Axonalgin

Leaflet accompanying the packaging: information for the user

Axonalgin, 1000 mg, coated tablets

Metamizole sodium monohydrate

Read the leaflet carefully before taking 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 the doctor or pharmacist.

• Keep this leaflet, you may need to read it again.
• If you need advice or additional information, consult a pharmacist.
• If the patient experiences any side effects, including those not listed in this leaflet, they should inform their doctor or pharmacist. See section 4.
• If the patient feels worse after 3-5 days, they should contact their doctor.

Table of contents of the leaflet

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

1. What is Axonalgin and what is it used for

Axonalgin contains the active substance metamizole sodium monohydrate, which belongs to a group of medicines called pyrazolone derivatives, with analgesic and antipyretic effects. Axonalgin is indicated for use in adolescents from 15 years of age and adults for the treatment of:

• severe pain after injuries or surgery
• colic (spasmodic abdominal pain)
• cancer pain
• other severe or chronic pain when other treatments are contraindicated
• high fever when other treatments are ineffective.

2. Important information before taking Axonalgin

When not to take Axonalgin:

• if the patient is allergic to metamizole or other pyrazolones (e.g. propyphenazone, phenazone), or pyrazolidines (e.g. phenylbutazone, oxyphenbutazone) - this also applies to patients who have experienced a significant decrease in certain white blood cells (agranulocytosis) after taking these medicines.
• if the patient is allergic to any of the other ingredients of this medicine (listed in section 6)
• if the patient has a proven intolerance to painkillers (aspirin asthma syndrome or intolerance to painkillers manifested by urticaria and/or angioedema). This applies to patients who, after exposure to painkillers such as salicylates, paracetamol, or other non-opioid painkillers (e.g. salicylates and paracetamol or diclofenac, ibuprofen, indomethacin, or naproxen), experience bronchospasm (sudden narrowing of the airways) or other symptoms of an allergic reaction, such as itching, rhinitis, and angioedema.

symptoms of an allergic reaction, such as itching, rhinitis, and angioedema.

• if the patient has ever had an allergic reaction to metamizole, such as severe skin reactions (see section 4)
• if the patient has disorders of bone marrow function (e.g. after cytostatic treatment for cancer)
• if the patient has blood disorders (hematological disorders)
• if the patient has a congenital defect associated with an increased risk of red blood cell destruction (genetically determined glucose-6-phosphate dehydrogenase deficiency)
• if the patient has a hereditary disease associated with disorders of hemoglobin synthesis (acute intermittent porphyria)
• if the patient is in the last three months of pregnancy

Warnings and precautions

Before taking Axonalgin, the patient should discuss it with their doctor or pharmacist. Axonalgin contains metamizole, which is associated with a rare but life-threatening risk of:

• sudden cardiac arrest
• agranulocytosis (severe disorder caused by a significant decrease in the number of certain white blood cells).

The patient should stop takingAxonalgin and immediately contact their doctorif they experience any of the following symptoms, which may indicate agranulocytosis:

• unexpected worsening of general condition (e.g. fever, chills, sore throat, difficulty swallowing)
• persistent or recurrent fever
• painful changes in the mucous membranes, mainly in the mouth, nose, throat, or genital and anal areas (see section 4 "Possible side effects").

The patient should stop takingAxonalgin and immediately contact their doctorif they experience symptoms of pancytopenia (such as general malaise, infection, persistent fever, bruising, bleeding, and pallor) or thrombocytopenia (such as increased bleeding tendency, small red spots on the skin and mucous membranes due to bleeding) (see section 4 "Possible side effects"). The doctor may regularly monitor the patient's blood count and stop treatment if certain changes in blood morphology occur.

Severe allergic reactions

• Patients who are allergic to Axonalgin are particularly prone to experiencing similar reactions when taking other painkillers.
• Patients who experience allergic reactions or other immune-related reactions to Axonalgin are also particularly prone to experiencing similar reactions to other pyrazolones and pyrazolidines (chemically similar substances) (e.g. phenazone, propyphenazone, phenylbutazone, oxyphenbutazone).
• If the patient experiences allergic reactions or other immune-related reactions to other pyrazolones, pyrazolidines, or painkillers, there is also a high risk of a reaction to Axonalgin in the same way.

The risk of severe allergic reactions to Axonalgin may increase significantly if the patient has any of the following disorders or intolerances:

• intolerance to non-steroidal anti-inflammatory drugs (used to treat pain, rheumatic diseases), with symptoms such as itching and angioedema. In such cases, Axonalgin should not be taken (see section 2 "When not to take Axonalgin").
• asthma attacks due to bronchial constriction (asthma), especially if the patient also has nasal and sinus inflammation and nasal polyps.
• chronic urticaria
• allergy to coloring agents (e.g. tartrazine) or preservatives (e.g. benzoates).
• alcohol intolerance, resulting in symptoms such as sneezing, tearing, and severe facial flushing even after small amounts of alcohol. Such alcohol intolerance may be a sign of previously undiagnosed painkiller intolerance (see section 2 "When not to take Axonalgin").

In patients with an increased risk of allergic reactions, Axonalgin may only be used after careful consideration of the potential risks and benefits. If Axonalgin is administered in such cases, the patient must be under close medical supervision, with easy access to rescue equipment. In patients with severe allergies, anaphylactic reactions may occur. Therefore, patients with asthma or a tendency to allergic reactions (atopy) should be treated with caution.

Severe skin reactions

During treatment with metamizole, life-threatening severe skin reactions have been reported, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). If symptoms of these severe skin reactions occur, as described in section 4, treatment with Axonalgin should be discontinued immediately and medical help sought. If the patient has ever experienced severe skin reactions, they should never be treated with Axonalgin again (see section 4).

Drop in blood pressure (hypotensive reaction)

Axonalgin may cause a drop in blood pressure (hypotensive reactions, see section 4 "Possible side effects"). The risk of such reactions is higher:

• if the patient has low blood pressure, is severely dehydrated, or has poor blood circulation, or if the patient has early stages of circulatory failure (e.g. after a heart attack or severe injuries).
• if the patient has a high fever.

The doctor will carefully consider the need to administer Axonalgin to such patients and will monitor them closely. To minimize the risk of a drop in blood pressure, preventive measures may be necessary (e.g. correcting circulatory disorders). It is essential to avoid lowering blood pressure (e.g. in cases of severe coronary artery disease or significant narrowing of blood vessels (stenosis) that restrict blood flow to the brain). Axonalgin can only be used under close monitoring of circulatory parameters.

Liver disorders

In patients taking metamizole, cases of liver inflammation have been reported, with symptoms appearing within a few days to several months after starting treatment. The patient should stop taking Axonalgin and contact their doctor if they experience liver disorders, such as 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. The doctor will check the patient's liver function. The patient should not take Axonalgin if they have previously taken metamizole-containing medicines and experienced liver disorders.

Patients with kidney or liver disorders

If kidney or liver function is impaired, Axonalgin should only be used after careful consideration of the potential risks and benefits, taking into account appropriate precautions (see section 3 "Patients with kidney or liver disorders").

Children and adolescents

Axonalgin should not be used in children and adolescents under 15 years of age.

Axonalgin and other medicines

The patient should tell their doctor or pharmacist about all medicines they are currently taking or have recently taken, as well as any medicines they plan to take. It is particularly important to inform the doctor if the patient is taking any of the following medicines:

• methotrexate, a medicine used to treat cancer or certain rheumatic diseases. Concurrent use of metamizole and methotrexate may enhance the harmful effects of methotrexate on blood formation, especially in elderly patients. Therefore, concurrent use of these two medicines should be avoided.
• chlorpromazine, a medicine used to treat mental illnesses. Taking Axonalgin with chlorpromazine may cause a significant drop in body temperature.
• cyclosporine, a medicine used to weaken the immune system.
• acetylsalicylic acid. Metamizole may reduce the effect of acetylsalicylic acid on platelets. If the patient is taking acetylsalicylic acid in low doses to prevent heart disease, Axonalgin should be used with caution.
• bupropion, a medicine used to treat depression or as an aid to smoking cessation.
• efavirenz, a medicine used to treat HIV infection (AIDS).
• methadone, a medicine used to treat opioid dependence.
• valproate, a medicine used to treat epilepsy or bipolar disorder.
• tacrolimus, a medicine used to prevent organ rejection in patients who have undergone a transplant.
• sertraline, a medicine used to treat depression.

Substances belonging to the pyrazolone group (to which metamizole also belongs) are known to have a potential for interactions with the following medicines:

• anticoagulant medicines (oral anticoagulants)
• medicines used to lower high blood pressure and certain heart diseases (captopril)
• a medicine used to treat mental illnesses (lithium)
• a medicine that increases urine production (triamterene)
• antihypertensive medicines (used to treat high blood pressure)

Effect on laboratory tests

Before performing laboratory tests, the patient should inform their doctor that they are taking Axonalgin, as metamizole may affect the results of certain tests (e.g. determination of creatinine, triglycerides, HDL cholesterol, or uric acid levels in blood serum).

Axonalgin and alcohol

The patient should not consume alcohol while taking Axonalgin.

Pregnancy and breastfeeding

If the patient is pregnant or breastfeeding, thinks they may be pregnant, or plans to have a child, they should consult their doctor or pharmacist before taking this medicine.

• Pregnancy

Available data on the use of metamizole during the first three months of pregnancy are limited, but they do not indicate a harmful effect on the fetus. In selected cases, when there are no other treatment options, taking single doses of metamizole during the first and second trimester of pregnancy may be acceptable after consulting a doctor or pharmacist and carefully weighing the benefits and risks of using metamizole. However, in general, it is not recommended to use metamizole during the first and second trimester of pregnancy. Axonalgin should not be taken 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 unborn child, 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, it is recommended to avoid repeated use of metamizole during breastfeeding. In the event 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, no adverse effects have been observed that would affect reaction time or concentration. However, as a precaution, the possibility of such adverse effects should be considered - at least at higher doses - and the patient should avoid operating machinery, driving vehicles, and other activities that involve a risk. This is especially true for patients who consume alcohol.

Axonalgin contains sodium

The medicine contains 71.3 mg of sodium (the main component of common salt) per tablet. This corresponds to 3.56% of the maximum recommended daily intake of sodium in the diet for adults.

3. How to take Axonalgin

This medicine should always be taken exactly as described in the patient leaflet or as directed by the doctor or pharmacist. In case of doubt, the patient should consult their doctor or pharmacist. The dosage depends on the severity of the pain or fever and the individual response of the patient to Axonalgin. The patient should always take the smallest dose necessary to relieve pain and fever. Adults and adolescents from 15 years of age (with a body weight over 53 kg) may take up to 1000 mg of metamizole in a single dose (1 tablet of 1000 mg), up to 4 times a day, at intervals of 6-8 hours. The maximum daily dose is 4000 mg (corresponding to 4 tablets of 1000 mg). A noticeable effect of the medicine can be expected 30-60 minutes after oral administration.

Elderly patients, weakened patients, and (or) patients with reduced creatinine clearance

In elderly patients, weakened patients, and patients with impaired renal function, the dose should be reduced, as the elimination of metamizole metabolites may be prolonged.

Patient with kidney or liver disorders

High doses should be avoided in patients with impaired kidney or liver function, due to the reduced elimination rate. Short-term use does not require dose reduction. There is a lack of experience with long-term use.

Use in children and adolescents

• Adolescents from 15 years of age and older (with a body weight over 53 kg): see dosing for adults.
• Axonalgin is not intended for use in children and adolescents under 15 years of age. Other forms and strengths of this medicine are available for younger children; the patient should consult their doctor or pharmacist.

Method of administration

Oral administration. The tablets should not be chewed. The tablets should be taken with a sufficient amount of liquid (e.g. a glass of water). The tablet can be divided into equal doses.

Duration of treatment

The duration of treatment depends on the nature and severity of the disease and will be determined by the treating doctor. It is not recommended to use painkillers for more than 3-5 days without consulting a doctor or dentist.

Overdose of Axonalgin

In case of the following overdose symptoms, the patient should call their doctor or go to the nearest hospital emergency department:

• nausea, vomiting, abdominal pain
• kidney dysfunction, including acute kidney failure (e.g. with symptoms of interstitial nephritis)
• dizziness, drowsiness (somnolence), loss of consciousness
• seizures
• drop in blood pressure, which can lead to circulatory failure (shock), arrhythmia (tachycardia)

In case of overdose, the patient should contact their doctor immediately so that appropriate treatment can be initiated. After taking very high doses, the excretion of a harmless metabolite (rubazonic acid) may cause the urine to turn red.

Missed dose of Axonalgin

The patient should not take a double dose to make up for a missed dose. If the patient has any further doubts about taking this medicine, they should consult their doctor or pharmacist.

4. Possible side effects

Like all medicines, Axonalgin can cause side effects, although not everybody gets them.

The following side effects may have serious consequences; the patient should stop taking Axonalgin and consult their doctor immediately:

If the following side effects occur suddenly or develop rapidly, the patient should consult their doctor immediately, as some reactions to the medicine (e.g. severe allergic reactions, severe skin reactions, such as Stevens-Johnson syndrome or toxic epidermal necrolysis, agranulocytosis, pancytopenia) can be life-threatening. In such cases, the patient should not take Axonalgin without medical supervision. Immediate discontinuation of the medicine may be crucial for recovery. The patient should stop taking Axonalgin and consult their doctor immediately if they experience any of the following symptoms:

• 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 pain in the upper abdomen. These symptoms may indicate liver damage. See also section 2 "Warnings and precautions".
• Allergic reactions(anaphylactic or anaphylactoid reactions) - rare side effects(may affect up to 1 in 1000 patients). Typical signs of mild reactions include symptoms such as burning eyes, coughing, rhinitis, sneezing, feeling of pressure in the chest, flushing of the skin (especially on the face and head), urticaria, and angioedema. Particular warning signs are a burning sensation, itching, and flushing on the tongue and under the tongue, as well as on the palms and soles. Such mild reactions can develop into severe generalized urticaria, severe angioedema (including laryngeal edema), severe bronchospasm (bronchial constriction), tachycardia (increased heart rate), arrhythmia, drop in blood pressure (sometimes with preceding hypertension), loss of consciousness, and anaphylactic shock. These reactions can also occur even if metamizole was previously taken without complications and may have a severe or life-threatening course, and in some cases even fatal consequences. In patients with aspirin asthma syndrome, allergic reactions usually take the form of asthma attacks (see section 2 "When not to take Axonalgin").
• Red, flat, patchy, or circular spots on the torso, often with blisters in the center, peeling of the skin, ulcers in the mouth, throat, nose, genitals, and eyes. These severe skin reactions may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome or toxic epidermal necrolysis) - very rare side effects(may affect up to 1 in 10,000 patients).
• Widespread rash, high fever, and swollen lymph nodes (DRESS syndrome or drug hypersensitivity syndrome) - frequency not known(frequency cannot be estimated from available data).
• Significant decrease in the number of certain white blood cells (agranulocytosis), including fatal cases, or decrease in platelet count (thrombocytopenia) - very rare side effects(may affect up to 1 in 10,000 patients). These reactions are likely to be immune-related. These reactions can also occur even if metamizole was previously taken without complications. There is isolated evidence suggesting that the risk of agranulocytosis increases if Axonalgin is administered for more than one week. Symptoms of agranulocytosis include high fever, chills, sore throat, difficulty swallowing, and inflammatory changes in the mucous membranes of the mouth, nose, throat, and genital or anal areas. However, in patients taking antibiotics, these symptoms may be minimal. The erythrocyte sedimentation rate (ESR) increases significantly, while lymph node swelling may be mild or absent. Typical signs of thrombocytopenia include increased bleeding tendency and petechiae (small red spots on the skin and mucous membranes due to bleeding). If symptoms of agranulocytosis, pancytopenia (see below), or thrombocytopenia occur, the patient should stop taking Axonalgin immediately and have a blood count (with smear) performed under medical supervision. The patient should stop taking Axonalgin before the laboratory test results are available.
• Decreased blood volume with concurrent bone marrow disorders (aplastic anemia), decreased white blood cell count, and decreased platelet count in the blood (pancytopenia), including fatal cases - frequency not known(frequency cannot be estimated from available data).

Symptoms of pancytopenia and aplastic anemia include general malaise, infection, persistent fever, bruising, bleeding, and pallor.

Other possible side effects

Uncommon(may affect up to 1 in 100 patients)

• purple to dark red skin rash, sometimes with blisters (drug rash).
• drop in blood pressure(isolated hypotensive reaction), which is likely to be caused by the direct action of the medicine and is not accompanied by other symptoms of an allergic reaction. Such a reaction causes a significant drop in blood pressure only in rare cases. The risk of a drop in blood pressure may be increased in patients with very high fever. Typical symptoms of a significant drop in blood pressure include increased heart rate, pallor, trembling, dizziness, nausea, and loss of consciousness.

Rare(may affect up to 1 in 1000 patients)

• decrease in white blood cell count (leukopenia)
• skin rash(e.g. papular rash)

Very rare(may affect up to 1 in 10,000 patients)

• asthma attack(shortness of breath due to bronchial constriction).
• acute worsening of kidney function, sometimes with minimal urine output or anuria, proteinuria (excretion of protein in the urine), or acute kidney failure; interstitial nephritis.

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

• anaphylactic shock.
• myocardial infarction as part of an allergic reaction(Kounis syndrome).
• hepatitis, jaundice, and elevated liver enzyme activity in the blood.
• gastrointestinal bleeding.

Red discoloration of the urine may be caused by the presence of a harmless metabolite of metamizole (rubazonic acid).

Reporting side effects

If the patient experiences any side effects, including those not listed in the leaflet, they should inform their doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety of 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. Side effects can also be reported to the marketing authorization holder. By reporting side effects, more information can be collected on the safety of the medicine.

5. How to store Axonalgin

The medicine should be stored out of sight and reach of children. Do not use this medicine after the expiry date stated on the blister pack and carton after EXP. The expiry date refers to the last day of the month stated. There are no special precautions for storing the medicine. Medicines should not be disposed of via wastewater or household waste. The patient should ask their 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 Axonalgin contains

• The active substance of the medicine 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 (E171), macrogol 8000, and talc.

What Axonalgin looks like and contents of the pack

White to almost white, biconvex, oblong tablets with a dividing line on one side. The tablet can be divided into equal doses. Blister packs of non-transparent PVC/Aluminum or PVC/PE/PVDC/Aluminum in a cardboard box. The packs contain 6 coated tablets.

Marketing authorization holder and manufacturer

Marketing authorization holder Aristo Pharma Sp. z o.o. ul. Baletowa 30 02-867 Warsaw tel: +48 22 855 40 93

Manufacturer Rontis Hellas Medical and Pharmaceutical Products S.A. P.O Box 3012, Larissa Industrial Area 41500 Larissa Greece Aristo Pharma GmbH Wallenroder Strasse 8-10 13435 Berlin Germany

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

Spain Turbet 1000 mg comprimidos recubiertos con película Germany Metamizol Aristo 1000 mg Filmtabletten Poland Axonalgin Portugal Metamizol Aristo 1000 mg comprimidos revestidos por película Hungary Metamizole Aristo 1000mg filmtabletta

Date of last revision of the leaflet: