Drugs List

Therapeutic Indications

Uses

B-cell chronic lymphocytic leukaemia unresponsive to alkylating regimen
Leukaemia - hairy cell - primary and secondary treatment

Primary or secondary treatment of Hairy Cell Leukaemia.
B-cell chronic lymphocytic leukaemia with an inadequate response to, or disease progression during/after, treatment with at least one standard alkylating agent containing regimen.

Administration

Leustat solution for infusion
For intravenous infusion only.

Litak injection
For subcutaneous injection only.
Patients may self-administer this product following appropriate training.

Contraindications

Children under 18 years
Breastfeeding
Moderate hepatic impairment
Moderate renal impairment
Pregnancy

Precautions and Warnings

Elderly
Immunosuppression
Infection
Predisposition to infection
Suspected infection
Dehydration
Mild hepatic impairment
Mild renal impairment
Myelosuppression

Administration of live vaccines is not recommended
Consider anti-infective prophylaxis in immunocompromised patients
Advise patient ability to drive or operate machinery may be impaired
Consider premedication with hypouricaemic agent
Give pre-treatment counselling and consideration of sperm cryopreservation
Maintain adequate hydration of patient prior / during treatment
Not all available brands are licensed for all routes of administration
Not all presentations are licensed for all indications
Treat and control infections prior to commencing therapy
Treatment to be initiated and supervised by a specialist
Consult local policy on the safe use of anti-cancer drugs
If extravasation occurs follow local policy & seek expert help immediately
Patients who require blood transfusion should only receive irradiated blood
Staff: Not to be handled by pregnant staff
Febrile event: Investigate with laboratory and radiological tests
Monitor blood counts regularly
Monitor closely any patient who develops new infection while on treatment
Monitor for signs of haematological and non-haematological toxicity
Monitor for signs of neurological toxicity
Monitor hepatic function
Monitor patients for development of second primary malignancies
Monitor patients for signs of tumour lysis syndrome
Monitor renal function
Monitor toxicity - discontinue or modify dose if necessary
Advise patient to report headaches, seizures, confusion, visual disturbance
Advise patient to report unexplained fever, sore throat, bruising, bleeding
Risk of developing opportunistic infections
Discontinue if Progressive multifocal leukoencephalopathy (PML) develops
Male & female: Contraception required during & for 6 months after treatment
Breastfeeding: Do not breastfeed during & for 6 months after treatment

Haematological and non-haematological toxicities including myelosuppression, acute renal toxicity and serious neurological toxicity have been reported. If severe toxicity occurs, consider delaying or discontinuing treatment. In the case of infections, initiate antimicrobial treatment as indicated.

Consider dose reduction and regular monitoring in patients with significant myelosuppression, in particular patients with disease related bone marrow infiltration or previous myelosuppressive treatment. Continuing monitoring of blood counts for 2 to 4 months after treatment is recommended by some manufacturers.

Progressive multifocal leukoencephalopathy syndrome (PML) has been reported, including cases 6 months to several years after treatment had finished. Consider PML as a potential diagnosis if patients present with new or worsening neurological, cognitive or behavioural signs or symptoms. Ensure patients are aware of the signs and symptoms and the possibility of delayed presentation. Suggested evaluation for PML includes neurology consultation, brain MRI and cerebrospinal fluid analysis for JC virus or a brain biopsy. Permanently discontinue treatment if PML is diagnosed. If no alternative diagnosis can be established, additional follow-up investigation is advised.

Patients who are or become Coombs' positive should be monitored for potential haemolysis.

Whilst local tissue damage is unlikely, implementation of local extravasation procedures are recommended by some manufacturers following accidental extravenous administration.

Pregnancy and Lactation

Pregnancy

Cladribine is contraindicated in pregnancy.

Animal studies have shown teratogenic, embryotoxic and mutagenic effects. At the time of writing, there is insufficient published information to assess the risk during human pregnancy. Other drugs which, like cladribine, inhibit DNA synthesis are known to be human teratogens.

As such, use during pregnancy is contraindicated.

If a patient becomes pregnant during treatment, inform them of the potential hazard to the foetus.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Cladribine is contraindicated in breastfeeding.

Excretion in human breast milk is unknown. The molecular weight, low plasma protein binding and infusion time indicates excretion is likely.

As such, breastfeeding is contraindicated during and for up to 6 months after treatment with cladribine.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Abnormal breath sounds
Abnormal chest sounds
Alopecia (transient)
Amyloidosis
Anaemia
Anxiety
Aplastic anaemia
Arrhythmias
Arthralgia
Arthritis
Asthenia
Ataxia
Blepharitis
Bone pain
Cachexia
Cardiac decompensation
Cardiac failure
Cellulitis
Chills
Cholecystitis
Confusion
Conjunctivitis
Constipation
Cough
Decreased appetite
Depression
Diaphoresis
Diarrhoea
Dizziness
Epistaxis
Erythema
Exanthema
Fatigue
Febrile neutropenia
Fever
Flatulence
Graft versus host disease
Haemolytic anaemia
Haemorrhage
Headache
Heart murmur
Hepatic failure
Hypereosinophilia
Hyperhidrosis
Hypersensitivity reactions
Hyperuricaemia
Hypotension
Ileus
Immunosuppression
Increase in serum transaminases
Infections
Injection site reactions
Insomnia
Lethargy
Lymphopenia
Malaise
Metabolic acidosis
Mucositis
Myalgia
Myelodysplastic syndrome
Myelosuppression
Myocardial ischaemia
Nausea
Neoplasms
Nephrotoxicity
Neurological effects
Neutropenia
Oedema
Pain
Pancytopenia
Paraesthesia
Paralysis
Petechiae
Pharyngitis
Phlebitis
Pneumonia
Polyneuropathy
Progressive multifocal leukoencephalopathy (PML)
Pruritus
Pulmonary embolism
Pulmonary infiltrates
Purpura
Rash
Renal failure
Seizures
Septicaemia
Serum bilirubin increased
Shortness of breath
Skin pain
Somnolence
Stevens-Johnson syndrome
Tachycardia
Thrombocytopenia
Toxic epidermal necrolysis
Tumour lysis syndrome
Urticaria
Vomiting

Presentation

Parenteral formulations of cladribine.

Drugs List

Therapeutic Indications

Uses

B-cell chronic lymphocytic leukaemia unresponsive to alkylating regimen
Leukaemia - hairy cell - primary and secondary treatment

Primary or secondary treatment of Hairy Cell Leukaemia.
B-cell chronic lymphocytic leukaemia with an inadequate response to, or disease progression during/after, treatment with at least one standard alkylating agent containing regimen.

Dosage

Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.

Adults

Administration

Leustat solution for infusion
For intravenous infusion only.

Litak injection
For subcutaneous injection only.
Patients may self-administer this product following appropriate training.

Contraindications

Children under 18 years
Breastfeeding
Moderate hepatic impairment
Moderate renal impairment
Pregnancy

Precautions and Warnings

Elderly
Immunosuppression
Infection
Predisposition to infection
Suspected infection
Dehydration
Mild hepatic impairment
Mild renal impairment
Myelosuppression

Administration of live vaccines is not recommended
Consider anti-infective prophylaxis in immunocompromised patients
Advise patient ability to drive or operate machinery may be impaired
Consider premedication with hypouricaemic agent
Give pre-treatment counselling and consideration of sperm cryopreservation
Maintain adequate hydration of patient prior / during treatment
Not all available brands are licensed for all routes of administration
Not all presentations are licensed for all indications
Treat and control infections prior to commencing therapy
Treatment to be initiated and supervised by a specialist
Consult local policy on the safe use of anti-cancer drugs
If extravasation occurs follow local policy & seek expert help immediately
Patients who require blood transfusion should only receive irradiated blood
Staff: Not to be handled by pregnant staff
Febrile event: Investigate with laboratory and radiological tests
Monitor blood counts regularly
Monitor closely any patient who develops new infection while on treatment
Monitor for signs of haematological and non-haematological toxicity
Monitor for signs of neurological toxicity
Monitor hepatic function
Monitor patients for development of second primary malignancies
Monitor patients for signs of tumour lysis syndrome
Monitor renal function
Monitor toxicity - discontinue or modify dose if necessary
Advise patient to report headaches, seizures, confusion, visual disturbance
Advise patient to report unexplained fever, sore throat, bruising, bleeding
Risk of developing opportunistic infections
Discontinue if Progressive multifocal leukoencephalopathy (PML) develops
Male & female: Contraception required during & for 6 months after treatment
Breastfeeding: Do not breastfeed during & for 6 months after treatment

Haematological and non-haematological toxicities including myelosuppression, acute renal toxicity and serious neurological toxicity have been reported. If severe toxicity occurs, consider delaying or discontinuing treatment. In the case of infections, initiate antimicrobial treatment as indicated.

Consider dose reduction and regular monitoring in patients with significant myelosuppression, in particular patients with disease related bone marrow infiltration or previous myelosuppressive treatment. Continuing monitoring of blood counts for 2 to 4 months after treatment is recommended by some manufacturers.

Progressive multifocal leukoencephalopathy syndrome (PML) has been reported, including cases 6 months to several years after treatment had finished. Consider PML as a potential diagnosis if patients present with new or worsening neurological, cognitive or behavioural signs or symptoms. Ensure patients are aware of the signs and symptoms and the possibility of delayed presentation. Suggested evaluation for PML includes neurology consultation, brain MRI and cerebrospinal fluid analysis for JC virus or a brain biopsy. Permanently discontinue treatment if PML is diagnosed. If no alternative diagnosis can be established, additional follow-up investigation is advised.

Patients who are or become Coombs' positive should be monitored for potential haemolysis.

Whilst local tissue damage is unlikely, implementation of local extravasation procedures are recommended by some manufacturers following accidental extravenous administration.

Pregnancy and Lactation

Pregnancy

Cladribine is contraindicated in pregnancy.

Animal studies have shown teratogenic, embryotoxic and mutagenic effects. At the time of writing, there is insufficient published information to assess the risk during human pregnancy. Other drugs which, like cladribine, inhibit DNA synthesis are known to be human teratogens.

As such, use during pregnancy is contraindicated.

If a patient becomes pregnant during treatment, inform them of the potential hazard to the foetus.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Cladribine is contraindicated in breastfeeding.

Excretion in human breast milk is unknown. The molecular weight, low plasma protein binding and infusion time indicates excretion is likely.

As such, breastfeeding is contraindicated during and for up to 6 months after treatment with cladribine.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Abnormal breath sounds
Abnormal chest sounds
Alopecia (transient)
Amyloidosis
Anaemia
Anxiety
Aplastic anaemia
Arrhythmias
Arthralgia
Arthritis
Asthenia
Ataxia
Blepharitis
Bone pain
Cachexia
Cardiac decompensation
Cardiac failure
Cellulitis
Chills
Cholecystitis
Confusion
Conjunctivitis
Constipation
Cough
Decreased appetite
Depression
Diaphoresis
Diarrhoea
Dizziness
Epistaxis
Erythema
Exanthema
Fatigue
Febrile neutropenia
Fever
Flatulence
Graft versus host disease
Haemolytic anaemia
Haemorrhage
Headache
Heart murmur
Hepatic failure
Hypereosinophilia
Hyperhidrosis
Hypersensitivity reactions
Hyperuricaemia
Hypotension
Ileus
Immunosuppression
Increase in serum transaminases
Infections
Injection site reactions
Insomnia
Lethargy
Lymphopenia
Malaise
Metabolic acidosis
Mucositis
Myalgia
Myelodysplastic syndrome
Myelosuppression
Myocardial ischaemia
Nausea
Neoplasms
Nephrotoxicity
Neurological effects
Neutropenia
Oedema
Pain
Pancytopenia
Paraesthesia
Paralysis
Petechiae
Pharyngitis
Phlebitis
Pneumonia
Polyneuropathy
Progressive multifocal leukoencephalopathy (PML)
Pruritus
Pulmonary embolism
Pulmonary infiltrates
Purpura
Rash
Renal failure
Seizures
Septicaemia
Serum bilirubin increased
Shortness of breath
Skin pain
Somnolence
Stevens-Johnson syndrome
Tachycardia
Thrombocytopenia
Toxic epidermal necrolysis
Tumour lysis syndrome
Urticaria
Vomiting

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: March 2018

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.

Summary of Product Characteristics: Leustat Injection. Janssen-Cilag Ltd. Revised November 2017.

Summary of Product Characteristics: Litak 2mg/ml solution for injection. Lipomed GmbH. Revised January 2018.

MHRA Drug Safety Update December 2017
Available at: https://www.mhra.gov.uk
Last accessed: 14 March 2018

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Cladribine Last revised: 11 April 2017
Last accessed: 14 March 2018