Ibrutinib (ibrutinib)
Ibrutinib is a bruton's tyrosine kinase (btk) inhibitor; oral small-molecule kinase inhibitor from Pharmacyclics LLC (an AbbVie company) and Janssen Biotech, Inc. (Johnson & Johnson) - developed and commercialised jointly; US distributor of record: Pharmacyclics LLC, marketed originally as Imbruvica. This monograph covers approved indications, mechanism, dosing, side effects and the manufacturer landscape.
Overview
Ibrutinib is an oral, once-daily Bruton's tyrosine kinase (BTK) inhibitor and the first drug of its class to reach the market, sold by AbbVie and Johnson & Johnson as Imbruvica (Chinese brand name 亿珂). It forms a covalent bond with a cysteine residue in the BTK active site, switching off the B-cell receptor signal that malignant B cells depend on for growth, trafficking and survival. Because the same signal drives B-cell-mediated inflammation, ibrutinib also treats chronic graft-versus-host disease. It is approved in adults for chronic lymphocytic leukemia / small lymphocytic lymphoma (including the 17p deletion subgroup, in which chemoimmunotherapy performs poorly) and for Waldenstrom's macroglobulinemia, and from one year of age for chronic GVHD after failure of at least one prior systemic therapy. The US accelerated approvals in mantle cell lymphoma and marginal zone lymphoma were withdrawn at the sponsors' request on 6 April 2023; those indications remain in some ex-US labels. Standard dosing is 420 mg once daily for CLL/SLL, WM and cGVHD (240 mg/m2 once daily, maximum 420 mg, for children aged 1 to under 12); capsules and tablets must be swallowed whole. Common adverse effects are cytopenias, diarrhoea, fatigue, musculoskeletal pain, rash, bruising, hypertension and infection. Atrial fibrillation, cardiac failure and bleeding are recognised serious risks that require active monitoring, and dose reduction rather than permanent withdrawal manages most reactions. As a small molecule, ibrutinib is copied through the ordinary generic route (an ANDA in the US) and bioequivalence studies - not biowaivers - are required. No generic has final US approval: Zydus and Natco hold tentative approvals only, pending remaining exclusivity.
How it works
Ibrutinib blocks BTK, a signalling enzyme that malignant B cells depend on to survive and multiply. Blocking it stops the cancer cells from receiving growth and survival signals, and also dampens B-cell-driven immune reactions, which is why it also works in chronic graft-versus-host disease.
Ibrutinib is a small-molecule inhibitor of Bruton's tyrosine kinase (BTK). It forms a covalent bond with a cysteine residue in the BTK active site, leading to inhibition of BTK enzymatic activity. BTK is a signalling molecule of the B-cell antigen receptor (BCR) and cytokine receptor pathways; signalling through B-cell surface receptors activates pathways necessary for B-cell trafficking, chemotaxis and adhesion. Nonclinical studies show ibrutinib inhibits malignant B-cell proliferation and survival.
Approved indications
- Adult patients with chronic lymphocytic leukemia (CLL) / small lymphocytic lymphoma (SLL) - FDA
- Adult patients with CLL/SLL with 17p deletion - FDA
- Adult patients with Waldenstrom's macroglobulinemia (WM) - FDA
- Adult and pediatric patients age 1 year and older with chronic graft-versus-host disease (cGVHD) after failure of one or more lines of systemic therapy - FDA
- Mantle cell lymphoma (MCL) after at least one prior therapy and marginal zone lymphoma (MZL) after at least one prior anti-CD20-based therapy - FDA accelerated approvals voluntarily withdrawn in the U. S. on 6 April 2023 by AbbVie/Janssen; these two indications are not affected in ex-U. S. labels
Dosage & administration
CLL/SLL and Waldenstrom's macroglobulinemia: 420 mg orally once daily until progression or unacceptable toxicity. cGVHD: 420 mg once daily in patients 12 years and older; 240 mg/m2 once daily (max 420 mg) in patients 1 to less than 12 years. MCL and MZL (US accelerated approvals, withdrawn April 2023): 560 mg once daily. Take at approximately the same time each day with a glass of water; swallow capsules/tablets whole - do not open, break, cut, crush or chew.
Dose adjustment
Adverse reactions: interrupt therapy; after recovery to Grade 1 or baseline restart at reduced dose (e. g. 560 mg start -> 420 mg -> 280 mg; 420 mg start -> 280 mg -> 140 mg; paediatric 240 mg/m2 -> 160 mg/m2 -> 80 mg/m2), discontinue for Grade 3 or 4 cardiac failure, Grade 4 cardiac arrhythmias, or after a third occurrence. CYP3A inhibitors: dose modification per label (e. g. posaconazole 70 mg; voriconazole 140 mg; moderate inhibitors 280 mg). Avoid strong CYP3A inducers. Hepatic impairment: avoid in severe impairment; reduce dose in mild or moderate impairment. Missed dose: take as soon as possible the same day; do not take extra doses.
Side effects
Diarrhoea · Fatigue · Musculoskeletal pain · Neutropenia · Rash · Anaemia · Bruising · Nausea · Hypertension · Pneumonia and other infections · Bleeding / haemorrhage
- Thrombocytopenia
- Atrial fibrillation / cardiac arrhythmias, cardiac failure and sudden death (boxed-warning-level warnings in some ex-U. S. labels; US label carries these as Warnings and Precautions, not a boxed warning)
- Second primary malignancies including non-melanoma skin cancer
- Tumour lysis syndrome (infrequent)
Monitoring
- Monitor for bleeding and manage haemorrhage
- Monitor for fever and infections; evaluate and treat promptly
- Monitor for symptoms of arrhythmias and cardiac failure; monitor blood pressure and treat hypertension
- Check complete blood counts monthly (cytopenias)
- Assess baseline tumour lysis syndrome risk and monitor/treat
- Surveillance for second primary malignancies including skin cancers
- Advise effective contraception in females of reproductive potential (embryo-fetal toxicity)
- Screen for hepatitis B before starting (HBV reactivation is a labelled risk in ex-U. S. labels and pharmacovigilance communications)
Generic and biosimilar landscape
Ibrutinib is a small molecule handled as a normal generic (ANDA in the US). The Medicines Patent Pool notes that bioequivalence studies are necessary and that biowavers will not be an option; a potential sublicensee would rely on US FDA Paragraph III, Swissmedic or EU-M4all registration routes. US: FDA has NOT granted final approval to any generic Imbruvica - Zydus Lifesciences received only a tentative approval (22 July 2025, ANDA 214296, 140/280/420 mg tablets) and Natco Pharma has also reported a tentative approval; tentative status is due to remaining market/pediatric exclusivity. The 560 mg tablet RLD is listed as discontinued. Bangladesh and India generics are marketed locally without US/EU marketing authorisation.
Who makes it
| Manufacturer | Country | Brand | Strength | Notes |
|---|---|---|---|---|
| Beacon Pharmaceuticals PLC | Bangladesh | Ibrucon | 140 mg capsule | Listed on MedEx Bangladesh; also traded internationally as Ibrutix/Ibrucon |
| Incepta Pharmaceuticals Ltd. | Bangladesh | Ibrucent | 140 mg capsule | Listed on MedEx Bangladesh |
| Drug International Ltd. | Bangladesh | Butinib | 140 mg capsule | Listed on MedEx Bangladesh |
| Eskayef Pharmaceuticals Ltd. | Bangladesh | Ibrutab | 140 mg tablet | Listed on MedEx Bangladesh |
| Everest Pharmaceuticals Ltd. | Bangladesh | Ibruxen | 140 mg capsule | Listed on MedEx Bangladesh |
| Jenphar Bangladesh Ltd. | Bangladesh | Ibrunib | 140 mg capsule | Listed on MedEx Bangladesh |
| General Pharmaceuticals Ltd. | Bangladesh | Ibutigen | 140 mg capsule | Listed on MedEx Bangladesh |
| Genvio Pharma Ltd. | Bangladesh | Notafol | 140 mg capsule | Listed on MedEx Bangladesh |
| Natco Pharma Ltd. | India | Ibrunat | 140 mg capsule | Launched in India in 2020 at about /month versus about lakh for the innovator; sale of generic ibrutinib in India was restrained by the Delhi High Court in January 2024 pending exp |
| Hetero Drugs Ltd. | India | Nitib | 140 mg capsule | Listed on Indian pharmacy platforms |
| Zydus Lifesciences Ltd. | India | 140 mg, 280 mg, 420 mg tablets | US FDA tentative approval only (July 2025, ANDA 214296); not commercially launched in the US |
Availability in Southeast Asia
| Country | Status | Notes |
|---|---|---|
| Bangladesh | available locally | Multiple locally manufactured 140 mg capsules/tablets listed on MedEx (Beacon, Incepta, Drug International, Eskayef, Everest, Jenphar, General, Genvio); originator Imbruvica not listed on MedEx ibrutinib brand list |
| Indonesia | registered with BPOM | BPOM assessment report for Imbruvica 140 mg capsules (registration file 01701329804) is published on the Indonesian national registration portal |
| Malaysia | not confirmed | |
| Thailand | not confirmed | |
| Philippines | not confirmed | |
| Vietnam | not confirmed |
Frequently asked questions
When does the ibrutinib (Imbruvica) patent expire in the US and China?
Ibrutinib (Bruton's tyrosine kinase (BTK) inhibitor; oral small-molecule kinase inhibitor, originally Imbruvica (Chinese brand name: 亿珂) by Pharmacyclics LLC (an AbbVie company) and Janssen Biotech, Inc. (Johnson & Johnson) - developed and commercialised jointly; US distributor of record: Pharmacyclics LLC) Ibrutinib blocks BTK, a signalling enzyme that malignant B cells depend on to survive and multiply. Blocking it stops the cancer cells from receiving growth and survival signals, and also dampens B-cell-driven immune reactions, which is why it also works in chronic graft-versus-host disease. CLL/SLL and Waldenstrom's macroglobulinemia: 420 mg orally once daily until progression or unacceptable toxicity. cGVHD: 420 mg once daily in patients 12 years and older; 240 mg/m2 once daily (max 420 mg) in patients 1 to less than 12 years. MCL and MZL (US accelerated approvals, withdrawn April 2023): 560 mg once daily. Take at approximately the same time each day with a glass of water; swallow c
Has the FDA approved a generic version of Imbruvica yet?
Ibrutinib is a small molecule handled as a normal generic (ANDA in the US). The Medicines Patent Pool notes that bioequivalence studies are necessary and that biowavers will not be an option; a potential sublicensee would rely on US FDA Paragraph III, Swissmedic or EU-M4all registration routes. US: FDA has NOT granted final approval to any generic Imbruvica - Zydus Lifesciences received only a tentative approval (22 July 2025, ANDA 214296, 140/280/420 mg tablets) and Natco Pharma has also reported a tentative approval; tentative status is due to remaining market/pediatric exclusivity. The 560 mg tablet RLD is listed as discontinued. Bangladesh and India generics are marketed locally without US/EU marketing authorisation. Manufacturers supplying ibrutinib generic versions include Beacon Pharmaceuticals PLC, Drug International Ltd. , Eskayef Pharmaceuticals Ltd. , Everest Pharmaceuticals Ltd. , General Pharmaceuticals Ltd. , Genvio Pharma Ltd. , Hetero Drugs Ltd. , Incepta Pharmaceuticals Ltd. . Brands registered in Bangladesh include Butinib, Ibrucent, Ibrucon, Ibrunib, Ibrutab, Ibruxen.
What is the difference between Ibrucon, Ibrucent and Ibrunat?
Ibrutinib (Bruton's tyrosine kinase (BTK) inhibitor; oral small-molecule kinase inhibitor, originally Imbruvica (Chinese brand name: 亿珂) by Pharmacyclics LLC (an AbbVie company) and Janssen Biotech, Inc. (Johnson & Johnson) - developed and commercialised jointly; US distributor of record: Pharmacyclics LLC) Ibrutinib blocks BTK, a signalling enzyme that malignant B cells depend on to survive and multiply. Blocking it stops the cancer cells from receiving growth and survival signals, and also dampens B-cell-driven immune reactions, which is why it also works in chronic graft-versus-host disease. CLL/SLL and Waldenstrom's macroglobulinemia: 420 mg orally once daily until progression or unacceptable toxicity. cGVHD: 420 mg once daily in patients 12 years and older; 240 mg/m2 once daily (max 420 mg) in patients 1 to less than 12 years. MCL and MZL (US accelerated approvals, withdrawn April 2023): 560 mg once daily. Take at approximately the same time each day with a glass of water; swallow c
What dose of ibrutinib is used for CLL and how is it reduced for side effects?
The most frequently reported side effects of ibrutinib are thrombocytopenia, diarrhoea, fatigue, musculoskeletal pain, neutropenia, rash, anaemia. Serious but less common reactions include thrombocytopenia, atrial fibrillation / cardiac arrhythmias, cardiac failure and sudden death (boxed-warning-level warnings in some ex-u. s. labels; us label carries these as warnings and precautions, not a boxed warning), second primary malignancies including non-melanoma skin cancer, tumour lysis syndrome (infrequent). Routine monitoring: Monitor for bleeding and manage haemorrhage; Monitor for fever and infections; evaluate and treat promptly; Monitor for symptoms of arrhythmias and cardiac failure; monitor blood pressure and treat hypertension. Report any new or worsening symptom to your treating physician — most adverse effects are managed by dose reduction rather than stopping treatment.
Does ibrutinib cause atrial fibrillation or heart failure?
Ibrutinib (Bruton's tyrosine kinase (BTK) inhibitor; oral small-molecule kinase inhibitor, originally Imbruvica (Chinese brand name: 亿珂) by Pharmacyclics LLC (an AbbVie company) and Janssen Biotech, Inc. (Johnson & Johnson) - developed and commercialised jointly; US distributor of record: Pharmacyclics LLC) Ibrutinib blocks BTK, a signalling enzyme that malignant B cells depend on to survive and multiply. Blocking it stops the cancer cells from receiving growth and survival signals, and also dampens B-cell-driven immune reactions, which is why it also works in chronic graft-versus-host disease. CLL/SLL and Waldenstrom's macroglobulinemia: 420 mg orally once daily until progression or unacceptable toxicity. cGVHD: 420 mg once daily in patients 12 years and older; 240 mg/m2 once daily (max 420 mg) in patients 1 to less than 12 years. MCL and MZL (US accelerated approvals, withdrawn April 2023): 560 mg once daily. Take at approximately the same time each day with a glass of water; swallow c
Why was ibrutinib withdrawn for mantle cell lymphoma in the United States?
Ibrutinib (Bruton's tyrosine kinase (BTK) inhibitor; oral small-molecule kinase inhibitor, originally Imbruvica (Chinese brand name: 亿珂) by Pharmacyclics LLC (an AbbVie company) and Janssen Biotech, Inc. (Johnson & Johnson) - developed and commercialised jointly; US distributor of record: Pharmacyclics LLC) Ibrutinib blocks BTK, a signalling enzyme that malignant B cells depend on to survive and multiply. Blocking it stops the cancer cells from receiving growth and survival signals, and also dampens B-cell-driven immune reactions, which is why it also works in chronic graft-versus-host disease. CLL/SLL and Waldenstrom's macroglobulinemia: 420 mg orally once daily until progression or unacceptable toxicity. cGVHD: 420 mg once daily in patients 12 years and older; 240 mg/m2 once daily (max 420 mg) in patients 1 to less than 12 years. MCL and MZL (US accelerated approvals, withdrawn April 2023): 560 mg once daily. Take at approximately the same time each day with a glass of water; swallow c
Can ibrutinib capsules be opened or crushed?
Ibrutinib (Bruton's tyrosine kinase (BTK) inhibitor; oral small-molecule kinase inhibitor, originally Imbruvica (Chinese brand name: 亿珂) by Pharmacyclics LLC (an AbbVie company) and Janssen Biotech, Inc. (Johnson & Johnson) - developed and commercialised jointly; US distributor of record: Pharmacyclics LLC) Ibrutinib blocks BTK, a signalling enzyme that malignant B cells depend on to survive and multiply. Blocking it stops the cancer cells from receiving growth and survival signals, and also dampens B-cell-driven immune reactions, which is why it also works in chronic graft-versus-host disease. CLL/SLL and Waldenstrom's macroglobulinemia: 420 mg orally once daily until progression or unacceptable toxicity. cGVHD: 420 mg once daily in patients 12 years and older; 240 mg/m2 once daily (max 420 mg) in patients 1 to less than 12 years. MCL and MZL (US accelerated approvals, withdrawn April 2023): 560 mg once daily. Take at approximately the same time each day with a glass of water; swallow c
How long does ibrutinib stay in the body (half-life) and how should it be stored?
Storage: Capsules and tablets: store in original packaging at room temperature 20-25 degrees C (68-77 degrees F); brief exposure to 15-30 degrees C permitted. Oral suspension: store at 2-25 degrees C, do not freeze, use within 60 days of first opening. Shelf life is reported as 3 years at room temperature for tablets and capsules. Keep the product in its original packaging and check the expiry date printed on the pack.
Is ibrutinib available in India and was its sale stopped by the Delhi High Court?
Ibrutinib is made by 11 suppliers tracked in this database, including Beacon Pharmaceuticals PLC, Drug International Ltd. , Eskayef Pharmaceuticals Ltd. , Everest Pharmaceuticals Ltd. , General Pharmaceuticals Ltd. , Genvio Pharma Ltd. , Hetero Drugs Ltd. , Incepta Pharmaceuticals Ltd. . Bangladesh-registered brands: Butinib, Ibrucent, Ibrucon, Ibrunib, Ibrutab, Ibruxen, Ibutigen, Notafol.
Sources
- https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/217003s000lbl.pdf
- https://medex.com.bd/generics/1382/ibrutinib/brand-names
- https://www.drugs.com/availability/generic-imbruvica.html
- https://www.onclive.com/view/fda-approves-generic-ibrutinib-tablets-for-b-cell-malignancies
- https://www.oncnursingnews.com/view/generic-ibrutinib-tablet-given-tentative-fda-approval-in-cll-sll-wm
- https://sg.finance.yahoo.com/news/natco-receives-tentative-approval-ibrutinib-025800792.html
- https://medicinespatentpool.org/uploads/2023/09/MPP_Snapshots_2023_2024_RD_PDF_-Ibrutinib.pdf
- https://www.jnj.com/media-center/press-releases/update-on-imbruvica-ibrutinib-u-s-accelerated-approvals-for-mantle-cell-lymphoma-and-marginal-zone-lymphoma-indications
- https://news.abbvie.com/2023-04-06-Update-on-IMBRUVICA-R-ibrutinib-U-S-Accelerated-Approvals-for-Mantle-Cell-Lymphoma-and-Marginal-Zone-Lymphoma-Indications
- https://www.1mg.com/drugs/ibrunat-capsule-654833
- https://m.economictimes.com/industry/healthcare/biotech/pharmaceuticals/natco-launches-cut-the data-versions-of-cancer-drug-ibrutinib-in-india/articleshow/72894811.cms
- https://spicyip.com/2024/01/the-ibrunitib-saga-dhc-restrains-generic-competitors-but-what-about-public-interest.html
- https://timesofindia.indiatimes.com/india/sale-of-generic-versions-of-cancer-drug-stops-as-delhi-hc-prohibits-patent-infringement/articleshow/106680023.cms
- https://registrasiobat.pom.go.id/files/assesment-reports/01701329804.pdf
- https://www.goodrx.com/imbruvica/how-much-is-imbruvica-without-insurance
- https://baike.baidu.com/item/%E4%BC%8A%E5%B8%83%E6%9B%BF%E5%B0%BC/67427588
- https://pharsight.greyb.com/drug/imbruvica-patent-expiration
This page is an information resource for healthcare professionals, licensed importers and patients under medical care. It is not medical advice, not a prescription service, and not an offer to sell prescription medicines to the public.
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