Nolotil 0,4 g/ml solution for injection and infusion

Package leaflet: Information for the user

Introduction

Package leaflet: Information for the user

Nolotil 0.4 g/ml solution for injection and infusion

Metamizole sodium magnesium

Read the entire leaflet carefully before you start using 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 other people, even if they have the same symptoms as you, because 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 Nolotil is and what it is used for
2. What you need to know before using Nolotil
3. How to use Nolotil
4. Possible adverse effects
5. How to store Nolotil
6. Contents of the pack and other information

1. What Nolotil is and what it is used for

Nolotil 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.

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

2. What you need to know before using Nolotil

Do not use Nolotil:

• If you have previously experienced 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 bone marrow problems or a disorder affecting the production or function of your blood cells.
• If you have previously had 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 allergic reactions to any of the other components of this medicine (listed in section 6).
• If you have experienced symptoms of asthma, rhinitis, or urticaria (reddish spots or hives on the skin that may cause itching) during treatment 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 Nolotil).
• If you suffer from acute intermittent porphyria (a disorder of blood pigment metabolism involved in hemoglobin formation).
  • If you have a genetic deficiency of glucose-6-phosphate dehydrogenase.
  • If you have experienced disturbances in bone marrow function (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 low blood pressure or circulatory problems, do not use Nolotil 0.4 g/ml injectable and parenteral infusion solution.
  • In intra-arterial injection.
  • If you have previously experienced very severe skin reactions (such as Stevens-Johnson syndrome or toxic epidermal necrolysis) with prior use of Nolotil or another medicine containing metamizole.

Warnings and precautions

Consult your doctor or pharmacist before starting to use Nolotil.

Lower than normal white blood cell count (agranulocytosis).

Nolotil can 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 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 mucous membranes (moist 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 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 Nolotil use 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 mucosa 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), platelets (thrombocytopenia), or failure in the production of all blood cells (aplastic anemia).
• If you experience dizziness, difficulty breathing, rhinitis, facial swelling, drop in blood pressure, or sudden appearance of reddish spots 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 suffer from asthma or allergic-type disorders (atopy).
• If you have bronchial asthma (especially in the presence of inflammation of the nasal mucosa and nasal polyps), chronic urticaria, or if you are intolerant to dyes and/or preservatives or alcohol, as the risk of possible severe allergic reactions is higher.
• If you have low blood pressure, hypovolemia (reduction in circulating blood volume or any other body fluid), dehydration, or unstable circulation (e.g., after acute myocardial infarction or multiple injuries). In these cases, or if intravenous injection has been too rapid, the risk of a sudden drop in blood pressure is higher.
• If you have impaired kidney or liver function, as you may eliminate the medicine with greater difficulty.
• If you are elderly, pay special attention to the occurrence of any of the disorders described above, as they may appear more frequently.

Liver problems:

Liver inflammation has been reported in patients taking metamizole, with symptoms developing from 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 malaise (nausea or vomiting), fever, feeling of fatigue, loss of appetite, dark urine, pale stools, yellowing of the skin or whites of the eyes, itching, rash, or upper abdominal pain. Your doctor will check your liver function.

You must not use Nolotil if you have previously taken any medicine containing metamizole and experienced 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 immediate medical attention if you notice any of the symptoms related to these severe skin reactions described in section 4.

If you have ever experienced severe skin reactions, you must not resume treatment with Nolotil at any time (see section 4).

Use of Nolotil with food, drinks, and alcohol

When taken with alcohol, the effects of both alcohol and the drug may be enhanced.

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 when 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 carefully evaluating the benefits and risks of using metamizole. However, in general, the use of metamizole during the first and second trimesters is not recommended.

During the last three months of pregnancy, you must not take Nolotil 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

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

Driving and using machines

Although adverse effects on concentration and reaction ability are not expected, at the higher end of the recommended doses, it should be taken into account that these abilities may be affected, and the use of machinery, driving vehicles, or other hazardous activities should be avoided.

Use of Nolotil with other medicines

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

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

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

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

If administered concomitantly with methotrexate or other antitumor medicines (antineoplastics), it may enhance the blood toxicity of antineoplastics, especially in elderly patients.

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

If administered concomitantly with bupropion (a medicine used to treat depression and/or to help quit smoking), efavirenz (a medicine used to treat HIV/AIDS), methadone (a medicine used to treat dependence on illicit 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, and therefore should be used with caution.

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

3. How to use Nolotil

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

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

The dose is determined according to the intensity of pain or fever and to the individual's sensitivity to treatment with Nolotil. Nolotil will be administered by injection into a vein or into a muscle. Accidental intra-arterial administration 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 diminished, your doctor may administer another dose, up to the maximum daily dose indicated below.

Adults and adolescents aged 15 years and older

For adults and adolescents aged 15 years and older (weighing more than 53 kg), a single dose of 1 to 2.5 ml may be administered intravenously or intramuscularly; if 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; if necessary, the daily dose may be increased up to 12.5 ml (corresponding to 5,000 mg of Nolotil).

In the indication of oncological pain, half an ampoule may be used orally as a single dose up to 4 times daily 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 oncological pain should not exceed 7 days.

Infants and children

The following table should be used as a guide for single-dose administration intravenously or intramuscularly:

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 within 30 minutes after parenteral administration.

Elderly individuals and patients with poor general health or renal insufficiency

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

Patients with renal or hepatic insufficiency

Since elimination rate decreases in cases of renal or hepatic insufficiency, repeated administration of high doses should be avoided. For short-term treatment, dose reduction is not necessary. Experience with prolonged treatment is lacking.

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

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

Precautionary measures for intravenous administration

The most common cause of a drop in blood pressure and shock is excessive injection speed. Intravenous injection must be administered very slowly to minimize the risk of hypotensive reaction. Blood pressure, heart rate, and respiration should be monitored. Since non-allergic hypotension is likely dose-dependent, administration of a single intravenous dose exceeding 1 g of metamizole sodium should be carefully considered.

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

If you use more Nolotil than you should

Nausea, vomiting, abdominal pain, impaired kidney function, and less commonly dizziness, somnolence, coma, seizures, decreased blood pressure, or even shock and increased heart rate (tachycardia) may occur.

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

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

Information for the physician: No specific antidote is known. After 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, maintaining airways free of obstruction, or administering oxygen. Pharmacological emergency measures include administration of adrenaline, fluid therapy, and glucocorticoids.

Careful monitoring of vital functions is advised, together with implementation of necessary general measures.

If you forget to use Nolotil

Do not administer 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 will experience them.

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

• Flat red patches, or circular or target-shaped rashes on the chest, frequently with central blisters, skin peeling, ulcers in the mouth, throat, nose, genitals, and eyes. These severe skin rashes may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome, toxic epidermal necrolysis).
• Generalized erythema, elevated body temperature, and enlarged lymph nodes (DRESS syndrome or drug hypersensitivity syndrome).

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

Feeling unwell (nausea or vomiting), fever, fatigue, 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 the feet, hands, lips, throat, and airways (angioedema), severe bronchospasm (narrowing of the bronchial walls), changes in heart rhythm, 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 skin reactions,
• pain at the injection site.

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

• allergic reactions, usually occurring during or shortly after injection, but also several hours later,
• skin rashes and appearance of wheals on the skin,
• 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 the appearance of blisters or vesicles (toxic epidermal necrolysis, Stevens-Johnson syndrome),
• kidney problems with reduced or suppressed urine output,
• increased excretion of protein in the urine,
• inflammation of the kidney (interstitial nephritis),
• severe decrease in white blood cells (agranulocytosis), which may lead to death due to severe 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),
• inflammation of the veins.

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

• sepsis (a serious infection causing a systemic inflammatory response that may be fatal),
• aplastic anemia (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 bleeding,
• chromaturia (abnormal discoloration of urine),
• local reactions at the injection site,
• liver inflammation, yellowing of the skin and whites of the eyes, increased blood levels 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 they are possible adverse effects not listed in this leaflet. You can also report them directly via the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse effects, you can help provide 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 expiry date stated on the packaging after EXP. The expiry date is the last day of the month indicated.

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

6. Contents of the pack and other information

Composition of Nolotil

• The active substance 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 injections.

Appearance of the product and contents of the pack

A slightly yellowish, transparent solution. It is supplied in 5 ml amber glass ampoules containing injectable and perfusion solution.

Available in packs containing 5 or 100 ampoules.

Only certain pack 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 most recent revision of this leaflet: November 2024

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