DAPTOMYCIN XELLIA

Package leaflet: Information for the patient

Daptomicin Xellia 350 mg powder for injectable/infusion solution

daptomicin
Equivalent medicine
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

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

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

The active substance of Daptomicina Xellia powder for solution for injection/infusion
(referred to as Daptomicina Xellia in this leaflet) is daptomycin. Daptomycin is an
antibacterial agent that can stop the growth of certain bacteria.
Daptomicina Xellia is used in adults and in children and adolescents (aged 1 to 17
years) to treat skin and underlying tissue (subcutaneous) infections. It is also
used to treat bloodstream infections when they are associated with skin infections.
Daptomicina Xellia is also used in adults to treat infections of the tissues lining the inside of the heart (including heart valves) caused by a type of bacterium called Staphylococcus aureus. It is also used to treat bloodstream infections caused by the same type of bacterium when they are associated with skin or heart infections.
Depending on the type of infection(s) you have, your doctor may also prescribe other antibacterial agents during treatment with Daptomicina Xellia.

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

Do not receive Daptomicin Xellia

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

If this applies to you, inform your doctor or nurse. If you think you may be
allergic, consult your doctor or nurse.
Warnings and precautions
Talk to your doctor, pharmacist, or nurse before you are given
Daptomicin Xellia:

• If you have or have previously had kidney problems. Your doctor may need to adjust the dose of Daptomicin Xellia (see section 3 of this leaflet).
• Patients treated with daptomycin may sometimes experience muscle pain, weakness, or discomfort (see section 4 of this leaflet for more information). If this occurs, inform your doctor. Your doctor will ensure you undergo a blood test and will advise whether you should continue or discontinue treatment with Daptomicin Xellia. Symptoms usually resolve within a few days after stopping Daptomicin Xellia.
• If you are overweight. Daptomycin blood levels may be higher than those observed in individuals of average weight, so you may need to be monitored more closely for side effects.

If any of these situations apply to you, inform your doctor or nurse before you are
given Daptomicin Xellia.
Inform your doctor immediately if any of the following symptoms occur (see
section 4):

• Severe acute allergic reactions have been observed in patients treated with nearly all antibacterial medicines, including daptomycin. Inform your doctor or nurse immediately if you experience symptoms suggestive of an allergic reaction such as wheezing, difficulty breathing, swelling of the face, neck, or throat, skin rash, hives, or fever.
• Unusual tingling or numbness in the hands or feet, loss of sensation, or difficulty moving. If this occurs, inform your doctor, who will decide whether to continue treatment.
• Diarrhea, especially if you notice blood or mucus, or if the diarrhea becomes severe or persistent. If this occurs, inform your doctor, who will decide whether to continue treatment.
• Onset or worsening of fever, cough, or difficulty breathing. These may be signs of a rare but serious lung disease called eosinophilic pneumonia. Your doctor will check your lung function and decide whether you should continue or stop treatment with Daptomicin Xellia.

Daptomicin Xellia may interfere with laboratory tests measuring blood coagulation. Test results may suggest a blood clotting problem even when none exists. It is therefore important that your doctor is aware that you are receiving Daptomicin Xellia. Inform your doctor that you are being treated with Daptomicin Xellia.
Your doctor will perform blood tests to monitor muscle function both before starting treatment and regularly during treatment. Inform your doctor that you are being treated with Daptomicin Xellia.
Children and adolescents
Daptomicin Xellia must not be given to children under one year of age, as animal studies have shown that serious adverse effects may occur in this age group.
Use in the elderly
People over 65 years of age can receive the same dose as adults, provided they have normal kidney function.
Other medicines and Daptomicin Xellia
Inform your doctor or nurse if you are taking, have recently taken, or might take any other medicines. It is particularly important to report if you are taking:

• Medicines called statins or fibrates (used to lower cholesterol) or cyclosporine (a medicine used in organ transplantation to prevent organ rejection or in other conditions such as rheumatoid arthritis or atopic dermatitis). If you take any of these medicines (and others that may affect muscles) during treatment with Daptomicin Xellia, the risk of muscle-related adverse effects may be increased. Your doctor may decide not to prescribe Daptomicin Xellia or may temporarily discontinue the other medicines.
• Analgesics called non-steroidal anti-inflammatory drugs ( NSAIDs ) or COX-2 inhibitors (e.g. celecoxib ). These may interfere with the renal effects of Daptomicin Xellia.
• Oral anticoagulants (e.g. warfarin ), which are medicines that prevent blood from clotting. Your doctor may need to monitor your blood clotting time.

Pregnancy and breastfeeding
Daptomycin is generally not administered to pregnant women. If you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breastfeeding, consult your doctor or pharmacist before receiving this medicine.
DO NOT breastfeed while receiving Daptomicin Xellia, as it may pass into breast milk and could therefore affect the infant.
Driving and using machines
Daptomycin has no known effects on the ability to drive or operate machinery.
Daptomicin Xellia contains sodium
Each 350 mg vial contains approximately 3.2 mg of sodium.
This medicine contains less than 1 mmol of sodium (23 mg) per vial and is therefore essentially "sodium-free".

3. How Daptomicin Xellia is administered

Daptomicin Xellia is normally administered by a doctor or nurse.
Adults (aged 18 years and older)
The dose depends on your body weight and the type of infection being treated. In adults, the usual dose is 4 mg per kilogram (kg) of body weight, administered once daily for skin infections, or 6 mg per kg of body weight administered once daily for heart infection or bloodstream infection associated with skin or heart infection. In adult patients, this dose is injected 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 individuals over 65 years of age, provided they have normal renal function.
If you have impaired renal function, you may receive Daptomicin Xellia less frequently, e.g., every other day. If you are on dialysis and the next dose of Daptomicin Xellia is to be administered on the same day as dialysis, Daptomicin Xellia is usually given after completion of dialysis.
Children and adolescents (from 1 to 17 years of age)
The dose for children and adolescents (from 1 to 17 years of age) depends on the patient's age and the type of infection being treated. This dose is injected directly into the bloodstream (into a vein) as an infusion lasting approximately 30–60 minutes.
Typically, for skin infections, a treatment course lasts from 1 to 2 weeks. For bloodstream or heart infections and skin infections, your doctor will decide how long your treatment should continue.
Detailed instructions for use and handling are provided at the end of this leaflet.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
The most serious side effects are described below:
Very rare serious side effects (may affect up to 1 in 10,000 patients):
In some cases, an allergic reaction (severe allergic reaction including anaphylaxis, angioedema, drug rash with eosinophilia and systemic symptoms (DRESS)) has been reported during administration of daptomycin. This severe allergic reaction requires immediate medical attention. Inform your doctor or nurse immediately if any of the following symptoms occur:

• Chest pain or tightness
• Skin rash with blistering, sometimes affecting the mouth and genitals
• Swelling around the throat
• Rapid or weak heartbeat
• Wheezing
• Fever
• Chills or shaking
• Hot flushes
• Dizziness
• Fainting
• Metallic taste in the mouth

If you notice unexplained muscle pain, tenderness or weakness, inform your doctor immediately. In very rare cases (reported in fewer than 1 in 10,000 patients), muscle problems may be severe, including muscle breakdown (rhabdomyolysis), which can lead to kidney damage.
Serious side effects with unknown frequency (frequency cannot be estimated from the available data):
A rare but potentially serious lung disease called eosinophilic pneumonia has been reported in patients receiving daptomycin, most often after more than 2 weeks of treatment. Symptoms may include difficulty breathing, new or worsening cough, or new or worsening fever. If you experience these symptoms, inform your doctor or nurse immediately.
If you notice raised or fluid-filled skin lesions over a large area of the body, inform your doctor or nurse immediately.
The more commonly reported side effects are described below:
Common side effects (may affect up to 1 in 10 patients):

• Fungal infections such as oral candidiasis
• Urinary tract infections
• Candida infections
• Reduced number of red blood cells (anaemia)
• Dizziness, anxiety, difficulty sleeping
• Headache
• Fever, weakness (asthenia)
• High or low blood pressure
• Constipation, abdominal pain
• Diarrhoea, nausea or vomiting
• Flatulence
• Abdominal swelling or bloating
• Skin rash or itching
• Pain, itching or redness at the infusion site
• Pain in arms or legs
• Increased levels of liver enzymes or creatine phosphokinase (CPK) in blood tests.

Other side effects that may occur with daptomycin treatment are listed below:
Uncommon side effects (may affect up to 1 in 100 patients):

• Blood abnormalities (such as increased number of small blood particles called platelets, which may increase the tendency for blood to clot, or increased levels of certain types of white blood cells)
• Loss of appetite
• Tingling or numbness in hands or feet, altered taste
• Tremor
• Vertigo
• Changes in heart rhythm, hot flushes
• Indigestion (dyspepsia), inflammation of the tongue
• Skin rash
• Muscle pain, cramps or muscle weakness, muscle inflammation (myositis), joint pain
• Kidney problems
• Vaginal inflammation and irritation
• Pain or weakness in general, tiredness (fatigue)
• Blood tests showing increased levels of blood sugar, serum creatinine, myoglobin or lactate dehydrogenase (LDH), prolonged blood clotting time, or electrolyte imbalance
• Itching of the eyes

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

• Yellowing of the skin and eyes
• Prolongation of prothrombin time

Frequency not known (frequency cannot be estimated from the available data):

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

Reporting of side effects
If you get any side effects, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects directly via the national reporting system at: http://www.aifa.gov.it/content/segnalazioni-reazioni-avverse
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Daptomycin 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 and
label after Exp. The expiry date refers to the last day of that month.
Store in a refrigerator (2°C – 8°C).

After reconstitution:
The chemical and physical in-use 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.
From a microbiological point of view, the medicine should be used immediately. If not used
immediately, the user is responsible for the in-use storage period and the conditions prior to use,
provided that reconstitution is carried out under controlled and validated aseptic conditions.

After dilution (performed immediately after reconstitution):
The chemical and physical in-use stability of the diluted solution in infusion bags has been
demonstrated for 12 hours at 25°C and up to 24 hours at 2°C – 8°C.
From a microbiological point of view, unless the method of opening/reconstitution/dilution
excludes the risk of microbial contamination, the medicine must be used immediately. If not used
immediately, the user is responsible for the in-use storage period and the conditions prior to use.

After reconstitution and dilution:
The chemical and physical in-use stability has been demonstrated for 12 hours at 25°C and up to 24 hours at
2°C – 8°C, referring to the total storage period (reconstituted solution in vial and diluted solution in infusion bag).
From a microbiological point of view, unless the method of opening/reconstitution/dilution
excludes the risk of microbial contamination, the medicine must be used immediately. If not used
immediately, the user is responsible for the storage period and conditions during use.

Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist
how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Daptomicin Xellia contains
The active substance is daptomycin. One vial of powder contains 350 mg of
daptomycin.
After reconstitution with 7 ml of sodium chloride solution 9 mg/ml (0.9%), 1 ml contains
50 mg of daptomycin.
The other component is sodium hydroxide.
Description of the appearance of Daptomicin Xellia and contents of the pack
Daptomicin Xellia powder for solution for injection/infusion is supplied as a
lyophilisate or pale yellow to light brown powder in a glass vial with a rubber stopper and a grey aluminium seal with a yellow overcap. Prior to administration, it is mixed with a solvent to form a liquid.
Daptomicin Xellia is available in packs containing 1 vial or 5 vials.
Not all pack sizes may be marketed.
Marketing Authorization Holder and Manufacturer
Xellia Pharmaceuticals Aps
Dalslandsgade 11, København S,
Copenhagen,
Denmark 2300
Marketing Authorization Holder for sale
Sun Pharma Italia Srl
Viale Giulio Richard, 1 – 20143 Milano
This medicinal product has been authorised in the EEA Member States under the following names:

The following information is intended exclusively for healthcare professionals

Important: Before prescribing, consult the Summary of Product Characteristics.
Instructions for use and handling
350 mg pack:
In adults, daptomycin may be administered intravenously as a 30-minute infusion or as a 2-minute injection. Daptomycin must not be administered as a 2-minute injection in pediatric patients. In pediatric patients aged 7 to 17 years, daptomycin should be administered as a 30-minute infusion. In pediatric patients under 7 years of age receiving a dose of 9–12 mg/kg, daptomycin must be administered over 60 minutes. Preparation of the infusion solution requires further dilution, as described below.

Administration of Daptomicina Xellia as a 30- or 60-minute intravenous infusion
A concentration of 50 mg/ml of Daptomicina Xellia for infusion is obtained by reconstituting the lyophilisate with 7 ml of sodium chloride 9 mg/ml (0.9%) injectable solution. Approximately 15 minutes are required for complete dissolution of the lyophilisate. The fully reconstituted medicinal product has a clear appearance, and there may be some bubbles or foam around the edges of the vial.

To prepare Daptomicina Xellia for intravenous infusion, follow the instructions below:
Throughout the entire process of reconstitution or dilution of Daptomicina Xellia lyophilisate, an aseptic technique must be used.

For Reconstitution:

1. Remove the polipropylene overcap to expose the central portion of the rubber stopper. Wipe the top of the rubber stopper with an alcohol-impregnated swab or other antiseptic solution and allow it to dry. After cleaning, do not touch the rubber stopper and do not allow it to come into contact with any other surface. Draw 7 ml of sodium chloride 9 mg/ml (0.9%) injectable solution into a syringe using a sterile transfer needle with a gauge of 21 or smaller, or a needle-free device, and slowly inject it into the vial, inserting the needle into the central part of the rubber stopper with the tip directed toward the vial wall.

2. Gently rotate the vial to ensure the product is completely wetted by the liquid, then allow it to stand for 10 minutes.

3. Finally, gently rotate the vial for a few minutes until a clear reconstituted solution is obtained. Avoid shaking or vigorous agitation of the vial to prevent foam formation.

4. Before use, the reconstituted solution must be carefully inspected to ensure the product is completely dissolved and visually checked for particulate matter. The color of the reconstituted Daptomicina Xellia solution may range from pale yellow to light brown.

5. The reconstituted solution must then be diluted with sodium chloride 9 mg/ml (0.9%) solution (typical volume 50 ml).

For Dilution:

1. Slowly withdraw the properly reconstituted liquid (50 mg daptomycin/ml) from the vial using a new sterile needle with a gauge of 21 or smaller, inverting the vial to allow the solution to flow toward the stopper. Using a syringe, insert the needle into the inverted vial. While keeping the vial inverted, position the needle tip at the bottom of the solution in the vial while aspirating the solution into the syringe. Before removing the needle from the vial, pull back the plunger to the end of the syringe barrel to aspirate the required amount of solution from the inverted vial.
2. Expel air, large bubbles, and excess solution until the required dose is obtained.
3. Transfer the required reconstituted dose into 50 ml of sodium chloride 9 mg/ml (0.9%).
4. The reconstituted and diluted solution must then be administered intravenously over 30 or 60 minutes.

Daptomicina Xellia is physically or chemically incompatible with glucose-containing solutions. The following agents have been shown to be compatible when added to infusion solutions containing Daptomicina Xellia: aztreonam, ceftazidime, ceftriaxone, gentamicin, fluconazole, levofloxacin, dopamine, heparin, and lidocaine.

After dilution (performed immediately after reconstitution):
The chemical and physical in-use stability of the diluted solution in infusion bags has been demonstrated for 12 hours at 25°C and up to 24 hours at 2°C – 8°C.
From a microbiological standpoint, unless the method of opening/reconstitution/dilution excludes the risk of microbial contamination, the medicinal product must be used immediately. If not used immediately, the user is responsible for the in-use storage period and conditions prior to use.

After reconstitution and dilution:
Chemical and physical in-use stability has been demonstrated for 12 hours at 25°C and up to 24 hours at 2°C – 8°C, referring to the total storage period (reconstituted solution in vial and diluted solution in infusion bag).
From a microbiological standpoint, unless the method of opening/reconstitution/dilution excludes the risk of microbial contamination, the medicinal product must be used immediately. If not used immediately, the user is responsible for the in-use storage period and conditions.

Administration of Daptomicina Xellia as a 2-minute intravenous injection (for adult patients only)
For reconstitution of Daptomicina Xellia for intravenous injection, water must not be used. Daptomicina Xellia must be reconstituted only with sodium chloride 9 mg/ml (0.9%).
A concentration of 50 mg/ml of Daptomicina Xellia for injection is obtained by reconstituting the lyophilisate with 7 ml of sodium chloride 9 mg/ml (0.9%) injectable solution.
Approximately 15 minutes are required for complete dissolution of the lyophilisate. The fully reconstituted medicinal product has a clear appearance, and there may be some bubbles or foam around the edges of the vial.

To prepare Daptomicina Xellia for intravenous injection, follow the instructions below: throughout the entire reconstitution process of Daptomicina Xellia lyophilisate, an aseptic technique must be used.

1. Remove the polipropylene overcap to expose the central portion of the rubber stopper. Wipe the top of the rubber stopper with an alcohol-impregnated swab or other antiseptic solution and allow it to dry. After cleaning, do not touch the rubber stopper and do not allow it to come into contact with any other surface. Draw 7 ml of sodium chloride 9 mg/ml (0.9%) injectable solution into a syringe using a sterile transfer needle with a gauge of 21 or smaller, or a needle-free device, and slowly inject it into the vial, inserting the needle into the central part of the rubber stopper with the tip directed toward the vial wall.

2. Gently rotate the vial to ensure the product is completely wetted by the liquid, then allow it to stand for 10 minutes.

3. Finally, gently rotate the vial for a few minutes until a clear reconstituted solution is obtained. Avoid shaking or vigorous agitation of the vial to prevent foam formation.

4. Before use, the reconstituted solution must be carefully inspected to ensure the product is completely dissolved and visually checked for particulate matter. The color of the reconstituted Daptomicina Xellia solution may range from pale yellow to light brown.

5. Invert the vial to allow the solution to flow toward the stopper. Using a new syringe, insert the needle into the inverted vial. While keeping the vial inverted, position the needle tip at the bottom of the solution in the vial while aspirating the solution into the syringe. Slowly withdraw the reconstituted liquid (50 mg of daptomycin/ml) from the vial using a sterile needle with a gauge of 21 or smaller.

6. Before removing the needle from the vial, pull back the plunger to the end of the syringe barrel to aspirate all the solution from the inverted vial.

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

8. Expel air, large bubbles, and excess solution until the required dose is obtained.

9. The reconstituted solution must then be slowly injected intravenously over 2 minutes.

After reconstitution:
The chemical and physical in-use 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.
From a microbiological standpoint, the medicinal product must be used immediately. If not used immediately, the user is responsible for the in-use storage period, which under normal circumstances should not exceed 24 hours at 2°C – 8°C, unless reconstitution is performed under controlled, validated aseptic conditions, as well as for the conditions prior to use.

The medicinal product must not be mixed with other products except those mentioned above.
Daptomicina Xellia vials are for single use only. Any unused solution remaining in the vial must be discarded.

Patient Information Leaflet

Daptomycin Xellia 500 mg powder for solution for injection/infusion

daptomycin
Equivalent medicine
Please read this leaflet carefully before using this medicine as it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

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

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

The active substance of Daptomicina Xellia powder for solution for injection/infusion
(referred to as Daptomicina Xellia in this leaflet) is daptomycin. Daptomycin is an
antibacterial agent that can stop the growth of certain bacteria.
Daptomicina Xellia is used in adults and in children and adolescents (aged 1 to 17
years) to treat skin and underlying tissue (subcutaneous) infections. It is also
used to treat bloodstream infections when associated with skin infections.
Daptomicina Xellia is also used in adults to treat infections of the tissues lining the inside of the heart (including heart valves) caused by a type of bacterium called Staphylococcus aureus. It is also used to treat bloodstream infections caused by the same type of bacterium when associated with skin or heart infections.
Depending on the type of infection(s) you have, your doctor may also prescribe other antibacterial agents during treatment with Daptomicina Xellia.

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

Do not receive Daptomicin Xellia

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

If this applies to you, inform your doctor or nurse. If you think you may be allergic, consult your doctor or nurse.
Warnings and precautions
Talk to your doctor, pharmacist, or nurse before you are given
Daptomicin Xellia:

• If you have or have previously had kidney problems. Your doctor may need to adjust the dose of Daptomicin Xellia (see section 3 of this leaflet).
• Patients treated with daptomycin sometimes experience muscle pain, weakness, or discomfort (see section 4 of this leaflet for more information). If this occurs, inform your doctor. Your doctor will ensure you undergo a blood test and will advise whether you should continue or stop treatment with Daptomicin Xellia. Symptoms usually resolve within a few days after stopping Daptomicin Xellia.
• If you are overweight. Daptomycin blood levels may be higher than those observed in individuals of average weight, so you may need closer monitoring for side effects.

If any of these situations apply to you, inform your doctor or nurse before you are
given Daptomicin Xellia.
Inform your doctor immediately if any of the following symptoms occur (see
section 4):

• Severe acute allergic reactions have been observed in patients treated with nearly all antibacterial medicines, including daptomycin. Inform your doctor or nurse immediately if you experience symptoms suggesting an allergic reaction, such as wheezing, difficulty breathing, swelling of the face, neck, or throat, skin rash, hives, or fever.
• Unusual tingling or numbness in the hands or feet, loss of sensation, or difficulty moving. If this occurs, inform your doctor, who will decide whether to continue treatment.
• Diarrhea, especially if you notice blood or mucus, or if diarrhea becomes severe or persistent. If this occurs, inform your doctor, who will decide whether to continue treatment.
• Onset or worsening of fever, cough, or difficulty breathing. These may be signs of a rare but serious lung disease called eosinophilic pneumonia. Your doctor will check your lung function and decide whether to continue or stop treatment with Daptomicin Xellia.

Daptomicin Xellia may interfere with laboratory tests measuring blood coagulation. The results may suggest a blood clotting problem even when none exists. It is therefore important that your doctor is aware that you are receiving Daptomicin Xellia. Inform your doctor that you are being treated with Daptomicin Xellia.
Your doctor will perform blood tests to monitor muscle function both before starting treatment and regularly during treatment. Inform your doctor that you are being treated with Daptomicin Xellia.
Children and adolescents
Daptomicin Xellia must not be given to children under one year of age, as animal studies have shown that serious adverse effects may occur in this age group.
Use in the elderly
People over 65 years of age may receive the same dose as adults, provided they have normal kidney function.
Other medicines and Daptomicin Xellia
Inform your doctor or nurse if you are taking, have recently taken, or might take any other medicines. It is particularly important to inform them if you are taking:

• Medicines called statins or fibrates (used to lower cholesterol) or cyclosporine (a medicine used in organ transplantation to prevent organ rejection or in other conditions such as rheumatoid arthritis or atopic dermatitis). If you are taking any of these medicines (and others that may affect muscles) during treatment with Daptomicin Xellia, the risk of muscle-related adverse effects may be increased. Your doctor may decide not to prescribe Daptomicin Xellia or may temporarily discontinue the other medicines.
• Painkillers called non-steroidal anti-inflammatory drugs (NSAIDs) or COX-2 inhibitors (e.g. celecoxib). These may interfere with the renal effects of Daptomicin Xellia.
• Oral anticoagulants (e.g. warfarin), which are medicines that prevent blood from clotting. Your doctor may need to monitor your blood clotting time.

Pregnancy and breastfeeding
Daptomycin is generally not administered to pregnant women. If you are pregnant, suspect you may be pregnant, are planning pregnancy, or are breastfeeding, consult your doctor or pharmacist before receiving this medicine.
DO NOT breastfeed while taking Daptomicin Xellia, as it may pass into breast milk and could therefore affect the infant.
Driving and using machines
Daptomycin has no known effects on the ability to drive or operate machinery.
Daptomicin Xellia contains sodium
Each 500 mg vial contains approximately 4.6 mg of sodium.
This medicine contains less than 1 mmol of sodium (23 mg) per vial and is therefore essentially "sodium-free".

3. How Daptomycin Xellia is administered

Daptomycin Xellia is usually administered by a doctor or nurse.
Adults (aged 18 years and older)
The dose depends on your body weight and the type of infection being treated. In adults, the usual dose is 4 mg per kilogram (kg) of body weight, administered once daily for skin infections, or 6 mg per kg of body weight administered once daily for heart infection or blood infection associated with skin or heart infection. In adult patients, this dose is injected 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 individuals over 65 years of age, provided they have normal renal function.
If you have impaired renal function, you may receive Daptomycin Xellia less frequently, e.g., every other day. If you are on dialysis and the next dose of Daptomycin Xellia is due on the same day as dialysis, Daptomycin Xellia is usually administered after completion of dialysis.
Children and adolescents (from 1 to 17 years of age)
The dose for children and adolescents (from 1 to 17 years of age) depends on the patient's age and the type of infection being treated. This dose is injected directly into the bloodstream (into a vein) as an infusion lasting approximately 30–60 minutes.
Typically, a course of treatment for skin infections lasts from 1 to 2 weeks. For blood or heart infections and skin infections, your doctor will decide how long your treatment should last.
Detailed instructions for use and handling are provided at the end of this leaflet.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them.
The most serious side effects are described below:
Very rare serious side effects (may affect up to 1 in 10,000 patients):
In some cases, hypersensitivity reactions (severe allergic reactions including anaphylaxis, angioedema, drug rash with eosinophilia and systemic symptoms (DRESS)) have been reported during administration of daptomycin. This severe allergic reaction requires immediate medical intervention. Inform your doctor or nurse immediately if any of the following symptoms occur:

• Chest pain or tightness
• Skin rash with blistering, sometimes affecting the mouth and genitals
• Swelling around the throat
• Rapid or weak heartbeat
• Wheezing
• Fever
• Chills or shivering
• Flushing
• Dizziness
• Fainting
• Metallic taste in the mouth.

If you notice unexplained muscle pain, tenderness, or weakness, inform your doctor immediately. In very rare cases (reported in fewer than 1 in 10,000 patients), muscle problems may be severe, including muscle breakdown (rhabdomyolysis), which can lead to kidney damage.
Serious side effects with unknown frequency (frequency cannot be determined from available data):
A rare but potentially serious lung disease called eosinophilic pneumonia has been reported in patients receiving daptomycin, in most cases after more than 2 weeks of treatment. Symptoms may include difficulty breathing, new or worsening cough, or new or worsening fever. If you experience these symptoms, inform your doctor or nurse immediately.
If you develop raised or fluid-filled skin lesions over a large area of the body, inform your doctor or nurse immediately.

The more frequently reported side effects are described below:
Common side effects (may affect up to 1 in 10 patients):

• Fungal infections such as oral candidiasis
• Urinary tract infections
• Candida infections
• Decrease in the number of red blood cells (anaemia)
• Dizziness, anxiety, difficulty sleeping
• Headache
• Fever, weakness (asthenia)
• High or low blood pressure
• Constipation, abdominal pain
• Diarrhoea, nausea or vomiting
• Flatulence
• Abdominal bloating or discomfort
• Skin rash or itching
• Pain, itching or redness at the infusion site
• Pain in arms or legs
• Increased levels of liver enzymes or creatine phosphokinase (CPK) shown in blood tests.

Other side effects that may occur during treatment with daptomycin are listed below:
Uncommon side effects (may affect up to 1 in 100 patients):

• Blood abnormalities (such as increased number of small blood particles called platelets, which may increase the tendency for blood to clot, or increased levels of certain types of white blood cells)
• Decreased appetite
• Tingling or numbness in hands or feet, altered taste
• Tremor
• Dizziness
• Changes in heart rhythm, flushing
• Indigestion (dyspepsia), inflammation of the tongue
• Skin rash
• Muscle pain, cramps or muscle weakness, inflammation of muscles (myositis), joint pain
• Kidney problems
• Vaginal inflammation and irritation
• Pain or general weakness, fatigue (tiredness)
• Blood tests showing increased levels of blood sugar, serum creatinine, myoglobin or lactate dehydrogenase (LDH), prolonged blood clotting time, or electrolyte imbalance.
• Itching of the eyes.

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

• Yellowing of the skin and eyes
• Prolongation of prothrombin time.

Frequency not known (frequency cannot be determined from available data):

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

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects directly via the national reporting system at: http://www.aifa.gov.it/content/segnalazioni-reazioni-avverse
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Daptomycin Xellia

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and label after Exp. The expiry date refers to the last day of that month.
Store in a refrigerator (2°C – 8°C).

After reconstitution:
The chemical and physical in-use 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.
From a microbiological point of view, the medicine should be used immediately. If not used immediately, the user is responsible for the storage period before use and the conditions under which it is kept, provided that reconstitution has been carried out under controlled and validated aseptic conditions.

After dilution (performed immediately after reconstitution):
The chemical and physical in-use stability of the diluted solution in infusion bags has been demonstrated for 12 hours at 25°C and up to 24 hours at 2°C – 8°C.
From a microbiological point of view, unless the method of opening/reconstitution/dilution excludes the risk of microbial contamination, the medicine must be used immediately. If not used immediately, the user is responsible for the duration of storage during use and the conditions prior to use.

After reconstitution and dilution:
The chemical and physical in-use stability has been demonstrated for 12 hours at 25°C and up to 24 hours at 2°C – 8°C, referring to the total storage period (reconstituted solution in vial and diluted solution in infusion bag).
From a microbiological point of view, unless the method of opening/reconstitution/dilution excludes the risk of microbial contamination, the medicine must be used immediately. If not used immediately, the user is responsible for the storage period and conditions during use.

Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer used. This will help protect the environment.

6. Package contents and other information

What Daptomicin Xellia contains
The active substance is daptomycin. One vial of powder contains 500 mg of
daptomycin.
After reconstitution with 10 ml of sodium chloride 9 mg/ml (0.9%) solution, 1 ml
contains 50 mg of daptomycin.
The other component is sodium hydroxide.

Description of the appearance of Daptomicin Xellia and contents of the pack
Daptomicin Xellia powder for solution for injection/infusion is supplied as a
lyophilisate or powder ranging in colour from pale yellow to light brown in a glass vial
with a rubber stopper and grey aluminium seal with a dark blue overcap. Prior to
administration, it is mixed with a solvent to form a liquid.
Daptomicin Xellia is available in packs containing 1 vial or 5 vials.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Xellia Pharmaceuticals Aps
Dalslandsgade 11, København S,
Copenhagen,
Denmark 2300

Marketing Authorisation Holder in Italy
Sun Pharma Italia Srl
Viale Giulio Richard, 1 – 20143 Milano

This medicinal product has been authorised in the EEA Member States under the following names:

The following information is intended exclusively for healthcare professionals

Important: Before prescribing, consult the Summary of Product Characteristics.
Instructions for use and handling

500 mg pack:
In adults, daptomycin may be administered intravenously either as a 30-minute infusion or as a 2-minute injection. Daptomycin must not be administered as a 2-minute injection in pediatric patients. In pediatric patients aged 7 to 17 years, daptomycin should be administered as a 30-minute infusion. In pediatric patients under 7 years of age receiving a dose of 9–12 mg/kg, daptomycin should be administered over 60 minutes. Preparation of the infusion solution requires further dilution, as described below.

Administration of Daptomicina Xellia as a 30- or 60-minute intravenous infusion

A concentration of 50 mg/ml of Daptomicina Xellia for infusion is obtained by reconstituting the lyophilisate with 10 ml of sodium chloride 9 mg/ml (0.9%) solution for injection.
Approximately 15 minutes are required for complete dissolution of the lyophilisate. The fully reconstituted medicinal product has a clear appearance, and there may be a few bubbles or foam around the edges of the vial.

To prepare Daptomicina Xellia for intravenous infusion, follow the instructions below. Throughout the entire process of reconstitution or dilution of Daptomicina Xellia lyophilisate, an aseptic technique must be used.

For Reconstitution:

1. Remove the polypropylene overcap to expose the central portion of the rubber stopper. Wipe the top of the rubber stopper with an alcohol-soaked or other antiseptic swab and allow it to dry. After cleaning, do not touch the rubber stopper or allow it to come into contact with any other surface. Draw 10 ml of sodium chloride 9 mg/ml (0.9%) solution for injection into a syringe using a sterile transfer needle with a gauge of 21 or smaller, or a needle-free device, and slowly inject it into the vial, inserting the needle through the center of the rubber stopper with the tip directed toward the vial wall.

2. Gently rotate the vial to ensure the product is completely wetted by the liquid, then allow it to stand for 10 minutes.

3. Finally, gently rotate the vial for several minutes until a clear reconstituted solution is obtained. Avoid vigorous shaking or agitation to prevent foam formation.

4. Before use, carefully inspect the reconstituted solution to ensure complete dissolution of the product and visually check for the absence of particulate matter. The color of the reconstituted Daptomicina Xellia solution may range from pale yellow to light brown.

5. The reconstituted solution must then be diluted with sodium chloride 9 mg/ml (0.9%) solution (typical volume 50 ml).

For Dilution:

1. Slowly withdraw the properly reconstituted liquid (50 mg of daptomycin/ml) from the vial using a new sterile needle with a gauge of 21 or smaller, inverting the vial to allow the solution to flow toward the stopper. Insert the syringe needle into the inverted vial. While keeping the vial inverted, position the needle tip at the bottom of the solution in the vial and aspirate the solution into the syringe. Before removing the needle from the vial, pull back the plunger to the end of the syringe barrel to withdraw the required amount of solution from the inverted vial.
2. Expel air, large bubbles, and excess solution until the required dose is obtained.
3. Transfer the required reconstituted dose into 50 ml of sodium chloride 9 mg/ml (0.9%) solution.
4. The reconstituted and diluted solution should then be administered intravenously over 30 or 60 minutes.

Daptomicina Xellia is physically and chemically incompatible with glucose-containing solutions. The following agents have been shown to be compatible when added to infusion solutions containing Daptomicina Xellia: aztreonam, ceftazidime, ceftriaxone, gentamicin, fluconazole, levofloxacin, dopamine, heparin, and lidocaine.

After dilution (performed immediately after reconstitution):
Chemical and physical in-use stability of the diluted solution in infusion bags has been demonstrated for 12 hours at 25°C and up to 24 hours at 2°C–8°C.
From a microbiological standpoint, unless the method of opening/reconstitution/dilution excludes the risk of microbial contamination, the medicinal product must be used immediately. If not used immediately, the user is responsible for the storage period and conditions prior to use.

After reconstitution and dilution:
Chemical and physical in-use stability has been demonstrated for 12 hours at 25°C and up to 24 hours at 2°C–8°C, referring to the total storage period (reconstituted solution in vial and diluted solution in infusion bag).
From a microbiological standpoint, unless the method of opening/reconstitution/dilution excludes the risk of microbial contamination, the medicinal product must be used immediately. If not used immediately, the user is responsible for the storage period and conditions during use.

Administration of Daptomicina Xellia as a 2-minute intravenous injection (adults only)

For reconstitution of Daptomicina Xellia for intravenous injection, water must not be used. Daptomicina Xellia must be reconstituted only with sodium chloride 9 mg/ml (0.9%).
A concentration of 50 mg/ml of Daptomicina Xellia for injection is obtained by reconstituting the lyophilisate with 10 ml of sodium chloride 9 mg/ml (0.9%) solution for injection.
Approximately 15 minutes are required for complete dissolution of the lyophilisate. The fully reconstituted medicinal product has a clear appearance, and there may be a few bubbles or foam around the edges of the vial.

To prepare Daptomicina Xellia for intravenous injection, follow the instructions below. Throughout the entire process of reconstitution of Daptomicina Xellia lyophilisate, an aseptic technique must be used.

1. Remove the polypropylene overcap to expose the central portion of the rubber stopper. Wipe the top of the rubber stopper with an alcohol-soaked or other antiseptic swab and allow it to dry. After cleaning, do not touch the rubber stopper or allow it to come into contact with any other surface. Draw 10 ml of sodium chloride 9 mg/ml (0.9%) solution for injection into a syringe using a sterile transfer needle with a gauge of 21 or smaller, or a needle-free device, and slowly inject it into the vial, inserting the needle through the center of the rubber stopper with the tip directed toward the vial wall.
2. Gently rotate the vial to ensure the product is completely wetted by the liquid, then allow it to stand for 10 minutes.
3. Finally, gently rotate the vial for several minutes until a clear reconstituted solution is obtained. Avoid vigorous shaking or agitation to prevent foam formation.
4. Before use, carefully inspect the reconstituted solution to ensure complete dissolution of the product and visually check for the absence of particulate matter. The color of the reconstituted Daptomicina Xellia solution may range from pale yellow to light brown.
5. Invert the vial to allow the solution to flow toward the stopper. Using a new syringe, insert the needle into the inverted vial. While keeping the vial inverted, position the needle tip at the bottom of the solution in the vial and aspirate the solution into the syringe. Slowly withdraw the reconstituted liquid (50 mg of daptomycin/ml) from the vial using a sterile needle with a gauge of 21 or smaller.
6. Before removing the needle from the vial, pull back the plunger to the end of the syringe barrel to withdraw all remaining solution from the inverted vial.
7. Replace the needle with a new needle suitable for intravenous injection.
8. Expel air, large bubbles, and excess solution until the required dose is obtained.
9. The reconstituted solution should then be administered slowly by intravenous injection over 2 minutes.

After reconstitution:
Chemical and physical in-use 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.
From a microbiological standpoint, the medicinal product must be used immediately. If not used immediately, the user is responsible for the storage period during use, which under normal circumstances should not exceed 24 hours at 2°C–8°C, unless reconstitution is performed under controlled and validated aseptic conditions, as well as the conditions prior to use.

The medicinal product must not be mixed with other products except those mentioned above.
Daptomicina Xellia vials are for single use only. Any unused solution remaining in the vial must be discarded.