PYREOX

Patient Information Leaflet

Pyreox, 500 mg, coated tablets
Metamizolum natricum monohydricum
Pyreox may cause abnormally low levels of white blood cells (agranulocytosis), which can lead to severe and life-threatening infections (see section 4).
Treatment must 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 the patient has ever experienced agranulocytosis while taking metamizole or similar medicines, this medicine must never be taken again in the future (see section 2).
Please read the entire leaflet carefully before taking this medicine, as it contains important information for the patient.
This medicine should always be taken exactly as described in this patient leaflet or as directed by the doctor, pharmacist, or nurse.

• Keep this leaflet, as you may need to read it again.
• If you need advice or further information, please contact your pharmacist.
• If you experience any adverse reactions, including any adverse reactions not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.
• If there is no improvement after 3–5 days, or if the patient feels worse, contact a doctor.

Contents of the leaflet

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

1. What Pyreox is and what it is used for

Pyreox is a medicinal product with analgesic (pain-relieving), antipyretic (fever-reducing), and antispasmodic (relaxing smooth muscle spasms) properties.
Pyreox is indicated for use in the following conditions:

• severe acute or chronic (long-term) pain;
• high fever unresponsive to other treatments.

This medicine is indicated for use in adults and adolescents aged 15 years and older.
If there is no improvement after 3–5 days, or if the patient feels worse, contact a doctor.

2. Important information before using Pyreox

When not to use Pyreox

• if the patient has previously experienced a significant decrease in the number of white blood cells called granulocytes, caused by metamizole or other similar medicines known as pyrazolones or pyrazolidines;
• if the patient has disorders of bone marrow function or a condition affecting the production or function of blood cells;
• if the patient is allergic to metamizole, other pyrazolones or pyrazolidines (e.g. phenazone or propyphenazone, phenylbutazone, oxyphenbutazone) or to any of the other ingredients of this medicine (listed in section 6);
• if the patient has previously had a reaction after using these active substances;
• if the patient has analgesic-related asthma or another form of analgesic intolerance, such as bronchospasm (sudden narrowing of the lower airways), or other allergic reactions such as urticaria, rhinitis, or angioedema (swelling of various body parts, most commonly face and throat), in response to analgesics such as salicylates, paracetamol, or other non-opioid analgesics, including non-steroidal anti-inflammatory drugs such as: diclofenac, ibuprofen, indometacin, or naproxen;
• if the patient has acute intermittent porphyria (a hereditary disorder affecting haemoglobin synthesis);
• if the patient has a congenital deficiency of the enzyme glucose-6-phosphate dehydrogenase;
• if the patient is in the last three months of pregnancy.

Warnings and precautions
Before starting to take Pyreox, discuss this with your doctor or pharmacist:

• if the patient has low systolic blood pressure (below 100 mmHg), heart disease or circulatory disorders (e.g. myocardial infarction, ischaemic heart disease, or multi-organ damage), narrowing of arteries supplying blood to the brain, reduced blood volume, or dehydration, as metamizole may lower blood pressure;
• if the patient has high fever;
• if the patient has impaired kidney and/or liver function;
• if the patient has bronchial asthma, particularly with coexisting rhinitis and sinusitis;
• if the patient belongs to a group at increased risk of allergy-like reactions, including atopic reactions and chronic urticaria;
• if the patient has intolerance to certain dyes (e.g. tartrazine) or preservatives (e.g. benzoates);
• if the patient has alcohol intolerance, manifesting as sneezing, tearing, and pronounced facial flushing even after small amounts of alcohol; this may indicate previously undiagnosed analgesic-related asthma.

Low white blood cell count (agranulocytosis)
Pyreox 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 stopped 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, throat, genital area, or anus. Your doctor will order laboratory tests to check your blood cell count.
If metamizole is taken for fever, some symptoms of developing agranulocytosis may go unnoticed. Similarly, symptoms may also be masked if the patient is receiving antibiotics.
Agranulocytosis may develop at any time during treatment with Pyreox, and even shortly after stopping metamizole.
Agranulocytosis may occur even if metamizole was previously administered without complications.

Liver problems
Cases of hepatitis have been reported in patients taking metamizole, with symptoms developing from several days to several months after starting treatment.
Treatment with Pyreox should be discontinued and a doctor consulted immediately if symptoms of liver problems occur, such as nausea (nausea or vomiting), fever, fatigue, loss of appetite, dark urine, pale stools, yellowing of the skin or whites of the eyes, itching, rash, or abdominal pain. The doctor will check liver function.
Pyreox should not be used if the patient previously took any medicine containing metamizole and experienced liver-related adverse effects.

Severe skin reactions
Severe skin reactions have been reported with the use of metamizole, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS). If any of the symptoms associated with these severe skin reactions described in section 4 occur, treatment with metamizole must be stopped immediately and urgent medical help sought.
If the patient has ever experienced a severe skin reaction, this medicine must never be restarted (see section 4).

Effect on laboratory test results
Abnormal results have been observed in laboratory and diagnostic tests based on Trinder's reaction or similar reactions (e.g. measurement of serum creatinine, triglycerides, HDL cholesterol, or uric acid) in patients treated with metamizole.

Pyreox and other medicines
Tell your doctor or pharmacist 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 about the use of the following medicines:

• cyclosporine and tacrolimus: medicines used to prevent organ transplant rejection;
• sertraline: a medicine used to treat depression;
• bupropion: a medicine used to treat depression or as an aid in smoking cessation;
• methotrexate: a medicine used to treat cancer or certain rheumatic diseases;
• efavirenz: a medicine used to treat HIV/AIDS infection;
• methadone: a medicine used to treat addiction to illegal opioids;
• valproate: a medicine used to treat epilepsy or bipolar affective disorder;
• acetylsalicylic acid. Metamizole may reduce its effect on platelets. Caution is advised when taking Pyreox together with low-dose acetylsalicylic acid used as a cardioprotective agent.

Pregnancy, breastfeeding, and fertility

If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a baby, she should consult her 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 harmful effects on the foetus. 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, following careful consideration of the benefits and risks associated with treatment. However, in general, the use of metamizole is not recommended during the first and second trimesters of pregnancy.
Pyreox must not be taken during the last three months of pregnancy due to an increased risk of complications for both mother and child (bleeding, premature closure in the foetus of an important blood vessel called the ductus arteriosus Botalli, which normally closes only after birth).

Breastfeeding
Metamizole metabolites pass into breast milk in significant amounts, and a 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 medicine.

Fertility
No information is available on this topic.

Driving and operating machinery
Pyreox, when taken at recommended doses, does not have a detrimental effect on the ability to drive or operate machinery. However, when higher doses are used, the medicine may affect the ability to drive and concentrate. In such cases, driving and operating machinery should be avoided.

Pyreox contains sodium
This medicine contains 32.73 mg of sodium (the main component of table salt) per tablet. This corresponds to 1.64% of the recommended maximum daily dietary intake of sodium for an adult.

3. How to use Pyreox

This medicine should always be taken exactly as described in this patient leaflet, or as directed by a doctor or pharmacist. If in doubt, consult a doctor or pharmacist.
The dose depends on the severity of pain or fever and the individual patient's response to Pyreox. The lowest effective dose required to control pain and fever should always be used.
Onset of noticeable effect can be expected within 30 to 60 minutes after oral administration.
The medicine should be taken orally, with an adequate amount of liquid (e.g. a glass of water). Pyreox may be taken with food or independently of meals.

Adults and adolescents aged 15 years and older
Adults and adolescents aged 15 years and older (with body weight above 53 kg) may take one to two tablets (500 mg to 1000 mg metamizole) no more than 4 times daily at intervals of 6–8 hours, corresponding to a maximum daily dose of 4000 mg.

Duration of treatment
Pyreox should not be used for longer than 3 to 5 days. If symptoms persist or worsen after this period, the patient should consult a doctor immediately.

Children and adolescents under 15 years of age
Pyreox should not be used in children and adolescents under 15 years of age. Other formulations and doses of this medicine are available for younger children; consult a doctor or pharmacist for further information.

Elderly patients and patients with poor general health and/or impaired kidney function
Dosage should be reduced in elderly patients, debilitated patients, and patients with impaired kidney function, as elimination of metamizole metabolites from the body may be delayed.

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. For short-term use, dose reduction is not required. Data on long-term use are lacking.

Use of a higher than recommended dose of Pyreox
Accidental overdose may lead to nausea, vomiting, abdominal pain, kidney dysfunction and/or kidney failure, nervous system disturbances (dizziness, drowsiness, coma, convulsions), hypotension, and cardiac arrhythmias. Higher doses of metamizole may cause harmless red discoloration of urine.

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

If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like any medicine, this medicine can cause adverse reactions, although not everybody will experience them.
The following adverse reactions may have serious consequences; if they occur, discontinue use of Pyreox
immediately and contact your doctor as soon as possible:

• Severe hypersensitivity reactions, severe skin reactions such as Stevens-Johnson syndrome or toxic epidermal necrolysis. In such cases, Pyreox must not be taken further without medical supervision. Prompt discontinuation of treatment may be crucial for recovery.

If symptoms of agranulocytosis occur (very rare), treatment with Pyreox must be stopped immediately.
The treating physician must monitor blood count results including blood smear. Do not delay discontinuation
of treatment until laboratory test results are available.
Pyreox must not be used further if any of the following symptoms occur, which may indicate agranulocytosis:

• Unexpected worsening of general well-being (e.g. fever, chills, sore throat, swallowing difficulties);
• Fever that does not resolve or that recurs;
• Painful lesions of mucous membranes, mainly in the oral cavity, nose, throat, or genital and anal areas. See also section 2. Warnings and precautions.

Discontinue use of Pyreox and contact your doctor immediately if any of the following symptoms occur:

• Nausea (feeling sick or vomiting), fever, feeling tired, loss of appetite, dark-coloured 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.

Possible adverse reactions
Common (may affect up to 1 in 10 people)

• Drowsiness;
• Headaches;
• Dizziness, dizziness with a spinning sensation;
• Drop in blood pressure occurring mainly during intravenous administration (hypotension);
• Rash, itching, urticaria.

Uncommon (may affect up to 1 in 100 people)

• Decrease in the number of white blood cells in the blood (leukopenia).

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

• Hypersensitivity reactions (anaphylactoid or anaphylactic reactions). Milder reactions usually present as irritated eyes, cough, runny nose, sneezing, chest tightness, skin redness (especially face and head), urticaria and facial swelling, and in rarer cases also nausea and stomach cramps. Specific warning signs include burning sensation, itching and feeling of warmth on or under the tongue, and particularly on the palms and soles.

Such mild reactions may progress to more severe reactions characterized by intense urticaria, severe angioedema (including in the laryngeal area), severe bronchospasm (narrowing of the lower airways due to constriction), palpitations (sometimes also bradycardia), cardiac arrhythmias, drop in blood pressure (sometimes preceded by a rise in blood pressure), loss of consciousness and circulatory shock. These reactions may also occur after repeated administration of the medicine without prior complications and may be severe, life-threatening, and even fatal. In patients with analgesic-related asthma, intolerance to the medicine usually manifests as asthma attacks (see section 2).

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

• Marked decrease in the number of certain white blood cells, which may result in death (agranulocytosis).

Frequency not known (cannot be estimated from available data)

• Myocardial infarction as a manifestation of an allergic reaction (Kounis syndrome);
• Anaemia with concurrent bone marrow dysfunction (aplastic anaemia), reduction in white blood cells (granulocytopenia) and platelets (thrombocytopenia);
• Dyspnoea;
• Nausea;
• Transient increase in liver transaminase activity (ALT, AST) and bilirubin concentration due to impaired liver function;
• Acute worsening of kidney function, in some cases with reduced urine output or absence of urine (oliguria or anuria), excretion of blood proteins in urine (proteinuria), or progression to acute kidney failure; kidney inflammation (acute interstitial nephritis);
• Skin rashes (e.g. maculopapular rash);
• Extensive blisters on the skin and separation of the upper skin layer (Stevens-Johnson syndrome or toxic epidermal necrolysis);
• Purple to dark red skin rash, partly blistering (erythema multiforme);
• Severe skin reactions, including drug reaction with eosinophilia and systemic symptoms (DRESS).

Reporting of adverse reactions
If any adverse effects occur, including any adverse effects 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
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions may also be reported to the marketing authorization holder.
Reporting adverse reactions helps provide more information on the safety of this medicine.

5. How to store Pyreox

Keep this medicine out of the sight and reach of children.
No special storage instructions apply to this medicine.
Do not use this medicine after the expiry date stated on the carton and blister pack 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. This will help protect the environment.

6. Contents of the pack and other information

What Pyreox contains

• The active substance is metamizole sodium monohydrate. Each coated tablet contains 500 mg of metamizole sodium monohydrate.
• Other components are:
  Tablet core: polyethylene glycol 4000, magnesium stearate
  Tablet coating: Opadry 03F280040 White [containing hypromellose (6 mPas), titanium dioxide (E 171), polyethylene glycol 8000, talc]

What Pyreox looks like and contents of the pack
Film-coated tablets, white to slightly yellowish, elongated, biconvex, with a score line on one side and smooth on the other.
Packaging:
6 or 12 film-coated tablets (1 or 2 blisters of 6 tablets) and 10 or 20 film-coated tablets (1 or 2 blisters of 10 tablets).
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Bausch Health Ireland Limited
3013 Lake Drive
Citywest Business Campus
Dublin 24, D24 PPT3
Ireland
Tel.: +48 17 865 51 00

Manufacturer
ICN Polfa Rzeszów S.A.
Przemysłowa 2
35-105 Rzeszów
Poland

This medicinal product is authorised in the European Economic Area countries under the following names:
Croatia: Metamizolnatrij hidrat Bausch Health 500 mg filmom obložene tablete
Poland: Pyreox
Czech Republic: Emitazem 500 mg
Slovakia: Emitazem 500 mg