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

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

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

daptomycin

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, ask your doctor or nurse.
• This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse reactions, consult your doctor or nurse, even if they are adverse reactions not listed in this leaflet. See section 4.

Contents of this leaflet

1. What Daptomicina Normon is and what it is used for
2. What you need to know before receiving Daptomicina Normon
3. How to use Daptomicina Normon
4. Possible side effects
5. How to store 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 injectable solution and for infusion is daptomycin. Daptomycin is an antibacterial agent capable of stopping the growth of certain bacteria. Daptomycin is used in adults and in children and adolescents (aged 1 to 17 years) to treat skin and soft tissue infections. It is also used to treat bloodstream infections when associated with a skin infection.

Daptomycin is also used in adults to treat infections of the tissues lining the inside of the heart (including the heart valves), caused by a type of bacterium called Staphylococcus aureus. It is also used to treat bloodstream infections caused by the same type of bacterium when associated with a heart infection.

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

2. What you need to know before receiving Daptomicina Normon

Do not receive Daptomicina Normon

If you are allergic to daptomycin or sodium hydroxide or to 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 receiving daptomycin:

• 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 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 you have a blood test and will advise whether or not it is advisable to continue using daptomycin. Symptoms usually resolve 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 serious kidney problems.
• If you have significant overweight, there is a possibility that your blood levels of daptomycin may be higher than those found 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 daptomycin.

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 nearly 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 disorders 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 areas of the chest or groin 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 daptomycin. 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 the diarrhea becomes severe or prolonged.
• Onset or worsening of fever, cough, or difficulty breathing. These may be signs of a rare but serious lung disorder 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 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 Normon

Inform your doctor or nurse if you are taking, have recently taken, or might need to take any other medicines. It is particularly important to mention the following:

• Medications 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 discontinue the other medication.
• Pain-relieving medicines called 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 plan 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 operate machinery.

Daptomicina Normon contains sodium

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

3. How to use Daptomycin Normon

Daptomycin will normally be administered to you by your doctor or nurse.

Adults (18 years of age and older)

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

If your kidneys are not functioning properly, you may receive daptomycin less frequently, e.g., once every other day. If you are undergoing dialysis and your next dose of daptomycin is scheduled on a dialysis day, you will usually receive daptomycin after the dialysis session.

Children and adolescents (from 1 to 17 years of age)

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

A full course of treatment for skin infections typically 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, this medicine can cause adverse effects, although not everyone experiences them.

Below are the most serious adverse effects:

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 daptomycin administration. 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 tightness,
• Rash or hives,
• Swelling around the throat,
• Rapid or weak pulse,
• Wheezing,
• Fever,
• Chills or shivering,
• Flushing,
• Dizziness,
• Fainting,
• Metallic taste.
• Contact your doctor immediately if you experience muscle pain, increased muscle sensitivity, or unexplained muscle weakness. Muscle problems can be serious, including 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 area 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 any of these symptoms, inform your doctor or nurse immediately. Your doctor will perform additional tests to establish a diagnosis.

Below are the more commonly 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 (anemia),
• Dizziness, anxiety, difficulty sleeping,
• Headache,
• Fever, weakness (asthenia),
• High or low blood pressure,
• Constipation, abdominal pain,
• Diarrhea, discomfort (nausea or vomiting),
• Flatulence,
• Abdominal bloating or distension,
• Skin rash or itching,
• Pain, itching, or redness at the infusion site,
• Pain in arms or legs,
• Elevated levels of liver enzymes or creatine phosphokinase (CPK) in blood tests.

Below are other adverse effects that may occur following 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 the 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,
• Generalized 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 diarrhea containing blood and/or mucus, associated with abdominal pain or fever), increased tendency to bruise, bleeding gums, or nosebleeds.

Reporting of adverse effects

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

5. Storage of Daptomycin Normon

Keep this medicine out of sight and reach of children.

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

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

Medicines must not be disposed of via wastewater or household waste. Dispose of empty containers and unused medicines at the SIGRE collection point at your pharmacy. If you are unsure, ask your pharmacist how to properly dispose of unused medicines and their packaging. This will help protect the environment.

6. Contents of the container and other information

Composition of Daptomicina Normon

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

Appearance of the product and contents of the container

Daptomicina Normon powder for injectable solution and for 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 prior to administration.

Daptomicina Normon is supplied in packs containing 1 vial.

Marketing Authorisation Holder and Manufacturer

LABORATORIOS NORMON, S.A.
Ronda de Valdecarrizo, 6 – 28760 Tres Cantos – Madrid (SPAIN)

Date of the most recent revision of this leaflet: September 2021

Detailed and up-to-date information on this medicine is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS) http://www.aemps.gob.es/.

This information is intended for healthcare professionals only:

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

Instructions for use and handling

500 mg presentation:

In adults, daptomycin may be administered intravenously either as an infusion over 30 minutes or as an injection over 2 minutes. Unlike adults, daptomycin must not be administered to paediatric patients as an injection over 2 minutes. Paediatric patients aged 7 to 17 years should receive daptomycin by infusion over 30 minutes. Paediatric patients under 7 years of age receiving doses of 9–12 mg/kg should receive daptomycin by infusion over 60 minutes. Preparation of the infusion solution requires an additional dilution step, as described below.

Daptomicina Normon administered as intravenous infusion over 30 or 60 minutes

Reconstituting the lyophilised product with 10 ml of an injectable solution containing 9 mg/ml sodium chloride (0.9%) yields a concentration of 50 mg/ml of Daptomicina Normon 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 Normon for intravenous infusion, follow the instructions below:

Throughout the process of reconstituting or diluting Daptomicina Normon lyophilised powder, aseptic technique must be used.

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 to dry. After cleaning, do not touch the rubber stopper or allow it to come into contact with any other surface. Draw 10 ml of an injectable solution containing 9 mg/ml sodium chloride (0.9%) into a syringe using a sterile transfer needle of gauge 21 or smaller, or a needle-free device, and slowly inject through the centre of the rubber stopper into the vial, directing the needle towards 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 check for the absence of suspended particles. The colour of the reconstituted Daptomicina Normon solution may vary from pale yellow to light brown.
5. The reconstituted solution should then be diluted with 9 mg/ml sodium chloride (0.9%) (typical volume 50 ml).

For dilution:

1. Slowly withdraw the appropriate volume of reconstituted liquid (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 towards 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 as the solution 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 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 should be administered intravenously over 30 or 60 minutes.

Daptomicina Normon 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 Normon: 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 as 12 hours at 25°C or 24 hours if refrigerated at 2°C – 8°C.

Daptomicina Normon administered as intravenous injection over 2 minutes (for adult patients only)

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

Reconstituting the lyophilised product with 10 ml of an injectable solution containing 9 mg/ml sodium chloride (0.9%) yields a concentration of 50 mg/ml of Daptomicina Normon 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 Normon for intravenous injection, follow the instructions below:

Throughout the process of reconstituting Daptomicina Normon lyophilised powder, aseptic technique must be used.

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 to dry. After cleaning, do not touch the rubber stopper or allow it to come into contact with any other surface. Draw 10 ml of an injectable solution containing 9 mg/ml sodium chloride (0.9%) into a syringe using a sterile transfer needle of gauge 21 or smaller, or a needle-free device, and slowly inject through the centre of the rubber stopper into the vial, directing the needle towards 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 check for the absence of suspended particles. The colour of the reconstituted Daptomicina Normon solution 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 of gauge 21 or smaller.

6. Invert the vial so that the solution flows towards 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 as the solution 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 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 should 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 responsibility of the user 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 medicine must not be mixed with other medicines except those mentioned above. Daptomicina Normon vials are for single use only. Any unused portion remaining in the vial must be discarded.