DAPTOMYCIN ACCORD 500 mg POWDER FOR SOLUTION FOR INJECTION AND INFUSION

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

You should not be given Daptomicina Accord

If you are allergic to daptomycin or sodium hydroxide 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, ask your doctor or nurse.

Warnings and precautions

Tell your doctor or nurse before you are given daptomycin.

• If you have or have ever had kidney problems. Your doctor may need to change the dose of daptomycin (see section 3 of this leaflet).
• Occasionally, patients who receive daptomycin 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 you should continue using daptomycin. The symptoms usually go away within a few days after stopping treatment with daptomycin.
• 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 daptomycin may be higher than those found in people of average weight, and you may need closer monitoring for side effects.

If any of the above applies to you, tell your doctor or nurse before you are given daptomycin.

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

• Severe allergic reactions have been observed in patients treated with almost all antibacterial agents, including daptomycin. Symptoms can include difficulty breathing, swelling of the face, neck, and throat, skin rash, and hives, fever.
• Severe skin diseases have been reported with the use of Cubicin. The symptoms that occur with these skin diseases can include:
• • Appearance of fever or worsening of it,
  • Red spots on the skin, 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 Cubicin. The symptoms can include fever and rash.
• Any type of tingling or numbness in the hands or feet, loss of sensitivity, or unusual movement difficulties. If this happens, tell your doctor, who will decide whether you should continue treatment.
• Diarrhea, especially if you notice blood or mucus in your stool or if the diarrhea becomes severe or lasts a long time.
• Appearance 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 you should continue treatment with daptomycin.

Daptomycin 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 daptomycin. Tell your doctor that you are being treated with daptomycin.

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

Children and adolescents

Daptomycin 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

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

Using Daptomicina Accord with other medicines

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 daptomycin. Your doctor may decide not to give you daptomycin 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 daptomycin by the kidneys.
• Oral anticoagulants (e.g., warfarin), which are medicines that prevent blood clotting. Your doctor may need to check your blood clotting times.

Pregnancy and breastfeeding

Daptomycin is not usually given to pregnant women. If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, ask your doctor or pharmacist for advice before receiving this medicine.

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

Driving and using machines

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

Daptomicina Accord contains sodium

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

3. How to take Daptomicina Accord

Daptomicina Accord will be administered 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 recommended dose for adults is 4 mg per kilogram of body weight once daily for skin infections or 6 mg per kilogram of body weight once daily for heart or bloodstream infections associated with skin or heart 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 daptomycin less frequently, e.g., every other day. If you are on dialysis and your next dose of daptomycin is due on a dialysis day, you will usually receive daptomycin after the dialysis session.

Children and adolescents (1 to 17 years of age)

The dose 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 bloodstream or heart infections and 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 the most serious side effects:

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

Some cases of hypersensitivity reactions (severe allergic reactions, including anaphylaxis, 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,
• Difficulty breathing,
• Fever,
• Chills or shaking,
• 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 daptomycin 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, appearance of cough or worsening of it, or appearance of fever or worsening of it.
• Severe skin diseases. The symptoms can include:

• Appearance of fever or worsening of it,
• Red spots on the skin, 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 the most common side effects:

Common side effects(may affect up to 1 in 10 people)

• Fungal infections, such as thrush,
• Urinary tract infections,
• 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,
• Bloating or gas (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.

Other side effects that may occur with the use of daptomycin are:

Uncommon side effects(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 sense of taste,
• Tremors,
• Changes in heart rhythm, flushing,
• Indigestion (dyspepsia), tongue inflammation,
• Itchy skin rash,
• Pain, cramps, or muscle 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.
• Itchy eyes

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

• Yellowing of the skin and eyes,
• 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 more easily, bleeding gums, or nosebleeds.

Reporting of side effects:

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

5. How to store Daptomicina Accord

• 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 and 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 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 at 2°C – 8°C.

After dilution:

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

For intravenous infusion over 30 minutes, the combined storage time (reconstituted solution in the vial and diluted solution in infusion bags; see section 6.6) at 25°C should not exceed 12 hours (or 24 hours at 2°C – 8°C).

For intravenous injection over 2 minutes, the storage time of the reconstituted solution in the vial (see section 6.6) 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. 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.

Do not use Daptomicina Accord if you notice any change in the appearance of the product (signs of moisture or presence of particles with a different color in the powder, or presence of particles, turbidity, or precipitation when the solution is reconstituted). Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Container contents and additional information

Composition ofDaptomycin Accord

• The active substance is daptomycin. A vial of powder contains 500 mg of daptomycin. One ml contains 50 mg of daptomycin after reconstitution with 10 ml of a 9 mg/ml (0.9%) sodium chloride solution.
• The other component is sodium hydroxide.

Appearance of the product and container contents

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

This medicinal product is presented in packs containing 1 vial or 5 vials.

Only certain pack sizes may be marketed.

Marketing authorisation holder and manufacturer

Marketing authorisation holder

Accord Healthcare, S.L.U.

World Trade Center

Moll de Barcelona, s/n

Edifici Est, 6ª planta

08039 Barcelona

Spain

Manufacturer

Medichem, S.A.

Narcís Monturiol 41

E-08970 Sant Joan Despí, Barcelona

Spain

Hikma Italia SpA

Viale Certosa 10

I-27100 Pavia

Italy

This pharmaceutical product is authorised in the EEA Member States under the following names:

Date of last revision of this leaflet:July 2023

This information is intended for healthcare professionals only:

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

Instructions for use and handling

500 mg presentation:

In adults, daptomycin can be administered intravenously as an infusion over 30 minutes or as an injection over 2 minutes. Unlike adults, daptomycin should not be administered to paediatric patients as an injection over 2 minutes. Paediatric patients from 7 to 17 years of age should receive daptomycin as an infusion over 30 minutes. For paediatric patients under 7 years of age receiving doses of 9-12 mg/kg, daptomycin should be administered. Preparation of the infusion solution requires an additional dilution phase, as described below.

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

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

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

To prepare Daptomycin Accord for intravenous infusion, follow these instructions:

To reconstitute the lyophilised product, aseptic technique must be used throughout the process.

1. The polypropylene "flip-off" closure cap should be removed to expose the central part of the rubber stopper. Clean the top of the rubber stopper with an alcohol swab or other antiseptic solution and let it dry. After cleaning, do not touch the rubber stopper or allow it to come into contact with any other surface. Draw up 7 ml of a 9 mg/ml (0.9%) sodium chloride injection solution into a syringe using a sterile transfer needle of 21 gauge or smaller, or a needleless device, and slowly inject it through the centre of the rubber stopper into the vial, aiming the needle towards the wall of the vial.
2. The vial should be gently rotated to ensure that the product is completely moistened, and then left to stand for 10 minutes.
3. Finally, the vial should be gently rotated/agitated for a few minutes until a transparent reconstituted solution is obtained. Avoid vigorous agitation to prevent foam formation.
4. The reconstituted solution should be carefully inspected before use to ensure that the substance is dissolved and to verify the absence of particles in suspension. The colour of the reconstituted solution may vary from pale yellow to light brown.
5. Slowly withdraw the reconstituted liquid (50 mg daptomycin/ml) from the vial using a sterile needle of 21 gauge or smaller.
6. The reconstituted solution should then be diluted with 9 mg/ml (0.9%) sodium chloride (typical volume of 50 ml).
7. 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 all the solution from the inverted vial.
8. Replace the needle with a new one for intravenous infusion.
9. Expel air, large bubbles, and any excess solution to obtain the required dose.
10. The reconstituted and diluted solution should be infused intravenously over 30 or 60 minutes.

Daptomycin 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: 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 Accord administered as an intravenous injection over 2 minutes

Water must not be used for the reconstitution of Daptomycin Accord for intravenous injection. This medicinal product must be reconstituted only with 9 mg/ml (0.9%) sodium chloride.

Reconstituting the lyophilised product with 10 ml of a 9 mg/ml (0.9%) sodium chloride injection solution yields a concentration of 50 mg/ml of daptomycin for injection.

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

To prepare Daptomycin Accord for intravenous injection, follow these instructions:

To reconstitute the lyophilised product, aseptic technique must be used throughout the process.

1. The polypropylene "flip-off" closure cap should be removed to expose the central part of the rubber stopper. Clean the top of the rubber stopper with an alcohol swab or other antiseptic solution and let it dry. After cleaning, do not touch the rubber stopper or allow it to come into contact with any other surface. Draw up 7 ml of a 9 mg/ml (0.9%) sodium chloride injection solution into a syringe using a sterile transfer needle of 21 gauge or smaller, or a needleless device, and slowly inject it through the centre of the rubber stopper into the vial, aiming the needle towards the wall of the vial.
2. The vial should be gently rotated to ensure that the product is completely moistened, and

then left to stand for 10 minutes.

1. Finally, the vial should be gently rotated/agitated for a few minutes until a transparent reconstituted solution is obtained. Avoid vigorous agitation to prevent foam formation.

A solution reconstituted

1. should be carefully inspected before use to ensure that the substance is dissolved and to verify the absence of particles in

suspension. The colour of the reconstituted solution may vary from pale yellow to light brown.

1. Slowly withdraw the reconstituted liquid (50 mg daptomycin/ml) from the vial using a sterile needle of 21 gauge or smaller.
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 all the solution from the inverted vial.

1. Replace the needle with a new one for intravenous injection.
2. Expel air, large bubbles, and any excess solution to obtain the required dose.
3. The reconstituted solution should be slowly injected 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 the times indicated above for physical and chemical stability during use.

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

The vials of Daptomycin Accord are for single use only. Any unused portion of the vial should be discarded.