DAPTOMYCIN 500 MG POWDER FOR SOLUTION FOR INJECTION OR INFUSION - patient leaflet, side effects, dosage

Patient leaflet - DAPTOMYCIN 500 MG POWDER FOR SOLUTION FOR INJECTION OR INFUSION

1. what daptomycin is and what it is used for

The active substance in Daptomycin powder for solution for injection or infusion is daptomycin. Daptomycin is an antibacterial that can stop the growth of certain bacteria. Daptomycin 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.

Daptomycin 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 daptomycin.

2. what you need to know before you are given daptomycin

You should not be given daptomycin

if you are allergic to daptomycin or to sodium hydroxide 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 daptomycin.

If you have, or have previously had kidney problems. Your doctor may need to change the dose of daptomycin (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 daptomycin. The symptoms generally go away within a few days of stopping daptomycin
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 daptomycin.

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

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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 daptomycin treatment.

Daptomycin 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 daptomycin. Please inform your doctor that you are on treatment with daptomycin.

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

Children and adolescents

Daptomycin 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 daptomycin

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 daptomycin. Your doctor may decide not to give you daptomycin 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 daptomycin 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

Daptomycin 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 for advice before taking this medicine. Do not breast-feed if you are receiving daptomycin, because it may pass into your breast milk and could affect the baby.

Driving and using machines

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

Daptomycin contains sodium

This medicine contains less than 1 mmol sodium (23mg) per dose, that is to say essentially ‘sodium-free’

3. How Daptomycin is given

Daptomycin will usually be given 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 4mg for every kilogram (kg) of body weight once daily for skin infections or 6mg 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 daptomycin less often, e.g. once every other day. If you are receiving dialysis, and

The following information is intended for healthcare professionals only

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

Instructions for use and handling

In adults, Daptomycin may be administered intravenously as an infusion over 30 minutes or as an injection over 2 minutes. Unlike in adults, Daptomycin should not be administered by injection over a 2-minute period in paediatric patients. Paediatric patients 7 to 17 years old should receive Daptomycin infused over

30 minutes. In paediatric patients under 7 years old receiving a 9–12 mg/kg dose, Daptomycin should be administered over 60 minutes. Preparation of the solution for infusion requires an additional dilution step as detailed below.

Daptomycin given as an intravenous infusion over 30 or 60 minutes

A 50mg/ml concentration of Daptomycin for infusion can be achieved by reconstituting the lyophilised product with 7ml (for Daptomycin 350mg powder) or 10ml (for Daptomycin 500mg powder) of sodium chloride 9mg/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 Daptomycin for intravenous infusion, please adhere to the following instructions.

Aseptic technique should be used throughout to reconstitute or dilute lyophilised Daptomycin.

For Reconstitution:

1. The polypropylene flip off cap should be removed to expose the central portions of the rubber stopper. Wipe 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 touch any other surface. Draw 7ml (for Daptomycin 350mg powder) or 10ml (for Daptomycin 500mg powder) of sodium chloride 9mg/ml (0.9 %) solution for injection into a syringe using a sterile transfer needle that is 21 gauge or smaller in diameter, or a needleless device, 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 Daptomycin range in colour from pale yellow to light brown.
5. The reconstituted solution should then be diluted with sodium chloride 9mg/ml (0.9 %) (typical volume 50ml).

For Dilution:

1. Slowly remove the appropriate reconstituted liquid (50mg daptomycin/ml) from the vial using a new sterile needle that is 21 gauge or smaller in diameter by inverting the vial in order to allow the solution to drain towards the stopper. Using a 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 the required solution from the inverted vial.
2. Expel air, large bubbles, and any excess solution in order to obtain the required dose.
3. Transfer the required reconstituted dose into 50ml sodium chloride 9mg/ml (0.9 %).
4. The reconstituted and diluted solution should then be infused intravenously over 30 or 60 minutes.

Daptomycin is not physically or chemically compatible with glucose-containing solutions. The following have been shown to be compatible when added to Daptomycin containing infusion solutions: aztreonam, ceftazidime, ceftriaxone, gentamicin, fluconazole, levofloxacin, dopamine, heparin and lidocaine. your next dose of daptomycin is due on a dialysis day, you will be usually given daptomycin 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.

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 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 daptomycin 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 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: 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 daptomycin

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

Store in a refrigerator (2°C-8°C).

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 Daptomycin contains

The active substance is daptomycin. Daptomycin 350mg: One vial of powder contains 350mg daptomycin. One ml provides 50mg of daptomycin after reconstitution with 7ml of sodium chloride 9mg/ml (0.9%) solution.

Daptomycin 500mg: One vial of powder contains 500mg daptomycin. One ml provides 50mg of daptomycin after reconstitution with 10ml of sodium chloride 9mg/ml (0.9%) solution.

The other ingredient is sodium hydroxide.

What Daptomycin looks like and contents of the pack

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

Daptomycin is available in packs containing 1 vial or 5 vials

Not all pack sizes may be marketed Marketing Authorisation Holder Wockhardt UK Ltd, Ash Road North, Wrexham LL13 9UF, UK

Manufacturer

Laboratori FUNDACIO DAU, C/ De la letra C, 12–14, Potfgono Industrial de la Zona Franca, 08040 Barcelona, Spain

Other formats:

To listen to or request a copy of this leaflet in Braille, large print or audio please call, free of charge: 0800 198 5000 (UK only).

Please be ready to give the following information:

Product name	Reference number
Daptomycin 350mg Powder for Solution for Injection or Infusion	29831/0723
Daptomycin 500mg Powder for Solution for Injection or Infusion	29831/0724

This is a service provided by the Royal National Institute of Blind People.

This leaflet was last revised in 11/2021

108479/1 13006521-A

Twockhardt

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.

Daptomycin given as 2-minute intravenous injection (adult patients only)

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

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