DAPTOMYCIN ACCORD 350 mg POWDER FOR SOLUTION FOR INJECTION AND FOR INFUSION

Introduction

Package Leaflet: Information for the Patient

Daptomicina Accord 350 mg powder for solution for injection and infusion EFG

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

Keep this leaflet, you may need to read it again.

If you have any further questions, ask your doctor or nurse.

This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet:

1. What Daptomicina Accord is and what it is used for
2. What you need to know before you are given Daptomicina Accord
3. How Daptomicina Accord is given
4. Possible side effects
5. How to store Daptomicina Accord
6. Contents of the pack and other information

1. What Daptomicina Accord is and what it is used for

The active substance of Daptomicina Accord powder for solution for injection and infusion is daptomycin.

Daptomycin is an antibacterial agent capable of stopping the growth of certain bacteria. Daptomycin is used in adults and in children and adolescents (aged 1 to 17 years) to treat skin and soft tissue infections. It is also used to treat bloodstream infections when associated with skin or soft tissue infections.

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

Depending on the type of infection(s) you have, your doctor may also prescribe other antibacterial agents while you are being treated with Daptomicina Accord.

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, consult your doctor or nurse.

Warnings and precautions

Tell your doctor or nurse before you are given 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 who receive daptomycin may develop increased sensitivity, muscle pain or 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 the presence of 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 important 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

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

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 may increase the risk of muscle side effects 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 relievers called non-steroidal anti-inflammatory drugs (NSAIDs) or COX-2 inhibitors (e.g. celecoxib). They 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 normally given to pregnant women. If you are pregnant or breastfeeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

You should not breastfeed if you are being treated with 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; this 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 a day for skin infections or 6 mg per kilogram of body weight once a day 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 properly.

If your kidneys do not work well, you may receive daptomycin less frequently, e.g. every other day. If you are undergoing dialysis and your next dose of daptomycin is due on a dialysis day, you will normally receive daptomycin after the dialysis session.

Children and adolescents (1 to 17 years of age)

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 bloodstream 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 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 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 serious, 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 problem 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 serious 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 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.

The following are described other side effects that may occur with the use of daptomycin:

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, changes in 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.
• Eye itching

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), easy bruising, 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. Storage of 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 on the label after EXP. The expiry date is the last day of the month shown.
• Store in a refrigerator (2°C - 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 ofDaptomicina Accord

• The active ingredient is daptomycin. A vial of powder contains 350 mg of daptomycin. One ml contains 50 mg of daptomycin after reconstitution with 7 ml of a 9 mg/ml (0.9%) sodium chloride solution.
• The other component is sodium hydroxide.

Appearance of the Product and Container Contents

Daptomicina 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 containers containing 1 vial or 5 vials.

Only certain pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization 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 authorized in the EEA Member States under the following names:

Date of the last revision of this leaflet:July 2023

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

Presentation of 350 mg:

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. The preparation of the solution for infusion requires an additional dilution phase, as described below.

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

Reconstituting the lyophilized product with 7 ml of a 9 mg/ml (0.9%) sodium chloride injectable solution can obtain a concentration of 50 mg/ml of daptomycin for infusion.

The lyophilized product takes approximately 15 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 Accord for intravenous infusion, follow these instructions:

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

1. The polypropylene "flip-off" closure cap must 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. Withdraw 7 ml of a 9 mg/ml (0.9%) sodium chloride injectable solution 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.
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/shaken for a few minutes until a transparent reconstituted solution is obtained. Avoid vigorous shaking to prevent foam generation.

Inspect the reconstituted solution carefully before use to ensure that the substance is dissolved and to verify the absence of particles in suspension. The color 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 with a diameter of 21 gauge or less.
2. The reconstituted solution must be diluted with 9 mg/ml (0.9%) sodium chloride

(typical volume of 50 ml).

1. 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 remove all the solution from the inverted vial.
2. Replace the needle with a new one for intravenous infusion.
3. Expel air, large bubbles, and any excess solution to obtain the required dose.
4. The reconstituted and diluted solution must 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.

Daptomicina Accord administered as an intravenous injection over 2 minutes

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

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

The lyophilized product takes approximately 15 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 Accord for intravenous injection, follow these instructions:

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

1. The polypropylene "flip-off" closure cap must 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. Withdraw 7 ml of a 9 mg/ml (0.9%) sodium chloride injectable solution 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.
2. The vial must 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/shaken for a few minutes until a

transparent reconstituted solution is obtained. Avoid vigorous shaking to prevent foam generation.

Inspect the reconstituted solution carefully before use to ensure that the substance is dissolved and to verify the absence of particles in suspension. The color 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 with a diameter of 21 gauge or less.
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 remove 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 must 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 should not normally 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 Daptomicina Accord are for single use only. Any unused remainder of the vial should be discarded.