Label: information for the patient

Daptomicin Xellia 500mg powder for injectable solution and for infusion EFG

Read this label carefully before starting to use this medication, as it contains important information for you.

• Keep this label, as you may need to read it again.

• If you have any doubts, consult your doctor, pharmacist, or nurse.

• This medication has been prescribed only to you, and you should not give it to other people even if they have the same symptoms as you, as it may harm them.

• If you experience adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this label. See section4.

1. What you need to know before starting to receive Daptomicin Xellia

1. How to administer Daptomicin Xellia

1. Possible adverse effects

1. Storage of Daptomicin Xellia

1. Contents of the package and additional information

The active ingredient of Daptomicina Xellia powder for injectable solution and for infusion (referred to as Daptomicina Xellia throughout this prospectus) 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 (ages 1 to 17 years) to treat skin and soft tissue infections. It is also used to treat blood infections when associated with a skin infection.

Daptomycin is also used in adults to treat infections in the tissues that cover the inside of the heart (including heart valves), caused by a type of bacteria called Staphylococcus aureus, and to treat blood 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 receive treatment with daptomycin.

Do not receiveDaptomicina Xellia

Si is allergic to daptomycin or sodium hydroxide or any of the other components of this medication (listed in section6).

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 starting to receive Daptomicina Xellia:

• If you have or have had kidney problems. Your doctor may need to change the dose of Daptomicina Xellia (see section3 of this prospectus).
• Occasionally, patients receiving daptomycin may develop increased sensitivity, muscle pain or weakness (see section4 of this prospectus for more information). Inform your doctor if this happens. Your doctor will ensure that you have a blood test and advise you whether it is recommended to continue using Daptomicina Xellia. Symptoms usually disappear within a few days after stopping treatment with Daptomicina Xellia.
• 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 more stringent monitoring in cases of adverse effects.

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

Inform your doctoror 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. Inform your doctor or nurseimmediatelyif you present symptoms indicative of an allergic reaction, such as rapid breathing, difficulty breathing, facial, neck and throat inflammation, skin rash and urticaria, or fever.
• Severe skin diseases have been reported with the use of daptomycin. The symptoms that occur with these skin diseases may include:
• appearance of fever or worsening of the same,
• red skin patches raised or filled with liquid, which may start in the armpits or in areas of the chest or groin and may spread over a large area of the body,
• blistering or sores in the mouth or genitals.
• Severe kidney problems have been reported with the use of daptomycin. 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.

• Diarrea, mainly if you observe the presence of blood or mucus in the stool or if the diarrhea becomes severe or lasts long. If this occurs, inform your doctor, who will decide whether to continue treatment.

• Appearance of fever or worsening of the same, cough or difficulty breathing. These may be signs of a rare but severe lung function deterioration called eosinophilic pneumonia. The doctor will check the state of your lungs and decide whether to continue or not the treatment with Daptomicina Xellia.

Daptomicina Xellia may interfere with laboratory tests that measure blood clotting capacity. Results mayappear to suggest poor clotting, despite the fact that there is no actual problem. Therefore, it is essential that your doctor takes into account that you are receiving Daptomicina Xellia. Inform your doctor that you are undergoing treatment 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 one yearof age, as animal studies have shown that this age group may experience severe adverse effects.

Use in elderly patients

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

Other medications andDaptomicina Xellia

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 calledstatinsorfibrates(to lower cholesterol) orciclosporin(a medication used in transplants to prevent organ rejection or for other pathologies, p.eg. 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 Daptomicina Xellia. Your doctor may decide not to administer Daptomicina Xellia or temporarily interrupt treatment with the other medication.

• Pain-relieving medications called nonsteroidal anti-inflammatory drugs (AINEs) or COX-2 inhibitors (p.eg.celecoxib). These may interfere with the elimination of Daptomicina Xellia by the kidneys.

• Oral anticoagulants (p.eg.warfarina), which are medications that prevent blood clotting. Your doctor may need to monitor your blood clotting times.

Pregnancy and breastfeeding

Daptomycin is usually not administered to pregnant women. If you are pregnant or breastfeeding, or if you think you may be pregnant or intend to become pregnant, consult your doctor or pharmacist before using this medication.

You should not breastfeed while receiving Daptomicina Xellia, 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.

Daptomicina Xellia contains sodium

This medication contains less than 1 mmol of sodium (23 mg) per vial; that is, it is essentially “sodium-free”.

Daptomicina will 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 usual dose for adults is 4 mg per kilogram (kg) of body weight once a day for skin infections or 6 mg per kg 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 the bloodstream (into a vein), either as a perfusion that lasts approximately 30 minutes or as an injection that lasts approximately 2 minutes. The same dose is recommended for people 65 years of age and older, provided their kidneys function correctly.

If your kidneys do not function well, you may receive daptomicina less frequently, e.g. once every other day. If you are undergoing dialysis and your next daptomicina dose is due on a day of dialysis, you will usually receive daptomicina 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 a perfusion that lasts 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.

At the end of the prospectus, detailed instructions for use and handling are provided.

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 of unknown frequency(cannot be estimated from available data):

• During daptomycin administration, some cases of hypersensitivity reactions (severe allergic reactions including anaphylaxis and angioedema) have been reported. These severe allergic reactions require immediate medical 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.
• Labored breathing.
• Fever.
• Chills or tremors.
• Headache.
• Dizziness.
• Loss of consciousness.
• Metallic taste.

• Consult your doctorimmediatelyif you experience pain, increased sensitivity, or muscle weakness of unknown origin. Muscle problems can be severe, including muscle degeneration (rhabdomyolysis), which can cause kidney damage.

Other side effects that have been reported with the use of daptomycin are:

• A rare but potentially severe lung condition called eosinophilic pneumonia, in most cases after more than 2weeks of treatment. Symptoms may include difficulty breathing, coughing, or worsening of cough, or fever or worsening of fever. If you experience these symptoms, inform your doctor or nurseimmediately.
• 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.
• Severe kidney problems. 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 most frequently reported side effects:

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

• Fungal infections, such as mouth ulcers.
• 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.
• Abdominal swelling or distension.
• Skin rash or itching.
• Pain, itching, or redness at the infusion site.
• Pain in arms or legs.
• Elevated liver enzymes or creatine phosphokinase (CPK) levels in blood tests.

The following are other side effects that may occur after treatment with daptomycin:

Rare side effects(may affect up to 1 in 100patients):

• Blood disorders (e.g., increased platelet count, which may increase the risk of developing blood clots, or increased levels of certain types of white blood cells).
• Loss of appetite.
• Tickling or numbness in the hands or feet, changes in taste.
• Tremors.
• Dizziness.
• Changes in heart rhythm, palpitations.
• Indigestion (dyspepsia), inflammation of the tongue.
• Rash with itching.
• Muscle pain, cramps, or weakness, muscle inflammation (myositis), joint pain.
• Kidney problems.
• Vaginal inflammation and irritation.
• Elevated blood sugar, creatinine, myoglobin, or lactate dehydrogenase (LDH) levels, prolonged bleeding time, or electrolyte imbalance in blood tests.
• Eye itching.

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

• Yellowing of the skin and eyes (jaundice).
• Prolonged prothrombin time.

Unknown frequency(cannot be estimated from available data):

Antibiotic-associated colitis, including pseudomembranous colitis (severe or persistent diarrhea with blood and/or mucus, associated with abdominal pain or fever), easy bruising, bleeding gums, or nasal bleeding.

Reporting side effects

If you experience any type of side effect, consult your doctor or pharmacistor nurse, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use: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 reach and sight of children.

Do not use this medication after the expiration date that appears on the box after CAD 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:

It has been demonstrated that the reconstituted solution in the vial is physically and chemically stable during use 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 storage time during use and the conditions before use are the responsibility of the user, and should normally not exceed 24 hours at 2°C – 8°C, unless the reconstitution took place in controlled and validated aseptic conditions.

After dilution (performed immediately after reconstitution):

It has been demonstrated that the diluted solution in infusion bags is physically and chemically stable during use 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 method of opening, reconstitution, and dilution excludes the risk of microbial contamination. If not used immediately, the storage time during use and the conditions before use 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 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 method of opening, reconstitution, and dilution excludes the risk of microbial contamination. If not used immediately, the storage time and conditions during use are the responsibility of the user.

Medicines should not be disposed of through the drainsor in the trash. Ask your pharmacist how to dispose of the packaging and the medication that you no longer need. In this way, you will help protect the environment.

CompositionofDaptomicin Xellia

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

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

The other component is sodium hydroxide.

Aspect of theproductand content of the packaging

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

Daptomicin Xellia is presented in containers of 1 or 5vials.

Only some sizes of containers may be commercially available.

Holder of the marketing authorization and responsible for manufacturing

Local representative

Sun Pharma Laboratorios, S.L.

Rambla de Catalunya 53-55

08007 – Barcelona

Spain

This medicine is authorized in the member states of theEconomic Area and in the United Kingdom with the following names:

Last review date of this leaflet:July 2021.

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This information is intended solely for healthcare professionals:

Important: Consult the SmPC or Product Characteristics before prescribing.

Instructions for use and handling

500mg presentation:

In adults, daptomycin can be administered intravenously as a 30-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 to 17 years should receive daptomycin as a 30-minute infusion. Pediatric patients under 7 years of age who receive doses of 9-12mg/kg should be administered daptomycin as a 60-minute infusion. The 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 10ml of a 9mg/ml sodium chloride (0.9%) injectable solution yields a 50mg/ml concentration for Daptomycin Xellia infusion.

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

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

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

1. The polipropylene "flip-off" closure 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 stopper, nor allow it to touch any other surface. Aspirate 10ml of a 9mg/ml sodium chloride (0.9%) injectable solution using a sterile transfer needle of calibre21 or smaller, or a device without a needle, and inject it slowly into the vial through the center of the stopper, directing the needle towards the vial wall.
2. The vial must be gently rotated to ensure the product is fully moistened, and then left to stand for 10minutes.
3. Finally, the vial must be gently rotated/agitated for a few minutes to obtain a transparent reconstituted solution. Vigorous agitation should be avoided to prevent foam formation.
4. The reconstituted solution must be carefully inspected before use to ensure the substance is dissolved and to verify the absence of particles in suspension. The color of the reconstituted solution of Daptomycin Xellia may vary from pale yellow to light brown.
5. The reconstituted solution must be diluted with sodium chloride 9 mg/ml (0.9%; typical volume of 50 ml).

To dilute:

1. Remove the reconstituted solution (50 mg daptomycin/ml) from the vial using a new sterile needle of calibre21 or smaller, inverting the vial to allow the solution to flow towards the stopper. Using a syringe, insert the needle into the inverted vial. Keeping the vial inverted, place the needle tip in the lowest point of the solution in the vial while aspirating the solution into the syringe. Remove the needle from the vial, leaving the solution in the syringe.
2. Expel the air, large bubbles, and any excess solution to obtain the required dose.
3. Transfer the reconstituted solution to 50 ml of sodium chloride 9mg/ml (0.9%).
4. The reconstituted and diluted solution must be infused intravenously over 30 or 60minutes.

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, ceftazidima, 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 during use for up to 12hours at 25°C and up to a maximum of 24hours at 2°C – 8°C.

From a microbiological point of view, the product must be used immediately, unless the opening, reconstitution, and dilution method excludes the risk of microbial contamination. If not used immediately, the storage time during use and the conditions before use 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), it has been demonstrated that physical and chemical stability during use is 12hours at 25°C or 24hours at 2°C – 8°C.

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

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

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

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

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

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

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

1. The polipropylene "flip-off" closure 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 stopper, nor allow it to touch any other surface. Aspirate 10ml of a 9mg/ml sodium chloride (0.9%) injectable solution using a sterile transfer needle of calibre21 or smaller, or a device without a needle, and inject it slowly into the vial through the center of the stopper, directing the needle towards the vial wall.
2. The vial must be gently rotated to ensure the product is fully moistened, and then left to stand for 10minutes.
3. Finally, the vial must be gently rotated/agitated for a few minutes to obtain a transparent reconstituted solution. Vigorous agitation should be avoided to prevent foam formation.
4. The reconstituted solution must be carefully inspected before use to ensure the substance is dissolved and to verify the absence of particles in suspension. The color of the reconstituted solution of Daptomycin Xellia may vary from pale yellow to light brown.
5. Invert the vial to allow the solution to flow 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 solution in the vial while aspirating the solution into the syringe. Remove the needle from the vial, leaving the solution in the syringe.
6. Remove the solution reconstituted (50mg daptomycin/ml) from the vial using a sterile needle of calibre21 or smaller.
7. Before removing the needle from the vial, pull the plunger back to the end of the syringe barrel to remove the solution from the inverted vial.
8. Change the needle to a new one for intravenous injection.
9. Expel the air, large bubbles, and any excess solution to obtain the required dose.
10. The reconstituted solution must be injected slowly intravenously over 2minutes.

After reconstitution:

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

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

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

The vials of Daptomycin Xellia are for single use only. Any remaining vial that has not been used must be discarded.

Further information on this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.es/