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

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

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

daptomycin

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 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 or nurse, even if they are effects not listed in this leaflet. See section 4.

Leaflet contents

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

2. What you need to know before using Daptomicin Avalon

3. How Daptomicin Avalon is administered

4. Possible side effects

5. How to store Daptomicin Avalon

6. Contents of the pack and other information

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

The active substance in this medicine is daptomycin. Daptomycin is an antibacterial agent capable of stopping the growth of certain bacteria.

Antibiotics are used to treat bacterial infections and are not effective against viral infections such as influenza 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 treatment, return it to the pharmacy for proper disposal. Do not dispose of medicines via the drain or in household waste.

Daptomycin is used in adults, 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 bacterium called Staphylococcus aureus. It is also used to treat bloodstream infections caused by the same type of bacterium when associated with a heart infection.

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

2. What you need to know before using Daptomycin Avalon

Do not use Daptomycin Avalon

If you are allergic to daptomycin or to 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 daptomycin.

• If you have or have previously had kidney problems. Your doctor may need to adjust the dose of daptomycin (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 this medicine. Symptoms usually resolve within a few days after stopping treatment with daptomycin.
• 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 people 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 this medicine.

Inform your doctor 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. Symptoms may include 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 associated 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 genital area.
• Serious kidney problems have been reported with the use of daptomycin. Symptoms may include fever and rash.
• Any 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.
• Onset or worsening of fever, cough, or difficulty breathing. These may be signs of a rare but serious lung disorder called eosinophilic pneumonia. Your doctor will check your lung function and decide whether or not to continue treatment with this medicine.

Daptomycin may interfere with laboratory tests measuring your blood's 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 daptomycin. Inform your doctor that you are being treated with this medicine.

Your doctor will perform blood tests to monitor your muscle health before starting treatment and regularly during treatment with daptomycin.

Children and adolescents

Daptomycin must not be given to children under one year of age. Animal studies have shown that this age group may experience serious adverse effects.

Use in elderly patients

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

Other medicines and daptomycin

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 daptomycin. Your doctor may decide not to administer daptomycin or to 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 this medicine.
• 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 receiving this medicine.

You must not breastfeed while receiving daptomycin, 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.

This medicine contains sodium

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

3. How Daptomicina Avalon 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 kg of body weight once daily for skin infections, or 6 mg per kg of body weight once daily for heart infection or blood infection associated with a 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 people aged 65 years and older, provided their kidneys are functioning properly.

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

Children and adolescents (from 1 to 17 years of age)

The recommended doses in children and adolescents (from 1 to 17 years of age) 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 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 your treatment for blood 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 most serious adverse effects are described below:

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

• Hypersensitivity reactions (serious allergic reactions including anaphylaxis and angioedema) have been reported during administration of daptomycin. These serious allergic reactions require immediate medical attention. Inform your doctor or nurse immediately if you experience any of the following symptoms:
• chest pain or pressure,
• rash or hives,
• swelling around the throat,
• rapid or weak pulse,
• wheezing,
• fever,
• chills or shaking,
• flushing,
• dizziness,
• fainting,
• metallic taste.

Contact your doctor immediately if you experience muscle pain, tenderness, or weakness of unknown origin. Muscle problems may be serious and include muscle breakdown (rhabdomyolysis), which may lead to kidney damage.

Other adverse effects reported with the use of daptomycin include:

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

• A rare but potentially serious lung disorder called eosinophilic pneumonia, mostly occurring after more than 2 weeks of treatment. Symptoms may include shortness of breath, new or worsening cough, or new or worsening fever.
• Serious skin disorders. Symptoms may include:
  • new 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 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 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 thrush (oral ulcers).
• Urinary tract infection.
• Decrease in the number of red blood cells (anaemia).
• Dizziness, anxiety, difficulty sleeping.
• Headache.
• Fever, weakness (asthenia).
• High or low blood pressure.
• Constipation, abdominal pain.
• Diarrhoea, 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.
• Changes in heart rhythm, flushing.
• Indigestion (dyspepsia), inflammation of the tongue.
• Itchy skin rash.
• Muscle pain, cramps or weakness, muscle inflammation (myositis), joint pain.
• Kidney problems.
• Inflammation and irritation of the vagina.
• Generalised pain or weakness, tiredness (fatigue).
• Elevated blood sugar, serum creatinine, myoglobin or lactate dehydrogenase (LDH) levels, prolonged blood clotting time, or electrolyte imbalance, as detected in blood tests.
• Itchy eyes.

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 diarrhoea 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, consult your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicinal Products: https://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Daptomicin Avalon

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date stated on the carton and label after EXP. The expiry date refers to the last day of the month indicated.
• 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 total storage time (reconstituted solution in the vial and diluted solution in infusion bags; see section 6.6) at 25°C must 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 must not exceed 12 hours (or 48 hours at 2°C – 8°C).

From a microbiological standpoint, the product should be used immediately. This medicine does not contain preservatives or bacteriostatic agents. If immediate use is not possible, 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 reconstitution/dilution has been carried out under controlled and validated aseptic conditions.

Do not use Daptomicin Avalon if you notice any change in the appearance of the product (signs of moisture or presence of differently colored particles in the powder, or presence of particles, cloudiness, or precipitate in the reconstituted solution).

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

6. Contents of the pack and other information

Composition of Daptomycin Avalon

• 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

Daptomycin Avalon powder for injectable solution and for 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 prior to 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, 41A
08970 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 poudre pour solution injectable/pour perfusion

Spain:

Daptomycin Avalon 350 mg powder for injectable solution and for infusion EFG

Date of latest review of this leaflet: February 2022

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

This information is intended for healthcare professionals only:

Important: Please consult the Summary of Product Characteristics or the Package Leaflet 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. In contrast to 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 (see sections 4.2 and 5.2). Preparation of the infusion solution requires an additional dilution step, as described below.

Daptomycin administered as intravenous infusion over 30 or 60 minutes

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

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

To prepare daptomycin for intravenous infusion, follow the instructions below:

An aseptic technique must be used throughout the reconstitution and dilution process.

For reconstitution:

1. Remove the polypropylene 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 to dry. After cleaning, do not touch the rubber stopper or allow it to contact any other surface. Draw 7 ml of an injectable solution containing 9 mg/ml of sodium chloride (0.9%) into a syringe using a sterile transfer needle of gauge 21 or smaller, or a needle-free device, and slowly inject through the center of the rubber stopper into the vial, 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 swirl the vial for several minutes until a clear, reconstituted solution is obtained. Avoid vigorous shaking to prevent foaming.
4. Carefully inspect the reconstituted solution before use to ensure complete dissolution and to verify the absence of suspended particles. The colour of the reconstituted Daptomycin Avalon solution may vary from pale yellow to light brown.
5. The reconstituted solution must then be diluted with 9 mg/ml sodium chloride (0.9%) (typical volume 50 ml).

For dilution:

1. Slowly withdraw the appropriate volume of reconstituted liquid (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 new syringe, insert the needle into the inverted vial. While keeping the vial inverted, place the needle tip at the lowest point of the liquid as the solution is withdrawn into the syringe. Before removing the needle from the vial, pull the plunger back to the end of the syringe barrel to withdraw all remaining solution from the inverted vial.
2. Expel air, large bubbles, and any excess solution to achieve 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 must be administered intravenously over 30 or 60 minutes.

Daptomycin 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: aztreonam, ceftazidime, ceftriaxone, gentamicin, fluconazole, levofloxacin, dopamine, heparin, and lidocaine.

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

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

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

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

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

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

To prepare daptomycin for intravenous injection, follow the instructions below:

An aseptic technique must be used throughout the reconstitution process.

1. Remove the polypropylene 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 to dry. After cleaning, do not touch the rubber stopper or allow it to contact any other surface. Draw 7 ml of an injectable solution containing 9 mg/ml sodium chloride (0.9%) into a syringe using a sterile transfer needle of gauge 21 or smaller, or a needle-free device, and slowly inject through the center of the rubber stopper into the vial, 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 swirl the vial for several minutes until a clear, reconstituted solution is obtained. Avoid vigorous shaking to prevent foaming.
4. Carefully inspect the reconstituted solution before use to ensure complete dissolution and to verify the absence of suspended particles. The colour 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 of gauge 21 or smaller.
6. 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 liquid as the solution is withdrawn into the syringe. Before removing the needle from the vial, pull the plunger back to the end of the syringe barrel to withdraw all remaining 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 achieve the required dose.
9. The reconstituted solution must be administered slowly by intravenous injection over 2 minutes.

Physical and chemical stability 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 standpoint, the product should be used immediately. If not used immediately, the storage time is the responsibility of the user and should normally not exceed 24 hours at 2°C – 8°C, unless reconstitution/dilution has taken place under controlled and validated aseptic conditions.

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

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