Caspofungin Hikma 70 mg powder for concentrate for infusion solution EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Caspofungin Hikma 50 mg powder for concentrate for solution for infusion EFG

Caspofungin Hikma 70 mg powder for concentrate for solution for infusion EFG

Caspofungin

Read all of this leaflet carefully before you or your child start using this medicine, because it contains important information for you.

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

Contents of the leaflet

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

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

What Caspofungin Hikma is

Caspofungin Hikma contains a medicine called caspofungin. It belongs to a group of medicines known as antifungal agents.

What caspofungin is used for

Caspofungin 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 may develop this type of infection include those who have recently undergone surgery or those with weakened immune systems. Fever and chills that do not respond to antibiotic treatment are the most common symptoms of this type of infection.

• Fungal infections in your nose, sinuses, or lungs (called "invasive aspergillosis") when other antifungal treatments have not worked or have caused adverse effects. This infection is caused by molds called Aspergillus.

People who may develop this type of infection include those receiving chemotherapy, those who have undergone transplantation, and those with weakened immune systems.

• Presumed fungal infections when you have fever and a low white blood cell count that have not improved with antibiotic treatment. People at risk of developing a fungal infection include those who have recently undergone surgery or those with weakened immune systems.

How caspofungin works

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

2. What you need to know before using Caspofungin Hikma

Do not use Caspofungin Hikma

• 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, pharmacist, or nurse before starting to use this medicine.

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting to use caspofungin if:

• you are allergic to any other medicine.
• you have ever had liver problems; you may require a different dose of this medicine.
• you are already taking cyclosporine (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 condition.

If any of the above apply to you (or if you are unsure), consult your doctor, pharmacist, or nurse before starting to use caspofungin.

Caspofungin may also cause serious skin reactions, such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).

Other medicines and Caspofungin Hikma

Inform your doctor, pharmacist, or nurse if you are using, have recently used, or might need to use any other medicines. This includes over-the-counter medicines and herbal supplements.

This is because caspofungin may affect how other medicines work. Likewise, other medicines may affect how caspofungin works.

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

• cyclosporine or tacrolimus (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 (used to treat seizures).
• dexamethasone (a steroid).
• rifampicin (an antibiotic).

If any of the above apply to you (or if you are unsure), consult your doctor, pharmacist, or nurse before starting to use Caspofungin.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to become pregnant, consult your doctor before using this medicine.

• Caspofungin has not been studied in pregnant women. It should only be used during pregnancy if the potential benefit justifies the potential risk to the developing baby.
• Women receiving caspofungin should not breastfeed.

Driving and using machines

There is no information suggesting that caspofungin affects the ability to drive or operate machinery.

3. How to use Caspofungin Hikma powder for concentrate for solution for infusion

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

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

Your doctor will determine how long your treatment will last and the amount of Caspofungin you will receive each day. Your doctor will monitor whether the medicine's effect is appropriate. If you weigh more than 80 kg, you may require a different dose.

Use in children and adolescents

The dose for children and adolescents may differ from the dose used in adults.

If you use more Caspofungin Hikma than you should

Your doctor will decide how much caspofungin you need and for how long each day. If you are concerned that you may have received too much caspofungin, inform your doctor or nurse immediately.

In case of overdose or accidental ingestion, contact your doctor or pharmacist immediately or call the Toxicology Information Service at: 91 562 04 20, indicating the medication and the amount ingested.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

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

• Rash, itching, feeling of warmth, swelling of the face, lips or throat, or breathing difficulties: you may be experiencing a histamine-type reaction to the medicine.
• Difficulty breathing with wheezing or worsening of an existing rash: 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 serious respiratory problem that could lead to respiratory failure, rash, skin peeling, sores in the mucous membranes, hives, or large areas of skin peeling.

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

Other adverse effects in adults include:

Frequent: may affect up to 1 in 10 people:

• Decrease in haemoglobin (reduction 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 blood potassium levels.
• Headache.
• Inflammation of the vein.
• Shortness of breath.
• Diarrhoea, nausea or vomiting.
• Changes in certain laboratory blood tests (such as increased values in some liver function tests).
• Itching, rash, skin redness or increased sweating.
• Joint pain.
• Chills, fever.
• Itching at the injection site.

Uncommon: may affect up to 1 in 100 people:

• Changes in certain laboratory blood tests (including blood clotting disorders, platelets, red blood cells and white blood cells).
• Loss of appetite, increased amount of body fluid, imbalance in body salts, high blood sugar levels, low blood calcium levels, high blood calcium levels, low blood magnesium levels, increased level of acids in the blood.
• Disorientation, feeling nervous, inability to sleep.
• Dizziness, decreased sensation or sensitivity (especially in the skin), restlessness, drowsiness, altered taste perception, tingling or numbness.
• Blurred vision, increased tearing, swollen eyelid, yellowing of the whites of the eyes.
• Sensation of rapid or irregular heartbeat, fast heartbeat, irregular heartbeat, abnormal heart rhythm, heart failure.
• Flushing, hot flushes, high blood pressure, low blood pressure, redness along a vein that is very tender to touch.
• Tightening of the muscle bands around the airways leading to wheezing or cough, rapid breathing rate, shortness of breath causing awakening, low oxygen levels in the blood, abnormal breathing sounds, crackling sounds in the lungs, wheezing, nasal congestion, cough, sore throat.
• Abdominal pain, upper abdominal pain, abdominal swelling, constipation, difficulty swallowing, dry mouth, indigestion, flatulence, gastric discomfort, swelling due to fluid accumulation around the abdomen.
• Decreased bile flow, enlarged liver, yellowing of the skin and/or whites of the eyes, liver injury caused by a medicine or chemical compound, liver disorder.
• Abnormal skin tissue, generalized itching, hives, rash with variable appearance, abnormal skin, red spots often with itching on arms and legs and sometimes on the face and other parts 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 surrounding tissue), inflammation of the vein at the injection site.
• Increased blood pressure and changes in certain laboratory blood tests (such as kidney electrolyte tests and coagulation tests), increased levels of medicines you are taking that suppress the immune system.
• Chest discomfort, chest pain, sensation of body temperature change, feeling generally unwell, general pain, facial swelling, swelling of ankles, hands or feet, swelling, tenderness on palpation, feeling of fatigue.

Other adverse effects in children and adolescents

Very common: may affect more than 1 in 10 people:

• Fever.

Frequent: may affect up to 1 in 10 people:

• Headache.
• Fast heartbeat.
• Flushing, low blood pressure.
• Changes in certain laboratory blood tests (increased values in some liver function tests).
• Itching, rash.
• Pain at the catheter site.
• Chills.
• Changes in certain laboratory blood tests.

Reporting of adverse effects:

If you experience any adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Caspofungin Hikma

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 indicate the year). The expiry date refers to the last day of the stated month.

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

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

If not used immediately, the solution may be stored for up to 24 hours at 25 °C or lower, or for up to 48 hours when the intravenous infusion bag (bottle) is refrigerated (2 to 8 °C) and diluted with sodium chloride solution 9 mg/ml (0.9%), 4.5 mg/ml (0.45%) or 2.25 mg/ml (0.225%) for infusion or lactated Ringer's solution. If not used immediately, the storage times and conditions prior to use are the responsibility of the user and should normally not exceed 24 hours between 2 and 8 °C, unless reconstitution and dilution have taken place under controlled, validated aseptic conditions.

Do not use the solution if you notice any signs of discolouration or particles in suspension.

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

6. Contents of the container and additional information

Composition of Caspofungin Hikma

• The active substance is caspofungin.

Caspofungin Hikma 50 mg powder for concentrate for solution for infusion EFG.

Each vial of Caspofungin Hikma contains 50 mg of caspofungin (as acetate).

Caspofungin Hikma 70 mg powder for concentrate for solution for infusion EFG.

Each vial of Caspofungin Hikma contains 70 mg of caspofungin (as acetate).

• The other components 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 starting to use Caspofungin Hikma).

Appearance of the product and contents of the container

Caspofungin Hikma is a sterile, compact powder with a white to off-white colour. The reconstituted solution is clear and transparent.

Caspofungin Hikma 50 mg powder for concentrate for solution for infusion EFG

10 ml type I glass vial with a bromobutyl stopper and a plastic cap with a red aluminium band.

Caspofungin Hikma 70 mg powder for concentrate for solution for infusion EFG

10 ml type I glass vial with a bromobutyl stopper and a plastic cap with an orange aluminium band.

Each container contains one vial of powder.

Marketing Authorization Holder and Manufacturing Responsible

Marketing Authorization Holder

Hikma Farmacêutica (Portugal), S.A.

Estrada do Rio da Mó n.º 8, 8A and 8B – Fervença

2705-906 Terrugem SNT

Portugal

Tel.: ++351 21 960 84 10

Fax: ++351 21 961 51 02

E-mail: [email protected]

Manufacturer responsible

Pharmadox healthcare, ltd

KW20A Kordin Industrial Park, Paola

PLA 3000 Malta

Galenicum Health, S.L.U.

Sant Gabriel, 50 Esplugues de Llobregat 08950

Barcelona, Spain

SAG Manufacturing S.L.U.

Ctra. N-I, Km 36

San Agustín de Guadalix, 28750

Madrid, Spain

Hikma Italia S.p.A.

Viale Certosa, 10

27100, Pavia (PV)

Italy

For further information regarding this medicinal product, please contact the local representative of the marketing authorization holder:

Hikma España, S.L.U.

Calle Anabel Segura nº11, Edificio A, planta 1ª, oficina 2

28108 - Alcobendas, Madrid

Spain

Date of the most recent review of this leaflet: JULY 2020

This information is intended for healthcare professionals only:

Instructions for reconstituting and diluting Caspofungin Hikma:

Reconstitution of caspofungin hikma

DO NOT USE DILUENTS CONTAINING DEXTROSE, as CASPOFUNGIN is not stable in diluents containing glucose. DO NOT MIX OR CO-ADMINISTER CASPOFUNGIN WITH ANY OTHER MEDICINE, as compatibility data of CASPOFUNGIN with other substances, additives, or intravenous pharmaceutical specialties are not available. The infusion solution should be inspected visually for solid particles or discoloration.

Caspofungin hikma 50 mg powder for concentrate for solution for infusion EFG

DIRECTIONS FOR USE IN ADULT PATIENTS (50 mg vial)

Step 1 Reconstitution of the vials

To reconstitute the powder, allow the vial to reach room temperature and then aseptically add 10.5 ml of water for injections. The concentration of the reconstituted vial will be 5.2 mg/ml.

The compact, white to off-white lyophilized powder will dissolve completely. Gently mix until a clear solution is obtained. Reconstituted solutions should be inspected visually for solid particles or discoloration. The reconstituted solution may be stored for up to 24 hours at a temperature not exceeding 25 °C.

Step 2 Adding reconstituted caspofungin to the patient's infusion solution

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

Vial 50 mg: PREPARATION OF THE INFUSION SOLUTION FOR ADULTS

DOSE*	Volume of reconstituted Caspofungin Hikma to be transferred to an intravenous bag or vial	Standard preparation (Reconstituted Caspofungin Hikma added to 250 ml) final concentration	Reduced volume infusion (Reconstituted Caspofungin Hikma added to 100 ml) final concentration
50 mg	10 ml	0.20 mg/ml	-
50 mg in reduced volume	10 ml	-	0.47 mg/ml
35 mg for moderate hepatic impairment (from a 50 mg vial)	7 ml	0.14 mg/ml	-
35 mg for moderate hepatic impairment (from a 50 mg vial) in reduced volume	7 ml	-	0.34 mg/ml

*10.5 ml must 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])

BSA (m²) =

Preparation of the 70 mg/m² infusion for pediatric patients >3 months of age (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) × 70 mg/m² = loading dose

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

2. Allow the refrigerated caspofungin vial to reach room temperature.
3. 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 result in a final caspofungin concentration of 5.2 mg/mL in the vial.

4. From the vial, withdraw a volume of the medication equal to the calculated loading dose (Step 1). Aseptically transfer this volume (mL) of reconstituted caspofungin into an IV bag (or vial) 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 caspofungin may be added to a reduced volume of 0.9%, 0.45%, or 0.225% sodium chloride injection solution, or lactated Ringer's solution, provided 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 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 by using the patient's BSA (as calculated 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 dose for the patient.

2. Allow the refrigerated caspofungin vial to reach room temperature.

3. Aseptically add 10.5 mL of Water for Injections.

a The reconstituted solution may be stored for up to 24 hours at a temperature not exceeding 25 °C.

b This will result in a final caspofungin concentration of 5.2 mg/mL in the vial.

4. Withdraw from the vial a volume of medication equal to the calculated daily maintenance dose (Step 1). Aseptically transfer this volume (mL)c of reconstituted caspofungin into an IV bag (or vial) containing 250 mL of 0.9%, 0.45%, or 0.225% sodium chloride injection solution, or lactated Ringer's solution. Alternatively, the volume (mL)c of reconstituted caspofungin may be added to a reduced volume of 0.9%, 0.45%, or 0.225% sodium chloride injection solution, or lactated Ringer's solution, provided 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 refrigerated between 2 and 8 °C.

Caspofungin Hikma 70 mg powder for concentrate for solution for infusion EFG

INSTRUCTIONS FOR USE IN ADULT PATIENTS (70 mg vial)

Step 1 Reconstitution of vials

To reconstitute the powder, allow the vial to reach room temperature and aseptically add 10.5 mL of Water for Injections. The concentration of the reconstituted vial will be 7.2 mg/mL.

The white to off-white compact lyophilized powder will dissolve completely. Gently mix until a clear solution is obtained. Reconstituted solutions should be inspected visually for particulate matter or discoloration. The reconstituted solution may be stored for up to 24 hours at a temperature not exceeding 25 °C.

Step 2 Addition of reconstituted Caspofungin 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 aseptically adding the appropriate amount of reconstituted concentrate (as shown in the following table) to a 250 mL infusion bag or bottle. Reduced-volume infusions of 100 mL may be used, if medically necessary, for daily doses of 50 mg or 35 mg. Do not use if the solution is cloudy or contains precipitate.

70 mg vial: PREPARATION OF THE INFUSION SOLUTION FOR ADULTS

DOSE*	Volume of reconstituted Caspofungin Hikma to be transferred to an intravenous bag or vial	Standard preparation (Reconstituted Caspofungin Hikma added to 250 ml) final concentration	Reduced volume infusion (Reconstituted Caspofungin Hikma 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 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.

DOSING INSTRUCTIONS FOR 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)

BSA (m²) =

Preparation of 70 mg/m² Infusion for Pediatric Patients >3 Months of Age (Using a 70 mg Vial)

1. Determine the actual loading dose to be administered to the pediatric patient using the patient’s BSA (as calculated 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 dose for the patient.

2. Allow the refrigerated caspofungin vial to reach room temperature before use.
3. Aseptically add 10.5 mL of Water for Injections to the vial.

a The reconstituted solution may be stored for up to 24 hours at a temperature not exceeding 25 °C.

b This will result in a final concentration of caspofungin of 7.2 mg/mL in the vial.

4. Withdraw from the vial a volume (in mL) of medication equal to the calculated loading dose (Step 1). Aseptically transfer this volume (mL)c of reconstituted caspofungin into 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)c of reconstituted caspofungin may be added to a reduced volume of 0.9%, 0.45%, or 0.225% sodium chloride injection solution or lactated Ringer’s solution, provided 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 between 2 and 8 °C.

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

1. Determine the actual daily maintenance dose to be administered to the pediatric patient using the patient's BSA (as calculated 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 dose for the patient.

2. Allow the refrigerated caspofungin vial to reach room temperature.

3. Aseptically add 10.5 mL of Water for Injections.

aThe reconstituted solution may be stored for up to 24 hours at a temperature not exceeding 25 °C.

bThis will result in a final caspofungin concentration of 7.2 mg/mL in the vial.

4. Withdraw from the vial a volume of medication equal to the calculated daily maintenance dose (Step 1). Aseptically transfer this volume (mL)c of reconstituted caspofungin into an IV bag (or vial) containing 250 mL of 0.9%, 0.45%, or 0.225% sodium chloride injection solution, or Lactated Ringer’s solution. Alternatively, the volume (mL)c of reconstituted caspofungin may be added to a reduced volume of 0.9%, 0.45%, or 0.225% sodium chloride injection solution or Lactated Ringer’s solution, provided 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 refrigerated between 2 and 8 °C.

Preparation Notes The white to off-white cake will completely dissolve. Mix gently until a clear solution is obtained. Visually inspect the reconstituted solution for the presence of particulate matter or discoloration during reconstitution and prior to infusion. Do not use if the solution is cloudy or has precipitated. Caspofungin is formulated to deliver the full dose from the vial stated in the package insert (70 mg) when 10 mL are withdrawn from the vial.

[1] Mosteller RD: Simplified Calculation of Body Surface Area. N Engl J Med 1987 Oct 22;317(17): 1098 (letter)