Daptomycin Dr. Reddy's 500 mg powder for solution for injection and for infusion EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Daptomicin Dr. Reddy's 500 mg powder for solution for injection and infusion EFG

daptomycin

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.

Contents of the leaflet

1. What Daptomicin Dr. Reddy's is and what it is used for
2. What you need to know before receiving Daptomicin Dr. Reddy's
3. How Daptomicin Dr. Reddy's is administered
4. Possible side effects
5. How to store Daptomicin Dr. Reddy's
6. Contents of the pack and other information

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

The active substance in Daptomicina 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 flu or the common cold.

It is important that you follow the instructions regarding dose, dosing interval, and duration of treatment as directed by your doctor.

Do not store or reuse this medicine. If you have any antibiotic left over after completing your treatment, return it to the pharmacy for proper disposal. Do not dispose of medicines via wastewater or household waste.

Daptomicina Dr. Reddys is used in adults and in children and adolescents (aged between 1 and 17 years) to treat skin and underlying tissue infections. It is also used to treat bloodstream infections when associated with a skin infection. Daptomicina Dr. Reddys is also used in adults to treat infections of the tissues lining the inside of the heart (including the heart valves), caused by a type of bacterium called Staphylococcus aureus. It is also used to treat bloodstream infections caused by the same type of bacterium when associated with heart infection.

Depending on the type of infection(s) you have, your doctor may also prescribe other antibacterial agents alongside treatment with Daptomicina Dr. Reddys.

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

Do not receive Daptomycin Dr. Reddy's

• if you are allergic to daptomycin, sodium hydroxide, or 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

Consult your doctor or nurse before receiving Daptomicina Dr. Reddys:

• If you have or have previously had kidney problems. Your doctor may need to adjust the dose of daptomicin (see section 3 of this leaflet).
• Occasionally, patients receiving daptomicin may develop muscle pain or 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 you should continue using daptomicin. Symptoms usually resolve within a few days after stopping treatment with daptomicin.
• If you have ever developed a severe skin rash, peeling skin, blisters and/or mouth sores, or serious kidney problems after taking daptomicin.
• If you have significant overweight, there is a possibility that your blood levels of daptomicin 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 Daptomicina.

Tell your doctor or nurse immediately if you experience any of the following symptoms:

• Severe and acute allergic reactions have been observed in patients treated with nearly all antibacterial agents, including daptomicin. Symptoms may include shortness of breath, difficulty breathing, swelling of the face, neck, and throat, skin rash, and hives, fever.
• Serious skin disorders have been reported with the use of daptomicin. Symptoms associated with these skin disorders may include:
  • new or worsening fever,
  • raised or fluid-filled red spots on the skin that may start in the armpits, chest, or groin and may spread to large areas of the body,
  • blisters or sores in the mouth or genital area.
• Serious kidney problems have been reported with the use of daptomicin. Symptoms may include fever and rash.
• Any unusual tingling or numbness in the hands or feet, loss of sensation, or difficulty with movement. 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 persistent.
• Onset of fever or worsening 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 daptomicin.

Daptomicin 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 daptomicin. Inform your doctor that you are being treated with daptomicin.

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

Children and adolescents

Daptomicin 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

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

Use of Daptomicina Dr. Reddys with other medicines

Inform your doctor or nurse if you are taking, have recently taken, or might need to take any other medicines.

It is particularly important to mention the following:

• Medicines called statins or fibrates (used to lower cholesterol) or cyclosporine (a medicine used in organ transplantation 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 daptomicin. Your doctor may decide not to administer daptomicin or to 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's elimination of daptomicin.
• 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 administered to pregnant women. If you are pregnant or breastfeeding, think you may be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before receiving this medicine.

You should 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.

Daptomicin Dr. Reddy's contains sodium hydroxide as excipient

This medicine contains less than 23 mg (1 mmol) of sodium per vial and is therefore considered essentially "sodium-free".

3. How Daptomycin Dr. Reddys is administered

Daptomycin Dr. Reddys 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 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 infections or bloodstream 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 aged 65 years and older, provided their kidneys are functioning properly.

If your kidneys are not functioning properly, you may receive daptomycin less frequently, e.g., once every other day. If you are undergoing dialysis and your next dose of daptomycin is due on a dialysis day, you will usually 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 of age) being treated for skin infections 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 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.

The following are the most serious adverse effects:

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

During administration of daptomycin, there have been rare reports of hypersensitivity reactions (serious allergic reactions including anaphylaxis, angioedema, drug rash with eosinophilia and systemic symptoms (DRESS)). These serious 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.

Inform your doctor immediately if you experience unexplained muscle pain, tenderness, or weakness. Muscle problems can be serious, including muscle breakdown (rhabdomyolysis), which may lead to kidney damage.

Other serious adverse effects reported with the use of daptomycin include:

• A rare but potentially serious lung disorder called eosinophilic pneumonia, mainly after more than 2 weeks of treatment. Symptoms may include difficulty breathing, new or worsening cough, or new or worsening fever.
• Serious skin disorders. Symptoms may include:
  • new or worsening fever,
  • raised red spots or fluid-filled blisters on the skin that may start in the armpits, chest, or groin and may spread to large areas 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 make a diagnosis.

The following are the most commonly reported adverse effects:

Frequent adverse 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, discomfort (nausea or vomiting),
• Flatulence,
• Swelling or bloating of the abdomen,
• 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.

The following are other adverse effects that may occur after treatment with daptomycin:

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 form blood clots, or increased number of certain types of white blood cells),
• Loss of appetite,
• Tingling or numbness in hands or feet, taste disturbances,
• Tremors,
• Changes in heart rhythm, flushing,
• Indigestion (dyspepsia), inflammation of the tongue,
• Itchy skin 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 blood sugar levels, serum creatinine, myoglobin, or lactate dehydrogenase (LDH), prolonged blood clotting time, or electrolyte imbalances 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, pharmacist, or nurse, 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 Medicines: https://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Daptomycin Dr. Reddy's

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

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

However, from a microbiological standpoint, the product should be used immediately. The product contains no preservatives or bacteriostatic agents. If immediate use is not possible, the storage time is the user's responsibility and normally should not exceed 24 hours at 2°C - 8°C, unless reconstitution/dilution has taken place under controlled and validated aseptic conditions.

Do not use this medicine after the expiry date stated on the carton after EXP and on the label after EXP. The expiry date refers to the last day of the month indicated.

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

Medicines must 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 other information

Composition of Daptomycin Dr. Reddy's

The active substance is daptomycin

The active substance is daptomycin. One vial of powder contains 500 mg of daptomycin.

One ml provides 50 mg of daptomycin after reconstitution with 10 ml of sodium chloride solution (0.9%).

The other component is sodium hydroxide.

Appearance of the product and contents of the container

Daptomycin Dr. Reddy's 500 mg powder for solution for injection for infusion EFG is supplied 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.

Daptomycin Dr. Reddy's is available in packs containing 1 vial.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation 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

Tel. No.: +44 1482860228

or

Betapharm Arzneimittel GmbH

Kobelweg 95,

86156 Augsburg, Germany

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

Denmark: Daptomycin beta 500 mg Pulver zur Herstellung einer Injektions-/Infusionslösung

Spain: Daptomycin Dr. Reddy's 500 mg, powder for solution for injection and for infusion EFG

United Kingdom: Daptomycin Dr. Reddy's 500 mg Powder For Solution For Injection/Infusion

Italy: Daptomycin Dr. Reddy's 500 mg, Powder for injectable solution or for infusion

France: Daptomycin Dr. Reddy's 500 mg, powder for injectable solution or for perfusion

Date of the most recent review 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

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

Daptomycin Dr. Reddy's administered as a 30- or 60-minute intravenous infusion

Reconstituting the lyophilized product with 10 mL of an injectable solution containing 9 mg/mL sodium chloride (0.9%) yields a concentration of 50 mg/mL of Daptomycin Dr. Reddy's for infusion.

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

To prepare Daptomycin Dr. Reddy's for intravenous infusion, follow the instructions below:

Throughout the reconstitution and dilution process, an aseptic technique must be used.

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 contact any other surface. Draw 10 mL of an injectable solution (for Daptomycin Dr. Reddy's 500 mg powder for solution for infusion EFG) containing 9 mg/mL sodium chloride (0.9%) into a syringe using a sterile transfer needle of 21 gauge or smaller, or a needle-free device, and slowly inject through the center of the rubber stopper into the vial, directing the needle toward the vial wall.
2. Gently rotate the vial to ensure complete wetting of the product, then allow it to stand for 10 minutes.
3. Finally, gently rotate or shake 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 verify the absence of suspended particles. The color of the reconstituted Daptomycin Dr. Reddy's solution may range from pale yellow to light brown.
5. The reconstituted solution must 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 sterile needle of 21 gauge or smaller and a new syringe, by inverting the vial so that the solution flows toward 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 solution in the vial as it is withdrawn into the syringe. Before removing the needle from the vial, pull the plunger back to the end of the syringe barrel to withdraw all required solution from the inverted vial.
2. Expel air, large bubbles, and any excess solution to achieve 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 via intravenous infusion over 30 or 60 minutes.

Daptomycin Dr. Reddy's 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: 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 as 12 hours at 25°C or 24 hours when refrigerated at 2°C – 8°C.

Daptomycin Dr. Reddy's administered as a 2-minute intravenous injection (for adult patients only)

Water must not be used for reconstitution of Daptomycin Dr. Reddy's for intravenous injection. Daptomycin Dr. Reddy's must be reconstituted only with 9 mg/mL sodium chloride (0.9%).

Reconstituting the lyophilized product with 10 mL of an injectable solution containing 9 mg/mL sodium chloride (0.9%) for injection yields a concentration of 50 mg/mL of Daptomycin Dr. Reddy's for injectable solution.

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

To prepare Daptomycin Dr. Reddy's for intravenous injection, follow the instructions below:

Throughout the reconstitution process, an aseptic technique must be used.

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 contact any other surface. Draw 10 mL of an injectable solution containing 9 mg/mL sodium chloride (0.9%) into a syringe using a sterile transfer needle of 21 gauge or smaller, or a needle-free device, and slowly inject through the center of the rubber stopper into the vial, directing the needle toward the vial wall.
2. Gently rotate the vial to ensure complete wetting of the product, then allow it to stand for 10 minutes.
3. Finally, gently rotate or shake 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 verify the absence of suspended particles. The color of the reconstituted Daptomycin Dr. Reddy's solution may range 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 flows toward 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 solution in the vial as it is withdrawn into the syringe. Before removing the needle from the vial, pull the plunger back to the end of the syringe barrel to withdraw all 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 achieve the required dose.
9. The reconstituted solution should be administered slowly via 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 should normally 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 Dr. Reddy's vials are for single use only. Any unused portion remaining in the vial must be discarded.