Xelltempra

Package leaflet: Information for the patient

Xelltempra 350 mg powder for solution for injection/infusion

Daptomycin
Generic medicine
Please read all of this leaflet carefully before you are given 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 or nurse.
• This medicine has been prescribed for you only. Do not pass it on to other people, even if they have the same symptoms as yours, as it may be harmful to them.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or nurse. See section 4.

Contents of this leaflet

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

1. What Xelltempra is and what it is used for

The active substance of Xelltempra powder for solution for injection/infusion is daptomycin.
Daptomycin is an antibacterial agent that can stop the growth of certain bacteria. Xelltempra 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.

Xelltempra 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 heart infections.

Depending on the type of infection(s) you have, your doctor may also prescribe other antibacterial agents during treatment with Xelltempra.

2. What you should know before being given Xelltempra

Xelltempra must not be administered to you
If you are allergic to daptomycin 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 or nurse before you are given Xelltempra:

• If you have or have previously had kidney problems. Your doctor may need to adjust the dose of Xelltempra (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 that you undergo a blood test

and will advise you whether or not to continue treatment with Xelltempra. Symptoms usually
disappear within a few days after stopping Xelltempra.

• If you have developed a severe skin reaction, skin peeling, blistering rash, and/or mouth ulcers or serious kidney problems after taking daptomycin.
• 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 adverse effects.

If any of these apply to you, inform your doctor or nurse before receiving Xelltempra.
Inform your doctor or nurse immediately if any of the following symptoms occur:

• Severe acute allergic reactions have been observed in patients treated with nearly all antibacterial medicines, including daptomycin. Symptoms may include wheezing, difficulty breathing, swelling of the face, neck, and throat, skin rash, hives, or fever.
• Serious skin disorders have been reported with the use of daptomycin. Symptoms associated with these skin disorders may include:
• onset or worsening of fever,
• raised red spots or fluid-filled lesions on the skin, which may appear under the arms or in the chest or groin areas and may spread over large areas of the body,
• blisters or sores in the mouth or on the genitals.
• A serious kidney problem has been reported with the use of daptomycin. Symptoms may include fever and skin rash.
• 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.
• Diarrhoea, especially if you notice blood or mucus, or if diarrhoea becomes severe or persistent.
• 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 condition and decide whether you should continue treatment with Xelltempra.

Xelltempra may interfere with laboratory tests measuring blood coagulation. Test results may suggest a blood clotting problem even when no actual problem exists. It is therefore important that your doctor is aware that you are receiving Xelltempra. Inform your doctor that you are being treated with Xelltempra.
Your doctor will perform blood tests to monitor your muscle condition, both before starting treatment and regularly during treatment with Xelltempra.
Children and adolescents
Xelltempra must not be given to children under one year of age, as animal studies have indicated 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 Xelltempra
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 ciclosporin (a medicine used in organ transplantation to prevent organ rejection or for 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 Xelltempra, the risk of muscle-related adverse effects may be increased. Your doctor may decide not to

prescribe Xelltempra or to 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 Xelltempra.
• 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
Xelltempra is generally not given to pregnant women. If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, ask your doctor or pharmacist for advice before this medicine is administered to you.
Do not breastfeed while taking Xelltempra, as daptomycin may pass into breast milk and could therefore affect the baby.
Driving and using machines
Xelltempra has no known effect on the ability to drive or operate machinery.

3. How Xelltempra is administered

Xelltempra 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, given once daily for skin infections, or 6 mg per kg of body weight given 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 Xelltempra less frequently, e.g., every other day. If you are undergoing dialysis and your next dose of Xelltempra is due on the day of dialysis, Xelltempra is usually administered after completion of dialysis.
Children and adolescents (1 to 17 years of age)
The dose for children and adolescents (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 to 60 minutes.
Typically, for skin infections, a treatment course lasts from 1 to 2 weeks. For blood 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 everybody gets them. The most serious side effects are listed below:
Serious side effects with unknown frequency (frequency cannot be estimated from the available data)

• In some cases, hypersensitivity reactions (severe allergic reactions including anaphylaxis and angioedema) have been reported during administration of daptomycin. This severe allergic reaction requires immediate medical attention. Inform your doctor or nurse immediately if you experience any of the following symptoms:

• Chest pain or tightness,

• Rash or hives,

• Swelling around the throat,

• Rapid or weak heartbeat,

• Wheezing,

• Fever,

• Chills or shivering,

• Flushing,

• Dizziness,

• Fainting,

• Metallic taste.

• If you notice unexplained muscle pain, tenderness, or weakness, inform your doctor immediately. Muscle problems may be serious, including destruction of muscle tissue (rhabdomyolysis), which may lead to kidney damage. Other serious side effects reported with the use of daptomycin include:

• A rare but potentially serious lung disease called eosinophilic pneumonia, occurring mostly after more than 2 weeks of treatment. Symptoms may include difficulty breathing, new or worsening cough, or new or worsening fever.

• Severe skin disorders. Symptoms may include:

  • new or worsening fever,
  • raised red skin lesions or fluid-filled blisters, which may appear under the arms or in the chest or groin area and may spread over large areas of the body,
  • blisters or sores in the mouth or on the 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 further tests to make a diagnosis.

The side effects reported most frequently are listed below:
Common side effects (may affect up to 1 in 10 people)

• Fungal infections such as candidiasis,
• Urinary tract 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, feeling unwell (nausea or vomiting),
• Flatulence,
• Abdominal swelling or bloated stomach,
• Rash (of the skin) or itching,
• Pain, itching or redness at the infusion site,
• Pain in the arms or legs,
• Increased levels of liver enzymes or creatine phosphokinase (CPK) shown by blood tests.

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

• Blood disorders (such as increased number of small blood particles called platelets, which could increase the tendency for blood to clot, or increased levels of certain types of white blood cells),
• Loss of appetite,
• Tingling or numbness in the hands or feet, altered taste,
• Tremor,
• Changes in heart rhythm, hot flushes,
• Indigestion (dyspepsia), inflammation of the tongue,
• Rash (of the skin) associated with itching,
• Muscle pain, cramps or weakness, inflammation of the muscles (myositis), joint pain,
• Kidney problems,
• Inflammation and irritation of the vagina,
• General pain or weakness, 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 people)

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

Frequency not known (frequency cannot be estimated from the available data)
Colitis associated with the use of antibacterial agents, 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 [appropriate national reporting system].
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Xelltempra

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./EXP. The expiry date refers to the last day of that month.
Store below 25 °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 72 hours at 2 °C–8 °C.

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 for 48 hours at 2 °C–8 °C.

After reconstitution and dilution:
The chemical and physical in-use stability has been demonstrated for 12 hours at 25 °C and for 48 hours at 2 °C–8 °C,
this period referring to the overall storage duration (reconstituted solution in the vial and diluted solution in the infusion bag).

However, from a microbiological standpoint, the medicine should be used immediately.
This medicine does not contain preservatives or bacteriostatic agents. 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/dilution has been carried out under controlled and validated aseptic conditions.

Do not dispose of medicines 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 Xelltempra contains
The active substance is daptomycin. One vial of powder contains 350 mg of daptomycin.
One ml contains 50 mg of daptomycin after reconstitution in the vial exclusively with 7 ml of
sterile water for injections.
The other components are arginine, histidine, isoleucine and concentrated hydrochloric acid (for pH
adjustment).

Description of the appearance of Xelltempra and contents of the pack
Xelltempra powder for solution for injection/infusion is supplied as a powder or lyophilisate in a light yellow to light brown colour in a clear glass vial, closed with a rubber stopper and an aluminium seal with a white plastic overcap. Prior to administration, it is mixed with a solvent to form a liquid.
Xelltempra is available in packs containing 1 vial.

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

The following information is intended exclusively for healthcare professionals

Important: Consult the Summary of Product Characteristics before prescribing.
Instructions for use and handling

Other formulations of daptomycin exist which differ with respect to reconstitution and storage methods. Carefully follow the reconstitution and storage procedures described in this document.

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

Administration of Xelltempra as a 30- or 60-minute intravenous infusion

Xelltempra must be reconstituted in the vial exclusively with sterile water for injections.
DO NOT use saline solutions for reconstitution in the vial.

A concentration of 50 mg/ml of Xelltempra for infusion is obtained by reconstituting the lyophilisate with 7 ml of sterile water for injections.
Less than 3 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 Xelltempra for intravenous infusion, follow the instructions below:
An aseptic technique must be used throughout the entire process of reconstitution and dilution of Xelltempra lyophilisate.

For reconstitution:

1. Remove the overcap made of polypropylene to expose the central part of the rubber stopper. Clean 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 contact any other surface. Draw 7 ml of sterile water for injections into a syringe using a sterile transfer needle with a diameter of 21 gauge or smaller, then inject it into the vial by inserting the needle into the central part of the rubber stopper with the tip directed toward the vial wall.
2. Rotate or gently agitate the contents of the vial for a few minutes until a completely reconstituted solution is obtained.
3. Before use, the reconstituted solution must be carefully inspected visually to ensure complete dissolution of the product and absence of particulate matter. The colour of the reconstituted Xelltempra solution may vary from pale yellow to light brown.
4. The reconstituted solution must then be diluted with 0.9% sodium chloride solution (9 mg/ml) (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 diameter of 21 gauge or smaller, by 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, place the tip of the needle 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 draw up 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 0.9% sodium chloride solution (9 mg/ml).
4. The reconstituted and diluted solution must then be administered intravenously over 30 or 60 minutes.

Xelltempra is physically and chemically incompatible with glucose-containing solutions. The following agents have been shown to be compatible when added to infusion solutions containing Xelltempra: 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 for 48 hours at 2 °C–8 °C.

After reconstitution and dilution:
Chemical and physical in-use stability has been demonstrated for 12 hours at 25 °C and for 48 hours at 2 °C–8 °C; this period refers to the total storage time (reconstituted solution in the vial and diluted solution in the infusion bag).

However, from a microbiological standpoint, the medicinal product should be used immediately. This medicinal product does not contain preservatives or bacteriostatic agents. If not used immediately, the user is responsible for the in-use storage period, which should not normally exceed 24 hours at 2 °C–8 °C, unless reconstitution/dilution was performed under controlled and validated aseptic conditions.

Administration of Xelltempra as a 2-minute intravenous injection (adults only):

Xelltempra must be reconstituted in the vial exclusively with sterile water for injections.
DO NOT use saline solutions for reconstitution in the vial, as this would result in a hyperosmotic solution which could cause infusion site reactions if the reconstituted product is administered as a 2-minute intravenous injection.

A concentration of 50 mg/ml of Xelltempra for injection is obtained by reconstituting the lyophilisate with 7 ml of sterile water for injections.
Less than 3 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 Xelltempra for intravenous injection, follow the instructions below:
An aseptic technique must be used throughout the entire process of reconstitution of Xelltempra lyophilisate.

1. Remove the overcap made of polypropylene to expose the central part of the rubber stopper. Clean 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 contact any other surface. Draw 7 ml of sterile water for injections into a syringe using a sterile transfer needle with a diameter of 21 gauge or smaller, then inject it into the vial by inserting the needle into the central part of the rubber stopper with the tip directed toward the vial wall.
2. Rotate or gently agitate the contents of the vial for a few minutes until a completely reconstituted solution is obtained.
3. Before use, the reconstituted solution must be carefully inspected visually to ensure complete dissolution of the product and absence of particulate matter. The colour of the reconstituted Xelltempra solution may vary from pale yellow to light brown.
4. Slowly withdraw the reconstituted liquid (50 mg daptomycin/ml) from the vial using a sterile needle with a diameter of 21 gauge or smaller.
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, place the tip of the needle 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 draw up all the solution from the inverted vial.
6. Replace the needle with a new needle for intravenous injection.
7. Expel air, large bubbles, and excess solution until the required dose is obtained.
8. The reconstituted solution must 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 72 hours at 2 °C–8 °C.

However, from a microbiological standpoint, the medicinal product should be used immediately.
This medicinal product does not contain preservatives or bacteriostatic agents. If not used immediately, the user is responsible for the in-use storage period, which should not normally exceed 24 hours at 2 °C–8 °C, unless reconstitution was performed under controlled and validated aseptic conditions.

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

Package leaflet: Information for the user

Xelltempra 500 mg powder for injectable/infusion solution

Daptomycin
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 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 could be harmful.
• If you experience any adverse reactions, including those not listed in this leaflet, contact your doctor or nurse. See section 4.

Contents of this leaflet

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

1. What Xelltempra is and what it is used for

The active substance of Xelltempra powder for injectable/infusion solution is daptomycin.
Daptomycin is an antibacterial agent that can stop the growth of certain bacteria. Xelltempra 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.
Xelltempra 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 heart infections.
Depending on the type of infection(s) you have, your doctor may also prescribe other antibacterial
agents during treatment with Xelltempra.

2. What you should know before being given Xelltempra

Do not be given Xelltempra
If you are allergic to daptomycin 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 or nurse before you are given Xelltempra:

• If you have or have previously had kidney problems. Your doctor may need to adjust your dose of Xelltempra (see section 3 of this leaflet).
• Patients treated with daptomycin have sometimes experienced muscle pain, weakness, or discomfort (see section 4 of this leaflet for more information). If this occurs, inform your doctor. Your doctor will ensure that you have a blood test and will advise you whether or not to continue treatment with Xelltempra. Symptoms usually disappear within a few days after stopping Xelltempra.
• If you have developed a severe skin reaction, skin peeling, blistering rash, mouth ulcers, or severe kidney problems after taking daptomycin.
• 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 adverse effects.

If any of these apply to you, inform your doctor or nurse before receiving Xelltempra.

Inform your doctor or nurse immediately if any of the following symptoms occur:

• Severe acute allergic reactions have been observed in patients treated with nearly all antibacterial medicines, including daptomycin. Symptoms may include wheezing, difficulty breathing, swelling of the face, neck, and throat, skin rash, hives, or fever.
• Serious skin disorders have been reported with the use of daptomycin. Symptoms associated with these skin conditions may include:
  • onset or worsening of fever,
  • raised or fluid-filled red spots on the skin, which may appear under the arms, or in the chest or groin areas, and may spread over large areas of the body,
  • blisters or sores in the mouth or on the genitals.
• A serious kidney problem has been reported with the use of daptomycin. Symptoms may include fever and skin rash.
• 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.
• 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 treatment with Xelltempra.

Xelltempra may interfere with laboratory tests measuring blood coagulation. Test results may suggest a blood clotting problem even when no actual problem exists. It is therefore important that your doctor knows you are taking Xelltempra. Inform your doctor that you are being treated with Xelltempra.

Your doctor will perform blood tests to monitor your muscle condition both before starting treatment and regularly during treatment with Xelltempra.

Children and adolescents
Xelltempra must not be given to children under one year of age, as animal studies have indicated 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 Xelltempra
Inform your doctor or nurse if you are taking, have recently taken, or might take any other medicines.

It is particularly important to inform your doctor 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 (or others that may cause muscle-related side effects) during treatment with Xelltempra, your risk of muscle-related adverse effects may be increased. Your doctor may decide not to prescribe Xelltempra 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 Xelltempra.

• 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
Xelltempra is generally not given to pregnant women. If you are pregnant, suspect you may be pregnant, are planning to become pregnant, or are breastfeeding, ask your doctor or pharmacist for advice before this medicine is administered.

Do not breastfeed while taking Xelltempra, as Xelltempra may pass into breast milk and could therefore affect the infant.

Driving and using machines
Xelltempra has no known effect on the ability to drive or operate machinery.

3. How Xelltempra is administered

Xelltempra 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, given once daily for skin infections, or 6 mg per kg of body weight given once daily for a heart infection
or a 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 Xelltempra less frequently, e.g., on alternate days. If you are undergoing dialysis and the next dose of Xelltempra is due on the same day as dialysis, Xelltempra will usually be administered after completion of dialysis.
Children and adolescents (aged 1 to 17 years)
The dose for children and adolescents (aged 1 to 17 years) 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 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 everybody gets them. The most serious side effects are described below:
Serious side effects with unknown frequency (frequency cannot be estimated from the available data)

• In some cases, hypersensitivity reactions (severe allergic reactions including anaphylaxis and angioedema) have been reported during administration of daptomycin. This severe allergic reaction requires immediate medical intervention. Inform your doctor or nurse immediately if you experience any of the following symptoms:

• Chest pain or tightness,

• Skin rash or hives,

• Swelling around the throat,

• Rapid or weak heartbeat,

• Wheezing,

• Fever,

• Chills or shivering,

• Hot flushes,

• Dizziness,

• Fainting,

• Metallic taste.

• If you notice unexplained muscle pain, tenderness, or weakness, inform your doctor immediately. Muscle problems can be serious, including destruction of muscle tissue (rhabdomyolysis), which may lead to kidney damage. Other serious side effects reported with daptomycin use include:

• A rare but potentially serious lung disease called eosinophilic pneumonia, usually occurring after more than 2 weeks of treatment. Symptoms may include difficulty breathing, new or worsening cough, or new or worsening fever.

• Severe skin disorders. Symptoms may include:

• New or worsening fever,

• Raised or fluid-filled red skin lesions that may appear under the arms, on the chest or groin area and may spread over large areas of the body,

• Blisters or sores in the mouth or on the genitals.

• Severe kidney problems. Symptoms may include fever and skin rash. If you experience these symptoms, inform your doctor or nurse immediately. Your doctor will perform further tests to make a diagnosis.

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

• Fungal infections such as candidiasis,
• Urinary tract 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, feeling unwell (nausea or vomiting),
• Flatulence,
• Abdominal swelling or bloated stomach,
• 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 Xelltempra are described below:
Uncommon side effects (may affect up to 1 in 100 people)

• Blood disorders (such as increased number of small blood particles called platelets, which may increase the tendency for blood clotting, or increased levels of certain types of white blood cells),
• Loss of appetite,
• Tingling or numbness in hands or feet, altered taste,
• Tremor,
• Changes in heart rhythm, hot flushes,
• Indigestion (dyspepsia), inflammation of the tongue,
• Skin rash associated with itching,
• Muscle pain, cramps or weakness, muscle inflammation (myositis), joint pain,
• Kidney problems,
• Vaginal inflammation and irritation,
• General pain or weakness, 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 people)

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

Frequency not known (frequency cannot be estimated from the available data)
Colitis associated with antibiotic use, 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.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Xelltempra

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./EXP. The expiry date refers to the last day of that month.
Store below 25 °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 72 hours at 2 °C–8 °C.

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 for 48 hours at 2 °C–8 °C.

After reconstitution and dilution:
The chemical and physical in-use stability has been demonstrated for 12 hours at 25 °C and for 48 hours at
2 °C–8 °C, a period referring to the total storage duration (reconstituted solution in the vial and diluted
solution in the infusion bag).

However, from a microbiological standpoint, the medicine should be used immediately.
This medicine does not contain preservatives or bacteriostatic agents. If immediate use is not possible,
the user is responsible for the in-use storage duration, which under normal circumstances should not exceed
24 hours at 2 °C–8 °C, unless reconstitution/dilution has been carried out under controlled and validated
aseptic conditions.

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

6. Package contents and other information

What Xelltempra contains
The active substance is daptomycin. One vial of powder contains 500 mg of daptomycin.
One ml contains 50 mg of daptomycin after reconstitution in the vial exclusively with 10 ml
of sterile water for injectable preparations.
The other components are arginine, histidine, isoleucine, and concentrated hydrochloric acid (for
pH adjustment).

Description of the appearance of Xelltempra and contents of the pack
Xelltempra powder for solution for injection/infusion is supplied as a powder or lyophilisate with a colour ranging from light yellow to light brown in a clear glass vial, with a rubber stopper and an aluminium seal with a purple plastic cap. Before administration, it is mixed with a solvent to form a liquid.
Xelltempra is available in packs containing 1 vial.

Marketing Authorization Holder and Manufacturer
Xellia Pharmaceuticals ApS
Dalslandsgade 11
2300 Copenhagen S, Denmark

The following information is intended exclusively for healthcare professionals

Important: Before prescribing, consult the Summary of Product Characteristics.
Instructions for use and handling
There are other formulations of daptomycin that differ with respect to reconstitution and storage
methods. Carefully follow the reconstitution and storage procedures described in this document.

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

Administration of Xelltempra as a 30- or 60-minute intravenous infusion
Xelltempra must be reconstituted in the vial exclusively with sterile water for injections.
DO NOT use saline solutions for reconstitution in the vial.
A concentration of 50 mg/ml of Xelltempra for infusion is obtained by reconstituting the lyophilisate with 10 ml of sterile water for injections.
Complete dissolution of the lyophilisate takes less than 3 minutes. 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 Xelltempra for intravenous infusion, follow the instructions below: throughout the entire process of reconstitution or dilution of Xelltempra lyophilisate, an aseptic technique must be used.

For reconstitution:

1. Remove the polypropylene overcap to expose the central portion of the rubber stopper. Clean 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 contact any other surface. Draw 10 ml of sterile water for injections into a syringe using a sterile transfer needle with a gauge of 21 or smaller, then inject it into the vial by inserting the needle into the central portion of the rubber stopper with the tip directed toward the vial wall.
2. Rotate or gently agitate the contents of the vial for a few minutes until a completely reconstituted solution is obtained.
3. Before use, the reconstituted solution must be carefully inspected visually to ensure complete dissolution of the product and absence of particulate matter. The color of the reconstituted Xelltempra solution may vary from pale yellow to light brown.
4. 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 tip of the needle 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 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.

Xelltempra is physically and chemically incompatible with glucose-containing solutions. The following agents have been shown to be compatible when added to infusion solutions containing Xelltempra: 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 for 48 hours at 2 °C–8 °C.
After reconstitution and dilution:
The chemical and physical in-use stability has been demonstrated for 12 hours at 25 °C and for 48 hours at 2 °C–8 °C; this period refers to the total storage period (reconstituted solution in the vial and diluted solution in the infusion bag).
However, from a microbiological standpoint, the medicinal product should be used immediately.
This medicinal product does not contain preservatives or bacteriostatic agents. If not used immediately, the user is responsible for the in-use storage period, which should not normally exceed 24 hours at 2 °C–8 °C, unless reconstitution/dilution was performed under controlled and validated aseptic conditions.

Administration of Xelltempra as a 2-minute intravenous injection (adults only):
Xelltempra must be reconstituted in the vial exclusively with sterile water for injections.
DO NOT use saline solutions for reconstitution in the vial, as this would result in a hyperosmotic solution that could cause infusion site reactions if the reconstituted product were administered as a 2-minute intravenous injection.
A concentration of 50 mg/ml of Xelltempra for injection is obtained by reconstituting the lyophilisate with 10 ml of sterile water for injections.
Complete dissolution of the lyophilisate takes less than 3 minutes. 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 Xelltempra for intravenous injection, follow the instructions below: throughout the entire process of reconstitution of Xelltempra lyophilisate, an aseptic technique must be used.

1. Remove the polypropylene overcap to expose the central portion of the rubber stopper. Clean 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 contact any other surface. Draw 10 ml of sterile water for injections into a syringe using a sterile transfer needle with a gauge of 21 or smaller, then inject it into the vial by inserting the needle into the central portion of the rubber stopper with the tip directed toward the vial wall.
2. Rotate or gently agitate the contents of the vial for a few minutes until a completely reconstituted solution is obtained.
3. Before use, the reconstituted solution must be carefully inspected visually to ensure complete dissolution of the product and absence of particulate matter. The color of the reconstituted Xelltempra solution may vary from pale yellow to light brown.
4. Slowly withdraw the reconstituted liquid (50 mg daptomycin/ml) from the vial using a sterile needle with a gauge of 21 or smaller.
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 tip of the needle 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 all the solution from the inverted vial.
6. Replace the needle with a new needle suitable for intravenous injection.
7. Expel air, large bubbles, and excess solution until the required dose is obtained.
8. The reconstituted solution must then be administered slowly by intravenous injection 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 72 hours at 2 °C–8 °C.
However, from a microbiological standpoint, the medicinal product should be used immediately.
This medicinal product does not contain preservatives or bacteriostatic agents. If not used immediately, the user is responsible for the in-use storage period, which should not normally exceed 24 hours at 2 °C–8 °C, unless reconstitution was performed under controlled and validated aseptic conditions.
The medicinal product must not be mixed with other products except those mentioned above.
Xelltempra vials are for single use only. Any unused solution remaining in the vial must be discarded.