Daptomycin Accord 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 Accord 500 mg powder for solution for injection and for 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 or nurse.
• This medicine has been prescribed for you only and must not be given to other people, even if they have the same symptoms as you, since it could harm them.
• If you experience any side effects, talk to your doctor or nurse, even if they are side effects not listed in this leaflet. See section 4.

Contents of this leaflet

1. What Daptomicina Accord is and what it is used for
2. What you need to know before receiving Daptomicina Accord
3. How Daptomicina Accord is administered
4. Possible side effects
5. How to store Daptomicina Accord
6. Contents of the pack and other information

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

The active substance in Daptomicina Accord for powder for solution for injection and infusion is daptomycin.

Daptomycin is an antibacterial agent that can stop the growth of certain bacteria. Daptomycin is used in adults and in children and adolescents (aged 1 to 17 years) to treat skin and underlying 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 in the tissues lining the inside of the heart (including the heart valves), caused by a type of bacteria called Staphylococcus aureus. It is also used 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 treatment with Daptomicina Accord.

2. What you need to know before starting Daptomicin Accord

Do not receive Daptomicin Accord

If you are allergic to daptomycin or sodium hydroxide or 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 receiving 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 muscle sensitivity, pain, or 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 daptomycin. 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 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 daptomycin.

Inform 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. Symptoms may include wheezing, difficulty breathing, swelling of the face, neck, and throat, skin rash, hives, and fever.
• Serious skin disorders have been reported with the use of Cubicin. 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 genitals.
• Serious kidney problems have been reported with the use of Cubicin. 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.
• 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 daptomycin.

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 daptomycin.

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, 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.

Use of Daptomicin Accord with other medicines

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

It is particularly important that you mention the following:

• Medications called statins or fibrates (used to lower cholesterol) or cyclosporine (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 daptomycin. Your doctor may decide not to administer daptomycin 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 kidney elimination of daptomycin.
• 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 receiving this medicine.

You must not breastfeed while receiving daptomycin, as it may pass into breast milk and harm the baby.

Driving and using machines

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

Daptomicin Accord contains sodium

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

3. How to take Daptomycin Accord

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 recommended 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 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 working properly, 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)

Doses in children and adolescents (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 to 60 minutes.

A full course of treatment for skin infections normally 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 most serious adverse effects are described below:

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

During administration of daptomycin, there have been some cases of hypersensitivity reactions (serious allergic reactions including anaphylaxis, angioedema). 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 shivering,
• 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, 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, mostly after more than 2 weeks of treatment. Symptoms may include difficulty breathing, new or worsening cough, or new or worsening fever.

• Serious skin diseases. Symptoms may include:

• new or worsening fever,

• raised red spots or fluid-filled blisters 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.

• A serious kidney problem. Symptoms may include fever and rash.

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

The more commonly reported adverse effects are described below:

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

• Fungal infections, such as thrush,
• 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,
• Bloating or gas (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 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 levels, serum creatinine, myoglobin or lactate dehydrogenase (LDH), prolonged blood clotting time, or electrolyte imbalance, detected in blood tests.
• Itchy eyes

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

• Yellowing of the skin and eyes,
• 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), bruising more easily, bleeding gums or nosebleeds.

Reporting of adverse effects:

If you experience any adverse effect, talk to your doctor or pharmacist, 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 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 Daptomycin Accord

• 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 following 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).

However, from a microbiological standpoint, the product should be used immediately. If not used immediately, the in-use storage time is the responsibility of the user and should normally not exceed 24 hours at 2°C–8°C.

Do not use Daptomycin Accord 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 precipitation when the solution is reconstituted). Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the container and other information

Composition of Daptomycin Accord

• The active substance is daptomycin. One vial of powder contains 500 mg of daptomycin. One ml contains 50 mg of daptomycin after reconstitution with 10 ml of sodium chloride solution 9 mg/ml (0.9%).
• The other component is sodium hydroxide.

Appearance of the product and contents of the container

Daptomycin Accord powder for solution for injection 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.

This medicine is available in packs containing 1 vial or 5 vials.

Only certain pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Accord Healthcare, S.L.U.

World Trade Center

Moll de Barcelona, s/n

Edifici Est, 6th floor

08039 Barcelona

Spain

Manufacturer

Medichem, S.A.

Narcís Monturiol 41

E-08970 Sant Joan Despí, Barcelona

Spain

Hikma Italia SpA

Viale Certosa 10

I-27100 Pavia

Italy

This medicinal product is authorized in the Member States of the EEA under the following names:

Date of last review of this leaflet: July 2023

This information is intended for healthcare professionals only:

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

Instructions for use and handling

500 mg presentation:

In adults, daptomycin may be administered intravenously either as an infusion over 30 minutes or as an injection over 2 minutes. 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 by infusion over 30 minutes. Pediatric patients under 7 years of age receiving doses of 9–12 mg/kg should be administered daptomycin. The preparation of infusion solution requires an additional dilution step, as described below.

Daptomycin Accord administered as intravenous infusion over 30 or 60 minutes

Reconstituting the lyophilized product with 10 ml of an injectable solution containing 9 mg/ml sodium chloride (0.9%) yields a concentration of 50 mg/ml daptomycin for infusion.

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

To prepare Daptomycin Accord for intravenous infusion, 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 it to dry. After cleaning, do not touch the rubber stopper or allow it to contact any other surface. Draw up 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 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 suspended particles. The color of the reconstituted solution 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. The reconstituted solution must then be diluted with 9 mg/ml sodium chloride (0.9%) (typical volume of 50 ml).
7. 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 and withdraw 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 all remaining solution from the inverted vial.
8. Replace the needle with a new one for intravenous infusion.
9. Expel air, large bubbles, and any excess solution to achieve the required dose.
10. 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 Accord administered as intravenous injection over 2 minutes

Water must not be used to reconstitute Daptomycin Accord for intravenous injection. This medicinal product must be reconstituted exclusively with 9 mg/ml sodium chloride (0.9%).

Reconstituting the lyophilized product with 10 ml of an injectable solution containing 9 mg/ml sodium chloride (0.9%) yields a concentration of 50 mg/ml daptomycin for injection.

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

To prepare Daptomycin Accord 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 it to dry. After cleaning, do not touch the rubber stopper or allow it to contact any other surface. Draw up 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 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 suspended particles. The color of the reconstituted solution 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 and withdraw 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 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.

The 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 in-use storage time is the responsibility of the user and should normally not exceed the time limits indicated above for chemical and physical stability during use.

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

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