CANCIDAS 70 mg POWDER FOR CONCENTRATE FOR INFUSION SOLUTION

2. What you need to know before you use Cancidas

Do not use Cancidas

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

If you are not sure, talk to your doctor, pharmacist, or nurse before using your medicine.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before using Cancidas 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 cyclosporin (which is used to prevent organ transplant rejection or to suppress your immune system), as your doctor may need to perform additional blood tests during treatment

• you have ever had any other medical problem.

If any of the above applies to you (or you are not sure), talk to your doctor, pharmacist, or nurse before using Cancidas.

Cancidas can also cause severe skin reactions, such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).

Other medicines and Cancidas

Tell your doctor, pharmacist, or nurse if you are using, have recently used, or might use any other medicines. This includes medicines obtained without a prescription, including herbal medicines. This is because Cancidas can affect how other medicines work. Also, other medicines can affect how Cancidas works.

Tell your doctor, pharmacist, or nurse if you are taking any of the following medicines:

• cyclosporin or tacrolimus (which are used to prevent organ transplant rejection or to suppress your immune system), as your doctor may need to perform additional blood tests during treatment
• certain anti-HIV medicines such as efavirenz or nevirapine
• phenytoin or carbamazepine (which are used to treat seizures)
• dexamethasone (a steroid)
• rifampicin (an antibiotic).

If any of the above applies to you (or you are not sure), talk to your doctor, pharmacist, or nurse before using Cancidas.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before using this medicine.

• Cancidas has not been studied in pregnant women. It should only be used during pregnancy if the potential benefit justifies the potential risk to the unborn baby.
• Women using Cancidas should not breastfeed.

Driving and using machines

There is no information to suggest that Cancidas affects your ability to drive or use machines.

Cancidas contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per vial; this is essentially “sodium-free”.

3. How to use Cancidas

Cancidas will always be prepared and given to you by a healthcare professional.

You will be given Cancidas:

• once a day
• by slow injection into a vein (intravenous infusion)
• over about 1 hour.

Your doctor will decide how long you should receive Cancidas and how much you should receive each day. Your doctor will monitor whether the effect of the medicine is adequate. If you weigh more than 80 kg, you may need a different dose.

Use in children and adolescents

The dose for children and adolescents may be different from the dose in adults.

If you use more Cancidas than you should

Your doctor will decide how much Cancidas you need and for how long each day. If you are worried that you have been given too much Cancidas, tell your doctor or nurse immediately.

If you have any other questions about the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Tell your doctor or nurse immediately if you notice any of the following side effects – you may need urgent medical treatment:

• rash, itching, feeling of warmth, swelling of your face, lips, or throat, or difficulty breathing: you may be having a histamine reaction to the medicine.
• difficulty breathing with wheezing or worsening of a rash that you already have: you may be having an allergic reaction to the medicine.
• cough, severe breathing difficulties: if you are an adult and have invasive aspergillosis, you may experience a severe respiratory problem that could lead to respiratory failure.
• rash, skin peeling, blisters on the mucous membrane, hives, large areas of skin peeling.

As with any prescription medicine, some side effects can be serious. Ask your doctor for more information.

Other side effects in adults include:

Common: may affect up to 1 in 10 people:

• decrease in hemoglobin (decrease in the substance that carries oxygen in the blood), decrease in white blood cells
• decrease in albumin (a type of protein) in your blood, decrease in potassium or low potassium levels in the blood
• headache
• vein inflammation
• shortness of breath
• diarrhea, nausea, or vomiting
• changes in some laboratory blood tests (such as increased values of some liver tests)
• itching, rash, redness of the skin, or sweating more than usual
• joint pain
• chills, fever
• itching at the injection site.

Uncommon: may affect up to 1 in 100 people:

• changes in some laboratory blood tests (including blood clotting disorders, platelets, red blood cells, and white blood cells)
• loss of appetite, increase in body fluid, imbalance of body salts, high blood sugar, low calcium levels in the blood, high calcium levels in the blood, low magnesium levels in the blood, increase in the level of medicines you are taking that weaken your immune system
• disorientation, feeling nervous, inability to sleep
• feeling dizzy, decrease in sensations or sensitivity (especially in the skin), agitation, feeling sleepy, change in the way things taste, tingling or numbness
• blurred vision, increased tears, swollen eyelid, yellowing of the white part of the eyes
• feeling of rapid or irregular heartbeats, rapid heartbeat, irregular heartbeat, abnormal heart rhythm, heart failure
• flushing, hot flashes, high blood pressure, low blood pressure, redness along a vein that is very sensitive to touch
• tightness in the muscle bands around the airways, leading to wheezing or cough, rapid breathing rate, waking up short of breath, lack of oxygen in the blood, abnormal breathing sounds, crackling sounds in the lungs, wheezing, nasal congestion, cough, sore throat
• abdominal pain, pain in the upper abdomen, abdominal swelling, constipation, difficulty swallowing, dry mouth, indigestion, passing gas, stomach upset, swelling due to fluid accumulation around the abdomen
• decrease in bile flow, increase in liver size, yellowing of the skin and/or the white part of the eyes, liver injury caused by a medicine or chemical, liver disorder
• abnormal skin tissue, generalized itching, hives, rash of varying appearance, abnormal skin, red spots, often with itching, on arms and legs and sometimes on the face and the rest of the body
• back pain, pain in an arm or leg, bone pain, muscle pain, muscle weakness
• loss of kidney function, sudden loss of kidney function
• pain at the catheter site, symptoms at the injection site (redness, hard lump, pain, swelling, irritation, rash, hives, leakage of fluid from the catheter into the tissue), vein inflammation at the injection site
• increase in blood pressure and changes in some laboratory blood tests (such as kidney electrolyte tests and coagulation tests), increase in levels of medicines you are taking that weaken your immune system
• chest discomfort, chest pain, feeling of change in body temperature, feeling unwell, general pain, swelling of the face, swelling of the ankles, hands, or feet, swelling, pain when touched, feeling tired.

Other 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 heartbeat
• flushing, low blood pressure
• changes in some laboratory blood tests (increased values of some liver tests)
• itching, rash
• pain at the catheter site
• chills
• changes in some laboratory blood tests

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if they are not listed in this leaflet. You can also report side effects directly through the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Cancidas

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and vial (the first two numbers are the month; the next four numbers are the year). The expiry date is the last day of the month stated.

Store in a refrigerator (between 2°C and 8°C).

Once Cancidas has been prepared, it should be used immediately. This is because it does not contain any preservative to prevent bacterial growth. Only a trained healthcare professional who has read the complete instructions should prepare the medicine (see “Instructions for reconstituting and diluting Cancidas” below).

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Container Contents and Additional Information

Composition of Cancidas

• The active ingredient is caspofungina.

Cancidas 50 mg powder for concentrate for solution for infusion

Each vial of Cancidas contains 50 mg of caspofungina.

Cancidas 70 mg powder for concentrate for solution for infusion

Each vial of Cancidas contains 70 mg of caspofungina.

• The other ingredients are sucrose, mannitol (E-421), glacial acetic acid, and sodium hydroxide (see section 2 What you need to know before you start using Cancidas).

Appearance of the Product and Container Contents

Cancidas is a compact, sterile, white to off-white powder.

Each container contains one vial of powder.

Marketing Authorization Holder and Manufacturer

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Date of Last Revision of this Leaflet:

Detailed information on this medicine is available on the European Medicines Agency website: https://www.ema.europa.eu.

This information is intended for healthcare professionals only:

Instructions for reconstituting and diluting CANCIDAS:

Reconstitution of CANCIDAS

DO NOT USE DILUENTS CONTAINING GLUCOSE, as CANCIDAS is not stable in diluents containing glucose. DO NOT MIX OR INFUSE CANCIDAS WITH ANY OTHER MEDICINE, as there are no data available on the compatibility of CANCIDAS with other substances, additives, or pharmaceutical intravenous products. The infusion solution should be inspected visually for particulate matter or color change.

CANCIDAS 50 mg powder for concentrate for solution for infusion

INSTRUCTIONS FOR USE IN ADULT PATIENTS (50 mg vial)

Step 1 Reconstitution of the vials

To reconstitute the powder, bring the vial to room temperature and add aseptically 10.5 ml of water for injectable preparations. The concentration of the reconstituted vial will be 5.2 mg/ml.

The compact, lyophilized, white to off-white powder will dissolve completely. Mix gently until a clear solution is obtained. The reconstituted solutions should be inspected visually for particulate matter or color change. The reconstituted solution can be stored for up to 24 hours at a temperature of 25°C or below.

Step 2 Addition of reconstituted CANCIDAS to the patient's infusion solution

The diluents for the final infusion solution are: sodium chloride injection solution or lactated Ringer's solution. The infusion solution is prepared by adding aseptically the appropriate amount of reconstituted concentrate (as shown in the table below) to a 250 ml IV bag or bottle. Reduced volume infusions in 100 ml can be used if medically necessary for daily doses of 50 mg or 35 mg. Do not use if the solution is turbid or has precipitated.

VIAL of 50 mg: PREPARATION OF THE INFUSION SOLUTION FOR ADULTS

*10.5 ml should be used for the reconstitution of all vials.

INSTRUCTIONS FOR USE IN PEDIATRIC PATIENTS (50 mg vial)

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[1])

Preparation of the 70 mg/m2 infusion for pediatric patients >3 months (using a 50 mg vial)

1. Determine the actual loading dose to be used in the pediatric patient using the patient's BSA (as calculated above) and the following equation:

BSA (m2) X 70 mg/m2 = loading dose

The maximum loading dose on day 1 should not exceed 70 mg, regardless of the calculated dose for the patient.

1. Wait for the refrigerated CANCIDAS vial to reach room temperature.
2. Aseptically, add 10.5 ml of water for injectable preparations. This reconstituted solution can be stored for up to 24 hours at a temperature of 25°C or below. This will result in a final concentration of caspofungina in the vial of 5.2 mg/ml.
3. Withdraw from the vial a volume of the drug equal to the calculated loading dose (Step 1). Transfer aseptically this volume (ml) of reconstituted CANCIDAS to an IV bag (or bottle) containing 250 ml of injectable sodium chloride solution 0.9%, 0.45%, or 0.225%, or lactated Ringer's solution. Alternatively, the volume (ml) of reconstituted CANCIDAS can be added to a reduced volume of injectable sodium chloride solution 0.9%, 0.45%, or 0.225%, or lactated Ringer's solution, without exceeding a final concentration of 0.5 mg/ml. This infusion solution should be used within 24 hours if stored at a temperature of 25°C or below or within 48 hours if stored refrigerated between 2 and 8°C.

Preparation of the 50 mg/m2 infusion for pediatric patients >3 months (using a 50 mg vial)

1. Determine the actual daily maintenance dose to be used in the pediatric patient using the patient's BSA (as calculated above) and the following equation:

BSA (m2) X 50 mg/m2 = daily maintenance dose

The daily maintenance dose should not exceed 70 mg, regardless of the calculated dose for the patient.

1. Wait for the refrigerated CANCIDAS vial to reach room temperature.
2. Aseptically, add 10.5 ml of water for injectable preparations. This reconstituted solution can be stored for up to 24 hours at a temperature of 25°C or below. This will result in a final concentration of caspofungina in the vial of 5.2 mg/ml.
3. Withdraw from the vial a volume of the drug equal to the calculated daily maintenance dose (Step 1). Transfer aseptically this volume (ml) of reconstituted CANCIDAS to an IV bag (or bottle) containing 250 ml of injectable sodium chloride solution 0.9%, 0.45%, or 0.225%, or lactated Ringer's solution. Alternatively, the volume (ml) of reconstituted CANCIDAS can be added to a reduced volume of injectable sodium chloride solution 0.9%, 0.45%, or 0.225%, or lactated Ringer's solution, without exceeding a final concentration of 0.5 mg/ml. This infusion solution should be used within 24 hours if stored at a temperature of 25°C or below or within 48 hours if stored refrigerated between 2 and 8°C.

Preparation Notes:

• The white to off-white cake will dissolve completely. Mix gently until a clear solution is obtained.

• Inspect the reconstituted solution visually for particulate matter or color change during reconstitution and before infusion. Do not use if the solution is turbid or has precipitated.

• CANCIDAS is formulated to provide the full dose of the vial as stated on the label (50 mg) when 10 ml is withdrawn from the vial.

CANCIDAS 70 mg powder for concentrate for solution for infusion

INSTRUCTIONS FOR USE IN ADULT PATIENTS (70 mg vial)

Step 1 Reconstitution of the vials

To reconstitute the powder, bring the vial to room temperature and add aseptically 10.5 ml of water for injectable preparations. The concentration of the reconstituted vial will be 7.2 mg/ml.

The compact, lyophilized, white to off-white powder will dissolve completely. Mix gently until a clear solution is obtained. The reconstituted solutions should be inspected visually for particulate matter or color change. The reconstituted solution can be stored for up to 24 hours at a temperature of 25°C or below.

Step 2 Addition of reconstituted CANCIDAS to the patient's infusion solution

The diluents for the final infusion solution are: sodium chloride injection solution or lactated Ringer's solution. The infusion solution is prepared by adding aseptically the appropriate amount of reconstituted concentrate (as shown in the table below) to a 250 ml IV bag or bottle. Reduced volume infusions in 100 ml can be used if medically necessary for daily doses of 50 mg or 35 mg. Do not use if the solution is turbid or has precipitated.

VIAL of 70 mg: PREPARATION OF THE INFUSION SOLUTION FOR ADULTS

*10.5 ml should be used for the reconstitution of 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 (70 mg vial)

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[2])

Preparation of the 70 mg/m2 infusion for pediatric patients >3 months (using a 70 mg vial)

1. Determine the actual loading dose to be used in the pediatric patient using the patient's BSA (as calculated above) and the following equation:

BSA (m2) X 70 mg/m2 = loading dose

The maximum loading dose on day 1 should not exceed 70 mg, regardless of the calculated dose for the patient.

1. Wait for the refrigerated CANCIDAS vial to reach room temperature.
2. Aseptically, add 10.5 ml of water for injectable preparations. This reconstituted solution can be stored for up to 24 hours at a temperature of 25°C or below. This will result in a final concentration of caspofungina in the vial of 7.2 mg/ml.
3. Withdraw from the vial a volume of the drug equal to the calculated loading dose (Step 1). Transfer aseptically this volume (ml) of reconstituted CANCIDAS to an IV bag (or bottle) containing 250 ml of injectable sodium chloride solution 0.9%, 0.45%, or 0.225%, or lactated Ringer's solution. Alternatively, the volume (ml) of reconstituted CANCIDAS can be added to a reduced volume of injectable sodium chloride solution 0.9%, 0.45%, or 0.225%, or lactated Ringer's solution, without exceeding a final concentration of 0.5 mg/ml. This infusion solution should be used within 24 hours if stored at a temperature of 25°C or below or within 48 hours if stored refrigerated between 2 and 8°C.

Preparation of the 50 mg/m2 infusion for pediatric patients >3 months (using a 70 mg vial)

1. Determine the actual daily maintenance dose to be used in the pediatric patient using the patient's BSA (as calculated above) and the following equation:

BSA (m2) X 50 mg/m2 = daily maintenance dose

The daily maintenance dose should not exceed 70 mg, regardless of the calculated dose for the patient.

1. Wait for the refrigerated CANCIDAS vial to reach room temperature.
2. Aseptically, add 10.5 ml of water for injectable preparations. This reconstituted solution can be stored for up to 24 hours at a temperature of 25°C or below. This will result in a final concentration of caspofungina in the vial of 7.2 mg/ml.

1. To reconstitute the powder, add 10.5 ml of water for injections to the vial. This reconstituted solution can be stored for up to 24 hours at a temperature of 25 °C or below. This will result in a final concentration of caspofungina in the vial of 7.2 mg/ml.
2. Withdraw from the vial a volume of the medication equal to the calculated daily maintenance dose (Step 1). Transfer this volume (ml) of reconstituted CANCIDAS aseptically to an IV bag (or bottle) containing 250 ml of 0.9%, 0.45%, or 0.225% sodium chloride injection solution, or lactated Ringer's solution. Alternatively, the volume (ml) of reconstituted CANCIDAS can be added to a reduced volume of 0.9%, 0.45%, or 0.225% sodium chloride injection solution, or lactated Ringer's solution, without exceeding a final concentration of 0.5 mg/ml. This infusion solution should be used within 24 hours if stored at a temperature of 25 °C or below, or within 48 hours if stored refrigerated between 2 and 8 °C.

Preparation Notes:

• The white to off-white cake will dissolve completely. Mix gently until a clear solution is obtained.

• Visually inspect the reconstituted solution for particulate matter or color change during reconstitution and prior to infusion. Do not use if the solution is cloudy or has precipitated.

• CANCIDAS is formulated to provide the full dose of the vial as stated on the label (70 mg) when 10 ml is withdrawn from the vial.

[1] Mosteller RD: Simplified Calculation of Body Surface Area. N Engl J Med1987 Oct 22;317(17):1098 (letter)

[2] Mosteller RD: Simplified Calculation of Body Surface Area. N Engl J Med1987 Oct 22;317(17):1098 (letter)