Prospect: information for the patient

Daptomicin Cipla 350 mg powder for injectable solution and for infusion EFG

Daptomicin Cipla 500 mg powder for injectable solution and for infusion EFG

Read this prospect carefully before starting to use this medication, as it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor or nurse.
• This medication has been prescribed only to you, and you must not give it to other people even if they have the same symptoms as you, as it may harm them.
• If you experience adverse effects, consult your doctor or nurse, even if they do not appear in this prospect. See section 4.

The active ingredient of Daptomicina Cipla powder for injectable solution and for infusion is daptomycin. Daptomycin is an antibacterial capable of stopping the growth of certain bacteria.

Daptomicina Cipla is used in adults and in 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 Cipla is also used in adults to treat infections in the tissues that cover the inside of the heart (including heart valves), caused by a type of bacteria called Staphylococcus aureus. It is also used to treat blood 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 antibacterials while you receive treatment with Daptomicina Cipla.

Do not take Daptomicina Cipla

If you are allergic to daptomycin or sodium hydroxide or any of the other ingredients 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 Cipla.

• If you have or have had kidney problems. Your doctor may need to change the dose of daptomycin (see section 3 of this leaflet).
• Occasionally, patients taking daptomycin may develop increased sensitivity, muscle pain or 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 taking daptomycin. Symptoms usually disappear 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 severe 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 that you may therefore need closer monitoring in cases of adverse effects.

If any of the above cases affect you, inform your doctor or nurse before receiving daptomycin.

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

• Severe allergic reactions have been observed in patients treated with almost all antibacterial agents, including daptomycin. Symptoms may include rapid breathing, difficulty breathing, facial, neck and throat inflammation, skin rash and urticaria, or fever.
• Severe skin diseases have been reported with the use of daptomycin. Symptoms that occur with these skin diseases may include:

• appearance of fever or worsening of the same,
• red skin patches elevated 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 sores in the mouth or genitals.

• Severe kidney problems have been reported with the use of daptomycin. Symptoms may include fever and rash.
• Any type of tingling or numbness in the hands or feet, loss of sensation or unusual difficulty moving. If this occurs, inform your doctor, who will decide whether to continue treatment.
• Diarrea, mainly if you observe the presence of blood or mucus in stools or if diarrhea becomes severe or lasts long.
• Appearance of fever or worsening of the same, cough or difficulty breathing. These may be signs of a rare but severe lung function deterioration called eosinophilic pneumonia. Your doctor will check your lung function and decide whether to continue treatment with daptomycin.

Daptomycin may interfere with laboratory tests that measure your blood's clotting ability. Results may appear to suggest poor clotting, despite no actual problem. Therefore, it is essential that your doctor is aware that you are receiving daptomycin. Inform your doctor that you are on daptomycin treatment.

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

Children and adolescents

Daptomycin should not be administered to children under one year of age, as animal studies have shown that this age group may experience severe adverse effects.

Use in elderly patients

Elderly patients over 65 years of age may receive the same dose as other adults, provided their kidneys function correctly.

Other medicines and Daptomicina Cipla

Inform your doctor or nurse if you are using, have used recently or may need to use any other medicine.

It is particularly important to mention the following:

• Medicines called statins or fibrates (to lower cholesterol) or cyclosporine (a medicine used in transplants to prevent organ rejection or for other conditions, e.g. rheumatoid arthritis or atopic dermatitis). There may be an increased risk of muscle adverse effects if you take any of these medicines (and other that may affect muscles) during treatment with daptomycin. Your doctor may decide not to administer daptomycin 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 daptomycin by the kidneys.
• 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 usually not administered to pregnant women. If you are pregnant or breastfeeding, or think you may be pregnant or intend to become pregnant, consult your doctor or pharmacist before using this medicine.

Do not breastfeed while receiving daptomycin, as it may pass into breast milk and affect the baby.

Driving and operating machinery

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; it is essentially "sodium-free".

Daptomicina Cipla will be administered 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 your bloodstream (in a vein), either as a 30-minute infusion or as a 2-minute injection. The same dose is recommended for people over 65 years old, provided their kidneys are functioning properly.

If your kidneys are not functioning well, you may receive Daptomicina Cipla less frequently, for example, once every other day. If you are undergoing dialysis and your next dose of Daptomicina Cipla is due on a dialysis day, you will usually 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) will depend on the patient's age and the type of infection being treated. This dose is administered directly into the bloodstream (in a vein), as a 30-60 minute infusion.

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 for skin infections.

Instructions for use and handling are provided in detail at the end of the prospectus.

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

The following are the most serious side effects:

Severe side effects of unknown frequency(cannot be estimated from available data)

During daptomycin administration, 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 experience any of the following symptoms:

• Chest pain or pressure,
• Rash or hives,
• Swelling around the throat,
• Fast or weak pulse,
• Labored breathing,
• Fever,
• Chills or tremors,
• Headache,
• 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 degeneration (rhabdomyolysis), which can cause kidney damage.

Other side effectsthat have been reported with the use of daptomycin are:

• A rare but potentially severe lung condition called eosinophilic pneumonia in patients treated with daptomycin, mostly after more than 2 weeks of treatment. Symptoms may include difficulty breathing, cough, or worsening of cough, or fever or worsening of fever.
• Severe skin diseases. Symptoms may include:
• • Fever or worsening of fever,
  • Red patches on the skin that are raised or filled with fluid, which may start in the armpits or on the chest or groin and may spread to a large area of the body,
  • Blisters or sores in the mouth or genitals.
• A severe 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 side effects reported most frequently:

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

• Fungal infections, such as mouth ulcers,
• Urinary tract infection,
• Decreased red blood cell count (anemia),
• Dizziness, anxiety, difficulty falling asleep,
• Headache,
• Fever, weakness (asthenia),
• High or low blood pressure,
• Constipation, abdominal pain,
• Diarrhea, nausea or vomiting,
• Flatulence,
• Abdominal swelling or distension,
• Rash or itching,
• Pain, itching, or redness at the infusion site,
• Pain in arms or legs,
• Elevated liver enzymes or creatine phosphokinase (CPK) levels in blood tests.

The following are other side effects that may occur after treatment with Daptomycin Cipla:

Rare 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 levels of certain types of white blood cells),
• Loss of appetite,
• Tingling or numbness in hands or feet, changes in taste,
• Tremors,
• Changes in heart rhythm, palpitations,
• Indigestion (dyspepsia), inflammation of the tongue,
• Rash with itching,
• Muscle pain, cramps, or weakness, muscle inflammation (myositis), joint pain,
• Kidney problems,
• Inflammation and irritation of the vagina,
• Elevated blood sugar, creatinine, myoglobin, or lactate dehydrogenase (LDH) levels, 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),

• Prolonged prothrombin time.

Unknown frequency(cannot be estimated from available data)

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

Reporting side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through the Spanish System for the Pharmacovigilance of Medicines for Human Use: https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

• Keep this medication out of the sight and reach of children.
• Store in refrigerator (between 2°C and 8°C).
• Do not use this medication after the expiration date that appears on the box and on the label after CAD. The expiration date is the last day of the month indicated.

• Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose ofthepackaging and themedicines that you no longerneed. This will help protect the environment.

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

Appearance of the product and contents of the package

Daptomycin Cipla powder for injection and infusion is presented in a glass vial as a powder or a yellowish-brownish cake. It is mixed with a solvent to form a solution before administration.

Daptomycin Cipla is presented in packages containing 1 vial or 5 vials.

Only some package sizes may be commercially available.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization

Cipla Europe NV

De Keyserlei 58-60,

Box 19, 2018 Antwerp

Belgium

Responsible for manufacturing

Kleva Pharmaceuticals S.A

Parnithos Ave. 189,

Acharnai Attiki, 13675

Greece

Cipla Europe NV

De Keyserlei 58-60,

Box 19, 2018 Antwerp

Belgium

Local representative

Cipla Europe NV subsidiary in Spain,

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

Spain

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

Germany: Daptomycin Cipla 350 mg powder for the preparation of an injection/infusion solution

Daptomycin Cipla 500 mg powder for the preparation of an injection/infusion solution

Spain: Daptomycin Cipla 350 mg powder for injection and infusion EFG

Daptomycin Cipla 500 mg powder for injection and infusion EFG

Portugal: Daptomycin Cipla

Daptomycin Cipla

Date of the last review of this leaflet: October 2020

The 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 solely for healthcare professionals:

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

Instructions for use and handling

In adults, daptomycin can be administered intravenously as a 30-minute infusion or as a 2-minute injection. Unlike adults, daptomycin should not be administered to pediatric patients as a 2-minute injection. Pediatric patients aged 7 to 17 years should receive daptomycin as a 30-minute infusion. Pediatric patients under 7 years of age who receive doses of 9-12 mg/kg should receive daptomycin as a 60-minute infusion. The preparation of the infusion solution requires an additional dilution phase, as described below.

Daptomycin Cipla administered as intravenous infusion for 30 or 60 minutes

Reconstituting the lyophilized product with 7 ml of a 9 mg/ml sodium chloride solution (0.9%) (for Daptomycin 350 mg) or 10 ml (for Daptomycin 500 mg) can obtain a concentration of 50 mg/ml of Daptomycin Cipla for infusion.

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

To prepare Daptomycin Cipla for intravenous infusion, follow the instructions below:

For reconstitution:

1. Remove the polipropylene flip-off cap to expose the central part of the rubber stopper. Clean the top of the rubber stopper with an alcohol-soaked cotton swab or other antiseptic solution and allow it to dry. After cleaning, do not touch the rubber stopper or allow it to touch any other surface. Remove 7 ml of a 9 mg/ml sodium chloride solution (0.9%) (for Daptomycin 350 mg) or 10 ml (for Daptomycin 500 mg) using a sterile transfer needle of calibre 21 or less, or a device without a needle, and inject slowly through the center of the rubber stopper into the vial, pointing the needle towards the vial wall.
2. The vial should be gently rotated to ensure that the product is fully moistened, and then left to stand for 10 minutes.
3. Finally, the vial should be gently rotated/agitated for a few minutes to obtain a transparent reconstituted solution. Vigorous agitation should be avoided 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 Daptomycin Cipla may vary from pale yellow to light brown.
5. The reconstituted solution should be diluted with 9 mg/ml sodium chloride solution (0.9%) (typical volume of 50 ml).

For dilution:

1. Remove the reconstituted solution (50 mg daptomycin/ml) from the vial using a new sterile needle of calibre 21 or less. Invert the vial to allow the solution to flow towards the rubber stopper. Using a 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 extracting the solution into the syringe. Before removing the needle from the vial, pull the plunger back to the end of the syringe barrel to remove the required solution from the inverted vial.
2. Expel air, large bubbles, and any excess solution to obtain the required dose.
3. Transfer the reconstituted solution to 50 ml of 9 mg/ml sodium chloride solution (0.9%).
4. The reconstituted and diluted solution should be infused intravenously for 30 or 60 minutes.

Daptomycin Cipla 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 Cipla: 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.

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

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

Reconstituting the lyophilized product with 7 ml of a 9 mg/ml sodium chloride solution (0.9%) (for Daptomycin 350 mg) or 10 ml (for Daptomycin 500 mg) can obtain a concentration of 50 mg/ml of Daptomycin Cipla for injection.

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

To prepare Daptomycin Cipla for intravenous injection, follow the instructions below:

For reconstitution:

1. Remove the polipropylene flip-off cap to expose the central part of the rubber stopper. Clean the top of the rubber stopper with an alcohol-soaked cotton swab or other antiseptic solution and allow it to dry. After cleaning, do not touch the rubber stopper or allow it to touch any other surface. Remove 7 ml of a 9 mg/ml sodium chloride solution (0.9%) (for Daptomycin 350 mg) or 10 ml (for Daptomycin 500 mg) using a sterile transfer needle of calibre 21 or less, or a device without a needle, and inject slowly through the center of the rubber stopper into the vial, pointing the needle towards the vial wall.
2. The vial should be gently rotated to ensure that the product is fully moistened, and then left to stand for 10 minutes.
3. Finally, the vial should be gently rotated/agitated for a few minutes to obtain a transparent reconstituted solution. Vigorous agitation should be avoided 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 Daptomycin Cipla may vary from pale yellow to light brown.
5. Remove the reconstituted solution (50 mg daptomycin/ml) from the vial using a sterile needle of calibre 21 or less.
6. Invert the vial to allow the solution to flow towards the rubber 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 extracting the solution into the syringe. Before removing the needle from the vial, pull the plunger back to the end of the syringe barrel to remove the entire solution from the inverted vial.
7. Replace the needle with a new one for the intravenous injection.
8. Expel air, large bubbles, and any excess solution to obtain the required dose.
9. The reconstituted solution should be injected slowly intravenously for 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 point of view, the product should be used immediately. If not used immediately, the storage time during use is the responsibility of the user and, normally, should not exceed 24 hours at 2°C - 8°C, unless the reconstitution/dissolution has taken place in controlled and validated aseptic conditions.

This medicine should not be mixed with other medicines that are not mentioned above.

The vials of Daptomycin Cipla are exclusively for single use. Any remaining vial that has not been used should be discarded.