DAPTOMYCIN Dr. Reddy's 350 mg POWDER FOR SOLUTION FOR INJECTION AND INFUSION

Introduction

Patient Information Leaflet

Daptomycin Dr. Reddys 350 mg powder for solution for injection and infusion EFG

daptomycin

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 further questions, ask your doctor or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you experience any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What is Daptomycin Dr. Reddys and what is it used for
2. What you need to know before you receive Daptomycin Dr. Reddys
3. How Daptomycin Dr. Reddys is administered
4. Possible side effects
5. Storage of Daptomycin Dr. Reddys

Contents of the pack and further information

1. What is Daptomycin Dr. Reddys and what is it used for

The active substance of Daptomycin Dr. Reddys is daptomycin. Daptomycin is an antibacterial agent capable of stopping the growth of certain bacteria.

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

It is essential that you follow the instructions regarding dosage, administration interval, and treatment duration as indicated by your doctor.

Do not store or reuse this medication. If you have any leftover antibiotic after completing treatment, return it to the pharmacy for proper disposal. Do not dispose of medications down the drain or in the trash.

Daptomycin Dr. Reddys is used in adults and in children and adolescents (ages 1 to 17 years) to treat skin and underlying tissue infections. It is also used to treat blood infections when associated with a skin infection. Daptomycin Dr. Reddys is also used in adults to treat infections in the tissues that line 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 heart infection.

Depending on the type of infection(s) you are suffering from, your doctor may also prescribe other antibacterial agents while you are receiving treatment with Daptomycin Dr. Reddys.

2. What you need to know before you receive Daptomycin Dr. Reddys

You must not receive Daptomycin Dr. Reddys

• 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 receiving Daptomycin Dr. Reddys:

• If you have or have previously had kidney problems. Your doctor may need to change the dose of daptomycin (see section 3 of this leaflet).
• Occasionally, patients who receive daptomycin tend to develop 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 daptomycin. The symptoms usually disappear within a few days after stopping treatment with daptomycin.
• If you have ever developed 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 or nurse immediately if you develop any of the following symptoms:

• Acute and severe allergic reactions have been observed in patients treated with almost all antibacterial agents, including daptomycin. The symptoms may include shortness of breath, difficulty breathing, swelling of the face, neck, and throat, skin rash, and hives, fever.
• Severe skin disorders have been reported with the use of daptomycin. The symptoms that occur with these skin disorders may include:
• new or worsening fever,
• red patches on the skin that are raised or filled with fluid that can start in the armpits or on the chest or groin and can spread to a large part of your body,
• blisters or sores in the mouth or genitals.
• A severe kidney problem has been reported with the use of daptomycin. The symptoms may include fever and rash.
• Any unusual tingling or numbness in the hands or feet, loss of sensitivity, or difficulty moving. If this happens, inform your doctor, who will decide whether you should continue treatment.
• Diarrhea, mainly if you notice the presence of blood or mucus in your stool or if the diarrhea becomes severe or persistent.
• Onset of fever or worsening of it, 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 you should 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 actual 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. 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.

Use of Daptomycin Dr. Reddys with other medicines

Tell your doctor or nurse if you are using, have recently used, or might use 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 the muscles) during treatment with daptomycin. Your doctor may decide not to administer daptomycin or temporarily interrupt treatment with the other medicine.
• Medicines 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 medicines 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 receiving this medicine.

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.

Daptomycin Dr. Reddys contains sodium hydroxide as an excipient

This medicine contains less than 23 mg (1 mmol) of sodium per vial, so it is considered essentially "sodium-free"

3. How Daptomycin Dr. Reddys is administered

Daptomycin Dr. Reddys 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 kg of body weight once daily for skin infections or 6 mg per kg of body weight once daily for heart or blood infections associated with skin infections. 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 correctly.

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

Children and adolescents (1 to 17 years of age)

The recommended doses in children and adolescents (1 to 17 years) being treated for skin infections 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 blood 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(frequency cannot be estimated from the available data)

Some cases of hypersensitivity reactions (severe allergic reactions including anaphylaxis, angioedema, drug rash with eosinophilia and systemic symptoms (DRESS)) 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,
• Rapid or weak pulse,
• Shortness of breath,
• Fever,
• Chills or shivering,
• Hot flashes,
• Dizziness,
• Fainting,
• Metallic taste.

Tell your doctor immediately if you experience pain, sensitivity, or unexplained muscle weakness. Muscle problems can be severe, including muscle breakdown (rhabdomyolysis), which can cause kidney damage.

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

• A rare but potentially serious lung disorder called eosinophilic pneumonia, mainly after more than 2 weeks of treatment. The symptoms may include difficulty breathing, new or worsening cough, or new or worsening fever.
• Severe skin disorders. The symptoms may include:
  • new or worsening fever,
  • red patches on the skin that are raised or filled with fluid that can start in the armpits or on the chest or groin and can spread to a large part of your 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, inform your doctor or nurse immediately. Your doctor will perform additional tests to make a diagnosis.

The following are described the most frequently reported side effects:

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

• Fungal infections, such as thrush (mouth ulcers),
• Urinary tract infection,
• Decreased 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 with treatment with daptomycin:

Uncommon 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 number of certain types of white blood cells),

• Decreased appetite,
• Numbness or tingling in hands or feet, taste disturbances,
• Tremors,
• Changes in heart rhythm, hot flashes,
• Indigestion (dyspepsia), tongue inflammation,
• Itchy skin 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), 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), 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 it is possible side effects not listed in this leaflet. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Daptomycin Dr. Reddys

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

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

After reconstitution: The chemical and physical stability of the reconstituted solution in the vial has been demonstrated for 12 hours at 25°C and up to 48 hours at 2°C - 8°C. The chemical and physical stability of the diluted solution in infusion bags is 12 hours at 25°C or 24 hours between 2°C - 8°C.

For the 30-minute intravenous infusion, the combined storage time (reconstituted solution in vial and diluted solution in infusion bag; see section 6.6) at 25°C should not exceed 12 hours (or 24 hours between 2°C -8°C).

For the 2-minute intravenous injection, the storage time of the reconstituted solution in the vial (see section 6.6) at 25°C should not exceed 12 hours (or 48 hours between 2°C - 8°C).

However, from a microbiological point of view, the product should be used immediately. The product does not contain preservatives or bacteriostatic agents. If not used immediately, the storage time is the responsibility of the user and will normally not exceed 24 hours at 2°C - 8°C, unless the reconstitution/dilution has taken place in controlled and validated aseptic conditions.

Do not use this medicine after the expiry date which is stated on the carton after EXP and on the label after EXP. The expiry date is the last day of the month shown.

Do not use this medicine if you notice visible signs of deterioration.

Medicines should 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 pack and further information

Composition of Daptomycin Dr. Reddys

The active substance is daptomycin

The active substance is daptomycin. One vial of powder contains 350 mg of daptomycin.

One ml provides 50 mg of daptomycin after reconstitution with 7 ml of sodium chloride solution (0.9%).

The other component is sodium hydroxide.

Appearance of the product and packaging contents

Daptomicina Dr. Reddys 350 mg powder for solution for injection/infusion EFG 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 Dr. Reddys is presented in packs containing 1 vial.

Marketing authorization holder and manufacturer

Marketing authorization holder

Reddy Pharma Iberia, S.A.

Avenida Josep Tarradellas, nº 38

08029 Barcelona-Spain

Tel.: +34 93 355 49 16

Fax: +34 93 355 49 61

Manufacturer

Dr. Reddy´s Laboratories (UK) Ltd.

6, Riverview Road, Beverley,

East Yorkshire, HU17 0LD

United Kingdom

Fax No: +44 1482872042

Phone No: +44 1482860228

or

Betapharm Arzneimittel GmbH

Kobelweg 95,

86156 Augsburg, Germany

This medicinal product is authorized in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:

Denmark: Daptomycin beta 350 mg Powder for solution for injection/infusion

Spain: Daptomicina Dr. Reddys 350 mg, powder for solution for injection and for infusion EFG

United Kingdom: Daptomycin Dr. Reddy's 350 mg Powder For Solution For Injection/Infusion

Italy: Daptomicina Dr. Reddy's 350 mg, Powder for solution for injection or for infusion

France: Daptomycine Dr. Reddy's 350 mg, powder for solution for injection or for infusion

Date of last revision of this leaflet: December 2021

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

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 as an infusion over 30 minutes. Pediatric patients under 7 years of age who receive doses of 9-12 mg/kg should be administered daptomycin as an infusion over 60 minutes. Preparation of the infusion solution requires an additional dilution phase, as described below.

Daptomicina Dr. Reddys administered as an intravenous infusion over 30 or 60 minutes

Reconstituting the lyophilized product with 7 ml of an injectable solution containing 9 mg/ml of sodium chloride (0.9%) yields a concentration of 50 mg/ml of Daptomicina Dr. Reddys for infusion.

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 Daptomicina Dr. Reddys for intravenous infusion, follow these instructions:

To reconstitute or dilute Daptomicina Dr. Reddys lyophilized product, aseptic technique must 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 an alcohol swab or other antiseptic solution and let it dry. After cleaning, do not touch the rubber stopper or allow it to touch any other surface. Withdraw 7 ml of an injectable solution (for Daptomicina Dr. Reddys 350 mg powder for solution for injection/infusion EFG) containing 9 mg/ml of sodium chloride (0.9%) into a syringe using a sterile transfer needle of 21 gauge or smaller, 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 clear 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 particles in suspension. The color of the reconstituted solution of Daptomicina Dr. Reddys 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 of 21 gauge or smaller, inverting 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 solution in the vial while it is being withdrawn 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 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.

Daptomicina Dr. Reddys 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: 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.

Daptomicina Dr. Reddys administered as an intravenous injection over 2 minutes (only for adult patients)

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

Reconstituting the lyophilized product with 7 ml of an injectable solution containing 9 mg/ml of sodium chloride (0.9%) for injection yields a concentration of 50 mg/ml of Daptomicina Dr. Reddys for solution for injection.

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 Daptomicina Dr. Reddys for intravenous injection, follow these instructions:

To reconstitute Daptomicina Dr. Reddys lyophilized product, aseptic technique must 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 an alcohol swab or other antiseptic solution and let it dry. After cleaning, do not touch the rubber stopper or allow it to touch any other surface. Withdraw 7 ml of an injectable solution containing 9 mg/ml of sodium chloride (0.9%) into a syringe using a sterile transfer needle of 21 gauge or smaller, 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 clear 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 particles in suspension. The color of the reconstituted solution of Daptomicina Dr. Reddys 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 21 gauge or smaller.
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 solution in the vial while it is being withdrawn 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 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 Daptomicina Dr. Reddys are for single use only. Any unused remainder of the vial should be discarded.