Daptomycin Dr. Reddy's 350 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 350 mg powder for solution for injection and infusion EFG

daptomicin

Read all of this 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, consult your doctor or nurse.
• This medicine has been prescribed for you only, and you should not give it to others, even if they have the same symptoms as you, since 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.

Package leaflet

1. What Daptomycin Dr. Reddy's is and what it is used for
2. What you need to know before receiving Daptomycin Dr. Reddy's
3. How Daptomycin Dr. Reddy's is administered
4. Possible side effects
5. How to store Daptomycin Dr. Reddy's

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 that can stop 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 your doctor's instructions regarding dose, dosing interval, and duration of treatment.

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

Daptomicina Dr. Reddys is used in adults and in children and adolescents (aged 1 to 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 bacteria called Staphylococcus aureus. It is also used to treat bloodstream infections caused by the same type of bacteria when associated with heart infection.

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

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

Contraindications

Do not use Daptomycin Dr. Reddys:

• If you are allergic to daptomycin or any of the other ingredients of this medicine (listed in section 6).
• If you have had severe allergic reactions to daptomycin.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before receiving Daptomycin Dr. Reddys.

Daptomycin is not suitable for treating pneumonia. This is because daptomycin becomes inactive in the lungs.

Tell your doctor if you have or have had:

• Muscle disorders, as daptomycin may cause muscle problems (see section 4). Your doctor may perform blood tests to check for muscle damage (measurement of creatine phosphokinase [CPK] levels).
• Liver problems.
• Kidney problems. If you have kidney problems, your doctor will adjust the dose.
• If you are undergoing dialysis, daptomycin can be removed from your body during the procedure. Your doctor may prescribe the dose after dialysis.

Children and adolescents

Daptomycin Dr. Reddys is not recommended for use in children and adolescents under 18 years of age.

Elderly

Your doctor may adjust the dose depending on your kidney function.

Other medicines and Daptomycin Dr. Reddys

Tell your doctor, pharmacist, or nurse if you are taking, have recently taken, or might take any other medicines.

In particular, tell your doctor if you are taking cyclosporine, as it may increase the risk of muscle problems.

Pregnancy and breastfeeding

If you are pregnant, think you may be pregnant, or are planning to become pregnant, ask your doctor if you can receive this medicine.

It is not known whether daptomycin passes into breast milk. Your doctor will decide whether you can receive the medicine or breastfeed.

Driving and using machines

Daptomycin Dr. Reddys is unlikely to affect your ability to drive or use machines. However, some patients have reported dizziness. If you feel dizzy, do not drive or operate machinery.

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 daptomycin (see section 3 of this leaflet).
• Occasionally, patients receiving daptomycin 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 treatment with daptomycin. Symptoms usually resolve within a few days after stopping daptomycin treatment.
• If you have ever developed a severe skin rash, peeling skin, blisters and/or mouth sores, or severe kidney problems after taking daptomycin.
• If you have significant overweight, there is a possibility that your blood levels of daptomycin may be higher than in individuals of average weight, and therefore you may require closer monitoring for adverse effects.

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

Immediately inform your doctor or nurse if you develop any of the following symptoms:

• Severe and acute allergic reactions have been observed in patients treated with nearly all antibacterial agents, including daptomycin. Symptoms may include shortness of breath, difficulty breathing, swelling of the face, neck, and throat, skin rash, and hives, as well as fever.
• Serious skin disorders have been reported with the use of daptomycin. 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.
• Severe kidney problems have been reported with the use of daptomycin. Symptoms may include fever and rash.
• Any unusual tingling or numbness in the hands or feet, loss of sensation, or movement difficulties. 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 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 daptomycin.

Daptomycin 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 daptomycin. Inform your doctor that you are being treated with daptomycin.

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

Children and adolescents

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

Use in elderly patients

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 that you 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 daptomycin. Your doctor may decide not to administer daptomycin 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 daptomycin.
• 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 use of machines

Daptomycin has no known effects on the ability to drive or operate machinery.

Daptomycin 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 Daptomicin Dr. Reddy's is administered

Daptomicin Dr. Reddy's 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 infection or bloodstream infection associated with skin or heart infection. 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 working 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 scheduled 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 to be 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 most serious adverse effects are described below:

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

During administration of daptomycin, there have been some cases 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 side 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 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.
• A serious kidney problem. Symptoms may include fever and rash.

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

The following are the most frequently reported adverse effects:

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

• Fungal infections, such as oral thrush (mouth ulcers),
• Urinary tract infection,
• Decrease in the number of red blood cells (anaemia),
• Dizziness, anxiety, difficulty sleeping,
• Headache,
• Fever, weakness (asthenia),
• High or low blood pressure,
• Constipation, abdominal pain,
• Diarrhoea, discomfort (nausea or vomiting),
• Flatulence,
• Swelling or bloating of the abdomen,
• 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 develop 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 rash,
• Muscle pain, cramps, or weakness, muscle inflammation (myositis), joint pain,
• Kidney problems,
• Inflammation and irritation of the vagina,
• Generalised pain or weakness, tiredness (fatigue),
• Elevated levels of blood sugar, serum creatinine, myoglobin, or lactate dehydrogenase (LDH), prolonged blood clotting time, or electrolyte imbalance in blood tests,
• Itchy eyes.

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

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

Frequency not known (cannot be estimated from available data)

Antibiotic-associated colitis, including pseudomembranous colitis (severe or persistent diarrhoea containing blood and/or mucus, associated with abdominal pain or fever), bruising more easily, 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 may 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 not used immediately, storage time is the responsibility of the user 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 which is stated on the carton after EXP and on the label after EXP. The expiry date refers to the last day of the stated month.

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 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 contents of the container

Daptomycin Dr. Reddys 350 mg powder for injectable solution for infusion EFG is presented in a glass vial as a pale yellow to light brown powder or cake. It is reconstituted with a solvent to form a solution prior to administration.

Daptomycin Dr. Reddys is available 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

Tel. 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 Pulver zur Herstellung einer Injektions-/Infusionslösung

Spain: Daptomycin Dr. Reddys 350 mg, powder for injectable solution 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, Polvere per soluzione iniettabile o per infusione

France: Daptomycine Dr. Reddy's 350 mg, poudre pour solution injectable ou pour perfusion

Date of the last 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

350 mg presentation:

In adults, daptomycin may be administered intravenously as a 30-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 intravenous infusion over 30 or 60 minutes

Reconstituting the lyophilized product with 7 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:

An aseptic technique must be used throughout the reconstitution and dilution process.

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 come into contact with any other surface. Using a sterile transfer needle of 21 gauge or smaller, or a needle-free device, draw 7 mL of an injectable solution containing 9 mg/mL sodium chloride (0.9%) (for Daptomycin Dr. Reddy’s 350 mg powder for solution for infusion) into a syringe, and slowly inject it 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. 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 check for 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 reconstituted liquid (50 mg daptomycin/mL) from the vial using a new sterile needle of 21 gauge or smaller, 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 needle tip at the lowest point of the solution in the vial as it is drawn 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 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 must be administered by intravenous infusion over 30 or 60 minutes.

Daptomycin Dr. Reddy’s is not physically or 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 the 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 for 12 hours at 25°C or 24 hours if refrigerated at 2°C – 8°C.

Daptomycin Dr. Reddy’s administered as intravenous injection over 2 minutes (for adult patients only)

Water for injection 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 7 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:

An aseptic technique must be used throughout the reconstitution process.

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 come into contact with any other surface. Using a sterile transfer needle of 21 gauge or smaller, or a needle-free device, draw 7 mL of an injectable solution containing 9 mg/mL sodium chloride (0.9%) into a syringe, and slowly inject it 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. 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 check for 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 needle tip at the lowest point of the solution in the vial as it is drawn 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 obtain the required dose.
9. The reconstituted solution must be administered slowly by 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 user’s responsibility and normally should 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.