DAPTOMYCIN XELLIA 500 mg POWDER FOR INJECTION AND INFUSION SOLUTION

Introduction

Package Leaflet: Information for the Patient

Daptomicina Xellia 500mg 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, pharmacist 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, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

1. What you need to know before you are given Daptomicina Xellia

1. How Daptomicina Xellia is given

1. Possible side effects

1. Storage of Daptomicina Xellia

1. Contents of the pack and further information

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

The active substance of Daptomicina Xellia powder for solution for injection and infusion (referred to as Daptomicina Xellia throughout this leaflet) is daptomycin. Daptomycin is an antibiotic that can stop the growth of certain bacteria.

Antibiotics are used to treat bacterial infections and will not work for viral infections such as the common cold or flu.

It is important that you follow the instructions regarding dose, administration interval and treatment duration as indicated by your doctor.

Do not keep or reuse this medicine. If you have any leftover antibiotic after you finish treatment, return it to the pharmacy for proper disposal. Do not throw away medicines via wastewater or household waste.

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 a skin infection.

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, and to treat bloodstream infections caused by the same type of bacteria when associated with a heart infection.

Depending on the type of infection(s) you have, your doctor may also prescribe other antibacterial agents while you are receiving treatment with daptomycin.

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

You should not be givenDaptomicina Xellia

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, 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 you start receiving Daptomicina Xellia:

• If you have or have had kidney problems. Your doctor may need to change the dose of Daptomicina Xellia (see section 3 of this leaflet).
• Occasionally, patients receiving daptomycin 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 it is recommended to continue using Daptomicina Xellia. The symptoms usually disappear within a few days after stopping treatment with Daptomicina Xellia.
• 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 stricter monitoring for side effects.

If any of the above applies to you, inform your doctor or nurse before receiving Daptomicina Xellia.

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

• Severe and serious allergic reactions have been observed in patients treated with virtually all antibacterial agents, including daptomycin. Inform your doctor or nurse immediatelyif you experience symptoms indicative of an allergic reaction, such as difficulty breathing, difficulty swallowing, swelling of the face, neck and throat, skin rash and hives, or fever.
• Severe skin diseases have been reported with the use of daptomycin. The symptoms that occur with these skin diseases may include:
• onset of fever or worsening of fever,
• red spots on the skin, raised or filled with fluid, which can start in the armpits or 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 daptomycin. The symptoms may include fever and rash.

• Any type of tingling or numbness in the hands or feet, loss of sensation or unusual movement difficulties. If this occurs, inform your doctor, who will decide whether 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. If this occurs, inform your doctor, who will decide whether to continue treatment.

• Onset of fever or worsening of fever, 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 to continue treatment with Daptomicina Xellia.

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

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

Children and adolescents

Daptomicina Xellia should not be administered to children under 1 year of age, as 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 functioning correctly.

Other medicines andDaptomicina Xellia

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 statinsor 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 Xellia. Your doctor may decide not to administer Daptomicina Xellia or temporarily interrupt 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 Xellia 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

Daptomycin is not usually 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 using this medicine.

You should not breastfeed if you are receiving Daptomicina Xellia, 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 Xellia contains sodium

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

3. How Daptomicina Xellia is given

Daptomicina Xellia 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 (kg) 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 a skin or heart infection. In adult patients, this dose is administered directly into the bloodstream (into a vein), either as an infusionlasting approximately 30 minutes or as an injectionlasting 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 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)

The recommended 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 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 and angioedema) have been reported during the administration of daptomycin. These severe allergic reactions require immediatemedical attention. Inform your doctor or nurse immediatelyif you experience 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.

• Consult your doctor immediatelyif 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 condition called eosinophilic pneumonia, in most cases after more than 2 weeks of treatment. The symptoms may include difficulty breathing, onset of cough or worsening of cough, or onset of fever or worsening of fever. If you experience these symptoms, inform your doctor or nurse immediately.
• Severe skin diseases. The symptoms may include:
• onset of fever or worsening of fever,
• red spots on the skin, raised or filled with fluid, which can start in the armpits or 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 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 people)

• Fungal infections, such as thrush (mouth ulcers).
• Urinary tract infection.
• Decrease in red blood cell count (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 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.
• Dizziness.
• Changes in heart rhythm, flushing.
• Indigestion (dyspepsia), tongue inflammation.
• Itchy 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 (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 more easily, bleeding gums or nosebleeds.

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist or nurse. 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: www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Daptomicina Xellia

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 (2°C - 8°C).

After reconstitution:

The reconstituted solution in the vial has been shown to be physically and chemically stable for up to 12 hours at 25°C and up to 48 hours at 2°C - 8°C.

From a microbiological point of view, the product should be used immediately. If not used immediately, the in-use storage time and conditions are the responsibility of the user and normally should not exceed 24 hours at 2°C - 8°C, unless the reconstitution has taken place in controlled and validated aseptic conditions.

After dilution (performed immediately after reconstitution):

The diluted solution in infusion bags has been shown to be physically and chemically stable for up to 12 hours at 25°C and up to 24 hours at 2°C - 8°C.

From a microbiological point of view, the product should be used immediately, unless the method of opening, reconstitution and dilution excludes the risk of microbial contamination. If not used immediately, the in-use storage time and conditions are the responsibility of the user.

After reconstitution and dilution:

Regarding the combined storage time (reconstituted solution in the vial and diluted solution in infusion bags), the in-use physical and chemical stability has been shown to be 12 hours at 25°C or 24 hours at 2°C - 8°C.

From a microbiological point of view, the product should be used immediately, unless the method of opening, reconstitution and dilution excludes the risk of microbial contamination. If not used immediately, the in-use storage time and conditions are the responsibility of the user.

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 Content and Additional Information

CompositionofDaptomycin Xellia

The active ingredient is daptomycin. A vial of powder contains 500 mg of daptomycin.

One ml provides 50 mg of daptomycin after reconstitution with 10 ml of a solution containing 9 mg/ml of sodium chloride (0.9%).

The other component is sodium hydroxide.

Appearance of theproductand container content

Daptomycin Xellia powder for solution for injection and infusion is presented as a pale yellow to light brown lyophilized powder or cake in a transparent glass vial with a rubber stopper and a gray aluminum seal with a dark blue "flip-off" closure cap. It is mixed with a solvent to form a liquid before administration.

Daptomycin Xellia is available in packs of 1 or 5 vials.

Only some pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Local Representative

Sun Pharma Laboratories, S.L.

Rambla de Catalunya 53-55

08007 – Barcelona

Spain

This medicinal product is authorized in the Member States of theEconomicEconomic Areaand in the United Kingdom under the following names:

Date of last revision of this leaflet:July 2021.

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This information is intended only for healthcare professionals:

Important: 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 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. Preparation of the infusion solution requires an additional dilution phase, as described below.

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

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

The lyophilized 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 Xellia for intravenous infusion, follow the instructions below:

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

For reconstitution:

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 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. Aspirate 10 ml of sodium chloride injection solution 9 mg/ml (0.9%) using a sterile transfer needle with a diameter of 21 gauge or less, or a needleless device, and slowly inject it into the vial through the center of the rubber stopper, directing the needle towards the vial wall.
2. The vial should be gently rotated to ensure that the product is completely wetted, and then left to stand for 10 minutes.
3. Finally, the vial should be gently rotated/shaken 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 suspended particles. The color of the reconstituted Daptomycin Xellia solution may vary from pale yellow to light brown.
5. The reconstituted solution should be diluted with sodium chloride 9 mg/ml (0.9%; typical volume of 50 ml).

For dilution:

1. 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, inverting the vial so that the solution falls towards the stopper. Using a syringe, insert the needle into the inverted vial. Keeping the vial inverted, place the tip of the needle at the lowest point of the solution in the vial while aspirating 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.
2. Expel air, large bubbles, and any excess solution to obtain the required dose.
3. Transfer the required reconstituted dose to the 50 ml of sodium chloride 9 mg/ml (0.9%).
4. The reconstituted and diluted solution should be infused intravenously over 30 or 60 minutes.

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

After dilution (performed immediately after reconstitution):

It has been demonstrated that the diluted solution in infusion bags is physically and chemically stable for up to 12 hours at 25°C and up to a maximum of 24 hours at 2°C – 8°C.

From a microbiological point of view, the product should be used immediately, unless the opening, reconstitution, and dilution method excludes the risk of microbial contamination. If not used immediately, the in-use storage time and conditions are the responsibility of the user.

After reconstitution and dilution:

In relation to the combined storage time (reconstituted solution in the vial and diluted solution in infusion bags), it has been demonstrated that the physical and chemical stability during use is 12 hours at 25°C or 24 hours at 2°C – 8°C.

From a microbiological point of view, the product should be used immediately, unless the opening, reconstitution, and dilution method excludes the risk of microbial contamination. If not used immediately, the in-use storage time and conditions are the responsibility of the user.

Daptomycin Xellia administered as an intravenous injection over 2minutes (only for adult patients)

Water for injectable preparations should not be used for Daptomycin Xellia. Daptomycin Xellia should be reconstituted only with sodium chloride 9 mg/ml (0.9%).

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

The lyophilized 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 Xellia for intravenous injection, follow the instructions below:

To reconstitute Daptomycin Xellia lyophilized 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 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. Aspirate 10 ml of sodium chloride injection solution 9 mg/ml (0.9%) using a sterile transfer needle with a diameter of 21 gauge or less, or a needleless device, and slowly inject it into the vial through the center of the rubber stopper, directing the needle towards the vial wall.
2. The vial should be gently rotated to ensure that the product is completely wetted, and then left to stand for 10 minutes.
3. Finally, the vial should be gently rotated/shaken 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 suspended particles. The color of the reconstituted Daptomycin Xellia solution may vary from pale yellow to light brown.
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 solution in the vial while aspirating the solution into the syringe. Slowly withdraw the reconstituted liquid (50 mg daptomycin/ml) from the vial using a sterile needle with a diameter of 21 gauge or less.
6. Before removing the needle from the vial, pull the plunger back to the end of the syringe cylinder to withdraw the entire 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.

After reconstitution:

It has been demonstrated that the reconstituted solution in the vial is physically and chemically stable for up to 12 hours at 25°C and up to a maximum of 48 hours at 2°C – 8°C.

From a microbiological point of view, the product should be used immediately. If not used immediately, the in-use storage time and conditions are the responsibility of the user, and normally should not exceed 24 hours at 2°C – 8°C, unless the reconstitution has taken place in controlled and validated aseptic conditions.

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

The vials of Daptomycin Xellia are for single use. Any unused remainder of the vial should be discarded.

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/