METAMIZOLE NORMON 0.4 G/ML INJECTABLE SOLUTION AND PERFUSION SOLUTION

2. What you need to know before taking Metamizol Normon

Do not use Metamizol Normon:

• 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 medicines called pyrazolones or pyrazolidines.

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

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

• If you have had 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 Metamizol Normon).

• 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 bone marrow function disorders (e.g., during or after receiving antitumor 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 low blood pressure or circulation problems, you should not use Metamizol Normon 0.4 g/ml solution for injection and infusion parenterally.

• Intra-arterial injection.

• If you have had severe skin reactions (e.g., Stevens-Johnson syndrome or toxic epidermal necrolysis) with previous use of metamizol or another medicine containing metamizol.

Warnings and precautions

Consult your doctor or pharmacist before starting to use Metamizol.

Low white blood cell count (agranulocytosis).

Metamizol Normon 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 Normon and even shortly after stopping metamizol.

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

Be particularly 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).

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 using Metamizol Normon 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.

You should not take Metamizol Normon if you have previously taken a medicine containing metamizol and had liver problems.

Severe skin reactions

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 restart treatment with Metamizol Normon at any time (see section 4).

Using Metamizol Normon with food, drinks, and alcohol

Together with alcohol, the effects of both alcohol and the medicine may 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 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 during breastfeeding should be avoided. If a single dose of metamizol is administered, mothers are recommended to 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 higher doses within the recommended range, 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.

Using Metamizol Normon with other medicines

Tell your doctor or pharmacist if you are using or have recently used or might use any other medicines.

Due to the possibility of incompatibilities, Metamizol should not be mixed with other medicines in the same syringe.

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

If administered together with chlorpromazine (a medicine for the treatment of psychoses), it may cause a decrease in body temperature.

If administered together with methotrexate or other medicines 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 platelet aggregation (antiplatelet effect) and should be used with caution in patients taking it to protect the heart (cardioprotective).

If administered together with bupropion (a medicine used for the treatment of depression and/or to help stop smoking), efavirenz (a medicine used for the treatment of HIV/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 transplant patients), or sertraline (a medicine used to treat depression), it may reduce the blood levels of these medicines, and caution should be exercised when using them together.

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

3. How to use Metamizol Normon

Follow the administration instructions for this medication exactly as indicated by your doctor. In case of doubt, consult your doctor or pharmacist again.

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

The dose is established based on the intensity of the pain or fever and the sensitivity of each person to treatment with Metamizol Normon. Metamizol Normon will be administered to you by injection into a vein or into a muscle. Accidental intra-arterial use can cause necrosis of the distal vascular area. The solution must be warmed to body temperature before injection.

If the effect of a single dose is insufficient or later, when the analgesic effect has decreased, your doctor may administer another dose until the maximum daily dose indicated below is reached.

Adults and adolescents 15 years of age or older

Adults and adolescents 15 years of age or older (who weigh more than 53 kg) may be administered 1 to 2.5 ml by intravenous or intramuscular route in a single dose; when necessary, the single dose may be increased up to 6.2 ml (corresponding to 2,480 mg of Metamizol Normon). The maximum daily dose is 10.0 ml; when necessary, the daily dose may be increased up to 12.5 ml (corresponding to 5,000 mg of metamizol).

In the indication of oncologic pain, half an ampoule may be used in a single dose by oral route up to 4 times a day, at intervals of 6 to 8 hours, corresponding to a maximum daily dose of 4,000 mg (a maximum of 2 ampoules per day). Oral use of the ampoule for the treatment of oncologic pain should not exceed 7 days.

Infants and children

The administration guideline for single doses by intravenous or intramuscular route should be used as a guide, according to the following table:

In case of fever, a dose of 10 mg of metamizol per kg of body weight is generally sufficient in children.

The effect of the medication usually appears 30 minutes after parenteral administration.

Elderly and patients with poor general health or renal insufficiency

The dose should be reduced in elderly patients, in debilitated patients, and in those with decreased renal function, since 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, repeated administration of high doses should be avoided. Only in short-term treatments is a dose reduction not necessary. There is no experience with prolonged treatments.

The contents of the ampoule should not be added to large-volume intravenous solutions for pH correction or parenteral nutrition (amino acids, lipids).

The contents of the ampoules may be incorporated into large-volume intravenous solutions such as glucose or saline solutions, but should not be mixed with other medications in the same syringe.

Precautions in intravenous administration

The most frequent cause of a drop in blood pressure and shock is excessive injection speed. Intravenous injection should be administered very slowly to minimize the risk of a hypotension reaction. Blood pressure, heart rate, and respiration should be monitored. Since the decrease in blood pressure not due to an allergic reaction is likely to be dose-dependent, the intravenous administration of a single dose of more than 1 g of metamizol magnesium should be carefully considered.

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

If you use more Metamizol Normon than you should

Nausea, vomiting, abdominal pain, deterioration of kidney function, and in rarer cases dizziness, drowsiness, coma, convulsions, drop in 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 when treatment is discontinued.

If you have used more medication than you should, consult your doctor or pharmacist, or the Toxicology Information Service, telephone 91 562 04 20.

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

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

Careful monitoring of vital functions is advised, as well as taking the necessary general measures.

If you forget to use Metamizol Normon

Donot administer a double dose to make up for forgotten doses.

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

4. Possible adverse effects

Like all medications, this medication can cause adverse effects, although not all people experience them.

Stop using Metamizol Normon 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 coloration of the skin or the white part 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.

Milder 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), 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 (decrease in blood pressure).

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

• skin rashes and reactions,
• pain at the injection site.

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

• allergic reactions that usually occur during or immediately after injection but also hours later,
• skin rashes and blisters,
• decrease in the number of white blood cells in the blood (leukopenia),
• asthma.

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

• skin reactions with blisters or bubbles (toxic epidermal necrolysis, Stevens-Johnson syndrome),
• kidney problems with decreased or suppressed urine output,
• increase in the amount of protein excreted in the urine,
• kidney inflammation (interstitial nephritis),
• severe decrease in white blood cells (agranulocytosis), which can lead to death due to severe infections,
• decrease in the number of platelets in the blood (thrombocytopenia), which can lead to inflammatory lesions in the mucous membranes, sore throat, and fever,
• shock (drastic drop in blood pressure),
• inflammation in the veins.

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

• sepsis (severe infection that involves an inflammatory reaction of the entire body and can lead to death),
• aplastic anemia (failure of the bone marrow and blood cells to produce),
• pancytopenia (low number of red, white, and platelet cells simultaneously),
• anaphylactic shock (severe allergic reaction that can lead to death),
• Kounis syndrome (a type of cardiac disorder),
• gastrointestinal bleeding,
• abnormal urine coloration,
• local reactions at the injection site,
• liver inflammation, yellowish coloration of the skin and the white part of the eyes, increased blood levels of liver enzymes.
• severe skin reactions: stop taking metamizol and seek immediate medical attention 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 redness, elevated body temperature, and enlarged lymph nodes (DRESS or drug hypersensitivity syndrome).

Reporting of adverse effects:

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

5. Conservation of Metamizol Normon

Keep this medication out of sight and reach of children.

No special storage conditions are required.

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

Medications should not be thrown down the drain or into the trash. Deposit the packaging and medications you no longer need at the SIGRE point in the pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and medications you no longer need. This will help protect the environment.

6. Package contents and additional information

Composition of Metamizol Normon

• The active principle is magnesium metamizole. Each 5 ml ampoule contains 2 g of magnesium metamizole. Each ml of solution contains 400 mg of magnesium metamizole.
• The other component is water for injectable preparations.

Appearance of the product and package contents

Transparent and slightly yellowish solution. Metamizol Normon is presented in packages of 5 ampoules, each ampoule containing 2 g of magnesium metamizole.

Marketing authorization holder and manufacturer

LABORATORIOS NORMON, S.A.

Ronda de Valdecarrizo, 6 – 28760 Tres Cantos – Madrid (SPAIN)

Date of the last revision of this prospectus: November 2024

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

You can access detailed and updated information about this medication by scanning the QR code included in the prospectus and packaging with your mobile phone (smartphone). You can also access this information at the following internet address: https://cima.aemps.es/cima/dochtml/p/63430/P_63430.html