Label: information for the user

Daptomicin Normon 500mgpowder for injectable solution and for EFG infusion

daptomicin

Read this label carefully before starting to use this medication, as it contains important information for you.

• Keep this label, as you may need to read it again.
• If you have any questions, consult your doctor or nurse.
• This medication has been prescribed only to you, 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 any adverse effects, consult your doctor or nurse, even if they are not listed in this label. See section 4.

The active ingredient of Daptomicina Normon powder for injectable solution and for infusion is daptomycin. Daptomycin is an antibacterial capable of stopping the growth of certain bacteria. Daptomycin is used in adults and in children and adolescents (ages 1 to 17 years) to treat skin and soft tissue infections. It is also used to treat blood infections when associated with a skin infection.

Daptomycin is also used in adults to treat infections in the tissues that cover the inside of the heart (including heart valves), caused by a type of bacteria called Staphylococcus aureus..It is also used to treat blood infections caused by the same type of bacteria when associated with a heart infection..

Depending on the type of infection(s) you have, your doctor may also prescribe other antibacterials while you receive treatment with daptomycin.

Do not receive Daptomicina Normon

If you are allergic to daptomycin or to sodium hydroxide or to any of the other components of this medication (listed in section 6).

If this is your case, inform your doctor or nurse. If you think you may be allergic, consult your doctor or nurse.

Warnings and precautions

Consult your doctor or nurse before starting to receive daptomycin:

• If you have or have had kidney problems. Your doctor may need to change the dose of daptomycin (see section 3 of this leaflet).
• Occasionally, patients receiving daptomycin may develop increased sensitivity, muscle pain or weakness (see section 4 of this leaflet for more information). Inform your doctor if this happens. Your doctor will ensure that you have a blood test and advise you whether it is recommended or not to continue using daptomycin. Symptoms usually disappear within a few days after stopping treatment with daptomycin.
• If you have ever had, after taking daptomycin, a severe skin rash or skin peeling, blisters and/or mouth sores, or serious kidney problems.
• If you have significant overweight, there is a possibility that your blood levels of daptomycin may be higher than those found in people of average weight, and that you may therefore need closer monitoring in cases of adverse effects.

If any of the above cases affect you, inform your doctor or nurse before receiving daptomycin.

Inform your doctor or nurse immediately if you develop any of the following symptoms:

• Severe and serious allergic reactions have been observed in patients treated with almost all antibacterial agents, including daptomycin. Symptoms may include rapid breathing, difficulty breathing, facial, neck and throat inflammation, skin rash and urticaria, or fever.
• Severe skin diseases have been reported with the use of daptomycin. Symptoms that occur with these skin diseases may include:
• • fever or worsening of fever,
  • red skin patches raised or filled with fluid, which may start in the armpits or in areas of the chest or groin and may spread over a large area of the body,
  • mouth sores or genital sores.
• Severe kidney problems have been reported with the use of daptomycin. Symptoms may include fever and rash.
• Any type of tingling or numbness in the hands or feet, loss of sensation or unusual difficulty moving. If this occurs, inform your doctor, who will decide whether you should continue treatment.
• Diarhea, especially if you notice blood or mucus in your stools or if diarrhea becomes severe or lasts long.
• Onset of fever or worsening of fever, cough or difficulty breathing. These may be signs of a rare but serious lung function deterioration called eosinophilic pneumonia. Your doctor will check your lung function and decide whether you should continue treatment with daptomycin.

Daptomycin may interfere with laboratory tests that measure your blood's clotting ability. Results may appear to suggest poor clotting, despite the fact that there is no actual problem. Therefore, it is essential that your doctor is aware that you are receiving daptomycin. Inform your doctor that you are on daptomycin treatment.

Your doctor will perform blood tests to monitor your muscle health, before starting treatment and frequently during treatment with daptomycin.

Children and adolescents

Daptomycin should not be administered to children under one year of age, as animal studies have shown that this age group may experience severe adverse effects.

Use in elderly patients

Elderly patients over 65 years of age may receive the same dose as other adults, provided their kidneys function correctly.

Other medications and Daptomicina Normon

Inform your doctor or nurse if you are using, have used recently or may need to use any other medication. It is particularly important to mention the following:

• Medications called statins or fibrates (to lower cholesterol) or cyclosporine (a medication used in transplants to prevent organ rejection or for other conditions, e.g. rheumatoid arthritis or atopic dermatitis). There may be an increased risk of muscle adverse effects if you take any of these medications (and others that may affect muscles) during treatment with daptomycin. Your doctor may decide not to administer daptomycin or temporarily interrupt treatment with the other medication.
• Pain-relieving medications called non-steroidal anti-inflammatory drugs (NSAIDs) or COX-2 inhibitors (e.g. celecoxib). These may interfere with the elimination of daptomycin by the kidneys.
• Oral anticoagulants (e.g. warfarin), which are medications that prevent blood clotting. Your doctor may need to monitor your blood clotting times.

Pregnancy and breastfeeding

Daptomycin is generally not administered to pregnant women. If you are pregnant or breastfeeding, or think you may be pregnant or intend to become pregnant, consult your doctor or pharmacist before using this medication.

Do not breastfeed while receiving daptomycin, as it may pass into breast milk and affect the baby.

Driving and operating machinery

Daptomycin has no known effects on the ability to drive or operate machinery.

Daptomina Normon contains sodium

This medication contains less than 1 mmol of sodium (23 mg) per dose, which is essentially "sodium-free".

Daptomicina will be administered by your doctor or nurse as usual.

Adults (18 years of age and older)

The dose will depend on your weight and the type of infection being treated. The usual dose for adults is 4 mg per kilogram of body weight once a day for skin infections or 6 mg per kilogram of body weight once a day for heart infections or blood infections associated with skin or heart infections. In adult patients, this dose is administered directly into your bloodstream (in a vein), either as an infusion lasting approximately 30 minutes or as an injection lasting approximately 2 minutes. The same dose is recommended for people over 65 years old, provided their kidneys function properly.

If your kidneys do not function well, you may receive daptomicina less frequently, for example, once every other day. If you are undergoing dialysis and your next daptomicina dose is due on a dialysis day, you will usually receive daptomicina after the dialysis session.

Children and adolescents (1 to 17 years of age)

The recommended doses in children and adolescents (1 to 17 years) will depend on the patient's age and the type of infection being treated. This dose is administered directly into the bloodstream (in a vein), as an infusion lasting approximately 30-60 minutes.

A complete treatment for skin infections usually lasts between 1 and 2 weeks. Your doctor will decide the duration of your treatment for blood or heart infections and for skin infections.

Instructions for use and handling are provided in detail at the end of the prospectus.

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

The following are the most serious side effects:

Severe side effects with unknown frequency(cannot be estimated from available data)

• During daptomycin administration, some cases of hypersensitivity reactions (severe allergic reactions including anaphylaxis and angioedema) have been reported. These severe allergic reactions require immediate medical attention. Inform your doctor or nurse immediately if you experience any of the following symptoms:
• Chest pain or pressure,
• Rash or hives,
• Swelling around thethroat,
• Fast or weak pulse,
• Labored breathing,
• Fever,
• Chills or tremors,
• Headache,
• Dizziness,
• Fainting,
• Metallic taste.
• Consult your doctor immediately if you experience pain, increased sensitivity, or muscle weakness of unknown origin. Muscle problems can be severe, including muscle degradation (rhabdomyolysis), which can cause kidney damage.

Other side effects reported with the use of daptomycin are:

• A rare but potentially severe lung condition called eosinophilic pneumonia, mostly after more than 2 weeks of treatment. Symptoms may include difficulty breathing, coughing, or worsening of cough, or fever or worsening of fever.
• Severe skin diseases. Symptoms may include:
• Fever or worsening of fever,
• Red patches on the skin that are raised or filled with fluid, which may start in the armpits or in areas of the chest or groin and may spread to a large area of the body,
• Blisters or sores in the mouth or genitals.
• A severe kidney problem. Symptoms may include fever and rash.

If you experience these symptoms, inform your doctor or nurse immediately. Your doctor will perform additional tests to establish a diagnosis.

The following are the side effects reported most frequently:

Frequent side effects(may affect up to 1 in 10 patients)

• Fungal infections, such as mouth ulcers,
• Urinary tract infection,
• Decreased red blood cell count (anemia),
• Dizziness, anxiety, difficulty falling asleep,
• Headache,
• Fever, weakness (asthenia),
• High or low blood pressure,
• Constipation, abdominal pain,
• Diarrhea, nausea or vomiting,
• Flatulence,
• Abdominal swelling or distension,
• Rash or itching,
• Pain, itching, or redness at the infusion site,
• Pain in arms or legs,
• Elevated liver enzyme or creatine phosphokinase (CPK) levels in blood tests.

The following are other side effects that may occur after treatment with daptomycin:

Rare side effects(may affect up to 1 in 100 patients)

• Blood disorders (e.g., increased platelet count, which may increase the tendency to develop blood clots, or increased count of certain types of white blood cells),
• Loss of appetite,
• Tickling or numbness in the hands or feet, alterations in taste,
• Tremors,
• Changes in heart rhythm, hot flashes,
• Indigestion (dyspepsia), inflammation of the tongue,
• Rash with itching,
• Muscle pain, cramps, or weakness, muscle inflammation (myositis), joint pain,
• Kidney problems,
• Inflammation and irritation of the vagina,
• Elevated blood sugar, creatinine, myoglobin, or lactate dehydrogenase (LDH) levels, increased blood clotting time, or electrolyte imbalance in blood tests,
• Itching eyes.

Rare side effects(may affect up to 1 in 1,000 patients)

• Yellowing of the skin and eyes (jaundice),
• Increased prothrombin time.

Unknown frequency(cannot be estimated from available data)

• Antibiotic-associated colitis, including pseudomembranous colitis (severe or persistent diarrhea containing blood and/or mucus, associated with abdominal pain or fever), bruising with increased ease, bleeding gums, or nasal bleeding.

Reporting side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, 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 the 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.

Do not use this medication after the expiration date that appears on the box and the bottle after “CAD”. The expiration date is the last day of the month indicated.

-Store in refrigerator (between 2°C and 8°C).

Medicines should not be thrown down the drains or in the trash. Dispose of the containers and medicines you no longer need at the SIGRE collection point of the pharmacy. If in doubt, ask your pharmacist how to dispose of the containers and medicines you no longer need. By doing so, you will help protect the environment.

Composition ofDaptomycin Normon

• The active ingredient is daptomycin. A vial of powder contains 500 mg of daptomycin.
• The other component is sodium hydroxide.

Appearance of the product and contents of the container

Daptomycin Normon powder for injectable solution and for infusion is presented in a glass vial as a powder or cake of pale yellow to light brown color. It is mixed with a solvent to form a solution before administration.

Daptomycin Normon is presented in containers containing 1 vial.

Holder of the marketing authorization and responsible for manufacturing

LABORATORIOS NORMON, S.A.

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

Last review date of this leaflet:September 2021

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

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This information is intended solely for healthcare professionals:

Important: Please consult the Technical Data Sheet or Summary of Product Characteristics before prescribing.

Instructions for use and handling

500 mg presentation:

In adults, daptomycin can be administered intravenously as a 30-minute infusion or as a 2-minute injection. Unlike adults, daptomycin should not be administered to pediatric patients as a 2-minute injection. Pediatric patients aged 7 to 17 years should receive daptomycin as a 30-minute infusion. Pediatric patients under 7 years of age who receive doses of 9-12 mg/kg should be administered daptomycin as a 60-minute infusion. The preparation of the infusion solution requires an additional dilution phase, as described below.

Daptomycin Normon administered as an intravenous infusion over 30 or 60 minutes

Reconstituting the lyophilized product with 10 ml of a 9 mg/ml sodium chloride (0.9%) injection solution can obtain a 50 mg/ml daptomycin Normon infusion solution concentration.

The lyophilized product takes approximately 15 minutes to dissolve. The fully reconstituted product has a transparent appearance and may present small bubbles or foam around the vial rim.

To prepare daptomycin Normon for intravenous infusion, follow the instructions below:

To reconstitute or dilute daptomycin Normon lyophilized, aseptic technique must be used throughout the process.

For reconstitution:

1. Remove the polipropylene "flip-off" cap to expose the central part of the rubber stopper. Clean the top of the rubber stopper with an alcohol-soaked cotton swab or other antiseptic solution and let it dry. After cleaning, do not touch the rubber stopper, nor allow it to touch any other surface. Using a sterile transfer needle of calibre 21 or smaller, or a device without a needle, extract 10 ml of a 9 mg/ml sodium chloride (0.9%) injection solution and inject it slowly through the center of the rubber stopper into the vial, pointing the needle towards the vial wall.
2. The vial should be gently rotated to ensure the product is fully moistened, and then left to stand for 10 minutes.
3. Finally, the vial should be gently rotated/agitated for a few minutes to obtain a transparent reconstituted solution. Vigorous agitation should be avoided to prevent foam formation.
4. The reconstituted solution should be carefully inspected before use to ensure the substance is dissolved and to verify the absence of particles in suspension. The color of the reconstituted daptomycin Normon solution may vary from pale yellow to light brown.
5. The reconstituted solution should be diluted with 9 mg/ml sodium chloride (0.9%) (typical volume of 50 ml).

For dilution:

1. Remove the reconstituted solution (50 mg daptomycin/ml) from the vial using a new sterile needle of calibre 21 or smaller. Invert the vial to allow the solution to flow towards the rubber stopper. Using a syringe, insert the needle into the inverted vial. Keeping the vial inverted, place the needle tip in the lowest part of the liquid while extracting the solution into the syringe. Before removing the needle from the vial, pull the plunger back to the end of the syringe barrel to remove the required solution from the inverted vial.
2. Expel air, large bubbles, and any excess solution to obtain the required dose.

1. Transfer the reconstituted solution to 50 ml of 9 mg/ml sodium chloride (0.9%).
2. The reconstituted and diluted solution should be infused intravenously over 30 or 60 minutes.

Daptomycin Normon is not physically or chemically compatible with solutions containing glucose. The following drugs have been shown to be compatible when added to infusion solutions containing daptomycin Normon: aztreonam, ceftazidime, ceftriaxone, gentamicin, fluconazole, levofloxacin, dopamine, heparin, and lidocaine.

The combined storage time (reconstituted solution in the vial and diluted solution in infusion bags) at 25°C should not exceed 12 hours (24 hours if refrigerated).

The stability of the diluted solution in infusion bags has been established for 12 hours at 25°C or 24 hours if refrigerated at 2°C – 8°C.

Daptomycin Normon administered as an intravenous injection over 2 minutes (only for adult patients)

Water should not be used for reconstituting daptomycin Normon for intravenous injection. Daptomycin Normon should only be reconstituted with 9 mg/ml sodium chloride (0.9%).

Reconstituting the lyophilized product with 10 ml of a 9 mg/ml sodium chloride (0.9%) injection solution can obtain a 50 mg/ml daptomycin Normon injection solution concentration.

The lyophilized product takes approximately 15 minutes to dissolve. The fully reconstituted product has a transparent appearance and may present small bubbles or foam around the vial rim.

To prepare daptomycin Normon for intravenous injection, follow the instructions below:

To reconstitute daptomycin Normon lyophilized, aseptic technique must be used throughout the process.

1. Remove the polipropylene "flip-off" cap to expose the central part of the rubber stopper. Clean the top of the rubber stopper with an alcohol-soaked cotton swab or other antiseptic solution and let it dry. After cleaning, do not touch the rubber stopper, nor allow it to touch any other surface. Using a sterile transfer needle of calibre 21 or smaller, or a device without a needle, extract 10 ml of a 9 mg/ml sodium chloride (0.9%) injection solution and inject it slowly through the center of the rubber stopper into the vial, pointing the needle towards the vial wall.
2. The vial should be gently rotated to ensure the product is fully moistened, and then left to stand for 10 minutes.
3. Finally, the vial should be gently rotated/agitated for a few minutes to obtain a transparent reconstituted solution. Vigorous agitation should be avoided to prevent foam formation.
4. The reconstituted solution should be carefully inspected before use to ensure the substance is dissolved and to verify the absence of particles in suspension. The color of the reconstituted daptomycin Normon solution may vary from pale yellow to light brown.
5. Remove the reconstituted solution (50 mg daptomycin/ml) from the vial using a sterile needle of calibre 21 or smaller.
6. Invert the vial to allow the solution to flow towards the rubber stopper. Using a new syringe, insert the needle into the inverted vial. Keeping the vial inverted, place the needle tip in the lowest part of the liquid while extracting the solution into the syringe. Before removing the needle from the vial, pull the plunger back to the end of the syringe barrel to remove the solution from the inverted vial.
7. Replace the needle with a new one for intravenous injection.
8. Expel air, large bubbles, and any excess solution to obtain the required dose.

The reconstituted solution should be injected slowly intravenously over 2 minutes.

The physical and chemical stability during use of the reconstituted solution in the vial has been demonstrated for 12 hours at 25°C and up to a maximum of 48 hours if refrigerated (2°C – 8°C).

However, from a microbiological point of view, the product should be used immediately. If not used immediately, the storage time during use is the responsibility of the user and, normally, should not exceed 24 hours at 2°C - 8°C, unless the reconstitution/dissolution took place in controlled and validated aseptic conditions.

This medicine should not be mixed with other medicines that are not mentioned above. The Daptomycin Normon vials are exclusively for single use. Any remaining vial that has not been used should be discarded.