Daptomycin Xellia 350 mg powder for solution for injection and for infusion EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Daptomicina Xellia 350mg powder for solution for injection and infusion EFG

Read the entire leaflet carefully before you start using this medicine, because it contains important information for you.

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

• If you have any questions, ask your doctor, pharmacist or nurse.

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

• If you experience any adverse effects, consult your doctor, pharmacist or nurse, even if they are adverse effects not listed in this leaflet. See section 4.

Contents of the leaflet

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

2. What you need to know before receiving Daptomicina Xellia

3. How Daptomicina Xellia is administered

4. Possible adverse effects

5. How to store Daptomicina Xellia

6. Contents of the pack and other information

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

The active substance of Daptomicina Xellia for injectable solution and for infusion (referred to as Daptomicina Xellia throughout this leaflet) is daptomycin. Daptomycin is an antibacterial agent capable of inhibiting the growth of certain bacteria.

Antibiotics are used to treat bacterial infections and are not effective against viral infections such as flu or the common cold.

It is important that you follow the instructions regarding dose, dosing interval, and duration of treatment as directed by your doctor.

Do not store or reuse this medicine. If you have any leftover antibiotic after completing treatment, return it to the pharmacy for proper disposal. Medicines must not be disposed of via wastewater or household waste.

Daptomycin is used in adults and in children and adolescents (aged 1 to 17 years) to treat skin and soft tissue infections. It is also used to treat bloodstream infections when associated with a skin infection.

Daptomycin 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, and to treat bloodstream infections caused by the same bacterium when associated with a heart infection.

Depending on the type of infection(s) you have, your doctor may also prescribe other antibacterial agents while you are receiving daptomycin treatment.

2. What you need to know before you start receiving Daptomicina Xellia

Do not receive Daptomicina Xellia

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

If this applies to you, inform your doctor or nurse. If you think you may be allergic, consult your doctor or nurse.

Warnings and precautions

Talk to your doctor or nurse before you start receiving Daptomicina Xellia:

• If you have or have previously had kidney problems. Your doctor may need to adjust the dose of Daptomicina Xellia (see section 3 of this leaflet).
• Occasionally, patients receiving daptomycin may develop increased sensitivity, pain, or muscle weakness (see section 4 of this leaflet for more information). Inform your doctor if this occurs. Your doctor will ensure that you have a blood test and will advise whether or not it is advisable to continue using Daptomicina Xellia. Symptoms usually resolve within a few days after stopping treatment with Daptomicina Xellia.
• If you have ever had, after taking daptomycin, a severe skin rash or skin peeling, blisters and/or mouth sores, or serious kidney problems.
• If you have significant overweight, there is a possibility that your blood levels of daptomycin may be higher than those found in individuals of average weight, and therefore you may require closer monitoring for adverse effects.

If any of the above-mentioned conditions apply to you, inform your doctor or nurse before receiving Daptomicina Xellia.

Tell your doctor or nurse immediately if you develop any of the following symptoms:

• Severe and serious allergic reactions have been observed in patients treated with almost all antibacterial agents, including daptomycin. Inform your doctor or nurse immediately if you experience symptoms indicating an allergic reaction, such as wheezing, difficulty breathing, swelling of the face, neck and throat, skin rash and hives, or fever.

• Serious skin disorders have been reported with the use of daptomycin. Symptoms occurring with these skin disorders may include:

• onset or worsening of fever,

• raised or fluid-filled red spots on the skin, which may start in the armpits or areas of the chest or groin and may spread over a large area of the body,

• blisters or sores in the mouth or genitals.

• Serious kidney problems have been reported with the use of daptomycin. Symptoms may include fever and rash.

• Any type of tingling or numbness in the hands or feet, loss of sensation, or unusual movement difficulties. If this occurs, inform your doctor, who will decide whether treatment should continue.

• Diarrhea, especially if you notice blood or mucus in the stool or if the diarrhea becomes severe or prolonged. If this occurs, inform your doctor, who will decide whether treatment should continue.

• Onset or worsening of fever, cough, or difficulty breathing. These may be signs of a rare but serious lung function deterioration known as eosinophilic pneumonia. Your doctor will check your lung condition and decide whether or not to continue treatment with Daptomicina Xellia.

Daptomicina Xellia may interfere with laboratory tests measuring blood clotting ability. Results may apparently suggest impaired coagulation, even though no actual problem exists. Therefore, it is important that your doctor is aware that you are receiving Daptomicina Xellia. Inform your doctor that you are being treated with Daptomicina Xellia.

Your doctor will perform blood tests to monitor your muscle health before starting treatment with Daptomicina Xellia and frequently during treatment.

Children and adolescents

Daptomicina Xellia must not be given to children under one year of age, as animal studies have shown that this age group may experience severe adverse effects.

Use in elderly patients

Patients over 65 years of age may receive the same dose as other adults, provided their kidneys are functioning properly.

Other medicines and Daptomicina Xellia

Tell your doctor or nurse if you are taking, have recently taken, or might need to take any other medicines. It is particularly important to mention the following:

• 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, e.g. rheumatoid arthritis or atopic dermatitis). The risk of muscle-related adverse effects may increase if you take any of these medicines (and others that may affect muscles) during treatment with Daptomicina Xellia. Your doctor may decide not to administer Daptomicina Xellia or to temporarily interrupt treatment with the other medicine.

• Pain-relieving medicines called non-steroidal anti-inflammatory drugs (NSAIDs) or COX-2 inhibitors (e.g. celecoxib). These may interfere with the elimination of Daptomicina Xellia by the kidneys.

• Oral anticoagulants (e.g. warfarin), which are medicines that prevent blood clotting. Your doctor may need to monitor your blood clotting times.

Pregnancy and breastfeeding

Daptomycin is generally not given to pregnant women. If you are pregnant or breastfeeding, think you may be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before using this medicine.

You must not breastfeed while receiving Daptomicina Xellia, as it may pass into breast milk and affect the baby.

Driving and using machines

Daptomycin has no known effects on the ability to drive or operate machinery.

Daptomicina Xellia contains sodium

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

3. How Daptomycin Xellia is administered

Daptomycin will normally be administered to you by your doctor or nurse.

Adults (18 years of age and older)

The dose will depend on your body weight and the type of infection being treated. The usual dose for adults is 4 mg per kilogram (kg) of body weight once daily for skin infections, or 6 mg per kg of body weight once daily for heart infection or bloodstream infection associated with skin or heart infection. In adult patients, this dose is administered 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 patients over 65 years of age, provided their kidneys are functioning properly.

If your kidneys are not functioning well, you may receive daptomycin less frequently, e.g., once every other day. If you are undergoing dialysis and your next dose of daptomycin is due on a dialysis day, you will usually receive daptomycin after the dialysis session.

Children and adolescents (1 to 17 years of age)

The recommended dose in 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 administered directly into the bloodstream (into a vein) as an infusion lasting approximately 30–60 minutes.

A complete course of treatment for skin infections usually lasts between 1 and 2 weeks. Your doctor will decide the duration of your treatment for bloodstream or heart infections and for skin infections.

Detailed instructions for use and handling are provided at the end of the leaflet.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

The following are the most serious adverse effects:

Serious adverse effects with unknown frequency (cannot be estimated from available data):

• Hypersensitivity reactions (severe allergic reactions including anaphylaxis and angioedema) have been reported during administration of daptomycin. These severe allergic reactions require 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 pulse.
• Wheezing.
• Fever.
• Chills or shivering.
• Flushing.
• Dizziness.
• Fainting.
• Metallic taste.
• Consult your doctor immediately if you experience muscle pain, tenderness, or weakness of unknown origin. Muscle problems can be serious, including muscle breakdown (rhabdomyolysis), which may lead to kidney damage.

Other adverse effects reported with the use of daptomycin include:

• A rare but potentially serious lung disorder called eosinophilic pneumonia, 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.
• Serious skin disorders. Symptoms may include:
• New or worsening fever,
• Raised or fluid-filled red spots on the skin, which may start in the armpits or on the chest or groin areas and may spread over a large area of the body,
• Blisters or sores in the mouth or genital area.
• A serious kidney problem. Symptoms may include fever and rash.

If you experience any of these symptoms, inform your doctor or nurse immediately. Your doctor will perform additional tests to establish a diagnosis.

The following are the most frequently reported adverse effects:

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

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

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

Uncommon adverse effects (may affect up to 1 in 100 patients):

• Blood disorders (e.g., increased number of platelets, which may increase the tendency to develop blood clots, or increased number of certain types of white blood cells).
• Loss of appetite.
• Tingling or numbness in hands or feet, disturbances in taste sensation.
• Tremors.
• Dizziness.
• Changes in heart rhythm, flushing.
• Indigestion (dyspepsia), inflammation of the tongue.
• Itchy rash.
• Muscle pain, cramps, or weakness, muscle inflammation (myositis), joint pain.
• Kidney problems.
• Inflammation and irritation of the vagina.
• Generalized pain or weakness, tiredness (fatigue).
• Elevated blood sugar, serum creatinine, myoglobin, or lactate dehydrogenase (LDH) levels, prolonged blood clotting time, or electrolyte imbalance in blood tests.
• Itchy eyes.

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

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

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

Antibiotic-associated colitis, including pseudomembranous colitis (severe or persistent diarrhea containing blood and/or mucus, associated with abdominal pain or fever), increased tendency to bruise, bleeding gums, or nosebleeds.

Reporting of adverse effects

If you experience any type of adverse effect, talk to your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly via the Spanish System for Pharmacovigilance of Human Medicines: www.notificaRAM.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Daptomycin Xellia

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton after "EXP" and on the label after "EXP". The expiry date refers to the last day of the month indicated.

Store in a refrigerator (between 2 °C and 8 °C).

After reconstitution:

The reconstituted solution in the vial has been shown to be physically and chemically stable for up to 12 hours at 25 °C and up to a maximum of 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 duration and conditions prior to use are the responsibility of the user, and should normally not exceed 24 hours at 2 °C – 8 °C, unless reconstitution has taken place under controlled and validated aseptic conditions.

After dilution (performed immediately after reconstitution):

The diluted solution in infusion bags has been shown to be physically and chemically stable for up to 12 hours at 25 °C and up to 24 hours at 2 °C – 8 °C.

From a microbiological standpoint, the product should be used immediately, unless the method of opening, reconstitution, and dilution excludes the risk of microbial contamination. If not used immediately, the in-use storage duration and conditions prior to use are the responsibility of the user.

After reconstitution and dilution:

Regarding the combined storage time (reconstituted solution in the vial and diluted solution in infusion bags), physical and chemical stability during use has been demonstrated for 12 hours at 25 °C or 24 hours at 2 °C – 8 °C.

From a microbiological standpoint, the product should be used immediately, unless the method of opening, reconstitution, and dilution excludes the risk of microbial contamination. If not used immediately, the in-use storage duration and conditions are the responsibility of the user.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging you no longer need. This will help protect the environment.

6. Contents of the container and other information

Composition of Daptomicina Xellia

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 a solution containing 9 mg/ml of sodium chloride (0.9%).

The other component is sodium hydroxide.

Appearance of the product and contents of the container

Daptomicina Xellia powder for injectable solution and for infusion is presented as a pale yellow to light brown powder or lyophilized cake in a clear glass vial with a rubber stopper and grey aluminium seal with a yellow "flip-off" cap. It is to be mixed with a solvent to form a liquid prior to administration.

Daptomicina Xellia is available in pack sizes of 1 or 5 vials.

Only certain pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Local representative

Sun Pharma Laboratorios, S.L.

Rambla de Catalunya 53-55

08007 – Barcelona

Spain

This medicinal product is authorized in the Member States of the European Economic Area and in the United Kingdom under the following names:

Date of last review of this leaflet: July 2021.

This information is intended for healthcare professionals only:

Important: Refer to the Summary of Product Characteristics or Technical Data Sheet before prescribing.

Instructions for use and handling

350 mg presentation:

In adults, daptomycin may be administered intravenously as an infusion over 30 minutes or as an injection over 2 minutes. Unlike adults, daptomycin must not be administered as an injection over 2 minutes in paediatric patients. Paediatric patients aged 7 to 17 years should receive daptomycin by infusion over 30 minutes. Paediatric patients under 7 years of age receiving doses of 9–12 mg/kg should receive daptomycin by infusion over 60 minutes. Preparation of the infusion solution requires an additional dilution step, as described below.

Daptomycin Xellia administered by intravenous infusion over 30 or 60 minutes

Reconstituting the lyophilised product with 7 ml of 9 mg/ml (0.9%) sodium chloride injection solution yields a concentration of 50 mg/ml for infusion of Daptomycin Xellia.

The lyophilised product takes approximately 15 minutes to dissolve. The fully reconstituted product is clear and may contain a few small bubbles or foam around the edge of the vial.

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

Throughout the reconstitution and dilution process, an aseptic technique must be used.

For reconstitution:

1. Remove the polipropylene "flip-off" cap to expose the central portion of the rubber stopper. Clean the top of the rubber stopper with an alcohol swab or other antiseptic solution and allow it to dry. After cleaning, do not touch the rubber stopper or allow it to come into contact with any other surface. Using a sterile transfer needle of gauge 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 through the center of the rubber stopper, directing the needle toward the vial wall.
2. Gently rotate the vial to ensure complete wetting of the product, then allow it to stand for 10 minutes.
3. Finally, gently rotate or shake the vial for a few minutes until a clear reconstituted solution is obtained. Avoid vigorous shaking to prevent foaming.
4. Carefully inspect the reconstituted solution before use to ensure the substance is fully dissolved and to check for the absence of particulate matter. The colour of the reconstituted Daptomycin Xellia solution may range from pale yellow to light brown.
5. The reconstituted solution must be diluted with 9 mg/ml (0.9%) sodium chloride solution (typical volume 50 ml).

For dilution:

1. Slowly withdraw the appropriate volume of reconstituted solution (50 mg daptomycin/ml) from the vial using a new sterile needle of gauge 21 or smaller, by inverting the vial so that the solution flows 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 lowest point of the solution in the vial as you draw the solution into the syringe. Before removing the needle from the vial, pull the plunger back to the end of the syringe barrel to withdraw the required solution from the inverted vial.
2. Expel air, large bubbles, and any excess solution to obtain the required dose.
3. Transfer the required reconstituted dose into 50 ml of 9 mg/ml (0.9%) sodium chloride solution.
4. The reconstituted and diluted solution should then be administered by intravenous infusion over 30 or 60 minutes.

Daptomycin Xellia is neither physically nor chemically compatible with glucose-containing solutions. The following drugs have been shown to be compatible when added to infusion solutions containing Daptomycin Xellia: aztreonam, ceftazidime, ceftriaxone, gentamicin, fluconazole, levofloxacin, dopamine, heparin, and lidocaine.

After dilution (performed immediately after reconstitution):

The diluted solution in infusion bags has been shown to be physically and chemically stable for up to 12 hours at 25°C and up to a maximum of 24 hours at 2°C – 8°C.

From a microbiological standpoint, the product should be used immediately unless the method of opening, reconstitution, and dilution excludes the risk of microbial contamination. If not used immediately, the in-use storage time and conditions prior to use are the responsibility of the user.

After reconstitution and dilution:

With regard to the combined storage time (reconstituted solution in the vial and diluted solution in infusion bags), physical and chemical stability during use has been demonstrated for 12 hours at 25°C or 24 hours at 2°C – 8°C.

From a microbiological standpoint, the product should be used immediately unless the method of opening, reconstitution, and dilution excludes the risk of microbial contamination. If not used immediately, the in-use storage time and conditions are the responsibility of the user.

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

Water for injection must not be used for the preparation of Daptomycin Xellia. Daptomycin Xellia must be reconstituted only with 9 mg/ml (0.9%) sodium chloride solution.

Reconstitute the lyophilised product with 7 ml of 9 mg/ml (0.9%) sodium chloride injection solution to obtain a concentration of 50 mg/ml for injection of Daptomycin Xellia.

The lyophilised product takes approximately 15 minutes to dissolve. The fully reconstituted product is clear and may contain a few small bubbles or foam around the edge of the vial.

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

An aseptic technique must be used throughout the reconstitution process.

1. Remove the polipropylene "flip-off" cap to expose the central portion of the rubber stopper. Clean the top of the rubber stopper with an alcohol swab or other antiseptic solution and allow it to dry. After cleaning, do not touch the rubber stopper or allow it to come into contact with any other surface. Using a sterile transfer needle of gauge 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 through the center of the rubber stopper, directing the needle toward the vial wall.
2. Gently rotate the vial to ensure complete wetting of the product, then allow it to stand for 10 minutes.
3. Finally, gently rotate or shake the vial for a few minutes until a clear reconstituted solution is obtained. Avoid vigorous shaking to prevent foaming.
4. Carefully inspect the reconstituted solution before use to ensure the substance is fully dissolved and to check for the absence of particulate matter. The colour of the reconstituted Daptomycin Xellia solution may range from pale yellow to light brown.
5. Invert the vial so that the solution flows 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 lowest point of the solution in the vial as you draw the solution into the syringe. Slowly withdraw the reconstituted solution (50 mg daptomycin/ml) from the vial using a sterile needle of gauge 21 or smaller.
6. Before removing the needle from the vial, pull the plunger back to the end of the syringe barrel to withdraw all the solution from the inverted vial.
7. Replace the needle with a new one for intravenous injection.
8. Expel air, large bubbles, and any excess solution to obtain the required dose.
9. The reconstituted solution should then be administered slowly by intravenous injection over 2 minutes.

After reconstitution:

The reconstituted solution in the vial has been shown to be physically and chemically stable for up to 12 hours at 25°C and up to a maximum of 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 time and conditions prior to use are the responsibility of the user, and normally should not exceed 24 hours at 2°C – 8°C, unless reconstitution was carried out under controlled and validated aseptic conditions.

This medicinal product must not be mixed with other medicinal products except those mentioned above.

Daptomycin Xellia vials are for single use only. Any unused portion remaining in the vial must be discarded.

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