Ibrutinib


Concise Prescribing Info
Indications/Uses
Listed in Dosage.
Dosage/Direction for Use
Adult : PO Mantle cell lymphoma; Marginal zone lymphoma Relapsed or refractory cases: 560 mg once daily. Chronic lymphocytic leukaemia; Small lymphocytic lymphoma As monotherapy or in combination with bendamustine and rituximab in patients with prior therapy or those with 17p deletion: 420 mg once daily. Waldenstrom's macroglobulinaemia; Chronic graft versus host disease 420 mg once daily. All doses are given until disease progression or unacceptable toxicity. If toxicity occurs, withhold doses until recovery to baseline or grade 1. Restart treatment at the starting dose for the 1st occurrence, then reduce by 140 mg after the 2nd occurrence, another reduction of 140 mg may be considered if needed. Discontinue following 2 dose reductions if toxicities persist.
Dosage Details
Oral
Mantle cell lymphoma, Marginal zone lymphoma
Adult: In patients with relapsed or refractory cases: 560 mg once daily, continue until disease progression or unacceptable toxicity. If toxicity occurs, withhold doses until recovery to baseline or grade 1. Restart treatment at the starting dose for the 1st occurrence, then reduce by 140 mg after the 2nd occurrence, another reduction of 140 mg may be considered if needed. Discontinue following 2 dose reductions if toxicities persist.

Oral
Chronic lymphocytic leukaemia, Small lymphocytic lymphoma
Adult: As monotherapy or in combination with bendamustine and rituximab in patients who have received at least 1 prior therapy or as 1st line treatment in patients with 17p deletion: 420 mg once daily, continue until disease progression or unacceptable toxicity. If toxicity occurs, withhold doses until recovery to baseline or grade 1. Restart treatment at the starting dose for the 1st occurrence, then reduce by 140 mg after the 2nd occurrence, another reduction of 140 mg may be considered if needed. Discontinue following 2 dose reductions if toxicities persist.

Oral
Chronic graft versus host disease, Waldenstrom's macroglobulinaemia
Adult: 420 mg once daily, continue until disease progression or unacceptable toxicity. If toxicity occurs, withhold doses until recovery to baseline or grade 1. Restart treatment at the starting dose for the 1st occurrence, then reduce by 140 mg after the 2nd occurrence, another reduction of 140 mg may be considered if needed. Discontinue following 2 dose reductions if toxicities persist.
Special Patient Group
Patients taking moderate CYP3A4 inhibitors (e.g. clotrimazole): 280 mg once daily.
Patients taking strong CYP3A4 inhibitors (e.g. ketoconazole): 140 mg once daily or withhold for up to 7 days.
Hepatic Impairment
Mild (Child-Pugh class A): Initially, 140 or 280 mg once daily. Moderate (Child-Pugh class B): Initially, 140 mg once daily. Severe (Child-Pugh class C): Contraindicated.
Administration
May be taken with or without food. Take at the same time each day. Swallow whole w/ water, do not open/break/chew. Do not take w/ grapefruit juice or bitter oranges.
Contraindications
Severe hepatic impairment. Lactation.
Special Precautions
Patient with cardiac risk factors, hypertension, acute infections, history of atrial fibrillation. Patients taking moderate or strong CY3A4 inhibitors. Renal and mild to moderate hepatic impairment. Pregnancy.
Adverse Reactions
Significant: Atrial fibrillation, atrial flutter, dizziness, fatigue, weakness, diarrhoea, neutropenia, thrombocytopenia, anaemia, lymphocytosis, hypertension, progressive multifocal encephalopathy, second primary malignancies (e.g. nonmelanoma skin cancer, other carcinomas) tumor lysis syndrome.
Eye disorders: Dry eye syndrome, increased lacrimation, blurred vision, decreased visual acuity.
Gastrointestinal disorders: Nausea, stomatitis, constipation, upper abdominal pain, vomiting, dyspepsia, GERD.
General disorders and administration site conditions: Fever, weakness.
Hepatobiliary disorders: Hypoalbuminaemia.
Infections and infestations: Infection, sepsis.
Injury, poisoning and procedural complications: Falling.
Investigations: Increased serum creatinine, decreased Hb.
Metabolism and nutrition disorders: Hyperuricaemia, hypokalaemia, dehydration, decreased appetite.
Musculoskeletal and connective tissue disorders: Muscle pain, muscle spasm, arthralgia, arthropathy, chills.
Nervous system disorders: Headache, peripheral oedema.
Psychiatric disorders: Anxiety. Renal and urinary disorders: UTI, haematuria.
Respiratory, thoracic and mediastinal disorders: Upper respiratory tract infection, dyspnoea, cough, sinusitis, pneumonia, oropharyngeal pain, bronchitis.
Skin and subcutaneous tissue disorders: Rash, pruritus, bruise, petechia.
Vascular disorders: Epistaxis.
Potentially Fatal: Haemorrhage (e.g. intracranial, subdural, gastrointestinal, haematuria, postprocedural), serious infections, renal failure.
Patient Counseling Information
This drug may cause dizziness, if affected, do not drive or operate machinery.
MonitoringParameters
Monitor CBC, LFT, renal function. Monitor for the occurrence of atrial fibrillation, leucostasis, fever, signs and symptoms of bleeding and infection, tumour lysis syndrome. Periodically perform ECG.
Drug Interactions
Increased exposure with CYP3A4 inhibitors (e.g. ketoconazole). Decreased exposure with CYP3A4 inducers (e.g. rifampicin). May reduce the efficacy of vaccines. Increased risk of bleeding with antiplatelet and anticoagulants (e.g. warfarin).
Food Interaction
Decreased serum concentration with St. John’s wort. Increased serum concentration with grapefruit juice, and Seville oranges.
Action
Description: Ibrutinib is an irreversible inhibitor of Bruton’s tyrosine kinase (BTK), a vital signalling molecule for the activation of B-cell antigen and cytokine receptor pathways responsible for the pathogenesis of B-cell malignancies. Inhibition results in decreased malignant B-cells proliferation, survival, migration and adhesion.
Pharmacokinetics:
Absorption: Rapidly absorbed in the gastrointestinal tract. Absolute bioavailability: 2.9%. Time to peak plasma concentration: 1-2 hours.
Distribution: Volume of distribution: Approx 10,000 L. Plasma protein binding: Approx 97%.
Metabolism: Metabolised in the liver by CYP3A4 enzyme into weakly active dihydrodiol metabolite.
Excretion: Mainly via faeces (80%, mainly as metabolites and 1% as unchanged drug); urine (<10%, as metabolites). Half-life: 4-13 hours.
Chemical Structure

Chemical Structure Image
Ibrutinib

Source: National Center for Biotechnology Information. PubChem Database. Ibrutinib, CID=24821094, https://pubchem.ncbi.nlm.nih.gov/compound/Ibrutinib (accessed on Jan. 21, 2020)

Storage
Store between 20-25°C.
Any unused portions should be disposed of in accordance with local requirements.
ATC Classification
L01XE27 - ibrutinib ; Belongs to the class of protein kinase inhibitors, other antineoplastic agents. Used in the treatment of cancer.
References
Anon. Ibrutinib. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 04/12/2017.

Buckingham R (ed). Ibrutinib. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 04/12/2017.

Imbruvica Capsule (Pharmacyclics LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 04/12/2017.

Joint Formulary Committee. Ibrutinib. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com\. Accessed 04/12/2017.

McEvoy GK, Snow EK, Miller J et al (eds). Ibrutinib. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 04/12/2017.

Disclaimer: This information is independently developed by MIMS based on Ibrutinib from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
Register or sign in to continue
Asia's one-stop resource for medical news, clinical reference and education
Sign up for free
Already a member? Sign in