Cubicin 350 mg powder for solution for injection or infusion

 

What is it and how is it used?

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.

What do you have to consider before using it?

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.

How is it used?

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.

What are possible side effects?

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.

How should it be stored?

  • 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 is it?

Cubicin is a powder that is made up into a solution for injection or infusion (drip into a vein). It contains the active substance daptomycin.

What is it used for?

Cubicin is used to treat adults (aged 18 years or over) with the following bacterial infections:

complicated infections of the skin and the soft tissues below the skin. Complicated means that the infection is difficult to treat, because it has spread to the deep tissues below the skin, treatment with surgery might be needed, or the patient has other conditions that might affect the response to treatment

right-sided infective endocarditis infection of the lining or the valves of the right side of the heart caused by the bacterium Staphylococcus aureus S. aureus. The decision to treat this type of infection with Cubicin should be based on the likelihood that the medicine will work against the infection and on advice from an expert

bacteraemia infection of the blood caused by S. aureus, associated with either of the two infections above.

Prescribers should consider official guidance on the use of antibiotics.

The medicine can only be obtained with a prescription.

How is it used?

Cubicin is given into a vein by a doctor or a nurse as an infusion lasting 30 minutes or as an injection lasting two minutes. For skin or soft tissue infections without bacteraemia, Cubicin is given at a dose of 4 mg per kilogram body weight once every 24 hours for seven to 14 days or until the infection has cleared up. For endocarditis and for skin or soft tissue infection with bacteraemia, the dose is 6 mg/kg every 24 hours. The duration of treatment depends on the risk of complications and official recommendations. Cubicin should not be given more than once a day.

Cubicin should only be used in patients who have problems with their kidneys if the benefit of treatment is greater than its potential risk, in which case it may need to be given less often. Depending on the type of infection being treated and whether a patient has more than one infection, other antibiotics may be given during treatment with Cubicin.

How does it work?

The active substance in Cubicin, daptomycin, is an antibiotic that belongs to the group ‘lipopeptides’. It can stop the growth of certain types of bacteria by attaching to the membrane around each bacterial cell and upsetting the essential functions that keep the cell alive. A list of bacteria against which Cubicin is active can be found in the summary of product characteristics (also part of the EPAR).

How has it been studied?

Cubicin infusions have been studied in two large studies involving 1,118 adults with complicated skin and soft tissue infections (mainly wound infections and major abscesses) and in one study involving 246 adults with bacteraemia caused by S. aureus, including 35 who also had right-sided infective endocarditis. In all three studies, Cubicin was compared with standard treatments for these infections (other antibiotics such as vancomycin or one of the penicillins, including oxacillin, cloxacillin, flucloxacillin and nafcillin). The studies looked at whether the infections had been cured or had improved.

Two further studies were carried out in a total of 40 healthy volunteers to show that Cubicin injections are as safe as the infusions, and that they produce similar levels of daptomycin in the blood.

What benefits has it shown during the studies?

Cubicin was as effective as the standard treatments.

In the studies of skin and soft tissue infections, the success rates at seven to 12 days after the last injection of Cubicin were 67% in one study and 85% in the other. The difference in response rates between the two studies was due to differences in the types of patients and infections being treated.

For the treatment of bacteraemia in patients with right-sided infective endocarditis, 42% of the patients receiving Cubicin (8 out of 19) and 44% of the patients receiving standard treatment (7 out of 16) were treated successfully. However, there was insufficient evidence to support the use of Cubicin to treat bacteraemia in patients who did not have either right-sided infective endocarditis or complicated skin and soft-tissue infections.

What is the risk associated?

The most common side effects with Cubicin (seen in between 1 and 10 patients in 100) are infections caused by fungi (moulds and yeasts), urinary tract infections (infection of the structures that carry urine), Candida infection (a fungal infection), anaemia (low red blood cell counts), anxiety, insomnia

(difficulty sleeping), dizziness, headache, hypertension (high blood pressure), hypotension (low blood pressure), gastrointestinal and abdominal pain (stomach ache), nausea (feeling sick), vomiting, constipation, diarrhoea, flatulence (gas), bloating and distension (feeling as if the tummy is full), rash, pruritus (itching), pain in the limbs (arms or legs), infusion site reactions, pyrexia (fever), asthenia (weakness), abnormal liver tests and raised levels in the blood of an enzyme called CPK (a marker of muscle damage). For the full list of all side effects reported with Cubicin, see the package leaflet.

Cubicin should not be used in people who may be hypersensitive (allergic) to daptomycin or the other ingredient (sodium hydroxide). Caution is needed when it is given to patients with kidney problems and the medicine may need to be given less often. All patients must have their CPK levels measured at the beginning of their treatment and at regular intervals, particularly if they have any known risk factors for muscle damage. For the full list of precautions, see the package leaflet.

Why has it been approved?

The CHMP decided that Cubicin’s benefits are greater than its risks and recommended that it be given marketing authorisation.

How has it been studied?

The company that makes Cubicin will carry out further studies with Cubicin to investigate whether it has an effect on the muscle, and to look at its safety and effectiveness in patients with kidney disease and in the elderly.

Further information

The European Commission granted a marketing authorisation valid throughout the European Union for Cubicin on 19 January 2006. The marketing authorisation holder is Novartis Europharm Limited. The marketing authorisation is valid for an unlimited period.

For more information about treatment with Cubicin, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.

This summary was last updated in 09-2010.