Drug Action
Ibrutinib is a tyrosine kinase inhibitor.
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Drug reference
Ibrutinib is a tyrosine kinase inhibitor.
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Mantle cell lymphoma (specialist use only) ▶BY MOUTH ▶Adult: 560 mg once daily, for dose adjustments due to side-effects—consult product literature Chronic lymphocytic leukaemia (specialist use only) | Waldenstrӧm’s macroglobulinaemia (specialist use only) ▶BY MOUTH ▶Adult: 420 mg once daily, for dose adjustments due to side-effects—consult product literature
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DUE TO INTERACTIONS ▶Manufacturer advises if concurrent use of moderate inhibitors of CYP3A4, amiodarone or ciprofloxacin is unavoidable, reduce dose to 280 mg once daily. ▶Manufacturer advises if concurrent use of potent inhibitors of CYP3A4 is unavoidable, reduce dose to 140 mg once daily, or withhold ibrutinib for up to 7 days.
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Family history of congenital short QT syndrome . increased lymphocytes—increased risk of leukostasis, consider withholding treatment temporarily and monitor closely. patients at risk from further shortening of QTc interval. personal history of congenital short QT syndrome. risk of haemorrhagic events—withhold ibrutinib treatment for at least 3 to 7 days before and after surgery depending on risk of bleeding
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NICE decisions ▶Ibrutinib for previously treated chronic lymphocytic leukaemia and untreated chronic lymphocytic leukaemia with 17p deletion or TP53 mutation (January 2017) NICE TA429 Ibrutinib (Imbruvica ®) alone is recommended within its marketing authorisation as an option for treating chronic lymphocytic leukaemia in adults who have had at least one prior therapy or who have a 17p deletion or TP53 mutation, and in whom chemo-immunotherapy is unsuitable, and only when the manufacturer provides ibrutinib with the discount agreed in the patient access scheme. www.nice.org.uk/guidance/ta429 ▶Ibrutinib for treating Waldenstrom’s macroglobulinaemia (November 2017) NICE TA491 Ibrutinib (Imbruvica ®) is recommended for use in the Cancer Drugs Fund as an option for treating Waldenstrom’s macroglobulinaemia in adults who have had at least one prior therapy, only if the conditions in the managed access agreement for ibrutinib are followed. 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/ta491 ▶Ibrutinib for treating relapsed or refractory mantle cell lymphoma (January 2018) NICE TA502 Ibrutinib (Imbruvica ®) is recommended as an option for treating relapsed or refractory mantle cell lymphoma in adults, only if: . they have had only one previous line of therapy, and . the manufacturer provides ibrutinib with the discount agreed in the commercial access agreement with NHS England. 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/ta502 Scottish Medicines Consortium (SMC) decisions SMC No. 1151/16 The Scottish Medicines Consortium has advised (April 2017) that ibrutinib (Imbruvica ®) is accepted for restricted use within NHS Scotland for the treatment of relapsed or refractory chronic lymphocytic leukaemia in adults who have received at least one prior therapy and for whom fludarabine-based regimens are inappropriate. This advice is contingent upon the continuing availability of the Patient Access Scheme in NHS Scotland or a list price that is equivalent or lower.
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RISKS OF INCORRECT DOSING OF ORAL ANTI-CANCER MEDICINES See Cytotoxic drugs p. 938. MHRA/CHM ADVICE: IBRUTINIB (IMBRUVICA ®): REPORTS OF VENTRICULAR TACHYARRHYTHMIA; RISK OF HEPATITIS B REACTIVATION AND OF OPPORTUNISTIC INFECTIONS (AUGUST 2017) Cases of ventricular tachyarrhythmia have been reported with the use of ibrutinib. The MHRA advises that ibrutinib should be temporarily discontinued in patients who develop symptoms suggestive of ventricular arrhythmia and to assess benefit-risk before restarting therapy. Immune system and malignant disease Hepatitis B virus status should be established before initiating therapy—for patients with positive hepatitis B serology, consultation with a liver disease expert is recommended before the start of treatment; monitor and manage patients according to local protocols to minimise the risk of hepatitis B virus reactivation. Prophylaxis should be considered for those at an increased risk of opportunistic infections.
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→Appendix 1: ibrutinib
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▶Common or very common Arrhythmias. arthralgia. broken nails. CNS haemorrhage. constipation. diarrhoea. dizziness. fever. haemorrhage. headache. hypertension. hyperuricaemia. increased leucocytes. increased risk of infection. interstitial lung disease. muscle spasms. musculoskeletal pain. nausea. neoplasms. neutropenia. peripheral neuropathy. peripheral oedema. sepsis. skin reactions. stomatitis. thrombocytopenia. tumour lysis syndrome. vision blurred. vomiting ▶Uncommon Angioedema. hepatitis B reactivation. leukostasis syndrome. panniculitis ▶Frequency not known Anaemia. hepatic failure. progressive multifocal leukoencephalopathy (PML). Stevens-Johnson syndrome
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Highly effective contraception (must include a non-hormonal method) required during and for 3 months after stopping treatment.
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Manufacturer advises avoid—toxicity in animal studies. See also Pregnancy and reproductive function in Cytotoxic drugs p. 938.
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Manufacturer advises discontinue breastfeeding—no information available.
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Manufacturer advises avoid in severe impairment (risk of increased exposure)—monitor for toxicity. Dose adjustments Manufacturer advises dose reduction to 280 mg daily in mild impairment and to 140 mg daily in moderate impairment with further adjustments if necessary–consult product literature.
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Use in severe impairment only if benefit outweighs risk and with close monitoring for toxicity. Monitoring Maintain hydration and monitor serum creatinine periodically in mild to moderate renal impairment.
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▶Monitor full blood count once a month. ▶Monitor for atrial fibrillation (increased risk in cardiac risk factors, acute infections and history of atrial fibrillation), monitor all patients periodically and complete ECG if arrhythmic symptoms or dyspnoea develop—consult product literature for treatment options.
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There can be variation in the licensing of different medicines containing the same drug. Tablet CAUTIONARY AND ADVISORY LABELS 25 ▶Imbruvica (Janssen-Cilag Ltd) Ibrutinib 140 mg Imbruvica 140mg tablets | 28 tablet P £1,430.80 Ibrutinib 280 mg Imbruvica 280mg tablets | 28 tablet P £2,861.60 Ibrutinib 420 mg Imbruvica 420mg tablets | 28 tablet P £4,292.40 Ibrutinib 560 mg Imbruvica 560mg tablets | 28 tablet P £5,723.20
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560 mg once daily, for dose adjustments due to
First-line fragment. Read the complete Indications and Dose section above.
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420 mg once daily, for dose adjustments due to
First-line fragment. Read the complete Indications and Dose section above.
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