Metamizol promedo

Package leaflet: Information for the patient

Metamizol Promedo, 500 mg, tablets
Metamizolum natricum monohydricum
Metamizol Promedo may cause abnormally low levels of white blood cells (agranulocytosis), which can lead to severe and life-threatening infections (see section 4).
Treatment with this medicine should be discontinued and immediate medical advice should be sought if any of the following symptoms occur: fever, chills, sore throat, painful ulcers in the nose, mouth or throat, or in the genital or anal area.
If the patient has ever experienced agranulocytosis during treatment with metamizole or similar medicines, this medicine must never be used again in the future (see section 2).
Please read this 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, pharmacist, or nurse.

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

Table of contents of the leaflet

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

1. What Metamizol Promedo is and what it is used for

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

• severe pain of various origins and fever, when the use of other agents is contraindicated or ineffective. Metamizol Promedo is indicated for use in adults and adolescents aged 15 years or older (˃53 kg).

2. Important information before using Metamizol Promedo

When not to use Metamizol Promedo:

• 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 has 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, 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 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 impaired bone marrow function (e.g. after treatment with immunosuppressive drugs) or blood morphology abnormalities such as reduced total number of white blood cells (leukopenia) or a specific type of white blood cells - granulocytes (agranulocytosis), or anemia;
• 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 inherited disorder);
• if the patient is taking a medicine from the group of pyrazolone or pyrazolidine derivatives (e.g. phenylbutazone, propyphenazone);
• if the patient is in the last three months of pregnancy;
• in children and adolescents under 15 years of age.

Warnings and precautions
Low white blood cell count (agranulocytosis)
Metamizol Promedo may cause agranulocytosis, i.e. 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 any of 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 in the genital or anal area. The doctor will order laboratory tests to check the patient's 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, and even shortly after discontinuation of metamizole.
Agranulocytosis may occur even if metamizole was previously administered without complications.
Before starting treatment with Metamizol Promedo, discuss this with your doctor or
pharmacist:

• if the patient has systolic blood pressure below 100 mm Hg or heart diseases and circulatory disorders (e.g. myocardial infarction, coronary artery disease or multi-organ trauma), cerebral vasoconstriction, reduced circulating blood volume, or in dehydrated patients, as the drug 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;
• in patients with bronchial asthma, especially if associated with nasal polyposis and sinusitis;
• in patients with allergic diseases, including atopic conditions, 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 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, e.g.:

• swelling of the face, lips, tongue and/or throat, which may cause difficulty swallowing or breathing;
• severe bronchospasm;
• skin and mucosal changes such as itching, burning, redness, urticaria;
• shock (decreased blood pressure, weakness, fainting). Patients who experience 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 during treatment in patients with asthma or atopy (e.g. atopic dermatitis or mucosal inflammation, hay fever, allergic asthma). Patients at increased risk of reactions resembling severe allergic reactions to metamizole should only be given the drug after careful benefit-risk assessment. If necessary, it should be administered under strict medical supervision with immediate access to emergency care.

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

• agranulocytosis symptoms such as elevated body temperature accompanied by chills, sore throat, difficulty swallowing and ulcers in the mouth, nose, throat, genital organs or rectum. The risk of agranulocytosis increases with high doses or prolonged use; therefore, the medicine should not be used for longer than 3-5 days. If long-term treatment is necessary, the doctor will strictly recommend blood morphology tests, as metamizole may damage bone marrow. Patients who have experienced agranulocytosis during treatment with metamizole are particularly at risk of a similar reaction when using other pyrazolones and pyrazolidines.
• thrombocytopenia, e.g.: skin and mucosal petechiae, bruises, recurrent bleeding from gums, nose, gastrointestinal tract;
• pancytopenia (marked reduction in all blood cells: red and white blood cells and platelets), e.g.: general malaise, fever, signs of infection, bruising, bleeding, pallor;
• severe allergic disease - Stevens-Johnson syndrome: blisters and erosions on the skin, in the mouth, eyes and genital organs, fever and joint pain; or severe, rapidly progressing allergic disease - toxic epidermal necrolysis: rupturing giant blisters, extensive skin erosions, shedding of large epidermal sheets, and fever. If any of these symptoms occur, metamizole must never be used again. The skin should be carefully monitored for these symptoms, especially during the first weeks of treatment.

Severe skin reactions
Severe skin reactions have been reported during treatment with metamizole, including
Stevens-Johnson syndrome, toxic epidermal necrolysis, and 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 discontinued and immediate medical help sought.
If the patient has ever experienced severe skin reactions, Metamizol Promedo must never be used 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.
Metamizol Promedo treatment must be discontinued and the doctor 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 eyes), itching, rash or upper abdominal pain. The doctor will assess liver function in the patient.
The patient should not take Metamizol Promedo if they have previously taken any medicinal products containing metamizole and experienced liver-related adverse effects.

Metamizol Promedo with other medicines
Inform your doctor about all medicines currently or recently taken, as well as any medicines the patient plans to take.
The use of Metamizol Promedo is contraindicated:

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

Metamizole (an analgesic and antipyretic agent) may reduce the effect of acetylsalicylic acid on platelet aggregation (clumping of blood cells and clot formation) when these medicines are used concomitantly. Therefore, caution should be exercised when using metamizole in patients receiving acetylsalicylic acid.
Inform your doctor if the patient is taking:

• anticoagulant coumarin derivatives;
• oral antidiabetic drugs;
• phenytoin (an anticonvulsant);
• sulfonamides (antibacterial agents);
• cyclosporine (an immunosuppressant 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 (an antidepressant);
• antihypertensive drugs (e.g. captopril);
• diuretics (e.g. triamterene);
• methotrexate (used in cancer treatment);
• bupropion (used in depression treatment or as an aid in smoking cessation);
• efavirenz (used in HIV infection (AIDS) treatment);
• methadone (used in treatment of addiction to illegal narcotic substances (so-called opioids));
• valproate (used in epilepsy or bipolar affective disorder treatment);
• tacrolimus (used to prevent organ rejection in transplant patients);
• sertraline (used in depression treatment).

Metamizol Promedo with food, drink and alcohol
The tablet should be swallowed whole with sufficient liquid (e.g. a glass of water).
Metamizol Promedo should be taken during or immediately after meals.
Alcohol must not be consumed during treatment with Metamizol Promedo. 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 plans to become pregnant, she should consult a doctor or pharmacist before using this medicine.

Pregnancy
Available data on metamizole use 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 a careful benefit-risk assessment is made. In principle, administration of metamizole during the first and second trimesters is not recommended.
Metamizol Promedo must not be taken during the last three months of pregnancy due to increased risk of complications for both 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 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 drug.

There are no data on the effect of metamizole on fertility.

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.

Metamizol Promedo contains sodium
The medicine contains 34.5 mg of sodium (the main component of table salt) per tablet.
This corresponds to 1.7% of the maximum recommended daily dietary sodium intake for adults.

3. How to use Metamizol Promedo

This medicine should always be taken exactly as described in the patient leaflet or as advised by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist.
The dose depends on the severity of pain or fever and the individual's response to Metamizol Promedo.
The lowest effective dose necessary 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, not 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.
Metamizol Promedo should not be used in children under 15 years of age. Other dosage forms and strengths of this medicine are available for younger children; consult your physician or pharmacist for further information.
The table below provides recommended single doses and maximum daily doses based on body weight or age:

Method of administration
Oral administration.
The tablet should be swallowed whole with an adequate amount of water (e.g. a glass of water).
The product should be taken during or immediately after meals.
Do not use the medicinal product for longer than 3-5 days without consulting a doctor, or seek immediate medical advice
if, despite taking the product, symptoms worsen.
Elderly persons and patients in poor general health or with renal impairment
In elderly patients, weakened 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. In case of short-term use, dose reduction is not required. There is no experience regarding long-term use.
Use of a higher than recommended dose of Metamizol Promedo
If a dose higher than recommended is taken, seek immediate advice from a doctor or pharmacist.
In case of overdose, symptoms may include dizziness, tinnitus, hearing disturbances, psychomotor agitation,
impaired consciousness, coma, tonic-clonic seizures, or decreased arterial blood pressure, cardiac arrhythmias (tachycardia). Overdose of metamizole may also cause abdominal pain, vomiting, erosions of the gastric and duodenal mucosa, bleeding, perforations, hepatocellular damage, interstitial nephritis, and allergic bronchospasm. Cases of skin rash, urticaria, edema, 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.
Disturbances in blood morphology 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 advice must be sought. Symptomatic and supportive treatment may be necessary.
Missed dose of Metamizol Promedo
Do not take a double dose to make up for a missed dose.
Discontinuation of treatment
If you have any doubts concerning the use of the medicinal product, consult a doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
Due to the risk of life-threatening reactions, the medicine must be discontinued immediately and medical help must be sought
if severe allergic (anaphylactic) reactions occur:

• 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.

The medicine must be discontinued immediately and a doctor must be consulted if any of the following very rare but serious adverse reactions occur:

• Stevens-Johnson syndrome (blisters progressing to erosions on the mucous membranes of the oral cavity, conjunctiva, and genital organs);
• Lyell’s syndrome (toxic epidermal necrolysis, erythematous-bullous skin and mucous membrane lesions leading to detachment of large areas of the epidermis and exposure of extensive skin surfaces);
• Pancytopenia (marked reduction in all blood cells: red and white blood cells and platelets), manifesting as general malaise, fever, signs of infection, bruising, bleeding, pallor of the skin;
• Agranulocytosis (complete or near-complete absence of granulocytes in the blood), manifesting as:
  • High fever, chills;
  • Sore throat, difficulty swallowing, and inflammatory lesions of the mucous membranes of the mouth, nose, throat, genital organs, and rectum;
  • Elevated ESR (erythrocyte sedimentation rate);
  • Hemoglobin, red blood cells, and platelet counts not always abnormal, although usually within normal limits;
  • Slightly enlarged lymph nodes and spleen, although often unchanged. Agranulocytosis may be fatal. See also section 2 "Warnings and precautions".

Discontinue treatment with Metamizol Promedo 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 skin reactions
Discontinue metamizole and seek immediate medical help if the patient develops any of the following serious adverse reactions:

• Red, flat lesions on the trunk in a target-like or circular shape, often with blisters in the center, skin peeling, oral, pharyngeal, nasal, genital, or ocular mucosal ulcers. Such severe skin eruptions may be preceded by fever and influenza-like symptoms (Stevens-Johnson syndrome, toxic epidermal necrolysis);
• Widespread rash, high body temperature, and enlarged lymph nodes (DRESS syndrome or drug-induced hypersensitivity syndrome).

Other adverse reactions:
Consult a doctor if any of the following adverse reactions occur:
Not very common (occurring in fewer than 1 in 100 patients):

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

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

• Papular-macular skin changes;
• Leukopenia (reduced number of white blood cells in the blood).

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

• Analgesic-induced asthma (see "When not to use the medicine..."), asthma attacks;
• Thrombocytopenia (bruising, bleeding);
• Sudden deterioration in 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;
• Hepatitis, jaundice (yellowing of the skin and whites of the eyes), increased liver enzyme activity in blood;
• Liver damage;
• Headache and 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 of 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 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 Metamizol Promedo

Keep this medicine out of sight and reach of children.
Store in the original packaging to protect from light and moisture.
There are no special storage temperature requirements for this medicine.
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.
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 Metamizol Promedo contains
The active substance is metamizole sodium monohydrate.
Each tablet contains 500 mg of metamizole sodium monohydrate.
Other ingredients are: Macrogol 4000, magnesium stearate.

What Metamizol Promedo looks like and contents of the pack
White or almost white, oval, biconvex tablets, packed in blisters made of
Aluminium/PVC/PVDC foil, with a package leaflet in a cardboard box.
The pack contains 6 tablets, 10 tablets, or 20 tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Promedo Pharma Products GmbH
Anklamer Straße 28
10115 Berlin, Germany
[email protected]

Manufacturer
Adamed Pharma S.A.
ul. Marszałka J. Piłsudskiego 5
95-200 Pabianice, Poland