Daptomycin Cipla 350 mg powder for injection and for infusion EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

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

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

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

• Keep this leaflet as you may need to read it again.
• If you have any questions, ask your doctor 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 adverse effects not listed in this leaflet. See section 4.

Leaflet contents

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

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

The active substance in Daptomicina Cipla powder for injectable solution and for infusion is daptomycin. Daptomycin is an antibacterial agent capable of inhibiting the growth of certain bacteria.

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

It is important that you follow your doctor's instructions regarding dosage, administration intervals, 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 wastewater or household waste.

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

Daptomicina Cipla is also used in adults to treat infections of the tissues lining the inside of the heart (including heart valves), caused by a type of 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 Cipla.

2. What you need to know before starting Daptomycin Cipla

Do not take Daptomycin Cipla

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 Daptomycin Cipla.

• 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 taking 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 daptomycin. Symptoms usually resolve within a few days after stopping treatment with daptomycin.
• If you have ever had a severe skin rash, skin peeling, blisters, and/or mouth sores, or serious kidney problems after taking daptomycin.
• 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 daptomycin.

Inform your doctor 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. 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 genitals.

• 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 condition called eosinophilic pneumonia. Your doctor will check your lung function 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.

Other medicines and Daptomycin Cipla

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 transplants 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 may 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 using 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.

Daptomycin Cipla contains sodium

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

3. How Daptomicina Cipla is administered

Daptomicina Cipla 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 adult dose 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 people aged 65 years and older, provided their kidneys are functioning properly.

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

Children and adolescents (1 to 17 years of age)

The recommended doses in children and adolescents (1 to 17 years of age) 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 usually lasts between 1 and 2 weeks. Your doctor will decide the duration of your treatment for bloodstream or heart infections and for skin infections.

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

4. Possible adverse effects

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

Below are the most serious adverse effects described:

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

Cases of 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 pressure,
• Rash or hives,
• Swelling around the throat,
• Rapid or weak pulse,
• Wheezing,
• Fever,
• Chills or shivering,
• Flushing,
• Dizziness,
• Fainting,
• Metallic taste.

Consult your doctor immediately if you experience muscle pain, tenderness, or weakness of unknown origin. Muscle problems 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 in patients treated with daptomycin, 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 skin lesions or fluid-filled blisters, which may start in the armpits or on 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 perform additional tests to establish a diagnosis.

Below are the more frequently reported adverse effects:

Frequent adverse 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, 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.

Below are other adverse effects that may occur after treatment with Daptomycin Cipla:

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),
• Decreased 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 rash,
• Muscle pain, cramps or weakness, muscle inflammation (myositis), joint pain,
• Kidney problems,
• Inflammation and irritation of the vagina,
• Generalized pain or weakness, tiredness (fatigue),
• Elevated levels of blood sugar, serum creatinine, myoglobin, or lactate dehydrogenase (LDH), prolonged blood clotting time, or electrolyte imbalance in blood tests,
• Itchy eyes.

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

• Yellowing of the skin and eyes (jaundice),
  • 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), increased tendency to bruise, 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 Cipla

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

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

• 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.

• Medicines should 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 container and other information

• The active substance is daptomycin.
• Daptomicina Cipla 350 mg powder for solution for injection and for infusion EFG: One vial of powder contains 350 mg of daptomycin. After reconstitution with 7 ml of sodium chloride solution 9 mg/ml (0.9%), 1 ml contains 50 mg of daptomycin.
• Daptomicina Cipla 500 mg powder for solution for injection and for infusion EFG: One vial of powder contains 500 mg of daptomycin. After reconstitution with 10 ml of sodium chloride solution 9 mg/ml (0.9%), 1 ml contains 50 mg of daptomycin.
• The other component is sodium hydroxide.

Appearance of the product and contents of the container

Daptomicina Cipla 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.

Daptomicina Cipla 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

Cipla Europe NV

De Keyserlei 60C, Bus-1301,

2018 Antwerp, Belgium

Manufacturer Responsible

Kleva Pharmaceuticals S.A

Parnithos Ave. 189,

Acharnai Attiki, 13675, Greece

Cipla Europe NV

De Keyserlei 60C, Bus-1301,

2018 Antwerp, Belgium

Local Representative

Cipla Europe NV, Spanish branch

C/Guzmán el Bueno, 133, Edif Britannia - 28003 - Madrid

Spain

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

Germany: Daptomycin Cipla 350 mg powder for solution for injection and infusion

Daptomycin Cipla 500 mg powder for solution for injection and infusion

Spain: Daptomycin Cipla 350 mg powder for injectable solution and for perfusion EFG

Daptomycin Cipla 500 mg powder for injectable solution and for perfusion EFG

Portugal: Daptomycin Cipla

Daptomycin Cipla

Date of the most recent review of this leaflet: October 2020

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

This information is intended for healthcare professionals only:

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

Instructions for use and handling

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

Daptomycin Cipla administered as intravenous infusion over 30 or 60 minutes

Reconstitute the lyophilised product with 7 mL of an injectable solution (for Daptomycin 350 mg) or 10 mL (for Daptomycin 500 mg) of 9 mg/mL sodium chloride (0.9%), to obtain a concentration of 50 mg/mL of Daptomycin Cipla for infusion.

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

To prepare Daptomycin Cipla 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 it to dry. After cleaning, do not touch the rubber stopper or allow it to come into contact with any other surface. Draw up 7 mL of an injectable solution (for Daptomycin 350 mg) or 10 mL (for Daptomycin 500 mg) of 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 centre of the rubber stopper into the vial, directing the needle towards 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 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 colour of the reconstituted Daptomycin Cipla solution may vary from pale yellow to light brown.
5. The reconstituted solution should then be diluted with 9 mg/mL sodium chloride (0.9%) (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 towards the stopper. Using a syringe, insert the needle into the inverted vial. While keeping the vial inverted, place the tip of the needle at the lowest point of the 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 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 to 50 mL of 9 mg/mL sodium chloride (0.9%).
4. The reconstituted and diluted solution should be administered intravenously over 30 or 60 minutes.

Daptomycin Cipla 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 Cipla: 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 for 12 hours at 25°C or 24 hours if refrigerated at 2°C – 8°C.

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

Water for injection must not be used to reconstitute Daptomycin Cipla for intravenous injection. Daptomycin Cipla must be reconstituted exclusively with 9 mg/mL sodium chloride (0.9%).

Reconstituting the lyophilised product with 7 mL of an injectable solution (for Daptomycin 350 mg) or 10 mL (for Daptomycin 500 mg) of 9 mg/mL sodium chloride (0.9%) yields a concentration of 50 mg/mL of Daptomycin Cipla for injection.

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

To prepare Daptomycin Cipla 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 come into contact with any other surface. Draw up 7 mL of an injectable solution (for Daptomycin 350 mg) or 10 mL (for Daptomycin 500 mg) of 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 centre of the rubber stopper into the vial, directing the needle towards 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 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 colour of the reconstituted Daptomycin Cipla solution may vary from pale yellow to light brown.
5. Slowly withdraw the reconstituted solution (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 towards the stopper. Using a new syringe, insert the needle into the inverted vial. While keeping the vial inverted, place the tip of the needle at the lowest point of the 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 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 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 normally should not exceed 24 hours at 2°C – 8°C, unless reconstitution/dissolution 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 Cipla vials are for single use only. Any unused portion remaining in the vial must be discarded.