Daptomycin Tarbis 500 mg powder for solution for injection and for infusion EFG

Patient Information Leaflet

Introduction

Package Leaflet: Information for the Patient

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

Read the entire leaflet carefully before you start using this medicine, as 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 others, 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.

Leaflet Contents

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

1. What Daptomicina Tarbis is and what it is used for

The active substance is daptomycin. Daptomycin is an antibacterial agent capable of inhibiting the growth of certain bacteria. This medicine is used in adults and in children and adolescents (aged between 1 and 17 years) to treat skin and soft tissue infections. It is also used to treat bloodstream infections when associated with a skin infection.

This medicine 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 a heart infection.

Depending on the type of infection(s) you have, your doctor may also prescribe other antibacterial medicines while you are receiving treatment with this medicine.

2. What you need to know before starting to receive Daptomycin Tarbis

Do not receive Daptomicina Tarbis

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

Talk to your doctor or nurse before starting treatment with Daptomicina Tarbis:

• If you have or have previously had kidney problems. Your doctor may need to adjust the dose of this medicine (see section 3 of this leaflet).
• Occasionally, patients receiving this medicine may develop increased sensitivity, pain, or muscle 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 you whether or not it is advisable to continue using this medicine. Symptoms usually resolve within a few days after stopping treatment with this medicine.

• If you have ever experienced, after taking daptomycin, a severe skin rash or skin peeling, blisters, and/or mouth sores, or serious kidney problems.
• If you have significant overweight, there is a possibility that your blood levels of this medicine may be higher than in individuals of average weight, and therefore you may require closer monitoring for adverse effects.

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

Inform 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. Symptoms may include wheezing, difficulty breathing, swelling of the face, neck, and throat, skin rash and hives, or fever.

• Serious skin diseases have been reported with the use of daptomycin. Symptoms associated with these skin conditions may include:

• onset or worsening of fever,

• raised red spots or fluid-filled lesions on the skin, which may start in the armpits or on the chest or groin areas and may spread over a large area of the body,

• blisters or sores in the mouth or genital area.

  • Serious kidney problems have been reported with the use of this medicine. Symptoms may include fever and rash.
  • Any type of tingling or numbness in the hands or feet, loss of sensation, or unusual 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 prolonged.
  • Onset or worsening of fever, cough, or difficulty breathing. These may be signs of a rare but serious lung function deterioration known as eosinophilic pneumonia. Your doctor will check your lung condition 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 must not be given 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.

Other medicines and Daptomicina Tarbis

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 known as non-steroidal anti-inflammatory drugs (NSAIDs) or COX-2 inhibitors (e.g. celecoxib). These may interfere with the kidney 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 given 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 using this medicine.

You must 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 use machines.

Daptomicina Tarbis contains sodium

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

3. How Daptomicina Tarbis is administered

Daptomycin Tarbis will normally be administered 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 (intravenously), either as an infusion lasting approximately 30 minutes or as an injection lasting approximately 2 minutes. The same dose is recommended for patients over 65 years of age, provided their kidneys function properly.

If your kidneys do not function properly, you may receive this medicine less frequently, e.g., once every other day. If you are undergoing dialysis and your next dose of this medicine is scheduled on a dialysis day, you will usually receive the dose 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) will depend on the patient's age and the type of infection being treated. This dose is administered directly into the bloodstream (intravenously) as an infusion lasting approximately 30 to 60 minutes.

A full course of treatment for skin infections usually lasts between 1 and 2 weeks. Your doctor will decide the duration of 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, daptomycin may cause adverse effects, although not everyone gets them. The most serious adverse effects are listed below:

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

• Hypersensitivity reactions (severe allergic reactions including anaphylaxis and angioedema) have been reported during administration of daptomycin. These severe 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 or shortness of breath,

• Fever,

• Chills or shivering,

• Flushing,

• Dizziness,

• Fainting,

• Metallic taste.

  • Consult your doctor immediately if you experience muscle pain, tenderness, or weakness of unknown origin. Muscle problems may be serious and include muscle breakdown (rhabdomyolysis), which may lead to kidney damage.

Other adverse effects reported with the use of daptomycin include:

• A rare but potentially serious lung disorder called eosinophilic pneumonia, mostly 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 lesions on the skin, which may start in the armpits or on the chest or groin and may spread over a large area 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 confirm the 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,
• Decreased 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,
• Abdominal swelling or bloating,
• Skin rash or itching,
• Pain, itching or redness at the infusion site,
• Pain in arms or legs,
• Increased levels of liver enzymes or creatine phosphokinase (CPK) in blood tests.

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

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, disturbances in taste sensation,
• 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),
• Increased blood sugar levels, 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),
• Prolonged 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), 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. Conservation of Daptomycin Tarbis

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

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

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

6. Contents of the pack and other information

Composition of Daptomicina Tarbis

The active substance is daptomycin.

One vial of powder contains 500 mg of daptomycin.

The other component (excipient) is sodium hydroxide.

Appearance of the product and contents of the container

Daptomicina Tarbis powder for injectable solution and for infusion EFG is presented in a glass vial as a pale yellow to light brown powder. It is mixed with a solvent to form a solution prior to administration.

Daptomicina Tarbis is available in pack sizes containing 1 vial or 5 vials.

Only certain pack sizes may be marketed.

Marketing Authorization Holder

Tarbis Farma S.L.

Gran Vía Carlos III, 94

08028 Barcelona

Spain

Manufacturer

Amarox Pharma B.V.

Rouboslaan 32

Voorschoten, 2252TR

Netherlands

This medicinal product is authorised in the European Economic Area member states under the following names:

Netherlands: Daptomycine Amarox 500 mg poeder voor oplossing voor injectie of infusie

Spain: Daptomicina Tarbis 500 mg powder for injectable solution and for infusion EFG

Germany: Daptomycin Amarox 500 mg Pulver zur Herstellung einer Injektions-/Infusionslösung

Date of the most recent review of this leaflet: May 2023

Detailed information on this medicinal product is available on the website of the Spanish Agency of 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 Technical Data Sheet or Summary of Product Characteristics before prescribing.

Instructions for use and handling

In adults, daptomycin may be administered intravenously either as a 30-minute infusion or as a 2-minute injection. Unlike adults, daptomycin must not be administered as a 2-minute injection in paediatric patients. Paediatric patients aged 7 to 17 years should receive daptomycin via a 30-minute infusion. Paediatric 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.

Daptomicina Tarbis administered as a 30- or 60-minute intravenous infusion

Reconstituting the lyophilised product with 10 ml of an injectable solution containing 9 mg/ml of sodium chloride (0.9%), yields a concentration of 50 mg/ml of Daptomicina Tarbis 500 mg powder for infusion.

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

To prepare Daptomicina Tarbis for intravenous infusion, follow the instructions below. An aseptic technique must be used throughout the reconstitution and dilution process.

For reconstitution:

1. Remove the polipropylene "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 of sodium chloride (0.9%) into a syringe using a sterile transfer needle of gauge 21 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 swirl 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 colour of the reconstituted Daptomicina Tarbis 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 new sterile needle of gauge 21 or smaller, by inverting the vial so that the solution flows toward the stopper. Using a 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 liquid while drawing the solution into the syringe. Before removing the needle from the vial, pull the plunger back to the end of the syringe barrel to withdraw the required solution from the inverted vial.
2. Expel air, large bubbles, and any excess solution to obtain the required dose.
3. Transfer the required reconstituted dose to 50 ml of 9 mg/ml sodium chloride (0.9%).
4. The reconstituted and diluted solution must be administered by intravenous infusion over 30 or 60 minutes.

Daptomicina Tarbis 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 Daptomicina Tarbis: aztreonam, ceftazidime, ceftriaxone, gentamicin, fluconazole, levofloxacin, dopamine, heparin, and lidocaine.

The combined 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 if refrigerated at 2°C–8°C.

Daptomicina Tarbis administered as a 2-minute intravenous injection (for adult patients only)

Water must not be used for reconstitution of Daptomicina Tarbis for intravenous injection. Daptomicina Tarbis must be reconstituted exclusively with 9 mg/ml sodium chloride (0.9%).

Reconstituting the lyophilised product with 10 ml of an injectable solution containing 9 mg/ml of sodium chloride (0.9%) yields a concentration of 50 mg/ml of Daptomicina Tarbis for injection.

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

To prepare Daptomicina Tarbis for intravenous injection, follow the instructions below. An aseptic technique must be used throughout the reconstitution process.

1. Remove the polipropylene "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 of sodium chloride (0.9%) into a syringe using a sterile transfer needle of gauge 21 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 swirl 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 colour of the reconstituted Daptomicina Tarbis 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 gauge 21 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 liquid while drawing the solution into the syringe. Before removing the needle from the vial, pull the plunger back to the end of the syringe barrel 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 must be administered slowly by intravenous injection over 2 minutes.

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.

Daptomicina Tarbis vials are for single use only. Any unused portion remaining in the vial must be discarded.