DAPTOMYCIN ACCORD HEALTHCARE 500 mg POWDER FOR SOLUTION FOR INJECTION AND FOR INFUSION

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

You should not be given Daptomicina Accord Healthcare

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

If this is the 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 Daptomicina.

• If you have or have had kidney problems in the past. Your doctor may need to change the dose of daptomicina (see section 3 of this leaflet).
• Occasionally, patients who receive daptomicina may develop increased sensitivity, pain, or muscle 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 or not it is recommended to continue using daptomicina. The symptoms usually disappear within a few days after stopping treatment with daptomicina.
• 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 daptomicina.
• If you are significantly overweight. There is a possibility that your blood levels of daptomicina may be higher than those found in people of average weight, and that you may therefore need stricter monitoring for adverse effects.

If any of the above cases apply to you, inform your doctor or nurse before receiving daptomicina.

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

• Severe allergic reactions have been observed in patients treated with almost all antibacterial agents, including daptomicina. The symptoms may include 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. The symptoms that occur with these skin diseases may 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 Daptomicina. The symptoms may 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, inform 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 prolonged.
• Appearance of fever or worsening of it, cough, or difficulty breathing. These may be signs of a rare but serious lung condition called eosinophilic pneumonia. Your doctor will check the condition of your lungs and decide whether or not to continue treatment with daptomicina.

Daptomicina 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. Inform your doctor that you are being treated with daptomicina.

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

Children and adolescents

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

Use in elderly patients

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

Use of Daptomicina Accord Healthcare with other medicines

Inform 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. Your doctor may decide not to administer daptomicina or temporarily interrupt treatment with the other medicine.
• Medicines for pain relief called non-steroidal anti-inflammatory drugs (NSAIDs) or COX-2 inhibitors (e.g., celecoxib). These may interfere with the elimination of daptomicina 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 is not usually administered 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 receiving this medicine.

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

Driving and using machines

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

Daptomicina Accord Healthcare contains sodium

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

3. How to take Daptomicina Accord Healthcare

This medicine 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 usual dose for adults is 4 mg per kilogram of body weight once a day for skin infections or 6 mg per kilogram of body weight once a day for heart or blood infections associated with skin infections. In adult patients, this dose is administered directly into the bloodstream (into 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 of age, provided their kidneys are functioning correctly.

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

If you use more Daptomicina Accord Healthcare than you should

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, telephone 91 562 04 20, indicating the medicine and the amount administered.

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 lasting approximately 30-60 minutes.

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

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

If you have any further questions on the use of this medicine, ask your doctor, pharmacist, or nurse.

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:

Severe 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 daptomicina. These severe allergic reactions require immediate medical attention. Inform 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,
• Shortness of breath,
• Fever,
• Chills or shivering,
• Flushing,
• Dizziness,
• Fainting,
• Metallic taste.

Consult 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 Accord Healthcare are:

• A rare but potentially severe lung condition called eosinophilic pneumonia, mostly after more than 2 weeks of treatment. The symptoms may include difficulty breathing, appearance of cough or worsening of it, or appearance of fever or worsening of it.
• Severe skin diseases. The symptoms may 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 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 described the most frequently reported side effects:

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

• Fungal infections, such as thrush,
• 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,
• 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 Daptomicina Accord Healthcare:

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

• 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 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 through 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 Healthcare

• 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 refers to the last day of the month shown.
• Store in a refrigerator (between 2°C and 8°C).

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

For the 2-minute intravenous injection, 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 times and conditions before use are the responsibility of the user and would normally not exceed 24 hours at 2 - 8°C, unless the reconstitution has been carried out under controlled and validated aseptic conditions.

After dilution:

The chemical and physical 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 the 30-minute intravenous infusion, the combined storage time (reconstituted solution in vial and diluted solution in infusion bag; see section 6.6) at 25°C should not exceed 12 hours (or 24 hours at 2°C - 8°C).

However, from a microbiological point of view, unless the method of reconstitution and dilution excludes the risk of microbial contamination, the product should be used immediately. If not used immediately, the storage times and conditions before use are the responsibility of the user.

6. Container contents and additional information

Composition ofDaptomycin Accord Healthcare

• The active ingredient is daptomycin.

Daptomycin Accord Healthcare 500 mg powder for solution for injection and infusion EFG

A vial of powder contains 500 mg of daptomycin.

• The other ingredients are sodium hydrogen phosphate dihydrate, sodium dihydrogen phosphate monohydrate, and sodium hydroxide.

Appearance of the product and container contents

Daptomycin Accord Healthcare 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.

Daptomycin Accord Healthcare is presented in containers containing 1 vial.

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

Accord Healthcare Polska Sp.z o.o.,

ul. Lutomierska 50,95-200 Pabianice,

Poland

or

Pharmadox Healthcare Ltd.

KW20A, Kordin Industrial Park,

Paola, PLA3000, Malta

or

Laboratori Fundació Dau

C/ C, 12-14 Pol. Ind. Zona Franca,

08040, Barcelona,

Spain

or

Accord Healthcare Single Member S.A.,

64th Km National Road Athens Lamia,

Schimatari, 32009,

Greece

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

Date of last revision of this leaflet:June 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 the Package Leaflet before prescribing.

Instructions for use and handling

Daptomycin Accord Healthcare 500 mg powder for solution for injection and infusion

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 pediatric patients as an injection over 2 minutes. Pediatric patients from 7 to 17 years of age should receive daptomycin as an infusion over 30 minutes. Pediatric patients under 7 years of age who receive doses of 9-12 mg/kg should be administered daptomycin over 60 minutes. Preparation of the infusion solution requires an additional dilution phase, as described below.

Daptomycin Accord Healthcare 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 injection solution can yield a concentration of 50 mg/ml of daptomycin for infusion.

The lyophilized product takes approximately 3 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 Healthcare for intravenous infusion, follow these instructions:

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

For reconstitution

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 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 center 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 wetted, and then left to stand for 3 minutes.
3. Finally, the vial should be gently rotated/agitated for a few minutes until a clear 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 color of the reconstituted daptomycin solution may vary from pale yellow to light brown.
5. The reconstituted solution must be diluted further with 9 mg/ml (0.9%) sodium chloride.

(typical volume of 50 ml).

For dilution:

1. Slowly withdraw the reconstituted liquid (50 mg daptomycin/ml) from the vial using a sterile needle of 21 gauge or smaller, inverting 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. Expel air, large bubbles, and any excess solution to obtain the required dose.
3. Transfer the required dose of reconstituted solution to 50 ml of 9 mg/ml (0.9%) sodium chloride.
4. The reconstituted and diluted solution should be infused intravenously over 30 or 60 minutes.

Daptomycin Accord Healthcare 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 Accord Healthcare: aztreonam, ceftazidime, ceftriaxone, gentamicin, fluconazole, levofloxacin, dopamine, heparin, and lidocaine.

For the stability of the reconstituted/diluted solution, see section 5.

Daptomycin Accord Healthcare administered as an intravenous injection over 2 minutes (adults only)

Water must not be used for the reconstitution of Daptomycin Accord Healthcare for intravenous injection. Daptomycin Accord Healthcare 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 injection solution yields a concentration of 50 mg/ml of Daptomycin Accord Healthcare for injection.

The lyophilized product takes approximately 3 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 Healthcare for intravenous injection, follow these instructions:

To reconstitute Daptomycin Accord Healthcare 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 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 center 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 wetted, and then left to stand for 3 minutes.
3. Finally, the vial should be gently rotated/agitated for a few minutes until a clear 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 color of the reconstituted Daptomycin Accord Healthcare 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. 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.
7. Replace the needle with a new one for intravenous injection.
8. Expel air, large bubbles, and any excess solution to obtain the required dose.
9. The reconstituted solution should be slowly injected intravenously over 2 minutes.

For the stability of the reconstituted/diluted solution, see section 5.

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

The vials of Daptomycin Accord Healthcare are for single use only. Any remaining contents of the vial that have not been used must be discarded.