Daptomycin Hikma

Package leaflet: Information for the patient

Daptomycin Hikma 500 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.
• If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of this leaflet

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

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

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

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

You must not be given Daptomicin Hikma
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 or nurse before you are given Daptomicin Hikma.

• If you have or have previously had kidney problems. Your doctor may need to adjust the dose of Daptomicin Hikma (see section 3 of this leaflet).
• Patients treated with daptomycin sometimes experience muscle pain, weakness or muscle damage (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 to continue or stop treatment with Daptomicin Hikma. Symptoms usually disappear within a few days after stopping Daptomicin Hikma.
• If you are overweight. Daptomycin blood levels may be higher than those observed in people 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 Hikma.
Inform your doctor 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. 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 or hives, fever (see section 4 of this leaflet for further information).
• 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 condition and decide whether you should continue treatment with Daptomicin Hikma.

Daptomicin Hikma may interfere with laboratory tests measuring blood coagulation.
Test results may suggest a blood clotting problem even when no actual problem exists.
Therefore, it is important that your doctor is aware that you are receiving Daptomicin Hikma.
Inform your doctor that you are being treated with Daptomicin Hikma.
Your doctor will perform blood tests to monitor your muscle condition both before starting
treatment and regularly during treatment with Daptomicin Hikma.
Children and adolescents
Daptomicin Hikma 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 aged 65 years and older can receive the same dose as adults, provided they have normal kidney function.
Other medicines and Daptomicin Hikma
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 take these medicines (and others that may affect muscles) during treatment with Daptomicin Hikma, the risk of muscle-related side effects may be increased. Your doctor may decide not to prescribe Daptomicin Hikma 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 Daptomicin Hikma.
• Oral anticoagulants (e.g. warfarin), which are medicines that prevent blood from clotting. Your doctor may need to monitor your clotting time. Pregnancy and breastfeeding

Daptomicin is generally not given to pregnant women. If you are pregnant, breastfeeding, suspect you may be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before receiving this medicine.
Do not breastfeed while taking Daptomicin Hikma, as Daptomicin Hikma may pass into breast milk and could therefore affect the infant.
Driving and using machines
Daptomicin has no known effects on the ability to drive or operate machinery.

3. How Daptomycin Hikma is administered

Daptomycin Hikma is usually administered by a doctor or nurse.
The dose administered 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 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.
Children and adolescents (1 to 17 years of age)
The dose for children and adolescents (1 to 17 years of age) used to treat skin infections depends on the patient's age. The recommended doses according to age are shown in the table below:

If you have impaired kidney function, you may receive Daptomycin Hikma less frequently,
e.g. on alternate days. If you are on dialysis and the next dose of Daptomycin Hikma is due
on the same day as dialysis, Daptomycin Hikma will usually be administered after dialysis is completed.
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 everybody 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, 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. Immediately inform your doctor or nurse 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,
• 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 serious, including muscle breakdown (rhabdomyolysis), which may 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 treated with daptomycin, in most cases after more than 2 weeks of treatment. Symptoms may include difficulty breathing, onset or worsening of cough, or onset or worsening of 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 your 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,
• Reduction 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 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) shown by blood tests.

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

• Blood abnormalities (such as increased number of small 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 sensation,
• Tremor,
• Changes in heart rate, hot flushes,
• Indigestion (dyspepsia), inflammation of the tongue,
• Skin rash associated with itching,
• Muscle pain or weakness, inflammation of 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 bleeding time or electrolyte imbalance.

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

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

Frequency not known (frequency cannot be estimated from the available data)
Colitis associated with antibiotic use, including pseudomembranous colitis (severe and persistent diarrhoea containing blood and/or mucus, associated with abdominal pain or fever).

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 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 Hikma

• 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: 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.

After dilution: chemical and physical stability of the diluted solution in infusion bags is established
for 12 hours at 25°C or for 24 hours at 2°C – 8°C.
For a 30-minute intravenous infusion, the total storage time (reconstituted solution in the vial and
diluted solution in the infusion bag; see section 6.6) at 25°C must not exceed 12 hours (or 24 hours at 2°C – 8°C).
For a 2-minute intravenous injection, the storage time of the reconstituted solution in the vial (see section 6.6) at 25°C must not exceed 12 hours (or 48 hours at 2°C – 8°C).
From a microbiological standpoint, the product should be used immediately. If not used immediately, the in-use storage times and conditions are the responsibility of the user and should normally not exceed 24 hours at 2°C – 8°C.
Do not use Daptomycin Hikma if you notice any change in the appearance of the product (signs of moisture or presence of differently coloured particles in the powder, or presence of particles, cloudiness or precipitate when the solution is reconstituted).
Do not dispose of medicines 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 Daptomicina Hikma contains

• The active substance is daptomycin. One vial of powder contains 500 mg of daptomycin. One ml provides 50 mg of daptomycin after reconstitution with 10 ml of sodium chloride solution 9 mg/ml (0.9%).
• The other component is sodium hydroxide.

Description of the appearance of Daptomicina Hikma and contents of the pack
Daptomicina Hikma powder for solution for injection or infusion is supplied as a
lyophilisate or pale yellow to light brown powder in a glass vial. Prior to
administration, it is mixed with a solvent to form a liquid.
Daptomicina Hikma is available in packs containing 1 vial or 5 vials.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Hikma Italia SpA
Viale Certosa 10
27100 Pavia
Italy

Manufacturer
Medichem, S.A.
Mossèn Jacint Verdaguer 67A
08970 Sant Joan Despí (Barcelona)
Spain
Hikma Italia SpA
Viale Certosa 10
27100 Pavia
Italy

This medicinal product is authorised in the European Economic Area countries under the
following names:
Germany:
Daptomycin-ratiopharm 350 mg Powder for solution for injection/infusion
Italy:
Daptomicina Hikma

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:
Daptomycin may be administered intravenously either as a 30- or 60-minute infusion or as a 2-minute injection. Preparation of the infusion solution requires further dilution, as described below.

Administration of Daptomicina Hikma as a 30- or 60-minute intravenous infusion
A concentration of 50 mg/ml of Daptomicina Hikma for infusion is obtained by reconstituting the lyophilized powder with 10 ml of sodium chloride 9 mg/ml (0.9%) injectable solution. Approximately 15 minutes are required for complete dissolution of the lyophilized powder. The fully reconstituted medicinal product has a clear appearance, although some bubbles or foam around the edges of the vial may be present.

To prepare Daptomicina Hikma for intravenous infusion, follow the instructions below. Throughout the entire reconstitution process, aseptic technique must be maintained.

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 another antiseptic solution and allow it to dry. After cleaning, do not touch the rubber stopper or allow it to contact any other surface. Using a sterile transfer needle of 21 gauge or smaller, or a needle-free device, draw 10 ml of 9 mg/ml (0.9%) sodium chloride injectable solution into a syringe 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 confirm complete dissolution and visually check for absence of particulate matter. The color of the reconstituted Daptomicina Hikma solution may vary from pale yellow to light brown.
5. Slowly withdraw the reconstituted liquid (50 mg daptomycin/ml) from the vial using a sterile needle of 21 gauge or smaller.
6. The reconstituted solution must then be diluted with 9 mg/ml (0.9%) sodium chloride intravenous infusion (typical volume 50 ml).
7. Invert the vial to allow the solution to drain toward the stopper. Using a new syringe, insert the needle into the inverted vial. While keeping the vial inverted, maintain the needle tip at the bottom of the solution 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 remaining solution from the inverted vial.
8. Replace the needle with a new needle for intravenous infusion.
9. Expel air, large bubbles, and excess solution to achieve the required dose.
10. The reconstituted and diluted solution should then be administered as an intravenous infusion over 30 or 60 minutes. Daptomicina Hikma is physically and chemically incompatible with glucose-containing solutions. The following agents have been shown to be compatible when added to daptomycin-containing infusion solutions: aztreonam, ceftazidime, ceftriaxone, gentamicin, fluconazole, levofloxacin, dopamine, heparin, and lidocaine.

The total storage period (reconstituted solution in the vial and diluted solution in the infusion bag) must not exceed 12 hours at 25°C (24 hours if refrigerated).
The stability of the diluted solution in the infusion bag is 12 hours at 25°C or 24 hours if stored refrigerated at 2°C – 8°C.

Administration of Daptomicina Hikma as a 2-minute intravenous injection
For reconstitution of Daptomicina Hikma for intravenous injection, water must not be used. Daptomicina Hikma must be reconstituted only with 9 mg/ml (0.9%) sodium chloride solution.

A concentration of 50 mg/ml of Daptomicina Hikma for injection is obtained by reconstituting the lyophilized powder with 10 ml of 9 mg/ml (0.9%) sodium chloride injectable solution. Approximately 15 minutes are required for complete dissolution of the lyophilized powder. The fully reconstituted medicinal product has a clear appearance, although some bubbles or foam around the edges of the vial may be present.

To prepare Daptomicina Hikma for intravenous injection, follow the instructions below. Throughout the entire reconstitution process, aseptic technique must be maintained.

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 another antiseptic solution and allow it to dry. After cleaning, do not touch the rubber stopper or allow it to contact any other surface. Using a sterile transfer needle of 21 gauge or smaller, or a needle-free device, draw 10 ml of 9 mg/ml (0.9%) sodium chloride injectable solution into a syringe 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 confirm complete dissolution and visually check for absence of particulate matter. The color of the reconstituted Daptomicina Hikma solution may vary from pale yellow to light brown.
5. Slowly withdraw the reconstituted liquid (50 mg daptomycin/ml) from the vial using a sterile needle of 21 gauge or smaller.
6. Invert the vial to allow the solution to drain 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 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 remaining solution from the inverted vial.
7. Replace the needle with a new needle for intravenous injection.
8. Expel air, large bubbles, and excess solution to achieve the required dose.
9. The reconstituted solution should then be administered slowly by intravenous injection over 2 minutes. Chemical and physical stability of the reconstituted solution in the vial has been demonstrated for 12 hours at 25°C and up to 48 hours if refrigerated (2°C – 8°C). However, from a microbiological standpoint, the medicinal product should be used immediately. If not used immediately, the user is responsible for the in-use storage period, which under normal circumstances should not exceed the above-mentioned time limits for in-use chemical and physical stability. The medicinal product must not be mixed with other products except those listed above. Daptomicina Hikma vials are for single use only. Any unused solution remaining in the vial must be discarded.

Patient information leaflet

Daptomicina Hikma 350 mg powder for solution for injection/infusion

daptomycin
“Generic 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.
• If you get any side effects, including those not listed in this leaflet, tell your doctor or nurse. See section 4.

Contents of this leaflet

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

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

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

2. What you should know before being given Daptomicin Hikma.

Do not receive Daptomicin Hikma
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 or nurse before you are given Daptomicin Hikma.

• If you have or have previously had kidney problems. Your doctor may need to adjust the dose of Daptomicin Hikma (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 Hikma. Symptoms usually resolve within a few days after stopping Daptomicin Hikma.
• 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 receiving
Daptomicin Hikma.
Inform your doctor 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. Inform your doctor or nurse immediately if you experience symptoms suggesting an allergic reaction such as wheezing, difficulty breathing, swelling of the face, neck, and throat, skin rashes, hives, or fever (see section 4 of this leaflet for further information).
• 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 in the stool, 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 examine your lungs and decide whether you should continue treatment with Daptomicin Hikma.

Daptomicin Hikma may interfere with laboratory tests measuring blood coagulation.
Test results may suggest impaired blood clotting even when no actual problem exists.
Therefore, it is important that your doctor is aware that you are receiving Daptomicin Hikma.
Inform your doctor that you are being treated with Daptomicin Hikma.
Your doctor will perform blood tests to monitor your muscle condition both before starting
treatment and regularly during treatment with Daptomicin Hikma.
Children and adolescents
Daptomicin Hikma must not be administered 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 Hikma
Inform your doctor or nurse if you are taking, have recently taken, or might take any other medicines.
It is particularly important that you 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 in other conditions such as rheumatoid arthritis or atopic dermatitis). If you take these medicines (and others that may affect muscles) during treatment with Daptomicin Hikma, the risk of muscle-related adverse effects may be increased. Your doctor may decide not to prescribe Daptomicin Hikma or to temporarily discontinue the other medicines.
• Analgesics known as non-steroidal anti-inflammatory drugs (NSAIDs) or COX-2 inhibitors (e.g., celecoxib). These may interfere with the renal effects of Daptomicin Hikma.
• Oral anticoagulants (e.g., warfarin), which are medicines that prevent blood from clotting. Your doctor may need to monitor your bleeding time. Pregnancy and breastfeeding

Daptomycin is generally not administered to pregnant women. If you are pregnant, breastfeeding, suspect you may be pregnant, or are planning a pregnancy, consult your doctor or pharmacist before receiving this medicine.
Do not breastfeed while taking Daptomicin Hikma, as Daptomicin Hikma may pass into breast milk and could therefore affect the infant.
Driving and using machines
Daptomicin has no known effect on the ability to drive or operate machinery.

3. How Daptomycin Hikma is administered

Daptomycin Hikma is normally administered by a doctor or nurse.
The dose administered 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 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 about 30 minutes or as an injection lasting about 2 minutes. The same dose is recommended for individuals over 65 years of age, provided they have normal renal function.
Children and adolescents (from 1 to 17 years of age)
The dose for children and adolescents (from 1 to 17 years of age) used to treat skin infections depends on the patient's age. The recommended doses according to age are shown in the table below:

If you have impaired kidney function, you may be given Daptomicin Hikma less frequently, for example, on alternate days. If you are on dialysis and the next dose of Daptomicin Hikma is due on the same day as dialysis, Daptomicin Hikma will usually be administered after completion of dialysis.
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 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 everybody 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, 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. Immediately inform your doctor or nurse if any of the following symptoms occur:

• Chest pain or tightness in the chest,
• Skin rash with blistering, sometimes affecting the mouth and genitals,
• Swelling around the throat,
• Rapid or weak heartbeat,
• Wheezing,
• Fever,
• Chills or shivering,
• 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 destruction of muscle tissue (rhabdomyolysis), which may 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 treated with 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 your 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,
• Reduction in the number of red blood cells in the blood (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) shown in blood tests.

Other side effects that may occur following 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 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,
• Changes in heart rhythm, hot flushes,
• Indigestion (dyspepsia), inflammation of the tongue,
• Skin rash associated with itching,
• Muscle pain or weakness, inflammation of muscles (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 bleeding time, or electrolyte imbalance.

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)
Colitis associated with the use of antibiotics, including pseudomembranous colitis (severe and persistent diarrhoea containing blood and/or mucus, associated with abdominal pain or fever).

Reporting of side effects
If you get any side effects, including any 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 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 Hikma

• 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: 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.

After dilution: chemical and physical stability of the diluted solution in infusion bags is established
for 12 hours at 25°C or for 24 hours at 2°C – 8°C.
For a 30-minute intravenous infusion, the total combined in-use storage time (reconstituted solution in
the vial and diluted solution in the infusion bag; see section 6.6) at 25°C must not exceed 12 hours (or 24 hours at 2°C – 8°C).
For a 2-minute intravenous injection, the storage time of the reconstituted solution in the
vial (see section 6.6) at 25°C must not exceed 12 hours (or 48 hours at 2°C – 8°C).
From a microbiological standpoint, the product should be used immediately. If not used immediately,
the responsibility for storage conditions and duration lies with the user and should normally not exceed 24 hours at 2°C – 8°C.
Do not use Daptomycin Hikma if you notice any change in the appearance of the product (signs of moisture or presence of particles with a different colour in the powder), or the presence of particles, cloudiness or precipitate once the solution has been reconstituted.
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 Daptomycin Hikma contains

• The active substance is daptomycin. One vial of powder contains 350 mg of daptomycin. One ml provides 50 mg of daptomycin after reconstitution with 7 ml of sodium chloride solution 9 mg/ml (0.9%).
• The other component is sodium hydroxide.

Description of the appearance of Daptomycin Hikma and contents of the pack
Daptomycin Hikma powder for solution for injection or infusion is supplied as a
lyophilisate or powder ranging in colour from light yellow to light brown, contained in a glass vial. Prior to administration, it is mixed with a solvent to form a liquid.
Daptomycin Hikma is available in packs containing 1 vial or 5 vials.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Hikma Italia SpA
Viale Certosa 10
27100 Pavia
Italy

Manufacturer
Medichem, S.A.
Mossèn Jacint Verdaguer 67A
08970 Sant Joan Despí (Barcelona)
Spain
Hikma Italia SpA
Viale Certosa 10
27100 Pavia
Italy

This medicinal product is authorised in the European Economic Area countries under the following names:
Germany:
Daptomycin-ratiopharm 350 mg Powder for the preparation of an injection/infusion solution
Italy:
Daptomicina Hikma

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:
Daptomycin can be administered intravenously as a 30- or 60-minute infusion or as a 2-minute injection. Preparation of the infusion solution requires further dilution, as described below.

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

A concentration of 50 mg/ml of Daptomicina Hikma for infusion is obtained by reconstituting the lyophilisate with 7 ml of sodium chloride 9 mg/ml (0.9%) injection 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 small bubbles or foam around the edges of the vial.
To prepare Daptomicina Hikma for intravenous infusion, follow the instructions below. An aseptic technique must be used throughout the entire reconstitution process of Daptomicina Hikma lyophilisate.

11. Remove the overcap made of polypropylene 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 avoid contact with any other surface. Using a sterile transfer needle with a gauge of 21 or smaller, or a needle-free device, draw 7 ml of 9 mg/ml (0.9%) sodium chloride injection solution into a syringe and slowly inject it into the vial, inserting the needle into the central portion of the rubber stopper with the tip directed toward the vial wall.
12. Gently rotate the vial to ensure the product is completely wetted by the liquid, then allow it to stand for 10 minutes.
13. Finally, gently rotate the vial for several minutes until a clear reconstituted solution is obtained. Avoid vigorous shaking or agitation to prevent foam formation.
14. Before use, carefully inspect the reconstituted solution visually to confirm complete dissolution of the product and absence of particulate matter. The color of the reconstituted Daptomicina Hikma solution may range from pale yellow to light brown.
15. Slowly withdraw the reconstituted liquid (50 mg of daptomycin/ml) from the vial using a sterile needle with a gauge of 21 or smaller.
16. The reconstituted solution must then be diluted with 9 mg/ml (0.9%) sodium chloride intravenous infusion (typical volume: 50 ml).
17. 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, keep the needle tip at the bottom of the solution as it is aspirated into the syringe. Before removing the needle from the vial, pull back the plunger to the end of the syringe barrel to aspirate all remaining solution from the inverted vial.
18. Replace the needle with a new needle for intravenous infusion.
19. Expel air, large bubbles, and excess solution until the required dose is obtained.
20. The reconstituted and diluted solution should then be administered as an intravenous infusion over 30 or 60 minutes. Daptomicina Hikma is physically and chemically incompatible with glucose-containing solutions. The following agents have been shown to be compatible when added to infusion solutions containing daptomycin: aztreonam, ceftazidime, ceftriaxone, gentamicin, fluconazole, levofloxacin, dopamine, heparin, and lidocaine.

The total storage time (reconstituted solution in the vial and diluted solution in the infusion bag) must not exceed 12 hours at 25°C (24 hours if refrigerated).
The stability of the diluted solution in the infusion bag is 12 hours at 25°C or 24 hours if stored refrigerated at 2°C – 8°C.

Administration of Daptomicina Hikma as a 2-minute intravenous injection

For reconstitution of Daptomicina Hikma for intravenous injection, water must not be used.
Daptomicina Hikma must only be reconstituted with 9 mg/ml (0.9%) sodium chloride solution.
A concentration of 50 mg/ml of Daptomicina Hikma for injection is obtained by reconstituting the lyophilisate with 7 ml of 9 mg/ml (0.9%) sodium chloride injection 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 small bubbles or foam around the edges of the vial.
To prepare Daptomicina Hikma for intravenous injection, follow the instructions below. An aseptic technique must be used throughout the entire reconstitution process of Daptomicina Hikma lyophilisate.

10. Remove the overcap made of polypropylene 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 avoid contact with any other surface. Using a sterile transfer needle with a gauge of 21 or smaller, or a needle-free device, draw 7 ml of 9 mg/ml (0.9%) sodium chloride injection solution into a syringe and slowly inject it into the vial, inserting the needle into the central portion of the rubber stopper with the tip directed toward the vial wall.
11. Gently rotate the vial to ensure the product is completely wetted by the liquid, then allow it to stand for 10 minutes.
12. Finally, gently rotate the vial for several minutes until a clear reconstituted solution is obtained. Avoid vigorous shaking or agitation to prevent foam formation.
13. Before use, carefully inspect the reconstituted solution visually to confirm complete dissolution of the product and absence of particulate matter. The color of the reconstituted Daptomicina Hikma solution may range from pale yellow to light brown.
14. Slowly withdraw the reconstituted liquid (50 mg of daptomycin/ml) from the vial using a sterile needle with a gauge of 21 or smaller.
15. 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 as it is aspirated into the syringe. Before removing the needle from the vial, pull back the plunger to the end of the syringe barrel to aspirate all remaining solution from the inverted vial.
16. Replace the needle with a new needle for intravenous injection.
17. Expel air, large bubbles, and excess solution until the required dose is obtained.
18. The reconstituted solution must then be administered slowly by intravenous injection over 2 minutes. Chemical and physical stability during use of the reconstituted solution in the vial has been demonstrated for 12 hours at 25°C and up to 48 hours if stored refrigerated (2°C – 8°C). However, from a microbiological standpoint, the medicinal product should be used immediately. If not used immediately, the user is responsible for ensuring the in-use storage period does not exceed the above-mentioned chemical and physical stability limits. The medicinal product must not be mixed with other products except those listed above. Daptomicina Hikma vials are for single use only. Any unused solution remaining in the vial must be discarded.