Metamizol Promedo

Leaflet attached to the packaging: patient information

Metamizol Promedo, 500 mg, tablets

Metamizolum natricum monohydricum

Medicine Metamizol Promedo may cause an abnormally low number of white blood cells (agranulocytosis), which can lead to severe and life-threatening infections (see section 4).

You should stop taking the medicine and contact your doctor immediately if you experience any of the following symptoms: fever, chills, sore throat, painful ulcers in the nose, mouth and throat or in the genital or anal area.

If the patient has ever had agranulocytosis while taking metamizol or similar medicines, they should never take this medicine again (see section

• 2).

You should carefully read the contents of the leaflet before taking the medicine, as it contains important information for the patient.

This medicine should always be taken exactly as described in the patient leaflet or as directed by your doctor, pharmacist, or nurse.

• You should keep this leaflet so that you can read it again if you need to.
• If you need advice or additional information, you should consult a pharmacist.
• If you experience any side effects, including any possible side effects not listed in the leaflet, you should tell your doctor or pharmacist. See section 4.
• If after 3-5 days there is no improvement or you feel worse, you should contact your doctor.

Table of contents of the leaflet

• 1. What is Metamizol Promedo and what is it 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. Package contents and other information

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

Metamizol Promedo belongs to non-opioid analgesics of the pyrazolone derivative group with analgesic and antipyretic effects.
It also has a spasmolytic effect on smooth muscles.
Metamizol Promedo is indicated for the treatment of:

• pain of various origins with high intensity and fever, when the use of other agents is contraindicated or ineffective. Metamizol Promedo is indicated for use in adults and adolescents over 15 years of age (over 53 kg).

2. Important information before taking Metamizol Promedo

When not to take Metamizol Promedo:

• if the patient has a history of significantly reduced white blood cell count caused by metamizol or other similar medicines called pyrazolones or pyrazolidines;
• if the patient has bone marrow disorders or a disease that affects the production or function of blood cells;
• if the patient is allergic to metamizol, other pyrazolone derivatives, and pyrazolidines or any of the other ingredients of this medicine (listed in section 6);
• if the patient has analgetic 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 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 has bone marrow disorders (e.g., after taking immunosuppressive drugs) or changes in blood morphology, such as a decrease in the total number of white blood cells (leukopenia) or a certain type of white blood cells - granulocytes (agranulocytosis), or anemia;
• if the patient has acute renal or liver failure, acute porphyria;
• if the patient has a congenital deficiency of glucose-6-phosphate dehydrogenase (a rare hereditary disease);
• if the patient is taking a medicine from the group of pyrazolone and 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

Agranulocytosis

Metamizol Promedo may cause agranulocytosis, 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 should stop taking metamizol and contact your doctor immediately if you experience any of the following symptoms, as they may indicate possible

agranulocytosis: chills, fever, sore throat, and painful ulcers of the mucous membranes, especially
in the mouth, nose, and throat or in the genital or anal area. The doctor will order a laboratory test to check the patient's blood count.

If metamizol is taken for fever, some symptoms of developing agranulocytosis may remain unnoticed. Similarly, symptoms may also be masked if the patient is taking antibiotics.

Agranulocytosis can develop at any time during treatment and even for a short time after stopping metamizol.

Agranulocytosis can occur even if metamizol was previously administered without complications

Before starting treatment with Metamizol Promedo, you should discuss it with your doctor or
pharmacist:

• if the patient has a systolic blood pressure below 100 mmHg or heart disease and circulatory disorders (e.g., heart attack, coronary artery disease, or multiple organ injuries), cerebral vasospasm, decreased circulating blood volume, as well as in dehydrated patients, as the medicine may cause a decrease in blood pressure;
• if the patient has a high fever;
• if the patient has renal and/or liver impairment;
• if the patient has gastric and duodenal ulcer disease;
• if the patient has bronchial asthma, especially if it is accompanied by polypous rhinosinusitis;
• if the patient has allergic diseases, including atopic diseases, chronic urticaria;
• if the patient has intolerance to certain dyes (e.g., tartrazine) or preservatives (e.g., benzoates);
• in patients with alcohol intolerance manifested by sneezing, tearing, and severe flushing of the face in response to even small amounts of alcohol; this may indicate previously undiagnosed analgetic asthma.

Due to the life-threateningnature of the condition, the medicine should be stopped immediately and medical help should be sought in case of symptoms of an allergic reaction (anaphylaxis), such as:

• swelling of the face, lips, tongue, and/or throat, which can 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 with a history of allergic reactions or other immunological reactions to metamizol are also at risk of a similar reaction to other pyrazolones and pyrazolidines and other non-opioid analgesics. In patients with allergies, anaphylactic shock may occur. Therefore, during treatment with the medicine, special caution is recommended in patients with asthma or atopy (e.g., atopic dermatitis or mucous membrane, hay fever, allergic asthma). Patients with an increased risk of reactions similar to severe allergic reactions to metamizol should only be given the medicine after careful consideration of the benefit-to-risk ratio. If necessary, it should be administered under close medical supervision, with the possibility of providing assistance in an emergency.

The medicine should be stopped immediately and a doctor should be consulted if symptoms occur:

• of agranulocytosis, such as elevated body temperature combined with chills, sore throat, difficulty swallowing, and ulcers in the mouth, nose, throat, genital, and anal areas. The use of the medicine in high doses or for a long time increases the risk of agranulocytosis, so the medicine should not be used for more than 3-5 days. In case of a need for long-term use of the medicine, the doctor will definitely prescribe tests to assess blood morphology, as metamizol can cause bone marrow damage. Patients who have developed agranulocytosis in response to metamizol treatment are particularly at risk of a similar reaction to the use of other pyrazolones and pyrazolidines.
• of thrombocytopenia, such as petechiae on the skin and mucous membranes, ecchymoses, recurrent bleeding from the gums, nose, gastrointestinal tract;
• of pancytopenia (significant decrease in the number of all blood cells: red and white blood cells and platelets), such as general malaise, fever, signs of infection, ecchymoses, bleeding, pallor;
• of severe allergic disease - Stevens-Johnson syndrome: blisters and erosions on the skin, in the mouth, eyes, and genitals, fever, and joint pain or severe, rapidly progressing allergic disease - toxic epidermal necrolysis: large blisters bursting, extensive erosions on the skin, peeling off large areas of the skin, and fever. In case of such symptoms, metamizol should never be used again. It is necessary to carefully monitor the skin for the occurrence of these symptoms, especially in the first weeks of treatment.

Severe skin reactions
Severe skin reactions have been reported with metamizol, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS). If the patient experiences any of these severe skin reactions, they should stop taking metamizol and seek medical attention immediately.
If the patient has ever had severe skin reactions, they should never take Metamizol Promedo again (see section 4).
Liver disorders
There have been reports of liver inflammation in patients taking metamizol, with symptoms appearing within a few days to several months after starting treatment.
The patient should stop taking Metamizol Promedo and consult a 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 Metamizol Promedo if they have previously taken any medicinal products containing metamizol and had liver disorders.

Metamizol Promedo and other medicines

The patient should tell their doctor about all medicines they are currently taking or have recently taken, as well as any medicines they plan to take.
The use of Metamizol Promedo is contraindicated:

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

Metamizol (a substance with analgesic and antipyretic effects) may reduce the effect of acetylsalicylic acid on platelet aggregation (clotting of blood cells and formation of a blood clot) if these medicines are taken at the same time. Therefore, caution should be exercised when taking metamizol in patients receiving acetylsalicylic acid.
The patient should inform their doctor about the use of:

• anticoagulant medicines of the coumarin derivative group;
• oral antidiabetic medicines;
• phenytoin (an antiepileptic medicine);
• sulfonamides (antibacterial medicines);
• cyclosporine (an immunosuppressive medicine used, among other things, to prevent transplant rejection);
• barbiturates (e.g., phenobarbital - a medicine used, among other things, in epilepsy);
• monoamine oxidase inhibitors (e.g., selegiline, moclobemide - medicines used, among other things, in depression);
• chlorpromazine (a medicine used, among other things, in the treatment of schizophrenia);
• lithium (an antidepressant medicine);
• medicines that lower blood pressure (e.g., captopril);
• diuretic medicines (e.g., triamterene);
• methotrexate (a medicine used in the treatment of cancer);
• bupropion (a medicine used in the treatment of depression or as an aid to smoking cessation);
• efavirenz (a medicine used in the treatment of HIV infection (AIDS));
• methadone (a medicine used in the treatment of opioid dependence);
• valproate (a medicine used in the treatment of epilepsy or bipolar disorder);
• tacrolimus (a medicine used to prevent transplant rejection);
• sertraline (a medicine used in the treatment of depression).

Metamizol Promedo with food, drink, and alcohol

The tablet should be swallowed whole with a sufficient amount of water (e.g., a glass of water).
Metamizol Promedo should be taken during or immediately after meals.
Alcohol should not be consumed during treatment with Metamizol Promedo. Alcohol may affect the efficacy of the medicine.

Pregnancy, breastfeeding, and fertility

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 metamizol during the first 3 months of pregnancy are limited, but they do not indicate a harmful effect on the fetus. In selected cases, if there are no other treatment options, after consulting a doctor or pharmacist, the patient may take single doses of metamizol in the first and second trimester, provided that the benefits and risks associated with taking the medicine are carefully considered. As a rule, the administration of metamizol in the first and second trimester is not recommended.
The patient should not take Metamizol Promedo 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, a vital blood vessel in the fetus that normally closes after birth).
Breastfeeding
Metamizol breakdown products pass into breast milk in significant amounts, and the risk to the breastfed infant cannot be excluded. Therefore, the use of metamizol should be avoided during breastfeeding. If a single dose of metamizol is administered, mothers should be advised to discard breast milk for 48 hours after administration.
There is no data on the effect of metamizol on fertility.

Driving and using machines

Within the recommended dose range, no impairment of concentration and reaction has been observed. However, when taking higher doses, caution should be exercised and the use of machines, driving, or performing activities that involve risk should be avoided.

Metamizol Promedo contains sodium

The medicine contains 34.5 mg of sodium (the main component of common salt) per tablet.
This corresponds to 1.7% of the maximum recommended daily intake of sodium in the diet for adults.

3. How to take Metamizol Promedo

This medicine should always be taken exactly as described in the patient leaflet or as directed by your doctor or pharmacist. In case of doubt, you should consult your doctor or pharmacist.
The dose depends on the severity of the pain or fever and the individual's response to Metamizol Promedo.
Always the smallest dose necessary to control the pain and/or fever should be chosen.
Adults and adolescents over 15 years of age (with a body weight over 53 kg) can be given a maximum of 1000 mg of metamizol in a single dose (2 tablets) no more than 4 times a day at 6-8 hour intervals. The maximum daily dose is 4000 mg (which corresponds to 8 tablets).
A noticeable effect can be expected within 30 to 60 minutes of oral administration.
Metamizol Promedo should not be used in children under 15 years of age. For younger children, other forms and strengths of this medicine are available; you should ask your doctor or pharmacist about this.
The following table shows the recommended single doses and maximum daily doses depending on body weight or age:

Method of administration
Oral administration.
The tablet should be swallowed whole with a sufficient amount of water (e.g., a glass of water).
The product should be taken during or immediately after meals.
The medicine should not be used for more than 3-5 dayswithout consulting a doctor or seeking medical attention immediately if, despite taking the medicine, the symptoms worsen.
Elderly patients 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 metamizol breakdown products.
Patients with renal or hepatic impairment
Due to the reduced elimination rate in patients with renal or hepatic impairment, high doses should be avoided. In the case of short-term use, dose reduction is not required. There is a lack of experience with long-term use.

Using a higher dose of Metamizol Promedo than recommended

In case of taking a higher dose of the medicine than recommended, you should immediately consult a doctor or pharmacist.
During overdose, dizziness, tinnitus, hearing disorders, psychomotor excitement, impaired consciousness, coma, tonic-clonic seizures, or decreased blood pressure, arrhythmias (tachycardia) may occur. Metamizol overdose can also cause abdominal pain, vomiting, ulcers of the gastric and duodenal mucosa, bleeding, perforation, liver cell damage, interstitial nephritis, and anaphylactic bronchospasm. There have been reports of rash, urticaria, edema, exfoliative dermatitis, and toxic epidermal necrolysis. After taking very high doses, the excretion of rubazonic acid may cause red discoloration of the urine.
There have also been reports of blood morphology disorders, such as bone marrow damage with a decrease in the number of white blood cells (leukopenia or agranulocytosis), platelets (thrombocytopenia), or red blood cells (aplastic anemia), sometimes fatal. There is no antidote for metamizol.
In case of overdose, you should immediately consult a doctor. Symptomatic and supportive treatment may be necessary.

Missing a dose of Metamizol Promedo

You should not take a double dose to make up for a missed dose.

Stopping treatment with Metamizol Promedo

If you have any doubts about taking the medicine, you should consult your doctor or pharmacist.

4. Possible side effects

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

Due to the life-threatening nature of the condition, the medicine should be stopped immediately and medical help should be sought in case of severe allergic reactions (anaphylaxis):

• rarely occurring swelling of the face, lips, tongue, and/or throat, which can cause difficulty swallowing or breathing;
• very rarely occurring severe bronchospasm;
• skin and mucous membrane changes, such as itching, burning, redness, urticaria;
• anaphylactic shock (life-threatening decrease in blood pressure, weakness, fainting) - frequency not known.

The medicine should be stopped immediately and a doctor should be consulted if the following very rare but serious side effects occur:

• Stevens-Johnson syndrome (blisters that transition to erosions on the mucous membranes of the mouth, eyes, genitals);
• Lyell's syndrome (toxic epidermal necrolysis, blistering rash on the skin and mucous membranes leading to peeling off large areas of the skin and exposure of large areas of skin);
• pancytopenia (significant decrease in the number of all blood cells: red and white blood cells and platelets), manifested by general malaise, fever, signs of infection, ecchymoses, bleeding, pallor;
• agranulocytosis (complete or almost complete disappearance of granulocytes in the blood), manifested by:
• high fever, chills;
• sore throat, difficulty swallowing, and inflammatory conditions of the mucous membranes of the mouth, nose, throat, genital, and anal areas;
• elevated OB;
• not always normal hemoglobin, erythrocyte, and platelet values, although they are usually normal;
• slightly enlarged lymph nodes and spleen, although they are usually unchanged. Agranulocytosis can be fatal. See also section 2 "Warnings and precautions".

The patient should stop taking Metamizol Promedo and seek medical attention immediately if they experience any of the following symptoms:

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".

Severe skin reactions

The patient should stop taking metamizol and seek medical attention immediately if they experience any of the following severe side effects:

• red, flat spots on the torso in a target shape or circular, often with blisters in the center, peeling of the skin, ulcers in the mouth, throat, nose, genitals, and eyes. The occurrence of such serious rashes can be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome, toxic epidermal necrolysis);
• widespread rash, high body temperature, and enlarged lymph nodes (DRESS or drug hypersensitivity syndrome).

Other side effects:

The patient should consult their doctor if they experience any of the following side effects:
Uncommon (less than 1 in 100 patients) side effects include:

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

Rare (less than 1 in 1,000 patients) side effects include:

• skin changes with a papular rash;
• leukopenia (decrease in the number of white blood cells in the blood).

Very rare (less than 1 in 10,000 patients) side effects include:

• analgetic asthma (see "When not to take the medicine..."), asthma attacks;
• thrombocytopenia (petechiae, bleeding);
• sudden worsening of renal function with proteinuria, oliguria, or anuria;
• acute renal failure; interstitial nephritis. Frequency not known (frequency cannot be estimated from available data):
• nausea, vomiting, abdominal pain, gastric irritation, diarrhea, dry mouth;
• hepatitis, yellowing of the skin and whites of the eyes, increased liver enzyme activity in the blood;
• liver damage;
• headache, dizziness;
• hemolytic anemia, aplastic anemia, bone marrow damage, sometimes fatal. In patients with glucose-6-phosphate dehydrogenase deficiency, the medicine causes hemolysis of red blood cells;
• red discoloration of the urine (after taking very high doses of metamizol).

Reporting side effects

If side effects occur, including any side effects not listed in the leaflet, the patient should tell their doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Drug Safety, Urząd Rejestracji Produktów Leczniczych, Wyrobów Medycznych i Produktów Biobójczych
Al. Jerozolimskie 181C
02-222 Warsaw
Phone: +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, it is possible to gather more information on the safety of the medicine.

5. How to store Metamizol Promedo

The medicine should be stored out of the sight and reach of children.
It should be stored in the original packaging to protect it from light and moisture.
There are no special recommendations for the storage temperature of the medicine.
The medicine should not be used after the expiry date stated on the packaging.
The expiry date stated on the packaging is the last day of the specified month.
The inscription on the blister pack after the abbreviation EXP indicates the expiry date, and after the abbreviation LOT, it indicates the batch number.
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. Package contents and other information

What Metamizol Promedo contains

The active substance of the medicine is metamizol sodium monohydrate.
One tablet contains 500 mg of metamizol sodium monohydrate.
The other ingredients are: Macrogol 4000, magnesium stearate.

What Metamizol Promedo looks like and what the package contains

The tablets are white or almost white, oval, biconvex, packaged in aluminum/PVC/PVDC blisters with a patient leaflet in a cardboard box.
The package contains 6 tablets or 10 tablets or 20 tablets.
Not all pack sizes may be marketed.

Marketing authorization holder

Promedo Pharma Products GmbH
Anklamer Straße 28
10115 Berlin, Germany
biuro@promedopharma.de

Manufacturer

Adamed Pharma S.A.
ul. Marszałka J. Piłsudskiego 5
95-200 Pabianice, Poland
Date of last revision of the leaflet: