NOLOTIL 0.4 g/ml INJECTABLE SOLUTION AND PERFUSION SOLUTION

2. What you need to know before taking Nolotil

Do not use Nolotil:

• If you have previously had a significant decrease in a type of white blood cell called granulocytes, which was caused by metamizole or other similar medicines 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 hematological reactions (decrease in white blood cells, red blood cells, or platelets in the blood) with medicines containing metamizole 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 metamizole (the active substance of Nolotil).
• If you have acute intermittent porphyria (a disorder of the metabolism of blood pigments that form 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 low blood pressure or circulation problems, you should not use Nolotil 0.4 g/ml solution for injection and infusion parenterally.
• Intra-arterial injection.
• If you have had severe skin reactions (such as Stevens-Johnson syndrome or toxic epidermal necrolysis) with previous use of Nolotil or another medicine that contained metamizole.

Warnings and Precautions

Consult your doctor or pharmacist before starting to use Nolotil.

Low White Blood Cell Count (Agranulocytosis).

Nolotil 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 metamizole 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 metamizole 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 Nolotil and even shortly after stopping metamizole.

You may develop agranulocytosis even if you have used metamizole 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 mouth or genital mucosa, 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, facial swelling, 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 problems, hypovolemia (decrease in circulating blood volume or any other body fluid), dehydration, or unstable circulation (for example, after a myocardial infarction or multiple injuries). In these cases, or if the intravenous injection has been too rapid, the risk of a sudden drop in blood pressure is higher.
• If you have decreased kidney or liver function, as you may have difficulty eliminating the medicine.
• 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 metamizole, with symptoms developing within a few days to a few months after starting treatment.

Stop using Nolotil 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 use Nolotil if you have previously taken a medicine containing metamizole 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 metamizole treatment. Stop taking metamizole 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 Nolotil at any time (see section 4).

Using Nolotil 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 metamizole 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 metamizole during the first and second trimester may be acceptable after consulting your doctor or pharmacist and carefully evaluating the benefits and risks of using metamizole. However, in general, the use of metamizole is not recommended during the first and second trimester.

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

Breastfeeding

Metamizole 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 metamizole should be avoided during breastfeeding. If a single dose of metamizole 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 ability 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 Nolotil with Other Medicines

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

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

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

If administered together with chlorpromazine (a medicine for the treatment of psychoses), it may cause a drop 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 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 medicine used for the treatment of depression and/or to help quit 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.

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

3. How to Use Nolotil

Follow your doctor's instructions for administering this medicine exactly. If you are unsure, consult your doctor or pharmacist again.

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

The dose is determined based on the intensity of the pain or fever and the individual's sensitivity to treatment with Nolotil. Nolotil will be administered to you by injection into a vein or muscle. Accidental intra-arterial use can cause necrosis of the distal vascular area. The solution should 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 injection in a single dose; when necessary, the single dose may be increased up to 6.2 ml (corresponding to 2,480 mg of Nolotil). 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 Nolotil).

In the indication of oncologic pain, half an ampoule may be used in a single dose by mouth 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). The 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 injection should be used as a guide, according to the following table:

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

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

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 metamizole degradation products may be delayed.

Patients with Renal or Hepatic Insufficiency

Since the elimination rate decreases in cases of renal or hepatic insufficiency, high repeated 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 can be incorporated into large-volume intravenous solutions such as glucose or saline solutions, but should not be mixed with other medicines in the same syringe.

Precautions in Intravenous Administration

The most common 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 magnesium metamizole 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 Nolotil Than You Should

Nausea, vomiting, abdominal pain, deterioration of kidney function, and in rarer 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 metamizole, a red coloration of the urine may occur, which disappears when treatment is stopped.

If you have used more medicine than you should, consult your doctor or pharmacist, or the Toxicology Information Service, phone 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, as metamizole 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 Use Nolotil

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

If you have any other 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 all people suffer from them.

Stop using 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 erythemas 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).

Stop using metamizol 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 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 can progress to more severe forms, e.g., generalized urticaria, swelling of feet, hands, lips, throat, and respiratory tract (angioedema), severe bronchospasm (constriction 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):

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

Rare (may affect up to 1 in 1000 people):

• allergic reactions that usually occur during or immediately after injection but also hours later,
• skin eruptions and appearance of hives,
• 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 cause death due to severe infections,
• decrease in the number of platelets in the blood (thrombocytopenia), in this case, inflammatory lesions in the mucous membranes, sore throat, and fever may occur,
• 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 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 coloration),
• local reactions at the injection site,
• liver inflammation, yellowish discoloration of the skin and the white part of the eyes, increased blood level of liver enzymes,
• severe skin reactions.

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 that is not listed in this prospectus. 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 Nolotil

Keep this medicine out of sight and reach of children.

No special storage conditions are required.

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.

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

6. Package Contents and Additional Information

Nolotil Composition

• The active ingredient 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.

Product Appearance and Package Contents

Transparent solution with a slightly yellowish color. It is presented in topaz glass ampoules with 5 ml of injectable and infusion solution.

It is available in packages containing 5 or 100 ampoules.

Only some package sizes may be marketed.

Marketing Authorization Holder:

Boehringer Ingelheim España, S.A.

Prat de la Riba, 50

08174 Sant Cugat del Vallès (Barcelona)

Spain

Manufacturer:

Boehringer Ingelheim España, S.A.

Prat de la Riba, 50

08174 Sant Cugat del Vallès (Barcelona)

Spain

Delpharm Dijon

6 Boulevard de l’Europe

21800 Quetigny

France

Date of the Last Revision of this Prospectus:November 2024

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