Pyralgina for pain and fever

Package leaflet: Information for the patient

Pyralgina Ból i Gorączka, 500 mg/sachet, granules for the preparation of oral solution
Metamizolum magnesicum
Pyralgina Ból i Gorączka may cause a severely low white blood cell count (agranulocytosis), which can lead to serious and life-threatening infections (see section 4).
Treatment with this medicine must be discontinued and medical advice must be sought immediately if any of the following symptoms occur: fever, chills, sore throat, painful ulcers in the nose, mouth, 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 so that you can read it again if necessary.
• 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, inform your doctor or pharmacist. See section 4.
• If there is no improvement or if you feel worse after 3–5 days, consult your doctor.

Contents of the leaflet

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

1. What Pyralgina Ból i Gorączka is and what it is used for

Pyralgina Ból i Gorączka belongs to the group of non-opioid analgesics, specifically pyrazolone derivatives, with analgesic and antipyretic properties.
It also exerts a spasmolytic effect on smooth muscles.
This medicine 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 Ból i Gorączka

When not to use Pyralgina Ból i Gorączka:

• if the patient has previously experienced a significant decrease in the number of 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 has analgesic-induced asthma syndrome or known intolerance to painkillers manifested by urticaria, angioedema (swelling of the tongue, face, lips and/or throat), i.e. patients who react with bronchospasm or other 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 acute renal or hepatic failure, or acute hepatic porphyria;
• if the patient has congenital glucose-6-phosphate dehydrogenase deficiency (a rare hereditary disease);
• if the patient is taking 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 Ból i Gorączka, 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 vasospasm, reduced circulating blood volume, or is dehydrated, as the medicine may cause a drop in blood pressure;
• if the patient has high fever;
• if the patient has renal and/or hepatic impairment;
• if the patient has peptic ulcer disease of the stomach or duodenum;
• if the patient has bronchial asthma, especially if associated with nasal polyposis and sinus mucosal inflammation;
• if the patient has 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, tearing eyes and severe facial flushing even after small amounts of alcohol; this may indicate previously undiagnosed analgesic-induced asthma.

Due to the risk of life-threatening reactions, 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 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 shown an allergic or other immunological reaction to metamizole are also at risk of similar reactions to other pyrazolones and pyrazolidines, as well as other non-opioid analgesics. In patients with hypersensitivity, anaphylactic shock may occur. Therefore, particular caution should be exercised when using the medicine in patients with asthma or atopy (e.g. atopic dermatitis or mucosal inflammation, hay fever, allergic asthma). Patients at increased risk of reactions similar to severe hypersensitivity reactions to metamizole should only receive the medicine after careful benefit-risk assessment. If necessary, it should be administered under strict medical supervision, with immediate access to emergency treatment.

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

• thrombocytopenia, e.g.: skin and mucous membrane petechiae, bruises, recurrent bleeding from gums, nose, gastrointestinal tract;
• pancytopenia (significant decrease 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 Ból i Gorączka 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 should be discontinued and medical advice should be sought immediately if the following symptoms occur, as they may indicate possible agranulocytosis: chills, fever, sore throat and painful mucosal ulcers, especially in the oral cavity, nose, throat or genital and anal areas.
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 Ból i Gorączka, 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, shedding 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 should be discontinued immediately and medical help should be sought.
If the patient has previously experienced severe skin reactions during treatment with metamizole, Pyralgina Ból i Gorączka or any other medicine containing metamizole should never be taken again (see section 4).

Liver-related disorders
Cases of hepatitis have occurred in patients taking metamizole, with symptoms appearing from several days to several months after starting treatment.
Treatment with Pyralgina Ból i Gorączka should be discontinued and a doctor should be consulted if the patient experiences 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 Ból i Gorączka if they have previously taken any medicines containing metamizole and experienced liver-related adverse effects.

Pyralgina Ból i Gorączka and other medicines
Inform your doctor or pharmacist about all medicines currently or recently taken, as well as any medicines planned for future use.
The use of Pyralgina Ból i Gorączka is contraindicated:

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

Inform your doctor if you are taking:

• anticoagulant drugs of the coumarin group;
• oral antidiabetic drugs;
• phenytoin (an 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 the treatment of schizophrenia);
• lithium, sertraline (antidepressants);
• bupropion (used in the treatment of depression 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 narcotics (so-called opioids));
• valproate (used in the treatment of epilepsy or bipolar affective disorder).

Metamizole may reduce the effect of acetylsalicylic acid on platelets.
Caution is advised when administering acetylsalicylic acid concurrently, especially when used for cardiovascular disease prevention.

Pyralgina Ból i Gorączka with food, drink and alcohol
Alcohol may affect the efficacy 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 that the benefit-risk balance is carefully considered. In principle, the use of metamizole during the first and second trimesters is not recommended.
Pyralgina Ból i Gorączka 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 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 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 administration of the medicine.

Driving and operating machinery
At the recommended dosage, 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 Ból i Gorączka contains sodium and sunset yellow (E110)
The medicine contains less than 1 mmol (23 mg) of sodium per sachet, meaning the medicine is considered "sodium-free".
The medicine may cause allergic reactions.
Each sachet contains 0.04 carbohydrate exchange units.

3. How to use the medicine Pyralgina Ból i Gorączka

This medicine should always be used exactly as described in the patient leaflet or as advised 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's response to Pyralgina Ból i Gorączka.
Always use the lowest effective dose necessary to control pain and (or) fever.
For adults and adolescents aged 15 years or older (with body weight exceeding 53 kg), the maximum single dose is 1000 mg of metamizole (2 sachets), administered no more frequently than 4 times daily at intervals of 6–8 hours. The maximum daily dose is 4000 mg (equivalent to 8 sachets).
Noticeable effects can be expected within 30 to 60 minutes after oral administration.
Pyralgina Ból i Gorączka should not be used in children under 15 years of age. For younger children, other formulations and strengths of this medicine are available; please consult a physician or pharmacist.

Method of administration:
The contents of the sachet should be dissolved in 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 doctor, 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, debilitated 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
Due to reduced elimination rate in patients with impaired renal or hepatic function, repeated administration of high doses should be avoided. Dose reduction is not required for short-term use. There is no experience regarding long-term use.

Use of a higher than recommended dose of Pyralgina Ból i Gorączka
If a higher than recommended dose is taken, seek immediate medical advice from a doctor or pharmacist.

Overdose may result in dizziness, tinnitus, hearing disturbances, psychomotor agitation, disturbances of consciousness, coma, tonic-clonic seizures, decreased arterial blood pressure, cardiac arrhythmias (tachycardia). Metamizole overdose may also cause abdominal pain, vomiting, gastric and duodenal mucosal erosions, bleeding, perforations, liver cell 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 effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
The medicine must be discontinued immediately and medical help sought if the patient experiences any of the following life-threatening adverse effects:

• 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, 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 body temperature, and enlarged lymph nodes (DRESS syndrome or drug hypersensitivity syndrome).

The medicine must be discontinued immediately and medical advice sought if any of the following severe adverse effects occur:

• pancytopenia (marked decrease in all blood cells: red and white blood cells and platelets), manifesting as general malaise, fever, signs of infection, bruising, bleeding, 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 oral cavity, nose, throat, genital organs, and rectum;
  • elevated ESR (erythrocyte sedimentation rate);
  • hemoglobin, erythrocyte, and platelet counts not always abnormal, although usually within normal range;
  • slightly enlarged lymph nodes and spleen, although often unchanged (see also section 2 "Warnings and precautions");
• 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".

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

• drug rash (transient rash of various types: nodular, macular, vesicular, erythematous);
• excessive decrease in blood pressure.

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

• maculopapular skin changes;
• leukopenia (decreased number of white blood cells in the blood).

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

• analgesic-induced asthma (see section 2 "When not to take Pyralgina Ból i Gorączka"), asthma attacks;
• agranulocytosis (complete or near-complete absence of granulocytes in the blood), including fatal cases (see above "The medicine must be discontinued immediately and medical advice sought if any of the following severe adverse effects occur");
• thrombocytopenia (bruising, bleeding);
• sudden deterioration in kidney function with proteinuria, oliguria or anuria included;
• acute kidney failure;
• interstitial nephritis.

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

• nausea, vomiting, abdominal pain, gastric irritation, diarrhoea, dry mouth;
• liver damage;
• hepatitis, jaundice (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 effects
If any adverse effects occur, including any adverse effects not listed in this leaflet, inform your doctor, pharmacist, or nurse. Adverse effects 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
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse effects can also be reported to the marketing authorization holder.
Reporting adverse effects helps to provide more information on the safety of the medicine.

5. How to store Pyralgina Ból i Gorączka

Keep this medicine out of the sight and reach of children.
Do not store above 30°C.
Do not use this medicine after the expiry date stated on the packaging.
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 package and other information

What Pyralgina Ból i Gorączka contains

• The active substance is magnesium metamizole. Each sachet contains 500 mg of magnesium metamizole in the form of magnesium metamizole hexahydrate.
• The other ingredients are: mannitol, povidone K29/32, sodium saccharin, orange flavour, sunset yellow (E110).

What Pyralgina Ból i Gorączka looks like and contents of the pack
Pyralgina Ból i Gorączka is an orange-coloured, non-hygroscopic, homogeneous granulate with an orange taste, packed in paper-aluminium foil sachets with a heat-sealed SURLYN layer, placed in a cardboard box.
The pack contains 6 sachets, each containing 1.168 g of granulate.

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
Laboratorios Alcala Farma, S.L.
Avenida de Madrid, n° 82
28802 Alcala de Henares (Madrid)
Spain
Zakłady Farmaceutyczne POLPHARMA S.A.
Production Site in Nowa Dęba
ul. Metalowca 2, 39-460 Nowa Dęba