Metamizole Combix 575 mg hard capsules EFG

Patient Information Leaflet

Introduction

Package leaflet: Information for the user

Metamizol Combix 575 mg hard capsules EFG

Magnesium metamizole

Metamizol Combix may cause lower than normal white blood cell count (agranulocytosis), which can lead to serious and potentially life-threatening infections (see section 4).

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

If you have ever had agranulocytosis with metamizole or similar medicines, you must never take this medicine again (see section 2).

Read the entire leaflet carefully before you start taking this medicine, as it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for you only, and you should not give it to others, even if they have the same symptoms as you, since it could harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are adverse effects not listed in this leaflet. See section 4.

Leaflet contents

1. What Metamizol Combix is and what it is used for
2. What you need to know before taking Metamizol Combix
3. How to take Metamizol Combix
4. Possible adverse effects
5. How to store Metamizol Combix
6. Contents of the pack and other information

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

This medicine belongs to a group of medicines called "Other Analgesics and Antipyretics".

This medicine is used for the treatment of moderate to severe acute pain following surgery or trauma, of colicky type, or of tumour origin. It is also used in cases of high fever unresponsive to other measures or other antipyretic medicines.

2. What you need to know before starting to take Metamizol Combix.

Do not take Metamizol Combix:

• If you have previously had a significant decrease in a type of white blood cells called granulocytes, caused by metamizole or other similar medicines known as pyrazolones or pyrazolidines.

• If you have problems with your bone marrow or a disorder affecting the production or function of your blood cells.

• If you have previously experienced allergic reactions or hematological reactions (reduction in white blood cells, red blood cells, or platelets in the blood) to medicines containing metamizole or other similar compounds, or if you are allergic to any of the other components of this medicine (listed in section 6).

• If you have experienced symptoms of asthma, rhinitis, or urticaria (reddish skin rashes or hives that may cause itching) while being treated with other painkillers such as acetylsalicylic acid, paracetamol, or non-steroidal anti-inflammatory drugs, since in these cases you may also be sensitive to metamizole (the active substance in this medicine).

• If you have acute intermittent porphyria (a metabolic disorder affecting blood pigments that are part of hemoglobin).

• If you have glucose-6-phosphate dehydrogenase deficiency (a genetic disorder).

• If you have experienced bone marrow dysfunction (responsible for blood cell formation); for example, during or after receiving antitumor (antineoplastic) chemotherapy, or if you have had diseases related to blood cell formation.

• If you are in the last three months of pregnancy.

• If you have previously experienced severe skin reactions (for example, Stevens-Johnson syndrome or toxic epidermal necrolysis) with prior use of this or any other medicine containing metamizole.

Warnings and precautions

Consult your doctor or pharmacist before starting to take this medicine.

Lower than normal white blood cell count (agranulocytosis).

Metamizol Combix can cause agranulocytosis, a very low level of a type of white blood cells called granulocytes, which are important in fighting infections (see section 4). You must stop taking metamizole and contact a doctor immediately if you experience the following symptoms, as they may indicate possible agranulocytosis: chills, fever, sore throat, and painful sores in the mucous membranes (wet body surfaces), especially in the mouth, nose, and throat, or in the genital or anal area. Your doctor will perform laboratory tests to check your blood cell levels.

If you are taking metamizole for fever, some symptoms of agranulocytosis may go unnoticed. Similarly, symptoms may be masked if you are taking antibiotics.

Agranulocytosis may occur at any time during treatment with Metamizol Combix, and even shortly after stopping metamizole.

You may develop agranulocytosis even if you have previously used metamizole without problems.

Take special care:

• If you experience general malaise, infection, persistent fever, sore throat, swelling in the mouth, nose or throat, lesions in the mucous membranes of the mouth or genitals, bruising, bleeding, or paleness, you must stop treatment and consult your doctor immediately. These disorders may be due to a decrease in the number of white blood cells in the blood (agranulocytosis), a decrease in platelets (thrombocytopenia), or failure in the production of all blood cells (aplastic anemia).

• If you experience dizziness, difficulty breathing, rhinitis, facial swelling, low blood pressure, or sudden appearance of reddish skin rashes, stop treatment and consult your doctor. These symptoms may be due to a severe allergic reaction known as anaphylactic shock. This reaction is more likely if you suffer from asthma or allergic-type disorders (atopy).

• If you have bronchial asthma (especially in the presence of nasal mucosal inflammation and nasal polyps), chronic urticaria, or if you are intolerant to dyes and/or preservatives or to alcohol, as the risk of severe allergic reactions is higher.

• If you have low blood pressure, hypovolemia (reduced circulating volume of blood or any other body fluid), dehydration, or unstable circulation, since the risk of a sudden drop in blood pressure is greater.

• Serious skin reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported in association with metamizole treatment. Stop taking metamizole and seek immediate medical attention if you notice any of the symptoms related to these serious skin reactions described in section 4.

If you have ever experienced serious skin reactions, you must never restart treatment with metamizole (see section 4).

• If you have impaired kidney or liver function, as you may eliminate the medicine with greater difficulty.

• If you are an elderly patient, be especially vigilant for the onset of any of the disorders described above, as they may occur more frequently.

Liver problems:

Hepatic inflammation has been reported in patients taking metamizole, with symptoms developing from a few days to several months after starting treatment.

Stop taking this medicine and contact a doctor if you experience symptoms of liver problems, such as malaise (nausea or vomiting), fever, feeling of fatigue, loss of appetite, dark urine, pale stools, yellowing of the skin or the whites of the eyes, itching, rash, or upper abdominal pain. Your doctor will check your liver function.

Do not take this medicine if you have previously taken any medicine containing metamizole and experienced liver problems.

Metamizol Combix use with food, drinks, and alcohol

When taken with alcohol, the effects of both alcohol and the medication may be intensified.

Pregnancy, breastfeeding and fertility

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 where no other treatment options are available, single doses of metamizole during the first and second trimesters may be acceptable after consulting with your doctor or pharmacist and following a careful assessment of the benefits and risks of using metamizole. However, in general, the use of metamizole is not recommended during the first and second trimesters.

During the last three months of pregnancy, you must not take metamizole due to the increased risk of complications for both mother and baby (bleeding, premature closure of an important fetal blood vessel called the ductus arteriosus, which normally closes after birth).

Breastfeeding

Metabolites of metamizole are excreted in breast milk in considerable amounts, and a risk to the breastfed infant cannot be excluded. Therefore, repeated use of metamizole should be avoided during breastfeeding. If a single dose of metamizole is administered, mothers are advised to express and discard breast milk for 48 hours following administration.

Driving and operating machinery

Although adverse effects on concentration and reaction ability are not expected, at the highest doses within the recommended range, it should be considered that these abilities may be impaired. Therefore, operating machinery, driving vehicles, or engaging in other hazardous activities should be avoided. This is especially applicable when alcohol has been consumed.

Taking Metamizol Combix with other medicines

Inform your doctor or pharmacist if you are using, have recently used, or may need to use any other medicines.

• If administered concomitantly with cyclosporine (a medicine used to prevent transplant rejection), it may reduce cyclosporine blood levels; therefore, cyclosporine levels should be monitored regularly.

• If administered together with chlorpromazine (a medicine used to treat psychosis), it may cause a decrease in body temperature.

• If administered concomitantly with methotrexate or other anticancer medicines (antineoplastics), it may enhance the blood-related toxic effects of antineoplastics, especially in elderly patients.

• If administered concomitantly with acetylsalicylic acid, it may reduce the antiplatelet effect of acetylsalicylic acid and therefore should be used with caution in patients taking it for cardioprotective purposes.

If administered concomitantly with bupropion (a medicine used to treat depression and/or to help stop smoking), efavirenz (a medicine used to treat HIV/AIDS), methadone (a medicine used to treat dependence on illegal drugs known as opioids), valproate (a medicine used to treat epilepsy or bipolar disorder), tacrolimus (a medicine used to prevent organ rejection in transplant patients), or sertraline (a medicine used to treat depression), it may reduce blood levels of these medicines; therefore, it should be used with caution.

Metamizol may alter the effect of antihypertensives (medicines that lower blood pressure) and diuretics (medicines that increase fluid elimination).

3. How to take Metamizol Combix.

Follow exactly the administration instructions given by your doctor. If in doubt, consult your doctor or pharmacist again.

This medicine is intended for short-term use. Your doctor will indicate the duration of your treatment.

This medicine should be taken orally. The capsules must be swallowed whole, without chewing, with a little liquid.

The dose is determined according to the intensity of pain or fever and to the individual's sensitivity to metamizole treatment. The lowest effective dose required to control pain and fever should always be used. Your doctor will advise you on how to take metamizole.

Adults and adolescents 15 years of age or older

Adults and adolescents 15 years of age or older (weighing more than 53 kg) may take 1 capsule (575 mg of metamizole) as a single dose, which can be administered up to 6 times a day at intervals of 4 to 6 hours. The maximum daily dose is 3,450 mg (equivalent to 6 capsules).

The effect of the medicine usually appears between 30 and 60 minutes after oral administration.

Children and adolescents under 15 years of age

Metamizole must not be used in children under 15 years of age. For younger children, other formulations and doses of this medicine are available; consult your doctor or pharmacist.

Elderly individuals and patients with poor general health or renal insufficiency

The dose should be reduced in elderly individuals, in debilitated patients, and in those with impaired renal function, as the elimination of metamizole degradation products may be delayed.

Patients with renal or hepatic impairment

Since elimination rate decreases in cases of renal or hepatic impairment, repeated administration of high doses should be avoided. Dose reduction is not necessary only for short-term treatments. Experience with long-term treatments is lacking.

If pain persists or worsens, consult a physician to investigate the cause of symptoms.

If you take more Metamizol Combixdel than you should

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service at telephone number: 91 562 04 20, indicating the medication and the amount ingested.

Symptoms may include nausea, vomiting, abdominal pain, impaired kidney function, and, more rarely, dizziness, drowsiness, coma, seizures, low blood pressure, or even shock and increased heart rate (tachycardia).

After administration of very high doses of metamizole, red discoloration of the urine may occur, which disappears upon discontinuation of treatment.

Information for the physician: There is no known specific antidote. Following an oral overdose, gastric lavage and induction of emesis may be possible. Forced diuresis or dialysis may be considered, as metamizole is dialyzable.

In case of severe allergic reactions, other standard emergency measures should also be applied, such as placing the patient in the lateral position, ensuring airway patency, or administering oxygen. Pharmacological emergency measures include administration of adrenaline, fluid therapy, and glucocorticoids.

Careful monitoring of vital functions is advised, along with implementation of all necessary general supportive measures.

If you forget to take Metamizol Combix

Do not take a double dose to make up for missed doses.

If you have any further questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.

Stop taking this medicine and contact a doctor immediately if you experience any of the following symptoms:

Feeling unwell (nausea or vomiting), fever, feeling tired, loss of appetite, dark urine, pale stools, yellowing of the skin or the whites of the eyes, itching, rash, or pain in the upper stomach area. These symptoms may be signs of liver damage. See also section 2 Warnings and precautions.

Mild allergic reactions (e.g. skin and mucous membrane reactions such as itching, burning, redness, swelling) as well as difficulty breathing and gastrointestinal discomfort may progress to more severe forms, e.g. generalized urticaria, swelling of feet, hands, lips, throat and airways (angioedema), severe bronchospasm (narrowing of the bronchial walls), changes in heart rhythm, and low blood pressure (sometimes preceded by a rise in blood pressure).

Other adverse effects that may occur with the following frequencies are:

Common (may affect up to 1 in 10 people):

• hypotension (low blood pressure).

Uncommon (may affect up to 1 in 100 people):

• Skin rashes and skin reactions.

Rare (may affect up to 1 in 1,000 people):

• allergic reactions, which usually occur during or shortly after administration but may also occur hours later, skin rashes and appearance of hives, decrease in the number of white blood cells in the blood (leucopenia), asthma.

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

• skin reactions with the appearance of blisters or vesicles (toxic epidermal necrolysis, Stevens-Johnson syndrome), kidney problems with reduced or suppressed urine output, increased amount of protein excreted in the urine, inflammation of the kidney (interstitial nephritis), severe decrease in white blood cells (agranulocytosis) which may result in death due to serious infections, decrease in the number of platelets in the blood (thrombocytopenia); in this case, inflammatory lesions in mucous membranes, sore throat and fever may occur, shock (a drastic drop in blood pressure).

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

• sepsis (a serious infection causing a systemic inflammatory response that may lead to death), aplastic anaemia (failure in the production of bone marrow and blood cells), pancytopenia (low levels of red blood cells, white blood cells and platelets simultaneously), anaphylactic shock (a severe allergic reaction that may be fatal), Kounis syndrome (a type of cardiac disorder), gastrointestinal haemorrhage, chromaturia (abnormal urine colour).

• Inflammation of the liver, yellowing of the skin and the whites of the eyes, increased blood levels of liver enzymes.

• Severe skin reactions.

Stop taking metamizole and seek immediate medical attention if you notice any of the following serious adverse effects:

• Non-elevated reddish patches, or circular or target-shaped rashes on the chest, often with central blisters, skin peeling, mouth, throat, nose, genital or eye ulcers. These severe cutaneous erythemas may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome, toxic epidermal necrolysis).

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

Reporting of adverse reactions:

If you experience any type of adverse reaction, consult your doctor or pharmacist, even if it is a possible adverse reaction not listed in this leaflet. You may also report them directly through the Spanish Pharmacovigilance System for Human Medicinal Products: https://www.notificaram.es. By reporting adverse reactions, you can help provide more information on the safety of this medicine.

5. Storage of Metamizol Combix

Keep this medicine out of sight and reach of children.

Do not use this medicine after the expiry date stated on the packaging after EXP. The expiry date is the last day of the month indicated.

No special storage conditions are required.

Medicines must not be disposed of via wastewater or household waste. Dispose of unused containers and medicines at the SIGRE collection point at your pharmacy. If in doubt, ask your pharmacist how to dispose of containers and medicines you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Metamizol Combix

• The active substance is magnesium metamizole. Each capsule contains 575 mg of magnesium metamizole.
• The other components are magnesium stearate, indigotine (E 132), erythrosine (E 127), titanium dioxide (E 171), and gelatin.

Appearance of the product and contents of the container

Hard gelatin capsules of size 0L with burgundy-colored body and cap, packed in PVC/PVdC-Aluminum blister packs containing 10, 20 or 500 capsules.

Marketing Authorization Holder

Laboratorios Combix, S.L.U.

C/ Badajoz 2, Edificio 2

28223 Pozuelo de Alarcón (Madrid)

Spain

Manufacturer:

Industria Química y Farmacéutica Vir, S.A.

C/ Laguna 66-70. Polígono industrial Urtinsa II.

28923 Alcorcón (Madrid)

Spain

Date of the most recent review of this leaflet:

November 2024

Detailed information on this medicinal product is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS) https://www.aemps.gob.es/.