Daptomycin Xellia 500 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 500 mg powder for solution for injection and infusion EFG

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.

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

• This medicine has been prescribed for you only. Do not pass it on to others, even if they have the same symptoms as you, because it could harm them.

• If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are 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 side 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 in Daptomicina Xellia powder for injectable solution and for infusion (referred to as Daptomicina Xellia throughout this leaflet) is daptomycin. Daptomycin is an antibacterial agent that can stop 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 your doctor's instructions regarding dose, dosing interval, and duration of treatment.

Do not store or reuse this medicine. If you have any antibiotic left over after completing your 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 the heart valves), caused by a type of bacteria called Staphylococcus aureus, and to treat bloodstream infections caused by the same type of bacteria 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 starting to receive 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 starting to receive Daptomicina Xellia:

• If you currently 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 muscle 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 experienced, after taking daptomycin, a severe skin rash, 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 observed in individuals of average weight, and therefore you may require closer monitoring for adverse effects.

If any of the above situations 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 nearly 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, hives, or fever.
• Serious skin disorders have been reported with the use of daptomycin. Symptoms associated with these skin conditions may include:
• onset or worsening of fever,
• raised or fluid-filled red spots on the skin, which may 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 genital area.
• 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 condition called eosinophilic pneumonia. Your doctor will check your lung function and decide whether or not to continue treatment with Daptomicina Xellia.

Daptomicina Xellia may interfere with laboratory tests measuring blood clotting ability. Results may falsely 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 regularly during treatment.

Children and adolescents

Daptomicina Xellia must not be administered 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

Inform 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 cyclosporine (a medicine used in transplant patients 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 may temporarily discontinue 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 kidney elimination of Daptomicina Xellia.
• 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 plan 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 use machines.

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 Daptomicina Xellia is administered

Daptomicina 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 infections or bloodstream infections associated with skin or heart infections. 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 individuals 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 scheduled on a dialysis day, you will normally 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 full course of treatment for skin infections typically lasts between 1 and 2 weeks. Your doctor will decide the duration of 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 experiences 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.

• Contact 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, usually occurring after more than 2 weeks of treatment. Symptoms may include difficulty breathing, new onset or worsening cough, or new onset or worsening fever. If you experience these symptoms, inform your doctor or nurse immediately.
• Serious skin disorders. Symptoms may include:
• new onset or worsening fever,
• raised red spots or fluid-filled blisters on the skin, which may start in the armpits or on the chest or groin area 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:

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

• Fungal infections, such as oral thrush (mouth ulcers).
• Urinary tract infection.
• Decrease in red blood cell count (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 platelet count, which may increase the tendency to form 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, 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.
• Generalized pain or weakness, tiredness (fatigue).
• Increased blood sugar, serum creatinine, myoglobin, or lactate dehydrogenase (LDH) levels; prolonged blood clotting time; or electrolyte imbalance in blood tests.
• Eye itching.

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

• Yellowing of the skin and eyes (jaundice).
• Prolonged 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), easy bruising, bleeding gums, or nosebleeds.

Reporting of adverse effects

If you experience any adverse effect, consult 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 Pharmacovigilance System for 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 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 normally should 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 up to 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 must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging that you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Daptomicina Xellia

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

The other component is sodium hydroxide.

Nature of the product and pack contents

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

Daptomicina Xellia is available in packs of 1 or 5 vials.

Only certain pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer Responsible

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 the most recent review of this leaflet: July 2021.

This information is intended for healthcare professionals only:

Important: Consult the Summary of Product Characteristics or SmPC before prescribing.

Instructions for use and handling

500 mg presentation:

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

Daptomycin Xellia administered as intravenous infusion over 30 or 60 minutes

Reconstituting the lyophilized product with 10 ml of 9 mg/ml (0.9%) sodium chloride injection solution yields a concentration of 50 mg/ml for Daptomycin Xellia infusion.

The lyophilized 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, aseptic technique must be maintained.

For reconstitution:

1. Remove the "flip-off" polipropylene 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 contact any other surface. Using a sterile transfer needle of gauge 21 or smaller, or a needle-free device, draw 10 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. Gently rotate or swirl the vial for a few minutes until a clear reconstituted solution is obtained. Avoid vigorous agitation 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 color 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 of 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 needle tip at the lowest point of the solution in the vial when withdrawing 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 must then be administered intravenously 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 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 storage duration 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 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 storage duration and conditions during use are the responsibility of the user.

Daptomycin Xellia administered as intravenous injection over 2 minutes (adults only)

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

Reconstitute the lyophilized product with 10 ml of 9 mg/ml (0.9%) sodium chloride injection solution to obtain a concentration of 50 mg/ml for Daptomycin Xellia injection.

The lyophilized 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:

Throughout the reconstitution process, aseptic technique must be maintained.

1. Remove the "flip-off" polipropylene 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 contact any other surface. Using a sterile transfer needle of gauge 21 or smaller, or a needle-free device, draw 10 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. Gently rotate or swirl the vial for a few minutes until a clear reconstituted solution is obtained. Avoid vigorous agitation 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 color 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 needle tip at the lowest point of the solution in the vial while drawing 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 must 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 48 hours at 2°C – 8°C.

From a microbiological standpoint, the product should be used immediately. If not used immediately, the storage duration and conditions during use are the responsibility of the user, and normally should not exceed 24 hours at 2°C – 8°C, unless reconstitution was performed 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 medicine is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS): http://www.aemps.es/