunosuppressive medicine) may increase the adverse effect of methotrexate on the hematopoietic system, especially in elderly patients. It is recommended to avoid concomitant use of these medicines.
Caution should be exercised when using Pyreoxing and aspirin administered to prevent cardiovascular events.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a child, you should consult your doctor or pharmacist 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 a harmful effect on the fetus. In selected cases, when there are no other treatment options, after consulting a doctor or pharmacist, the patient may take single doses of metamizole in the first and second trimester of pregnancy, provided that the benefits and risks associated with taking metamizole are carefully weighed. However, the use of metamizole is not recommended during the first and second trimesters of pregnancy.
You should not take Pyreoxing 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 child, also known as the Botall duct, which closes naturally 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, mothers are advised to express and discard breast milk for 48 hours after taking the medicine.

Driving and using machines

Within the recommended dose range, the medicine does not affect the ability to drive and use machines.
Taking Pyreoxing in doses higher than recommended and concurrent alcohol consumption impair reaction and concentration abilities. In such cases, you should not drive or operate machines.
Pyreoxing contains sodium.
This medicine contains 32.7 mg of sodium (the main component of table salt) per milliliter of solution for injection, which corresponds to 1.63% of the maximum recommended daily intake of sodium in the diet for adults.

3. How to use Pyreoxing

This medicine should always be used as directed by your doctor or pharmacist. If you are unsure, you should consult your doctor or pharmacist.
The dose depends on the severity of the pain or fever and the individual patient's sensitivity to Pyreoxing. Pyreoxing will be administered as an intravenous or intramuscular injection. The onset of action is observed 30 minutes after administration, and the duration of action is usually about 4 hours.
If the analgesic effect after a single dose of the medicine is insufficient or if the effect wears off after some time, the doctor may administer another dose, not exceeding the maximum daily dose listed in the table below.
Adults and adolescents over 15 years old
Adults and adolescents over 15 years old (with a body weight over 53 kg) can be given the medicine intravenously or intramuscularly in a single dose of 1-2 ml; if necessary, a single dose can be increased to 5 ml (which corresponds to 2500 mg of Pyreoxing). The maximum daily dose is 8 ml; if necessary, the daily dose can be increased to 10 ml (which corresponds to 5000 mg of Pyreoxing).
Infants and children
You should follow the following scheme for administering single intravenous or intramuscular doses:

Elderly patients and patients in poor general condition and (or) with impaired renal function
In the case of 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.
Patients with impaired renal or hepatic function
Since the elimination rate is reduced in patients with impaired renal or hepatic function, it is recommended to avoid repeated administration of large doses, as the elimination rate of the medicine is slowed down in these patients. Dose reduction is not required in the case of short-term use. There are no data available on long-term use.
It is essential to monitor the patient's condition closely during injection, and the doctor should carefully monitor the patient's condition after administering the medicine.

Using a higher dose of Pyreoxing than recommended

The medicine is administered by a doctor, so overdose is unlikely.
Symptoms of acute overdose include nausea, vomiting, abdominal pain, kidney dysfunction and (or) kidney failure, nervous system disorders (dizziness, drowsiness, coma, convulsions), hypotension, and arrhythmias. Very high doses may cause harmless discoloration of the urine to a red color.

Missing a dose of Pyreoxing

You should not take a double dose to make up for a missed dose.
If you have any further doubts about using this medicine, you should consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, Pyreoxing can cause side effects, although not everybody gets them.
Side effects are ranked according to frequency of occurrence as follows: very common (≥ 1/10), common (≥ 1/100 to <1>You should stop using Pyreoxing and contact your doctor immediately if you experience any of the following symptoms:
nausea or vomiting, fever, fatigue, loss of appetite, dark urine, light-colored stools, yellowing of the skin or whites of the eyes, itching, rash, or pain in the upper abdomen. These symptoms may be signs of liver damage. See also section 2 "Warnings and precautions".

You should stop using metamizole and contact your doctor immediately if you experience any of the following side effects (frequency not known):

red, flat, plate-like, or round spots on the torso, often with blisters in the center, peeling of the skin, ulcers in the mouth, throat, or genital or anal area, or eye area. The occurrence of these severe skin rashes may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome; toxic epidermal necrolysis);

• a widespread rash, high body temperature, and swollen lymph nodes (DRESS syndrome or hypersensitivity syndrome).

Blood and lymphatic system disorders
Rarely: blood disorders may occur, such as a decrease in the number of red blood cells due to bone marrow suppression (aplastic anemia), a decrease or disappearance of one type of white blood cell (agranulocytosis), and a decrease in the number of red blood cells, white blood cells, and platelets (pancytopenia), including cases leading to death, a decrease in the number of white blood cells (leukopenia), and thrombocytopenia (a decrease in the number of platelets).
Very rarely: typical symptoms of thrombocytopenia include an increased tendency to bleed and the appearance of small, reddish-brown spots (petechiae) on the skin and mucous membranes, while symptoms of agranulocytosis include inflammatory changes in the mucous membranes, mainly in the mouth, nose, and throat, as well as inflammatory changes in the rectum and genital area, sore throat, and fever (which unexpectedly does not subside or recurs). However, in patients treated with antibiotics, these symptoms may have minimal severity. There is a significant increase in the Biernacki reaction (moderate or absent lymph node enlargement).
Immune system disorders
Rarely: metamizole may cause allergic reactions (anaphylactic shock, anaphylactic, and (or) anaphylactoid reactions), which can be severe and life-threatening and sometimes fatal. These reactions may occur even if metamizole was previously taken multiple times without complications.
They usually develop within the first hour after taking Pyreoxing but may occur immediately or several hours later.
Moderate anaphylactic and (or) anaphylactoid reactions cause symptoms from the skin and mucous membranes (such as itching, burning, redness, hives, and swelling), in the form of respiratory problems or rarely in the form of gastrointestinal disorders. However, these symptoms may transform into a severe form of hives all over the body, and severe cases are characterized by facial swelling, tongue, throat, or laryngeal edema (angioedema), significant shortness of breath, arrhythmias, low blood pressure (which is sometimes preceded by an increase in blood pressure), and shock. In patients with asthma, these reactions take the form of asthma attacks.
Frequency not known: Kounis syndrome (a heart condition caused by an allergic reaction).
Vascular disorders
Frequency not known: transient, rarely critical, isolated drop in blood pressure without further symptoms of an allergic reaction.
Skin and subcutaneous tissue disorders
Rarely: rash.
Frequency not known: severe skin reactions.
Renal and urinary disorders
Very rarely: transient kidney dysfunction with reduced urine output (oliguria) or urinary retention (anuria) or acute kidney failure, which may be accompanied by proteinuria.
Frequency not known: kidney inflammation (interstitial nephritis).
General disorders and administration site conditions
Frequency not known: pain at the injection site, phlebitis.
The medicine may affect the results of some blood tests (e.g., creatinine, triglycerides, HDL cholesterol, and uric acid levels).
Hepatobiliary disorders
Frequency not known:
liver inflammation, jaundice, and increased liver enzyme activity in the blood.

Reporting side effects

If you experience any side effects, including any side effects not listed in this leaflet, you should tell your doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety Monitoring of the 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
Side effects can also be reported to the marketing authorization holder.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Pyreoxing

Do not store above 25°C. Store in the original packaging to protect from light.
Medicines should be kept out of the sight and reach of children.
Do not use this medicine after the expiry date (EXP) stated on the carton and label. The expiry date refers to the last day of the month.
Medicines should not be disposed of via wastewater or household waste. You should ask your pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the packaging and other information

What Pyreoxing contains

• The active substance of Pyreoxing is metamizole sodium. Each milliliter of solution contains 500 mg of metamizole sodium.
• The other ingredient is water for injections.

What Pyreoxing looks like and contents of the pack

A clear, colorless to slightly brownish-yellow solution, practically free from particulate matter.
Ampoules made of orange glass containing the solution, placed in a PVC blister pack in a cardboard box.
Pack sizes: 10 ampoules of 2 ml, 10 ampoules of 5 ml, 5 ampoules of 2 ml, 5 ampoules of 5 ml.
Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder:

Bausch Health Ireland Limited
3013 Lake Drive
Citywest Business Campus
Dublin 24, D24PPT3
Ireland
phone: +48 17 865 51 00

Manufacturer:

Przedsiębiorstwo Farmaceutyczne Jelfa S.A.
ul. Wincentego Pola 21
58-500 Jelenia Góra

This medicine is authorized in the Member States of the European Economic Area under the following names:

Bulgaria
Амизолмет 500 mg/ml инжекционен разтвор
Poland
Pyreoxing
Lithuania
Metamizole sodium Bausch Health 500 mg/ml injekcinis tirpalas
Date of last revision of the leaflet:11/2024
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Information intended for healthcare professionals only:
Parenteral administration is associated with a high risk of anaphylactic and (or) anaphylactoid reactions.
If administration of metamizole to children aged 3 to 11 months is considered, it should be remembered that metamizole should only be administered intramuscularly to these children.
It is crucial to ensure that the administration of the medicinal product is discontinued in case of the first symptoms of an anaphylactic and (or) anaphylactoid reaction and to minimize the risk of isolated hypotension.
During parenteral administration, it is necessary to ensure that the patient is in a supine position and under close medical supervision. Furthermore, to prevent hypotensive reactions, intravenous injection should be performed very slowly, i.e., no more than 1 ml (500 mg of metamizole) per minute.
The solution for injection can be diluted with a 5% glucose solution, 0.9% sodium chloride solution, or Ringer's solution, but these solutions should be administered immediately, as their stability is limited.
Due to possible incompatibilities, the metamizole solution should not be administered with other injectable medicines.