Caspofungin zentiva

Caspofungin Zentiva, 70 mg
powder for solution for infusion concentrate
Caspofunginum
Please read the entire leaflet carefully before use, as it contains important information for the patient.

• Keep this leaflet for future reference.
• If you have any questions, consult your doctor or pharmacist.
• If you experience any side effects, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Leaflet Contents

1. What Caspofungin Zentiva is and what it is used for
2. Important information before using Caspofungin Zentiva
3. How to use Caspofungin Zentiva
4. Possible side effects
5. How to store Caspofungin Zentiva
6. Contents of the pack and other information

1. What Caspofungin Zentiva is and what it is used for

What Caspofungin Zentiva is
Caspofungin Zentiva contains a medicine called caspofungin, which belongs to a group of antifungal medicines.

What Caspofungin Zentiva is used for
Caspofungin Zentiva is used to treat the following infections in children, adolescents, and adults:

• Severe fungal infections of tissues and organs (called "invasive candidiasis"). This infection is caused by fungi (yeasts) called Candida. Patients at risk of developing this type of infection include those who have recently undergone surgery or have a weakened immune system. The most common symptoms of this infection are fever and chills that do not respond to antibiotic treatment.
• Fungal infections of the nose, sinuses, or lungs (called "invasive aspergillosis") when other antifungal medicines have not worked or have caused side effects. These infections are caused by a mould called Aspergillus. Patients at risk of developing this type of infection include those receiving chemotherapy, organ transplant recipients, and patients with weakened immune systems.
• Suspected fungal infection in patients with fever and low white blood cell count whose condition has not improved after antibiotic treatment. Patients at risk of developing fungal infection include those who have recently undergone surgery or have a weakened immune system.

How Caspofungin Zentiva works
Caspofungin Zentiva weakens fungal cells and inhibits their normal growth. This prevents the spread of the infection and allows the body's natural defense mechanisms to eliminate it completely.

2. Important information before using Caspofungin Zentiva

When not to use Caspofungin Zentiva

• if the patient is allergic to caspofungin or any of the other ingredients of this medicine (listed in section 6).

If in doubt before administering the medicine, consult a doctor, pharmacist, or nurse.
Warnings and precautions
Before starting treatment with Caspofungin Zentiva, discuss this with your doctor, nurse,
or pharmacist:

• if the patient is allergic to any medicines;
• if the patient has ever had liver problems – a different dose of the medicine may be necessary;
• if the patient is taking cyclosporine (a medicine used to prevent transplant rejection or to suppress the immune system), as the doctor may order additional blood tests during treatment;
• if the patient has ever had any other health problems.

If any of the above statements apply to the patient (or are suspected),
consult a doctor, pharmacist, or nurse before using Caspofungin Zentiva.
Caspofungin Zentiva may also cause serious skin-related adverse reactions, such as
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).
Caspofungin Zentiva with other medicines
Inform your doctor, nurse, or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take, including over-the-counter medicines and herbal supplements, because Caspofungin Zentiva may affect how other medicines work. Likewise, some other medicines may affect the action of Caspofungin Zentiva.
If the patient is taking any of the following medicines, inform the doctor, nurse, or pharmacist:

• cyclosporine or tacrolimus (medicines used to prevent transplant rejection or to suppress the immune system), as the doctor may order additional blood tests during treatment;
• certain medicines used to treat HIV infection, such as efavirenz or nevirapine;
• phenytoin or carbamazepine (used to treat seizures);
• dexamethasone (a steroid medicine);
• rifampicin (an antibiotic).

If any of the above statements apply to the patient (or are suspected),
inform the doctor, nurse, or pharmacist before using Caspofungin Zentiva.
Pregnancy and breastfeeding
During pregnancy, while breastfeeding, or if pregnancy is suspected, consult a doctor before using any medicine.

• Studies on the use of Caspofungin Zentiva in pregnant women have not been conducted. This medicine should be used during pregnancy only if the potential benefits justify the potential risk to the unborn child.
• Women receiving Caspofungin Zentiva should not breastfeed.

Driving and operating machinery
There is no information indicating that Caspofungin Zentiva may affect the ability to drive or
operate machinery.
Caspofungin Zentiva contains sodium.
This medicine contains less than 1 mmol (23 mg) of sodium per vial, meaning the medicine is considered "sodium-free".

3. How to use Caspofungin Zentiva

Caspofungin Zentiva will always be prepared and administered by medical personnel.
Caspofungin Zentiva will be given:

• once daily;
• as a slow intravenous infusion (intravenous infusion);
• over approximately 1 hour.

The duration of treatment and the daily dose of Caspofungin Zentiva will be determined by the treating physician.
The physician will monitor the effectiveness of the medicine in the patient. For patients with a body weight above 80 kg, a different dose may be required.
Children and adolescents
The dose intended for children and adolescents may differ from the dose used in adults.
Use of a higher than recommended dose of Caspofungin Zentiva
The treating physician will decide what daily dose of Caspofungin Zentiva the patient requires and how long the treatment should last. However, if there is any concern that the patient may have received too high a dose of Caspofungin Zentiva, immediate advice should be sought from the treating physician or nurse.
If there are any further doubts regarding the use of this medicine, consult the doctor, nurse, or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them.
Some of these side effects may be serious.
If you notice any of the side effects listed below, you must
immediately contact your doctor or nurse, as you may require
immediate medical attention:

• rash, itching, feeling of warmth, swelling of the face, lips or throat, or difficulty breathing – possible occurrence of a histamine reaction to the medicine;
• difficulty breathing with wheezing or worsening rash – possible occurrence of an allergic reaction to the medicine;
• cough, severe breathing problems – in adults with invasive aspergillosis, severe breathing problems may occur, which could progress to respiratory failure;
• rash, skin peeling, mucosal ulceration, urticaria, peeling of large areas of skin.

As with all prescription medicines, some of the side effects may be severe. Please consult your doctor for additional information.
Other side effects observed in adults include:
Common ( may occur in no more than 1 in 10 people):

• decreased hemoglobin concentration (reduced concentration in blood of the substance transporting oxygen), decreased number of white blood cells;
• decreased concentration of albumin (a type of protein) in blood, decreased potassium concentration or low blood potassium levels;
• headache;
• phlebitis;
• dyspnea;
• diarrhea, nausea or vomiting;
• changes in results of certain blood laboratory tests (including increased values of certain liver function tests);
• itching, rash, skin redness or excessive sweating compared to usual;
• joint pain;
• chills, fever;
• itching at the injection site.

Uncommon (may occur in no more than 1 in 100 people):

• changes in results of certain blood laboratory tests (including blood coagulation, platelet count, red blood cells and white blood cells);
• loss of appetite, increased volume of body fluids, electrolyte imbalance, high blood sugar, low blood calcium, low blood magnesium, increased blood acidity;
• disorientation, feeling of nervousness, inability to sleep;
• dizziness, reduced sensation or sensitivity (especially of the skin), tremor, drowsiness, altered taste, tingling or numbness;
• blurred vision, increased tear production, eyelid swelling, yellowing of the sclera (whites of the eyes);
• sensation of rapid or irregular heartbeat, fast heartbeat, irregular heartbeat, abnormal heart rhythm, heart failure;
• facial flushing, hot flushes, high blood pressure, low blood pressure, redness of the skin along the vein, abnormally sensitive to touch;
• bronchospasm causing wheezing or cough, rapid breathing, dyspnea causing awakening from sleep, hypoxia, abnormal breath sounds, crackles in the lungs, wheezing, nasal congestion, cough, sore throat;
• abdominal pain, epigastric pain, bloating, constipation, difficulty swallowing, dry mouth, indigestion, flatulence, stomach discomfort, swelling due to fluid accumulation in the abdominal cavity;
• reduced bile flow, enlarged liver, jaundice (yellowing of the skin and/or sclera), chemical or drug-induced liver injury, liver function disorders;
• abnormal skin changes, generalized itching, urticaria, polymorphic rash, abnormal skin appearance, presence of red, often itchy spots on hands and feet, and sometimes on the face and other parts of the body;
• back pain, pain in arms or legs, bone pain, muscle pain, muscle weakness;
• impaired kidney function, sudden worsening of kidney function;
• pain at the catheter site, injection site reactions (redness, induration, pain, swelling, irritation, rash, urticaria, leakage of fluid from the catheter into tissues), phlebitis at the injection site;
• elevated blood pressure and changes in results of certain blood laboratory tests (including those assessing kidney function, electrolytes and blood coagulation), increased concentrations of immunosuppressive drugs administered;
• discomfort in the chest, chest pain, sensation of body temperature change, general malaise, generalized pain, facial swelling, swelling of ankles, hands or feet, edema, tenderness, feeling of fatigue.

Side effects in children and adolescents
Very common (may occur in more than 1 in 10 people):

• fever.

Common ( may occur in no more than 1 in 10 people):

• headache;
• rapid heartbeat;
• sudden facial flushing, low blood pressure;
• changes in results of certain blood laboratory tests (increased values of certain liver function tests);
• itching, rash;
• pain at the catheter site;
• chills;
• changes in results of certain blood laboratory tests.

Reporting of side effects
If any adverse effects occur, including any adverse effects not listed in this leaflet, inform your doctor, pharmacist or nurse. Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products.
Al. Jerozolimskie 181 C
02 - 222 Warsaw
Tel.: + 48 22 49 21 301
Fax: + 48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse effects can also be reported to the marketing authorization holder or its representative in Poland.
By reporting adverse effects, additional information on the safety of the medicine can be collected.

5. How to store Caspofungin Zentiva

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the vial label and outer packaging, following "Expiry (EXP)". The expiry date refers to the last day of the stated month.
Closed vials: store in a refrigerator (2°C – 8°C).
Chemical and physical stability studies have demonstrated that the product remains stable for up to 24 hours when stored at temperatures up to 25°C or between 2°C and 8°C, provided the powder was reconstituted with water for injections.
From a microbiological point of view, the medicine should be used immediately, unless the method of opening/reconstitution/dilution excludes the risk of microbiological contamination.
After preparation, the medicine should be used immediately, as it does not contain any antibacterial preservatives. If it is not used immediately, the person administering the medicine is responsible for the storage duration and conditions.
Stability studies have shown that the product may be used within 48 hours if stored between 2°C and 8°C or at room temperature (25°C), provided dilution was performed using sodium chloride solution 9 mg/ml (0.9%), 4.5 mg/ml (0.45%), or 2.25 mg/ml (0.225%) or lactated Ringer's solution.
From a microbiological standpoint, the product should be used immediately. If not used immediately, the person administering the medicine is responsible for storage conditions prior to use, and the storage time should not exceed 24 hours at 2°C to 8°C, unless reconstitution and dilution were performed under validated, controlled aseptic conditions.
This medicine must be prepared only by trained medical personnel who have read and understood all instructions (see below, "Instructions for reconstitution and dilution of Caspofungin Zentiva").
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. These measures will help protect the environment.

6. Contents of the pack and other information

What Caspofungin Zentiva contains

• The active substance is caspofungin. Each vial contains 70 mg of caspofungin (as caspofungin acetate). After reconstitution with 10.5 ml of water for injections, 1 ml of concentrate contains 7.2 mg of caspofungin.
• Other ingredients: sucrose, mannitol, glacial acetic acid, sodium hydroxide (for pH adjustment).

What Caspofungin Zentiva looks like and contents of the pack
Caspofungin Zentiva is a sterile, white or almost white powder.
Each pack contains 1 vial (10 ml) with powder.

Marketing Authorisation Holder
Zentiva, k. s.
U Kabelovny 130
Dolní Měcholupy
102 37 Prague 10
Czech Republic

Manufacturer/Importer:
Pharmathen S.A.
6 Dervenakion str.
153 51 Pallini, Athens
Greece
Pharmadox Healthcare Ltd
KW20A Kordin Industrial Park
Paola, PLA 3000
Malta
Elpen Pharmaceutical Co., Inc
Marathonos Ave. 95,
Pikermi Attiki,
19009,
Greece

For further information about this medicinal product and its names in the European Economic Area countries, please contact the local representative of the Marketing Authorisation Holder in Poland:
Zentiva Polska Sp. z o.o.
ul. Bonifraterska 17
00-203 Warsaw
tel.: +48 22 375 92 00

Information intended exclusively for medical personnel:
Instructions for reconstitution and dilution of Caspofungin Zentiva:

Reconstitution of Caspofungin Zentiva

DO NOT USE ANY SOLUTIONS CONTAINING DEXTROSE, as the medicinal product Caspofungin Zentiva is not stable in solutions containing glucose. DO NOT MIX OR ADMINISTER IN THE SAME INFUSION LINE WITH OTHER MEDICINAL PRODUCTS, as there are no data on the compatibility of Caspofungin Zentiva with other intravenous active substances, excipients, or medicinal products. The infusion solution should be inspected visually for particulate matter and discoloration.

Caspofungin Zentiva, 70 mg,
powder for solution for infusion concentrate

INSTRUCTIONS FOR USE IN ADULT PATIENTS

Step 1: Reconstitute the vial contents
To dissolve the powder, allow the unopened vial to reach room temperature, then aseptically add 10.5 ml of water for injections. The resulting concentration of the concentrate will be 7.2 mg/ml.
Gently swirl the vial to dissolve the white or almost white, viscous, lyophilized powder until a clear solution is obtained. The reconstituted solution should be inspected visually for particulate matter and discoloration. The prepared solution may be stored for up to 24 hours at a temperature not exceeding 25°C or at 2°C to 8°C.

Step 2: Add the reconstituted Caspofungin Zentiva solution to the patient's infusion solution
The following infusion solutions may be used to prepare the final infusion solution: sodium chloride 0.9% solution for infusion or Ringer's lactate solution. Prepare the final infusion solution by aseptically adding the appropriate volume of the prepared concentrate (as shown in the table below) to a 250 ml infusion bag or bottle. A daily dose of 50 mg or 35 mg, if indicated, may be administered in a reduced volume infusion of 100 ml. Do not use the solution if cloudiness or precipitation occurs.

PREPARATION OF INFUSION SOLUTION FOR ADULTS

* To reconstitute the contents of each vial, use 10.5 ml of diluent.
** If a vial containing 70 mg of medicinal product is not available, a 70 mg dose can be
obtained from two vials of 50 mg each.
INSTRUCTIONS FOR USE IN CHILDREN AND ADOLESCENTS
Calculation of body surface area (Body Surface Area, BSA) for dose determination in children
and adolescents
Before preparing the infusion, calculate the patient's body surface area using the
following formula (Mosteller formula):

Preparation of intravenous infusion containing a dose of 70 mg/m for children and adolescents aged
>3 months (using a vial containing 70 mg of product)

1. Determine the actual loading dose for children and adolescents based on body surface area (calculated as described above) using the following equation: BSA (m ) x 70 mg/m = loading dose. The maximum loading dose administered on day 1 of therapy should not exceed 70 mg, regardless of the calculated dose for a given patient.
2. Remove the Caspofungin Zentiva 70 mg vial from the refrigerator and allow it to warm to room temperature.
3. Under aseptic conditions, add 10.5 ml of water for injections. The resulting solution may be stored for no longer than 24 hours at a temperature not exceeding 25°C or at 2°C to 8°C. This yields a final concentration of caspofungin of 7.2 mg/ml in the vial.
4. Withdraw from the vial the volume of medicinal product corresponding to the calculated loading dose (step 1). Under aseptic conditions, transfer this volume (ml) of diluted Caspofungin Zentiva 70 mg into an intravenous infusion bag (or bottle) containing 250 ml of 0.9%, 0.45%, or 0.225% sodium chloride solution for injection or lactated Ringer's solution for injection. Alternatively, the specified volume (ml) of diluted Caspofungin Zentiva 70 mg may be added to a smaller volume of 0.9%, 0.45%, or 0.225% sodium chloride solution for injection or lactated Ringer's solution for injection, provided that the final concentration does not exceed 0.5 mg/ml. The ready-to-use infusion solution should be used within 48 hours if stored at 2°C to 8°C or at room temperature (25°C).

Preparation of intravenous infusion containing a dose of 50 mg/m for children and adolescents aged
>3 months (using a vial containing 70 mg of product)

1. Determine the actual daily maintenance dose for children and adolescents based on body surface area (calculated as described above) using the following equation: BSA (m ) x 50 mg/m = daily maintenance dose. The daily maintenance dose should not exceed 70 mg, regardless of the calculated dose for a given patient.
2. Remove the Caspofungin Zentiva 70 mg vial from the refrigerator and allow it to warm to room temperature.
3. Under aseptic conditions, add 10.5 ml of water for injections. The resulting solution may be stored for no longer than 24 hours at a temperature not exceeding 25°C or at 2°C to 8°C. This yields a final concentration of caspofungin of 5.2 mg/ml in the vial.
4. Withdraw from the vial the volume of medicinal product corresponding to the calculated daily maintenance dose (step 1). Under aseptic conditions, transfer this volume (ml) of diluted Caspofungin Zentiva 70 mg into an intravenous infusion bag (or bottle) containing 250 ml of 0.9%, 0.45%, or 0.225% sodium chloride solution for injection or lactated Ringer's solution for injection. Alternatively, the specified volume (ml) of diluted Caspofungin Zentiva 70 mg may be added to a smaller volume of 0.9%, 0.45%, or 0.225% sodium chloride solution for injection or lactated Ringer's solution for injection, provided that the final concentration does not exceed 0.5 mg/ml. The ready-to-use infusion solution should be used within 48 hours if stored at 2°C to 8°C or at room temperature (25°C).

Notes on preparation of the medicinal product:
a. The white or almost white compact substance should dissolve completely. Gently mix the contents until a clear, transparent solution is obtained.
b. The prepared solution should be inspected during dilution and before administration for the presence of particulate matter or discoloration. If the solution is cloudy or contains precipitate, it should not be administered.
c. The medicinal product Caspofungin Zentiva is formulated so that the full dose stated on the vial label (70 mg) is delivered when 10 ml of solution is withdrawn from the vial.