Clofarabine vivanta

Package leaflet: Information for the user

Clofarabine Vivanta, 1 mg/ml, concentrate for solution for infusion
Clofarabinum
Please read all of this leaflet carefully before this medicine is administered, because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, please ask your doctor.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm them even if their symptoms are the same as yours.
• If you experience any adverse reactions, including any possible side effects not listed in this leaflet, inform your doctor. See section 4.

Contents of the leaflet

1. What Clofarabine Vivanta is and what it is used for
2. Important information before using Clofarabine Vivanta
3. How to use Clofarabine Vivanta
4. Possible side effects
5. How to store Clofarabine Vivanta
6. Contents of the pack and other information

1. What Clofarabine Vivanta is and what it is used for

The active substance in Clofarabine Vivanta is clofarabine. Clofarabine belongs to a family of cytotoxic medicines. The medicine works by inhibiting the growth of abnormal white blood cells, leading consequently to their death. It works best on rapidly dividing cells—such as cancer cells.
Clofarabine Vivanta is used to treat children (≥ 1 year of age), adolescents, and young adults up to 21 years of age with acute lymphoblastic leukaemia (ALL), when previous treatments have not worked or are no longer effective. Acute lymphoblastic leukaemia is caused by abnormal development of a certain type of white blood cells.

2. Information before using Clofarabine Vivanta

When not to use Clofarabine Vivanta:

• if the patient is allergic to clofarabine or any of the other ingredients of this medicine (listed in section 6);
• if the patient is breastfeeding (please read the section "Pregnancy and breastfeeding" below);
• if the patient has severe kidney or liver disease.

Inform the doctor if any of the above conditions apply to the patient.
The parent of a child receiving Clofarabine Vivanta should inform the doctor if any of the above conditions apply to their child.

Warnings and precautions

Inform the doctor if any of the following conditions apply to the patient. Clofarabine Vivanta may not be suitable for the patient:

• if the patient has experienced a severe reaction to a previous treatment with this medicine;
• if the patient has or has previously had kidney disease;
• if the patient has or has previously had liver disease;
• if the patient has or has previously had heart disease.

Contact the doctor or caregiver immediately if the patient experiences any of the following symptoms:

• if the patient develops fever or elevated temperature – clofarabine reduces the number of blood cells produced by the bone marrow, making the patient more susceptible to infections;
• if the patient experiences difficulty breathing, breathes rapidly, or has shortness of breath;
• if the patient feels changes in heart rhythm;
• if the patient experiences dizziness (a feeling of emptiness in the head) or fainting – these may be signs of low blood pressure;
• if the patient vomits or has diarrhoea (loose stools);
• if the patient's urine is darker than usual – remember to drink plenty of fluids to avoid dehydration;
• if the patient develops blistering rash or mouth ulcers;
• if the patient loses appetite, feels nauseous, vomits, has diarrhoea, urine is darker than usual, stools are lighter than usual, has abdominal pain, jaundice (visible yellowing of the skin and whites of the eyes), or feels generally unwell – these may be symptoms of liver inflammation or damage (liver failure);
• if the patient passes little or no urine, or feels drowsy, nauseous, vomits, feels short of breath, has no appetite, and/or feels weak – these may be symptoms of acute kidney failure.

The parent of a child receiving Clofarabine Vivanta should inform the doctor if any of the above symptoms occur in their child.

During treatment with Clofarabine Vivanta, the doctor will perform regular blood tests and other examinations to monitor the patient's health. The mechanism of action of this medicine affects the patient's blood and other organs.

Consult the doctor about contraception. Young men and women must use effective contraception during and after completion of treatment. See the section "Pregnancy and breastfeeding" below. Clofarabine Vivanta may damage male and female reproductive organs. Ask the doctor for advice on how to protect the patient and on the possibility of having children in the future.

Clofarabine Vivanta and other medicines

Tell the doctor about all medicines currently used or recently used by the patient, such as:

• medicines used for heart conditions;
• any medicines affecting blood pressure;
• medicines affecting the liver or kidneys;
• any other medicines, including those available without a prescription.

Pregnancy and breastfeeding

Clofarabine should not be used during pregnancy, except when clearly necessary.

Women of childbearing potential: the patient must use effective contraception during treatment with clofarabine and for 6 months after treatment ends. Clofarabine taken by pregnant women may be harmful to the unborn baby. If the patient is pregnant or becomes pregnant during treatment with clofarabine, seek medical advice immediately.

Men must also use effective contraception and should be advised not to father a child during treatment with clofarabine and for 3 months after treatment ends.

If the patient is breastfeeding, breastfeeding must be stopped before starting treatment and must not be resumed during treatment or for 2 weeks after treatment ends.

Driving and operating machinery

Do not drive or operate machinery if the patient experiences dizziness, a feeling of emptiness in the head, or fainting.

Clofarabine Vivanta contains sodium

One vial of this medicine contains 71 mg of sodium (the main component of table salt). This corresponds to 3.5% of the recommended maximum daily sodium intake for an adult. Patients, especially those monitoring salt (sodium) intake in their diet, who are receiving 5 or more vials per day over a prolonged period, should consult a pharmacist or doctor.

3. How to use Clofarabine Vivanta

Clofarabine Vivanta should be administered by a qualified physician experienced in the treatment of leukemias.
The physician will determine the appropriate dose for the patient based on height, body weight, and overall health status. Prior to administration, Clofarabine Vivanta will be diluted with sodium chloride solution (a saline solution of salt and water). Patients on a salt-restricted diet should inform their physician, as this may influence the method of drug administration.

The physician will administer Clofarabine Vivanta daily for 5 consecutive days. The medication will be given as an intravenous infusion via a long, thin tube inserted into a vein (intravenous drip) or through a small device implanted under the skin (an implanted intravenous access device), if one has been placed in the patient (or child). The infusion will last 2 hours. If the patient’s (or child’s) body weight is less than 20 kg, the infusion duration may be extended.

The physician will monitor the patient’s health condition and may adjust the dose depending on the response to treatment. It is important to drink plenty of fluids to prevent dehydration.

Overdose of Clofarabine Vivanta
If the patient suspects that a higher than recommended dose has been administered, they should immediately inform the physician.

Missed dose of Clofarabine Vivanta
The physician will inform the patient when the medication is to be administered. If a dose is missed, the patient should immediately notify the physician.

If there are any doubts regarding the use of this medication, the patient should consult their treating physician.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everybody will experience them.

Very common (may affect more than 1 in 10 people):

• anxiety, headache, fever, fatigue;
• nausea and vomiting, diarrhoea (loose stools);
• sudden flushing and skin inflammation with itching, mucositis (e.g. in the mouth or other sites);
• increased frequency of infections, as clofarabine may reduce the number of certain types of blood cells in the patient's body;
• skin rashes which may cause itching, red, painful or peeling skin on hands and feet, or red or purple spots under the skin.

Common (may affect up to 1 in 10 people):

• blood infections, pneumonia, shingles, implant infections, oral infections such as candidiasis or cold sores;
• changes in blood biochemical test results, changes in white blood cells;
• allergic reactions;
• feeling thirsty, dark-coloured urine or reduced urine volume compared to usual, decreased or loss of appetite, weight loss;
• restlessness, irritability or agitation;
• numbness or weakness in arms and legs, skin tingling, drowsiness, dizziness, tremor;
• hearing disturbances;
• fluid accumulation around the heart, rapid heart rate;
• low blood pressure, induration associated with bruising;
• leakage from small blood vessels, rapid breathing, nosebleeds, difficulty breathing, shortness of breath, cough;
• vomiting blood, stomach pain, anal pain;
• bleeding inside the head, stomach, intestines or lungs, from the mouth or gums, mouth ulcers, inflammation of the oral mucosa;
• yellowing of the skin and eyes (also known as jaundice) or other liver function abnormalities;
• bruising, hair loss, skin colour changes, increased sweating, dry skin or other skin problems;
• chest wall or bone, neck or back pain, limb, muscle or joint pain;
• blood in the urine;
• organ failure, pain, increased muscle tension, fluid retention and swelling of parts of the body including arms and legs, changes in mental state, feeling hot, cold or generally unwell;
• clofarabine may affect levels of certain substances in the blood. Your doctor will perform regular blood tests to monitor whether your body is functioning properly;
• liver damage (liver failure);
• reduced urine output or no urine production, drowsiness, nausea, vomiting, shortness of breath, loss of appetite and/or weakness (possible symptoms of acute kidney injury or kidney failure).

Uncommon (may affect up to 1 in 100 people):

• hepatitis.

Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform your doctor. Adverse reactions can also be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, telephone: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the representative of the marketing authorisation holder.
Reporting adverse reactions helps provide more information on the safety of the medicine.

5. How to store Clofarabine Vivanta

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the vial label and on the carton after "EXP". The expiry date refers to the last day of the stated month.
There are no special storage requirements for this medicine.
Storage instructions after dilution:
After preparation and dilution, Clofarabine Vivanta should be used immediately or within 24 hours if stored refrigerated (at 2°C to 8°C).
Medicines should not be disposed of via wastewater. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

What Clofarabine Vivanta contains

• The active substance is clofarabine. Each ml contains 1 mg of clofarabine. Each 20 ml vial contains 20 mg of clofarabine.
• The other ingredients are sodium chloride and water for injections.

What Clofarabine Vivanta looks like and contents of the pack
Clofarabine Vivanta is a concentrate for solution for infusion. It is a clear, practically colourless solution which must be prepared and diluted before use. The medicine is supplied in 20 ml vials. The vials contain 20 mg of clofarabine and are packaged in cardboard boxes. Each cardboard box contains 1, 3, 4, 10 or 20 vials, although not all pack sizes may be marketed.

Marketing Authorisation Holder:
Vivanta Generics s.r.o.
Třtinová 260/1, Čakovice
196 00 Prague 9
Czech Republic
Tel.: (+48) 699 711 147

Importer:
Pharmadox Healthcare Ltd.
KW20A Kordin Industrial Park
Paola, PLA 3000
Malta

This medicinal product is authorised for marketing in the European Economic Area countries under the following names:
Portugal: Clofarabina Vivanta 1 mg/ml de concentrado para solução para perfusão
Czech Republic: Clofarabine Vivanta
Hungary: Clofarabine Vivanta 1 mg/ml koncentrátum oldatos infúzióhoz
Poland: Clofarabine Vivanta
Romania: Clofarabine Vivanta 1 mg/ml concentraat voor oplossing voor infusie
Netherlands: Clofarabine Vivanta 1 mg/ml concentrat pentru soluţie perfuzabilă

Clofarabine Vivanta contains the same active substance and works in the same way as the “reference medicinal product” already authorised in EU countries. The reference medicinal product for Clofarabine Vivanta was authorised under “exceptional circumstances”. This means that, due to the rarity of the disease, it was not possible to obtain complete information on the reference medicinal product. The European Medicines Agency reviews all new information on the reference medicinal product annually, and any updates to the reference product are also included in the relevant information for Clofarabine Vivanta, such as this leaflet.

Instructions for use for healthcare professionals

Handling of clofarabine

Information intended exclusively for healthcare professionals:

Special precautions for the preparation of the medicinal product for administration

Before administration, Clofarabine Vivanta 1 mg/ml concentrate for solution for infusion must be diluted. It should be filtered through a sterile syringe filter with a pore size of 0.2 micrometres and then diluted with sodium chloride 9 mg/ml (0.9%) solution for injection to achieve a total volume according to the example provided in the table below. However, the final dilution volume may vary depending on the patient's clinical condition and the physician's decision. (If a syringe filter with a pore size of 0.2 micrometres is not available, the concentrate should first be filtered through a filter with a pore size of 5 micrometres, then diluted, and administered through an in-line filter with a pore size of 0.22 micrometres.)

The diluted concentrate should be a clear, colourless solution. It should be inspected visually for particulate matter and discoloration prior to administration.
The diluted concentrate is chemically and physically stable for 3 days at a temperature of 2°C to 8°C and at room temperature (up to 25°C). From a microbiological point of view, the medicinal product should be used immediately. If not used immediately, the user is responsible for the storage time and conditions prior to use. This time should not exceed 24 hours at a temperature of 2°C to 8°C, unless dilution took place under controlled and validated aseptic conditions. Do not freeze.
Administration instructions
Appropriate procedures for handling cytotoxic drugs must be observed. Caution should be exercised when handling cytotoxic medicinal products.
When handling the medicinal product containing clofarabine, it is recommended to wear disposable gloves and protective clothing. In case of contact with eyes, skin or mucous membranes, the affected area should be immediately flushed with copious amounts of water.
Pregnant women should avoid contact with clofarabine.
Disposal of unused product
Clofarabine is intended for single use only. Any unused residues of the medicinal product or waste materials should be disposed of in accordance with local regulations.