DAPTOXEL 350 MG POWDER FOR SOLUTION FOR INJECTION/INFUSION – patient leaflet, side effects, dosage

1. What DAPTOXEL is and what it is used for

The active substance in DAPTOXEL powder for solution for injection/infusion is daptomycin. Daptomycin is

an antibacterial that can stop the growth of certain bacteria. DAPTOXEL is used in adults and in children and

adolescents (age from 1 to 17 years) to treat infections of the skin and the tissues below the skin. It is also

used to treat infections in the blood when associated with skin infection.

DAPTOXEL 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 type of bacteria called Staphylococcus aureus. It is also used to treat

infections in the blood caused by the same type of bacteria when associated with heart infection.

Depending on the type of infection(s) that you have, your doctor may also prescribe other antibacterials while

you are receiving treatment with DAPTOXEL.

2. What you need to know before you are given DAPTOXEL

You should not be given DAPTOXEL

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

If this applies to you, tell your doctor or nurse. If you think you may be allergic, ask your doctor or nurse for

advice.

Warnings and precautions

Talk to your doctor or nurse before you are given DAPTOXEL:

• If you have, or have previously had kidney problems. Your doctor may need to change the dose of

  DAPTOXEL (see section 3 of this leaflet).

• Occasionally, patients receiving daptomycin 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 DAPTOXEL. The symptoms

  generally go away within a few days of stopping DAPTOXEL.

• If you have ever developed a severe skin rash or skin peeling, blistering and/or mouth sores, or serious

  kidney problems after taking daptomycin.

• If you are very overweight. There is a possibility that your blood levels of daptomycin 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 DAPTOXEL.

Tell your doctor or nurse 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 daptomycin. The symptoms can include wheezing, difficulty breathing, swelling of the face, neck

  and throat, rashes and hives, or fever.

• Serious skin disorders have been reported with the use of daptomycin. The symptoms that occur with

  these skin disorders can include:

  • a new or worsening fever,

  • red raised or fluid-filled skin spots which may start in your armpits or on your chest or groin areas and

    which can spread over a large area of your body,

  • blisters or sores in your mouth or on your genitals.

• A serious kidney problem has been reported with the use of daptomycin. The symptoms can include fever

  and rash.

• 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 or mucus, 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 DAPTOXEL treatment.

DAPTOXEL 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 DAPTOXEL. Please inform your doctor that you are on treatment with DAPTOXEL.

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

Children and adolescents

DAPTOXEL should not be administered to children below one year of age as studies in animals have indicated that this age group may experience severe side effects.

Use in elderly

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

Other medicines and DAPTOXEL

Tell your doctor or nurse if you are taking, have recently taken or might take any other medicines. 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. rheumatoid 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 DAPTOXEL. Your doctor may decide not to give you DAPTOXEL 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 DAPTOXEL 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

DAPTOXEL is not usually given to pregnant women. If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before you are given this medicine.

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

Driving and using machines

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

3. How DAPTOXEL is given

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

Adults (18 years of age and above)

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. In adult patients, 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 DAPTOXEL less often, e.g. once every other day. If you are receiving dialysis, and your next dose of DAPTOXEL is due on a dialysis day, you will be usually given DAPTOXEL after the dialysis session.

Children and adolescents (1 to 17 years of age)

The dose for children and adolescents (1 to 17 years of age) will depend on the age of patient and the type of infection being treated. This dose is given directly into the blood stream (into a vein), as an infusion lasting about 30-60 minutes.

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.

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

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4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. The most serious side effects are described below:

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

• A hypersensitivity reaction (serious allergic reaction including anaphylaxis and angioedema) has been

  reported, in some cases during administration of daptomycin. 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 or hives,
  • 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.

  Muscle problems can be serious, including muscle breakdown (rhabdomyolysis), which can result in kidney damage.

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

• A rare but potentially serious lung disorder called eosinophilic pneumonia, mostly after more than 2 weeks

  of treatment. The symptoms can include difficulty breathing, new or worsening cough, or new or worsening fever.

• Serious skin disorders. The symptoms can include:

  • a new or worsening fever,
  • red raised or fluid-filled skin spots which may start in your armpits or on your chest or groin areas and which can spread over a large area of your body,
  • blisters or sores in your mouth or on your genitals.
• A serious kidney problem. The symptoms can include fever and rash.

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

The most frequently reported side effects are described below:

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

• 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).

Other side effects which may occur following DAPTOXEL treatment are described below:

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

• 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, cramping, 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,

  • Itchy eyes.

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

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

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

Antibacterial-associated colitis, including pseudomembranous colitis (severe or persistent diarrhoea containing blood and/or mucus, associated with abdominal pain or fever), easy bruising, bleeding gums, or nosebleeds.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store DAPTOXEL

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 label after EXP. The expiry date refers to the last day of the month.

Store below 25 °C.

After reconstitution:

Chemical and physical in-use stability of the reconstituted solution in the vial has been demonstrated for 12 hours at 25 °C and up to 72 hours at 2 °C – 8 °C.

After dilution (which was performed immediately after reconstitution):

Chemical and physical in-use stability of the diluted solution in infusion bags has been demonstrated for 12 hours at 25 °C and 48 hours at 2 °C – 8 °C.

After reconstitution and dilution:

Chemical and physical in-use stability has been demonstrated for 12 hours at 25 °C or 48 hours at 2 °C – 8 °C, which relates to the combined storage time (reconstituted solution in vial and diluted solution in infusion bag).

However, from a microbiological point of view the product should be used immediately. No preservative or bacteriostatic agent is present in this product. 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.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What DAPTOXEL contains

The active substance is daptomycin. One vial of powder contains 350 mg daptomycin.

One ml provides 50 mg of daptomycin after reconstitution within the vial only with 7 ml of sterile water for injection.

The other ingredients are arginine, histidine, isoleucine, and hydrochloric acid (for pH-adjustment).

What DAPTOXEL looks like and contents of the pack

DAPTOXEL powder for solution for injection/infusion is supplied as a pale yellow to light brown lyophilised powder or cake in a clear glass vial with rubber stoppers and aluminium closures with white plastic flip off caps. It is mixed with a solvent to form a liquid before it is administered.

DAPTOXEL is available in packs containing 1 vial.

Marketing Authorisation Holder and Manufacturer

Xellia Pharmaceuticals ApS

Dalslandsgade 11

2300 Copenhagen S

Denmark

Distributor

SUN PHARMA UK LIMITED

6-9 The Square,

Stockley Park,

Uxbridge, UB11 1FW

United Kingdom

This leaflet was last revised in April 2024.

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