Package Insert: Information for the Patient

Daptomicina Accord 350 mg Powder for Injection and Infusion EFG

Read this package insert carefully before starting to use this medication, because

it contains important information for you.

• Keep this package insert, as you may need to read it again.
• If you have any questions, consult your doctor or nurse.
• This medication has been prescribed to you alone, 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 package insert. See section 4.

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

2. What you need to know before receiving Daptomicina Accord

3. How to administer Daptomicina Accord

4. Possible adverse effects

5. Storage of Daptomicina Accord

6. Contents of the package and information

The active ingredient of Daptomicina Accord 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 underlying tissue infections. It is also used to treat blood infections when associated with a skin infection.

Daptomycin is also used in adults to treat tissue infections 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 heart infection.

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

You should not receive Daptomicina Accord

If you are allergic to daptomycin or sodium hydroxide or 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 receiving 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 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 severe 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 life-threatening 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, fever
• Severe skin diseases have been reported with the use of Cubicin. Symptoms that occur with these skin diseases may include:
• • fever or worsening of the same,
  • red skin patches elevated 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 Cubicin. 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.
• Diarrhea, especially if you notice blood or mucus in your stool or if diarrhea becomes severe or lasts long.
• Onset of fever or worsening of the same, 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 treatment with daptomycin.

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.

Use of Daptomycin Accord with other medications

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 other 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, consult your doctor or pharmacist before receiving this medication.

You should 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.

Daptomycin Accord contains sodium

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

Daptomicinawill be administered 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 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 correctly.

If your kidneys do not function well, you may receivedaptomicinaless frequently, for example, once every other day. If you are undergoing dialysis and your next dose ofdaptomicinais due on a day of dialysis, you will usually receivedaptomicinaafter the dialysis session.

Children and adolescents (1 to 17 years of age)

Doses in children and adolescents (1 to 17years) 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 on the duration of 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 the administration ofdaptomycinsome cases of hypersensitivity reactions (severe allergic reactions including anaphylaxis, 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 the throat,
• Fast or weak pulse,
• Labored breathing,
• Fever,
• Chills or tremors,
• Flushes,
• Dizziness,
• Loss of consciousness,
• 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 breakdown (rhabdomyolysis), which can cause kidney damage.

Other side effectsthat have been reported with the use ofdaptomycinare:

• A rare but potentially serious 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 on 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 cold sores,
• 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,
• Swelling or gas (abdominal 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 withdaptomycin:

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, changes in taste,
• Tremors,
• Changes in heart rhythm, flushes,
• 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,
• Generalized pain or weakness, fatigue,
• Elevated blood sugar, creatinine, myoglobin, or lactate dehydrogenase (LDH) levels, prolonged blood clotting time, or electrolyte imbalance in blood tests.
• Eye itching

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

• Yellowing of the skin and eyes,
• Prolonged 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 more easily, bleeding gums or nasal hemorrhages.

Reporting of side effects:

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this prospectus. 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 on the label after CAD. The expiration date is the last day of the month indicated.
• Store in refrigerator (between 2°C and 8°C).

After reconstitution:

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 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 be greater than 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 through the drains or in the trash. Ask your pharmacist how to dispose of the medicines that are no longer needed. These measures will help protect the environment.

Composition ofDaptomicin 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 sodium chloride solution (0.9%).
• The other component is sodium hydroxide.

Appearance of the product and contents of the package

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

This medicine is presented in packages containing 1 vial or 5 vials.

Only some package sizes may be marketed.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization

Accord Healthcare, S.L.U.

World Trade Center

Moll de Barcelona, s/n

Edifici Est, 6th floor

08039 Barcelona

Spain

Responsible for manufacturing

Medichem, S.A.

Narcís Monturiol, 41

E-08970 Sant Joan Despí, Barcelona

Spain

Hikma Italia SpA

Viale Certosa 10

I-27100 Pavia

Italy

This medicinal product is authorized in the Member States of the EEA under the following names:

Last review date of this leaflet:July 2023

For detailed information on this medicine, please visit the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.es/

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

350 mg presentation:

In adults, daptomycin can be administered intravenously as a 30- or 60-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 7-17 years should receive daptomycin as a 30-minute infusion. Pediatric patients under 7 years old who receive doses of 9-12 mg/kg should receive daptomycin. The 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 lyophilized product with 7 ml of a 9 mg/ml sodium chloride solution (0.9%) can obtain a concentration of 50 mg/ml of daptomycin for infusion.

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 edge of the vial.

To prepare Daptomycin Accord for intravenous infusion, follow the instructions below:

1. The polystyrene flip-off cap must 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 allow it to 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 7 ml of a 9 mg/ml sodium chloride solution (0.9%) and inject it slowly through the centre of the rubber stopper into the vial, pointing the needle towards the vial wall.
2. The vial should be gently rotated to ensure that the product is fully moistened, and

then left to stand for 10 minutes.

1. Finally, the vial should be gently rotated/agitated for a few minutes to obtain a reconstituted solution. Vigorous agitation should be avoided to prevent foam generation.
2. 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.
3. Retire the reconstituted solution (50 mg daptomycin/ml) from the vial using a sterile needle of calibre 21 or smaller.
4. The reconstituted solution should then be diluted with 9 mg/ml sodium chloride solution (0.9%) (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 needle tip in the lowest point of the liquid while extracting the solution into the syringe. Before removing the needle from the vial, push the plunger back to the end of the syringe barrel to remove all the solution from the inverted vial.
2. Replace the needle with a new one for intravenous infusion.
3. Expel the air, large bubbles, and any excess solution to obtain the required dose.
4. 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 should not be used for reconstituting Daptomycin Accord for intravenous injection. This medicine should only be reconstituted with 9 mg/ml sodium chloride solution (0.9%).

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

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 edge of the vial.

To prepare Daptomycin Accord for intravenous injection, follow the instructions below:

For reconstituting the lyophilized product, aseptic technique should be used throughout the process.

1. The polystyrene flip-off cap must 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 allow it to 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 7 ml of a 9 mg/ml sodium chloride solution (0.9%) and inject it slowly through the centre of the rubber stopper into the vial, pointing the needle towards the vial wall.
2. The vial should be gently rotated to ensure that the product is fully moistened, and

then left to stand for 10 minutes.

1. Finally, the vial should be gently rotated/agitated for a few minutes to obtain a reconstituted solution. Vigorous agitation should be avoided to prevent foam generation.
2. 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.
3. Retire the reconstituted solution (50 mg daptomycin/ml) from the vial using a sterile needle of calibre 21 or smaller.
4. 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 needle tip in the lowest point of the liquid while extracting the solution into the syringe. Before removing the needle from the vial, push the plunger back to the end of the syringe barrel to remove all the solution from the inverted vial.

7. Replace the needle with a new one for intravenous injection.

8. Expel the air, large bubbles, and any excess solution to obtain the required dose.

9. 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 the times indicated above for chemical and physical stability in use.

This medicine should not be mixed with other medicines that are not mentioned above.

The vials of Daptomycin Accord are exclusively for single use. Any remaining vial that has not been used should be discarded.