Cubicin 500 mg polvo para solucion inyectable y para perfusion

Label: information for the patient

Cubicin 500mg powder for injectable solution and for infusion

daptomycin

Read this label carefully before starting to use this medication, as it contains important information for you.

• Keep this label, as you may need to read it again.
• If you have any questions, consult your doctor or nurse.
• This medication has been prescribed only to you, and you should not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor or nurse, even if they are not listed in this label. See section4.

The active ingredient of Cubicinpowder for solutionfor injection andfor infusionis daptomycin. Daptomycin is an antibacterial agent capable of stopping the growth of certain bacteria. Cubicin is used in adults and in children and adolescents (ages 1 to 17years) to treat skin and soft tissue infections. It is also used to treat blood infections when associated with a skin infection.

Cubicin is also used in adults to treat infections in the tissues that cover the inside of the heart (including heart valves), caused by a type of bacteria calledStaphylococcus aureus. It is also usedto 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 receive treatment with Cubicin.

Do not receive Cubicin

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

If this is your case, 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 starting to receive Cubicin:

• If you have or have had kidney problems. Your doctor may need to change the dose of Cubicin (seesection3 of this prospectus).
• Occasionally, patients receiving Cubicin may develop increased sensitivity, muscle pain or weakness (seesection4 of this prospectus for more information).Inform your doctor if this happens. Your doctor will ensure that you have a blood test and advise you whether it is recommended to continue using Cubicin. Symptoms usually disappear within a few days after stopping treatment with Cubicin.
• 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 Cubicin may be higher than those found in people of average weight, and that you may therefore need stricter monitoring in cases of adverse effects.

If any of the above cases affect you, inform your doctor or nurse before receiving Cubicin.

Inform your doctor or nurse immediatelyif you develop any of the following symptoms:

• Severe and intense allergic reactions have been observed in patients treated with almost all antibacterial agents, including Cubicin. 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 Cubicin. Symptoms that occur with these skin diseases may include:

• appearance of fever or worsening of the same,
• red skin patches 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 sores in the mouth or genitals.

• Severe kidney problems have been reported with the use of Cubicin. 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 you should continue treatment.
• Diarhea, especially if you notice the presence of blood or mucus in stools 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 severe lung function deterioration called eosinophilic pneumonia. Your doctor will check your lung function and decide whether you should continue treatment with Cubicin.

Cubicin may interfere with laboratory tests that measure your blood's clotting ability. Results may appear to suggest poor clotting, despite no actual problem. Therefore, it is essential that your doctor is aware that you are receiving Cubicin. Inform your doctor that you are on treatment with Cubicin.

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

Children and adolescents

Cubicin 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 function correctly.

Other medications and Cubicin

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 Cubicin. Your doctor may decide not to administer Cubicin or temporarily interrupt treatment with the other medication.
• Medications to relieve pain called nonsteroidal anti-inflammatory drugs (NSAIDs) or COX-2 inhibitors (e.g. celecoxib). These may interfere with the elimination of Cubicin 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

Cubicin is usually not administered to pregnant women.If you are pregnant or breastfeeding, or think you may be pregnant or intend to become pregnant, consult your doctor or pharmacist before using this medication.

You should not breastfeed while receiving Cubicin, as it may pass into breast milk and affect the baby.

Driving and operating machinery

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

Cubicin contains sodium

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

Cubicin will be administered by your doctor or nurse as usual.

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 (in 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 Cubicin less frequently, for example, once every other day. If you are undergoing dialysis and your next Cubicin dose is due on a dialysis day, you will usually receive Cubicin 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 (in 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 on 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 this leaflet.

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 Cubicin 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,

-Rash or hives,

-Swelling around the throat,

-Fast or weak pulse,

-Labored breathing,

-Fever,

-Chills or tremors,

-Headache,

-Dizziness,

-Fainting,

-Bitter 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 effectsthat have been reported with the use of Cubicin are:

• A rare but potentially severe lung condition called eosinophilic pneumonia, mostly after more than 2weeks of treatment. Symptoms may include difficulty breathing, coughing, or worsening of cough, or fever or worsening of fever.
• Severe skin diseases. Symptoms may include:
• fever or worsening of fever,
• red patches on the skin that are raised or filled with fluid, which may start in the armpits or on the chest or groin and may spread to a large area of the body,
• blistering or lesions 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 10patients)

-Fungal infections, such as mouth ulcers,

-Urinary tract infection,

-Anemia (decreased red blood cell count),

-Dizziness, anxiety, difficulty falling asleep,

-Headache,

-Fever, weakness (asthenia),

-High or low blood pressure,

-Constipation, abdominal pain,

-Diarrhea, nausea or vomiting,

-Flatulence,

-Abdominal distension or bloating,

-Rash or itching,

-Pain, itching, or redness at the infusion site,

-Pain in arms or legs,

-Elevated liver enzyme or creatine phosphokinase (CPK) levels in blood tests.

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

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

• Blood disorders (e.g., increased platelet count, which may increase the risk of developing 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, hot flashes,
• Indigestion (dyspepsia), inflammation of the tongue,
• Rash with itching,
• Pain, cramps, or muscle weakness, muscle inflammation (myositis), joint pain,
• Kidney problems,
• Inflammation and irritation of the vagina,
• Generalized pain or weakness, fatigue,
• 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 1,000patients)

-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), bruising with ease, bleeding gums or nosebleeds.

Reporting of side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse,even if it is a possible side effect that does not appear in this leaflet.You can also report them directly throughthe national notification system included in theAppendix V. 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 after CAD and on the label after EXP. The expiration date is the last day of the month indicated.
• Store in refrigerator (between 2°C and 8°C).

Composition of Cubicin

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

Appearance of the product and contents of the container

Cubicin 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.

Cubicin is presented in containers containing 1vial or 5vials.

Marketing Authorization Holder

Merck Sharp & Dohme B.V., Waarderweg 39, 2031 BN Haarlem,Netherlands

Responsible for manufacturing

FAREVA Mirabel,Route de Marsat, Riom, 63963, Clermont-Ferrand Cedex 9,France

You can request more information about this medication by contacting the local representative of the marketing authorization holder:

Last review date of this leaflet:<{MM/AAAA}><{mes AAAA}>.

The detailed information about this medicine is available on the website of the European Medicines Agency:http://www.ema.europa.eu

This information is intended solely for healthcare professionals:

Important: Please consult the SmPC or Product Characteristics before prescribing.

Instructions for use and handling

Presentation of 500mg:

In adults, daptomycin can be administered by intravenous infusion over 30minutes or by intravenous injection over 2minutes. Unlike adults, daptomycin should not be administered to pediatric patients as an injection over 2minutes. Pediatric patients aged 7to17years should receive daptomycin by infusion over 30minutes. Pediatric patients under 7years who receive doses of 9‑12mg/kg should be administered daptomycin by infusion over 60minutes. The preparation of the infusion solution requires an additional dilution phase, as described below.

Cubicin administered as intravenous infusion over 30 or 60minutes

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

The lyophilized product takes approximately 15minutes 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 Cubicin for intravenous infusion, follow the instructions below:

For reconstitution:

1. The polypropylene flip-off cap should be removed to expose the central part of the rubber stopper. Clean the top of the rubber stopper with an alcohol swab or other antisepsis solution and allow it to dry. After cleaning, do not touch the rubber stopper, nor allow it to touch any other surface. Remove 10ml of a 9mg/ml sodium chloride solution (0.9%) using a sterile transfer needle of calibre 21 or smaller, or a device without a needle, and inject slowly through the center of the rubber stopper into the vial, pointing the needle towards the vial wall.
2. The vial should be gently rotated to ensure that it is fully moistened, and then left to stand for 10minutes.
3. Finally, the vial should be gently rotated/agitated for a few minutes until a transparent reconstituted solution is obtained. Vigorous agitation should be avoided to prevent foam generation.
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 Cubicin solution may vary from pale yellow to light brown.
5. The reconstituted solution should then be diluted with 9mg/ml sodium chloride solution (0.9%) (typical volume of 50ml).

For dilution:

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

Cubicin is not physically or chemically compatible with solutions containing glucose. The following medications have been shown to be compatible when added to infusion solutions containing Cubicin: 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 12hours (24hours if refrigerated).

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

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

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

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

The lyophilized product takes approximately 15minutes 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 Cubicin for intravenous injection, follow the instructions below:

For reconstitution:

1. The polypropylene flip-off cap should be removed to expose the central part of the rubber stopper. Clean the top of the rubber stopper with an alcohol swab or other antisepsis solution and allow it to dry. After cleaning, do not touch the rubber stopper, nor allow it to touch any other surface. Remove 10ml of a 9mg/ml sodium chloride solution (0.9%) using a sterile transfer needle of calibre 21 or smaller, or a device without a needle, and inject slowly through the center of the rubber stopper into the vial, pointing the needle towards the vial wall.
2. The vial should be gently rotated to ensure that it is fully moistened, and then left to stand for 10minutes.
3. Finally, the vial should be gently rotated/agitated for a few minutes until a transparent reconstituted solution is obtained. Vigorous agitation should be avoided to prevent foam generation.
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 Cubicin solution may vary from pale yellow to light brown.
5. Remove the reconstituted solution (50mg 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 rubber stopper. Using a new syringe, insert the needle into the inverted vial. Keeping the vial inverted, place the needle tip in the lowest point of the liquid while extracting the solution into the syringe. Before removing the needle from the vial, pull the plunger back to the end of the syringe barrel to remove the solution from the inverted vial.
7. Replace the needle with a new one for the intravenous injection.
8. Expel the air, large bubbles, and any excess solution to obtain the required dose.
9. The reconstituted solution should be injected slowly intravenously over 2minutes.

The physical and chemical stability during the use of the reconstituted solution in the vial has been demonstrated for 12hours at 25°C and up to a maximum of 48hours 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, normally, should not exceed 24hours at 2°C‑8°C, unless the reconstitution/dilution has taken place in controlled and validated aseptic conditions.

This medicine should not be mixed with other medicines that are not mentioned above.

The Cubicin vials are exclusively for single use. Any remaining vial that has not been used should be discarded.