Daptomycin polpharma

Package leaflet: Information for the patient

Warning! Keep the leaflet, information on the outer packaging in a foreign language.
Daptomycin Polpharma (Daptomicina Normon)
500 mg, powder for solution for injection/infusion
Daptomycinum
Daptomycin Polpharma and Daptomicina Normon are different trade names for the same medicine.
Please read this leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet so that you can read it again if necessary.
• If you have any doubts, please consult your doctor or nurse.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same as yours.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet

1. What Daptomycin Polpharma is and what it is used for
2. Important information before receiving Daptomycin Polpharma
3. How to take Daptomycin Polpharma
4. Possible side effects
5. How to store Daptomycin Polpharma
6. Contents of the pack and other information

1. What Daptomycin Polpharma is and what it is used for

The active substance in Daptomycin Polpharma, a powder for solution for injection/infusion, is daptomycin. Daptomycin is an antibacterial agent that can inhibit the growth of certain bacteria. Daptomycin Polpharma is used in adults and children and adolescents (aged 1 to 17 years) for the treatment of skin and soft tissue infections. Daptomycin Polpharma is also used in the treatment of bloodstream infections associated with skin infections.
Daptomycin Polpharma is also used in adults for the treatment of infections of the inner lining of the heart chambers and valves (including heart valves) caused by a bacterium called Staphylococcus aureus. Daptomycin Polpharma is also used in the treatment of bloodstream infections caused by the same bacterium responsible for heart infections.
Depending on the type of infection(s), during treatment with Daptomycin Polpharma, your doctor may also prescribe other antibacterial medicines.

2. Important information before administering Daptomycin Polpharma

When not to use Daptomycin Polpharma

• if the patient is allergic to daptomycin or sodium hydroxide (listed in section 6).

The patient should inform the doctor or nurse if they have any allergies or hypersensitivity.
If the patient suspects they may be allergic to any of the listed substances, they should
consult a doctor or nurse for advice.

Warnings and precautions
Before starting treatment with Daptomycin Polpharma, consult a doctor or
nurse:

• if the patient has or has previously had kidney problems. The doctor may need to adjust the dose of Daptomycin Polpharma (see section 3 of this leaflet).
• muscle pain, tenderness, or muscle weakness may occasionally occur in patients receiving Daptomycin Polpharma (more information on this in section 4 of this leaflet). In such cases, the patient should inform the doctor. The doctor will arrange for blood tests and decide whether treatment with Daptomycin Polpharma can continue. These symptoms usually resolve within a few days after stopping Daptomycin Polpharma.
• if the patient has ever experienced severe skin rash, skin peeling, blisters, and/or mouth ulcers, or serious kidney problems after receiving daptomycin.
• in cases of significant overweight. Blood concentrations of Daptomycin Polpharma may be higher than in individuals with normal body weight, and careful monitoring is required if adverse effects occur. If any of the above points apply, the patient should inform their doctor or nurse before starting treatment with Daptomycin Polpharma.

The patient should immediately inform the doctor or nurse if any of the following symptoms occur:

• severe, acute allergic reactions have been observed in patients treated with nearly all antibacterial agents, including Daptomycin Polpharma. Symptoms may include wheezing, difficulty breathing, swelling of the face, neck, and throat, rash, and hives, fever.
• serious skin disorders have been reported during treatment with daptomycin. Symptoms associated with these disorders may include:
• onset or worsening of fever,
• red, raised, or fluid-filled blisters on the skin, which may appear under the arms, on the chest, or in the groin area, and may spread over large areas of the body,
• blisters or ulcers in the mouth or on the genitals.
• serious kidney problems have been reported during daptomycin treatment. Symptoms may include fever and rash.
• tingling or numbness in the hands or feet, loss of sensation, or difficulty moving. If any of these symptoms occur, the patient should inform the doctor, who will decide whether to discontinue or continue treatment.
• diarrhoea, especially if blood or mucus is present, or if diarrhoea becomes severe or persistent.
• onset or worsening of fever, cough, or difficulty breathing. These may be symptoms of a rare but serious lung disorder called eosinophilic pneumonia. The doctor will examine lung function and decide whether to continue or discontinue treatment with Daptomycin Polpharma. Daptomycin Polpharma may affect laboratory test results assessing blood coagulation. Laboratory results may indicate poor coagulation even when blood coagulation is actually normal. Therefore, it is important that the doctor takes into account that the patient is receiving Daptomycin Polpharma. The patient should inform the doctor about the use of Daptomycin Polpharma.

To monitor muscle function, the doctor may order blood tests both before and repeatedly during treatment with Daptomycin Polpharma.

Children and adolescents
Daptomycin Polpharma must not be given to children under one year of age, as animal studies have shown that severe adverse reactions may occur in this age group.

Use in elderly patients
Patients aged 65 years and older may receive the same dose as recommended for adults, provided no kidney disease has been diagnosed.

Daptomycin Polpharma with other medicines
The patient should inform the doctor or nurse about all medicines currently used, recently taken, or planned for use.
It is especially important to inform the doctor about:

• medicines that lower cholesterol levels (called statins or fibrates) or cyclosporine (a medicine used in transplantation to prevent organ rejection or in other conditions such as rheumatoid arthritis or atopic dermatitis). Using any of these (or other muscle-affecting) medicines during treatment with Daptomycin Polpharma may increase the risk of developing adverse muscle symptoms. The doctor will decide whether to discontinue Daptomycin Polpharma or temporarily suspend the use of the other medicines.
• painkillers called non-steroidal anti-inflammatory drugs (NSAIDs) or COX-2 inhibitors (e.g. celecoxib). These may affect the impact of Daptomycin Polpharma on the kidneys.
• oral anticoagulant medicines (e.g. warfarin) used to prevent blood clotting. The doctor may need to monitor blood clotting time.

Pregnancy and breastfeeding
Daptomycin Polpharma is generally not given to pregnant women.
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to become pregnant, she should consult a doctor or pharmacist before using this medicine.
The medicine should not be used during breastfeeding, as Daptomycin Polpharma may pass into breast milk and may harm the baby.

Driving and operating machinery
There are no known effects of Daptomycin Polpharma on the ability to drive
motor vehicles or operate machinery.

Daptomycin Polpharma contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per vial, i.e. the medicine is considered "sodium-free".

3. How to take Daptomycin Polpharma

Daptomycin Polpharma is usually administered by a doctor or nurse.
Adults (aged 18 years and above)
The dose depends on body weight and the type of infection being treated. The usual dose for adults is 4 mg per kilogram (kg) of body weight once daily for skin infections, or 6 mg per kilogram of body weight once daily for heart infections or bloodstream infections associated with skin or heart infections. In adult patients, this dose is given directly into the blood (intravenously) as an infusion lasting approximately 30 minutes or as an injection lasting approximately 2 minutes. The same dose is recommended for individuals over 65 years of age, provided they do not have kidney disease.
If kidney function is impaired, Daptomycin Polpharma may be given less frequently, for example every other day. In dialysed patients, if the next dose of Daptomycin Polpharma is scheduled on a dialysis day, the drug is usually administered after completion of dialysis.
Children and adolescents (aged 1 to 17 years)
The dose for children and adolescents (aged 1 to 17 years) will depend on the patient's age and the type of infection being treated.
The dose is administered directly into the bloodstream (intravenously) as an infusion lasting approximately 30–60 minutes.
Treatment usually lasts from 1 to 2 weeks for skin infections. For bloodstream or heart infections, as well as for skin infections with prolonged duration, the duration of treatment will be determined by the physician.
Detailed instructions for the preparation and administration of the medicinal product are provided at the end of this leaflet.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them.
The most serious side effects are described below:
Serious side effects with unknown frequency (frequency cannot be estimated from the available data)
Cases of hypersensitivity reactions (severe allergic reactions, including anaphylaxis and angioedema) have been reported during administration of Daptomycin Polpharma. This severe allergic reaction requires immediate medical attention. Immediately inform your doctor or nurse if you experience any of the following symptoms:

• chest pain or tightness in the chest,
• rash or hives,
• swelling of the throat,
• rapid or weak pulse,
• wheezing,
• fever,
• chills or shivering,
• hot flushes,
• dizziness,
• fainting,
• metallic taste in the mouth.

If you experience unexplained muscle pain, tenderness or weakness, inform your doctor immediately. Muscle-related symptoms may be serious. Muscle cells may break down (a condition known as rhabdomyolysis), which may lead to kidney damage.

Other serious side effects reported with daptomycin include:
Serious side effects with unknown frequency (frequency cannot be estimated from the available data):

• Rare but potentially serious lung disorder called eosinophilic pneumonia, occurring during treatment lasting longer than 2 weeks. Symptoms include difficulty breathing, new or worsening cough, new or worsening fever.
• Serious skin disorders. Symptoms may include:
  • new or worsening fever,
  • red raised or fluid-filled blisters on the skin, which may appear under the arms, on the chest or in the genital area, and which may spread over large areas of the body,
  • blisters or ulcers in the mouth or on the genitals.
• Serious kidney problems. Symptoms may include fever and rash.

Immediately inform your doctor or nurse if you experience any of these symptoms. Your doctor will perform additional tests to establish a diagnosis.
The most commonly reported side effects are described below:
Common side effects (may affect less than 1 in 10 people)

• fungal infections, such as candidiasis,
• urinary tract infection,
• reduced number of red blood cells (anaemia),
• anxiety, sleep disturbances,
• dizziness, headache,
• fever, weakness (asthenia),
• increased or decreased blood pressure,
• constipation, abdominal pain,
• diarrhoea, nausea or vomiting,
• flatulence, abdominal distension or bloating,
• skin rash or itching,
• pain, itching or redness around the infusion site,
• pain in arms or legs,
• increased levels of liver enzymes or creatine phosphokinase (CPK) in the blood.

Other side effects that may occur after administration of Daptomycin Polpharma are described below:
Uncommon side effects (may affect less than 1 in 100 people)

• blood disorders (e.g. increased number of small blood cells called platelets, which may increase blood clotting, or increased number of certain types of white blood cells),
• decreased appetite,
• tingling or numbness of hands or feet, taste disturbances,
• tremor,
• changes in heart rhythm, sudden flushing of the face,
• indigestion (dyspepsia), inflammation of the tongue,
• itchy skin rash,
• muscle pain, cramps or weakness, muscle inflammation, joint pain,
• kidney problems,
• vaginal inflammation or irritation,
• general feeling of pain or weakness, fatigue (tiredness),
• increased blood glucose, serum creatinine, myoglobin, lactate dehydrogenase (LDH) activity, prolonged blood clotting time or electrolyte imbalance,
• eye itching.

Rare side effects (may affect less than 1 in 1,000 people)

• yellowing of the skin and eyes,
• prolonged prothrombin time.
  Frequency unknown (frequency cannot be estimated from the available data)
• inflammation of the large intestine associated with antibacterial effect, including pseudomembranous colitis (severe or persistent diarrhoea with blood and (or) mucus, associated with abdominal pain or fever),
• easy bruising,
• bleeding from gums or nosebleeds.

Reporting of side effects
If you experience any side effects, including any not listed in this leaflet, tell your doctor, pharmacist or nurse. Side effects can also be reported directly to the Department of Monitoring of Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:
Al. Jerozolimskie 181C,
02-222 Warsaw
tel.: + 48 22 49 21 301,
fax: + 48 22 49 21 309,
website: https://smz.ezdrowie.gov.pl
Reporting side effects helps to provide more information on the safety of this medicine.

5. How to store Daptomycin Polpharma

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the container. The expiry date refers to the last day of the stated month.
Store in a refrigerator (2°C – 8°C).

6. Contents of the pack and other information

What Daptomycin Polpharma contains

• The active substance is daptomycin. One vial of powder contains 500 mg of daptomycin.
• Other ingredient: sodium hydroxide (for pH adjustment).

What Daptomycin Polpharma looks like and contents of the pack
Daptomycin Polpharma, powder for solution for injection/infusion, is available as a yellowish to light brown tablet or powder in vials made of colourless glass.
Before administration, the powder must be mixed with a solvent to form a solution.
Daptomycin Polpharma is available in packs containing 1 vial.
For further information, please contact the marketing authorisation holder or the parallel importer.
Marketing authorisation holder in Spain, country of export:
Laboratorios Normon, S.A.
Ronda de Valdecarrizo, 6 – 28760 Tres Cantos – Madrid
Spain
Manufacturer:
Laboratorios Normon, S.A.
Ronda de Valdecarrizo, 6 – 28760 Tres Cantos – Madrid
Spain
Parallel importer:
Zakłady Farmaceutyczne POLPHARMA S.A.
ul. Pelplińska 19
83-200 Starogard Gdański
Repackaged in:
CEFEA Sp. z o.o. Sp. komandytowa
ul. Działkowa 56
02-234 Warsaw
LABOR Przedsiębiorstwo Farmaceutyczno-Chemiczne Sp. z o.o.
ul. Długosza 49
51-162 Wrocław
Marketing authorisation number in Spain, country of export: 726192.6
Parallel import authorisation number: 266/25
[parallel importer logo]

Information intended exclusively for healthcare professionals

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. In contrast to adult patients, daptomycin should not be administered as a 2-minute injection to children and adolescents. For children and adolescents aged 7 to 17 years, daptomycin should be administered as a 30-minute infusion. For children under 7 years of age receiving a dose of 9 to 12 mg/kg body weight, daptomycin should be administered over 60 minutes.
Preparation of the infusion solution requires an additional reconstitution step as described below.

Daptomycin Polpharma for intravenous infusion lasting 30 or 60 minutes
The concentration of Daptomycin Polpharma in the infusion solution of 50 mg/ml is achieved by
reconstituting the lyophilized product with 10 ml of 9 mg/ml (0.9%) sodium chloride solution for injection.
Dissolution of the lyophilized product usually takes 20 minutes. The fully reconstituted solution is
clear and may contain a few small air bubbles or foam at the edge of the vial.
To prepare Daptomycin Polpharma for intravenous infusion, follow the instructions below.
Throughout the reconstitution and dilution process of the lyophilized Daptomycin Polpharma, aseptic techniques must be strictly maintained.

Reconstitution:

1. Remove the plastic flip-off cap to expose the central portion of the rubber stopper. Wipe the top of the rubber stopper with an alcohol-impregnated swab or other antiseptic solution and allow it to dry. After cleaning, do not touch the rubber stopper or allow it to come into contact with any other surface. Draw 10 ml of 9 mg/ml (0.9%) sodium chloride solution for injection (physiological saline) into a syringe using a sterile 21 G needle or smaller gauge, or a needle-free device. Then slowly pierce the center of the rubber stopper with the needle and inject the contents of the syringe, directing the needle against the vial wall.
2. Gently rotate the vial to completely wet the lyophilized powder and leave it to stand for 10 minutes.
3. Finally, gently rotate or swirl the vial for several minutes until a clear solution is obtained. Avoid vigorous shaking to prevent foaming.
4. Carefully inspect the reconstituted solution before use to ensure the product is completely dissolved and free from particulate matter. The reconstituted Daptomycin Polpharma solution is pale yellow to light brown in color.
5. Dilute the reconstituted solution with 9 mg/ml (0.9%) sodium chloride solution (typically 50 ml).

Dilution:

1. Slowly withdraw the required amount of reconstituted solution (50 mg daptomycin/ml) from the vial using a new sterile 21 G needle or smaller gauge by inverting the vial so that the solution flows toward the stopper. Using a syringe, insert the needle into the inverted vial. While holding the vial upside down, place the needle tip as deep as possible into the solution during withdrawal. Before removing the needle from the vial, pull the syringe plunger fully back to withdraw the desired volume from the inverted vial.
2. Remove air, large bubbles, and excess solution from the syringe to obtain the required dose.
3. Transfer the required amount of reconstituted solution to 50 ml of 9 mg/ml (0.9%) sodium chloride solution.
4. The reconstituted and diluted solution may then be administered as an intravenous infusion over 30 or 60 minutes.

Daptomycin Polpharma is physically and chemically incompatible with glucose-containing solutions.
The following drugs have shown no incompatibility when added to Daptomycin Polpharma solution:
aztreonam, ceftazidime, ceftriaxone, gentamicin, fluconazole, levofloxacin, dopamine, heparin, and
lidocaine.
The total storage time (reconstituted solution in vial and diluted solution in infusion bag) must not exceed 12 hours at 25°C or 24 hours if stored refrigerated.
The stability of the diluted solution in the infusion bag is 12 hours at 25°C or 24 hours if stored refrigerated at 2°C–8°C.

Daptomycin Polpharma administered as a 2-minute intravenous injection (adults only)
Do not use water to reconstitute Daptomycin Polpharma for intravenous injection.
Daptomycin Polpharma must be reconstituted exclusively with 9 mg/ml (0.9%) sodium chloride solution.
The concentration of 50 mg/ml for the injection solution is achieved by reconstituting the lyophilized product with 10 ml of 9 mg/ml (0.9%) sodium chloride solution for injection.
The lyophilized product dissolves in approximately 20 minutes. The fully dissolved solution becomes clear and may contain a few small bubbles or foam at the edge of the vial.
To prepare Daptomycin Polpharma for intravenous injection, follow the instructions below.
Throughout the reconstitution process of the lyophilized Daptomycin Polpharma, aseptic techniques must be strictly maintained.

1. Remove the plastic flip-off cap to expose the central portion of the rubber stopper. Wipe the rubber stopper with an alcohol-impregnated swab or other antiseptic solution and allow it to dry. After cleaning, do not touch the rubber stopper or allow it to come into contact with any other surface. Draw 10 ml of 9 mg/ml (0.9%) sodium chloride solution for injection (physiological saline) into a syringe using a sterile 21 G needle or smaller gauge, or a needle-free device. Then slowly pierce the center of the rubber stopper with the needle and inject the contents of the syringe, directing the needle against the vial wall.
2. Gently rotate the vial to completely wet the lyophilized powder and leave it to stand for 10 minutes.
3. Finally, gently rotate or swirl the vial for several minutes until a clear solution is obtained. Avoid vigorous shaking to prevent foaming.
4. Carefully inspect the reconstituted solution before use to ensure the product is completely dissolved and free from particulate matter. The reconstituted Daptomycin Polpharma solution is pale yellow to light brown in color.
5. Slowly withdraw the reconstituted solution (50 mg daptomycin/ml) from the vial using a sterile 21 G needle or smaller gauge.
6. Invert the vial so that the solution flows toward the stopper. Using a new syringe, insert the needle into the inverted vial. While holding the vial upside down, place the needle tip as deep as possible into the solution during withdrawal. Before removing the needle from the vial, pull the syringe plunger fully back to withdraw the entire solution from the inverted vial.
7. Replace the needle with a new one suitable for intravenous injection.
8. Remove air, large bubbles, and excess solution from the syringe to obtain the required dose.
9. The reconstituted solution should be injected slowly into the vein over 2 minutes.

Chemical and physical stability of the reconstituted solution in the vial is 12 hours at 25°C or up to
48 hours when stored refrigerated (2°C–8°C).
However, from a microbiological standpoint, the prepared medicinal product should be used immediately. If not used immediately, the storage time and conditions are the responsibility of the user, typically no longer than 24 hours at 2°C–8°C, unless reconstitution and dilution were performed under controlled and validated aseptic conditions.

Daptomycin Polpharma must not be mixed with other medicinal products except those listed above.
Vials containing Daptomycin Polpharma are for single use only.
Any unused medicinal product or waste material should be disposed of appropriately.