Package leaflet: Information for the patient

Pyralgina MAX, 1000 mg, coated tablets
Metamizolum natricum monohydricum
Pyralgina MAX may cause a severely low white blood cell count (agranulocytosis), which can lead to severe and life-threatening infections (see section 4).
Treatment with this medicine 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, throat, genital area or around the anus.
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 this leaflet carefully before taking the medicine, as it contains important information for the patient.

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

Contents of the leaflet

What Pyralgina MAX is and what it is used for
Important information before taking Pyralgina MAX
How to take Pyralgina MAX
Possible side effects
How to store Pyralgina MAX
Contents of the pack and other information

1. What Pyralgina MAX is and what it is used for

Pyralgina MAX contains as the active substance metamizole sodium monohydrate, which belongs to a group of medicines called pyrazolone derivatives, with analgesic and antipyretic effects.
Pyralgina MAX is indicated for use in adolescents aged 15 years and older and adults for the treatment of:
acute, severe pain following injuries or surgery;
spasmodic abdominal pain (colic);
cancer-related pain;
other acute or chronic severe pain when other medicinal treatments are contraindicated;
high fever unresponsive to other treatments.

2. Important information before using Pyralgina MAX

When not to use Pyralgina MAX

if the patient is allergic to metamizole or other pyrazolone derivatives (e.g. phenazone, propyphenazone) or pyrazolidine derivatives (e.g. phenylbutazone, oxyphenbutazone);
if the patient is allergic to any of the other ingredients of this medicine (listed in section 6);
if the patient has previously experienced a significant reduction in the number of white blood cells called granulocytes, caused by metamizole or other similar medicines known as pyrazolones or pyrazolidines;
if the patient suffers from intolerance to painkillers (analgesic asthma syndrome or urticaria-type and/or angioedema intolerance). This applies to patients who experience bronchospasm (sudden narrowing of the lower airways) or other hypersensitivity reactions such as itching, rhinitis and swelling (urticaria, rhinitis, angioedema) after taking painkillers such as salicylates and paracetamol or diclofenac, ibuprofen, indometacin, naproxen;
if the patient has ever had an allergic reaction to metamizole, such as severe skin reactions (see section 4. "Possible side effects");
if the patient has bone marrow dysfunction or a disease affecting blood cell production or function;
if the patient has congenital glucose-6-phosphate dehydrogenase deficiency (a hereditary condition associated with the risk of red blood cell breakdown);
if the patient has acute intermittent hepatic porphyria (a hereditary condition associated with disturbances in haemoglobin formation);
during the last three months of pregnancy.

Warnings and precautions
Before starting treatment with Pyralgina MAX, discuss this with your doctor or pharmacist.
Pyralgina MAX contains metamizole, the use of which is associated with a rare but life-threatening risk of:

sudden circulatory collapse (shock);
agranulocytosis.

Abnormally low white blood cell count (agranulocytosis)
Pyralgina MAX 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). You must stop taking metamizole and contact your doctor immediately if you experience the following symptoms, 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.
Your doctor will order laboratory tests 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 receiving antibiotics.
Agranulocytosis may develop at any time during treatment with Pyralgina MAX, and even shortly after stopping metamizole.
Agranulocytosis may occur even if metamizole was previously administered without complications.
Pyralgina MAX should be discontinued and you should seek immediate medical advice if symptoms of pancytopenia (such as general malaise, signs of infection, persistent fever, bruising, bleeding and pallor) or thrombocytopenia (such as increased tendency to bleed and small red spots on the skin and mucous membranes caused by bleeding) occur (see section 4. "Possible side effects").

Severe hypersensitivity reactions

Patients who experience hypersensitivity reactions (anaphylactic reactions) to Pyralgina MAX are also particularly at risk of similar reactions to other painkillers.
Patients who have an allergic or other immunological reaction to Pyralgina MAX (e.g. agranulocytosis) are also particularly at risk of similar reactions to other pyrazolones and pyrazolidines (chemically similar substances) (painkillers such as phenazone, propyphenazone, phenylbutazone, oxyphenbutazone).
If the patient has an allergic reaction or another immune system reaction to other pyrazolones, pyrazolidines or other painkillers, there is also a high risk of the same reaction occurring with Pyralgina MAX.
The risk of severe hypersensitivity reactions to Pyralgina MAX may be significantly increased if the patient has any of the following disorders and/or intolerances:
allergy to non-steroidal anti-inflammatory drugs (used to treat pain and rheumatism), with symptoms such as itching and swelling (urticaria, angioedema). In such cases, Pyralgina MAX must not be used (see section 2 "When not to use Pyralgina MAX");
asthma attacks caused by bronchiolar constriction (bronchial asthma), especially if accompanied by inflammation of the nasal and sinus mucosa (sinusitis) and nasal polyps;
chronic urticaria (urticaria);
hypersensitivity to dyes (e.g. tartrazine) or preservatives (e.g. benzoates);
alcohol intolerance, manifesting as sneezing, tearing and severe facial flushing even after small amounts of alcohol; this may indicate previously undiagnosed intolerance to painkillers (see section 2. "When not to use Pyralgina MAX").

In patients at increased risk of hypersensitivity reactions, Pyralgina MAX may be used only after careful consideration of the benefit-risk ratio.
If Pyralgina MAX is administered in such cases, the patient must be under strict medical supervision, with immediate access to emergency equipment.
Anaphylactic reactions may occur in particularly sensitive patients. Therefore, patients with asthma or predisposition to hypersensitivity (atopy) should exercise particular caution.
Severe skin reactions
Severe skin reactions, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), have been reported in association with metamizole treatment. If the patient develops any of these symptoms related to severe skin reactions listed in section 4, metamizole treatment must be discontinued and immediate medical help sought.
If the patient has previously experienced severe skin reactions during metamizole treatment, Pyralgina MAX must never be taken again in the future (see section 4).
Reduction in blood pressure (hypotensive reaction)
During treatment with Pyralgina MAX, a decrease (drop) in blood pressure may occur (hypotensive reactions, see section 4. "Possible side effects"). This risk increases:

if the patient has low blood pressure (pre-existing hypotension), severe dehydration, poor circulation, or is in the early stages of circulatory failure (e.g. in case of heart attack or severe trauma),
if the patient has high fever. The doctor will carefully consider treatment and closely monitor the patient's condition. Preventive measures (correction of circulatory disturbances) may be applied if necessary to reduce the risk of potential blood pressure drop.

In patients in whom a drop in blood pressure must absolutely be avoided (e.g. in case of severe ischaemic heart disease or significant stenosis of blood vessels supplying blood to the brain), Pyralgina MAX may be used only under strict monitoring of circulatory parameters.
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 Pyralgina MAX should be discontinued and medical advice sought 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 Pyralgina MAX if they have previously taken any medicines containing metamizole and experienced liver-related problems.
Patients with impaired kidney or liver function
In cases of impaired kidney or liver function, Pyralgina MAX should be used only after careful consideration of benefit versus risk and with appropriate precautions (see section 3, subsection "Patients with impaired kidney or liver function").
Children and adolescents
Do not use this medicine in children and adolescents under 15 years of age.
Pyralgina MAX and other medicines
Tell your doctor about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take.
Inform your doctor especially about the use of:

methotrexate (a medicine used to treat cancer or certain rheumatic diseases). Concurrent use of metamizole and methotrexate may increase the potential risk of blood cell damage by methotrexate, especially in elderly patients. Concomitant use of both medicines should be avoided.
chlorpromazine (a medicine used, among others, to treat symptoms of psychiatric disorders). Taking Pyralgina MAX together with chlorpromazine may cause excessive lowering of body temperature.
cyclosporine (a medicine used to suppress the immune system);
acetylsalicylic acid. Metamizole may reduce the effect of acetylsalicylic acid on platelets. Caution is advised when using Pyralgina MAX together with low-dose acetylsalicylic acid used for prevention of heart disease.
bupropion (a medicine used to treat depression or as an aid in smoking cessation);
efavirenz (a medicine used to treat HIV infection (AIDS));
methadone (a medicine used to treat 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 (an antidepressant).

Active substances from the pyrazolone group (including metamizole) may cause interactions with:

anticoagulant medicines (oral anticoagulants);
medicines used to lower high blood pressure and in certain heart diseases (captopril);
medicines used to treat psychiatric disorders (lithium);
diuretics (diuretic medicines, e.g. triamterene),
medicines used to lower high blood pressure (medicines used to treat arterial hypertension).

Effect on laboratory test results
Before undergoing any laboratory tests, inform your doctor that you are taking Pyralgina MAX, as metamizole may affect the results of certain tests (such as creatinine, triglycerides, HDL cholesterol or serum uric acid levels).
Pyralgina MAX and alcohol
Do not drink alcohol while taking this medicine.
Pregnancy, breastfeeding and fertility
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, 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 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 the benefit and risks of taking the medicine are carefully considered. In principle, administration of metamizole during the first and second trimesters is not recommended.
Pyralgina MAX must not be taken during the last three months of pregnancy due to increased risk of complications for mother and child (bleeding, premature closure of an important blood vessel in the unborn child (so-called ductus arteriosus Botalli), 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 during breastfeeding should be particularly avoided.
After a single dose of metamizole, mothers should be advised to express and discard breast milk for 48 hours after taking the medicine.
Driving and operating machinery
At the recommended dosage range, no adverse effects affecting concentration and reaction ability are known. However, as a precaution, the possibility of such adverse effects should be considered—especially when higher doses are used—and refraining from operating machinery, driving vehicles or performing tasks involving risk should be considered.
This particularly applies to individuals consuming alcohol.
Pyralgina MAX contains sodium
This medicine contains 71.3 mg of sodium (the main component of table salt) per tablet.
This corresponds to 3.56% of the maximum recommended daily dietary sodium intake for adults.

3. How to use Pyralgina MAX

This medicine should always be taken 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 on the individual's response to the medicine.
The lowest effective dose required to control pain and (or) fever should always be used.
The doctor will inform the patient how to use Pyralgina MAX.
For adults and adolescents aged 15 years and older (with body weight exceeding 53 kg), the maximum single dose is 1000 mg of metamizole (1 tablet of 1000 mg), administered no more than 4 times daily at intervals of 6–8 hours. The maximum daily dose is 4000 mg (equivalent to 4 tablets of 1000 mg).
A clear effect can be expected within 30 to 60 minutes after oral administration.

Elderly patients and patients in poor general health or with renal impairment
In elderly patients, weakened patients, and those 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. For short-term use, dose reduction is not required. There is no experience with long-term use.

Use in children and adolescents

Adolescents aged 15 years and older (body weight above 53 kg): see dosing as for adults.
Pyralgina MAX should not be used in children and adolescents under 15 years of age. Other formulations and strengths of this medicine are available for younger children; consult the attending doctor or pharmacist.

Method of administration
Oral administration.
Do not chew the tablets. Tablets should be taken with sufficient fluid (e.g. a glass of water). Tablets may be divided into equal doses.

Overdose of Pyralgina MAX
If any of the following symptoms of overdose occur, seek immediate medical attention from a doctor or go to the nearest hospital emergency department:

nausea, vomiting, abdominal pain,
kidney dysfunction, even acute renal failure (e.g. with symptoms of interstitial nephritis),
dizziness, drowsiness, disturbances of consciousness,
seizures,
decreased blood pressure, up to circulatory collapse (shock),
cardiac arrhythmias (tachycardia).

In case of overdose, immediate medical advice must be sought. Appropriate countermeasures may be necessary.
After ingestion of very high doses, excretion of the harmless metabolite (rubazonic acid) may cause red discoloration of urine.

Missed dose of Pyralgina MAX
Do not take a double dose to make up for a missed dose.
If there are any further doubts about the use of this medicine, consult a doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
The medicine should be discontinued and medical advice sought if any of the following adverse reactions occur; they may have serious consequences.
If any of these adverse reactions appear suddenly or worsen rapidly, the doctor should be consulted immediately, as some reactions to the medicine (e.g. severe hypersensitivity reactions, severe skin reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, agranulocytosis, pancytopenia) may be life-threatening.
In such cases, Pyralgina MAX must not be taken without medical supervision.
Immediate discontinuation of the medicine is crucial for recovery.
You should stop taking Pyralgina MAX and seek immediate medical help if any of the following symptoms occur:

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".
Severe allergic reactions (anaphylactoid or anaphylactic reactions) - adverse reactions occurring rarely (occurring no more frequently than in 1 out of 1,000 people). Typical symptoms of mild reactions may include: burning eyes, cough, runny nose, sneezing, chest tightness, redness of the skin (especially face and head), urticaria and facial swelling, and less frequently nausea and abdominal cramps. Particularly important symptoms include burning, itching and redness of the tongue and under the tongue, and especially on the palms and soles. Mild reactions may progress to more severe forms, with generalized urticaria, severe angioedema (including in the larynx), severe bronchospasm (spastic narrowing of the lower airways), increased heart rate, cardiac arrhythmias, decreased blood pressure (sometimes preceded by an increase), loss of consciousness and circulatory shock. These reactions may also occur despite previous use of metamizole without complications and may be severe or life-threatening, sometimes even leading to death. In patients with analgesic-induced asthma syndrome, allergic reactions manifest as asthma attacks (see section 2 "When not to use Pyralgina MAX").
Red, flat lesions on the trunk resembling a target (bull's eye) or circular lesions, often with blisters in the center, skin peeling, ulceration 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 ) - adverse reactions occurring very rarely (occurring no more frequently than in 1 out of 10,000 people).
Widespread rash, high body temperature and enlarged lymph nodes (DRESS syndrome or drug hypersensitivity syndrome) - adverse reactions occurring with unknown frequency (frequency cannot be estimated from available data).
Marked decrease in certain types of white blood cells (agranulocytosis), including fatal cases (see section 2 "Warnings and precautions"), or reduced platelet count (thrombocytopenia) - adverse reactions occurring very rarely (occurring no more frequently than in 1 out of 10,000 people). These reactions are probably immunological. They may also occur even if metamizole was previously administered without complications. Symptoms of agranulocytosis: high fever, chills, sore throat, difficulty swallowing, and inflammatory conditions in the mouth, nose, throat or genital and anal areas. However, in patients receiving antibiotics (medicines used for bacterial infections), these symptoms may be less pronounced. Erythrocyte sedimentation rate is markedly increased, while lymph nodes are usually only slightly enlarged or not enlarged at all.

Symptoms of thrombocytopenia include increased tendency to bleeding and petechiae (pinpoint bleeding into the skin and mucous membranes).
If symptoms of agranulocytosis, pancytopenia (see below) or thrombocytopenia occur, treatment with Pyralgina MAX must be stopped immediately and the doctor will recommend a blood count test (including blood morphology with smear). Do not delay discontinuation of treatment until laboratory results are obtained.

Reduced blood volume with accompanying bone marrow dysfunction ( aplastic anaemia ), reduced numbers of white and red blood cells and platelets ( pancytopenia ), including cases with fatal outcome - adverse reactions occurring with unknown frequency (frequency cannot be estimated from available data). Symptoms of pancytopenia and aplastic anaemia include: general malaise, infections, persistent fever, bruising, bleeding and skin pallor.

Other possible adverse reactions
Not very common (occurring no more frequently than in 1 out of 100 people):

Purple to dark red skin rash, sometimes with blisters ( drug eruption ),
Decreased blood pressure (isolated hypotensive reaction), probably due to the direct effect of the medicine and not accompanied by other hypersensitivity symptoms. Such a reaction causes a severe drop in blood pressure only in rare cases. The risk of decreased blood pressure may be increased in patients with very high fever (hyperpyrexia). Typical symptoms of severe hypotension include: increased heart rate, pallor, trembling, dizziness, nausea and loss of consciousness.

Rarely (occurring no more frequently than in 1 out of 1,000 people):

Decreased number of white blood cells ( leukopenia ),
Skin rash (e.g. maculopapular rash).

Very rarely (occurring no more frequently than in 1 out of 10,000 people):

Asthma attacks (shortness of breath caused by bronchiolar constriction),
Acute worsening of kidney function , in some cases with absence or reduced volume of urine output (oliguria or anuria), increased protein excretion in urine (proteinuria) or acute kidney failure; kidney inflammation (acute interstitial nephritis).

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

Anaphylactic shock ,
Myocardial infarction occurring during an allergic reaction (Kounis syndrome),
Hepatitis , yellowing of the skin and whites of the eyes, increased liver enzyme activity in blood,
Gastrointestinal bleeding .

Excretion of a harmless metabolite (rubazonic acid) may cause red discoloration of urine.
Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions 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, 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 provide more information on the safety of the medicine.

5. How to store Pyralgina MAX

Keep the medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and blister after EXP.
The expiry date refers to the last day of the stated month.
The marking on the packaging: after the abbreviation EXP indicates the expiry date, and after the abbreviation Lot indicates the batch number.
No special storage instructions apply.
Medicines should not be disposed of via wastewater or household waste. 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 Pyralgina MAX contains

The active substance is metamizole sodium monohydrate. Each tablet contains 1000 mg of metamizole sodium monohydrate.
The other ingredients are: sodium croscarmellose, magnesium stearate, hypromellose 2910 (6±2 mPa∙s), titanium dioxide (E 171), macrogol 8000, and talc.

What Pyralgina MAX looks like and contents of the pack
White or almost white, biconvex, elongated coated tablets, with a division line on one side. The tablet can be divided into equal doses.
Pyralgina MAX is packed in opaque perforated or non-perforated blisters made of PVC/Aluminum or PVC/PE/PVDC/Aluminum foil, and placed in a cardboard box.
The pack contains 6, 10, 20, 28, 30, 56, 60 or 90 coated tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Zakłady Farmaceutyczne POLPHARMA S.A.
ul. Pelplińska 19, 83-200 Starogard Gdański
tel. + 48 22 364 61 01

Manufacturer
Rontis Hellas Medical and Pharmaceutical Products S.A.
P.O. Box 3012 Larissa Industrial Area
41500 Larissa
Greece

This medicinal product is authorised in the European Economic Area countries under the following names:
Poland: Pyralgina MAX
Hungary: Pyralgina

Pyralgina max