DAPTOMYCIN FOSUN PHARMA 350 mg POWDER FOR INJECTABLE SOLUTION AND FOR INFUSION

2. What you need to know before you are given Daptomicina Fosun Pharma

You should not be given Daptomicina Fosun Pharma

• If you are allergic to daptomycin or sodium hydroxide or any of the other components 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 you start receiving Daptomicina Fosun Pharma:

• If you have or have had kidney problems in the past. Your doctor may need to change the dose of this medicine (see section 3 of this leaflet).
• Occasionally, patients receiving this medicine 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 using this medicine. The symptoms usually disappear within a few days after stopping treatment with this medicine.
• If you have ever had a severe skin rash or skin peeling, blisters, and/or sores in the mouth after taking daptomycin, or severe kidney problems.
• If you are significantly overweight, there is a possibility that your blood levels of this medicine may be higher than those found in people of average weight, and you may need stricter control in case of side effects.
• If you develop a superinfection during treatment, as the use of antibacterial agents may promote the overgrowth of non-susceptible microorganisms. In this case, appropriate measures should be taken.

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

Tell 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. Inform your doctor or nurse of any symptoms that suggest an allergic reaction, such as difficulty breathing, swelling of the face, neck, and throat, skin rash, and hives, or fever (see section 4 of this leaflet for more information).
• Severe skin diseases have been reported with the use of daptomycin. The symptoms that occur with these skin diseases may include:
• 1. - onset of fever or worsening of fever,

• red spots on the skin, raised or filled with fluid, which can start in the armpits or areas of the chest or groin and can 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. The symptoms may include fever and rash.
  • Any type of tingling or numbness in the hands or feet, loss of sensitivity, or unusual movement difficulties. If this occurs, inform your doctor, who will decide whether to continue treatment.
  • Diarrhea, mainly if you notice the presence of blood or mucus in stool or if diarrhea becomes severe or prolonged.
  • Onset of fever 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 the condition of your lungs and decide whether to continue treatment with daptomycin.

Daptomycin may interfere with laboratory tests that measure the blood's ability to clot. The results may appear to suggest poor clotting, even if there is no problem. Therefore, it is essential 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 the health of your muscles before you start 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 side effects.

Use in elderly patients

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

Other medicines and Daptomicina Fosun Pharma

Tell your doctor or nurse if you aretaking,haverecentlytakenor might take any other medicines.It is particularly important that you mention the following:

• Medicines called statins or fibrates (to lower cholesterol) or cyclosporin (a medicine 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 medicines (and others 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

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.

Pregnancy

Daptomycin is not usually 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.

Breastfeeding

You should 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 Fosun Pharma contains sodium

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

3. How Daptomicina Fosun Pharma is given

This medicine will be administered to you 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 or blood infections associated with skin or heart infections. 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 over 65 years of age, provided their kidneys are functioning correctly.

If your kidneys do not function well, you may receive this medicine less frequently, e.g., every other day. If you are undergoing dialysis and your next dose of this medicine is due on a dialysis day, you will usually receive this medicine 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 (into a vein), as an infusion lasting 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 blood or heart infections and skin infections.

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

4. Possible side effects

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

The following are the most serious side effects:

• Severe side effects with unknown frequency(cannot be estimated from 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. Tell your doctor or nurse immediately if you have any of the following symptoms:
• - Chest pain or pressure,
• - Rash or hives,
• - Swelling around the throat,
• - Rapid or weak pulse,
• - Difficulty breathing,
• - Fever,
• - Chills or shivering,
• - Hot flashes,
• - Dizziness,
• - Fainting,
• - Metallic taste.

Consult your doctor immediately if you have muscle pain, increased sensitivity, or 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, mostly after more than 2 weeks of treatment. The symptoms may include difficulty breathing, onset of cough or worsening of cough, or onset of fever or worsening of fever.
• Severe skin diseases. The symptoms may include:

• onset of fever or worsening of fever,
• red spots on the skin, raised or filled with fluid, which can start in the armpits or areas of the chest or groin and can spread over a large area of the body,
• blisters or sores in the mouth or genitals.
  • A severe kidney problem. The symptoms may include fever and rash.

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

The following are the most commonly reported 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 red blood cell count (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 abdominal 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 other side effects that may occur after treatment with Daptomicina Fosun Pharma:

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, hot flashes,
• Indigestion (dyspepsia), tongue inflammation,
• Itchy rash
• Muscle pain, cramps, or 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) 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.

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), bruising more easily, bleeding gums, or nosebleeds.

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if you think they are not serious. You can also report side effects directly through the Spanish Medicines Monitoring System for Human Use: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Daptomicina Fosun Pharma

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

Do not use this medicine after the expiry date stated on the label and carton after EXP.

The expiry date is the last day of the month stated.

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

6. Container Content and Additional Information

Composition ofDaptomycin Fosun Pharma

• The active ingredient is daptomycin. One vial of powder contains 350 mg of daptomycin.
• The other component is sodium hydroxide (for pH adjustment)

Appearance of the Product and Container Content

Daptomycin Fosun Pharma 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.

Daptomycin Fosun Pharma is presented in packs containing 1 vial.

Marketing Authorization Holder and Manufacturer

Fosun Pharma Sp. Z o.o

Zajecza 15, 00-351 Warsaw (Poland)

This Medicinal Product is Authorized in the Member States of the European Economic Area under the following Names:

Austria: Daptomycin Fosun Pharma

Germany: Daptomycin Fosun Pharma 350 mg Powder for Solution for Injection/Infusion

Spain: Daptomycin Fosun Pharma 350 mg Powder for Solution for Injection and Infusion

France: Daptomycin Fosun Pharma

Italy: Daptomycin Fosun Pharma

Poland: Daptomycin Fosun Pharma

Date of Last Revision of this Leaflet:March 2022.

Detailed information on this medicinal product 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 for Healthcare Professionals Only:

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

Instructions for Use and Handling for the 350 mg Presentation:

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. Preparation of the infusion solution requires an additional dilution phase, as described below.

Daptomycin Fosun Pharma Administered as Intravenous Infusion over 30 or 60 Minutes

The concentration of 50 mg/ml of Daptomycin Fosun Pharma 350 mg Powder for Infusion is obtained by reconstituting the lyophilized product with 7 ml of a 9 mg/ml (0.9%) sodium chloride injection solution.

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

To Prepare Daptomycin Fosun Pharma for Intravenous Infusion, Follow these Instructions:

To Reconstitute or Dilute Daptomycin Fosun Pharma Lyophilized Product, a Sterile Technique should be Used Throughout the Process.

For Reconstitution:

1. The polypropylene "flip-off" closure cap should be removed to expose the central part of the rubber stopper. Clean the top of the rubber stopper with a cotton swab moistened with alcohol or another antiseptic solution and let it dry. After cleaning, do not touch the rubber stopper or allow it to come into contact with any other surface. Withdraw 7 ml of a 9 mg/ml (0.9%) sodium chloride injection solution 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 towards 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/agitated 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 Fosun Pharma may vary from pale yellow to light brown.
5. The reconstituted solution should then be diluted with 9 mg/ml (0.9%) sodium chloride (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 (0.9%) sodium chloride.
4. The reconstituted and diluted solution should be infused intravenously over 30 or 60 minutes as described in Section 4.2 of the Summary of Product Characteristics.

The following medicinal products have been shown to be compatible when added to infusion solutions containing Daptomycin Fosun Pharma: aztreonam, ceftazidime, ceftriaxone, gentamicin, fluconazole, levofloxacin, dopamine, heparin, and lidocaine.

After Reconstitution: The chemical and physical stability during use of the reconstituted solution has been demonstrated for 12 hours at 25°C and up to a maximum of 48 hours at 2°C – 8°C.

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.

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.

Daptomycin Fosun Pharma Administered as Intravenous Injection over 2 Minutes (Only for Adult Patients)

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

The concentration of 50 mg/ml of Daptomycin Fosun Pharma 350 mg Powder for Solution for Injection and Infusion is obtained by reconstituting the lyophilized product with 7 ml of a 9 mg/ml (0.9%) sodium chloride injection solution.

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

To Prepare Daptomycin Fosun Pharma for Intravenous Injection, Follow these Instructions:

To Reconstitute Daptomycin Fosun Pharma Lyophilized Product, a Sterile Technique should be Used Throughout the Process.

1. The polypropylene "flip-off" closure cap should be removed to expose the central part of the rubber stopper. Clean the top of the rubber stopper with a cotton swab moistened with alcohol or another antiseptic solution and let it dry. After cleaning, do not touch the rubber stopper or allow it to come into contact with any other surface. Withdraw 7 ml of a 9 mg/ml (0.9%) sodium chloride injection solution 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 towards 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/agitated 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 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 as described in Section 4.2 of the Summary of Product Characteristics.

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 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 Medicinal Product should not be Mixed with other Medicinal Products except those mentioned above.

The Vials of Daptomycin Fosun Pharma are for Single Use Only.

Disposal of the Unused Medicinal Product and all Materials that have come into Contact with it should be carried out in accordance with local regulations.