CASPOFUNGINA NORMON 50 mg POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION

2. What you need to know before you start using Caspofungin Normon

Do not use Caspofungin Normon

• 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 starting to use your medicine.

Warnings and precautions

Talk to 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 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 you are not sure), talk to your doctor, pharmacist, or nurse before starting to use caspofungin.

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

Using Caspofungin Normon with other medicines

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 your treatment.
• Some 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 you are not sure), talk to 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 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 Normon 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 Normon

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).
• Over 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 Normon 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, talk to your doctor or pharmacist 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 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 sweating more than usual.
• Pain in the joints.
• 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, high calcium levels in the blood, low magnesium levels in the blood, increase in the level of medicines you are taking that weaken the immune system.
• 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 heart rhythm, heart failure.
• Flushing, hot flashes, high blood pressure, low blood pressure, redness along a vein that is very sensitive to the touch.
• Tension 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, abdominal 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 medicine or a 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 you are taking that weaken the immune system.
• Chest discomfort, chest pain, feeling of changed body temperature, feeling unwell, general pain, swelling of the face, swelling of the ankles, hands, or feet, swelling, pain when touched, feeling of tiredness.

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, even if they are not listed in this leaflet. You can also report side effects directly through the Spanish Medicines Monitoring System: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Caspofungin Normon

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 (after “EXP”). The expiry date is the last day of the month stated.

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

Caspofungin Normon does not contain preservatives. From a microbiological point of view, the product should be used immediately. If not used immediately, the in-use storage times and conditions before use are the responsibility of the user and should not be greater than 24 hours between 2 and 8°C, unless the reconstitution and dilution have taken place in controlled and validated aseptic conditions.

Only a healthcare professional who has read the complete instructions should prepare the medicine (see “Instructions for reconstituting and diluting Caspofungin Normon” below).

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

6. Container Content and Additional Information

Composition ofCaspofungina Normon

• The active ingredient is caspofungina. Each vial of Caspofungina Normon contains 50 mg of caspofungina.
• The other components are sucrose, mannitol, glacial acetic acid, and sodium hydroxide (see section 2. What you need to know before you start using Caspofungina Normon).

Appearance of the Product and Container Content

Caspofungina Normon is a compact, sterile, white to off-white powder.

Each container contains one vial of powder.

Marketing Authorization Holder and Manufacturer

Other Sources of Information

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

This information is intended only for healthcare professionals:

Instructions for reconstituting and diluting Caspofungina Normon:

Reconstitution of Caspofungina Normon

DO NOT USE DILUENTS CONTAINING GLUCOSE, as Caspofungina Normon is not stable in diluents containing glucose. DO NOT MIX OR INFUSE Caspofungina Normon WITH ANY OTHER MEDICINE, as there is no data on the compatibility of Caspofungina Normon with other substances, additives, or intravenous pharmaceutical specialties. The infusion solution should be visually inspected for solid particles 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 injectable preparations aseptically. The concentration of the reconstituted vial will be 5.2 mg/ml.

The compact white to off-white lyophilized powder will dissolve completely. Mix gently until a clear solution is obtained. The reconstituted solutions should be visually inspected for 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 Caspofungina Normon 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 adding the appropriate amount of reconstituted concentrate (as shown in the table below) aseptically 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 turbid or has precipitated.

PREPARATION OF THE INFUSION SOLUTION FOR ADULTS

*10.5 ml should 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 body surface area (BSA) of the patient using the following formula: (Mosteller's formula[1])

Preparation of theinfusionof 70mg/m2for pediatric patients >3months (using a 50mg 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 vial of Caspofungina Normon to reach room temperature.
2. Asceptically, add 10.5 ml of water for injectable preparations. This reconstituted solution can be stored for up to 24 hours at a temperature equal to or below 25 °C. This will result in a final concentration of caspofungina in the vial of 5.2 mg/ml.
3. Withdraw from the vial a volume of the medication equal to the calculated loading dose (Step 1). Transfer this volume (ml) of reconstituted Caspofungina Normon aseptically to an intravenous (IV) bag or bottle containing 250 ml of 0.9% or 0.225% sodium chloride injection solution, or lactated Ringer's solution. Alternatively, the volume (ml) of reconstituted Caspofungina Normon can be added to a reduced volume of sodium chloride injection solution 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 equal to or below 25 °C or within 48 hours if stored refrigerated between 2 and 8 °C.

Preparation of the infusion of 50mg/m2for pediatric patients >3months (using a 50mg 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 vial of Caspofungina Normon to reach room temperature.
2. Asceptically, add 10.5 ml of water for injectable preparations. This reconstituted solution can be stored for up to 24 hours at a temperature equal to or below 25 °C. This will result in a final concentration of caspofungina in the vial of 5.2 mg/ml.
3. Withdraw from the vial a volume of the medication equal to the calculated daily maintenance dose (Step 1). Transfer this volume (ml) of reconstituted Caspofungina Normon aseptically to an IV bag or bottle containing 250 ml of 0.9% or 0.225% sodium chloride injection solution, or lactated Ringer's solution. Alternatively, the volume (ml) of reconstituted Caspofungina Normon can be added to a reduced volume of sodium chloride injection solution 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 equal to or below 25 °C or within 48 hours if stored refrigerated between 2 and 8 °C.

Preparation Notes:

• The white to off-white cake will dissolve completely. Mix gently until a clear solution is obtained.

• Visually inspect the reconstituted solution for solid particles or a change in color during reconstitution and before infusion. Do not use if the solution is turbid or has precipitated.

• Caspofungina Normon is formulated to provide the full dose of the vial as stated in the technical data sheet (50 mg) when 10 ml is withdrawn from the vial.

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