METAMIZOLE COMBIX 575 mg HARD CAPSULES

Introduction

Package Leaflet: Information for the User

Metamizol Combix 575 mg hard capsules EFG

Metamizol magnesium

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

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

If you have ever had agranulocytosis with metamizol or similar medications, you should never take this medication again (see section 2).

Read the entire package leaflet carefully before starting to take this medication, as it contains important information for you.

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

Contents of the package leaflet

1. What is Metamizol Combix and what is it used for
2. What you need to know before taking Metamizol Combix
3. How to take Metamizol Combix
4. Possible side effects
5. Storage of Metamizol Combix
6. Package contents and additional information

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

This medication belongs to the group of medications called "Other Analgesics and Antipyretics".

This medication is used to treat moderate or severe acute post-operative or post-traumatic pain, colic pain, or pain of tumor origin. It is also used in cases of high fever that does not respond to other measures or medications for fever.

2. What you need to know before taking Metamizol Combix.

Do not take Metamizol Combix:

• If you have previously had a significant decrease in a type of white blood cell called granulocytes, which was caused by metamizol or other similar medications called pyrazolones or pyrazolidines.

• If you have bone marrow problems or have a disorder that affects the way your blood cells are produced or function.

• If you have had previous allergic reactions or hematologic reactions (decrease in white blood cells, red blood cells, or platelets in the blood) with medications containing metamizol or other similar compounds, or allergic reactions to any of the other components of this medication (listed in section 6).

• If you have experienced symptoms of asthma, rhinitis, or urticaria (red patches or hives on the skin that can cause itching) during treatment with other analgesics such as acetylsalicylic acid, paracetamol, or non-steroidal anti-inflammatory drugs, as you may also be sensitive to metamizol (the active substance of this medication).

• If you have acute intermittent porphyria (a disorder of the metabolism of blood pigments that are part of hemoglobin).
• If you have a genetic deficiency of glucose-6-phosphate dehydrogenase.

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

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

• If you have had severe skin reactions (such as Stevens-Johnson syndrome or toxic epidermal necrolysis) with the previous use of this or another medication containing metamizol.

Warnings and precautions

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

Low white blood cell count (agranulocytosis).

Metamizol Combix may cause agranulocytosis, a very low level of a type of white blood cell called granulocytes, which are important for fighting infections (see section 4). You should stop taking metamizol and contact a doctor immediately if you experience any of the following symptoms, as they may indicate possible agranulocytosis: chills, fever, sore throat, and painful sores in the mucous membranes (wet surfaces of the body), 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 count.

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

Agranulocytosis can occur at any time during the use of Metamizol Combix and even shortly after stopping metamizol.

You may develop agranulocytosis even if you have used metamizol without problems in the past.

Be especially careful:

• If you experience general discomfort, infection, persistent fever, sore throat, inflammation in the mouth, nose, or throat, lesions in the mucous membranes of the mouth or genitals, bruising, bleeding, or paleness, you should 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), platelets (thrombocytopenia), or a failure in the production of all blood cells (aplastic anemia).

• If you experience dizziness, difficulty breathing, rhinitis, swelling of the face, decreased blood pressure, sudden onset of red patches on the skin, stop treatment and consult your doctor. These symptoms may be due to a severe allergic reaction called anaphylactic shock. This reaction is more likely if you have asthma or allergic disorders (atopy).

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

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

• Severe 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 metamizol treatment. Stop taking metamizol and seek medical attention immediately if you observe any of the symptoms related to these severe skin reactions described in section 4.

If you have ever had severe skin reactions, you should not resume treatment with metamizol at any time (see section 4).

• If you have impaired kidney or liver function, as you may have difficulty eliminating the medication.

• If you are an elderly patient, be especially alert to the appearance of any of the disorders described above, as they may occur more frequently.

Liver problems:

Inflammation of the liver has been reported in patients taking metamizol, with symptoms developing within a few days to a few months after starting treatment.

Stop taking this medication and contact a doctor if you experience symptoms of liver problems, such as discomfort (nausea or vomiting), fever, feeling tired, loss of appetite, dark urine, light-colored stools, yellowing of the skin or the white part of the eyes, itching, rash, or upper abdominal pain. Your doctor will check your liver function.

Do not take this medication if you have previously taken a medication containing metamizol and had liver problems

Taking Metamizol Combix with food, drinks, and alcohol

Together with alcohol, the effects of both can be enhanced.

Pregnancy, breastfeeding, and fertility

Pregnancy

Available data on the use of metamizol during the first three months of pregnancy are limited, but they do not indicate harmful effects on the embryo. In selected cases, when there are no other treatment options, single doses of metamizol during the first and second trimester may be acceptable after consulting with your doctor or pharmacist and carefully evaluating the benefits and risks of using metamizol. However, in general, the use of metamizol is not recommended during the first and second trimester.

During the last three months of pregnancy, you should not take metamizol due to the increased risk of complications for the mother and the baby (bleeding, premature closure of a vital blood vessel for the fetus, called the ductus arteriosus, which closes naturally after birth).

Breastfeeding

Metamizol degradation products are excreted in breast milk in significant amounts, and it cannot be excluded that there is a risk for the breastfed infant. Therefore, repeated use of metamizol should be avoided during breastfeeding. If a single dose of metamizol is administered, mothers should express and discard breast milk for 48 hours after administration.

Driving and using machines

Although no adverse effects on concentration and reaction abilities are expected, at the highest recommended doses, it should be taken into account that these abilities may be affected, and you should avoid using machines, driving vehicles, or engaging in other hazardous activities. This is especially applicable when alcohol has been consumed.

Taking Metamizol Combix with other medications

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

• If administered together with cyclosporin (a medication that prevents transplant rejection), it may reduce cyclosporin blood levels, and these should be regularly monitored.

• If administered with chlorpromazine (a medication for the treatment of psychoses), it may cause a drop in body temperature.

• If administered together with methotrexate or other medications for the treatment of tumors (antineoplastics), it may enhance the toxic effects on the blood of antineoplastics, especially in elderly patients.

• If administered together with acetylsalicylic acid, it may reduce the effect of acetylsalicylic acid on decreasing platelet aggregation (antiplatelet) and should be used with caution in patients taking it to protect the heart (cardioprotector).

If administered together with bupropion (a medication used for the treatment of depression and/or to help quit smoking), efavirenz (a medication used for the treatment of HIV/AIDS), methadone (a medication used to treat opioid dependence), valproate (a medication used to treat epilepsy or bipolar disorder), tacrolimus (a medication used to prevent organ rejection in transplant patients), or sertraline (a medication used to treat depression), it may reduce the blood levels of these medications, and caution should be exercised.

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

3. How to take Metamizol Combix.

Follow your doctor's instructions for administration of this medication exactly. If in doubt, consult your doctor or pharmacist again.

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

This medication should be administered orally. The capsules should be swallowed whole, without chewing, with a little liquid.

The dose is established based on the intensity of the pain or fever and the individual's sensitivity to treatment with metamizol. The lowest necessary dose should always be selected to control the pain and fever. Your doctor will indicate how to take metamizol.

Adults and adolescents 15 years of age or older

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

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

Children and adolescents under 15 years of age

Metamizol should not be used in children under 15 years of age. Other presentations and doses of this medication are available for younger children; consult your doctor or pharmacist.

Elderly patients and patients with poor general health or renal insufficiency

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

Patients with renal or hepatic insufficiency

Since the elimination rate decreases in cases of renal or hepatic insufficiency, administration of high repeated doses should be avoided. Only in short-term treatments is a dose reduction not necessary. There is no experience with long-term treatments.

If the pain persists or worsens, you should consult a doctor to investigate the cause of the symptoms.

If you take more Metamizol Combix than you should

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

Nausea, vomiting, abdominal pain, deterioration of kidney function, and, in rare cases, dizziness, drowsiness, coma, convulsions, decreased blood pressure, or even shock and increased heart rate (tachycardia) may occur.

After administration of very high doses of metamizol, a red coloration of the urine may occur, which disappears upon discontinuation of treatment.

Information for the doctor:No specific antidote is known. After oral overdose, gastric lavage and forced vomiting may be performed. Forcing diuresis or dialysis may be considered, as metamizol is dialyzable.

In case of severe allergic reactions, other usual emergency measures should be applied, such as placing the patient on their side, keeping the airways clear of obstruction, or administering oxygen. Pharmacological emergency measures include the administration of adrenaline, fluid therapy, and glucocorticoids.

Careful monitoring of vital functions and taking necessary general measures is advised.

If you forget to take Metamizol Combix

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

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

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

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

Feeling of illness (nausea or vomiting), fever, feeling of tiredness, loss of appetite, dark urine, light-colored stools, yellowish discoloration of the skin or the white part of the eyes, itching, rash, or pain in the upper abdominal 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 can progress to more severe forms, e.g., generalized urticaria, swelling of feet, hands, lips, throat, and respiratory tract (angioedema), severe bronchospasm (narrowing of the bronchial walls), heart rhythm disturbances, and decreased blood pressure (sometimes preceded by an increase in blood pressure).

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

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

• Hypotension (decreased blood pressure).

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

• Rashes and skin reactions.

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

• Allergic reactions that usually occur during or immediately after administration but also hours later, rashes, and the appearance of hives on the skin, decreased white blood cell count in the blood (leukopenia), asthma.

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

• Skin reactions in which blisters or bubbles appear (toxic epidermal necrolysis, Stevens-Johnson syndrome), kidney problems with decreased or suppressed urine output, increased protein excretion in the urine, kidney inflammation (interstitial nephritis), severe decrease in white blood cells (agranulocytosis) that can cause death due to severe infections, decreased platelet count in the blood (thrombocytopenia), in this case, inflammatory lesions in the mucous membranes, sore throat, and fever, shock (drastic drop in blood pressure).

Frequency Not Known (cannot be estimated from available data):

• Sepsis (severe infection that involves an inflammatory reaction of the entire body and can cause death), aplastic anemia (failure to produce bone marrow and blood cells), pancytopenia (low number of red, white, and platelet cells simultaneously), anaphylactic shock (severe allergic reaction that can cause death), Kounis syndrome (a type of cardiac disorder), gastrointestinal bleeding, chromaturia (abnormal urine color).

• Liver inflammation, yellowish discoloration of the skin and the white part of the eyes, increased blood levels of liver enzymes.

• Severe skin reactions.

Stop taking metamizol and seek medical attention immediately if you observe any of the following serious adverse effects:

• Red patches that are not raised, or circular or target-shaped patches on the chest, often with central blisters, skin peeling, ulcers in the mouth, throat, nose, genitals, and eyes. These severe skin rashes can be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome, toxic epidermal necrolysis).
• Generalized erythema, elevated body temperature, and enlarged lymph nodes (DRESS or drug hypersensitivity syndrome).

Reporting Adverse Effects:

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that is not listed in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Metamizol Combix

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiration date that appears on the packaging after CAD. The expiration date is the last day of the month indicated.

No special storage conditions are required.

Medicines should not be disposed of through wastewater or household waste. Deposit the packaging and medicines you no longer need at the SIGRE Point in the pharmacy. In case of doubt, ask your pharmacist how to dispose of the packaging and medicines you no longer need. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Metamizol Combix

• The active ingredient 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 Package Contents

Hard gelatin capsules, size 0L, with a pink body and cap, packaged 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 Last Revision of this Leaflet:

November 2024

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