Patient Information Leaflet

Daptomicin Zentiva 500 mg powder for injection and infusion EFG

daptomicin

Read this leaflet carefully before you start taking 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, consult your doctor or nurse.
• This medicine has been prescribed for you only, and you must not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor or nurse, even if they are not listed in this leaflet.See section 4.

6.Contents of the pack and additional information

The active ingredient of this medication is daptomycin. Daptomycin is an antibacterial capable of stopping the growth of certain bacteria.

Do not store or reuse this medication. If you have leftover antibiotics after treatment, return them to the pharmacy for proper disposal. Do not dispose of medications through the drain or in the trash.

Daptomycin is used in adults, children, and adolescents (ages 1 to 17 years) to treat skin and soft tissue infections. It is also used to treat blood infections when associated with a skin infection..

Daptomycin is also used in adults to treat infections in the tissues that line the interior of the heart (including cardiac 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 a heart infection.

Depending on the type of infection(s) you have, your doctor may also prescribe other antibacterials while you receive treatment with daptomycin.

No use Daptomicina Zentiva

If you are allergic to daptomycin or sodium hydroxide or any of the other components of this medication (listed in section 6).

Inform your doctor or nurse if this is the case. If you think you may be allergic, consult your doctor or nurse.

Warnings and precautions

Consult your doctor or nurse before starting to take daptomycin.

• If you have or have had kidney problems. Your doctor may need to change the dose of daptomycin (see section 3 of this leaflet).
• Occasionally, patients taking daptomycin may develop increased sensitivity, muscle pain or weakness (see section 4 of this leaflet for more information). Inform your doctor if this happens. Your doctor will ensure that you have a blood test and advise whether it is recommended to continue using this medication. Symptoms usually disappear within a few days after stopping treatment with daptomycin.
• If you have ever had, after taking daptomycin, a severe skin rash or skin peeling, blisters and/or mouth sores, or severe kidney problems.
• If you have significant overweight, there is a possibility that your blood levels of daptomycin may be higher than those found in people of average weight, and that you may therefore need closer monitoring for adverse effects.

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

Inform your doctor immediately if you develop any of the following symptoms:

• Severe allergic reactions have been observed in patients treated with almost all antibacterial agents, including daptomycin. Symptoms may include rapid breathing, difficulty breathing, facial, neck and throat inflammation, skin rash and urticaria, or fever.
• Severe skin diseases have been reported with the use of daptomycin. Symptoms that occur with these skin diseases may include:
• • Appearance of fever or worsening of the same,
  • Red skin patches elevated or filled with fluid, which may start in the armpits or in areas of the chest or groin and may spread over a large area of the body,
  • Blisters or sores in the mouth or genitals.
• Severe kidney problems have been reported with the use of daptomycin. Symptoms may include fever and rash.
• Any type of tingling or numbness in the hands or feet, loss of sensation or unusual difficulty moving. If this occurs, inform your doctor, who will decide whether to continue treatment.
• Diarrea, especially if you notice the presence of blood or mucus in your stool or if diarrhea becomes severe or lasts long.
• Appearance of fever or worsening of the same, cough or difficulty breathing. These may be signs of a rare but serious lung function deterioration called eosinophilic pneumonia. Your doctor will check your lung function and decide whether to continue treatment with this medication.

Daptomycin may interfere with laboratory tests that measure your blood's clotting ability. Results may appear to suggest poor clotting, despite the fact that 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 on this medication.

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

Children and adolescents

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

Use in elderly patients

Elderly patients over 65 years of age may receive the same dose as other adults, provided their kidneys function correctly.

Other medications and daptomycin

Inform your doctor or nurse if you are using, have used recently, or may need to use any other medication.

It is particularly important to mention the following:

• Medications called statins or fibrates (to lower cholesterol) or cyclosporine (a medication used in transplants to prevent organ rejection or for other conditions, e.g. rheumatoid arthritis or atopic dermatitis). There may be an increased risk of muscle adverse effects if you take any of these medications (and other that may affect muscles) during treatment with daptomycin. Your doctor may decide not to administer daptomycin or temporarily interrupt treatment with the other medication.
• Pain-relieving medications called nonsteroidal anti-inflammatory drugs (NSAIDs) or COX-2 inhibitors (e.g. celecoxib). These may interfere with the elimination of this medication by the kidneys.
• Oral anticoagulants (e.g. warfarin), which are medications 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, or think you may be pregnant, consult your doctor or pharmacist before receiving this medication.

Do not breastfeed while receiving daptomycin, as it may pass into breast milk and affect the baby.

Driving and operating machinery

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

This medication contains sodium

This medication contains less than 23 mgof sodium (1 mmol) per dose; this is essentially “sodium-free”.

Daptomicina will be administered by your doctor or nurse.

Adults (18 years of age and older)

The dose will depend on your weight and the type of infection being treated. The usual dose for adults is 4 mg per kilogram of body weight once a day for skin infections or 6 mg per kilogram of body weight once a day for heart infections or blood infections associated with skin or heart infections. In adult patients, this dose is administered directly into your bloodstream (into a vein), either as an infusion lasting approximately 30 minutes or as an injection lasting approximately 2 minutes. The same dose is recommended for people over 65 years old, provided their kidneys function properly.

If your kidneys do not function well, you may receive daptomicina more frequently, for example, once every other day. If you are undergoing dialysis and your next daptomicina dose is due on a day of dialysis, you will usually receive the medication after the dialysis session.

Children and adolescents (1 to 17 years of age)

The recommended doses in children and adolescents (1 to 17 years) will depend on the patient's age and the type of infection being treated. This dose is administered directly into the bloodstream (into a vein), as an infusion lasting approximately 30-60 minutes.

A complete treatment for skin infections usually lasts between 1 and 2 weeks. Your doctor will decide the duration of your treatment for blood or heart infections and for skin infections.

Instructions for use and handling are provided in detail at the end of the prospectus.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

The following are the most serious side effects:

Severe side effects of unknown frequency(cannot be estimated from available data)

• During daptomycin administration, some cases of hypersensitivity reactions (severe allergic reactions including anaphylaxis and angioedema) have been reported. 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,
• eruption or hives,
• inflammation around the throat,
• rapid or weak pulse,
• labored breathing,
• fever,
• chills or tremors,
• headache,
• dizziness,
• syncope,
• metallic taste.

• Consult your doctor immediately if you experience pain, increased sensitivity, or muscle weakness of unknown origin. Muscle problems can be severe, including muscle degeneration (rhabdomyolysis), which can cause kidney damage.

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

• A rare but potentially severe lung condition called eosinophilic pneumonia, mostly after more than 2 weeks of treatment. Symptoms may include difficulty breathing, appearance of cough or worsening of it, or appearance of fever or worsening of it.
• Severe skin diseases. Symptoms may include:
• • appearance of fever or worsening of it,
  • red patches on the skin that are raised or filled with fluid, which may start in the armpits or in areas of the chest or groin and may spread to a large area of the body,
  • blistering or ulcers in the mouth or genitals.
• A severe 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 establish a diagnosis.

The following are the most frequently reported side effects:

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

• Fungal infections, such as mouth ulcers.
• Urinary tract infection.
• Decreased red blood cell count (anemia).
• Dizziness, anxiety, difficulty falling asleep.
• 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 or weakness in arms or legs.
• Elevated liver enzymes or creatine phosphokinase (CPK) levels in blood tests.

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

Rare 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 count of certain types of white blood cells).
• Loss of appetite.
• Tickling or numbness in the hands or feet, alterations in taste,
• Tremors.
• Changes in heart rhythm, palpitations.
• Indigestion (dyspepsia), inflammation of the tongue.
• Skin rash with itching.
• Muscle pain, cramps, or weakness, muscle inflammation (myositis), joint pain.
• Kidney problems.
• Vaginal inflammation and irritation.
• Elevated blood sugar, creatinine, myoglobin, or lactate dehydrogenase (LDH) levels, prolonged blood clotting time, or electrolyte imbalance in blood tests.
• Eye itching.

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

-Yellowing of the skin and eyes (jaundice).

-Prolonged prothrombin time.

Unknown frequency(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), easy bruising, bleeding gums, or nasal bleeding.

Reporting of side effects

If you experience any type of side effect, consult your doctor, pharmacist, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through the Spanish System for the Pharmacovigilance of Medicines for Human Use:https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

• Keep this medication out of the sight and reach of children.
• Do not use this medication after the expiration date that appears on the box and on the label after CAD. The expiration date is the last day of the month indicated.
• Store in refrigerator (between 2°C and 8°C).

After reconstitution:

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 at 2°C – 8°C.

After dilution:

The physical and chemical stability of the diluted solution in infusion bags has been established for 12 hours at 25°C or 24 hours at 2°C – 8°C.

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

For intravenous injection over 2 minutes, 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 at 2°C – 8°C).

From a microbiological point of view, the product should be used immediately. This medication does not contain preservatives or bacteriostatic agents. If not used immediately, the storage time and conditions during use are the responsibility of the user and, normally, should not be greater than 24 hours at 2°C - 8°C, unless reconstitution/dilution has taken place in controlled and validated aseptic conditions.

Do not useDaptomycin Zentivaif you observe any change in the appearance of the product (signs of moisture or presence of particles in the powder of a different color, or presence of particles, turbidity or precipitate once the solution has been reconstituted).

Medicines should not be disposed of through the drains or in the trash. Ask your pharmacisthow to disposeofthepackaging and of themedicines that you no longerneed. In this way, you will help protect the environment.

Composition of Daptomycin Zentiva

• The active ingredient is daptomycin. A vial of powder contains 500 mg of daptomycin. One ml provides 50 mg of daptomycin after reconstitution with 10 ml of a solution containing 9 mg/ml of sodium chloride (0.9%).
• The other component is sodium hydroxide.

Appearance of the product and contents of the package

Daptomycin Zentiva powder for injectable solution and for infusion is presented in a glass vial as a powder or a pale yellow to light brown cake. It is mixed with a solvent to form a solution before administration.

It is available in packages containing 1 vial or 5 vials.

Only some package sizes may be marketed.

Marketing Authorization Holder

Zentiva k.s.,

U kabelovny 130,

Dolní Mecholupy,

102 37 Prague 10

Czech Republic

Responsible for manufacturing

Medichem, S.A.

Narcís Monturiol, 41A08970 Sant Joan Despí (Barcelona)

Spain

or

Hikma Italia SpA

10 Viale Certosa

27100 Pavia

Italy

Further information on this medicinal product can be obtained by contacting the local representative of the marketing authorization holder:

Zentiva Spain S.L.U.

Avenida de Europa, 19, Edificio 3, Planta 1.

28224 Pozuelo de Alarcón, Madrid

Spain

This medicinal product is authorized in the Member States of the European Economic Area with the following names:

France:

Daptomycine Medac 500 mg powder for injectable solution/for infusion

Spain:

Daptomicina Zentiva 500 mg powder for injectable solution and for infusion EFG

Last review date of this leaflet: February 2022

Further detailed information on this medicinal product is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.es/

This information is intended solely for healthcare professionals:

Important: Please consult the Technical Data Sheet or Summary of Product Characteristics before prescribing.

Instructions for use and handling

500 mg presentation:

In adults, daptomycin can be administered intravenously as a 30-minute infusion or as a 2-minute injection. Unlike adults, daptomycin should not be administered to pediatric patients as a 2-minute injection. Pediatric patients aged 7 to 17 years should receive daptomycin as a 30-minute infusion. Pediatric patients under 7 years of age receiving doses of 9-12 mg/kg should be administered daptomycin as a 60-minute infusion (see sections 4.2 and 5.2). The preparation of the infusion solution requires an additional dilution phase, as described below.

Daptomycin administered as an intravenous infusion over 30 or 60 minutes

Reconstituting the lyophilized product with 10 ml of a 9 mg/ml sodium chloride (0.9%) solution can provide a daptomycin concentration of 50 mg/ml for infusion.

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

To prepare daptomycin for intravenous infusion, follow the instructions below:

To reconstitute or dilute daptomycin lyophilisate, aseptic technique must be used throughout the process.

To reconstitute:

1. The polipropylene "flip-off" closure cap must be removed to expose the central part of the rubber stopper. Clean the top of the rubber stopper with an alcohol-soaked cotton swab or other antiseptic solution and allow it to dry. After cleaning, do not touch the rubber stopper, nor allow it to touch any other surface. Extract 10 ml of a 9 mg/ml sodium chloride (0.9%) solution using a sterile transfer needle of calibre 21 or smaller, or a device without a needle, and inject it slowly through the centre of the rubber stopper into the vial, pointing the needle towards the vial wall.
2. The vial must be gently rotated to ensure the product is fully moistened, and then left to stand for 10 minutes.
3. Finally, the vial must be gently rotated/agitated for a few minutes to obtain a transparent reconstituted solution. Vigorous agitation should be avoided to prevent foam formation.
4. The reconstituted solution must be carefully inspected before use to ensure the substance is dissolved and to verify the absence of particles in suspension. The colour of the reconstituted solution of Daptomycin Zentiva may vary from pale yellow to light brown.
5. The reconstituted solution must be diluted further with 9 mg/ml sodium chloride (0.9%) (typical volume of 50 ml).

To dilute:

1. Remove the reconstituted solution (50 mg daptomycin/ml) from the vial using a new sterile needle of calibre 21 or smaller, inverting the vial in the process to allow the solution to flow towards the stopper. Using a syringe, insert the needle into the inverted vial. Keeping the vial inverted, place the tip of the needle at the lowest point of the liquid while extracting the solution into the syringe. Before removing the needle from the vial, push the plunger back to the end of the syringe barrel to remove all the solution from the inverted vial.
2. Expel air, large bubbles, and any excess solution to obtain the required dose.
3. Transfer the reconstituted dose required to 50 ml of 9 mg/ml sodium chloride (0.9%).
4. The reconstituted and diluted solution must be infused intravenously over 30 or 60 minutes.

Daptomycin 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.

Daptomycin Zentiva administered as an intravenous injection over 2 minutes (only for adult patients)

Water should not be used for reconstituting Daptomycin Zentiva for intravenous injection. Daptomycin Zentiva must be reconstituted only with 9 mg/ml sodium chloride (0.9%).

Reconstituting the lyophilized product with 10 ml of a 9 mg/ml sodium chloride (0.9%) solution can provide a daptomycin concentration of 50 mg/ml for injection.

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

To prepare Daptomycin Zentiva for intravenous injection, follow the instructions below:

To reconstitute Daptomycin Zentiva lyophilisate, aseptic technique must be used throughout the process.

1. The polipropylene "flip-off" closure cap must be removed to expose the central part of the rubber stopper. Clean the top of the rubber stopper with an alcohol-soaked cotton swab or other antiseptic solution and allow it to dry. After cleaning, do not touch the rubber stopper, nor allow it to touch any other surface. Extract 10 ml of a 9 mg/ml sodium chloride (0.9%) solution using a sterile transfer needle of calibre 21 or smaller, or a device without a needle, and inject it slowly through the centre of the rubber stopper into the vial, pointing the needle towards the vial wall.
2. The vial must be gently rotated to ensure the product is fully moistened, and then left to stand for 10 minutes.
3. Finally, the vial must be gently rotated/agitated for a few minutes to obtain a transparent reconstituted solution. Vigorous agitation should be avoided to prevent foam formation.
4. The reconstituted solution must be carefully inspected before use to ensure the substance is dissolved and to verify the absence of particles in suspension. The colour of the reconstituted solution of this medicinal product may vary from pale yellow to light brown.
5. Remove the reconstituted solution (50 mg daptomycin/ml) from the vial using a sterile needle of calibre 21 or smaller.
6. Invert the vial to allow the solution to flow towards the stopper. Using a new syringe, insert the needle into the inverted vial. Keeping the vial inverted, place the tip of the needle at the lowest point of the liquid while extracting the solution into the syringe. Before removing the needle from the vial, push the plunger back to the end of the syringe barrel to remove all the solution from the inverted vial.
7. Replace the needle with a new one for the intravenous injection.
8. Expel air, large bubbles, and any excess solution to obtain the required dose.
9. The reconstituted solution must be injected slowly 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, 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 in controlled and validated aseptic conditions.

This medicinal product should not be mixed with other medicinal products that are not mentioned above.

The vials of Daptomycin Zentiva are exclusively for single use. Any remaining vial that has not been used must be discarded.