CASPOFUNGINA OLPHA 50 mg POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION

2. What you need to know before you use Caspofungina Olpha

Do not use Caspofungina Olpha

• if you are allergic to caspofungina 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 you start using your medicine.

Warnings and precautions

Talk to your doctor, pharmacist or nurse before you start using Caspofungina 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 cause suppression of your immune system), as your doctor will probably need to do extra blood tests during your treatment.
• you have ever had any other medical problem.

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

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

Other medicines and caspofungina

Tell your doctor, pharmacist or nurse if you are using, have recently used or might use any other medicines. This includes medicines bought without a prescription, including herbal medicines.

This is because Caspofungina can affect how other medicines work. Other medicines can also affect how Caspofungina 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 cause suppression of your immune system), as your doctor will probably need to do extra blood tests during your 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 if you are not sure), talk to your doctor, pharmacist or nurse before you start using Caspofungina.

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 taking this medicine.

• Caspofungina 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 who use Caspofungina must not breastfeed.

Driving and using machines

There is no information to suggest that Caspofungina affects the ability to drive or use machines.

3. How to use Caspofungina Olpha

Caspofungina will always be prepared and given to you by a healthcare professional. You will be given Caspofungina:

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

Your doctor will decide how long you should be treated with Caspofungina and how much Caspofungina you should be given 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 caspofungina than you should

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

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

If you have any further questions on 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 already exists: 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 breathing 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 more sweating 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 coagulation disorders, platelets, red blood cells and white blood cells).
• loss of appetite, increase in body fluid, imbalance in body salt, high blood sugar, low calcium levels in the blood, high calcium levels in blood, low magnesium levels in the blood, increase in the level of acids in the blood.
• disorientation, feeling nervous, inability to sleep.
• feeling dizzy, decreased sensations or sensitivity (especially in the skin), agitation, feeling sleepy, change in the way things taste, tingling or numbness.
• blurred vision, increased tearing, swollen eyelid, yellowing of the white part of the eyes.
• feeling of rapid or irregular heartbeats, rapid heartbeat, irregular heartbeat, abnormal heartbeat, heart failure.
• flushing, hot flashes, high blood pressure, low blood pressure, redness along a vein that is very sensitive to the touch.
• tightness in the muscle bands around the airways leading to wheezing or cough, rapid breathing rate, shortness of breath that wakes you up, 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, swelling, constipation, difficulty swallowing, dry mouth, indigestion, 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 drug 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 the 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

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 or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly through the Spanish Medicines Monitoring System for Human Use: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Conservation of Caspofungina Olpha

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 on the vial after EXP (the first two numbers are the month and the next four numbers are the year). The expiry date is the last day of the month shown.

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

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

If it is not used immediately, the solution can be used within the next 24 hours if stored at 25 °C or less, or within the next 48 hours if the intravenous infusion bag (bottle) is stored refrigerated (between 2 and 8 °C) and diluted with sodium chloride 9 mg / ml (0.9%), 4.5 mg / ml (0.45%) or 2.25 mg / ml (0.225%) solution for infusion, or with Ringer's lactate solution. If not used immediately, the storage times during use and the conditions before use are the responsibility of the user and will normally not exceed 24 hours between 2 and 8 °C, unless it has been reconstituted and diluted under validated and controlled aseptic conditions.

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

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

6. Container Contents and Additional Information

Caspofungin Composition

• The active ingredient is caspofungin.

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

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

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

Each vial of Caspofungin 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).

Product Appearance and Container Contents

Caspofungin is a compact, sterile, white to off-white powder. The reconstituted solution is transparent.

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

Caspofungin is available in 10 ml glass vials with a bromobutyl stopper and an aluminum flip-off seal with a red plastic flip-off cap.

Caspofungina Olpha 70 mg powder for concentrate for solution for infusion EFG

Caspofungin is available in 10 ml glass vials with a bromobutyl stopper and an aluminum flip-off seal with an orange plastic flip-off cap.

Each container contains one vial of powder.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Olpha AS,

Rupnicu iela 5,

Olaine, Olaines novads, LV-2114,

Latvia

Manufacturer

Pharmadox Healthcare, Ltd.

KW20A Kordin Industrial Park

Paola

PLA 3000

Malta

Or

SAG Manufacturing S.L.U

Ctra. N-I, Km 36. San Agustín de Guadalix

28750, Madrid, Spain

Or

Galenicum Health S.L.U

Sant Gabriel, 50

08950, Esplugues de Llobregat

Barcelona-Spain

Or

Hikma Italia S.p.A.

Viale Certosa, 10,

27100, Pavia (PV) Italy

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

Malta: Caspofungin Galenicum 50, 70 mg powder for concentrate for solution for infusion

Croatia: Kaspofungin PharmaS 50 mg powder for concentrate for solution for infusion

Portugal: Caspofungina Generis

Greece: Fungizor 50, 70 mg

Date of the Last Revision of this Leaflet:

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

This information is intended only for healthcare professionals:

Instructions for reconstituting and diluting CASPOFUNGINA:

Reconstitution of CASPOFUNGINA

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

Caspofungina Olpha 50 mg powder for concentrate for solution for infusion EFG

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 transparent solution is obtained. The reconstituted solutions should be visually inspected for particulate matter or a change in color. The reconstituted solution can be stored for a maximum of 24 hours at a temperature of 25 °C or below.

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

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

VIAL of 50 mg: PREPARATION OF THE INFUSION SOLUTION IN 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)

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 CASPOFUNGINA 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 caspofungin in the vial of 5.2 mg/ml.

1. Withdraw from the vial a volume of the medication equal to the calculated loading dose (Step 1). Transfer aseptically this volume (ml) of reconstituted CASPOFUNGINA to an intravenous bag or bottle containing 250 ml of sodium chloride injection solution 0.9%, 0.45%, or 0.225%, or Ringer's lactate solution. Alternatively, the volume (ml) of reconstituted CASPOFUNGINA can be added to a reduced volume of sodium chloride injection solution 0.9%, 0.45%, or 0.225%, or Ringer's lactate 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 CASPOFUNGINA vial to reach room temperature. 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 caspofungin in the vial of 5.2 mg/ml.

1. Withdraw from the vial a volume of the medication equal to the calculated daily maintenance dose (Step 1). Transfer aseptically this volume (ml) of reconstituted CASPOFUNGINA to an intravenous bag or bottle containing 250 ml of sodium chloride injection solution 0.9%, 0.45%, or 0.225%, or Ringer's lactate solution. Alternatively, the volume (ml) of reconstituted CASPOFUNGINA can be added to a reduced volume of sodium chloride injection solution 0.9%, 0.45%, or 0.225%, or Ringer's lactate 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.

Caspofungina Olpha 70 mg powder for concentrate for solution for infusion EFG

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 transparent solution is obtained. The reconstituted solutions should be visually inspected for particulate matter or a change in color. The reconstituted solution can be stored for a maximum of 24 hours at a temperature of 25 °C or below.

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

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

VIAL of 70 mg: PREPARATION OF THE INFUSION SOLUTION IN 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)

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 CASPOFUNGINA 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 caspofungin in the vial of 7.2 mg/ml.

1. Withdraw from the vial a volume of the medication equal to the calculated loading dose (Step 1). Transfer aseptically this volume (ml) of reconstituted CASPOFUNGINA to an intravenous bag or bottle containing 250 ml of sodium chloride injection solution 0.9%, 0.45%, or 0.225%, or Ringer's lactate solution. Alternatively, the volume (ml) of reconstituted CASPOFUNGINA can be added to a reduced volume of sodium chloride injection solution 0.9%, 0.45%, or 0.225%, or Ringer's lactate 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 CASPOFUNGINA 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 caspofungin in the vial of 7.2 mg/ml.

1. Withdraw from the vial a volume of the medication equal to the calculated daily maintenance dose (Step 1). Transfer aseptically this volume (ml) of reconstituted CASPOFUNGINA to an intravenous bag or bottle containing 250 ml of sodium chloride injection solution 0.9%, 0.45%, or 0.225%, or Ringer's lactate solution. Alternatively, the volume (ml) of reconstituted CASPOFUNGINA can be added to a reduced volume of sodium chloride injection solution 0.9%, 0.45%, or 0.225%, or Ringer's lactate 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.