CASPOFUNGINA TILLOMED 70 mg POWDER FOR CONCENTRATE FOR INFUSION SOLUTION

2. What you need to know before you use Caspofungin Tillomed

Do not use caspofungin

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

If you are not sure, talk to your doctor, pharmacist, or nurse before using your medicine.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before using caspofungin 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 perform additional blood tests during 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 using caspofungin.

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

Other medicines and caspofungin

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

This is because caspofungin can affect how other medicines work. Other medicines can also affect how caspofungin 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 perform additional blood tests during 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 using caspofungin.

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 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 using caspofungin should not breastfeed.

Driving and using machines

There is no information to suggest that caspofungin affects your ability to drive or use machines.

Caspofungin Tillomed contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per vial; this is essentially "sodium-free".

3. How to use Caspofungin Tillomed

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

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

Your doctor will decide how long you should receive caspofungin and how much you should receive 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 caspofungin 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, tell your doctor or nurse immediately.

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

If you have any further questions on the use of this product, 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 severe respiratory 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 of body salts, high blood sugar, low calcium levels in the blood, low magnesium levels in the blood, increase in acid levels in the blood.
• Disorientation, feeling nervous, inability to sleep.
• Dizziness, decreased sensation or sensitivity (especially in the skin), agitation, drowsiness, 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 heart rhythm, 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.
• Decreased bile flow, enlarged liver, yellowing of the skin and/or the white part of the eyes, liver damage 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.
• Increased blood pressure and changes in some laboratory blood tests (such as kidney electrolyte tests and coagulation tests), increased levels of medicines that 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, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Conservation of Caspofungin Tillomed

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 vial (the first two numbers are the month; the next four numbers are the year). The expiry date is the last day of the month stated.

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

Once caspofungin 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 reconstituting and diluting caspofungin" below).

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. Contents of the pack and further information

Composition of Caspofungin Tillomed

• The active substance is caspofungin. Each vial of Caspofungin Tillomed contains 70 mg of caspofungin.
• The other ingredients are: sucrose, mannitol (E421), sodium hydroxide (E524), and glacial acetic acid (E260) (see section 2. What you need to know before you use Caspofungin Tillomed).

Appearance and packaging

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

Each pack contains one vial of powder.

Marketing authorization holder and manufacturer

Marketing authorization holder

Laboratorios Tillomed Spain, S.L.

C/ Cardenal Marcelo Spínola, 8

28016 Madrid (Spain)

Manufacturer1

MIAS Pharma Limited

Suite 2,

Stafford House,

Strand Road,

Portmarnock,

Co. Dublin,

Ireland

Tillomed Malta Limited,

Malta Life Sciences Park

LS2.01.06 Industrial Estate

San Gwann, SGN 3000, Malta

1 only the current manufacturer of the product is indicated in the leaflet.

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

Netherlands: Caspofungine Tillomed 70 mg Powder for concentrate for solution for infusion

Austria: Caspofungin Tillomed 70 mg Pulver für ein Konzentrat zur Herstellung einer Infusionslösung

Denmark: Caspofungin Tillomed

Finland: Caspofungin Tillomed 70 mg kuiva-aine välikonsentraatiksi infuusionestettä varten, liuos

Norway: Caspofungin Tillomed

Sweden: Caspofungin Tillomed 70 mg pulver till koncentrat till infusionsvätska, lösning

Italy: Caspofungin Tillomed

Spain: Caspofungina Tillomed 70 mg polvo para concentrado para solución para perfusión EFG

Date of last revision of this leaflet: Jul 2022

Other sources of information

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

________________________________________________________________________

This information is intended only for healthcare professionals:

Instructions for reconstituting and diluting caspofungin:

Reconstitution of caspofungin

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

INSTRUCTIONS FOR USE IN ADULT PATIENTS

Step 1 Reconstitution of the vials

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

The compact, lyophilized powder, white to off-white in color, will dissolve completely. Mix gently until a clear solution is obtained. 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 caspofungin to the infusion solution for the patient

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

PREPARATION OF THE SOLUTION FOR INFUSION 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

Calculation of body surface area (BSA) for pediatric dosing

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

Preparation of the 70 mg/m^2 infusion

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 (m^2) x 70 mg/m^2 = 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 caspofungin 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.
3. Withdraw from the vial a volume of the drug equal to the calculated loading dose (Step 1). Aseptically transfer this volume (ml) of reconstituted caspofungin to an IV bag (or bottle) containing 250 ml of sodium chloride injection solution at 0.9%, 0.45%, or 0.225%, or lactated Ringer's solution. Alternatively, the volume (ml) of reconstituted caspofungin can be added to a reduced volume of sodium chloride injection solution at 0.9%, 0.45%, or 0.225%, or lactated Ringer's 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/m^2 infusion

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 (m^2) x 50 mg/m^2 = 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 caspofungin 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.
3. Withdraw from the vial a volume of the drug equal to the calculated daily maintenance dose (Step 1). Aseptically transfer this volume (ml) of reconstituted caspofungin to an IV bag (or bottle) containing 250 ml of sodium chloride injection solution at 0.9%, 0.45%, or 0.225%, or lactated Ringer's solution. Alternatively, the volume (ml) of reconstituted caspofungin can be added to a reduced volume of sodium chloride injection solution at 0.9%, 0.45%, or 0.225%, or lactated Ringer's 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.

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