Cubicin 350 mg powder for solution for injection or infusion

The active substance in Cubicin powder for solution for injection or infusion is daptomycin. Daptomycin is an antibiotic that can stop the growth of certain bacteria. Cubicin is used in adults to treat infections of the skin and the tissues below the skin. It is also used in adults to treat infections in the tissues that line the inside of the heart (including heart valves) which are caused by a bacterium called Staphyloccocus aureus and to treat infections in the blood caused by the same bacterium when associated with skin or heart infection.

Depending on the type of infection(s) that you have, your doctor may also prescribe other antibiotics while you are receiving treatment with Cubicin.

You should not be given Cubicin

If you are allergic (hypersensitive) to daptomycin or to sodium hydroxide.
If this applies to you, tell your doctor or nurse. If you think you may be allergic, ask your doctor or nurse for advice.

Take special care with Cubicin

• If you have, or have previously had kidney problems. Your doctor may need to change the dose of Cubicin (see section 3 of this leaflet).
• Occasionally, patients receiving Cubicin may develop tender or aching muscles or muscle weakness (see section 4 of this leaflet for more information). If this happens tell your doctor. Your doctor will make sure you have a blood test and will advise whether or not to continue with Cubicin. The symptoms generally go away within a few days of stopping Cubicin.
• If you are very overweight. There is a possibility that your blood levels of Cubicin could be higher than those found in persons of average weight and you may need careful monitoring in case of side effects. If any of these applies to you, tell your doctor or nurse before you are given Cubicin.

Tell your doctor straight away if you develop any of the following symptoms:

• Serious, acute allergic reactions have been observed in patients treated with nearly all antibacterial agents, including Cubicin. Tell a doctor or a nurse straight away if you experience symptoms suggestive of allergic reaction, such as wheezing, difficulty breathing, rashes and hives, fever (see section 4 of this leaflet for more information).
• Any unusual tingling or numbness of the hands or feet, loss of feeling or difficulties with movements. If this happens, tell your doctor who will decide whether you should continue the treatment.
• Diarrhoea, especially if you notice blood ormucus, or if diarrhoea becomes severe or persistent.
• New or worsening fever, cough or difficulty breathing. These may be signs of a rare but serious lung disorder called eosinophilic pneumonia. Your doctor will check the condition of your lungs and decide whether or not you should continue Cubicin treatment.

Cubicin may interfere with laboratory tests that measure how well your blood is clotting. The results can suggest poor blood clotting when, in fact, there is no problem. Therefore it is important that your doctor takes into account that you are receiving Cubicin. Please inform your doctor that you are on treatment with Cubicin.

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

Use in children

The use of Cubicin in children has not been studied and is therefore not recommended.

Use in elderly

People over the age of 65 can be given the same dose as other adults, provided their kidneys are working well.

Taking other medicines
Please tell your doctor, nurse or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.
It is particularly important that you mention the following:

• Medicines called statins or fibrates (to lower cholesterol) or ciclosporin (a medicinal product used in transplantation to prevent organ rejection or for other conditions, e.g. rheumathoid arthritis or atopic dermatitis). It is possible that the risk of side effects affecting the muscles may be higher when any of these medicines (and some others that can affect muscles) is taken during treatment with Cubicin. Your doctor may decide not to give you Cubicin or to stop the other medicine for a while.
• Pain killing medicines called non-steroidal anti-inflammatory drugs (NSAIDs) or COX-2 inhibitors (e.g. celecoxib). These could interfere with the effects of Cubicin in the kidney.
• Oral anti-coagulants (e.g. warfarin), which are medicines that prevent blood from clotting. It may be necessary for your doctor to monitor your blood clotting times.

Pregnancy and breast-feeding

Cubicin is not usually given to pregnant women. Tell your doctor if you are pregnant, think you may be pregnant, or are planning to become pregnant.

Do not breast-feed if you are receiving Cubicin, because it may pass into your breast milk and could affect the baby.

Driving and using machines
Cubicin has no known effects on the ability to drive or use machines.

Cubicin will usually be given to you by a doctor or a nurse.

The dose will depend on how much you weigh and the type of infection being treated. The usual dose for adults is 4 mg for every kilogram (kg) of body weight once daily for skin infections or 6 mg for every kg of body weight once daily for a heart infection or a blood infection associated with skin or heart infection. This dose is given directly into your blood stream (into a vein), either as an infusion lasting about 30 minutes or as an injection lasting about 2 minutes. The same dose is recommended in people aged over 65 years provided their kidneys are working well.

If your kidneys do not work well, you may receive Cubicin less often, e.g. once every other day. If you are receiving dialysis, and your next dose of Cubicin is due on a dialysis day, you will be usually given Cubicin after the dialysis session.

A course of treatment usually lasts for 1 to 2 weeks for skin infections. For blood or heart infections and skin infections your doctor will decide how long you should be treated.

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

The frequency of possible side effects listed below is defined using the following convention:

Very common affects more than 1 user in 10 Common affects 1 to 10 users in 100 Uncommon affects 1 to 10 users in 1,000 Rare affects 1 to 10 users in 10,000 Very rare affects less than 1 user in 10,000 Not known frequency cannot be estimated from the available data.

Some side effects are very rare
A hypersensitivity reaction (serious allergic reaction including anaphylaxis) has been reported, in some cases during administration of Cubicin. This serious allergic reaction needs immediate medical attention. Tell your doctor or nurse straight away if you experience any of the following symptoms:

• Chest pain or tightness
• Rash with blistering, sometimes affecting the mouth and genitals
• Swelling around throat
• Rapid or weak pulse
• Wheezing
• Fever
• Shivering or trembling
• Hot flushes
• Dizziness
• Fainting
• Metallic taste

Tell your doctor straight away if you experience unexplained muscle pain, tenderness, or weakness. In very rare cases (reported in less than 1 in every 10,000 patients), muscle problems can be serious, including muscle breakdown (rhabdomyolysis), which can result in kidney damage.

Cubicin may also cause other side effects:

Some side effects are common

• Fungal infections such as thrush,
• Urinary tract infection,
• Decreased number of red blood cells (anaemia),
• Dizziness, anxiety, difficulty in sleeping,
• Headache,
• Fever, weakness (asthenia),
• High or low blood pressure,
• Constipation, abdominal pain,
• Diarrhoea, feeling sick (nausea) or being sick (vomiting),
• Flatulence,
• Abdominal swelling or bloating,
• Skin rash or itching,
• Pain, itchiness or redness at the site of infusion,
• Pain in arms or legs,
• Blood testing showing higher levels of liver enzymes or creatine phosphokinase (CPK).

Some side effects are uncommon

• Blood disorders (e.g increased number of small blood particles called platelets, which may increase the tendency for blood clotting, or higher levels of certain types of white blood cells),
• Decreased appetite,
• Tingling or numbness of the hands or feet, taste disturbance,
• Trembling,
• Changes in heart rhythm, flushes,
• Indigestion (dyspepsia), inflammation of the tongue,
• Itchy rash of skin,
• Muscle pain or weakness, inflammation of the muscles (myositis), joint pain,
• kidney problems,
• Inflammation and irritation of the vagina,
• General pain or weakness, tiredness (fatigue),
• Blood test showing increased levels of blood sugar, serum creatinine, myoglobin, or lactate dehydrogenase (LDH), prolonged blood clotting time or imbalance of salts.

Some side effects are rare

• Yellowing of the skin and eyes,
• Prothrombin time prolonged.

Frequency not known

Antibiotic-associated colitis, including pseudomembranous colitis (severe or persistent diarrhoea containing blood and/or mucus, associated with abdominal pain or fever).

A rare but potentially serious lung disorder called eosinophilic pneumonia has been reported in patients given Cubicin, mostly after more than 2 weeks of treatment. The symptoms can include difficulty breathing, new or worsening cough, or new or worsening fever. If you experience these symptoms, tell your doctor or nurse straight away.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor, nurse or pharmacist.

• Keep out of the reach and sight of children.
• Do not use Cubicin after the expiry date which is stated on the carton and label. The expiry date refers to the last day of the month.
• Store in a refrigerator (2°C ? 8°C).
• Dispose of in accordance with local requirements.

What Cubicin contains

• The active substance is daptomycin. One vial of powder contains 350 mg daptomycin.
• The other ingredient is sodium hydroxide.

What Cubicin looks like and contents of the pack

Cubicin powder for solution for injection or infusion is supplied as a pale yellow to light brown powder in a glass vial. It is mixed with a solvent to form a liquid before it is administered.

Cubicin is available in packs containing 1 vial or 5 vials.

Marketing Authorisation Holder
Novartis Europharm Limited
Wimblehurst Road
Horsham
West Sussex, RH12 5AB
United Kingdom

Manufacturer

Novartis Pharmaceuticals UK Limited
Wimblehurst Road
Horsham
West Sussex, RH12 5AB
United Kingdom

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder.

BelgiëBelgiqueBelgien Novartis Pharma N.V. TélTel 32 2 246 16 11 LuxembourgLuxemburg Novartis Pharma GmbH TélTel 49 911 273 0

Novartis Pharma Services Inc. . 359 2 489 98 28 Magyarország Novartis Hungária Kft. Pharma Tel. 36 1 457 65 00

eská republika Novartis s.r.o. Tel 420 225 775 111 Malta Novartis Pharma Services Inc. Tel 356 2298 3217

Danmark Novartis Healthcare AS Tlf 45 39 16 84 00 Nederland Novartis Pharma B.V. Tel 31 26 37 82 111

Deutschland Novartis Pharma GmbH Tel 49 911 273 0 Norge Novartis Norge AS Tlf 47 23 05 20 00

Eesti Novartis Pharma Services Inc. Tel 372 66 30 810 Österreich Novartis Pharma GmbH Tel 43 1 86 6570

Novartis Hellas A.E.B.E. 30 210 281 17 12 Polska Novartis Poland Sp. z o.o. Tel. 48 22 375 4888

España Novartis Farmacéutica, S.A. Tel 34 93 306 42 00 Portugal Novartis Farma - Produtos Farmacêuticos, S.A. Tel 351 21 000 8600

France Novartis Pharma S.A.S. Tél 33 1 55 47 66 00 România Novartis Pharma Services Inc. Tel 40 21 31299 01

Ireland Novartis Ireland Limited Tel 353 1 260 12 55 Slovenija Novartis Pharma Services Inc. Tel 386 1 300 75 50

Ísland Vistor hf. Sími 354 535 7000 Slovenská republika Novartis Slovakia s.r.o. Tel 421 2 5542 5439

Italia Novartis Farma S.p.A. Tel 39 02 96 54 1 SuomiFinland Novartis Finland Oy PuhTel 358 010 6133 200

Novartis Pharma Services Inc. 357 22 690 690 Sverige Novartis Sverige AB Tel 46 8 732 32 00

Latvija Novartis Pharma Services Inc. Tel 371 67 887 070 United Kingdom Novartis Pharmaceuticals UK Ltd. Tel 44 1276 698370

Lietuva
Novartis Pharma Services Inc.
Tel: +370 5 269 16 50

This leaflet was last approved in

The following information is intended for medical or healthcare professionals only

Important: Please refer to the Summary of Product Characteristics before prescribing.

Instructions for use and handling

350 mg presentation:

Daptomycin may be administered intravenously as an infusion over 30 minutes or as an injection over 2 minutes. Preparation of the solution for infusion requires an additional dilution step as detailed below.

Cubicin given as 30-minute intravenous infusion

A 50 mg/ml concentration of Cubicin for infusion can be achieved by reconstituting the lyophilised product with 7 ml of sodium chloride 9 mg/ml (0.9%) solution for injection.

The lyophilised product takes approximately 15 minutes to dissolve. The fully reconstituted product will appear clear and may have a few small bubbles or foam around the edge of the vial.

To prepare Cubicin for intravenous infusion, please adhere to the following instructions: Aseptic technique should be used throughout to reconstitute lyophilised Cubicin.

1. The polypropylene flip off cap should be removed to expose the central portions of the rubber stopper. Draw 7 ml of sodium chloride 9 mg/ml (0.9%) solution for injection into a syringe, then slowly inject through the centre of the rubber stopper into the vial pointing the needle towards the wall of the vial.

2. The vial should be gently rotated to ensure complete wetting of the product and then allowed to stand for 10 minutes.

3. Finally the vial should be gently rotated/swirled for a few minutes as needed to obtain a clear reconstituted solution. Vigorous shaking/agitation should be avoided to prevent foaming of the product.

4. The reconstituted solution should be checked carefully to ensure that the product is in solution and visually inspected for the absence of particulates prior to use. Reconstituted solutions of Cubicin range in colour from pale yellow to light brown.

5. The reconstituted solution should then be diluted with sodium chloride 9 mg/ml (0.9%) (typical volume 50 ml).

6. Invert the vial in order to allow the solution to drain towards the stopper. Using a new syringe, insert the needle into the inverted vial. Keeping the vial inverted, position the needle tip at the very bottom of the solution in the vial when drawing the solution into the syringe. Before removing the needle from the vial, pull the plunger all the way back to the end of the syringe barrel in order to remove all of the solution from the inverted vial.

7. Replace needle with a new needle for the intravenous infusion.

8. Expel air, large bubbles, and any excess solution in order to obtain the required dose.

9. The reconstituted and diluted solution should then be infused intravenously over 30 minutes.

Cubicin is not physically or chemically compatible with glucose-containing solutions. The following have been shown to be compatible when added to Cubicin containing infusion solutions: aztreonam, ceftazidime, ceftriaxone, gentamicin, fluconazole, levofloxacin, dopamine, heparin and lidocaine.

The combined storage time (reconstituted solution in vial and diluted solution in infusion bag) at 25°C must not exceed 12 hours (24 hours if refrigerated).

Stability of the diluted solution in infusion bags is established as 12 hours at 25°C or 24 hours if stored under refrigeration at 2°C ? 8°C.

Cubicin given as 2-minute intravenous injection

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

A 50 mg/ml concentration of Cubicin for injection is obtained by reconstituting the lyophilised product with 7 ml of sodium chloride 9 mg/ml (0.9%) solution for injection.

The lyophilised product takes approximately 15 minutes to dissolve. The fully reconstituted product will appear clear and may have a few small bubbles or foam around the edge of the vial.

To prepare Cubicin for intravenous injection, please adhere to the following instructions: Aseptic technique should be used throughout to reconstitute lyophilised Cubicin.

1. The polypropylene flip off cap should be removed to expose the central portions of the rubber stopper. Draw 7 ml of sodium chloride 9 mg/ml (0.9%) solution for injection into a syringe, then slowly inject through the centre of the rubber stopper into the vial pointing the needle towards the wall of the vial.

2. The vial should be gently rotated to ensure complete wetting of the product and then allowed to stand for 10 minutes.

3. Finally the vial should be gently rotated/swirled for a few minutes as needed to obtain a clear reconstituted solution. Vigorous shaking/agitation should be avoided to prevent foaming of the product.

4. The reconstituted solution should be checked carefully to ensure that the product is in solution and visually inspected for the absence of particulates prior to use. Reconstituted solutions of Cubicin range in colour from pale yellow to light brown.

5. Invert the vial in order to allow the solution to drain towards the stopper. Using a new syringe, insert the needle into the inverted vial. Keeping the vial inverted, position the needle tip at the very bottom of the solution in the vial when drawing the solution into the syringe. Before removing the needle from the vial, pull the plunger all the way back to the end of the syringe barrel in order to remove all of the solution from the inverted vial.

6. Replace needle with a new needle for the intravenous injection.

7. Expel air, large bubbles, and any excess solution in order to obtain the required dose.

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

Chemical and physical in-use stability on the reconstituted solution in the vial has been demonstrated for 12 hours at 25°C and up to 48 hours if stored under refrigeration (2°C ? 8°C).

However, from a microbiological point of view the product should be used immediately. If not used immediately, in-use storage times are the responsibility of the user and would normally not be longer than 24 hours at 2°C ? 8°C unless reconstitution /dilution has taken place in controlled and validated aseptic conditions.

This medicinal product must not be mixed with other medicinal products except those mentioned above.

Cubicin vials are for single-use only. Any unused portion remaining in the vial should be discarded.