Caspofungin Hikma: detailed information

Package Leaflet: Information for the User

Caspofungin Hikma 50 mg powder for concentrate for solution for infusion

Caspofungin
Generic Medicine
Please read this leaflet carefully before this medicine is administered to you or
to the child, as it contains important information for you.

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

Contents of this leaflet

What Caspofungin is and what it is used for
What you need to know before being given Caspofungin
How to use Caspofungin
Possible side effects
How to store Caspofungin
Contents of the pack and other information

1. What is Caspofungin and what is it used for

What is Caspofungin
Caspofungin Hikma contains a medicine called caspofungin. This belongs to a
group of medicines called antifungals.
What Caspofungin Hikma is used for
Caspofungin Hikma is used to treat the following infections in children, adolescents and adults:

serious fungal infections in tissues and organs (called 'invasive candidiasis'). This infection is caused by fungal cells (yeasts) called Candida. People who may get this type of infection include those who have recently undergone surgery or those who have a weakened immune system. Fever and chills that do not respond to antibiotics are the most common signs of this type of infection.
fungal infections of the nose, sinuses or lungs (called 'invasive aspergillosis') when other antifungal treatments have not worked or have caused unwanted effects. This infection is caused by a mould called Aspergillus. People who may get this type of infection include those receiving chemotherapy, those who have undergone organ transplantation, and those who have a weakened immune system.
suspected fungal infections: if you have fever and a low white blood cell count without improvement after antibiotic therapy. People at risk of developing a fungal infection include those who have recently undergone surgery or those who have a weakened immune system.

How Caspofungin works
Caspofungin makes fungal cells fragile and prevents the fungus from growing properly.
This stops the spread of the infection and allows the body's natural defences the chance
to completely eliminate the infection.

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

Do not use Caspofungin

if you are allergic to caspofungin or to any of the other ingredients of this medicine (listed in section 6). If you are unsure, consult your doctor, nurse, or pharmacist before being administered this medicine.

Warnings and precautions
Talk to your doctor, nurse, or pharmacist before you are given Caspofungin if:

you are allergic to any other medicine
you have ever had liver problems – you may need a different dose of this medicine
you are already taking cyclosporine (used to help prevent organ transplant rejection or suppress the immune system), as your doctor may need additional blood tests during treatment
you have ever had any other medical conditions. If any of the above conditions apply to you (or if you are unsure), consult your doctor, nurse, or pharmacist before being administered Caspofungin. Caspofungin may also cause serious skin adverse reactions such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).

Other medicines and Caspofungin
Inform your doctor, nurse, or pharmacist if you are taking, have recently taken, or might take any other medicines. This includes medicines obtained without a prescription, including herbal medicines. This is because Caspofungin may interfere with the way some other medicines work. Likewise, some other medicines may interfere with the way Caspofungin works.
Inform your doctor, nurse, or pharmacist if you are taking any of the following medicines:

cyclosporine or tacrolimus (used to help prevent organ transplant rejection or suppress the immune system), as your doctor may need additional blood tests during treatment
certain HIV medicines such as efavirenz or nevirapine
phenytoin or carbamazepine (used to treat seizures)
dexamethasone (a steroid)
rifampicin (an antibiotic). If any of the above conditions apply to you (or if you are unsure), consult your doctor, nurse, or pharmacist before being administered Caspofungin.

Pregnancy and breastfeeding
If you are pregnant, breastfeeding, or suspect you may be pregnant, ask your doctor for advice before taking any medicine.

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

Driving and using machines
There is no information suggesting that Caspofungin has an effect on the ability to drive or operate machinery.

3. How to use Caspofungin

Caspofungin must always be prepared and administered by a healthcare professional.
Caspofungin will be administered to you:

Once daily
As a slow injection into a vein (intravenous infusion)
Over approximately 1 hour.

Your doctor will determine the duration of treatment and the daily amount of Caspofungin to be administered. Your doctor will monitor the effect of the medicine on you. If your body weight is over 80 kg, you may require a different dose.

Children and adolescents
The dose for children and adolescents may differ from that for adults.

If you have been given more Caspofungin than you should have
Your doctor will decide the daily amount of Caspofungin you need and the duration of treatment. If you are concerned that you have received too much Caspofungin, inform your doctor or nurse immediately. If you have any doubts about the use of this medicine, consult your doctor, nurse, or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them.
Contact your doctor or nurse immediately if you notice any of the following side effects – you may need urgent medical treatment:

Rash (redness), itching, feeling of warmth, swelling of the face, lips or throat, or breathing difficulties – you may be experiencing a histamine reaction to the medicine.
Breathing difficulties with wheezing or a worsening rash – you may be experiencing an allergic reaction to the medicine.
Cough, severe breathing difficulties – if you are an adult with invasive aspergillosis, you may be experiencing a serious respiratory problem that could lead to respiratory failure.
Rash, skin peeling, sores in the mucous membranes, hives, extensive areas of skin peeling. As with any other prescription medicine, some side effects can be serious. For further information, consult your doctor.

Other side effects in adults include
Common: may affect up to 1 in 10 people:

Decreased hemoglobin (reduced substance in the blood that carries oxygen), decreased white blood cells
Decreased blood albumin (a type of protein), decreased potassium or low potassium levels in the blood
Headache
Phlebitis (inflammation of the vein)
Shortness of breath
Diarrhea, nausea, vomiting
Changes in certain blood test values (including increased values of certain liver parameters)
Itching, rash, skin redness, or excessive sweating
Joint pain
Chills, fever
Itching at the injection site.

Uncommon: may affect up to 1 in 100 people:

Changes in certain blood test values (including blood clotting disorders, platelets, red blood cells, and white blood cells)
Loss of appetite, increased body fluid, electrolyte imbalance, high blood sugar, low blood calcium, increased blood calcium, low blood magnesium, increased blood acid levels
Disorientation, feeling nervous, inability to sleep
Dizziness, decreased sensation or sensitivity (especially at skin level), tremor, drowsiness, altered taste, tingling or numbness
Blurred vision, increased tear production, swollen eyelid, yellowing of the whites of the eyes
Sensation of rapid or irregular heartbeat, fast heartbeat, irregular heartbeat, abnormal heart rhythm, heart failure
Hot flushes, flushing, high blood pressure, low blood pressure, redness of a vein that is extremely painful to pressure
Constriction of the muscular bands in the airways causing shortness of breath or cough, rapid breathing, shortness of breath waking the patient, reduced oxygen in the blood, abnormal breathing sounds, rubbing noise in the lungs, dyspnea, nasal congestion, cough, sore throat
Abdominal pain, upper abdominal pain, abdominal distension, constipation, difficulty swallowing, dry mouth, indigestion, gas, stomach discomfort, swelling due to fluid accumulation in the abdomen
Decreased bile flow, enlarged liver, yellowing of the skin and/or whites of the eyes, liver damage caused by a medicine or chemical agents, liver disorder
Abnormal skin tissue, generalized itching, hives, various types of skin rash, abnormal skin, red spots often itchy on arms and legs and sometimes on the face and other parts of the body
Back pain, pain in arms or legs, bone pain, muscle pain, muscle weakness
Kidney function impairment, sudden loss of kidney function
Pain at catheter site, injection site reactions (redness, small hard lump, pain, swelling, irritation, rash, hives, leakage of fluid from catheter into tissue), phlebitis at injection site
Increased blood pressure and changes in certain blood test values (including renal electrolytes and coagulation parameters), increased levels of medicines you are taking that weaken the immune system
Chest discomfort, chest pain, sensation of body temperature changes, feeling of general malaise, general pain, facial swelling, swelling of ankles, hands or feet, swelling, hypersensitivity, 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
Tachycardia
Flushing, low blood pressure
Changes in certain blood test values (increased values of certain liver tests)
Itching, rash
Pain at catheter site
Chills
Changes in certain blood test values.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, contact your doctor, nurse, or pharmacist. You can also report side effects directly via the national reporting system at the website
www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Caspofungin

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
(the first two digits indicate the month, the following four digits the year). The expiry date refers to the last day of the stated month.
Store in a refrigerator (2°C – 8°C).
Once Caspofungin has been prepared, it must be used immediately. This is because it does not contain ingredients to prevent bacterial growth. Only a trained healthcare professional who has read the complete instructions should prepare this medicine (see below “Instructions for reconstitution and dilution of Caspofungin”).
If not used immediately, the solution may be stored for up to 24 hours at a temperature not exceeding 25°C, or for up to 48 hours when the intravenous infusion bag (bottle) is refrigerated (2°C – 8°C) and diluted with sodium chloride solution for infusion 9 mg/ml (0.9%), 4.5 mg/ml (0.45%) or 2.25 mg/ml (0.225%) or with Ringer's lactate solution. If not used immediately, the storage times and conditions of use are under the responsibility of the user and normally should not exceed 24 hours at 2–8°C, unless reconstitution and dilution have been carried out under controlled, validated aseptic conditions.
Do not use the solution if you notice any signs of discoloration or the presence of particles.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Caspofungin contains

The active substance is caspofungin. Each vial of Caspofungin contains 50 mg of caspofungin (as acetate).
The other excipients are sucrose, mannitol, hydrochloric acid (for pH adjustment), sodium hydroxide (for pH adjustment), carbon dioxide (for pH adjustment) (see section 2. What you need to know before Caspofungin is administered to you).

Description of the appearance of Caspofungin and contents of the pack
A sterile, compact, white to off-white lyophilized powder. The reconstituted solution is clear.
10 ml Type I glass vial with a bromobutyl rubber stopper and a red plastic cap sealed with an aluminum band.
Each pack contains 1 vial of powder.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Hikma Farmacêutica (Portugal) S.A.
Estrada do Rio da Mó n. 8, 8A, 8B
Fervença
2705-906 Terrugem SNT
Portugal

Manufacturer
Pharmadox Healthcare, Ltd
KW20A Kordin Industrial Park, Paola
PLA 3000
Malta

The following information is intended exclusively for medical professionals or healthcare practitioners

Instructions for reconstituting and diluting CASPOFUNGIN:

Reconstitution of CASPOFUNGIN
DO NOT USE DILUENTS CONTAINING DEXTROSE, as CASPOFUNGIN is not stable in diluents containing glucose. DO NOT MIX OR ADMINISTER CASPOFUNGIN IN THE SAME INTRAVENOUS LINE WITH ANY OTHER MEDICINAL PRODUCT, as there are no data available on the compatibility of CASPOFUNGIN with other substances, additives, or intravenous medicinal products. Visually inspect the infusion solution for the presence of particles or discoloration.

INSTRUCTIONS FOR USE IN ADULT PATIENTS

Step 1: Reconstitution of conventional vials
To reconstitute the powder, bring the vial to room temperature and aseptically add 10.5 ml of water for injections. The concentration of the reconstituted solution will be 5.2 mg/ml.
The white to off-white lyophilized powder will dissolve completely. Gently swirl until a clear solution is obtained. Reconstituted solutions must be visually inspected for the presence of particles or color change. The reconstituted solution may be stored for up to 24 hours at temperatures not exceeding 25°C.

Step 2: Adding reconstituted CASPOFUNGIN to the patient's infusion solution
The diluents for the final intravenous infusion solution are: sodium chloride solution for injection or lactated Ringer's solution. The intravenous infusion solution is prepared by aseptically adding the appropriate volume of the reconstituted concentrate (as shown in the following table) to a 250 ml infusion bag or bottle. If medically necessary, reduced infusion volumes down to 100 ml may be used for daily doses of 50 mg or 35 mg. Do not use the solution if it is cloudy or contains precipitates.

PREPARATION OF THE INFUSION SOLUTION FOR ADULTS

DOSE*	Volume of CASPOFUNGINS	Standard preparation (CASPOFUNGINS reconstituted added to 250 ml) final concentration	Reduced infusion volume (CASPOFUNGINS reconstituted added to 100 ml) final concentration
	reconstituted for transfer to IV bag or vial
50 mg	10 ml	0.20 mg/ml
50 mg reduced volume	10 ml		0.47 mg/ml
35 mg for moderate hepatic impairment (from one 50 mg vial)	7 ml	0.14 mg/ml
35 mg for moderate hepatic impairment (from one 50 mg vial) reduced volume	7 ml		0.34 mg/ml

*10.5 ml must be used to reconstitute all vials
INSTRUCTIONS FOR USE IN PEDIATRIC PATIENTS
Calculation of Body Surface Area (BSA) for Pediatric Dosing
Prior to preparing the infusion, calculate the patient's body surface area (BSA) using the following formula: (Mosteller Formula)

Mathematical formula for calculating body surface area BSA in square meters equal to the square root of

Preparation of the 70 mg/m 2 infusion for pediatric patients aged >3 months (using a 50 mg vial)

Determine the appropriate loading dose for pediatric patients using the patient’s BSA (calculated as above) and the following equation: BSA (m²) × 70 mg/m² = Loading Dose. The maximum loading dose on Day 1 must not exceed 70 mg, regardless of the calculated patient dose.
Allow the refrigerated CASPOFUNGIN vial to reach room temperature.
Aseptically add 10.5 ml of Water for Injections. This reconstituted solution may be stored for up to 24 hours at a temperature not exceeding 25°C. This will yield a final caspofungin concentration of 5.2 mg/ml in the vial.
Withdraw from the vial the volume (ml) corresponding to the calculated loading dose (step 1). Aseptically transfer this volume (ml) of reconstituted CASPOFUNGIN into an intravenous (IV) infusion bag (or bottle) containing 250 ml of 0.9%, 0.45%, or 0.225% Sodium Chloride for Injection, or Lactated Ringer’s for Injection. Alternatively, the volume (ml) of reconstituted CASPOFUNGIN may be added to a reduced volume of 0.9%, 0.45%, or 0.225% Sodium Chloride for Injection, or Lactated Ringer’s for Injection, provided that the final concentration does not exceed 0.5 mg/ml. This infusion solution must be used within 24 hours if stored at or below 25°C, or within 48 hours if refrigerated at 2–8°C.

Preparation of the 50 mg/m 2 infusion for pediatric patients aged >3 months (using a 50 mg vial)

Determine the appropriate daily maintenance dose for the pediatric patient using the patient’s BSA (calculated as above) and the following equation: BSA (m²) × 50 mg/m² = Daily Maintenance Dose. The daily maintenance dose must not exceed 70 mg, regardless of the calculated patient dose.
Allow the refrigerated CASPOFUNGIN vial to reach room temperature.
Aseptically add 10.5 ml of Water for Injections. This reconstituted solution may be stored for up to 24 hours at a temperature not exceeding 25°C. This will yield a final caspofungin concentration of 5.2 mg/ml in the vial.
Withdraw from the vial the volume (ml) corresponding to the calculated daily maintenance dose (step 1). Aseptically transfer this volume (ml) of reconstituted CASPOFUNGIN into an intravenous (IV) infusion bag (or bottle) containing 250 ml of 0.9%, 0.45%, or 0.225% Sodium Chloride for Injection, or Lactated Ringer’s for Injection. Alternatively, the volume (ml) of reconstituted CASPOFUNGIN may be added to a reduced volume of 0.9%, 0.45%, or 0.225% Sodium Chloride for Injection, or Lactated Ringer’s for Injection, provided that the final concentration does not exceed 0.5 mg/ml. This infusion solution must be used within 24 hours if stored at or below 25°C, or within 48 hours if refrigerated at 2–8°C.

Preparation Notes:
a The compound, ranging from white to off-white, will dissolve completely. Gently swirl until the solution becomes clear.
b Visually inspect the reconstituted solution for particles or discoloration during reconstitution and before infusion. Do not use if the solution is not clear or contains precipitates.
c CASPOFUNGIN is formulated to deliver the full dose stated on the label (50 mg) when 10 ml is withdrawn from the vial.

Package Leaflet: Information for the User

Caspofungin Hikma 70 mg powder for concentrate for solution for infusion

Caspofungin
Generic Medicine
Please read this leaflet carefully before this medicine is administered to you or
the child, as it contains important information for you

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor, nurse or pharmacist.
If you get any side effects, including those not listed in this leaflet, contact your doctor, nurse or pharmacist. See section 4.

Contents of this leaflet

What Caspofungin is and what it is used for
What you need to know before Caspofungin is administered to you
How to use Caspofungin
Possible side effects
How to store Caspofungin
Contents of the pack and other information

1. What Caspofungin is and what it is used for

What Caspofungin is
Caspofungin Hikma contains a medicine called caspofungin. This belongs to a group of medicines known as antifungals.
What Caspofungin is used for
Caspofungin is used to treat the following infections in children, adolescents, and adults:

severe fungal infections in tissues or organs (called 'invasive candidiasis'). This infection is caused by fungal cells (yeasts) called Candida. People who may get this type of infection include those who have recently undergone surgery or those with a weakened immune system. Fever and chills that do not respond to antibiotics are the most common signs of this type of infection.
fungal infections of the nose, sinuses, or lungs (called 'invasive aspergillosis') when other antifungal treatments have not worked or have caused unwanted effects. This infection is caused by a mold called Aspergillus. People who may get this type of infection include those receiving chemotherapy, those who have undergone organ transplantation, and those with a weakened immune system.
suspected fungal infections: if you have fever and a low white blood cell count without improvement after antibiotic therapy. People at risk of developing a fungal infection include those who have recently undergone surgery or those with a weakened immune system.

How Caspofungin works
Caspofungin makes fungal cells fragile and prevents the fungus from growing properly.
This stops the spread of the infection and allows the body's natural defenses the opportunity to completely eliminate the infection.

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

Do not use Caspofungin

if you are allergic to caspofungin or to any of the other ingredients of this medicine (listed in section 6). If you are unsure, consult your doctor, nurse or pharmacist before being administered this medicine.

Warnings and precautions
Consult your doctor, nurse or pharmacist before being administered
Caspofungin if:

you are allergic to any other medicine
you have ever had liver problems – you may need a different dose of this medicine
you are already taking cyclosporine (used to help prevent rejection of a transplanted organ or to suppress the immune system), as your doctor may need to perform additional blood tests during treatment
you have ever had any other medical condition. If any of the conditions listed above apply to you (or if you are unsure), consult your doctor, nurse or pharmacist before being administered Caspofungin. Caspofungin may also cause serious skin adverse reactions such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).

Other medicines and Caspofungin
Inform your doctor, nurse or pharmacist if you are taking, have recently taken, or might take any other medicines. This includes medicines obtained without a prescription, including herbal medicines. This is because Caspofungin may interfere with the way some other medicines work. Likewise, some other medicines may interfere with the way Caspofungin works.
Inform your doctor, nurse or pharmacist if you are taking any of the following
medicines:

cyclosporine or tacrolimus (used to help prevent rejection of a transplanted organ or to suppress the immune system), as your doctor may need to perform additional blood tests during treatment
certain HIV medicines such as efavirenz or nevirapine
phenytoin or carbamazepine (used to treat seizures)
dexamethasone (a steroid)
rifampicin (an antibiotic).

If any of the conditions listed above apply to you (or if you are unsure), consult your
doctor, nurse or pharmacist before being administered Caspofungin.
Pregnancy and breastfeeding
If you are pregnant, breastfeeding, or think you might be pregnant,
seek advice from your doctor before taking any medicine.

Caspofungin has not been studied in pregnant women. It should be used during pregnancy only if the potential benefit justifies the potential risk to the unborn child.
Women receiving Caspofungin must not breast-feed.

Driving and using machines
There are no data suggesting that Caspofungin has an effect on the
ability to drive or use machinery.

3. How to use Caspofungin

Caspofungin must always be prepared and administered by a healthcare professional.
You will receive Caspofungin:

Once daily
As a slow injection into a vein (intravenous infusion)
Over approximately 1 hour.

Your doctor will determine how long your treatment will last and the daily amount of Caspofungin you will receive. Your doctor will monitor the effect of the medicine on you. If your body weight is over 80 kg, you may require a different dose.

Children and adolescents
The dose for children and adolescents may differ from that for adults.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Contact your doctor or nurse immediately if you notice any of the following side effects – you may need urgent medical treatment:

Rash (redness), itching, feeling of warmth, swelling of the face, lips or throat, or difficulty breathing – you may be experiencing a histamine reaction to the medicine.
Difficulty breathing with wheezing or a worsening rash – you may be experiencing an allergic reaction to the medicine.
Cough, severe breathing difficulties – if you are an adult with invasive aspergillosis, you may be experiencing a serious respiratory problem that could lead to respiratory failure.
Rash, skin peeling, mouth mucosa sores, hives, extensive areas of skin peeling. As with any other prescription medicine, some side effects can be serious. For further information, consult your doctor.

Other side effects in adults include

Common: may affect up to 1 in 10 people:

Decreased hemoglobin (reduced substance in the blood that carries oxygen), decreased white blood cells
Decreased blood albumin (a type of protein), decreased potassium or low blood potassium levels
Headache
Inflammation of the vein
Shortness of breath
Diarrhea, nausea, vomiting
Changes in certain blood test values (including increased values of some liver parameters)
Itching, rash, skin redness, or excessive sweating
Joint pain
Chills, fever
Itching at the injection site.

Uncommon: may affect up to 1 in 100 people:

Changes in certain blood test values (including blood clotting disorders, platelets, red blood cells, and white blood cells)
Loss of appetite, increased body fluid, electrolyte imbalance, high blood sugar, low blood calcium, increased blood calcium, low blood magnesium, increased blood acid levels
Disorientation, feeling nervous, inability to sleep
Dizziness, reduced sensation or sensitivity (especially skin-related), tremor, drowsiness, altered taste, tingling or numbness
Blurred vision, increased tear production, swollen eyelid, yellowing of the whites of the eyes
Sensation of rapid or irregular heartbeat, fast heartbeat, irregular heartbeat, abnormal heart rhythm, heart failure
Hot flushes, flushing, high blood pressure, low blood pressure, redness of a vein that is extremely painful to pressure
Constriction of muscle bands in the airways causing shortness of breath or cough, rapid breathing, shortness of breath waking the patient, reduced oxygen in the blood, abnormal breathing sounds, lung friction noise, dyspnea, nasal congestion, cough, sore throat
Abdominal pain, upper abdominal pain, abdominal distension, constipation, difficulty swallowing, dry mouth, indigestion, flatulence, stomach discomfort, swelling due to fluid accumulation in the abdomen
Decreased bile flow, enlarged liver, yellowing of the skin and/or whites of the eyes, liver damage caused by a medicine or chemical agents, liver disorder
Abnormal skin tissue, generalized itching, hives, various types of skin rash, abnormal skin, red spots often itchy on arms and legs and sometimes on the face and rest of the body
Back pain, arm or leg pain, bone pain, muscle pain, muscle weakness
Loss of kidney function, sudden loss of kidney function
Pain at catheter site, discomfort at injection site (redness, small hard lump, pain, swelling, irritation, rash, hives, leakage of fluid from catheter into tissue), inflammation of the vein at injection site
Increased blood pressure and changes in certain blood test values (including renal electrolytes and coagulation parameters), increased levels of medicines you are taking that weaken the immune system
Chest discomfort, chest pain, sensation of body temperature change, feeling of general malaise, general pain, facial swelling, swelling of ankles, hands or feet, swelling, hypersensitivity, 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
Tachycardia
Flushing, low blood pressure
Changes in certain blood test values (increased values in some liver-related tests)
Itching, rash
Pain at catheter site
Chills
Changes in certain blood test values.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, nurse, or pharmacist. You can also report side effects directly via the national reporting system at the website
http://www.agenziafarmaco.gov.it/it/responsabili
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Caspofungin

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
(the first two digits indicate the month, the following four digits the year). The expiry date refers to the last day of the month.
Store in the refrigerator (2 °C–8 °C).
Once Caspofungin has been prepared, it must be used immediately. This is because it does not contain ingredients to prevent bacterial growth. Only a trained healthcare professional who has read the complete instructions should prepare this medicine (see below “Instructions for reconstitution and dilution of Caspofungin”).
If not used immediately, the solution may be stored for up to 24 hours at a temperature not exceeding 25°C, or for up to 48 hours when the intravenous infusion bag (bottle) is refrigerated (2°C–8°C) and diluted with sodium chloride 9 mg/ml (0.9%), 4.5 mg/ml (0.45%), or 2.25 mg/ml (0.225%) solution for infusion or Ringer’s lactate solution. If not used immediately, the storage times and conditions prior to use are the responsibility of the user and normally should not exceed 24 hours at 2–8°C, unless reconstitution and dilution have been carried out under controlled and validated aseptic conditions.
Do not use the solution if you notice any signs of discoloration or particles in suspension.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Caspofungin contains

The active substance is caspofungin. Each Caspofungin vial contains 70 mg of caspofungin (as acetate).
The other excipients are sucrose, mannitol, hydrochloric acid (for pH adjustment), sodium hydroxide (for pH adjustment), and carbon dioxide (for pH adjustment) (see section 2. What you need to know before Caspofungin is given to you).

Description of the appearance of Caspofungin and contents of the pack
A sterile, white to off-white lyophilized compact powder. The reconstituted solution is clear.
10 ml glass vial of type I, with a bromobutyl rubber stopper and an orange plastic cap sealed with an aluminium seal.
Each pack contains 1 vial of powder.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Hikma Farmacêutica (Portugal) S.A.
Estrada do Rio da Mó n. 8, 8A, 8B
Fervença
2705-906 Terrugem SNT
Portugal

Manufacturer
Pharmadox Healthcare, Ltd
KW20A Kordin Industrial Park, Paola
PLA 3000
Malta

The following information is intended exclusively for medical professionals or healthcare practitioners
Instructions for reconstituting and diluting CASPOFUNGIN:
Reconstitution of CASPOFUNGIN
DO NOT USE DILUENTS CONTAINING GLUCOSE as CASPOFUNGIN is not stable in diluents containing glucose. DO NOT MIX OR ADMINISTER CASPOFUNGIN THROUGH THE SAME INTRAVENOUS LINE AS ANY OTHER MEDICINAL PRODUCT, as there are no data available on the compatibility of CASPOFUNGIN with other substances, additives, or intravenous medicinal products. Visually inspect the infusion solution for the presence of particles or discoloration.

INSTRUCTIONS FOR USE IN ADULT PATIENTS
Step 1: Reconstitution of conventional vials
To reconstitute the powder, allow the vial to reach room temperature and aseptically add 10.5 ml of water for injection. The concentration of the reconstituted solution will be 7.2 mg/ml.
The white to off-white lyophilized compact powder will dissolve completely. Gently swirl until a clear solution is obtained. Reconstituted solutions must be visually inspected for the presence of particles or color change. This reconstituted solution may be stored for up to 24 hours at temperatures equal to or below 25°C.

Step 2: Adding reconstituted CASPOFUNGIN to the patient's infusion solution
The diluents for the final intravenous infusion solution are: sodium chloride solution for injection or lactated Ringer's solution. The intravenous infusion solution is prepared by aseptically adding the appropriate amount of reconstituted concentrate (as shown in the table below) to a 250 ml infusion bag or bottle. From a medical standpoint, if necessary, reduced infusion volumes of 100 ml may be used for daily doses of 50 mg or 35 mg. Do not use if the solution is cloudy or contains precipitates.

PREPARATION OF THE INFUSION SOLUTION IN ADULTS

DOSE*	Volume of reconstituted CASPOFUNGIN to be transferred into the intravenous bag or bottle	Standard preparation (reconstituted CASPOFUNGIN added to 250 ml) final concentration	Reduced infusion volume (reconstituted CASPOFUNGIN added to 100 ml) final concentration
70 mg	10 ml	0.28 mg/ml	Not recommended
70 mg (from two 50 mg vials)**	14 ml	0.28 mg/ml	Not recommended
35 mg for moderate hepatic impairment (from one 70 mg vial)	5 ml	0.14 mg/ml	0.34 mg/ml

*10.5 ml must be used to reconstitute all vials
**if the 70 mg vial is not available, the 70 mg dose can be prepared from two
50 mg vials

INSTRUCTIONS FOR USE IN PEDIATRIC PATIENTS
Calculation of Body Surface Area (BSA) for pediatric dosing
Before preparing the infusion, calculate the patient's body surface area (BSA) using the following formula: (Mosteller Formula)

Mathematical formula for calculating body surface area BSA in square meters relating height in cm and weight in kg divided by 3600

Preparation of 70 mg/m infusion for pediatric patients aged >3 months (using a
70 mg vial)

Determine the appropriate loading dose to be used in pediatric patients using the patient’s BSA (calculated as above) and the following equation: BSA (m²) × 70 mg/m² = Loading Dose. The maximum loading dose on Day 1 must not exceed 70 mg, regardless of the calculated patient dose.
Allow the refrigerated CASPOFUNGIN vial to reach room temperature.
Aseptically add 10.5 ml of Water for Injections.

The reconstituted solution may be stored for up to 24 hours at a temperature not exceeding 25°C.
This will provide a final caspofungin concentration in the vial of 7.2 mg/ml.

Withdraw from the vial the volume (ml) of medication corresponding to the calculated loading dose (Step 1). Aseptically transfer this volume (ml) of reconstituted CASPOFUNGIN into an intravenous infusion bag (or bottle) containing 250 ml of 0.9%, 0.45%, or 0.225% Sodium Chloride for Injection, or Lactated Ringer's for Injection. Alternatively, the volume (ml) of reconstituted CASPOFUNGIN may be added to a reduced volume of 0.9%, 0.45%, or 0.225% Sodium Chloride for Injection, or Lactated Ringer's for Injection, provided that the final concentration does not exceed 0.5 mg/ml. This infusion solution must be used within 24 hours if stored at a temperature not exceeding 25°C, or within 48 hours if stored refrigerated between 2°C and 8°C.

Preparation of 50 mg/m infusion for pediatric patients aged >3 months (using a
70 mg vial)

Determine the appropriate daily maintenance dose to be used in the pediatric patient using the patient’s BSA (calculated as above) and the following equation: BSA (m²) × 50 mg/m² = Daily Maintenance Dose. The daily maintenance dose must not exceed 70 mg, regardless of the calculated patient dose.
Allow the refrigerated CASPOFUNGIN vial to reach room temperature.
Aseptically add 10.5 ml of Water for Injections. The reconstituted solution may be stored for up to 24 hours at a temperature not exceeding 25°C. This will provide a final caspofungin concentration in the vial of 7.2 mg/ml.
Withdraw from the vial the volume (ml) of medication corresponding to the calculated daily maintenance dose (Step 1). Aseptically transfer this volume (ml) of reconstituted CASPOFUNGIN into an intravenous infusion bag (or bottle) containing 250 ml of 0.9%, 0.45%, or 0.225% Sodium Chloride for Injection, or Lactated Ringer's for Injection. Alternatively, the volume (ml) of reconstituted CASPOFUNGIN may be added to a reduced volume of 0.9%, 0.45%, or 0.225% Sodium Chloride for Injection, or Lactated Ringer's for Injection, provided that the final concentration does not exceed 0.5 mg/ml. This infusion solution must be used within 24 hours if stored at a temperature not exceeding 25°C, or within 48 hours if stored refrigerated between 2°C and 8°C.

Preparation Notes:
a The white to off-white powder will dissolve completely. Gently swirl until the solution becomes clear.
b Visually inspect the reconstituted solution for particles or discoloration during reconstitution and before infusion. Do not use if the solution is not clear or contains precipitates.
c CASPOFUNGIN is formulated to deliver the full labeled dose (70 mg) when 10 ml are withdrawn from the vial.