DAPTOMYCIN NORMON 500 mg POWDER FOR INJECTABLE SOLUTION AND FOR INFUSION

Introduction

Package Leaflet: Information for the User

Daptomicina Normon 500mgpowder for solution for injection and infusion EFG

daptomicina

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

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

Contents of the pack

1. What Daptomicina Normon is and what it is used for
2. What you need to know before you are given Daptomicina Normon
3. How Daptomicina Normon is given
4. Possible side effects
5. Storing Daptomicina Normon
6. Contents of the pack and other information

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

The active substance in Daptomicina Normon powder for solution for injection and infusion is daptomicin. Daptomicin is an antibacterial agent capable of stopping the growth of certain bacteria. Daptomicin is used in adults and in children and adolescents (aged 1 to 17 years) to treat infections of the skin and soft tissues. It is also used to treat infections in the blood when associated with a skin infection.

Daptomicin is also used in adults to treat infections of the tissues that line the inside of the heart (including heart valves), caused by a type of bacteria called Staphylococcus aureus.It is also used to treat blood infections caused by the same type of bacteria when associated with a heart infection.

Depending on the type of infection(s) you have, your doctor may also prescribe other antibacterial agents while you are being treated with daptomicin.

2. What you need to know before you are given Daptomicina Normon

You must not be given Daptomicina Normon

If you are allergic to daptomicin or sodium hydroxide or any of the other ingredients of this medicine (listed in section 6).

If this is the case, tell 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 you start receiving daptomicin:

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

If any of the above applies to you, tell your doctor or nurse before you receive daptomicin.

Tell 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 daptomicin. Symptoms may include shortness of breath, difficulty breathing, swelling of the face, neck and throat, skin rash and hives, or fever.
• Severe skin diseases have been reported with the use of daptomicin. The symptoms that occur with these skin diseases may include:
• • appearance of fever or worsening of it,
  • red spots on the skin, raised or filled with fluid, which can start in the armpits or in areas of the chest or groin and can 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 daptomicin. The symptoms may include fever and rash.
• Any type of tingling or numbness in the hands or feet, loss of sensitivity or unusual movement difficulties. If this happens, tell your doctor, who will decide whether you should continue treatment.
• Diarrhea, especially if you notice the presence of blood or mucus in the stool or if the diarrhea becomes severe or lasts a long time.
• Appearance of fever or worsening of it, cough or difficulty breathing. These can be signs of a rare but serious lung problem called eosinophilic pneumonia. Your doctor will check the condition of your lungs and decide whether you should continue treatment with daptomicin.

Daptomicin may interfere with laboratory tests that measure your blood's ability to clot. The results may apparently suggest poor clotting, even if there is no actual problem. Therefore, it is essential that your doctor is aware that you are receiving daptomicin. Tell your doctor that you are being treated with daptomicin.

Your doctor will perform blood tests to monitor the health of your muscles before you start treatment and frequently during treatment with daptomicin.

Children and adolescents

Daptomicin should not be given to children under one year of age. Animal studies have shown that this age group may experience severe side effects.

Use in elderly patients

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

Other medicines and Daptomicina Normon

Tell your doctor or nurse if you are using, have recently used, or might use any other medicines. It is particularly important that you mention the following:

• Medicines called statins or fibrates (to lower cholesterol) or cyclosporin (a medicine used in transplants to prevent organ rejection or for other conditions, e.g. rheumatoid arthritis or atopic dermatitis). It is possible that the risk of muscle side effects may increase if you take any of these medicines (and others that may affect the muscles) during treatment with daptomicin. Your doctor may decide not to give you daptomicin or temporarily stop 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 elimination of daptomicin by the kidneys.
• 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

Daptomicin is not usually given to pregnant women. If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

You should not breastfeed if you are receiving daptomicin, as it may pass into breast milk and affect the baby.

Driving and using machines

Daptomicin has no known effects on the ability to drive or use machines.

Daptomicina Normon contains sodium

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

3. How Daptomicina Normon is given

Daptomicina will be administered to you by your doctor or nurse.

Adults (18 years of age and older)

The dose will depend on your weight and the type of infection being treated. The usual dose for adults is 4 mg per kg of body weight once daily for skin infections or 6 mg per kg of body weight once daily for heart 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 that lasts approximately 30 minutes or as an injection that lasts approximately 2 minutes. The same dose is recommended for people over 65 years of age, provided their kidneys are working properly.

If your kidneys do not work well, you may receive daptomicin less frequently, e.g. every other day. If you are undergoing dialysis and your next dose of daptomicin is due on a dialysis day, you will usually receive daptomicin 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 that lasts approximately 30-60 minutes.

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

Detailed instructions for use and handling are provided at the end of the leaflet.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

The following are described the most serious side effects:

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

• Some cases of hypersensitivity reactions (severe allergic reactions including anaphylaxis and angioedema) have been reported during the administration of daptomicin. These severe allergic reactions require immediate medical attention. Tell your doctor or nurse immediately if you have any of the following symptoms:
• Chest pain or pressure,
• Rash or hives,
• Swelling around the throat,
• Fast or weak pulse,
• Shortness of breath,
• Fever,
• Chills or shivering,
• Flushing,
• Dizziness,
• Fainting,
• Metallic taste.
• Tell your doctor immediately if you have pain, increased sensitivity, or muscle weakness of unknown origin. Muscle problems can be severe, including muscle breakdown (rhabdomyolysis), which can cause kidney damage.

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

• A rare but potentially serious lung condition called eosinophilic pneumonia, mostly after more than 2 weeks of treatment. The symptoms may include difficulty breathing, appearance of cough or worsening of it, or appearance of fever or worsening of it.
• Severe skin diseases. The symptoms may include:
• appearance of fever or worsening of it,
• red spots on the skin, raised or filled with fluid, which can start in the armpits or in areas of the chest or groin and can spread over a large area of the body,
• blisters or sores in the mouth or genitals.
• A serious kidney problem. The symptoms may include fever and rash.

If you experience these symptoms, tell your doctor or nurse immediately. Your doctor will perform additional tests to establish a diagnosis.

The following are described the most frequently reported side effects:

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

• Fungal infections, such as thrush (mouth ulcers),
• Urinary tract infection,
• Decreased number of red blood cells (anemia),
• Dizziness, anxiety, difficulty sleeping,
• Headache,
• Fever, weakness (asthenia),
• High or low blood pressure,
• Constipation, abdominal pain,
• Diarrhea, nausea or vomiting,
• Flatulence,
• Abdominal swelling or abdominal distension,
• Skin rash or itching,
• Pain, itching, or redness at the infusion site,
• Pain in arms or legs,
• High levels of liver enzymes or creatine phosphokinase (CPK) in blood tests.

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

Uncommon side effects(may affect up to 1 in 100 patients)

• Blood disorders (e.g. increased platelet count, which can increase the tendency to develop blood clots, or increased number of certain types of white blood cells),
• Decreased appetite,
• Numbness or tingling in the hands or feet, altered sense of taste,
• Tremors,
• Changes in heart rhythm, flushing,
• Indigestion (dyspepsia), tongue inflammation,
• Itchy rash,
• Pain, cramps, or muscle weakness, muscle inflammation (myositis), joint pain,
• Kidney problems,
• Vaginal inflammation and irritation,
• Generalized pain or weakness, fatigue (fatigue),
• High blood sugar, serum creatinine, myoglobin, or lactate dehydrogenase (LDH), prolonged blood clotting time, or electrolyte imbalance in blood tests,
• Eye itching.

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

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

Frequency not known(cannot be estimated from the available data)

• Antibiotic-associated colitis, including pseudomembranous colitis (severe or persistent diarrhea containing blood and/or mucus, associated with abdominal pain or fever), bruising more easily, bleeding gums, or nosebleeds.

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if it is possible side effects not listed in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storing Daptomicina Normon

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 on the vial after “EXP”. The expiry date is the last day of the month stated.

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

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Container Content and Additional Information

Composition ofDaptomycinNormon

• The active ingredient is daptomycin. One vial of powder contains 500 mg of daptomycin.
• The other component is sodium hydroxide.

Appearance of the Product and Container Content

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

Daptomycin Normon is presented in containers containing 1 vial.

Marketing Authorization Holder and Manufacturer

LABORATORIOS NORMON, S.A.

Ronda de Valdecarrizo, 6 – 28760 Tres Cantos – Madrid (SPAIN)

Date of Last Revision of this Prospectus:September 2021

Detailed and updated information on this medicinal product is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/.

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This information is intended exclusively for healthcare professionals:

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

Instructions for Use and Handling

Presentation of 500 mg:

In adults, daptomycin can be administered intravenously as an infusion over 30 minutes or as an injection over 2 minutes. Unlike adults, daptomycin should not be administered to pediatric patients as an injection over 2 minutes. Pediatric patients from 7 to 17 years of age should receive daptomycin by infusion over 30 minutes. Pediatric patients under 7 years of age who receive doses of 9-12 mg/kg should be administered daptomycin by infusion over 60 minutes. The preparation of the solution for infusion requires an additional dilution phase, as described below.

Daptomycin Normon Administered as Intravenous Infusion over 30 or 60 Minutes

Reconstituting the lyophilized 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 Daptomycin Normon for infusion.

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

To prepare Daptomycin Normon for intravenous infusion, follow these instructions:

To reconstitute or dilute Daptomycin Normon lyophilized product, an aseptic technique must be used throughout the process.

For Reconstitution:

1. The polypropylene "flip-off" closure cap must be removed to expose the central part of the rubber stopper. Clean the top of the rubber stopper with a cotton swab with alcohol or another antiseptic solution and let it dry. After cleaning, do not touch the rubber stopper or allow it to come into contact with any other surface. Withdraw 10 ml of an injectable solution containing 9 mg/ml of sodium chloride (0.9%) into a syringe using a sterile transfer needle with a diameter of 21 gauge or less, or a needleless device, and slowly inject it through the center of the rubber stopper into the vial, aiming the needle towards the wall of the vial.
2. The vial should be gently rotated to ensure that the product is completely moistened, and then left to stand for 10 minutes.
3. Finally, the vial should be gently rotated/shaken for a few minutes until a transparent reconstituted solution is obtained. Avoid vigorous agitation to prevent foam formation.
4. The reconstituted solution should be carefully inspected before use to ensure that the substance is dissolved and to verify the absence of particles in suspension. The color of the reconstituted solution of Daptomycin Normon may vary from pale yellow to light brown.
5. The reconstituted solution should then be diluted with 9 mg/ml of sodium chloride (0.9%) (typical volume of 50 ml).

For Dilution:

1. Slowly withdraw the appropriate reconstituted liquid (50 mg daptomycin/ml) from the vial using a new sterile needle with a diameter of 21 gauge or less, inverting the vial so that the solution falls 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 withdrawing the solution into the syringe. Before removing the needle from the vial, pull the plunger back to the end of the syringe cylinder to withdraw the required solution from the inverted vial.
2. Expel air, large bubbles, and any excess solution to obtain the required dose.

1. Transfer the required reconstituted dose to 50 ml of 9 mg/ml sodium chloride (0.9%).
2. The reconstituted and diluted solution should be infused intravenously over 30 or 60 minutes.

Daptomycin Normon 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 Normon: 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 Normon Administered as Intravenous Injection over 2 Minutes (Only for Adult Patients)

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

Reconstituting the lyophilized 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 Daptomycin Normon for injection.

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

To prepare Daptomycin Normon for intravenous injection, follow these instructions:

To reconstitute Daptomycin Normon lyophilized product, an aseptic technique must be used throughout the process.

1. The polypropylene "flip-off" closure cap must be removed to expose the central part of the rubber stopper. Clean the top of the rubber stopper with a cotton swab with alcohol or another antiseptic solution and let it dry. After cleaning, do not touch the rubber stopper or allow it to come into contact with any other surface. Withdraw 10 ml of an injectable solution containing 9 mg/ml of sodium chloride (0.9%) into a syringe using a sterile transfer needle with a diameter of 21 gauge or less, or a needleless device, and slowly inject it through the center of the rubber stopper into the vial, aiming the needle towards the wall of the vial.
2. The vial should be gently rotated to ensure that the product is completely moistened, and then left to stand for 10 minutes.
3. Finally, the vial should be gently rotated/shaken for a few minutes until a transparent reconstituted solution is obtained. Avoid vigorous agitation to prevent foam formation.
4. The reconstituted solution should be carefully inspected before use to ensure that the substance is dissolved and to verify the absence of particles in suspension. The color of the reconstituted solution of Daptomycin Normon may vary from pale yellow to light brown.
5. Slowly withdraw the reconstituted liquid (50 mg daptomycin/ml) from the vial using a sterile needle with a diameter of 21 gauge or less.
6. Invert the vial so that the solution falls towards the stopper. Using a new syringe, insert the needle into the inverted vial. Keeping the vial inverted, place the tip of the needle at the lowest point of the liquid while withdrawing the solution into the syringe. Before removing the needle from the vial, pull the plunger back to the end of the syringe cylinder to withdraw all the solution from the inverted vial.
7. Replace the needle with a new one for intravenous injection.
8. Expel air, large bubbles, and any excess solution to obtain the required dose.

1. The reconstituted solution should be slowly injected intravenously over 2 minutes.

The physical and chemical stability during use of the reconstituted solution in the vial has been demonstrated for 12 hours at 25°C and up to a maximum of 48 hours if refrigerated (2°C – 8°C).

However, from a microbiological point of view, the product should be used immediately. If not used immediately, the storage time during use is the responsibility of the user and should not normally exceed 24 hours at 2°C - 8°C, unless the reconstitution/dissolution has taken place in controlled and validated aseptic conditions.

This medicinal product should not be mixed with other medicinal products except those mentioned above. The vials of Daptomycin Normon are for single use only. Any unused remainder of the vial should be discarded.