Prospect: Information for the User

Nolotil 0.4 g/ml injectable solution and for perfusion

Magnesium Metamizol

Read this prospect carefully before starting to use this medicine, because it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribed only to you and must not be given to other people even if they have the same symptoms as you, as it may harm them.
• If you experience adverse effects, consult your doctor or pharmacist, even if they do not appear in this prospect. See section 4.

Nolotil belongs to the group of medications known as “Other Analgesics and Antipyretics”.

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

Nolotil injectable solution and for perfusion should only be administered by parenteral route (intravenous or intramuscular injection) in cases of severe acute pain if enteral administration (oral) is not considered appropriate.

No use Nolotil:

• If you have had a significant drop in a type of white blood cells called granulocytes, which was caused by metamizol or other similar medications called pyrazolones or pyrazolidines.
• If you have problems with your bone marrow 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 spots or hives on the skin that can cause itching) during treatment with other analgesics such as acetylsalicylic acid, paracetamol, or nonsteroidal anti-inflammatory drugs, as in these cases you may also have sensitivity to metamizol (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 (producer of blood cells); for example, during or after receiving chemotherapy (antineoplastic) or if you have 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, do not use Nolotil 0.4 g/ml injectable solution and for parenteral perfusion.
• By intraarterial injection.
• If you have had severe skin reactions (such as Stevens-Johnson syndrome or toxic epidermal necrolysis) with the use of Nolotil or another medication containing metamizol.

Warnings and Precautions

Consult your doctor or pharmacist before starting to use Nolotil.

Lower than normal white blood cell count (agranulocytosis).

Nolotil may cause agranulocytosis, a very low level of a type of white blood cells called granulocytes, which are important for fighting infections (see section 4). You should stop taking metamizol 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 (moist 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 be overlooked. Similarly, symptoms may be masked if you are taking antibiotics.

Agranulocytosis can occur at any time during the use of Nolotil and even 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, mucosal lesions, bruises, bleeding, or pallor, discontinue 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, low blood pressure, sudden appearance of red spots on the skin, discontinue 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 with nasal mucosa inflammation and nasal polyps), chronic urticaria, or intolerance to dyes and/or preservatives or alcohol, as the risk of severe allergic reactions is higher.
• If you have low blood pressure or 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 liver or kidney function, as you may eliminate the medication with greater difficulty.
• If you are an elderly patient, be especially attentive to the appearance of any of the disorders described above, as they may occur more frequently.

Problems with the liver:

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

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

You should not use Nolotil if you have previously taken a medication 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, do not resume treatment with Nolotil at any time (see section 4).

Use of Nolotil with food, drinks, and alcohol

Along with alcohol, the effects of both may be potentiated.

Pregnancy, breastfeeding, and fertility

Pregnancy

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

During the last three months of pregnancy, do not take Nolotil due to the increased risk of complications for the mother and baby (bleeding, premature closure of a major 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 ruled out that there is a risk to the infant. Therefore, repeated use of metamizol during breastfeeding should be avoided. In the event of a single dose of metamizol, mothers are recommended to express and discard breast milk for 48 hours after administration.

Driving and operating machines

Although no adverse effects on concentration and reaction capacity are expected, at higher doses within the recommended range, you should be aware that these capacities may be affected, and you should avoid using machines, driving vehicles, or other hazardous activities.

Use of Nolotil with other medications

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

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

If administered together with ciclosporin (a medication that prevents transplant rejection), it may reduce ciclosporin levels in the blood and therefore these should be measured regularly.

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

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

If administered together with acetylsalicylic acid, it may reduce the effect of acetylsalicylic acid to decrease platelet aggregation (antiplaquetary) and therefore should be used with caution in patients taking it for heart protection (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 levels of these medications in the blood, and therefore should be used with caution.

Metamizol may modify the effect of antihypertensive medications (medications that reduce blood pressure) and diuretics (medications that increase the elimination of liquids).

Follow exactly the administration instructions of this medication 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 Nolotil. Nolotil will be administered through injection into a vein or muscle. Accidental intraarterial use may 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 to reach the maximum daily dose indicated below.

Adults and adolescents 15 years of age or older

To adults and adolescents 15 years of age or older (who weigh more than 53 kg), 1 to 2.5 ml can be administered via intravenous or intramuscular injection in a single dose; when necessary, the single dose can be increased to 6.2 ml (corresponding to 2,480 mg of Nolotil). The maximum daily dose is 10.0 ml; when necessary, the daily dose can be increased to 12.5 ml (corresponding to 5,000 mg of Nolotil).

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

Infants and children

A dosage guide for single doses via intravenous or intramuscular injection is provided in the following table:

In the 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.

Older adults and patients with poor general health or renal insufficiency

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

Patients with renal or hepatic insufficiency

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

Precautions for 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 hypotensive reaction. Blood pressure, heart rate, and respiration should be monitored. Since the drop 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 considered carefully.

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

Using more Nolotil than you should

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

After administration of very high doses of metamizol, a reddish discoloration 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 Toxicological 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 metamizol is dialyzable.

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

Careful monitoring of vital functions and taking general measures is recommended.

If you forgot to use Nolotil

Do not administer a double dose to compensate for the missed doses.

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

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Stop using metamizol and seek medical attention immediately if you observe any of the following severe side effects:

• Flat red patches, or circular or target-shaped patches on the chest, often with central blisters, skin peeling, mouth ulcers, throat, nose, genital, and eye ulcers. These severe skin eruptions may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome, toxic epidermal necrolysis).
• Generalized erythema, elevated body temperature, and lymph node enlargement (DRESS syndrome or drug hypersensitivity syndrome).

Stop using metamizol and contact a doctor immediately if you experience any of the following symptoms:

Nausea or vomiting, fever, fatigue, loss of appetite, dark urine, light-colored stools, yellow discoloration of the skin or white part of the eyes, itching, rash, or stomach pain. 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 bronchial walls), heart rhythm disturbances, and decreased blood pressure (sometimes preceded by increased blood pressure).

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

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

• hypotension (decreased blood pressure).

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

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

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

• Allergic reactions that usually occur during or shortly after injection but also hours later,
• skin eruptions and appearance of blisters,
• decreased white blood cell count in blood (leucopenia),
• asthma.

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

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

Frequency unknown (cannot be estimated from available data):

• sepsis (severe infection that involves a systemic inflammatory reaction and may cause death),
• aplastic anemia (failure in the production of bone marrow and blood cells),
• pancytopenia (low count of red and white blood cells and platelets simultaneously),
• anaphylactic shock (severe allergic reaction that may cause death),
• Kounis syndrome (a type of cardiac disorder),
• gastrointestinal bleeding,
• cyanosis (abnormal coloration of urine),
• local reactions at the injection site,
• inflammation of the liver, yellow discoloration of the skin and white part of the eyes, increased liver enzyme levels in blood,
• severe skin reactions.

Reporting of side effects:

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

Keep this medication out of the 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 disposed of through drains or in the trash. Dispose of packaging and unused medications at the SIGRE collection point at the pharmacy. If in doubt, ask your pharmacist how to dispose of unused packaging and medications. By doing so, you will help protect the environment.

Composition of Nolotil

• The active ingredient is metamizol magnesium. Each 5 ml ampoule contains 2 g of metamizol magnesium. Each ml of solution contains 400 mg of metamizol magnesium.
• The other component is water for injection preparations.

Appearance of the product and contents of the packaging

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

It is available in packaging containing 5 or 100 ampoules.

Only some sizes of packaging may be marketed.

Marketing Authorization Holder:

Boehringer Ingelheim España, S.A.

Prat de la Riba, 50

08174 Sant Cugat del Vallès (Barcelona)

Spain

Responsible for manufacturing:

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

Last review date of this leaflet:November 2024

The detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/.