Pyralgina

Package leaflet: Information for the patient

Pyralgina, 500 mg, tablets
Metamizolum natricum
Pyralgina may cause a severely low white blood cell count (agranulocytosis), which
can lead to serious and life-threatening infections (see section 4).
You must stop taking the medicine and contact your doctor immediately 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 using the 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 your doctor, pharmacist, or nurse.

• Keep this leaflet so that you can read it again if necessary.
• If you need advice or further information, please consult your pharmacist.
• If you experience any adverse effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.
• If there is no improvement after 3–5 days, or if you feel worse, contact your doctor.

Leaflet contents

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

1. What Pyralgina is and what it is used for

Pyralgina belongs to a group of non-opioid analgesic drugs known as pyrazolone derivatives, which have analgesic and antipyretic effects.
It also has a spasmolytic effect on smooth muscles.
Pyralgina is indicated for the treatment of:

• severe pain of various origins and fever, when the use of other agents is contraindicated or ineffective.

2. Important information before using Pyralgina

When not to use Pyralgina:

• if the patient has previously experienced a significant decrease in white blood cells called granulocytes, caused by metamizole or other similar drugs known as pyrazolones or pyrazolidines;
• if the patient suffers from impaired bone marrow function or a condition affecting the production or function of blood cells;
• if the patient is allergic to metamizole, other pyrazolone or pyrazolidine derivatives (e.g. propyphenazone, phenazone or phenylbutazone), or any of the other ingredients of this medicine (listed in section 6);
• if the patient suffers from analgesic-induced asthma syndrome or known intolerance to painkillers manifesting as urticaria, angioedema (swelling of the tongue, face, lips and/or throat), 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 suffers from acute renal or hepatic failure, or acute hepatic porphyria;
• if the patient has congenital glucose-6-phosphate dehydrogenase deficiency (a rare inherited disorder);
• if the patient is currently using a drug from the group of pyrazolone and pyrazolidine derivatives (e.g. phenylbutazone, propyphenazone);
• if the patient is in the last three months of pregnancy.

Warnings and precautions
Before starting treatment with Pyralgina, discuss this with your doctor or pharmacist:

• if the patient has systolic blood pressure below 100 mm Hg or suffers from heart disease and circulatory disorders (e.g. myocardial infarction, coronary artery disease or multi-organ trauma), cerebral vasoconstriction, reduced circulating blood volume, or if the patient is dehydrated, as the drug may cause a drop in blood pressure;
• if the patient has high fever;
• if the patient suffers from renal and/or hepatic insufficiency;
• if the patient has peptic ulcer disease of the stomach or duodenum;
• if the patient suffers from bronchial asthma, particularly if associated with nasal polyposis and sinus mucosal inflammation;
• if the patient suffers from allergic diseases, including atopy, chronic urticaria;
• if the patient has intolerance to certain dyes (e.g. tartrazine) or preservatives (e.g. benzoates);
• in patients with alcohol intolerance manifesting as sneezing, lacrimation and severe facial flushing even after small amounts of alcohol; this may indicate previously undiagnosed analgesic-induced asthma.

Due to life-threatening risk, the medicine must be discontinued immediately and medical help should be sought if symptoms of an allergic (anaphylactic) reaction occur, such as:

• swelling of the face, lips, tongue and/or throat, which may cause difficulty in swallowing or breathing;
• severe bronchospasm;
• skin and mucous membrane changes such as itching, burning, redness, urticaria;
• shock (decreased blood pressure, weakness, fainting). Patients who have experienced an allergic or other immunological reaction to metamizole are also at risk of a similar reaction to other pyrazolones and pyrazolidines, as well as other non-opioid analgesics. Anaphylactic shock may occur in patients with hypersensitivity. Therefore, particular caution is advised when using the drug in patients with asthma or atopy (e.g. atopic dermatitis or mucosal inflammation, hay fever, allergic asthma). Patients at increased risk of severe hypersensitivity-like reactions to metamizole should only receive the drug after careful consideration of the benefit-risk ratio. If necessary, it should be administered under strict medical supervision, with emergency treatment readily available.

The medicine must be discontinued immediately and a doctor consulted if any of the following symptoms occur:

• thrombocytopenia, e.g.: petechiae on the skin and mucous membranes, bruises, recurrent bleeding from gums, nose, gastrointestinal tract;
• pancytopenia (significant reduction in all types of blood cells: red and white blood cells and platelets), e.g.: general malaise, fever, signs of infection, bruising, bleeding, pallor.

Low white blood cell count (agranulocytosis)
Pyralgina 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).
Metamizole intake 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, particularly in the oral cavity, 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 Pyralgina, and even shortly after discontinuation of metamizole.
Agranulocytosis may occur even if metamizole was previously administered without complications.

Severe skin reactions
Severe skin reactions have been reported with metamizole treatment, including Stevens-Johnson syndrome: blisters and erosions on the skin, in the mouth, eyes and genital organs, fever and joint pain; toxic epidermal necrolysis: rupturing of large blisters, extensive skin erosions, peeling of large sheets of epidermis, and fever; drug reaction with eosinophilia and systemic symptoms (DRESS syndrome). If any of these symptoms related to severe skin reactions listed in section 4 occur, metamizole treatment must be stopped immediately and medical help sought.
If the patient has ever experienced severe skin reactions during treatment with metamizole, Pyralgina or any other medicine containing metamizole should never be taken again in the future (see section 4).

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.
Pyralgina should be discontinued and a doctor consulted if the patient experiences any 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.
Patients should not take Pyralgina if they have previously taken any medicine containing metamizole and experienced liver-related disorders.

Pyralgina and other medicines
Inform your doctor about all medicines currently or recently taken, as well as any medicines the patient plans to take.
Concomitant use of Pyralgina is contraindicated:

• with medicines from the group of pyrazolone and pyrazolidine derivatives (phenylbutazone, propyphenazone).

Inform your doctor if the patient is taking:

• anticoagulants of the coumarin derivatives;
• oral antidiabetic drugs;
• phenytoin (antiepileptic medicine);
• sulfonamides (antibacterial agents);
• cyclosporine, tacrolimus (immunosuppressive drugs used, among others, to prevent transplant rejection);
• barbiturates (e.g. phenobarbital – used, among others, in epilepsy);
• monoamine oxidase inhibitors (e.g. selegiline, moclobemide – used, among others, in depression);
• chlorpromazine (used, among others, in schizophrenia treatment);
• lithium, sertraline (antidepressants);
• bupropion (used in depression treatment or as an aid in smoking cessation);
• antihypertensive drugs (e.g. captopril);
• diuretics (e.g. triamterene);
• methotrexate (used in the treatment of neoplastic diseases);
• efavirenz (used in the treatment of HIV infection (AIDS));
• methadone (used in the treatment of addiction to illegal narcotic substances (so-called opioids));
• valproate (used in epilepsy or bipolar affective disorder treatment).

Metamizole may reduce the effect of acetylsalicylic acid on platelets.
Caution is advised when administering acetylsalicylic acid concomitantly for the prevention of heart disease.

Pyralgina, food, drink and alcohol
See section 3. Alcohol may affect the effectiveness of the 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 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-risk ratio is carefully considered. In principle, administration of metamizole during the first and second trimesters is not recommended.
Pyralgina 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 a vital fetal blood vessel, the so-called 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 drug.

Driving and operating machinery
At the recommended dosage range, no impairment of concentration or reaction ability has been observed. However, when higher doses are used, caution should be exercised and patients should refrain from operating machinery, driving vehicles or performing tasks involving risk.

Pyralgina contains sodium
The medicine contains 34.5 mg of sodium (the main component of table salt) in each tablet.
This corresponds to 1.7% of the maximum recommended daily sodium intake in the adult diet.

3. How to use Pyralgina

This medicine should always be used exactly as described in the patient leaflet or as directed by a
physician or pharmacist. If in doubt, consult a physician or pharmacist.
The dose depends on the severity of pain or fever and the individual's response to Pyralgina.
The lowest effective dose required to control pain and (or) fever should always be used.
For adults and adolescents aged 15 years or older (with body weight exceeding 53 kg), a maximum single dose of 1000 mg of metamizole (2 tablets) may be administered no more than 4 times daily, at intervals of 6–8 hours. The maximum daily dose is 4000 mg (equivalent to 8 tablets).
A noticeable effect can be expected within 30 to 60 minutes after oral administration.
Pyralgina should not be used in children under 15 years of age. Other formulations and strengths of this medicine are available for younger children; consult the attending physician or pharmacist.
Tablets should be taken with sufficient fluid (e.g. a glass of water).
The medicine should be taken during or immediately after meals.
Do not use the medicine for longer than 3–5 days without consulting a physician, or seek immediate medical advice if symptoms worsen despite taking the medicine.

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

Use of a higher than recommended dose of Pyralgina:
If an overdose is taken, seek immediate advice from a physician or pharmacist.
Symptoms of overdose may include dizziness, tinnitus, hearing disturbances, psychomotor agitation, disturbances of consciousness, coma, tonic-clonic seizures, hypotension, and cardiac arrhythmias (tachycardia). Overdose of metamizole may also cause abdominal pain, vomiting, gastric and duodenal mucosal erosions, bleeding, perforations, hepatocellular damage, interstitial nephritis, and allergic bronchospasm. Cases of skin rash, urticaria, angioedema, exfoliative dermatitis, and toxic epidermal necrolysis have been reported.
After ingestion of very high doses, excretion of rubazonic acid may cause red discoloration of urine.
Blood morphology disorders have also been reported, such as bone marrow damage leading to reduced white blood cell count (leukopenia or agranulocytosis), reduced platelet count (thrombocytopenia), or aplastic anemia.
There is no specific antidote for metamizole.
In case of overdose, immediate medical attention is required. Symptomatic and supportive treatment may be necessary.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
The medicine must be discontinued immediately and medical help should be sought if the patient develops any of the following serious adverse reactions:

• Severe allergic (anaphylactic) reactions:
• Rare swelling of the face, lips, tongue, and (or) throat, which may cause difficulty in swallowing or breathing;
• Very rare severe bronchospasm;
• Skin and mucous membrane changes such as itching, burning sensation, redness, urticaria;
• Anaphylactic shock (life-threatening drop in blood pressure, weakness, fainting) – frequency unknown;
• Severe skin reactions:
• Red, flat rash on the trunk in the shape of a target or circular lesions, often with blisters in the center, skin peeling, and 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);
• Widespread rash, high fever, and enlarged lymph nodes (DRESS syndrome or drug hypersensitivity syndrome).

The medicine should be discontinued immediately and a doctor should be consulted if any of the following serious adverse reactions occur:

• Pancytopenia (marked reduction in all blood cells: red and white blood cells and platelets), manifesting as general malaise, fever, signs of infection, bruising, bleeding, and pale skin;
• Agranulocytosis (complete or near-complete absence of granulocytes in the blood), including fatal cases, manifesting as:
• Fever, chills;
• Sore throat, difficulty swallowing, and inflammatory conditions of the mucous membranes of the mouth, nose, throat, genital organs, and rectum;
• Elevated ESR (erythrocyte sedimentation rate);
• Hemoglobin, erythrocyte, and platelet levels not always abnormal, though usually within normal range;
• Slight enlargement of lymph nodes and spleen, although often unchanged (see also section 2 "Warnings and precautions");
• General 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 upper abdominal pain. These may be symptoms of liver damage. See also section 2 "Warnings and precautions".

Other adverse reactions:
Consult a doctor if any of the following adverse reactions occur:
Uncommon (occurring in fewer than 1 in 100 patients):

• Drug eruption (transient rash of various types: nodular, macular, vesicular, erythematous);
• Excessive drop in blood pressure.

Rare (occurring in fewer than 1 in 1,000 patients):

• Maculopapular skin changes;
• Leukopenia (reduced number of white blood cells in blood).

Very rare (occurring in fewer than 1 in 10,000 patients):

• Analgesic-induced asthma (see section 2 "When not to take Pyralgina"), asthma attacks;
• Agranulocytosis (complete or near-complete absence of granulocytes in blood), including fatal cases (see above "The medicine should be discontinued immediately and a doctor should be consulted if any of the following serious adverse reactions occur");
• Thrombocytopenia (bruising, bleeding);
• Sudden worsening of kidney function with proteinuria, oliguria, or anuria;
• Acute kidney failure;
• Interstitial nephritis.

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

• Nausea, vomiting, abdominal pain, gastric irritation, diarrhea, dry mouth;
• Liver damage;
• Hepatitis, yellowing of the skin and whites of the eyes, increased liver enzyme activity in blood;
• Headache, dizziness;
• Hemolytic anemia, aplastic anemia, bone marrow damage, sometimes leading to death. In patients with glucose-6-phosphate dehydrogenase deficiency, the medicine causes hemolysis of red blood cells;
• Red discoloration of urine (after administration of very high doses of metamizole).

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Reactions of Medicinal Products at the 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 to provide more information on the safety of the medicine.

5. How to store the medicine Pyralgina

Keep the medicine out of sight and reach of children.
Store in the original packaging.
Do not store above 25°C.
Do not use this medicine after the expiry date stated on the carton and blister.
The expiry date refers to the last day of the stated month.
The marking on the blister after the abbreviation EXP indicates the expiry date, and after the abbreviation LOT indicates the batch number.
Medicines must 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 contains

• The active substance is metamizole sodium monohydrate. Each tablet contains 500 mg of metamizole sodium monohydrate.
• Other ingredients are: potato starch, gelatin, magnesium stearate.

What Pyralgina looks like and contents of the pack
White or almost white, elongated, biconvex tablets.
The pack contains 2, 6, 12, 18, 20 or 24 tablets.
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
Zakłady Farmaceutyczne POLPHARMA S.A.
ul. Pelplińska 19, 83-200 Starogard Gdański
tel. + 48 22 364 61 01