SUMMARY CMI

LITAK^®

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I using LITAK?

LITAK contains the active ingredient cladribine. LITAK is used to treat hairy cell leukaemia and lymphoplasmacytic lymphoma (also known as Waldenström's Macroglobulinaemia).

For more information, see Section 1. Why am I using LITAK? in the full CMI.

2. What should I know before I use LITAK?

Do not use if you have ever had an allergic reaction to LITAK or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I use LITAK? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with LITAK and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use LITAK?

• LITAK should only be administered by a doctor or nurse.

More instructions can be found in Section 4. How do I use LITAK? in the full CMI.

5. What should I know while using LITAK?

For more information, see Section 5. What should I know while using LITAK? in the full CMI.

6. Are there any side effects?

Tell your doctor or nurse if you experience any of the following: serious bacterial infection of the blood (blood poisoning), allergic reactions, anaemia, confusion, including disorientation, liver disease, swollen runny eyes, lung disease, itchy rash, renal failure, fatigue, headache, dizziness, decreased appetite, weakness/feebleness, and chills, feeling sick, upset stomach, vomiting, stomach pain, flatulence, constipation, diarrhoea, painful joints, muscle or bone, sleeplessness, anxiety.

Tell your doctor or nurse as soon as possible if you notice any of the following: bleeding, bruising more easily than normal, symptoms suggestive of infections; numbness and tingling, usually of the hands and feet, signs of an infection (such as fever, severe chills, sore throat, cough or mouth ulcers), shortness of breath, tiredness, weakness, dizziness, looking pale, difficulty or changes to breathing, yellowing of the skin and/or eyes, skin rash, itchiness, swelling in hands, ankles or feet, any unexplained changes in your behaviour or in your mental and emotional states, any neurological changes such as eye & speech problems or walking.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.

FULL CMI

LITAK^®

Active ingredient: cladribine

Consumer Medicine Information (CMI)

This leaflet provides important information about using LITAK. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using LITAK.

Where to find information in this leaflet:

1. Why am I using LITAK?
2. What should I know before I use LITAK?
3. What if I am taking other medicines?
4. How do I use LITAK?
5. What should I know while using LITAK?
6. Are there any side effects?
7. Product details

1. Why am I using LITAK?

LITAK contains the active ingredient cladribine. LITAK belongs to a group of medicines called antineoplastic medicines (cytotoxic or chemotherapy agents). This medicine works by helping to stop the uncontrolled increase and abnormal growth of cancer cells.

LITAK is used to treat:

• hairy cell leukaemia
• lymphoplasmacytic lymphoma (also known as Waldenström's Macroglobulinaemia)

Ask your doctor if you have any questions about why this medicine has been prescribed for you.

LITAK is only available on a doctor's prescription.

2. What should I know before I use LITAK?

Warnings

Do not use LITAK if:

• you are allergic to any medicine containing cladribine, or any of the ingredients listed at the end of this leaflet. Some of the symptoms of an allergic reaction may include:
  - shortness of breath
  - wheezing or difficulty breathing
  - swelling of the face, lips, tongue or other parts of the body
  - rash, itching or hives on the skin
  Always check the ingredients to make sure you can use this medicine.
• you have kidney or liver disease
• you are using other chemotherapy drugs

Do not give this medicine to a child under the age of 18 years.

Safety and effectiveness in children younger than 18 years have not been established.

Check with your doctor if you:

• are pregnant or planning to become pregnant
• are breastfeeding or wish to breastfeed
• are trying to make your partner pregnant
• have allergies to any other medicines, foods, preservatives or dyes.
• have or have had any of the following medical conditions:
  - any allergies
  - any infections
  - kidney disease
  - liver disease
  - a fever

If you suffer from an infection, this will be treated before treatment with LITAK.

Before you start treatment with LITAK and during treatment, you will have regular blood tests to check whether it is safe for you to continue with your treatment.

In addition, the function of your liver and your kidneys will be checked.

Your doctor may decide that you should receive an additional medicine containing the active substance allopurinol in order to reduce excess of uric acid.

If you have not told your doctor about any of the above, tell them before you start receiving LITAK.

Your doctor will advise you whether or not to have the LITAK injection or if you need to adjust the dose or adapt your treatment.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Do not receive this medicine if you are pregnant.

It may affect your developing baby if you take it during pregnancy.

Do not breastfeed if you are taking this medicine.

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

Do not take vaccines prepared from live microorganisms or functional viruses, because they may increase your risk of infections.

Some medicines and LITAK may interfere with each other. These include:

• medicines which interfere with the process of production of blood cells in the bone marrow
• corticosteroids, medicines used to reduce inflammation or to suppress the immune system

These medicines may be affected by LITAK or may affect how well it works. You may need different amounts of your medicines, or you may need to take different medicines.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking this medicine.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect LITAK.

4. How do I use LITAK?

Therapy with LITAK should be initiated by a qualified doctor with experience in cancer chemotherapy.

How much is given

Your doctor will decide what dose you will receive. This depends on your condition and other factors, such as your weight. The recommended dosages for the following conditions are:

Hairy Cell Leukaemia

• Subcutaneous bolus injection:
  A single course of LITAK is given by subcutaneous bolus injection at a dose of 0.14 mg per kilogram of body weight, per day, for five consecutive days.
• Intravenous infusion:
  A single course of LITAK is given at a dose of 0.10 mg per kilogram of body weight, per day, for seven consecutive days.

Lymphoplasmacytic lymphoma

• Subcutaneous bolus injection:
  A dose of 0.10 mg per kilogram of body weight, per day, for five consecutive days at monthly intervals.

How it is given

LITAK is injected under your skin (subcutaneous injection) or directly into the veins (intravenous infusion).

LITAK should only be administered by a doctor or nurse.

For subcutaneous bolus injection: the recommended dose is directly withdrawn by a syringe and injected without dilution.

For intravenous infusion: the infusion is prepared daily. The recommended dose is diluted in 500 mL of a 0.9% sodium chloride solution.

LITAK is a cytotoxic agent and precautions are necessary when handling, preparing and administering it. The use of disposable gloves and protective garments is recommended. If LITAK contacts the skin or mucous membrane, rinse the involved surface immediately with copious amounts of water.

How long it is given

Your doctor will decide how long to continue your treatment with LITAK.

If you use too much LITAK

As LITAK is given to you in hospital under the supervision of your doctor, it is unlikely that you will receive an overdose.

However, if you experience any side effects after being given LITAK, you should immediately:

• Tell your doctor or nurse
• phone the Poisons Information Centre
  (Australia telephone 13 11 26) for advice, or
• go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

You may need urgent medical attention.

Symptoms of an overdose may include:

• nausea
• vomiting
• diarrhoea

5. What should I know while using LITAK?

Things you should do

• If you are about to be started on any new medicine, remind your doctor and pharmacist that you are taking LITAK.
• Tell any other doctors, dentists and pharmacists who treat you that you are taking this medicine.
• If you become pregnant while taking this medicine, tell your doctor immediately.
  You must take adequate contraceptive precautions during therapy and for at least six months after LITAK is no longer being given to you.
• Keep all of your doctor's appointments so that your progress can be checked.
  Your doctor may do some tests from time to time to make sure the medicine is working and to prevent unwanted side effects.
• Using LITAK can increase your chance of getting an infection or bleeding. The following precautions should be taken to reduce your risk:
  - avoid people who have infections. Check with your doctor immediately if you think you may be getting an infection, or if you get a fever, chills, cough, hoarse throat, lower back or side pain, or find it painful or difficult to urinate
  - be careful when using a toothbrush, toothpick or dental floss. Your doctor, dentist, nurse, or pharmacist may recommend other ways to clean your teeth and gums. Check with your doctor before having any dental work
  - be careful not to cut yourself when you are using sharp objects such as a razor or nail clippers
  - avoid contact sports or other situations where you may bruise or get injured

Things you should not do

• Do not take any other medicines while using LITAK unless you have discussed this with your doctor or pharmacist.
• This includes medicines you can buy without a prescription from a pharmacy, supermarket, or health food shop.
• Do not give this medicine to anyone else, even if their symptoms seem similar to yours.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how LITAK affects you.

This medicine may cause dizziness, tiredness, and drowsiness in some people. If you have any of these symptoms, do not drive, operate machinery or do anything else that could be dangerous.

Looking after your medicine

Keep LITAK in its original packaging until it is time to use it.

Store LITAK between 2°C and 8°C. Do not store it:

• in the bathroom or near a sink, or
• in the car or on window sills.

Heat and dampness can destroy some medicines.

Keep it where young children cannot reach it.

A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Getting rid of any unwanted medicine

If your doctor tells you to stop taking this medicine or the expiry date has passed, ask your pharmacist what to do with any medicine that is left over.

6. Are there any side effects?

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are being treated with LITAK.

As with other medicines that treat cancer, LITAK may have unwanted side effects, some of which may be serious. You may need medical treatment if you get some of these side effects.

Do not be alarmed by the following lists of side effects. You may not experience any of them.

Ask your doctor or nurse to answer any questions you may have.

Because of your condition, your blood may already be weakened so that you are more susceptible to infections, you may be tired because of anaemia and any cuts may take longer to clot and heal. Although LITAK is selective and kills mainly leukaemia cells, it may further weaken your blood before strengthening it.

Less serious to Serious side effects

More serious side effects

Tell your doctor or nurse if you notice anything that is making you feel unwell.

Other side effects not listed above may also occur in some people.

Because of the prolonged action of this drug on the body some side effects may occur after the treatment has been completed.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What LITAK contains

Do not take this medicine if you are allergic to any of these ingredients.

What LITAK looks like

LITAK is a clear, colourless, odourless solution, preservative-free, isotonic solution.

LITAK is packaged in a 10 mL clear type I glass vial with a grey bromobutyl rubber stopper with a red flip-off aluminium polypropylene cap.

It is available in a pack size of 1 single use vial.

(AUST R 104283).

Sponsor

Viatris Pty Ltd
Level 1, 30 The Bond
30-34 Hickson Road
Millers Point NSW 2000
www.viatris.com.au
Phone: 1800 274 276

This leaflet was prepared in May 2022.

LITAK^® is licensed to the Viatris company group

LITAK_cmi\May22/00

Published by MIMS July 2022

1 Name of Medicine

Cladribine.

2 Qualitative and Quantitative Composition

Each 5 mL of the preservative-free, isotonic solution contains 10 mg of cladribine as the active ingredient, 45 mg of sodium chloride and water for injections to make the solution up to 5 mL. The product may also contain sodium hydroxide or hydrochloric acid to adjust the pH. The pH range of the solution is 6.5 - 7.5.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Litak is available in single-use vials containing 10 mg of cladribine in 5 mL of solution, ready-to-use for subcutaneous injection without dilution or can be diluted for intravenous infusion.
The solution for injection is presented as a clear, colourless, odourless solution.

4 Clinical Particulars

4.1 Therapeutic Indications

Litak is indicated for the treatment of hairy cell leukaemia and the second line treatment of lymphoplasmacytic lymphoma (Waldenstrom's macroglobulinaemia), i.e. after failure of alkylating agents.

4.2 Dose and Method of Administration

Therapy with Litak should be initiated by a qualified physician with experience in cancer chemotherapy.
Litak contains no antimicrobial agent. Product is for single use in one patient only. Opened vials should be used immediately to assure sterility. Discard any residue.
Litak is supplied as ready to use solution for subcutaneous bolus injection or can be diluted for intravenous infusion. Aseptic technique and proper environment precautions must be observed while handling Litak solution and preparing infusions.

For subcutaneous bolus injection.

Hairy cell leukaemia.

Subcutaneous bolus injection.

Intravenous infusion.

Lymphoplasmacytic lymphoma.

Subcutaneous bolus injection.

Instruction for handling and disposal.

4.3 Contraindications

Litak is contraindicated in patients with a history of hypersensitivity to cladribine or any of its excipients.
Litak is also contraindicated:
During pregnancy and lactation.
In patients less than 18 years of age.
In patients with moderate to severe renal impairment (creatinine clearance ≤ 50 mL/min) or moderate to severe hepatic impairment (Child-Pugh score > 6) (also see Section 4.4 Special Warnings and Precautions for Use).
In concomitant use of other myelosuppressive medicinal products.

4.4 Special Warnings and Precautions for Use

Cladribine is an antineoplastic and immunosuppressive substance that can induce considerable toxic adverse effects, like myelo- and immunosuppression, long lasting lymphocytopenia, and opportunistic infections. Patients undergoing treatment with cladribine should be closely monitored for signs of haematologic and nonhaematologic toxicities.
Particular caution is advised and risks/ benefits should be carefully evaluated if administration of cladribine is considered in patients with increased infection risk, manifested bone marrow failure or infiltration, myelosuppressive pre-treatments, as well as in patients with suspected or manifested renal and hepatic insufficiency. Patients with active infection should be treated for the underlying condition prior to receiving therapy with Litak. Patients who are or who become Coombs' positive should be monitored closely for occurrence of haemolysis.
If severe toxicity occurs, the physician should consider delaying or discontinuing the therapy with the medicinal product until serious complications resolve. In case of infections, antibiotic treatment should be initiated as required.
There have been reports of graft-versus-host disease in patients treated with cladribine who have received transfusions of non-irradiated cellular blood components/products. Fatal cases have been reported. See Section 4.8 Adverse Effects (Undesirable Effects).
It is recommended that patients receiving cladribine should receive irradiated cellular blood components/products to prevent transfusion-related graft-versus-host disease (Ta-GVHD).
Acute, irreversible neuro- and nephrotoxicity have only been observed at high doses of cladribine (≥ 4 times the recommended dose).

Progressive multifocal leukoencephalopathy (PML).

Secondary malignancies.

Haematology.

Impaired bone marrow.

Prevention of tumour lysis syndrome.

Use in hepatic impairment.

Use in renal impairment.

Use in the elderly.

Paediatric use.

Effects on laboratory tests.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Interactions with other medicinal products are not known.
Due to a potential increase of haematological toxicity and bone marrow suppression, Litak should not be used concomitantly with other myelosuppressive drugs. Cross reactions with other antineoplastic agents in vitro (e.g. doxorubicin, vincristine, cytarabine) and in vivo have not been observed.
Due to the similar intracellular metabolism, cross-resistance with other nucleoside analogues, such as fludarabine or 2'-deoxycoformycin may occur. Therefore, simultaneous administration of nucleoside analogues with cladribine is not advisable.
Corticosteroids have been shown to enhance the risk for severe infections when used in combination with cladribine and should not be given concomitantly with cladribine.
Since interactions with medicinal products undergoing intracellular phosphorylation, such as antiviral agents, or with inhibitors of adenosine uptake may be expected, their concomitant use with cladribine is not recommended.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

4.7 Effects on Ability to Drive and Use Machines

Litak may strongly impair the patient's performance. In case of drowsiness, driving a vehicle or operating machines should be avoided.

4.8 Adverse Effects (Undesirable Effects)

Very common side effects observed during the three most relevant clinical trials with Litak in 279 patients treated for various indications and in 62 patients with hairy cell leukaemia (HCL) are shown in Table 1.
Haematological toxicity may be more pronounced with subcutaneous compared to intravenous administration (see Table 2).
Culture negative fever following treatment with Litak occurs in 10-40% of patients with hairy cell leukaemia and is rarely observed in patients with other neoplastic disorders. Skin rashes (2-31%) are mainly described in patients with other concomitant medications known to cause rash (antibiotics and/or allopurinol). Gastrointestinal side effects like nausea (5-28%), vomiting (1-13%), and diarrhoea (3-12%) as well as fatigue (2-48%), headache (1-23%), and decreased appetite (1-22%) have been reported during treatment with Litak. There are only isolated reports of alopecia, mucositis or conjunctivitis.

Non-haematological adverse effects.

Blood counts.

Infections.

Rare serious adverse reactions.

Fatal outcome.

Reporting suspected adverse effects.

4.9 Overdose

Common symptoms after overdosage are 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-Barré syndrome, and Brown-Séquard syndrome. The neurological complications 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 antidotal therapy exists. Immediate discontinuation of therapy, careful observation, and initiation of appropriate supportive measures (blood transfusions, dialysis, haemofiltration, anti-infectious therapy, etc.) are the indicated treatment of overdosage of Litak. Patients who have been exposed to overdosage of Litak should be monitored haematologically for at least four weeks.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Cellular resistance and sensitivity.

Clinical trials.

Hairy cell leukaemia.

Lymphoplasmacytic lymphoma (Waldenstrom's macroglobulinaemia).

5.2 Pharmacokinetic Properties

Absorption.

Distribution.

Metabolism.

Excretion.

Pharmacokinetics in special clinical situations.

5.3 Preclinical Safety Data

Genotoxicity.

Carcinogenicity.

6 Pharmaceutical Particulars

6.1 List of Excipients

Litak solution contains sodium chloride, sodium hydroxide or hydrochloric acid (for pH adjustment) and water for injections.

6.2 Incompatibilities

The use of glucose 5% as diluent is not recommended due to an expected degradation of cladribine. No data about incompatibilities with other parenteral diluents, additives, infusion systems, and cytostatic drugs are available. Litak solution should not be diluted with other applicable drugs or additives for IV use. If the same infusion tube is used for consequent administration of several different drugs, the tubes should be rinsed by a compatible diluent prior to and after application of cladribine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store at 2°C to 8°C (Refrigerate. Do not freeze). Vials for single use only. Discard any residue.

6.5 Nature and Contents of Container

The solution is supplied in a 10 mL clear type I glass vial with a grey bromobutyl rubber stopper with a red flip-off aluminium polypropylene cap.
Pack sizes: 1 or 5 vials.
Some strengths, pack sizes and/or pack types may not be marketed.

Australian register of therapeutic goods (ARTG).

6.6 Special Precautions for Disposal

Procedures for proper handling and disposal of antineoplastic drugs should be considered. Cytotoxic drugs should be handled with caution. Avoid contact by pregnant women and keep out of the reach of children.
In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Chemical structure.

CAS number.

7 Medicine Schedule (Poisons Standard)

S4 (Prescription Only Medicine).

Summary Table of Changes