Prospect: information for the user

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

Caspofungin

Read this prospect carefully before starting to take this medicine, because it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor, pharmacist, or nurse.
• If you experience adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this prospect. See section 4.

5Storage of Caspofungin Lorien powder for concentrate for solution for infusion

6.Contents of the package and additional information

What is caspofungina powder for concentrate for solution for infusion

Caspofungina powder for concentrate for solution for infusion contains a medicine called caspofungina. This belongs to a group of medicines called antifungals.

What is caspofungina powder for concentrate for solution for infusion used for

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

•severe fungal infections in their tissues or organs (designated “invasive candidiasis”). This infection is caused by fungal cells (yeast) called Candida. People who may suffer from this type of infection include those who have recently undergone surgery or those whose immune system is weakened. Fever and chills that do not respond to antibiotic treatment are the most common symptoms of this type of infection.

•fungal infections in their nose, nasal sinuses, or lungs (designated “invasive aspergillosis”) if other antifungal treatments have not worked or have caused side effects. This infection is caused by molds called Aspergillus.

People who may suffer from this type of infection include those undergoing chemotherapy, those who have undergone a transplant, and those whose immune system is weakened.

•presumed fungal infections if you have fever and a low white blood cell count, which have not improved with antibiotic treatment. People who are at risk of developing a fungal infection include those who have recently undergone surgery or those whose immune system is weakened.

How caspofungina powder for concentrate for solution for infusion works

Caspofungina makes fungal cells fragile and prevents the fungus from growing properly. This prevents the infection from spreading and gives the body's natural defenses the opportunity to completely get rid of the infection.

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

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

If you are unsure, consult your doctor, pharmacist or nurse before starting to use your medication.

Warnings and precautions

Consult your doctor, pharmacist or nurse before starting to use Caspofungin Lorien powder for concentrate for solution for infusion if:

• you are allergic to any other medication.
• you have ever had liver problems; you may need a different dose of this medication.
• you are already taking ciclosporin (used to prevent organ transplant rejection or to cause suppression of your immune system), as your doctor may need to perform additional blood tests during treatment.
• you have ever had any other medical condition.

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

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

Use of Caspofungin Lorien powder for concentrate for solution for infusion with other medications

Inform your doctor, pharmacist or nurse if you are using, have used recently or may need to use any other medication. This includes medications obtained without a prescription, including herbal remedies.

This is because Caspofungin Lorien may affect the way other medications work. Also, other medications may affect the way Caspofungin Lorien works.

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

• ciclosporin or tacrolimus (used to prevent organ transplant rejection or to cause suppression of your immune system), as your doctor may need to perform additional blood tests during your treatment.
• some HIV medications such as efavirenz or nevirapina.
• phenytoin or carbamazepine (used to treat seizures).
• dexamethasone (a steroid).
• rifampicin (an antibiotic).

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

Pregnancy and breastfeeding

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

• Caspofungin 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 fetus.
• Women using Caspofungin Lorien should not breastfeed.

Driving and operating machinery

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

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

• once a day.
• through slow injection into a vein (intravenous infusion).
• for around 1 hour.

Your doctor will determine the duration of treatment and the amount of Caspofungin to be administered each day. Your doctor will monitor if the medication's effect 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 adult dose.

If you use more Lorien Caspofungin Powder for Concentrate for Infusion Solution 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, consult your doctor or pharmacist immediately or call the Toxicological Information Service, phone: 91 562 04 20, indicating the medication and the amount ingested.

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

Like all medicines, this medicine may cause side effects, although not everyone will experience them.

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

• eruption, itching, sensation of heat, 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 an existing eruption: you may be having an allergic reaction to the medicine.
• cough, severe breathing difficulties: if you are an adult and have invasive aspergillosis, you may experience a severe respiratory problem that could lead to respiratory failure.
• eruption, skin peeling, mucous membrane ulcers, rashes, large areas of skin peeling

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

Other side effects in adults include:

Frequent: may affect up to 1 in 10 people:

• Decreased hemoglobin (decrease 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.
• Vein inflammation.
• Shortness of breath.
• Diarrhea, nausea, or vomiting.
• Changes in some laboratory blood tests (such as increased values of some liver function tests).
• Itching, eruption, redness of the skin, or excessive sweating.
• Joint pain.
• Chills, fever.
• Itching at the injection site.

Rare: may affect up to 1 in 100 people:

• Changes in some laboratory blood tests (including blood clotting disorders, platelets, red blood cells, and white blood cells).
• Loss of appetite, increased body fluid, electrolyte imbalance, high blood sugar levels, low calcium levels in the blood, low magnesium levels in the blood, high blood acidity levels.
• Disorientation, nervousness, inability to sleep.
• Sensation of dizziness, decreased sensations or sensitivity (especially in the skin), agitation, drowsiness, change in the way things taste, tingling or numbness.
• Blurred vision, increased tearing, swollen eyelid, yellow discoloration of the white part of the eyes.
• Sensation of rapid or irregular heartbeats, rapid heartbeat, irregular heartbeat, abnormal heart rhythm, heart failure.
• Flush, hot flashes, high blood pressure, low blood pressure, redness along a vein that is very sensitive to the touch.
• Tension in the bands of muscle around the airways that leads to wheezing or cough, rapid breathing, shortness of breath that wakes you up, lack of oxygen in the blood, abnormal respiratory sounds, crepitant sounds in the lungs, wheezing, nasal congestion, cough, sore throat.
• Abdominal pain, upper abdominal pain, swelling, constipation, difficulty swallowing, dry mouth, indigestion, gas, stomach discomfort, swelling due to fluid accumulation around the abdomen.
• Decreased bile flow, enlarged liver, yellow discoloration of the skin and/or white part of the eyes, liver damage caused by a drug or chemical compound, liver disorder.
• Abnormal skin tissue, generalized itching, rashes, varied eruption, abnormal skin, red spots, often with itching, on arms and legs and sometimes on the face and rest of the body.
• Back pain, arm or leg pain, 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, eruption, rashes, fluid leakage from the catheter into the tissue), vein inflammation at the injection site.
• Increased blood pressure and alterations in some laboratory blood tests (such as kidney electrolyte tests and coagulation tests), increased levels of medications you are taking that weaken the immune system.
• Chest discomfort, chest pain, sensation of temperature change, feeling generally unwell, general pain, swelling of the face, swelling of the ankles, hands, or feet, swelling, pain on palpation, feeling tired

Other side effects in children and adolescents

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

• Fever.

Frequent:may affect up to 1 in 10 people:

• Headache.
• Rapid heartbeat.
• Flush, low blood pressure.
• Changes in some laboratory blood tests (increased values of some liver function tests).
• Itching, eruption.
• Pain at the catheter site.
• Chills.
• Changes in some laboratory blood tests.

Reporting of side effects:

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through the Spanish System for the Pharmacovigilance of Medicines for Human Use: https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the box and on the vial after CAD. The expiration date is the last day of the month indicated.

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

Once Caspofungina 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 medication (see later "Instructions to reconstitute and dilute Caspofungina Lorien").

Medications should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. In this way, you will help to protect the environment.

Composition of Caspofungin Lorien

• The active ingredient 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 package

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

Each package contains a vial of powder.

Marketing Authorization Holder

Laboratorios Lorien S.L

Av. Josep Tarradellas, 8. 1st floor

08029 Barcelona

Spain

Responsible for manufacturing

Laboratori Fundació DAU

C/ C, 12-14 Pol. Ind. Zona Franca

08040 Barcelona

Spain

This medicine is authorized in the member states of the European Economic Area with the following names:

Last review date of this leaflet: September 2016

The detailed and updated information of this medicine is available on the website of the Spanish Agency of Medicines and Medical Devices (AEMPS) http://www.aemps.gob.es.

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This information is intended solely for healthcare professionals:

Instructions for reconstitution and dilution of Caspofungin Lorien 50 mg:

Reconstitution of Caspofungin Lorien 50 mg

DO NOT USE DILUENTS CONTAINING GLUCOSE, as Caspofungin Lorien is not stable in diluents containing glucose. DO NOT MIX OR INFUSE CONCURRENTLY Caspofungin Lorien WITH ANY OTHER MEDICINE, as there are no data on the compatibility of Caspofungin Lorien with other substances, additives or intravenous medications. The infusion solution must be visually inspected for the presence of solid particles or a change in color.

INSTRUCTIONS FOR USE IN ADULT PATIENTS

Step 1 Reconstitution of vials

To reconstitute the powder, temper the vial and add asetically 10.5 ml of water for injection. The concentration of the reconstituted vials will be 5.2 mg/ml.

The compact lyophilized powder of white to off-white color will completely dissolve. Gently mix until a transparent, colorless or slightly yellowish solution is obtained. The reconstituted solutions must be visually inspected for the presence of solid particles or a change in color. The reconstituted solution can be stored for a maximum of 24 hours at a temperature equal to or below 25 °C.

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

The diluents for the final infusion solution are: sodium chloride injection solution or Ringer lactate solution. The infusion solution is prepared by adding asetically the appropriate amount of the reconstituted concentrate (as shown in the following table) 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 turbid or has precipitated.

PREPARATION OF THE INFUSION SOLUTION IN ADULTS

*10.5 ml must be used for the reconstitution of all vials

INSTRUCTIONS FOR USE IN PEDIATRIC PATIENTS

Calculation of body surface area (SC) for pediatric dosing

Before preparing the infusion, calculate the patient's body surface area (SC) using the following formula: (Mosteller formula)

Preparation of the 70 mg/m2infusion 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 SC (as calculated above) and the following equation: SC (m2) X 70 mg/m2= loading dose. The maximum loading dose on day 1 should not exceed 70 mg regardless of the dose calculated for the patient.

2.Wait for the vial of Caspofungin Lorien to reach room temperature.

3.Add asetically 10.5 ml of water for injection.aThis reconstituted solution can be stored for up to 24 hours at a temperature equal to or below 25°C.bThis will result in a final concentration of caspofungin in the vial of 5.2 mg/ml.

4.Extract from the vial a volume of medication equal to the calculated loading dose (Step 1). Transfer asetically this volume (ml)cof Caspofungin Lorien reconstituted to an IV bag or bottle that contains 250 ml of sodium chloride injection solution 0.9%, 0.45%, or 0.225%, or Ringer lactate solution. Alternatively, the volume (ml)cof Caspofungin Lorien reconstituted can be added to a reduced volume of sodium chloride injection solution 0.9%, 0.45%, or 0.225%, or Ringer 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 equal to or below 25°C or within 48 hours if stored in the refrigerator between 2 and 8°C.

Preparation of the 50 mg/m2infusion 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 SC (as calculated above) and the following equation: SC (m2) X 50 mg/m2= daily maintenance dose. The daily maintenance dose should not exceed 70 mg regardless of the dose calculated for the patient.

2.Wait for the vial of Caspofungin Lorien to reach room temperature.

3.Add asetically 10.5 ml of water for injection.aThis reconstituted solution can be stored for up to 24 hours at a temperature equal to or below 25°C.bThis will result in a final concentration of caspofungin in the vial of 5.2 mg/ml.

4.Extract from the vial a volume of medication equal to the calculated daily maintenance dose (Step 1). Transfer asetically this volume (ml)cof Caspofungin Lorien reconstituted to an IV bag or bottle that contains 250 ml of sodium chloride injection solution 0.9%, 0.45%, or 0.225%, or Ringer lactate solution. Alternatively, the volume (ml)cof Caspofungin Lorien reconstituted can be added to a reduced volume of sodium chloride injection solution 0.9%, 0.45%, or 0.225%, or Ringer 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 equal to or below 25°C or within 48 hours if stored in the refrigerator between 2 and 8°C.

1Mosteller RD: Simplified Calculation of Body Surface Area.N Engl J Med1987 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 GLUCOSE, as Caspofungin Lorien is not stable in diluents containing glucose. DO NOT MIX OR INFUSE CONCURRENTLY Caspofungin Lorien WITH ANY OTHER MEDICINE, as there are no data on the compatibility of Caspofungin Lorien with other substances, additives or intravenous medications. The infusion solution must be visually inspected for the presence of solid particles or a change in color.

INSTRUCTIONS FOR USE IN ADULT PATIENTS

Step 1 Reconstitution of vials

To reconstitute the powder, let the vial temper at room temperature and add asetically 10.5 ml of water for injection. The concentration of the reconstituted vials will be 7.2 mg/ml.

The compact lyophilized powder of white to off-white color will completely dissolve. Gently mix until a transparent, colorless or slightly yellowish solution is obtained. The reconstituted solutions must be visually inspected for the presence of solid particles or a change in color. The reconstituted solution can be stored for a maximum of 24 hours at a temperature equal to or below 25 °C.

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

The diluents for the final infusion solution are: sodium chloride injection solution or Ringer lactate solution. The infusion solution is prepared by adding asetically the appropriate amount of the reconstituted concentrate (as shown in the following table) 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 turbid or has precipitated.

PREPARATION OF THE INFUSION SOLUTION IN ADULTS

*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

INSTRUCTIONS FOR USE IN PEDIATRIC PATIENTS

Calculation of body surface area (SC) for pediatric dosing

Before preparing the infusion, calculate the patient's body surface area (SC) using the following formula: (Mosteller formula)

Preparation of the 70 mg/m2infusion 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 SC (as calculated above) and the following equation: SC (m2) X 70 mg/m2= loading dose. The maximum loading dose on day 1 should not exceed 70 mg regardless of the dose calculated for the patient.

2.Wait for the vial of Caspofungin Lorien to reach room temperature.

3.Add asetically 10.5 ml of water for injection.aThis reconstituted solution can be stored for up to 24 hours at a temperature equal to or below 25°C.bThis will result in a final concentration of caspofungin in the vial of 7.2 mg/ml.

4.Extract from the vial a volume of medication equal to the calculated loading dose (Step 1). Transfer asetically this volume (ml)cof Caspofungin Lorien reconstituted to an IV bag or bottle that contains 250 ml of sodium chloride injection solution 0.9%, 0.45%, or 0.225%, or Ringer lactate solution. Alternatively, the volume (ml)cof Caspofungin Lorien reconstituted can be added to a reduced volume of sodium chloride injection solution 0.9%, 0.45%, or 0.225%, or Ringer 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 equal to or below 25°C or within 48 hours if stored in the refrigerator between 2 and 8°C.

Preparation of the 50 mg/m2infusion 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 SC (as calculated above) and the following equation: SC (m2) X 50 mg/m2= daily maintenance dose. The daily maintenance dose should not exceed 70 mg regardless of the dose calculated for the patient.

2.Wait for the vial of Caspofungin Lorien to reach room temperature.

3.Add asetically 10.5 ml of water for injection.aThis reconstituted solution can be stored for up to 24 hours at a temperature equal to or below 25°C.bThis will result in a final concentration of caspofungin in the vial of 7.2 mg/ml.

4.Extract from the vial a volume of medication equal to the calculated daily maintenance dose (Step 1). Transfer asetically this volume (ml)cof Caspofungin Lorien reconstituted to an IV bag or bottle that contains 250 ml of sodium chloride injection solution 0.9%, 0.45%, or 0.225%, or Ringer lactate solution. Alternatively, the volume (ml)cof Caspofungin Lorien reconstituted can be added to a reduced volume of sodium chloride injection solution 0.9%, 0.45%, or 0.225%, or Ringer 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 equal to or below 25°C or within 48 hours if stored in the refrigerator between 2 and 8°C.

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