Caspofungin Lorién 50 mg powder for concentrate for infusion solution EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

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

Caspofungin

Read the entire leaflet carefully before you start taking 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 experience any adverse reactions, consult your doctor, pharmacist, or nurse, even if they are adverse reactions not listed in this leaflet. See section 4.

Leaflet contents

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

1. What Caspofungin Lorien Powder for Concentrate for Solution for Infusion Is and What It Is Used For

What is caspofungin powder for concentrate for solution for infusion

Caspofungin powder for concentrate for solution for infusion contains a medicine called caspofungin. This belongs to a group of medicines known as antifungals.

What caspofungin powder for concentrate for solution for infusion 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 organ transplantation, and those with weakened immune systems.

• Presumed fungal infections if you have fever and 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 powder for concentrate for solution for infusion works

Caspofungin weakens fungal cells 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 Caspofungina Lorien powder for concentrate for solution for infusion

Do not use Caspofungina Lorien powder for concentrate for solution for infusion

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

If you are not sure, consult your doctor, pharmacist, or nurse before starting to use this medicine.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before starting to use Caspofungina Lorien powder for concentrate for solution for infusion 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 prevent organ transplant rejection or to suppress your immune system), as your doctor may need to carry out additional blood tests during treatment.
• you have ever had any other medical condition.

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

If any of the above apply to you (or you are not sure), consult your doctor, pharmacist, or nurse before starting to use Caspofungina Lorien.

Use of Caspofungina Lorien powder for concentrate for solution for infusion with other medicines

Inform your doctor, pharmacist, or nurse if you are taking, have recently taken, or might need to take any other medicines. This includes medicines obtained without a prescription, including herbal medicines.

This is because Caspofungina Lorien may affect how other medicines work. Also, other medicines may affect how Caspofungina Lorien 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 carry out 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 you are not sure), consult your doctor, pharmacist, or nurse before starting to use Caspofungina Lorien.

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.

• Caspofungina Lorien has not been studied in pregnant women. It should only be used during pregnancy if the potential benefit justifies the possible risks to the developing baby.
• Women receiving Caspofungina Lorien must not breast-feed.

Driving and using machines

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

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

Caspofungin will always be prepared and administered to you 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 the duration of treatment and the amount of caspofungin you will receive each day. Your doctor will monitor whether the medicine's effect is adequate. 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 in adults.

If you use more caspofungin powder for concentrate for solution for infusion 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 been given 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 medicine 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 may 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 require urgent medical treatment:

• rash, itching, feeling of warmth, swelling of your 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, 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:

Common: may affect up to 1 in 10 people:

• Decreased hemoglobin (reduction in the substance that carries oxygen in the blood), decreased white blood cells.
• Decreased 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.
• Diarrhea, 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 body fluid, imbalance in body salts, elevated blood sugar levels, low calcium levels in the blood, low magnesium levels in the blood, increased levels of acid in the blood.
• Disorientation, feeling nervous, inability to sleep.
• Dizziness, decreased sensation or sensitivity (especially in the skin), restlessness, 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, rapid heartbeat, irregular heartbeat, abnormal heart rhythm, heart failure.
• Flushing, hot flushes, high blood pressure, low blood pressure, redness along a vein that is very sensitive to touch.
• Muscle tightness around the airways leading to wheezing or coughing, rapid breathing, 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, bloating, 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 drug 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.
• Decreased kidney function, sudden loss of kidney function.
• Pain at the catheter site, injection site symptoms (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 medications you are taking that suppress the immune system.
• Chest discomfort, chest pain, sensation of body temperature change, general malaise, general pain, facial swelling, swelling of ankles, hands or feet, swelling, tenderness, feeling tired.

Other adverse 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 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 type of adverse effect, consult your doctor or pharmacist, even if they are possible adverse effects 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 Lorien Powder for concentrate for infusion solution

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

Do not use this medicine after the expiry date stated on the carton and vial after EXP. The expiry date refers to the last day of the month indicated.

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

Once Caspofungin Lorien 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 later “Instructions for reconstitution and dilution of Caspofungin Lorien”).

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 pack and other information

Composition of Caspofungin Lorien

• The active substance is caspofungin. Each vial contains 50 mg of caspofungin.

After reconstitution, each ml of concentrate contains 5.2 mg of caspofungin.

• The other components are sucrose, mannitol (E421), succinic acid (E363), and sodium hydroxide (for pH adjustment) (E524).

Appearance of the product and contents of the pack

Caspofungin Lorien is a compact powder, white to off-white in color.

Each pack contains one vial of powder.

Marketing Authorization Holder

Laboratorios Lorien S.L
Av. Josep Tarradellas, 8. Ático 1ª
08029 Barcelona
Spain

Manufacturer

Laboratori Fundació DAU
C/ C, 12-14 Pol. Ind. Zona Franca
08040 Barcelona
Spain

This medicinal product is authorized in the Member States of the European Economic Area under the following names:

Date of the most recent review of this leaflet: September 2016

Detailed and up-to-date information on this medicine is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS) http://www.aemps.gob.es.

This information is intended for healthcare professionals only:

Instructions for reconstitution and dilution of Caspofungin Lorien 50 mg:

Reconstitution of Caspofungin Lorien 50 mg

DO NOT USE DILUENTS CONTAINING DEXTROSE, as Caspofungin Lorien is not stable in diluents containing dextrose. DO NOT MIX OR CO-INFUSE Caspofungin Lorien WITH ANY OTHER MEDICATION, as compatibility data with other substances, additives, or intravenous drugs are not available. The infusion solution should be visually inspected for the presence of particulate matter or discoloration.

INSTRUCTIONS FOR USE IN ADULT PATIENTS

Step 1 Reconstitution of the 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 vials will be 5.2 mg/ml.

The white to off-white compact lyophilized powder will dissolve completely. Gently swirl to obtain a clear, colorless or slightly yellow solution. Reconstituted solutions should be visually inspected for the presence of 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 Lorien to the patient's infusion solution

Diluents suitable for the final infusion solution are: sodium chloride solution for injection or lactated Ringer's solution. The infusion solution is prepared by aseptically adding the appropriate amount of the reconstituted concentrate (as shown in the table below) to a 250 ml infusion bag or bottle. For daily doses of 50 mg or 35 mg, reduced-volume infusions of 100 ml may be used if medically necessary. Do not use if the solution is cloudy or contains precipitates.

PREPARATION OF THE INFUSION SOLUTION FOR ADULTS

*10.5 ml must be used for the reconstitution of all 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 Formula1)

Preparation of 70 mg/m2* Infusion for Pediatric Patients >3 Months (Using a 50 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) X 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 Caspofungin Lorien vial to reach room temperature.
3. Aseptically add 10.5 ml of Water for Injections. aThis 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 5.2 mg/ml in the vial.
4. Withdraw from the vial a volume of medication equal to the calculated loading dose (Step 1). Aseptically transfer this volume (ml)c of reconstituted Caspofungin Lorien 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 Lorien 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 of 50 mg/m2* Infusion for Pediatric Patients >3 Months (Using a 50 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) X 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 Caspofungin Lorien vial to reach room temperature.
3. Aseptically add 10.5 ml of Water for Injections. aThis 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 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 Lorien 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 Lorien 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 lyophilized plug will dissolve completely. Gently mix until a clear, colorless or slightly yellow solution is obtained.

• Visually inspect the reconstituted solution for the presence of solid particles or discoloration during reconstitution and before infusion. Do not use if the solution is cloudy or has precipitated.

• Caspofungin Lorien is formulated to deliver the full vial dose stated in the product information (50 mg) when 10 ml is withdrawn from the vial.

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

Instructions for Reconstitution and Dilution of Caspofungin Lorien 70 mg:

Reconstitution of Caspofungin Lorien 70 mg

DO NOT USE DILUENTS CONTAINING DEXTROSE, as Caspofungin Lorien is not stable in diluents containing glucose. DO NOT MIX OR CO-ADMINISTER Caspofungin Lorien WITH ANY OTHER DRUG, as compatibility data with other substances, additives, or intravenous medications are not available. The infusion solution must be visually inspected for the presence of particulate matter or discoloration.

INSTRUCTIONS FOR USE IN ADULT PATIENTS

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 vials will be 7.2 mg/ml.

The white to off-white lyophilized powder will dissolve completely. Gently mix until a clear, colorless or slightly yellow solution is obtained. Reconstituted solutions must be visually inspected 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 Lorien to 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 table below) to a 250 ml infusion bag or bottle. For daily doses of 50 mg or 35 mg, reduced-volume infusions of 100 ml may be used if medically necessary. Do not use if the solution is cloudy or has precipitated.

PREPARATION OF INFUSION SOLUTION FOR ADULTS

*10.5 ml must be used for 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

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 Formula²)

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

1. Determine the actual loading dose to be used for 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 Caspofungin Lorien 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 loading dose (Step 1). Aseptically transfer this volume (ml)^c of reconstituted Caspofungin Lorien to an IV bag (or vial) containing 250 ml of 0.9%, 0.45%, or 0.225% Sodium Chloride Injection, or Lactated Ringer’s solution. Alternatively, the volume (ml)^c of reconstituted Caspofungin Lorien may be added to a reduced volume of 0.9%, 0.45%, or 0.225% Sodium Chloride Injection, 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 at 2 to 8°C.

Preparation of 50 mg/m² Infusion for Pediatric Patients >3 Months (Using a 70 mg Vial)

1. Determine the actual daily maintenance dose to be used for 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.

1. Allow the Caspofungin Lorien vial to reach room temperature.
2. 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.
3. 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 Lorien to an IV bag (or vial) containing 250 ml of 0.9%, 0.45%, or 0.225% Sodium Chloride Injection, or Lactated Ringer’s solution. Alternatively, the volume (ml)^c of reconstituted Caspofungin Lorien may be added to a reduced volume of 0.9%, 0.45%, or 0.225% Sodium Chloride Injection, 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 at 2 to 8°C.

Preparation Notes:

• The white to off-white powder will completely dissolve. Gently mix until a clear, colorless or slightly yellow solution is obtained.

• Visually inspect the reconstituted solution for the presence of solid particles or discoloration during reconstitution and before infusion. Do not use if the solution is cloudy or contains precipitates.

• Caspofungin Lorien is formulated to deliver the full labeled vial dose (70 mg) when 10 ml is withdrawn from the vial.

² Mosteller RD: Simplified Calculation of Body Surface Area. N Engl J Med 1987 Oct 22;317(17): 1098 (letter)