Daptomycin Tillymed

Package leaflet: Information for the patient

Daptomicina Tillomed 350 mg powder for solution for injection or infusion, 500 mg powder for solution for injection or infusion

daptomycin
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, because it may be harmful.
• 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 Daptomicina Tillomed is and what it is used for
2. What you need to know before being given Daptomicina Tillomed
3. How Daptomicina Tillomed is administered
4. Possible side effects
5. How to store Daptomicina Tillomed
6. Contents of the pack and other information

1. What Daptomycin Tillomed is and what it is used for

The active substance of Daptomycin Tillomed powder for injectable solution or for infusion is
daptomycin. Daptomycin is an antibacterial agent that can inhibit the growth of certain bacteria.
Daptomycin Tillomed is used in adults and in children and adolescents (aged 1 to 17 years)
to treat skin and subcutaneous tissue infections (below the skin). It is also used to treat bloodstream
infections when associated with skin infections.
Daptomycin Tillomed 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 Daptomycin Tillomed.

2. What you should know before being given Daptomicin Tillomed

Do not be given Daptomicin Tillomed 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 Tillomed:

• If you have or have previously had kidney problems. Your doctor may need to adjust the dose of Daptomicin Tillomed (see section 3 of this leaflet).
• Patients treated with Daptomicin Tillomed 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 undergo a blood test and will advise you whether or not to continue treatment with Daptomicin Tillomed. Symptoms usually resolve within a few days after stopping Daptomicin Tillomed.
• If you have ever developed a severe skin reaction, skin peeling, blisters, and/or mouth ulcers, or serious kidney problems after taking daptomycin.
• If you are overweight. Daptomicin Tillomed 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 situations apply to you, inform your doctor or nurse before receiving Daptomicin Tillomed.

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 Daptomicin Tillomed. Symptoms may include wheezing, difficulty breathing, swelling of the face, neck, and throat, skin rashes, hives, and fever.
• Serious skin disorders have been reported with the use of Daptomicin Tillomed. Symptoms associated with these skin disorders may include:
  • Onset or worsening of fever,
  • Raised red spots or fluid-filled lesions appearing under the arms, chest, or groin areas, which may spread over large areas of the body,
  • Blisters or ulcers in the mouth or on the genitals.
• A serious kidney problem has been reported with the use of Daptomicin Tillomed. Symptoms may include fever and skin rash.
• Any 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 you should 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 or discontinue treatment with Daptomicin Tillomed.

Daptomicin Tillomed may interfere with laboratory tests measuring blood coagulation. Test results may suggest poor blood clotting even when no actual problem exists. It is therefore important that your doctor is aware that you are receiving Daptomicin Tillomed. Inform your doctor that you are being treated with Daptomicin Tillomed.

Your doctor will perform blood tests to monitor muscle function both before starting treatment and regularly during treatment with Daptomicin Tillomed.

Children and adolescents

Daptomicin Tillomed 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 can be given the same dose as adults, provided they have normal kidney function.

Other medicines and Daptomicin Tillomed

Inform your doctor or nurse if you are taking, have recently taken, or might take any other medicines.

It is especially 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 take any of these medicines (and certain others that may cause muscle-related side effects) during treatment with Daptomicin Tillomed, your risk of muscle-related adverse effects may be increased. Your doctor may decide not to administer Daptomicin Tillomed 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 Tillomed.
• 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

Daptomicin Tillomed is generally not given to pregnant women. If you are pregnant or breastfeeding, or suspect you may be pregnant or are planning a pregnancy, ask your doctor or pharmacist for advice before receiving this medicine.

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

Driving and using machines

Daptomicin Tillomed has no known effect on the ability to drive or use machinery.

Daptomicin Tillomed contains sodium

This medicine contains less than 1 mmol (23 mg) of sodium per vial, i.e., it is essentially “sodium-free”.

3. How Daptomicina Tillomed is administered

Daptomicina Tillomed will normally be 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 given 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 Daptomicina Tillomed less frequently, e.g., every other day. If you are undergoing dialysis and your next dose of Daptomicina Tillomed is due on the same day as dialysis, Daptomicina Tillomed will usually be 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 administered 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 everyone experiences 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 Tillomed. This severe allergic reaction requires immediate medical intervention. Immediately inform your doctor or nurse if you experience any of the following symptoms:

• Chest pain or tightness in the chest,
• Rash or hives,
• Swelling around the throat,
• Rapid or weak pulse,
• 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 may be serious, including muscle breakdown (rhabdomyolysis), which can 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, 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 red spots or fluid-filled blisters on the skin, which may appear under the arms, on the chest or groin area, and may spread over a large area of the body,
  • blisters or ulcers in the mouth or on the genitals.
• A serious kidney problem. 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 more frequently reported side effects are described below:
Common side effects (may affect up to 1 in 10 people)

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

Other side effects that may occur during treatment with daptomycin 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 the hands or feet, altered taste sensation,
• Tremor,
• Changes in heart rhythm, hot flushes,
• Indigestion (dyspepsia), inflammation of the tongue,
• Itchy rash,
• Muscle pain, cramps or weakness, muscle inflammation (myositis), joint pain,
• Kidney problems,
• Vaginal inflammation and irritation,
• Generalised 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 (jaundice),
• 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 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 the following website:
https://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 Tillomed

• Keep this medicine out of the sight and reach of children.
• Store in the refrigerator (2°C - 8°C).
• 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.

6. Package contents and other information

What Daptomicina Tillomed contains

• The active substance is daptomycin.
• Daptomycin 350 mg: one vial of powder contains 350 mg of daptomycin. After reconstitution with 7 ml of sodium chloride (0.9%), one ml provides 50 mg of daptomycin.
• Daptomycin 500 mg: one vial of powder contains 500 mg of daptomycin. After reconstitution with 10 ml of sodium chloride (0.9%), one ml provides 50 mg of daptomycin.
• The other component is sodium hydroxide.

Description of the appearance of Daptomicina Tillomed and contents of the pack
Daptomicina Tillomed powder for solution for injection or infusion is supplied as a lyophilisate or powder ranging in colour from pale yellow to light brown in a glass vial. Prior to administration, it is mixed with a solvent to form a liquid.
Daptomicina Tillomed is available in packs containing 1 vial or 5 vials.

Marketing Authorisation Holder
Tillomed Italia S.r.l.
Viale Giulio Richard, 1 - Torre A
Milan
Italy

Manufacturer
Kleva Pharmaceuticals S.A.
Parnithos Ave. 189
Acharnai Attiki 13675
Greece
MIAS Pharma Limited
Suite 2, Stafford House, Strand Road
Portmarnock, Co. Dublin
Ireland
Tillomed Malta Limited
Malta Life Sciences Park
LS2.01.06 Industrial Estate
San Gwann, SGN 3000, Malta

This medicinal product is authorised in the Member States of the European Economic Area under the following names:
Portugal Daptomycin BE Pharma
Germany Daptomycin Tillomed 350 mg Powder for solution for injection/infusion
Daptomycin Tillomed 500 mg Powder for solution for injection/infusion
Spain Daptomicina Tillomed 350 mg powder for injectable solution and for perfusion EFG
Daptomicina Tillomed 500 mg powder for injectable solution and for perfusion EFG
Finland Daptomycin BE Pharma 350 mg powder for solution for injection or infusion
Daptomycin BE Pharma 500 mg powder for solution for injection or infusion
Italy Daptomicina Tillomed
Sweden Daptomycin BE Pharma 350 mg powder for injection or infusion solution
Daptomycin BE Pharma 500 mg powder for injection or infusion solution

The following information is intended exclusively for healthcare professionals

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

In adults, daptomycin may be administered intravenously either as a 30-minute infusion or as a 2-minute injection. In contrast to adults, daptomycin must not be administered as a 2-minute injection in pediatric patients. In pediatric patients aged 7 to 17 years, daptomycin must 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 at least 60 minutes. Preparation of the infusion solution requires further dilution, as described below.

Administration of Daptomicina Tillomed as an intravenous infusion over 30 or 60 minutes

A concentration of 50 mg/ml of Daptomicina Tillomed for infusion is obtained by reconstituting the lyophilisate with 7 ml (for daptomycin 350 mg powder) or 10 ml (for daptomycin 500 mg powder) 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 a few small bubbles or foam around the edges of the vial may be present.

To prepare Daptomicina Tillomed for intravenous infusion, the following instructions must be followed: an aseptic technique must be used throughout the entire process of reconstitution and dilution of the Daptomicina Tillomed lyophilisate.

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 another antiseptic solution 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 7 ml (for daptomycin 350 mg powder) or 10 ml (for daptomycin 500 mg powder) of sodium chloride 9 mg/ml (0.9%) injection solution into a syringe using a sterile transfer needle with a gauge of 21 or smaller, or a needle-free device, and then slowly inject it into the vial, inserting the needle into 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 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 Tillomed solution may vary 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, 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, 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 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 Tillomed 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 Tillomed: 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 stored 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 Tillomed as a 2-minute intravenous injection (adults only)

For reconstitution of Daptomicina Tillomed for intravenous injection, water must not be used. Daptomicina Tillomed must only be reconstituted with sodium chloride 9 mg/ml (0.9%).

A concentration of 50 mg/ml of Daptomicina Tillomed for injection is obtained by reconstituting the lyophilisate with 7 ml (for daptomycin 350 mg powder) or 10 ml (for daptomycin 500 mg powder) 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 a few small bubbles or foam around the edges of the vial may be present.

To prepare Daptomicina Tillomed for intravenous injection, the following instructions must be followed: an aseptic technique must be used throughout the entire process of reconstitution of the Daptomicina Tillomed lyophilisate.

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 come into contact with any other surface. Draw 7 ml (for daptomycin 350 mg powder) or 10 ml (for daptomycin 500 mg powder) of sodium chloride 9 mg/ml (0.9%) injection solution into a syringe using a sterile transfer needle with a gauge of 21 or smaller, or a needle-free device, and then slowly inject it into the vial, inserting the needle into 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 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 Tillomed solution may vary from pale yellow to light brown.

5. 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. 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. 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 suitable 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.

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 when 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 24 hours at 2°C – 8°C, unless reconstitution/dilution has been carried out under controlled and validated aseptic conditions.

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