CASPOFUNGINA HIKMA 50 mg POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION

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

Do not use Caspofungina Hikma

• 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 using your medicine.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before 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 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 caspofungina.

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

Other medicines and Caspofungina Hikma

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 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 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 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 using 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 developing baby.
• Women using 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 Hikma

Caspofungina will always be prepared and administered 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 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 Hikma 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, 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, mucous membrane lesions, blisters, 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.
• Veno-occlusive disease.
• 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, 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 tears, 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, 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, fluid leakage from the catheter to the tissue), inflammation of the vein 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 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, even if they are 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 Caspofungina Hikma

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 indicated.

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

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

If not used immediately, the solution can be stored for up to 24 hours at 25°C or less or for 48 hours when the intravenous infusion bag (bottle) is stored refrigerated (2 to 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 lactated Ringer's solution. If not used immediately, the storage times and conditions before use are the responsibility of the user and should not normally exceed 24 hours between 2 and 8°C, unless reconstitution and dilution have taken place under validated controlled aseptic conditions.

Do not use the solution if you notice 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. This will help protect the environment.

6. Contents of the pack and further information

Composition of Caspofungina Hikma

• The active substance is caspofungina.

Caspofungina Hikma 50 mg powder for concentrate for solution for infusion EFG.

Each vial of Caspofungina Hikma contains 50 mg of caspofungina (as acetate).

Caspofungina Hikma 70 mg powder for concentrate for solution for infusion EFG.

Each vial of Caspofungina Hikma contains 70 mg of caspofungina (as acetate).

• The other ingredients are sucrose, mannitol, hydrochloric acid (for pH adjustment), sodium hydroxide (for pH adjustment), carbon dioxide (for pH adjustment) (see section 2. What you need to know before you use Caspofungina Hikma).

Appearance and packaging

Caspofungina Hikma is a compact, sterile, white to off-white powder. The reconstituted solution is clear.

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

10 ml Type I glass vial with a bromobutyl stopper and a plastic cap with a red aluminum band.

Caspofungina Hikma 70 mg powder for concentrate for solution for infusion EFG.

10 ml Type I glass vial with a bromobutyl stopper and a plastic cap with an orange aluminum band.

Each pack contains one vial of powder.

Marketing authorization holder and manufacturer

Marketing authorization holder

Hikma Farmacêutica (Portugal), S.A.

Estrada do Rio da Mó n.º 8, 8A e 8B – Fervença

2705-906 Terrugem SNT

Portugal

Tel.: ++351 21 960 84 10

Fax: ++351 21 961 51 02

E-mail: [email protected]

Manufacturer

Pharmadox healthcare, ltd

KW20A Kordin Industrial Park, Paola

PLA 3000Malta

Galenicum Health, S.L.U.

Sant Gabriel, 50Esplugues de Llobregat 08950

Barcelona, España

SAG Manufacturing S.L.U.

Ctra. N-I, Km 36

San Agustín de Guadalix, 28750,

Madrid, España

Hikma Italia S.p.A.

Viale Certosa, 10,

27100, Pavia (PV),

Italia

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Hikma España, S.L.U.

Calle Anabel Segura nº11, Edificio A, planta 1ª, oficina 2

28108 - Alcobendas, Madrid

España

Date of last revision of this leaflet:JULY 2020

This information is intended only for healthcare professionals:

Instructions for reconstituting and diluting Caspofungina Hikma:

Reconstitution of caspofungina hikma

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 on the compatibility of CASPOFUNGINA with other substances, additives, or intravenous pharmaceutical specialties. The infusion solution should be visually inspected for particulate matter or a change in color.

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

INSTRUCTIONS FOR USE IN ADULT PATIENTS(vial 50 mg)

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 powder of white to off-white color will dissolve completely. Mix gently until a clear solution is obtained. The reconstituted solutions must be inspected visually 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 caspofungin 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 cloudy or has precipitated.

Vial 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

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 formula [1])

BSA (m2) =

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 dose calculated 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 equal to or below 25 °C

• 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 caspofungin 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 caspofungin 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 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 50 mg/m

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 dose calculated 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.

a This reconstituted solution can be stored for up to 24 hours at a temperature equal to or below 25 °C.

b 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 caspofungin 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 caspofungin 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 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.

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

INSTRUCTIONS FOR USE IN ADULT PATIENTS(vial 70 mg)

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 powder of white to off-white color will dissolve completely. Mix gently until a clear solution is obtained. The reconstituted solutions must be inspected visually 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 Caspofungin reconstituted 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 cloudy or has precipitated.

70 mg vial: 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 body surface area (BSA) of the patient using the following formula: (Mosteller formula)

BSA (m2) =

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 dose calculated 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

a This reconstituted solution can be stored for up to 24 hours at a temperature equal to or below 25 °C

b 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 caspofungin 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 caspofungin 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 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 50 mg/m

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 dose calculated 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.

a This reconstituted solution can be stored for up to 24 hours at a temperature equal to or below 25 °C.

b 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 caspofungin 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 caspofungin 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 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.

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