DAPTOMYCIN NORIDEM 500 mg POWDER FOR INJECTABLE SOLUTION AND FOR INFUSION

2. What you need to know before you are given Daptomicina Noridem

You should not be given Daptomicina Noridem

• If you are allergic to daptomycin or any of the other ingredients of this medicine (listed in section 6).

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

Warnings and precautions

Tell your doctor or nurse before you start receiving Daptomicina Noridem:

• If you have or have had kidney problems in the past. Your doctor may need to change the dose of Daptomicina Noridem (see section 3 of this leaflet).
• Occasionally, patients receiving Daptomicina Noridem may develop increased sensitivity, pain, or muscle weakness (see section 4 of this leaflet for more information). Tell your doctor if this happens. Your doctor will make sure you have a blood test and advise whether or not it is recommended to continue using Daptomicina Noridem. The symptoms usually go away within a few days after stopping treatment with Daptomicina Noridem.
• If you have ever had a severe skin rash or skin peeling, blisters, and/or sores in the mouth, or severe kidney problems after taking daptomycin.
• If you are significantly overweight, there is a possibility that your blood levels of Daptomicina Noridem may be higher than those found in people of average weight, and you may need stricter monitoring for side effects.

If any of the above applies to you, tell your doctor or nurse before you receive Daptomicina Noridem.

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

• Severe and serious allergic reactions have been reported in patients treated with almost all antibacterial agents, including daptomycin. The symptoms can include wheezing, difficulty breathing, swelling of the face, neck, and throat, skin rash, and hives, or fever.
• Severe skin diseases have been reported with the use of Daptomicina Noridem. The symptoms that occur with these skin diseases can include:
• • onset of fever or worsening of it,
  • red spots on the skin that are raised or filled with fluid, which can start in the armpits or in areas of the chest or groin and can spread over a large area of the body,
  • blisters or sores in the mouth or genitals.
• Severe kidney problems have been reported with the use of Daptomicina Noridem. The symptoms can include fever and rash.
• Any type of tingling or numbness in the hands or feet, loss of sensation, or unusual movement difficulties. If this happens, tell your doctor, who will decide whether or not to continue treatment.
• Diarrhea, especially if you notice the presence of blood or mucus in your stool or if the diarrhea becomes severe or lasts a long time.
• Onset of fever or worsening of it, cough, or difficulty breathing. These can be signs of a rare but serious lung problem called eosinophilic pneumonia. Your doctor will check the condition of your lungs and decide whether or not to continue treatment with Daptomicina Noridem.

Daptomicina Noridem may interfere with laboratory tests that measure the blood's ability to clot. The results may appear to suggest poor clotting, even if there is no actual problem. Therefore, it is essential that your doctor is aware that you are receiving Daptomicina Noridem. Tell your doctor that you are being treated with Daptomicina Noridem.

Your doctor will perform blood tests to monitor the health of your muscles before you start treatment and frequently during treatment with Daptomicina Noridem.

Children and adolescents

Daptomicina Noridem should not be given to children under 1 year of age. Animal studies have shown that this age group may experience severe side effects.

Use in elderly patients

Patient over 65 years of age may receive the same dose as other adults, provided their kidneys are working correctly.

Other medicines and Daptomicina Noridem

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

It is particularly important that you mention the following:

• Medicines called statins or fibrates (to lower cholesterol) or cyclosporin (a medicine used in transplants to prevent organ rejection or for other conditions, e.g., rheumatoid arthritis or atopic dermatitis). It is possible that the risk of muscle side effects may increase if you take any of these medicines (and others that may affect the muscles) during treatment with Daptomicina Noridem. Your doctor may decide not to give you Daptomicina Noridem or temporarily stop treatment with the other medicine.
• Pain-relieving medicines called non-steroidal anti-inflammatory drugs (NSAIDs) or COX-2 inhibitors (e.g., celecoxib). These may interfere with the elimination of Daptomicina Noridem by the kidneys.
• Oral anticoagulants (e.g., warfarin), which are medicines that prevent blood clotting. Your doctor may need to monitor your blood clotting times.

Pregnancy and breastfeeding

Daptomicina Noridem is not usually given to pregnant women. If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

You should not breastfeed if you are receiving Daptomicina Noridem, as it may pass into breast milk and affect the baby.

Driving and using machines

Daptomicina Noridem has no known effects on the ability to drive or use machines.

Daptomicina Noridem contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per vial; this is essentially "sodium-free".

3. How Daptomicina Noridem is given

Daptomicina Noridem will be given to you by your doctor or nurse.

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 kg of body weight once a day for skin infections or 6 mg per kg of body weight once a day for heart or blood infections associated with skin infections. In adult patients, this dose is administered directly into your bloodstream (into a vein), either as an infusion that lasts about 30 minutes or as an injection that lasts about 2 minutes. The same dose is recommended for people over 65 years of age, provided their kidneys are working correctly.

If your kidneys do not work well, you may receive Daptomicina Noridem less frequently, e.g., every other day. If you are undergoing dialysis and your next dose of Daptomicina Noridem is due on a dialysis day, you will usually receive Daptomicina Noridem 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 (into a vein), as an infusion that lasts about 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.

Detailed instructions for use and handling are provided at the end of the leaflet.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

The following are described the most serious side effects:

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

• Some cases of hypersensitivity reactions (severe allergic reactions including anaphylaxis and angioedema) have been reported during the administration of daptomycin. These severe allergic reactions require immediate medical attention. Tell your doctor or nurse immediately if you have any of the following symptoms:
• Chest pain or pressure,
• Rash or hives,
• Swelling around the throat,
• Fast or weak pulse,
• Wheezing,
• Fever,
• Chills or shivering,
• Flushing,
• Dizziness,
• Fainting,
• Metallic taste.

Tell your doctor immediately if you have pain, increased sensitivity, or muscle weakness of unknown origin. Muscle problems can be severe, including muscle breakdown (rhabdomyolysis), which can cause kidney damage.

Other side effects that have been reported with the use of Daptomicina Noridem are:

• A rare but potentially serious lung condition called eosinophilic pneumonia, mostly after more than 2 weeks of treatment. The symptoms can include difficulty breathing, onset of cough or worsening of it, or onset of fever or worsening of it.
• Severe skin diseases. The symptoms can include:
• onset of fever or worsening of it,
• red spots on the skin that are raised or filled with fluid, which can start in the armpits or in areas of the chest or groin and can spread over a large area of the body,
• blisters or sores in the mouth or genitals.
• A severe kidney problem. The symptoms can include fever and rash.

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

The following are described the most frequently reported side effects:

Common(may affect up to 1 in 10 people)

• Fungal infections, such as thrush (mouth ulcers),
• Urinary tract infection,
• Decrease in the number of red blood cells (anemia),
• Dizziness, anxiety, difficulty sleeping,
• Headache,
• Fever, weakness (asthenia),
• High or low blood pressure,
• Constipation, abdominal pain,
• Diarrhea, nausea or vomiting,
• Flatulence,
• Abdominal swelling or abdominal distension,
• Skin rash or itching,
• Pain, itching, or redness at the infusion site,
• Pain in arms or legs,
• High levels of liver enzymes or creatine phosphokinase (CPK) in blood tests.

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

Uncommon(may affect up to 1 in 100 people)

• Blood disorders (e.g., increased platelet count, which can increase the tendency to develop blood clots, or increased white blood cell count),
• Decreased appetite,
• Numbness or tingling in the hands or feet, altered taste,
• Tremors,
• Changes in heart rhythm, flushing,
• Indigestion (dyspepsia), tongue inflammation,
• Itchy rash,
• Muscle pain, cramps, or weakness, muscle inflammation (myositis), joint pain,
• Kidney problems,
• Vaginal inflammation and irritation,
• Generalized pain or weakness, fatigue (fatigue),
• High blood sugar, serum creatinine, myoglobin, or lactate dehydrogenase (LDH), prolonged blood clotting time, or electrolyte imbalance in blood tests,
• Eye itching.

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

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

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

Antibiotic-associated colitis, including pseudomembranous colitis (severe or persistent diarrhea containing blood and/or mucus, associated with abdominal pain or fever), bruising easily, gum bleeding, or nosebleeds.

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if it is possible side effects not listed in this leaflet. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Daptomicina Noridem

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton after EXP and on the label after EXP. The expiry date is the last day of the month shown.

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

After reconstitution:

The chemical and physical stability of the reconstituted solution in the vial has been demonstrated for 12 hours at 25°C and up to a maximum of 48 hours at 2°C-8°C.

After dilution:

The chemical and physical stability of the diluted solution in infusion bags has been demonstrated for 12 hours at 25°C and up to a maximum of 24 hours at 2°C-8°C.

In the case of intravenous infusion of 30 minutes duration, the combined storage time (reconstituted solution in the vial and diluted solution in the infusion bag) at 25°C should not exceed 12 hours (or 24 hours at 2°C-8°C).

In the case of intravenous injection of 2 minutes duration, the storage time of the reconstituted solution in the vial at 25°C should not exceed 12 hours (or 48 hours at 2°C-8°C).

However, from a microbiological point of view, the product should be used immediately. This product does not contain preservatives or bacteriostatic antibiotics. If not used immediately, the storage times and conditions until use are the responsibility of the user and should not generally exceed 24 hours at 2°C-8°C, unless the reconstitution/dilution has been carried out under validated and controlled aseptic conditions.

After mixing:

The chemical and physical stability of the mixtures has been established for 2 hours at 25°C.

If you notice signs of moisture or if the solution for reconstitution is not clear or contains particles in suspension, do not use this medicine.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Container Contents and Additional Information

Composition of Daptomicina Noridem

• The active ingredient is daptomycin. A vial of powder contains 350 mg or 500 mg of daptomycin. The other component is sodium hydroxide.

Appearance of the Product and Container Contents

Daptomicina Noridem is presented in a glass vial as a pale yellow to light brown powder or cake. It must be mixed with a solvent to form a solution before administration.

Daptomicina Noridem is presented in containers containing 1, 5, 10, or 50 vials.

Only some package sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Noridem Enterprises Limited

Evagorou & Makariou

Mitsi Building 3, Office 115

1065 Nicosia, Cyprus

Manufacturer

DEMO S.A. PHARMACEUTICAL INDUSTRY

21st Km National Road Athens-Lamia.

14568 Greece

This medicinal product is authorized in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:

Date of the last revision of this leaflet: October 2024

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

This information is intended only for healthcare professionals:

Important: Please consult the Summary of Product Characteristics or Package Leaflet before prescribing.

Instructions for use and handling

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

• Daptomicina Noridem administered as an intravenous infusion over 30 or 60 minutes

350 mg presentation:

Reconstituting the lyophilized product with 7 ml of an injectable solution containing 9 mg/ml of sodium chloride (0.9%), a concentration of 50 mg/ml of Daptomicina Noridem for infusion can be obtained.

500 mg presentation:

A concentration of 50 mg/ml of Daptomicina Noridem can be obtained by reconstituting the lyophilized product with 10 ml of a 0.9% sodium chloride injectable solution (9 mg/ml).

The lyophilized product takes approximately 5 minutes to dissolve. The completely reconstituted product has a transparent appearance and may present some small bubbles or foam around the edge of the vial.

To prepare Daptomicina Noridem for intravenous infusion, follow these instructions:

To reconstitute or dilute Daptomicina Noridem lyophilized product, aseptic technique must be used throughout the process.

For reconstitution:

1. The plastic "flip-off" closure cap should be removed to expose the central part of the rubber stopper. Clean the top of the rubber stopper with a cotton swab with alcohol or another antiseptic solution and let it dry. After cleaning, do not touch the rubber stopper or allow it to touch any other surface.

• In the case of Daptomicina Noridem 350 mg powder for solution for injection and infusion, withdraw 7 ml of a 0.9% sodium chloride injectable solution (9 mg/ml) into a syringe using a sterile transfer needle with a diameter of 21 gauge or less, or a needleless device, and slowly inject it through the center of the rubber stopper into the vial, aiming the needle at the vial wall.
• In the case of Daptomicina Noridem 500 mg powder for solution for injection and infusion, withdraw 10 ml of a 0.9% sodium chloride injectable solution (9 mg/ml) into a syringe using a sterile transfer needle with a diameter of 21 gauge or less, or a needleless device, and slowly inject it through the center of the rubber stopper into the vial, aiming the needle at the vial wall.

1. The vial should be gently rotated to ensure that the product is completely wetted, and then left to stand for 10 minutes.
2. Finally, the vial should be gently rotated/shaken for a few minutes until a clear reconstituted solution is obtained. Avoid vigorous shaking to prevent foam formation.
3. The reconstituted solution should be carefully inspected before use to ensure that the substance is dissolved and to verify the absence of suspended particles. The color of the reconstituted solution of Daptomicina Noridem may vary from pale yellow to light brown.
4. The reconstituted liquid should be slowly withdrawn from the vial using a new sterile needle with a diameter of 21 gauge or less.

For dilution:

1. Slowly withdraw the appropriate reconstituted liquid (50 mg daptomycin/ml) from the vial using a new sterile needle.
2. Invert the vial so that the solution falls towards the stopper. Using a new syringe, insert the needle into the inverted vial. Keeping the vial inverted, place the tip of the needle at the lowest point of the liquid while withdrawing the solution into the syringe. Before removing the needle from the vial, pull the plunger back to the end of the syringe cylinder to withdraw the required solution from the inverted vial.
3. Expel air, large bubbles, and any excess solution to obtain the required dose.
4. Transfer the required reconstituted dose to 50 ml of a 0.9% sodium chloride injectable solution (9 mg/ml).
5. The reconstituted and diluted solution should be infused intravenously over 30 or 60 minutes.

Daptomicina Noridem 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 Daptomicina Noridem: aztreonam, ceftazidime, ceftriaxone, gentamicin, fluconazole, levofloxacin, dopamine, heparin, and lidocaine.

After reconstitution:

The chemical and physical stability of the reconstituted solution in the vial has been demonstrated for 12 hours at 25°C and up to a maximum of 48 hours at 2°C-8°C.

After dilution:

The chemical and physical stability of the diluted solution in infusion bags has been demonstrated for 12 hours at 25°C and up to a maximum of 24 hours at 2°C-8°C.

In the case of intravenous infusion over 30 minutes, 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).

In the case of intravenous injection over 2 minutes, the storage time of the reconstituted solution in the vial at 25°C should not exceed 12 hours (or 48 hours at 2°C-8°C).

However, from a microbiological point of view, the product should be used immediately. This product does not contain preservatives or bacteriostatic antibiotics. If not used immediately, the storage time and conditions until use are the responsibility of the user and should not normally exceed 24 hours at 2°C-8°C, unless the reconstitution/dilution has taken place in validated and controlled aseptic conditions.

After mixing:

The chemical and physical stability of the mixtures has been established for 2 hours at 25°C.

Daptomicina Noridem administered as an intravenous injection over 2 minutes (only for adult patients)

Water should not be used for the reconstitution of Daptomicina Noridem for intravenous injection. Daptomicina Noridem should be reconstituted only with a 0.9% sodium chloride injectable solution (9 mg/ml).

350 mg presentation:

Reconstituting the lyophilized product with 7 ml of a 0.9% sodium chloride injectable solution (9 mg/ml) yields a concentration of 50 mg/ml of Daptomicina Noridem for injection.

500 mg presentation:

A concentration of 50 mg/ml of Daptomicina Noridem can be obtained by reconstituting the lyophilized product with 10 ml of a 0.9% sodium chloride injectable solution (9 mg/ml).

The lyophilized product takes approximately 5 minutes to dissolve. The completely reconstituted product has a transparent appearance and may present some small bubbles or foam around the edge of the vial.

To prepare Daptomicina Noridem for intravenous injection, follow these instructions:

To reconstitute Daptomicina Noridem lyophilized product, aseptic technique must be used throughout the process.

1. The plastic "flip-off" closure cap should be removed to expose the central part of the rubber stopper. Clean the top of the rubber stopper with a cotton swab with alcohol or another antiseptic solution and let it dry. After cleaning, do not touch the rubber stopper or allow it to touch any other surface.

• In the case of Daptomicina Noridem 350 mg powder for solution for injection and infusion, withdraw 7 ml of a 0.9% sodium chloride injectable solution (9 mg/ml) into a syringe through a sterile transfer needle with a diameter of 21 gauge or less, or a needleless device. Then, slowly inject it through the center of the rubber stopper into the vial, aiming the needle at the vial wall.
• In the case of Daptomicina Noridem 500 mg powder for solution for injection and infusion, withdraw 10 ml of a 0.9% sodium chloride injectable solution (9 mg/ml) into a syringe through a sterile transfer needle with a diameter of 21 gauge or less, or a needleless device. Then, slowly inject it through the center of the rubber stopper into the vial, aiming the needle at the vial wall.

1. The vial should be gently rotated to ensure that the product is completely wetted, and then left to stand for 10 minutes.
2. Finally, the vial should be gently rotated/shaken for a few minutes until a clear reconstituted solution is obtained. Avoid vigorous shaking to prevent foam formation.
3. The reconstituted solution should be carefully inspected before use to ensure that the substance is dissolved and to verify the absence of suspended particles. The color of the reconstituted solution of Daptomicina Noridem may vary from pale yellow to light brown.
4. Slowly withdraw the reconstituted liquid (50 mg daptomycin/ml) from the vial using a new sterile needle with a diameter of 21 gauge or less.
5. Invert the vial so that the solution falls towards the stopper. Using a new syringe, insert the needle into the inverted vial. Keeping the vial inverted, place the tip of the needle at the lowest point of the liquid while withdrawing the solution into the syringe. Before removing the needle from the vial, pull the plunger back to the end of the syringe cylinder to withdraw the required solution from the inverted vial.
6. Replace the needle with a new one for intravenous injection.
7. Expel air, large bubbles, and any excess solution to obtain the required dose.
8. The reconstituted solution should be slowly injected intravenously over 2 minutes.

The physical and chemical stability 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 should not normally exceed 24 hours at 2°C-8°C, unless the reconstitution has taken place in validated and controlled aseptic conditions.

This medicinal product should not be mixed with other medicinal products except those mentioned above.

The vials of Daptomicina Noridem are for single use only. The disposal of unused medicinal products and all materials that have come into contact with them should be carried out in accordance with local regulations.