Drug reference
Cladribine is a nucleoside analogue that is cytotoxic particularly to lymphocytes and monocytes, inhibiting both DNA synthesis and repair. Its effect on B- and T-lymphocytes is thought to interrupt the cascade of immune events central to multiple sclerosis.
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Hairy cell leukaemia (specialist use only) ▶BY SUBCUTANEOUS INJECTION, OR BY INTRAVENOUS INFUSION ▶Adult: (consult product literature or local protocols) B-cell chronic lymphocytic leukaemia (specialist use only) ▶BY INTRAVENOUS INFUSION ▶Adult: (consult product literature or local protocols) Highly active relapsing-remitting multiple sclerosis (specialist use only) ▶BY MOUTH ▶Adult: (consult product literature or local protocols)
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▶With oral use Active chronic hepatitis. active chronic tuberculosis. active malignancy. HIV infection. immunocompromised patients
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GENERAL CAUTIONS Acute infection. use irradiated blood only (haematology consultation advised) SPECIFIC CAUTIONS ▶With intravenous use or subcutaneous use High tumour burden—consult product literature. symptomatic or severe bone marrow depression ▶With oral use No prior exposure to varicella zoster virus. prior malignancy (consider if potential benefit outweighs risk) CAUTIONS, FURTHER INFORMATION ▶Immunosuppressive effect of cladribine ▶With intravenous use or subcutaneous use Cladribine has potent and prolonged myelosuppressive and immunosuppressive effects. Patients treated with cladribine are more prone to serious bacterial, opportunistic fungal, and viral infections, and prophylactic therapy should be considered in those at risk. Acute infections should be treated before initiating cladribine. To prevent potentially fatal transfusion-related graft- versus-host reaction, only irradiated blood products should be administered. Prescribers should consult specialist literature when using highly immunosuppressive drugs. ▶Varicella zoster virus ▶With oral use Manufacturer advises vaccination prior to initiation of therapy in patients who have no history of exposure to varicella zoster virus; delay treatment for 4–6 weeks after vaccination.
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▶With oral use Manufacturer advises exclude HIV infection, active or latent tuberculosis and active or latent hepatitis before starting each treatment course—delay treatment until infection adequately treated.
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NICE decisions ▶Cladribine for treating relapsing–remitting multiple sclerosis (December 2019) NICE TA616 Cladribine (Mavenclad ®) is recommended as an option for treating highly active multiple sclerosis in adults, only if the person has: . rapidly evolving severe relapsing-remitting multiple sclerosis, that is with at least: . two relapses in the previous year, and . one T1 gadolinium-enhancing lesion at baseline MRI or a significant increase in T2 lesion load compared with a previous MRI, or . relapsing-remitting multiple sclerosis that has responded inadequately to treatment with disease- modifying therapy, defined as one relapse in the previous year and MRI evidence of disease activity. Patients whose treatment was started within the NHS before this guidance was published should have the option to continue treatment, without change to their funding arrangements, until they and their NHS clinician consider it appropriate to stop. www.nice.org.uk/guidance/ta616 Scottish Medicines Consortium (SMC) decisions The Scottish Medicines Consortium has advised (February 2018) that cladribine (Mavenclad ®) is accepted for restricted use within NHS Scotland for the treatment of adults with: . rapidly evolving severe relapsing-remitting multiple sclerosis: patients with two or more relapses in the prior year whether on treatment or not, and at least one T1 gadolinium-enhancing lesion, or . sub-optimal therapy relapsing-remitting multiple sclerosis: patients with one or more relapses in the previous year while on disease modifying therapy, and at least one T1 gadolinium-enhancing lesion or nine T2 lesions.
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MHRA/CHM ADVICE: CLADRIBINE FOR LEUKAEMIA: REPORTS OF PROGRESSIVE MULTIFOCAL ENCEPHALOPATHY (PML); STOP TREATMENT IF PML SUSPECTED (DECEMBER 2017) The MHRA is aware of 3 confirmed cases of progressive multifocal encephalopathy (PML) that developed 6 months to several years after cladribine treatment for Immune system and malignant disease haematological conditions. An association between cladribine and prolonged lymphopenia has been reported. PML should be considered in the differential diagnosis for patients with new or worsening neurological signs or symptoms. Patients should be monitored for signs and symptoms of new neurological dysfunction, and advised to seek urgent medical attention if they experience symptoms—stop treatment immediately if PML is suspected and ensure specialist investigation is received.
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→Appendix 1: cladribine
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GENERAL SIDE-EFFECTS ▶Common or very common Increased risk of infection SPECIFIC SIDE-EFFECTS ▶Common or very common ▶With intravenous use Anaemia. anxiety. appetite decreased. arrhythmias. arthritis. asthenia. chest pain. chills. confusion. conjunctivitis. constipation. cough. diarrhoea . dizziness. dyspnoea. febrile neutropenia. fever. flatulence. gastrointestinal discomfort. haemolytic anaemia. headache. hyperhidrosis. hypersensitivity. insomnia. joint disorders. malaise. muscle weakness. myalgia. myocardial ischaemia. nausea. neoplasms. oedema. pain. renal impairment. respiratory disorders. secondary malignancy. septic shock. skin reactions. thrombocytopenia. vomiting ▶With oral use Alopecia. lymphopenia. rash ▶With subcutaneous use Anaemia. anxiety. appetite decreased. arrhythmias. arthralgia. arthritis. asthenia. bone marrow disorders. chills. constipation. cough. diarrhoea. dizziness. dyspnoea. fever. gastrointestinal disorders. gastrointestinal pain. haemorrhage. headache. hyperhidrosis. hypotension. immunosuppression. insomnia. lymphopenia. malaise. mucositis. myalgia. myocardial ischaemia. nausea. neutropenia. oedema. pain. respiratory disorders. secondary malignancy. sepsis Immune system and malignant disease . skin reactions. thrombocytopenia. vomiting ▶Uncommon ▶With intravenous use Bone marrow disorders. hypereosinophilia. level of consciousness decreased. nerve disorders. neurotoxicity (with high doses). paralysis . paraparesis. Stevens-Johnson syndrome. tumour lysis syndrome ▶With subcutaneous use Ataxia. cachexia. confusion. drowsiness. eye inflammation. haemolytic anaemia. paraesthesia. polyneuropathy ▶Rare or very rare ▶With intravenous use Heart failure ▶With subcutaneous use Amyloidosis. cholecystitis. depression. dysphagia. epilepsy. graft versus host disease . heart failure. hepatic failure. hypereosinophilia. pulmonary embolism. renal failure. severe cutaneous adverse reactions (SCARs). speech disorder. tumour lysis syndrome ▶Frequency not known ▶With oral use Malignancy
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Manufacturer advises effective contraception during treatment and for at least 6 months after the last dose in men and women of childbearing potential. ▶With oral use Manufacturer advises exclude pregnancy before each treatment course; if using a hormonal contraceptive, a barrier method should also be used for at least 4 weeks after the last dose of each course.
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Manufacturer advises avoid—teratogenic in animal studies. See also Pregnancy and reproductive function in Cytotoxic drugs p. 938.
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▶With intravenous use or subcutaneous use Manufacturer advises avoid during treatment and for 6 months after the last dose—no information available. ▶With oral use Manufacturer advises avoid during treatment and for 1 week after the last dose—no information available.
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▶With intravenous use Manufacturer advises caution (limited information available). ▶With subcutaneous use Manufacturer advises caution in mild impairment; avoid in moderate to severe impairment (no information available). ▶With oral use Manufacturer advises avoid in moderate to severe impairment (no information available).
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▶With subcutaneous use Manufacturer advises caution in mild impairment; avoid in moderate-to-severe impairment. ▶With oral use Manufacturer advises avoid in moderate-to- severe impairment—no information available. ▶With intravenous use Manufacturer advises caution—limited information available.
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▶Manufacturer advises monitor for malignancy—follow routine cancer screening guidelines. ▶Manufacturer advises monitor for progressive multifocal leucoencephalopathy—perform a baseline MRI. ▶Manufacturer advises monitor for haemolysis in patients who are or who become Coombs’ positive. ▶Manufacturer advises haematological monitoring required—consult product literature. ▶With intravenous use or subcutaneous use Renal and hepatic function should be monitored periodically as clinically indicated.
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Litak ® for subcutaneous use only—no dilution required; manufacturer advises patients may self-administer, after appropriate training. Leustat ® for infusion use only. l HANDLING AND STORAGE LITAK ® Manufacturer advises store in a refrigerator (2–8°C). LEUSTAT ® Manufacturer advises store in a refrigerator (2–8°C).
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There can be variation in the licensing of different medicines containing the same drug. Solution for injection ▶Litak (Lipomed GmbH) Cladribine 2 mg per 1 ml Litak 10mg/5ml solution for injection vials | 1 vial P £165.00 (Hospital only) Solution for infusion ELECTROLYTES: May contain Sodium ▶Leustat (Janssen-Cilag Ltd) Cladribine 1 mg per 1 ml Leustat 10mg/10ml solution for infusion vials | 1 vial P £159.70 Tablet ▶Mavenclad (Merck Serono Ltd) Cladribine 10 mg Mavenclad 10mg tablets | 1 tablet P £2,047.24 | 4 tablet P £8,188.97 | 6 tablet P £12,283.46
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Driving and skilled tasks ▶With intravenous use or subcutaneous use Manufacturer advises patients and carers should be counselled on the effects on driving and performance of skilled tasks— increased risk of dizziness and drowsiness.
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(consult product literature or local protocols)
First-line fragment. Read the complete Indications and Dose section above.
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(consult product literature or local protocols)
First-line fragment. Read the complete Indications and Dose section above.
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(consult product literature or local protocols)
First-line fragment. Read the complete Indications and Dose section above.
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