DAPTOMYCIN AVALON 350 mg POWDER FOR INJECTION AND INFUSION SOLUTION

Introduction

Patient Information Leaflet

Daptomicina Avalon350 mg powder for solution for injection and infusion EFG

daptomicina

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 further questions, ask your doctor or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you experience 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 the pack

1. What is Daptomicina Avalon and what is it used for
2. What you need to know before you take Daptomicina Avalon
3. How to take Daptomicina Avalon
4. Possible side effects
5. Storing Daptomicina Avalon

1. Contents of the pack and further information

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

The active substance of this medicine is daptomicina. Daptomicina is an antibacterial agent capable of stopping the growth of certain bacteria.

Antibiotics are used to treat bacterial infections and do not work for viral infections such as the flu or the common cold.

It is essential that you follow the instructions regarding dosage, administration interval, and treatment duration indicated by your doctor.

Do not store or reuse this medicine. If you have any leftover antibiotic after finishing treatment, return it to the pharmacy for proper disposal. Do not throw away medicines via wastewater or household waste.

Daptomicina is used in adults, children, and adolescents (ages 1 to 17 years) to treat skin and soft tissue infections. It is also used to treat blood infections when associated with a skin infection.

Daptomicina is also used in adults to treat infections of the tissues that line the inside of the heart (including heart valves), caused by a bacterium called Staphylococcus aureus.It is also used to treat blood infections caused by the same type of bacterium when associated with a heart infection.

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

2. What you need to know before you use Daptomicina Avalon

Do not use DaptomicinaAvalon

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

If this is the case, inform your doctor or nurse. If you think you may be allergic, consult your doctor or nurse.

Warnings and precautions

Consult your doctor or nurse before starting to take daptomicina.

• If you have or have previously had kidney problems. Your doctor may need to change the dose of daptomicina (see section 3 of this leaflet).
• Occasionally, patients who receive daptomicina may develop increased sensitivity, pain, or muscle weakness (see section 4 of this leaflet for more information). Inform your doctor if this happens. Your doctor will ensure that you have a blood test and advise whether it is recommended to continue using this medicine. The symptoms usually disappear within a few days after stopping treatment with daptomicina.
• If you have ever had, after taking daptomicina, a severe skin rash or skin peeling, blisters, and/or ulcers in the mouth, or severe kidney problems.
• If you are significantly overweight, there is a possibility that your blood levels of daptomicina may be higher than those found in people of average weight, and you may therefore need stricter control in case of side effects.

If any of the above cases apply to you, inform your doctor or nurse before receiving this medicine.

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

• Severe allergic reactions have been observed in patients treated with virtually all antibacterial agents, including daptomicina. The symptoms may include shortness of breath, difficulty breathing, swelling of the face, neck, and throat, skin rash, and hives, or fever.
• Serious skin diseases have been reported with the use of daptomicina. The symptoms that occur with these skin diseases may include:
• • Appearance of fever or worsening of it,
  • Red spots on the skin, raised or filled with fluid, which may start in the armpits or in areas of the chest or groin and may spread over a large area of the body,
  • Blisters or ulcers in the mouth or genitals.
• Serious kidney problems have been reported with the use of daptomicina. The symptoms may include fever and rash.
• Any type of tingling or numbness in the hands or feet, loss of sensitivity, or unusual movement difficulties. If this occurs, inform your doctor, who will decide whether to continue treatment.
• Diarrhea, mainly if you observe the presence of blood or mucus in stools or if the diarrhea becomes severe or prolonged.
• Appearance of fever or worsening of it, cough, or difficulty breathing. These may be signs of a rare but serious lung condition called eosinophilic pneumonia. Your doctor will check the condition of your lungs and decide whether to continue treatment with this medicine.

Daptomicina may interfere with laboratory tests that measure the blood's ability to clot. The results may appear to suggest poor clotting, even if there is no actual problem. Therefore, it is essential that your doctor is aware that you are receiving daptomicina. Inform your doctor that you are being treated with this medicine.

Your doctor will perform blood tests to monitor the health of your muscles before you start treatment and frequently during treatment with daptomicina.

Children and adolescents

Daptomicina should not be administered to children under one year of age. Animal studies have shown that this age group may experience severe side effects.

Use in elderly patients

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

Other medicines and daptomicina

Tell your doctor or nurse if you are using, have recently used, or might use any other medicines.

It is particularly important that you mention the following:

• Medicines called statins or fibrates (to lower cholesterol) or cyclosporin (a medicine used in transplants to prevent organ rejection or for other conditions, e.g., rheumatoid arthritis or atopic dermatitis). It is possible that the risk of muscle side effects may increase if you take any of these medicines (and others that may affect the muscles) during treatment with daptomicina. Your doctor may decide not to administer daptomicina or 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 this medicine by the kidneys.
• Oral anticoagulants (e.g., warfarin), which are medicines that prevent blood clotting. It may be necessary for your doctor to monitor your blood clotting times.

Pregnancy and breastfeeding

Daptomicina is not usually administered 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 receiving this medicine.

Do not breastfeed if you are receiving daptomicina, as it may pass into breast milk and affect the baby.

Driving and using machines

Daptomicina has no known effects on the ability to drive or use machines.

This medicine contains sodium

This medicine contains less than 23 mg of sodium (1 mmol) per dose; this is essentially "sodium-free".

3. How to take Daptomicina Avalon

Daptomicina will be administered to you by your doctor or nurse.

Adults (18 years of age and older)

The dose will depend on your weight and the type of infection being treated. The usual dose for adults is 4 mg per kilogram of body weight once a day for skin infections or 6 mg per kilogram of body weight once a day for heart infections or blood 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 that lasts approximately 30 minutes or as an injection that lasts approximately 2 minutes. The same dose is recommended for people over 65 years of age, provided their kidneys are functioning correctly.

If your kidneys do not function well, you may receive daptomicina more frequently, e.g., every other day. If you are undergoing dialysis and your next dose of daptomicina is due on a dialysis day, you will usually receive the medicine after the dialysis session.

Children and adolescents (1 to 17 years of age)

The recommended doses in children and adolescents (1 to 17 years) will depend 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 that lasts approximately 30-60 minutes.

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

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

The following are described the most serious side effects:

Serious side effects with unknown frequency(cannot be estimated from the available data)

• During the administration of daptomicina, some cases of hypersensitivity reactions (severe allergic reactions, including anaphylaxis and angioedema) have been reported. These severe allergic reactions require immediate medical attention. Inform your doctor or nurse immediately if you have any of the following symptoms:
• chest pain or pressure,
• rash or hives,
• swelling around the throat,
• rapid or weak pulse,
• shortness of breath,
• fever,
• chills or shivering,
• flushing,
• dizziness,
• fainting,
• metallic taste.

Consult your doctor immediately if you experience pain, increased sensitivity, or muscle weakness of unknown origin. Muscle problems can be severe, including muscle breakdown (rhabdomyolysis), which can cause kidney damage.

Other side effects that have been reported with the use of daptomicina are:

Serious side effects with unknown frequency(cannot be estimated from the available data)

• a rare but potentially serious lung condition called eosinophilic pneumonia, mostly after more than 2 weeks of treatment. The symptoms may include difficulty breathing, appearance of cough or worsening of it, or appearance of fever or worsening of it.
• Serious skin diseases. The symptoms may include:
• • appearance of fever or worsening of it,
  • red spots on the skin, raised or filled with fluid, which may start in the armpits or in areas of the chest or groin and may spread over a large area of the body,
  • blisters or ulcers in the mouth or genitals.
• A serious kidney problem. The symptoms may include fever and rash.

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

The following are described the most frequently reported side effects:

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

• Fungal infections, such as 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, nausea or vomiting .
• Flatulence.
• Abdominal swelling or abdominal 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 described other side effects that may occur after treatment with daptomicina:

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

• Blood disorders (e.g., increased platelet count, which may increase the tendency to develop blood clots, or increased white blood cell count) .
• Decreased appetite.
• Tingling or numbness in the hands or feet, altered taste.
• Tremors.
• Changes in heart rhythm, flushing.
• Indigestion (dyspepsia), tongue inflammation.
• Skin rash with itching.
• Pain, cramps, or muscle weakness, muscle inflammation (myositis), joint pain.
• Kidney problems.
• Vaginal inflammation and irritation.
• Generalized pain or weakness, fatigue.
• Elevated levels of blood sugar, serum creatinine, myoglobin, or lactate dehydrogenase (LDH), prolonged blood clotting time, or electrolyte imbalance in blood tests.
• Eye itching

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

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

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

Antibiotic-associated colitis, including pseudomembranous colitis (severe or persistent diarrhea containing blood and/or mucus, associated with abdominal pain or fever), bruising more easily, bleeding gums, or nosebleeds.

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Spanish Medicines Monitoring System for Human Use: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storing Daptomicina Avalon

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date which is stated on the carton and label after EXP. The expiry date is the last day of the month stated.
• Store in a refrigerator (between 2°C and 8°C).

After reconstitution:

The physical and chemical stability during use of the reconstituted solution in the vial has been demonstrated for 12 hours at 25°C and up to a maximum of 48 hours at 2°C – 8°C.

After dilution:

The physical and chemical stability of the diluted solution in infusion bags has been established for 12 hours at 25°C or 24 hours at 2°C – 8°C.

For intravenous infusion over 30 minutes, the combined storage time (reconstituted solution in the vial and diluted solution in infusion bags; see section 6.6) at 25°C should not exceed 12 hours (or 24 hours at 2°C – 8°C).

For intravenous injection over 2 minutes, the storage time of the reconstituted solution in the vial (see section 6.6) at 25°C should not exceed 12 hours (or 48 hours at 2°C – 8°C).

From a microbiological point of view, the product should be used immediately. This medicine does not contain preservatives or bacteriostatic agents. If not used immediately, the storage time and conditions during use are the responsibility of the user and, normally, should not exceed 24 hours at 2°C - 8°C, unless the reconstitution/dilution has taken place in controlled and validated aseptic conditions.

Do not use Daptomicina Avalon if you notice any change in the appearance of the product (signs of moisture or presence of particles in the powder of a different color, or presence of particles, turbidity, or precipitate once the solution is reconstituted.

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

6. Container Content and Additional Information

Composition of Daptomicina Avalon

• The active ingredient is daptomycin. A 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 Container Content

Daptomicina Avalon powder for solution for injection and infusion is presented in a glass vial as a pale yellow to light brown powder or cake. It is mixed with a solvent to form a solution before administration.

It is available in packs containing 1 vial or 5 vials.

Only some pack sizes may be marketed.

Marketing Authorization Holder

Avalon Laboratorios, S.L.

Calle La Cora, 4 Local 1,

18006 Granada, Spain

Manufacturer

Medichem, S.A.

Narcís Monturiol, 41A08970 Sant Joan Despí (Barcelona)

Spain

or

Hikma Italia SpA

10 Viale Certosa

27100 Pavia

Italy

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

France:

Daptomycine Medac 350 mg powder for solution for injection/infusion

Spain:

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

Date of the last revision of this leaflet: February 2022

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

This information is intended only for healthcare professionals:

Important: Please consult the Summary of Product Characteristics or Package Leaflet before prescribing.

Instructions for use and handling

Presentation of 350 mg:

In adults, daptomycin can be administered intravenously as an infusion over 30 minutes or as an injection over 2 minutes. Unlike adults, daptomycin should not be administered to pediatric patients as an injection over 2 minutes. Pediatric patients from 7 to 17 years of age should receive daptomycin by infusion over 30 minutes. Pediatric patients under 7 years of age who receive doses of 9-12 mg/kg should be administered daptomycin by infusion over 60 minutes (see sections 4.2 and 5.2). The preparation of the solution for infusion requires an additional dilution phase, as described below.

Daptomycin administered as an intravenous infusion over 30 or 60 minutes

Reconstituting the lyophilized product with 7 ml of an injectable solution containing 9 mg/ml of sodium chloride (0.9%) can obtain a concentration of 50 mg/ml of daptomycin for infusion.

The lyophilized product takes approximately 15 minutes to dissolve. The fully reconstituted product has a transparent appearance and may present some small bubbles or foam around the edge of the vial.

To prepare daptomycin for intravenous infusion, follow these instructions:

To reconstitute or dilute daptomycin lyophilized, aseptic technique must be used throughout the process.

For reconstitution:

1. The polypropylene "flip-off" closure cap must be removed to make the central part of the rubber stopper visible. Clean the top of the rubber stopper with a cotton swab with alcohol or another antiseptic solution and let it dry. After cleaning, do not touch the rubber stopper or allow it to touch any other surface. Withdraw 7 ml of an injectable solution containing 9 mg/ml of sodium chloride (0.9%) into a syringe using a sterile transfer needle with a diameter of 21 gauge or less, or a needleless device, and slowly inject it through the center of the rubber stopper into the vial, aiming the needle at the vial wall.
2. The vial should be gently rotated to ensure that the product is completely wetted, and then left to stand for 10 minutes.
3. Finally, the vial should be gently rotated/agitated for a few minutes until a transparent reconstituted solution is obtained. Avoid vigorous agitation to prevent foam formation.
4. The reconstituted solution should be carefully inspected before use to ensure that the substance is dissolved and to verify the absence of particles in suspension. The color of the reconstituted solution of Daptomicina Avalon may vary from pale yellow to light brown.
5. The reconstituted solution should be diluted with 9 mg/ml of sodium chloride (0.9%) (typical volume of 50 ml).

For dilution:

1. Slowly withdraw the appropriate reconstituted liquid (50 mg daptomycin/ml) from the vial using a new sterile needle with a diameter of 21 gauge or less, inverting the vial so that the solution falls towards the stopper. Using a new syringe, insert the needle into the inverted vial. Keeping the vial inverted, place the tip of the needle at the lowest point of the liquid while withdrawing the solution into the syringe. Before removing the needle from the vial, pull the plunger back to the end of the syringe cylinder to remove all the 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 to 50 ml of 9 mg/ml sodium chloride (0.9%).
4. The reconstituted and diluted solution should be infused intravenously over 30 or 60 minutes.

Daptomycin is not physically or chemically compatible with solutions containing glucose. The following drugs have been shown to be compatible when added to infusion solutions containing daptomycin: aztreonam, ceftazidime, ceftriaxone, gentamicin, fluconazole, levofloxacin, dopamine, heparin, and lidocaine.

The combined storage time (reconstituted solution in the vial and diluted solution in infusion bags) at 25°C should not exceed 12 hours (24 hours if refrigerated).

The stability of the diluted solution in infusion bags has been established for 12 hours at 25°C or 24 hours if refrigerated at 2°C - 8°C.

Daptomicina Avalon administered as an intravenous injection over 2 minutes (only for adult patients)

Water should not be used for the reconstitution of daptomycin for intravenous injection. Daptomicina Avalon should be reconstituted only with 9 mg/ml of sodium chloride (0.9%).

Reconstituting the lyophilized product with 7 ml of an injectable solution containing 9 mg/ml of sodium chloride (0.9%) can obtain a concentration of 50 mg/ml of daptomycin for injection.

The lyophilized product takes approximately 15 minutes to dissolve. The fully reconstituted product has a transparent appearance and may present some small bubbles or foam around the edge of the vial.

To prepare daptomycin for intravenous injection, follow these instructions:

To reconstitute daptomycin lyophilized, aseptic technique must be used throughout the process.

1. The polypropylene "flip-off" closure cap must be removed to make the central part of the rubber stopper visible. Clean the top of the rubber stopper with a cotton swab with alcohol or another antiseptic solution and let it dry. After cleaning, do not touch the rubber stopper or allow it to touch any other surface. Withdraw 7 ml of an injectable solution containing 9 mg/ml of sodium chloride (0.9%) into a syringe using a sterile transfer needle with a diameter of 21 gauge or less, or a needleless device, and slowly inject it through the center of the rubber stopper into the vial, aiming the needle at the vial wall.
2. The vial should be gently rotated to ensure that the product is completely wetted, and then left to stand for 10 minutes.
3. Finally, the vial should be gently rotated/agitated for a few minutes until a transparent reconstituted solution is obtained. Avoid vigorous agitation to prevent foam formation.
4. The reconstituted solution should be carefully inspected before use to ensure that the substance is dissolved and to verify the absence of particles in suspension. The color of the reconstituted solution of this medicinal product 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 with a diameter of 21 gauge or less.
6. Invert the vial so that the solution falls towards the stopper. Using a new syringe, insert the needle into the inverted vial. Keeping the vial inverted, place the tip of the needle at the lowest point of the liquid while withdrawing the solution into the syringe. Before removing the needle from the vial, pull the plunger back to the end of the syringe cylinder to remove 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 be slowly injected intravenously over 2 minutes.

The physical and chemical stability during use of the reconstituted solution in the vial has been demonstrated for 12 hours at 25°C and up to a maximum of 48 hours if refrigerated (2°C - 8°C).

However, from a microbiological point of view, the product should be used immediately. If not used immediately, the storage time is the responsibility of the user and, normally, should not exceed 24 hours at 2°C - 8°C, unless the reconstitution/dilution has taken place in controlled and validated aseptic conditions.

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

The vials of Daptomicina Avalon are for single use only. Any unused remainder of the vial should be discarded.