CASPOFUNGINA TEVAGEN 50 mg POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION

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

Do not use Caspofungin Tevagen

• if you are allergic to caspofungin or 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 your medicine.

Warnings and precautions

Consult your doctor, pharmacist or nurse before starting to use Caspofungin 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 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), consult your doctor, pharmacist or nurse before starting to use caspofungin.

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

Using Caspofungin Tevagen with other medicines

Tell your doctor, pharmacist or nurse if you are taking, have recently taken or might take any other medicines. This includes medicines obtained without a prescription, including herbal medicines. This is because Caspofungin may affect the way other medicines work. Other medicines may also affect the way 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 you are not sure), consult your doctor, pharmacist or nurse before starting to use Caspofungin.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking 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 who use Caspofungin should not breast-feed.

Driving and using machines

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

Caspofungin Tevagen contains sodium

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

3. How to use Caspofungin Tevagen

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 be treated with Caspofungin and how much 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 Caspofungin Tevagen 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, telephone: 91 562 04 20, indicating the medicine and the amount ingested.

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 you already have: 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 may 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 haemoglobin (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.
• Diarrhoea, 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 clotting 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, high levels of some medicines that you are taking that weaken the immune system.
• Disorientation, feeling nervous, inability to sleep.
• Feeling dizzy, decreased sensation or sensitivity (especially in the skin), agitation, feeling sleepy, change in the way things taste, tingling or numbness.
• Blurred vision, increased tearing, swollen eyelid, yellow coloration of the white of the eyes.
• Feeling of rapid or irregular heartbeats, rapid heartbeat, irregular heartbeat, abnormal heartbeat, heart failure.
• Flushing, hot flushes, high blood pressure, low blood pressure, redness along a vein that is very sensitive to touch.
• Tightness in the muscle bands around the airways that leads to wheezing or cough, rapid breathing rate, waking up short of breath, 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, passing gas, stomach upset, swelling due to fluid accumulation around the abdomen.
• Decreased bile flow, enlarged liver, yellow coloration of the skin and/or the white of the eyes, liver injury caused by a medicine or a chemical, liver disorder.
• Abnormal skin tissue, generalised 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.
• High blood pressure and changes in some laboratory blood tests (such as kidney electrolyte tests and coagulation tests), high 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, feeling tired

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 get 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 via the Spanish Medicines Surveillance 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 Caspofungin Tevagen

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 refers to the last day of the month shown.

Unopened vial: store in a refrigerator (2°C - 8°C).

The stability data have shown that the concentrate for solution for infusion can be stored for up to 24 hours when the vial is stored at a temperature of 25°C or below and at 5 ± 3°C when reconstituted with water for injections. From a microbiological point of view, unless the opening/reconstitution/dilution method prevents the risk of microbial contamination, the product should be used immediately.

This is because it does not contain any ingredient to prevent the growth of bacteria. If not used immediately, the in-use storage times and conditions before use are the responsibility of the user.

The stability data of the diluted solution for infusion to the patient have shown that the product can be used within 48 hours between 2 and 8°C and at room temperature (25°C) when diluted in 9 mg/ml (0.9%) or 4.5 mg/ml (0.45%) or 2.25 mg/ml (0.225%) sodium chloride solution for infusion, or with Ringer's lactate solution.

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 exceed 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 Tevagen” 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. Container Content and Additional Information

Composition of Caspofungina Tevagen

Caspofungina Tevagen50 mg powder for concentrate for solution for infusion EFG

• The active ingredient is caspofungina. Each vial contains 50 mg of caspofungina (as acetate). After reconstitution in 10.5 ml, each ml of concentrate contains 5.2 mg of caspofungina.
• The other components are sucrose, mannitol, glacial acetic acid, and sodium hydroxide.

Caspofungina Tevagen70 mg powder for concentrate for solution for infusion EFG

• The active ingredient is caspofungina. Each vial contains 70 mg of caspofungina (as acetate). After reconstitution in 10.5 ml, each ml of concentrate contains 7.2 mg of caspofungina.
• The other components are sucrose, mannitol, glacial acetic acid, and sodium hydroxide.

Appearance of the Product and Container Content

Caspofungina Tevagen is a white to off-white lyophilized powder.

Each container contains a vial (10 ml) of powder.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Teva Pharma S.L.U.

C/ Anabel Segura, 11 Edificio Albatros B, 1ª planta

28108 Alcobendas Madrid

Spain

Manufacturer

Pharmathen S.A.

Dervenakion str., Pallini, Attiki

153 51, Greece

Or

Pharmadox Healthcare Ltd

KW20A Kordin Industrial Park, Paola

PLA 3000, Malta

Or

Merckle GmbH

Ludwig-Merckle-Strasse 3, Blaubeuren

Baden-Wuerttemberg

89143 Germany

Or

Teva Pharma B.V.

Swensweg 5

Haarlem

2031GA Netherlands

Or

ELPEN PHARMACEUTICAL CO.,

Marathonos Ave. 95, Pikermi Attiki,

19009 Greece

This pharmaceutical product is authorized in the EEA Member States under the following names:

Austria Caspofungin ratiopharm GmbH 50 mg Powder for concentrate for solution for infusion

Caspofungin ratiopharm GmbH 70 mg Powder for concentrate for solution for infusion

Belgium Caspofungin Teva Generics 50 mg powder for concentrate for solution for infusion / poudre pour solution à diluer pour perfusion / Pulver für ein Konzentrat zur Herstellung einer Infusionslösung

Caspofungin Teva Generics 70 mg powder for concentrate for solution for infusion / poudre pour solution à diluer pour perfusion / Pulver für ein Konzentrat zur Herstellung einer Infusionslösung

Croatia Kaspofungin Pliva 50 mg powder for concentrate for solution for infusion

Kaspofungin Pliva 70 mg powder for concentrate for solution for infusion

Denmark Caspofungin Teva B.V.

Estonia Caspofungin Teva Generics

France Caspofungine Teva Sante 50mg poudre pour solution à diluer pour perfusion

Caspofungine Teva Sante 70mg poudre pour solution à diluer pour perfusion

Germany Caspofungin-ratiopharm 50 mg Pulver für ein Konzentrat zur Herstellung einer Infusionslösung

Caspofungin-ratiopharm 70 mg Pulver für ein Konzentrat zur Herstellung einer Infusionslösung

Greece Caspofungin/Teva 50 mg κόνις για πυκνό διάλυμα για παρασκευή διαλύματος προς έγχυση

Caspofungin/Teva 70 mg κόνις για πυκνό διάλυμα για παρασκευή διαλύματος προς έγχυση

Hungary Caspofungin ratiopharm 50 mg por oldatos infúzióhoz való koncentrátumhoz

Caspofungin ratiopharm 70 mg por oldatos infúzióhoz való koncentrátumhoz

Italy Caspofungin Teva Italia

Lithuania Caspofungin Teva Generics 50 mg milteliai infuzinio tirpalo koncentratui

Caspofungin Teva Generics 70 mg milteliai infuzinio tirpalo koncentratui

Netherlands Caspofungine 50 mg Teva, poeder voor concentraat voor oplossing voor infusie

Caspofungine 70 mg Teva, poeder voor concentraat voor oplossing voor infusie

Poland Caspofungin Teva Pharmaceuticals

Portugal Caspofungina Teva

Slovenia Kaspofungin Teva 50 mg mg prašek za koncentrat za raztopino za infundiranje

Kaspofungin Teva 70 mg mg prašek za koncentrat za raztopino za infundiranje

Slovakia Caspofungin Teva B.V. 50 mg

Caspofungin Teva B.V. 70 mg

Spain Caspofungina Tevagen 50 & 70 mg polvo para concentrado para solución para perfusión EFG

United Kingdom Caspofungin Teva 50 mg & 70 mg Powder For Concentrate For Solution For Infusion

Date of the last revision of this leaflet: April 2020

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

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This information is intended only for healthcare professionals:

Instructions for reconstituting and diluting Caspofungina Tevagen:

Reconstitution of Caspofungina Tevagen

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

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

INSTRUCTIONS FOR USE IN ADULT PATIENTS

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 white to off-white lyophilized powder will dissolve completely. Mix gently until a clear solution is obtained. The reconstituted solutions should be inspected visually for particulate matter or discoloration. The reconstituted solution can be stored for a maximum of 24 hours at a temperature of 25°C or 5 ± 3°C.

Step 2 Addition of reconstituted Caspofungina Tevagen 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 aseptically the appropriate amount of reconstituted concentrate (as shown in the following table) 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 IN 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 patient's body surface area (BSA) 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 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 Tevagen 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 5 ± 3°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 aseptically this volume (ml) of reconstituted Caspofungina Tevagen to an intravenous bag or bottle containing 250 ml of sodium chloride injection solution 0.9%, 0.45%, or 0.225%, or lactated Ringer's solution. Alternatively, the volume (ml) of reconstituted Caspofungina Tevagen can be added to a reduced volume of sodium chloride injection solution 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 48 hours if stored refrigerated between 2 and 8°C or at room temperature (25°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 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 Tevagen 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 5 ± 3°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 aseptically this volume (ml) of reconstituted Caspofungina Tevagen to an intravenous bag or bottle containing 250 ml of sodium chloride injection solution 0.9%, 0.45%, or 0.225%, or lactated Ringer's solution. Alternatively, the volume (ml) of reconstituted Caspofungina Tevagen can be added to a reduced volume of sodium chloride injection solution 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 48 hours if stored refrigerated between 2 and 8°C or at room temperature (25°C).

Preparation Notes:

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

INSTRUCTIONS FOR USE IN ADULT PATIENTS

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 white to off-white lyophilized powder will dissolve completely. Mix gently until a clear solution is obtained. The reconstituted solutions should be inspected visually for particulate matter or discoloration. The reconstituted solution can be stored for a maximum of 24 hours at a temperature of 25°C or 5 ± 3°C.

Step 2 Addition of reconstituted Caspofungina Tevagen 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 aseptically the appropriate amount of reconstituted concentrate (as shown in the following table) 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 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 patient's body surface area (BSA) 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 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 Tevagen 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 5 ± 3°C. This will result in a final concentration of caspofungina in the vial of 7.2 mg/ml.
3. 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 Tevagen to an intravenous bag or bottle containing 250 ml of sodium chloride injection solution 0.9%, 0.45%, or 0.225%, or lactated Ringer's solution. Alternatively, the volume (ml) of reconstituted Caspofungina Tevagen can be added to a reduced volume of sodium chloride injection solution 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 48 hours if stored refrigerated between 2 and 8°C or at room temperature (25°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 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 Tevagen 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 5 ± 3°C. This will result in a final concentration of caspofungina in the vial of 7.2 mg/ml.
3. 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 Tevagen to an intravenous bag or bottle containing 250 ml of sodium chloride injection solution 0.9%, 0.45%, or 0.225%, or lactated Ringer's solution. Alternatively, the volume (ml) of reconstituted Caspofungina Tevagen can be added to a reduced volume of sodium chloride injection solution 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 48 hours if stored refrigerated between 2 and 8°C or at room temperature (25°C).

Preparation Notes:

1. The white to off-white cake will dissolve completely. Mix gently until a clear solution is obtained.
2. Inspect the reconstituted solution visually for particulate matter or discoloration during reconstitution and before infusion. Do not use if the solution is turbid or has precipitated.
3. Caspofungina Tevagen is formulated to provide the full dose of the vial as stated in the package insert (70 mg) when the appropriate volume is withdrawn from the vial.

1. 10 ml from the vial.