Cancidas (previously Caspofungin MSD) - patient leaflet, side effects, dosage

B. PACKAGE LEAFLET

Package Leaflet: Information for the user

Cancidas 50 mg powder for concentrate for solution for infusion

Cancidas 70 mg powder for concentrate for solution for infusion caspofungin

Read all of this leaflet carefully before you or your child are given this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have further questions, please ask your doctor, nurse or pharmacist.
• If you get any side effects, talk to your doctor, nurse or pharmacist. This includes any possible

side effects not listed in this leaflet. See section 4.

What is in this leaflet

• 1. What Cancidas is and what it is used for

• 2. What you need to know before you are given Cancidas

• 3. How to use Cancidas

• 4. Possible side effects

• 5. How to store Cancidas

• 6. Contents of the pack and other information

1. What Cancidas is and what it is used for

What Cancidas is

Cancidas contains a medicine called caspofungin. This belongs to a group of medicines called anti-fungals.

What Cancidas is used for

Cancidas is used to treat the following infections in children, adolescents and adults:

• serious fungal infections in your tissues or organs (called ‘invasive candidiasis’). This infection is caused by fungal (yeast) cells called Candida.

People who might get this type of infection include those who have just had an operation or those whose immune systems are weak. Fever and chills that do not respond to an antibiotic are the most common signs of this type of infection.

• fungal infections in your nose, nasal sinuses or lungs (called ‘invasive aspergillosis’) if other anti-fungal treatments have not worked or have caused side effects. This infection is caused by a mould called Aspergillus.

People who might get this type of infection include those having chemotherapy, those who have had a transplant and those whose immune systems are weak.

• suspected fungal infections if you have a fever and a low white cell count that have not

improved on treatment with an antibiotic. People who are at risk of getting a fungal infection include those who have just had an operation or those whose immune systems are weak.

How Cancidas works

Cancidas makes fungal cells fragile and stops the fungus from growing properly. This stops the infection from spreading and gives the body’s natural defences a chance to completely get rid of the infection.

2. What you need to know before you are given 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, nurse or pharmacist before you are given your medicine.

Warnings and precautions

Talk to your doctor, nurse or pharmacist before you are given Cancidas if:

• you are allergic to any other medicines
• you have ever had liver problems – you might need a different dose of this medicine
• you are already taking cyclosporin (used to help prevent organ transplant rejection or to suppress your immune system) – as your doctor may need to run extra blood tests during your treatment.
• if 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, nurse or pharmacist before you are given Cancidas.

Cancidas may also cause Serious Cutaneous Adverse Reactions such as Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN).

Other medicines and Cancidas

Please tell 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 Cancidas can affect the way some other medicines work. Also, some other medicines can affect the way Cancidas works.

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

• cyclosporin or tacrolimus (used to help prevent organ transplant rejection or to suppress your immune system) as your doctor may need to run extra blood tests during your treatment
• some HIV medicines such as efavirenz or nevirapine
• phenytoin or carbamazepine (used for the treatment of seizures)
• dexamethasone (a steroid)
• rifampicin (an antibiotic).

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

Pregnancy and breast-feeding

Ask your doctor for advice before taking any medicine, if you are pregnant or breast-feeding or think you are pregnant.

• Cancidas has not been studied in pregnant women. It should be used in pregnancy only if the

potential benefit justifies the potential risk to the unborn baby.

• Women given Cancidas should not breast-feed.

Driving and using machines

There is no information to suggest that Cancidas affects your ability to drive or operate machinery.

Cancidas contains sodium

This medicine contains less than 1 mmol sodium (23 mg) per vial, that is to say 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 each day
• by slow injection into a vein (intravenous infusion)
• over about 1 hour.

Your doctor will determine the duration of your treatment and how much Cancidas you will be given each day. Your doctor will monitor how well the medicine works for you. If you weigh more than 80 kg, you may need a different dose.

Children and adolescents

The dose for children and adolescents may differ from the adult dose.

If you have been given 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 may have been given too much Cancidas, tell your doctor or nurse straight away.

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

4. Possible side effects

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

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

• rash, itching, feeling warm, 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 a rash that gets worse – you may be having an allergic

reaction to the medicine.

• cough, serious breathing difficulties – if you are an adult and have invasive aspergillosis you may be experiencing a serious respiratory problem that could result in respiratory failure.
• rash, skin peeling, mucous membrane sores, hives, large areas of peeling skin.

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

Other side effects in adults include:

Common : may affect up to 1 in 10 people:

• Decreased haemoglobin (decreased oxygen carrying substance in the blood), decreased white blood cells
• Decreased blood albumin (a type of protein) in your blood, decreased potassium or low potassium levels in the blood
• Headache
• Inflammation of the vein
• Shortness of breath
• Diarrhoea, nausea or vomiting
• Changes in some laboratory blood tests (including increased values of some liver tests)
• Itching, rash, skin redness 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 disease of blood clotting, platelets, red blood cells and white blood cells)
• Loss of appetite, increase in amount of body fluid, imbalance of salt in the body, high sugar level in the blood, low calcium level in the blood, increase calcium level in the blood, low magnesium level in the blood, increase in acid level in the blood
• Disorientation, feeling nervous, being unable to sleep
• Feeling dizzy, decreased feeling or sensitivity (especially in the skin), shaking, feeling sleepy, change in the way things taste, tingling or numbness
• Blurred vision, increase in tears, swollen eyelid, yellowing of the whites of the eyes
• Sensation of fast or irregular heartbeats, rapid heartbeat, irregular heartbeat, abnormal heart

rhythm, heart failure

• Flushing, hot flush, high blood pressure, low blood pressure, redness along a vein which is extremely tender when touched
• Tightening of the bands of muscle around the airways resulting in wheezing or coughing, fast

breathing rate, shortness of breath that wakes you up, shortage of oxygen in the blood, abnormal breath sounds, crackling sounds in the lungs, wheezing, nasal congestion, cough, throat pain

• Belly pain, upper belly pain, bloating, constipation, difficulty swallowing, dry mouth,

indigestion, passing gas, stomach discomfort, swelling due to build-up of fluid around the belly

• Decreased flow of bile, enlarged liver, yellowing of the skin and/or whites of the eyes, liver injury caused by a drug or chemical, liver disorder
• Abnormal skin tissue, generalised itching, hives, rash of varying appearance, abnormal skin, red often itchy spots on your 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
• Catheter site pain, injection site complaints (redness, hard lump, pain, swelling, irritation, rash,

hives, leaking of fluid from the catheter into the tissue), inflammation of vein at injection site

• Increased blood pressure and alterations in some laboratory blood tests (including kidney electrolyte and clotting tests), increased levels of the medicines you are taking that weaken the immune system
• Chest discomfort, chest pain, feeling of body temperature change, generally feeling unwell,

general pain, swelling of the face, swelling of the ankles, hands or feet, swelling, tenderness, feeling tired.

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
• Fast heart beat
• Flushing, low blood pressure
• Changes in some laboratory blood tests (increased values of some liver tests)
• Itching, rash
• Catheter site pain
• Chills
• Changes in some laboratory blood tests.

Reporting of side effects

If you get any side effects, talk to your doctor, nurse or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store 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 the vial (the first two numbers are the month; the next four numbers are the year). The expiry date refers to the last day of that month.

Store in a refrigerator (2°C to 8°C).

Once Cancidas has been prepared, it should be used straight away. This is because it does not contain any ingredients to stop the growth of bacteria. Only a trained healthcare professional who has read the complete directions should prepare the medicine (please see below “Instructions of how to reconstitute and dilute Cancidas”).

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help to protect the environment.

6. Contents of the pack and other information

The other ingredients are sucrose, mannitol (E421), glacial acetic acid and sodium hydroxide (please see section 2 What you need to know before you are given Cancidas).

What Cancidas looks like and contents of the pack

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

Each pack contains one vial of powder.

Marketing Authorisation Holder and Manufacturer

For any information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

E^^rapus

MepK Oapn u ^oyM E^nrapna EOO^

Te^.: +359 2 819 3737

Česká republika

Merck Sharp & Dohme s.r.o.

Tel.: +420 233 010 111

Danmark

MSD Danmark ApS

Tlf: +45 44 82 40 00

Deutschland

MSD Sharp & Dohme GmbH

Tel: 0800 673 673 673 (+49 (0) 89 4561 0)

Eesti

Merck Sharp & Dohme OÜ

Tel.: +372 6144 200

EZZárta

MSD A.O.B.E.E

TqX: + 30 210 98 97 300

España

Merck Sharp & Dohme de España, S.A.

Tel: +34 91 321 06 00

France

MSD France

Tél: + 33 (0) 1 80 46 40 40

Hrvatska

Merck Sharp & Dohme d.o.o.

Tel: + 385 1 6611 333

Ireland

Merck Sharp & Dohme Ireland (Human Health)

Limited

Tel: +353 (0)1 2998700

Ísland

Vistor hf.

Sími: +354 535 7000

Luxembourg/Lu­xemburg

MSD Belgium

Tél/Tel: +32(0)27766211

Magyarország

MSD Pharma Hungary Kft.

Tel.: +36 1 888 5300

Malta

Merck Sharp & Dohme Cyprus Limited

Tel.: 8007 4433 (+ 356 99917558)

Nederland

Merck Sharp & Dohme B.V.

Tel: 0800 9999000 (+31 23 5153153)

Norge

MSD (Norge) AS

Tlf: +47 32 20 73 00

Österreich

Merck Sharp & Dohme Ges.m.b.H.

Tel: +43 (0) 1 26 044

Polska

MSD Polska Sp. z o.o.

Tel.: +48 22 549 51 00

Portugal

Merck Sharp & Dohme, Lda

Tel: +351 21 4465700

România

Merck Sharp & Dohme Romania S.R.L.

Tel: + 4021 529 29 00

Slovenija

Merck Sharp & Dohme, inovativna zdravila d.o.o.

Tel: + 386 1 5204201

Slovenská republika

Merck Sharp & Dohme, s. r. o.

Tel.: +421 2 58282010

Italia

MSD Italia S.r.l.

Tel: +39 06 361911

Knnpoç

Merck Sharp & Dohme Cyprus Limited

TqX.: 800 00 673 (+357 22866700)

Latvija

SIA Merck Sharp & Dohme Latvija

Tel: +371 67364 224

Suomi/Finland

MSD Finland Oy

Puh/Tel: +358 (0) 9 804 650

Sverige

Merck Sharp & Dohme (Sweden) AB

Tel: +46 (0)77 5700488

United Kingdom (Northern Ireland)

Merck Sharp & Dohme Ireland (Human

Health) Limited

Tel: +353 (0)1 2998700

This leaflet was last revised in

Detailed information on this medicine is available on the European Medicines Agency web site:

http://www.ema­.europa.eu.

The following information is intended for medical or healthcare professionals only:

Instructions of how to reconstitute and dilute CANCIDAS:

Reconstitution of CANCIDAS

DO NOT USE ANY DILUENTS CONTAINING GLUCOSE as CANCIDAS is not stable in diluents containing glucose. DO NOT MIX OR CO-INFUSE CANCIDAS WITH ANY OTHER MEDICINES, as there are no data available on the compatibility of CANCIDAS with other intravenous substances, additives, or medicinal products. Visually inspect the infusion solution for particulate matter or discolouration.

CANCIDAS 50 mg powder for concentrate for solution for infusion

INSTRUCTIONS FOR USE IN ADULT PATIENTS (50 mg vial)

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 injection. The concentrations of the reconstituted vials will be 5.2 mg/ml.

The white to off-white compact lyophilised powder will dissolve completely. Mix gently until a clear solution is obtained. Reconstituted solutions should be visually inspected for particulate matter or discolouration. This reconstituted solution may be stored for up to 24 hours at or below 25°C.

Step 2 Addition of reconstituted CANCIDAS to patient infusion solution

Diluents for the final solution for infusion are: sodium chloride solution for injection, or lactated Ringer’s solution. The solution for infusion 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. Reduced volume infusions in 100 ml may be used, when medically necessary, for 50 mg or 35 mg daily doses. Do not use if the solution is cloudy or has precipitated.

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

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

INSTRUCTIONS FOR USE IN PAEDIATRIC PATIENTS (50 mg vial)

Calculation of Body Surface Area (BSA) for paediatric dosing

Before preparation of infusion, calculate the body surface area (BSA) of the patient using the following formula: (MostellerFormula)

• I.* ¡Height ¡c mjX/ Weight (kg)~ EISA im2) – ¥ .....3B00: .....

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

• 1. Determine the actual loading dose to be used in the paediatric patient by 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 patient's cal­culated dose.

• 2. Equilibrate the refrigerated vial of CANCIDAS to room temperature.

• 3. Aseptically add 10.5 ml of water for injection.a This reconstituted solution may be stored for up to 24 hours at or below 25°C.b This will give a final caspofungin concentration in the vial of 5.2 mg/ml.

• 4. Remove the volume of medicine equal to the calculated loading dose (Step 1) from the vial. Aseptically transfer this volume (ml)c of reconstituted CANCIDAS to an IV bag (or bottle) containing 250 ml of 0.9 %, 0.45 %, or 0.225 % Sodium Chloride Injection, or Lactated Ringers Injection. Alternatively, the volume (ml)c of reconstituted CANCIDAS can be added to a reduced volume of 0.9 %, 0.45 %, or 0.225 % Sodium Chloride Injection or Lactated Ringers Injection, not to exceed a final concentration of 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 stored refrigerated at 2 to 8°C.

Preparation of the 50 mg/m2 infusion for paediatric patients >3 months of age (using a 50-mg vial) 1. Determine the actual daily maintenance dose to be used in the paediatric patient by 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 patient's cal­culated dose.

• 2. Equilibrate the refrigerated vial of CANCIDAS to room temperature.

• 3. Aseptically add 10.5 ml of water for injection.a This reconstituted solution may be stored for up to 24 hours at or below 25°C.b This will give a final caspofungin concentration in the vial of 5.2 mg/ml.

• 4. Remove the volume of medicine equal to the calculated daily maintenance dose (Step 1) from the vial. Aseptically transfer this volume (ml)c of reconstituted CANCIDAS to an IV bag (or bottle) containing 250 ml of 0.9 %, 0.45 %, or 0.225 % Sodium Chloride Injection, or Lactated Ringers Injection. Alternatively, the volume (ml)c of reconstituted CANCIDAS can be added to a reduced volume of 0.9 %, 0.45 %, or 0.225 % Sodium Chloride Injection or Lactated Ringers Injection, not to exceed a final concentration of 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 stored refrigerated at 2 to 8°C.

Preparation notes:

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

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

c CANCIDAS is formulated to provide the full labelled vial dose (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 conventional vials

To reconstitute the powder bring the vial to room temperature and aseptically add 10.5 ml of water for injection. The concentrations of the reconstituted vials will be: 7.2 mg/ml.

The white to off-white compact lyophilised powder will dissolve completely. Mix gently until a clear solution is obtained. Reconstituted solutions should be visually inspected for particulate matter or discolouration. This reconstituted solution may be stored for up to 24 hours at or below 25°C.

Step 2 Addition of reconstituted CANCIDAS to patient infusion solution

Diluents for the final solution for infusion are: sodium chloride solution for injection, or lactated Ringer’s solution. The solution for infusion 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. Reduced volume infusions in 100 ml may be used, when medically necessary, for 50 mg or 35 mg daily doses. Do not use if the solution is cloudy or has precipitated.

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

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

If 70 mg vial is not available, the 70 mg dose can be prepared from two 50 mg vials.

INSTRUCTIONS FOR USE IN PAEDIATRIC PATIENTS (70 mg vial)

Calculation of Body Surface Area (BSA) , for paediatric dosing

Before preparation of infusion, calculate the body surface area (BSA) of the patient using the

following formula: (MostellerFormula)

. / Height (c m)Weight (kg) BSA (m2) – V.....3BO0– .....

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

• 1. Determine the actual loading dose to be used in the paediatric patient by 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 patient's cal­culated dose.

• 2. Equilibrate the refrigerated vial of CANCIDAS to room temperature.

• 3. Aseptically add 10.5 ml of water for injection.a This reconstituted solution may be stored for up to 24 hours at or below 25°C.b This will give a final caspofungin concentration in the vial of 7.2 mg/ml.

• 4. Remove the volume of medicine equal to the calculated loading dose (Step 1) from the vial. Aseptically transfer this volume (ml)c of reconstituted CANCIDAS to an IV bag (or bottle) containing 250 ml of 0.9 %, 0.45 %, or 0.225 % Sodium Chloride Injection, or Lactated Ringers Injection. Alternatively, the volume (ml)c of reconstituted CANCIDAS can be added to a reduced volume of 0.9 %, 0.45 %, or 0.225 % Sodium Chloride Injection or Lactated Ringers Injection, not to exceed a final concentration of 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 stored refrigerated at 2 to 8°C.

Preparation of the 50 mg/m2 infusion for paediatric patients >3 months of age (using a 70-mg vial) 1. Determine the actual daily maintenance dose to be used in the paediatric patient by 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 patient's cal­culated dose.

• 2. Equilibrate the refrigerated vial of CANCIDAS to room temperature.

• 3. Aseptically add 10.5 ml of water for injection.a This reconstituted solution may be stored for up to 24 hours at or below 25°C.b This will give a final caspofungin concentration in the vial of 7.2 mg/ml.

• 4. Remove the volume of medicine equal to the calculated daily maintenance dose (Step 1) from the vial. Aseptically transfer this volume (ml)c of reconstituted CANCIDAS to an IV bag (or bottle) containing 250 ml of 0.9 %, 0.45 %, or 0.225 % Sodium Chloride Injection, or Lactated Ringers Injection. Alternatively, the volume (ml)c of reconstituted CANCIDAS can be added to a reduced volume of 0.9 %, 0.45 %, or 0.225 % Sodium Chloride Injection or Lactated Ringers

Injection, not to exceed a final concentration of 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 stored refrigerated at 2 to 8°C.

Preparation notes:

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

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

• c. CANCIDAS is formulated to provide the full labelled vial dose (70 mg) when 10 ml is withdrawn from the vial.