Cladribine 1mg/Ml Concentrate For Solution For Infusion
Package leaflet: Information for the user
Cladribine 1mg/ml Concentrate for Solution for Infusion
Cladribine
Cladribine 1mg/ml Concentrate for Solution for Infusion will be referred to as Cladribine throughout the package leaflet.
Read all of this leaflet carefully before you start using this medicine because it contains important information for you.
• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist or nurse.
• If you get any side effects, talk to your doctor or pharmacist or nurse. This includes any possible side effects not listed in this leaflet.
What is in this leaflet:
1. What Cladribine is and what it is used for
2. What you need to know before you use Cladribine
3. How to use Cladribine
4. Possible side effects
5. How to store Cladribine
6. Contents of the pack and other information
1. What Cladribine is and what it is used for
Cladribine contains a medicine called Cladribine. This belongs to a group of medicines called antineoplatic agents used to treat cancer (called ‘cytotoxic drugs’).
Cladribine is indicated for illness caused by the abnormal growth of white blood cells. This is called Hairy Cell Leukaemia (HCL).
Cladribine works by killing abnormal white blood cells.
2. What you need to know before you use Cladribine Do not take Cladribine if:
• you are allergic to Cladribine or any of the other ingredients of this medicine (listed in Section 6).
• if you are breast-feeding
• if you have moderate to severe kidney or liver impairment
• if you have an infection
Warnings and precautions
Tell your doctor if you have or have had:
- liver or kidney problems
- infections
• if you suffer from an infection, this will be treated before you start using Cladribine
• if you notice any signs of infections (such as flu-like symptoms or fever) during or after treatment with Cladribine, inform your doctor immediately.
- fever
Before and during treatment with Cladribine, you will have regular blood tests to check whether it is safe for you to continue with your treatment. Your doctor may decide that you should receive blood transfusions to improve your level of blood cells. In addition, the proper function of your liver and your kidneys will be checked.
If you want to father a child, please tell your doctor before treatment with Cladribine is started. You should not father a child during treatment and up to 6 months after treatment with Cladribine.
Children and adolescents
Cladribine has not been fully tested for use in children.
Other medicines and Cladribine Tell your doctor or pharmacist if you are using, have recently used or might use any other medicines. This includes medicines that you buy without a prescription or herbal medicines.
In particular tell your doctor if you are already taking or are to be given:
• A live vaccine while being treated with Cladribine
• Medicines to treat viral infections including HIV (such as didanosine, tenofovir, adefovir)
• corticosteroids, commonly used to treat inflammation
You must not use Cladribine with other medicines that affect the production of blood cells in the bone marrow (myelosuppression).
Pregnancy, breast-feeding and fertility
Do not use this medicine if you are pregnant, think you may be pregnant or are planning to have a baby. Ask your doctor or pharmacist for advice before taking this medicine. This is because it may affect the baby.
If pregnancy occurs during your treatment, you must immediately inform your doctor.
You must not breast-feed while you are being treated with Cladribine, or for 6 months after your treatment ends.
Men should not father a child until at least 6 months after the last dose of Cladribine.
Driving and using machines
Cladribine has a major effect on the ability to drive and use machines. If you feel drowsy, which may occur due to a low number of red blood cells caused by Cladribine treatment, or dizzy, you should not drive or use machines.
Cladribine contains Sodium
If you need to control your salt intake (controlled sodium diet) be aware that:
• Each Cladribine vial contains approximately 1.55 mmol sodium (35.4mg)
• The contents of the vial are diluted in a salt solution (called ‘saline’) before being given to you. This salt solution also contains sodium.
3. How to use Cladribine How your medicine is given
Cladribine is put in a drip and given slowly into a vein. It is normally diluted in a salt solution (called ‘saline’).
You will never be expected to give yourself this medicine. A doctor experienced at using this type of medicine will give it to you. Check with your doctor or pharmacist if you are not sure.
Adults and the elderly
The dose of Cladribine is based on your body weight in kilograms.
For abnormal growth of hairy white blood cells (HCL):
• The usual dose is 0.09mg per kilogram each day
• The dose is given over 24 hours every day for 7 days, without a break
Use in children and adolescents
Cladribine has not been fully tested for use in children.
If you use more Cladribine than you should
Tell your doctor or nurse straight away if you think you have been given too much Cladribine.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist or nurse.
4. Possible side effects
Like all medicines, Cladribine can cause side effects, although not everybody gets them. Some side effects may be the same as symptoms of the illness. Your doctor may decide to delay or stop using Cladribine if you get side effects.
Tell your doctor or nurse straight away if you notice any of the following serious side effects. You may need urgent medical treatment.
• The sudden appearance of rash, itching, hives (also known as nettle rash or urticaria), swollen face or lips, or shortness of breath. These may be signs of an allergic reaction.
• Fever and chills (affects more than 1 in 10 people). These may be the first signs that you have an infection. The infection may happen because of a fall in the number of white
blood cells (neutropenia). Some infections are more common than others. Infection can happen anywhere in your body including:
o Your chest (cough, shortness of breath or difficulty breathing, noisy breathing, pneumonia)
o Your urinary system (pain or discomfort on passing water) Your skin (bacterial, fungal or viral infections that may leave the skin tender, hot or red) o Your mouth (a fungal infection called thrush) o Your gut (infection or inflammation of the intestines) o Your blood (septicaemia)
• Easier bruising and bleeding under the skin (thrombocytopenia) or red or purple spots under the skin (petechiae). This can be caused by a fall in the number of small blood cells called platelets (affects more than 1 in 10 people) or problems with blood clotting.
• Feeling weak or breathless. This can be caused by a fall in the number of red blood cells (anaemia). The anaemia may be severe (affects more than 1 in 10 people)
• Build-up of fluid under the skin called oedema (affects more than 1 in 10 people)
• Swelling and clotting in a vein called phlebitis (affects less than 1 in 10 people)
• Stevens-Johnson syndrome (a serious illness with blistering of the skin, mouth, eyes and genitals) (affects less than 1 in 100 people)
• Tumour lysis syndrome (a serious condition resulting from breakdown of tumour cells. This can lead to heart and kidney problems, weakness and fits) (affects less than 1 in 100 people)
• Repeated occurrence of malignant (cancerous) disease cannot be excluded. This means that the risk that you develop a malignant disease in the future is slightly higher than for healthy people. This slightly increased risk can be due to your disease or to therapies used to treat the disease including Cladribine.
Tell your doctor or nurse at your next appointment if you notice any of the following side effects:
Very common (affects more than 1 in 10 people)
• Feeling dizzy or tired
• Headache
• Rash, sweating
• Feeling sick (nausea), being sick (vomiting)
• Redness, swelling or pain where the injection was given
Common (affects less than 1 in 10 people)
• Faster heart beat
• Stomach pain or wind (flatulence)
• Having less appetite
• Constipation or diarrhoea
• Joint pain, muscle pains or weakness
• Generalised pain
• Anxiety or difficulty sleeping (insomnia)
• Itching (pruritus)
• Conjunctivitis
• Generally feeing unwell Uncommon (affects less than 1 in 100 people)
• A problem that affects the body being able to produce white blood cells, red blood cells and small blood cells (platelets). The effects may need further treatment
• An increase in a particular type of white blood cell (eosinophil)
• A decrease in the ability of your kidneys being able to get rid of waste products from the blood, and a decrease in urine production
• Serious nerve damage. The effects include partial or complete paralysis and may be permanent
• An increase in liver enzymes (shown in blood tests)
• Confusion, reduced consciousness, co-ordination problems (ataxia)
If any of the side effects gets serious, or if you notice any other side effects not listed in this leaflet, please tell your doctor or nurse.
5. How to store Cladribine
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 label, carton after EXP. The expiry date refers to the last day of that month.
Store in a refrigerator.
After Dilution:
Chemical and Physical in-use stability has been demonstrated for 24 hours at 25° C.
From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are responsibility of the user and would not normally be longer than 24 hours at 2° to 8°C , unless dilution has taken place in controlled and validated aseptic conditions
Do not use this medicine if:
• the seal is broken or a dose has already taken from the vial
• you notice discoloration or you can see particles flowing in it
• it has been diluted and refrigerated for more than 8 hours
• it has been diluted with a solution of 5% dextrose
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.
6. Contents of the pack and other information
What Cladribine contains
The active substance is cladribine.
Each ml of Cladribine contains 1mg of cladribine. Each vial contains 10 mg of Cladribine (in 10 ml of liquid).
The other ingredients are Sodium chloride, Phosphoric acid, Disodium phosphate anhydrous and Water for Injections.
What Cladribine looks like and contents of the pack
It is supplied in glass vials containing clear, colourless solution.
It is available in 20 ml vials, in a box containing 1 & 7 vials.
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation holder
Mylan
Potters Bar, Hertfordshire, EN6 1TL, United Kingdom. Manufacturer
Agila Specialties Polska Sp.z.o.o 10, Daniszewska Str,
03-230 Warsaw, Poland
The leaflet was last revised in 10/2014
This information is intended for medical or healthcare professionals only.
INFORMATION FOR THE HEALTHCARE PROFESSIONALS
Please see the Summary of Product Characteristics for more information.
Preparation and administration of intravenous solutions:
Cladribine must be diluted with the designated diluent prior to administration. Since the drug product does not contain any anti-microbial preservative or bacteriostatic agent, aseptic technique and proper environmental precautions must be observed in preparation of a solution of Cladribine.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. A precipitate may occur during the exposure of Cladribine to low temperatures; it may be resolubilised by allowing the solution to warm naturally to room temperature and by shaking vigorously. DO NOT HEAT OR MICROWAVE.
Care must be taken to assure the sterility of prepared solutions. Once diluted, solutions of Cladribine should be administered promptly or stored in the refrigerator (2° to 8°C) for no more than 8 hours prior to start of administration. Vials of Cladribine are for single-use only. Any unused portion should be discarded in an appropriate manner.
The potential hazards associated with cytotoxic agents are well established and proper precautions should be taken when handling, preparing, and administering Cladribine. The use of disposable gloves and protective garments is recommended. If Cladribine contacts the skin or mucous membranes, wash the involved surface immediately with copious amounts of water.
Preparation of a Single Daily Dose:
Add the calculated dose for a 24 hour period (0.09 mg/kg or 0.09 ml/kg or 3.6 mg/m2) of Cladribine to an infusion bag containing 100 ml to 500 ml of 0.9% sodium chloride injection (PhEur). Infuse intravenously continuously over 24 hours. Repeat daily for a total of 7 consecutive days.
The use of 5% dextrose as a diluent is not recommended because of increased degradation of cladribine. Admixtures of Cladribine are chemically and physically stable for at least 24 hours at room temperature under normal room fluorescent light in most commonly available PVC infusion containers.
|
DOSE OF CLADRIBINE |
RECOMMENDED DILUENT |
QUANTITY OF DILUENT | |
|
HCL: 24-hour infusion method |
0.09 mg/kg/day |
0.9% sodium chloride injection, PhEur |
100 ml to 500 ml |
Any unused product or waste material should be disposed of in accordance with local requirements.
How to store Cladribine
Store in a refrigerator.
After Dilution:
Chemical and Physical in-use stability has been demonstrated for 24 hours at 25° C.
From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are responsibility of the user and would not normally be longer than 24 hours at 2° to 8°C, unless dilution has taken place in controlled and validated aseptic conditions
Posology
Usual dose:
Adults and elderly:
The recommended treatment for Hairy Cell Leukaemia is a single course of Cladribine given by continuous intravenous infusion for 7 consecutive days at a dose of 0.09 mg/kg/day (3.6 mg/m2/day). Deviations from this dosage regimen are not advised. Physicians should consider delaying or discontinuing the drug if neurotoxicity or renal toxicity occurs.
If a patient with HCL does not respond to the initial course of cladribine, it is not likely that the patient will benefit from additional courses.
Children:
Safety and efficacy in children have not been established.
Specific risk factors predisposing to increased toxicity from Cladribine have not been defined. In view of the known toxicities of agents of this class, it would be prudent to proceed carefully in patients with known or suspected renal insufficiency or severe bone marrow impairment of any aetiology. Patients should be monitored closely for haematological and renal and hepatic toxicity.
Overdose
Signs and symptoms of overdose may include nausea, vomiting, diarrhoea, severe bone marrow depression (including anaemia, thrombocytopenia, leukopenia, and agranulocytosis), acute renal insufficiency, as well as irreversible neurologic toxicity (paraparesis/quadriparesis), Guillain Barre and Brown Sequard syndromes. Acute, irreversible neuro- and nephrotoxicity have been described in individual patients treated at a dose which was ^ 4 times higher than the recommended regimen for hairy cell leukaemia.
No specific antidote exists. Immediate discontinuation of therapy, careful observation, and initiation of appropriate supportive measures (blood transfusions, dialysis, haemofiltration, antiinfectious therapy, etc.) are the indicated treatment of overdose of cladribine. Patients who have received an overdose of cladribine should be monitored haematologically.