DAPTOMYCIN CIPLA 500 mg POWDER FOR INJECTION AND INFUSION SOLUTION

2. What you need to know before you take Daptomicina Cipla

Do not take Daptomicina Cipla

If you are allergic to daptomycin or sodium hydroxide or any of the other components of this medication (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 in the past. Your doctor may need to change 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 happens. Your doctor will ensure that you have a blood test and advise whether or not it is recommended to continue using daptomycin. The symptoms usually disappear within a few days after stopping treatment with daptomycin.
• If you have ever had a severe skin rash or skin peeling, blisters, and/or sores in the mouth, or severe kidney problems after taking daptomycin.
• If you are significantly overweight, there is a possibility that your blood levels of daptomycin may be higher than those found in people of average weight, and you may need stricter control in case of side effects.

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

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

• Severe allergic reactions, including anaphylaxis and angioedema, have been observed in patients treated with virtually all antibacterial agents, including daptomycin. The symptoms may include:
• Shortness of breath,
• Dizziness,
• Facial swelling,
• Rapid or weak pulse,
• Abnormal heart rhythm,
• Fever,
• Chills or tremors,
• Flushing,
• Dizziness,
• Fainting,
• Metallic taste.

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

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

• A rare but potentially serious lung condition called eosinophilic pneumonia in patients treated with daptomycin, mostly after more than 2 weeks of treatment. The symptoms may include:

• Difficulty breathing,
• Cough or worsening cough,
• Fever or worsening fever.

• Severe skin diseases. The symptoms may include:
• • Fever or worsening fever,
  • Red patches on the skin, raised or filled with fluid, which can start in the armpits or on the chest or groin and can spread over a large area of the body,
  • Blisters or sores in the mouth or genitals.
• A serious kidney problem. The symptoms may include fever and rash.

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

Children and adolescents

Daptomycin should not be administered to children under 1 year of age, as animal studies have shown that this age group may experience severe side effects.

Use in elderly patients

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

Other medications and Daptomicina Cipla

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

It is particularly important that you mention the following:

• Medications called statins or fibrates (to lower cholesterol) or cyclosporin (a medication used in transplants to prevent organ rejection or for other conditions, e.g., rheumatoid arthritis or atopic dermatitis). It is possible that the risk of muscle side effects may increase if you take any of these medications (and others that may affect the muscles) during treatment with daptomycin. Your doctor may decide not to administer daptomycin or temporarily interrupt treatment with the other medication.
• Medications to relieve pain 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 medications that prevent blood clotting. It may be necessary for your doctor to monitor your blood clotting times.

Pregnancy and breastfeeding

Daptomycin is not usually administered to pregnant women. If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medication.

Do not breastfeed if you are 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 use machines.

Daptomicina Cipla contains sodium

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

3. How to take Daptomicina Cipla

Daptomicina Cipla will be administered to you normally 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 normal dose for adults is 4 mg per kg of body weight once a day for skin infections or 6 mg per kg of body weight once a day for a heart infection or a bloodstream infection associated with a skin or heart infection. In adult patients, this dose is administered directly into your bloodstream (in a vein), either as an infusion that lasts approximately 30 minutes or as an injection that lasts approximately 2 minutes. The same dose is recommended for people over 65 years of age, provided their kidneys are functioning properly.

If your kidneys do not function well, you may receive Daptomicina Cipla less frequently, e.g., 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) 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 an infusion that lasts approximately 30-60 minutes.

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

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

4. Possible side effects

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

The following are described the most serious side effects:

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

Some cases of hypersensitivity reactions (severe allergic reactions including anaphylaxis and angioedema) have been reported during the administration of daptomycin. These severe allergic reactions require immediate medical attention. Inform your doctor or nurse immediately if you have any of the following symptoms:

• Chest pain or pressure,
• Rash or hives,
• Swelling around the throat,
• Fast or weak pulse,
• Shortness of breath,
• Fever,
• Chills or shivers,
• Flushing,
• Dizziness,
• Fainting,
• Metallic taste.

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

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

• A rare but potentially serious lung condition called eosinophilic pneumonia in patients treated with daptomycin, mostly after more than 2 weeks of treatment. The symptoms may include:

• Difficulty breathing,
• Cough or worsening cough,
• Fever or worsening fever.

• Severe skin diseases. The symptoms may include:
• • Fever or worsening fever,
  • Red patches on the skin, raised or filled with fluid, which can start in the armpits or on the chest or groin and can spread over a large area of the body,
  • Blisters or sores in the mouth or genitals.
• A serious kidney problem. The symptoms may include fever and rash.

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

The following are described the most common side effects:

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

• Fungal infections, such as thrush (mouth ulcers),
• Urinary tract infection,
• Decrease in the number of red blood cells (anemia),
• Dizziness, anxiety, difficulty sleeping,
• Headache,
• Fever, weakness (asthenia),
• High or low blood pressure,
• Constipation, abdominal pain,
• Diarrhea, nausea or vomiting,
• Flatulence,
• Abdominal swelling or distension,
• Skin rash or itching,
• Pain, itching, or redness at the infusion site,
• Pain in arms or legs,
• High levels of liver enzymes or creatine phosphokinase (CPK) in blood tests.

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

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

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

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

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

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

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

Reporting of side effects

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

5. Storing Daptomicina Cipla

• Keep this medication out of sight and reach of children.
• • Store in the refrigerator (between 2°C and 8°C).
  • Do not use this medication after the expiration date stated on the carton and label after EXP. The expiration date is 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 no longer required. This will help protect the environment.

6. Contents of the pack and other information

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

Appearance and packaging

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

Daptomicina Cipla is presented in packs containing 1 vial or 5 vials.

Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder

Cipla Europe NV

De Keyserlei 58-60,

Box 19, 2018 Antwerp

Belgium

Manufacturer

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, Spanish branch,

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

Spain

This pharmaceutical product is authorized in the Member States of the EEA 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: Daptomicina Cipla 350 mg powder for solution for injection and infusion EFG

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

Portugal: Daptomicina Cipla

Daptomicina Cipla

Date of the last review of this prospectus: October 2020

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

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This information is intended solely for healthcare professionals:

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

Instructions for use and handling

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

Daptomycin Cipla administered as an intravenous infusion over 30 or 60 minutes

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

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

To prepare Daptomycin Cipla for intravenous infusion, follow these instructions:

To reconstitute or dilute Daptomycin Cipla lyophilized, an aseptic technique must be used throughout the process.

For reconstitution:

1. The polypropylene "flip-off" closure cap must be removed to make the central part of the rubber stopper visible. Clean the top of the rubber stopper with a cotton swab with alcohol or another antiseptic solution and let it dry. After cleaning, do not touch the rubber stopper or allow it to touch any other surface. Draw up 7 ml of an injectable solution (for Daptomycin 350 mg) or 10 ml (for Daptomycin 500 mg) with 9 mg/ml of sodium chloride (0.9%) into a syringe using a sterile transfer needle with a diameter of 21 gauge or less, or a needleless device, and slowly inject it through the center of the rubber stopper into the vial, aiming the needle at the vial wall.
2. The vial should be gently rotated to ensure that the product is completely moistened, and then left to stand for 10 minutes.
3. Finally, the vial should be gently rotated/shaken for a few minutes until a transparent reconstituted solution is obtained. Avoid vigorous agitation to prevent foam formation.
4. The reconstituted solution should be carefully inspected before use to ensure that the substance is dissolved and to verify the absence of suspended particles. The color of the reconstituted solution of Daptomycin Cipla may vary from pale yellow to light brown.
5. The reconstituted solution should then be diluted with 9 mg/ml of sodium chloride (0.9%) (typical volume of 50 ml).

For dilution:

1. Slowly withdraw the appropriate reconstituted liquid (50 mg daptomycin/ml) from the vial using a new sterile needle with a diameter of 21 gauge or less, inverting the vial so that the solution falls towards the stopper. Using a syringe, insert the needle into the inverted vial. Keeping the vial inverted, place the tip of the needle at the lowest point of the liquid while withdrawing the solution into the syringe. Before removing the needle from the vial, pull the plunger back to the end of the syringe cylinder to 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 infused intravenously over 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 kept refrigerated at 2°C – 8°C.

Daptomycin Cipla administered as an intravenous injection over 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 of sodium chloride (0.9%).

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

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

To prepare Daptomycin Cipla for intravenous injection, follow these instructions:

To reconstitute Daptomycin Cipla lyophilized, an aseptic technique must be used throughout the process.

1. The polypropylene "flip-off" closure cap must be removed to make the central part of the rubber stopper visible. Clean the top of the rubber stopper with a cotton swab with alcohol or another antiseptic solution and let it dry. After cleaning, do not touch the rubber stopper or allow it to touch any other surface. Draw up 7 ml of an injectable solution (for Daptomycin 350 mg) or 10 ml (for Daptomycin 500 mg) with 9 mg/ml of sodium chloride (0.9%) into a syringe using a sterile transfer needle with a diameter of 21 gauge or less, or a needleless device, and slowly inject it through the center of the rubber stopper into the vial, aiming the needle at the vial wall.
2. The vial should be gently rotated to ensure that the product is completely moistened, and then left to stand for 10 minutes.
3. Finally, the vial should be gently rotated/shaken for a few minutes until a transparent reconstituted solution is obtained. Avoid vigorous agitation to prevent foam formation.
4. The reconstituted solution should be carefully inspected before use to ensure that the substance is dissolved and to verify the absence of suspended particles. The color of the reconstituted solution of Daptomycin Cipla may vary from pale yellow to light brown.
5. Slowly withdraw the reconstituted liquid (50 mg daptomycin/ml) from the vial using a sterile needle with a diameter of 21 gauge or less.
6. Invert the vial so that the solution falls towards the stopper. Using a new syringe, insert the needle into the inverted vial. Keeping the vial inverted, place the tip of the needle at the lowest point of the liquid while withdrawing the solution into the syringe. Before removing the needle from the vial, pull the plunger back to the end of the syringe cylinder to 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 slowly injected intravenously 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 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 should not normally exceed 24 hours at 2°C - 8°C, unless the reconstitution/dissolution has taken place in controlled and validated aseptic conditions.

This medication should not be mixed with other medications except those mentioned above.

The vials of Daptomycin Cipla are for single use only. Any remaining contents of the vial that have not been used should be discarded.