Caspofungin adamed

Package leaflet: Information for the user

Caspofungin Adamed, 50 mg, powder for solution for infusion
Caspofunginum
Please read all of this leaflet carefully before this medicine is given to an adult or a child,
as it contains important information for the patient.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of the leaflet

1. What Caspofungin Adamed is and what it is used for
2. What you need to know before you are given Caspofungin Adamed
3. How to use Caspofungin Adamed
4. Possible side effects
5. How to store Caspofungin Adamed
6. Contents of the pack and other information

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

What Caspofungin Adamed is
Caspofungin Adamed contains the active substance called caspofungin. It belongs to a group of medicines known as antifungal agents.

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

• Severe fungal infections of tissues or organs (called invasive candidiasis). This infection is caused by fungal (yeast) cells called Candida. This type of infection may occur in people who have recently undergone surgery or in those with weakened immune systems. The most common symptoms of this infection are fever and chills that do not resolve after antibiotic treatment;
• Fungal infections of the nose, sinuses, or lungs (called invasive aspergillosis) when other antifungal treatments have been ineffective or caused side effects. This infection is caused by mould fungi called Aspergillus. This type of infection may occur in people undergoing chemotherapy, those who have had an organ transplant, or those with weakened immune systems;
• Suspected fungal infections when fever and low white blood cell count are present, and the patient's condition has not improved with antibiotic treatment. People at risk of fungal infection include those who have recently undergone surgery or those with weakened immune systems.

How Caspofungin Adamed works
Caspofungin Adamed causes fungal cells to become susceptible to damage and inhibits normal fungal growth. This stops the spread of the infection and allows the body's immune system to completely eliminate the infection.

2. Important information before administering Caspofungin Adamed

When not to use Caspofungin Adamed

• if the patient is allergic to caspofungin or to any of the other ingredients of this medicine (listed in section 6). If in doubt, discuss this with the doctor, pharmacist, or nurse before starting treatment.

Warnings and precautions
Before starting treatment with Caspofungin Adamed, discuss this with the doctor, pharmacist,
or nurse:

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

If any of the above situations apply to the patient (or if the patient is unsure),
this should be reported to the doctor, pharmacist, or nurse before starting treatment with
Caspofungin Adamed.
Caspofungin Adamed may also cause severe skin-related adverse reactions, such as
Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN).
Caspofungin Adamed with other medicines
Inform the doctor, pharmacist, or nurse about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take. This includes medicines available without a prescription, including herbal medicines. This should be done because Caspofungin Adamed may affect the way some other medicines work. Similarly, some other medicines may affect the way Caspofungin Adamed works.
Inform the doctor, pharmacist, or nurse if the patient is taking any of the following medicines:

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

If any of the above situations apply to the patient (or if the patient is unsure),
this should be reported to the doctor, pharmacist, or nurse before starting treatment with
Caspofungin Adamed.
Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a
child, she should consult her doctor before using this medicine.

• Caspofungin Adamed has not been studied in pregnant women. It may be used during pregnancy only if the potential benefit outweighs the potential risk to the unborn child.
• Women receiving Caspofungin Adamed should not breastfeed.

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

3. How to use Caspofungin Adamed

Caspofungin Adamed is always prepared and administered by a healthcare professional. Caspofungin Adamed will be given:

• once daily,
• by slow injection into a vein (intravenous infusion),
• over approximately 1 hour. The doctor will determine the duration of treatment and the amount of Caspofungin Adamed to be given each day. The doctor will monitor the patient's response to the treatment. Patients weighing more than 80 kg may require a different dose.

Use in children and adolescents
The dose used in children and adolescents may differ from the dose used in adults.
If more Caspofungin Adamed has been given than recommended
The doctor will determine the required amount of Caspofungin Adamed and the duration of administration each day. If there is any concern that too much Caspofungin Adamed has been administered, seek immediate advice from a doctor or nurse.
If you have any further questions about the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicinal product can cause side effects, although not everybody will experience them.
If any of the following adverse reactions occur, you must immediately inform your doctor or nurse, as immediate medical intervention may be required:

• Rash, itching, feeling of warmth, swelling of the face, lips or throat, or difficulty breathing – an anaphylactic reaction to the medicine may have occurred;
• Worsening difficulty in breathing accompanied by wheezing or rash – an allergic reaction to the medicine may have occurred;
• Cough, severe breathing difficulties – in adults with invasive aspergillosis, serious respiratory problems may occur, leading to respiratory failure;
• Rash, skin peeling, mucosal ulcers, urticaria, extensive skin exfoliation.

As with any prescription medicine, some side effects may be serious. You should consult your doctor for additional information.
Other side effects in adults
Common: may affect up to 1 in 10 people:

• Decreased haemoglobin concentration (reduced amount of oxygen-carrying substance in the blood), decreased white blood cell count;
• Decreased blood albumin levels (a type of protein), low or decreased blood potassium levels;
• Headache;
• Phlebitis (inflammation of a vein);
• Dyspnoea (shortness of breath);
• Diarrhoea, nausea or vomiting;
• Abnormal results in certain blood laboratory tests (including elevated values in certain liver function tests);
• Itching, rash, skin redness, or increased sweating more than usual;
• Joint pain;
• Chills, fever;
• Itching at the injection site.

Uncommon: may affect up to 1 in 100 people:

• Abnormal results in certain blood laboratory tests (including blood coagulation, platelet count, red blood cells and white blood cells);
• Loss of appetite, increased body fluids, disturbances in salt concentration in the body, high blood sugar levels, low blood calcium levels, increased blood calcium levels, low blood magnesium levels, increased blood acidity;
• Confusion, nervousness, difficulty sleeping;
• Dizziness, reduced sensation or sensitivity (especially of the skin), chills, drowsiness, altered taste perception, tingling or numbness;
• Blurred vision, increased lacrimation, eyelid swelling, yellowing of the sclera of the eye;
• Sensation of rapid or irregular heartbeat, palpitations, irregular heart rhythm, abnormal heart rhythm, heart failure;
• Redness, hot flushes, elevated blood pressure, low blood pressure, redness along the vein which is unusually sensitive to touch;
• Constriction of muscle fibres around the airways causing wheezing or coughing, rapid breathing, breathlessness waking from sleep, low blood oxygen levels, unusual breath sounds, crackles in the lungs, wheezing, nasal inflammation, cough, sore throat;
• Lower abdominal pain, upper abdominal pain, bloating, constipation, difficulty swallowing, dry mouth, indigestion, gas, stomach discomfort, swelling due to accumulation of excess fluid in the abdominal area;
• Reduced bile flow, enlarged liver, yellowing of the skin and (or) sclera of the eye, liver damage caused by a medicine or chemical substance, liver function disorder;
• Abnormal skin tissue, generalized itching, urticaria, rash of various appearance, abnormal skin appearance, red and often itchy patches on hands and legs, and sometimes also on the face and other body parts;
• Back pain, pain in arms and legs, bone pain, muscle pain, muscle weakness;
• Impaired kidney function, sudden loss of kidney function;
• Pain at the catheter insertion site, injection site reactions (redness, hardening, pain, swelling, irritation, rash, urticaria, leakage of fluid from the catheter into tissue), phlebitis at the injection site;
• Increased blood pressure and abnormal results in certain blood laboratory tests (including kidney function, electrolytes and blood coagulation), increased concentration of medicines taken by the patient that suppress the immune system;
• Chest discomfort, chest pain, sensation of body temperature changes, general malaise, general pain, facial swelling, ankle, hand or foot swelling, oedema, tenderness, feeling of fatigue.

Side effects in children and adolescents
Very common: may affect more than 1 in 10 people:

• Fever.

Common: may affect up to 1 in 10 people:

• Headache;
• Rapid heart rate;
• Redness, low blood pressure;
• Abnormal results in certain blood laboratory tests (elevated values in certain liver function tests);
• Itching, rash;
• Pain at the catheter site;
• Chills;
• Abnormal results in 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. Side effects can be reported directly to:
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
Side effects can also be reported to the marketing authorisation holder.
Reporting adverse reactions helps provide more information on the safety of the medicine.

5. How to store Caspofungin Adamed

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and vial after EXP.
The expiry date refers to the last day of the stated month.
Unopened vials: store in a refrigerator (2°C – 8°C).
It has been demonstrated that the chemical and physical in-use stability of the reconstituted concentrate for solution for infusion, stored at temperatures up to 25°C or 5°C ± 3°C, is 24 hours when water for injections is used for reconstitution.
From a microbiological point of view, if the method of opening/reconstitution/dilution does not exclude the risk of microbiological contamination, the product should be used immediately, due to the absence of any antibacterial preservatives. If not used immediately, the user is responsible for the storage duration and conditions prior to use.
It has been demonstrated that the chemical and physical in-use stability of the diluted solution for infusion for the patient, stored at 2°C – 8°C or at 25°C, is 48 hours when diluted with sodium chloride solution for injection at concentrations of 9 mg/ml (0.9%), 4.5 mg/ml (0.45%), or 2.25 mg/ml (0.225%), or with Ringer's lactate solution.
From a microbiological standpoint, the product should be used immediately. If this is not the case, the user is responsible for the storage duration and conditions prior to use. Under normal circumstances, storage should not exceed 24 hours at 2°C – 8°C, unless reconstitution and dilution were performed under controlled and validated aseptic conditions.
This medicine must be prepared only by trained healthcare personnel, after reading all instructions (see “Instructions for reconstitution and dilution of Caspofungin Adamed” below).
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

What Caspofungin Adamed contains

• The active substance is caspofungin.
• Each vial contains 50 mg of caspofungin (as caspofungin acetate).
• After reconstitution with 10.5 ml of water for injections, 1 ml of concentrate contains 5.2 mg of caspofungin.
• Other components: sucrose, mannitol, glacial acetic acid, and sodium hydroxide (for pH adjustment).

What Caspofungin Adamed looks like and contents of the pack
Caspofungin Adamed is a white or almost white, lyophilized powder.
Each pack contains one vial of powder.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Adamed Pharma S.A.
Pieńków, ul. M. Adamkiewicza 6A
05-152 Czosnów

Manufacturer/Importer:
Pharmathen S.A.
6 Dervenakion str., Pallini, Attiki
153 51 Greece
Pharmadox Healthcare Ltd
KW20A Kordin Industrial Park, Paola
PLA 3000 Malta
Adamed Pharma S.A.
Pieńków, ul. M. Adamkiewicza 6A
05-152 Czosnów
ELPEN PHARMACEUTICAL CO., INC
Marathonos Ave. 95,
Pikermi Attiki,
19009 Greece

This medicinal product is authorised in the European Economic Area member countries under the following names:
Denmark CASMYG
Poland Caspofungin Adamed
Greece CASMYG
France CASPOFUNGINE STRAGEN® 50 mg powder for solution for infusion

Information intended exclusively for medical professionals:

Instructions for reconstitution and dilution of Caspofungin Adamed
Reconstitution of Caspofungin Adamed
DO NOT USE SOLVENTS CONTAINING GLUCOSE, as Caspofungin Adamed is not stable in solutions containing glucose. DO NOT MIX OR ADMINISTER Caspofungin Adamed IN THE SAME INFUSION WITH OTHER MEDICINAL PRODUCTS, due to lack of available data on compatibility of Caspofungin Adamed with other substances, additives, or intravenous drugs. The infusion solution should be inspected visually for presence of particulate matter or discoloration.

Caspofungin Adamed 50 mg, powder for concentrate solution for infusion
INSTRUCTIONS FOR USE IN ADULT PATIENTS
Step 1 Reconstitution of the vial contents
To reconstitute the powder, bring the unopened vial to room temperature and then aseptically add 10.5 mL of Water for Injections. The concentration of the resulting concentrate will be 5.2 mg/mL.
The white or almost white lyophilized powder should dissolve completely. Gently swirl to obtain a clear solution. The prepared solution should be inspected visually for particulate matter and discoloration. The reconstituted solution may be stored for 24 hours at 25°C or below, or at 5°±3°C.

Step 2 Adding reconstituted Caspofungin Adamed to the patient's infusion solution
The following solutions may be used to prepare the final infusion solution: Sodium Chloride 0.9% Injection or Lactated Ringer's Solution. The final infusion solution should be prepared by aseptically adding the appropriate volume of the prepared concentrate (as shown in the table below) to a 250 mL infusion bag or bottle. The daily dose of 50 mg or 35 mg, if indicated, may be administered in a reduced infusion volume of up to 100 mL. This infusion solution must be used within 48 hours if stored at 2–8°C or at 25°C. Do not use the solution if cloudiness or precipitation occurs.

PREPARATION OF INFUSION SOLUTION FOR ADULTS

* To dissolve the contents of each vial, 10.5 ml of diluent should be used.
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/m² for children and adolescents aged > 3 months (using a vial containing 50 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 (m²) × 70 mg/m² = loading dose. The maximum loading dose administered on day 1 of therapy should not exceed 70 mg, regardless of the calculated dose for the individual patient.
2. Remove the Caspofungin Adamed vial from the refrigerator and allow it to warm to room temperature.
3. Under aseptic conditions, add 10.5 ml of water for injection. The resulting solution may be stored for up to 24 hours at a temperature not exceeding 25°C or at 5°C ± 3°C. This results in a vial concentration of caspofungin of 5.2 mg/ml.
4. Withdraw from the vial the volume corresponding to the calculated loading dose (step 1). Under aseptic conditions, transfer this volume (ml) of diluted Caspofungin Adamed product into an intravenous infusion bag (or bottle) containing 250 ml of 0.9%, 0.45%, or 0.225% sodium chloride injection or lactated Ringer's solution. Alternatively, the specified volume (ml) of diluted Caspofungin Adamed product may be added to a smaller volume of 0.9%, 0.45%, or 0.225% sodium chloride injection or lactated Ringer's solution, provided that the final concentration does not exceed 0.5 mg/ml. The prepared infusion solution should be used within 48 hours if stored at 2°C–8°C or at 25°C.

Mosteller RD: Simplified Calculation of Body Surface Area. N Engl J Med 1987 Oct 22;317(17):1098 (letter)
Preparation of intravenous infusion containing a dose of 50 mg/m² for children and adolescents aged >3 months (using a vial containing 50 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 (m²) × 50 mg/m² = daily maintenance dose. The daily maintenance dose should not exceed 70 mg, regardless of the calculated dose for the individual patient.
2. Remove the Caspofungin Adamed vial from the refrigerator and allow it to warm to room temperature.
3. Under aseptic conditions, add 10.5 ml of water for injection. The resulting solution may be stored for no longer than 24 hours at a temperature not exceeding 25°C or at 5°C ± 3°C. This results in a vial concentration of caspofungin of 5.2 mg/ml.
4. Withdraw from the vial the volume corresponding to the calculated daily maintenance dose (step 1). Under aseptic conditions, transfer this volume (ml) of diluted Caspofungin Adamed product into an intravenous infusion bag (or bottle) containing 250 ml of 0.9%, 0.45%, or 0.225% sodium chloride injection or lactated Ringer's solution. Alternatively, the specified volume (ml) of diluted Caspofungin Adamed product may be added to a smaller volume of 0.9%, 0.45%, or 0.225% sodium chloride injection or lactated Ringer's solution, provided that the final concentration does not exceed 0.5 mg/ml. The prepared infusion solution should be used within 48 hours if stored at 2°C–8°C or at 25°C.

Notes on preparation of the medicinal product:
a. The white or almost white compact substance should dissolve completely. Gently swirl the contents until a clear solution is obtained.
b. The prepared solution should be inspected visually for particulate matter and discoloration prior to administration. If the solution is cloudy or contains precipitate, it should not be administered.
c. Caspofungin Adamed is formulated so that the full dose stated on the vial label (50 mg) can be withdrawn as 10 ml of solution.