Ibrutinib

Ibrutinib is a small-molecule inhibitor of Bruton’s tyrosine kinase (BTK). Ibrutinib forms a covalent bond with a cysteine residue in the BTK active site, leading to inhibition of BTK enzymatic activity.

• IMBRUVICA is a kinase inhibitor indicated for the treatment of: Adult patients with chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL) ( 1.1 ). Adult patients with chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL) with 17p deletion ( 1.2 ).ICD-10: C85.90, C95.90

• None None ( 4 )contraindicated

CLL/SLL and WM : 420 mg taken orally once daily ( 2.1 ). cGVHD : ◦ Patients 12 years and older: 420 mg taken orally once daily ( 2.1 ). ◦ Patients 1 to less than 12 years of age: 240 mg/m 2 taken orally once daily (up to a dose of 420 mg) ( 2.1 ). Tablets or capsules should be taken orally with a glass of water. Do not open, break, or chew the capsules. Do not cut, crush, or chew the tablets. See full prescribing information for oral suspension administration instructions ( 2.1 ). 2.1 Recommended Dosage Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma and Waldenström’s Macroglobulinemia The recommended dosage of IMBRUVICA for CLL/SLL and WM is 420 mg orally once daily until disease progression or unacceptable toxicity. For CLL/SLL, IMBRUVICA can be administered as a single agent, in combination with rituximab or obinutuzumab, or in combination with bendamustine and rituximab (BR). For WM, IMBRUVICA can be administered as a single agent or in combination with rituximab. When administering IMBRUVICA in combination with rituximab or obinutuzumab, consider administering IMBRUVICA prior to rituximab or obinutuzumab when given on the same day. Chronic Graft versus Host Disease The recommended dosage of IMBRUVICA for patients age 12 years and older with cGVHD is 420 mg orally once daily, and for patients 1 to less than 12 years of age with cGVHD is 240 mg/m 2 orally once daily (up to a dose of 420 mg), until cGVHD progression, recurrence of an underlying malignancy, or unacceptable toxicity.

Hemorrhage : Monitor for bleeding and manage ( 5.1 ). Infections : Monitor patients for fever and infections, evaluate promptly, and treat ( 5.2 ). Cardiac Arrhythmias , Cardiac Failure , and Sudden Death : Monitor for symptoms of arrhythmias and cardiac failure and manage ( 5.3 ). Hypertension : Monitor blood pressure and treat ( 5.4 ). Cytopenias : Check complete blood counts monthly ( 5.5 ). Second Primary Malignancies : Other malignancies have occurred in patients, including skin cancers, and other carcinomas ( 5.6 ). Hepatotoxicity, Including Drug- Induced Liver Injury : Monitor hepatic function throughout treatment ( 5.7 ). Tumor Lysis Syndrome (TLS) : Assess baseline risk and take precautions. Monitor and treat for TLS ( 5.8 ). Embryo-Fetal Toxicity : Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception ( 5.9 , 8.1 , 8.3 ). 5.1 Hemorrhage Fatal bleeding events have occurred in patients who received IMBRUVICA. Major hemorrhage (≥ Grade 3, serious, or any central nervous system events; e.g., intracranial hemorrhage [including subdural hematoma], gastrointestinal bleeding, hematuria, and post procedural hemorrhage) occurred in 4.2% of patients, with fatalities occurring in 0.4% of 2,838 patients who received IMBRUVICA in 27 clinical trials. Bleeding events of any grade including bruising and petechiae occurred in 39%, and excluding bruising and petechiae occurred in 23% of patients who received IMBRUVICA, respectively [see Adverse Reactions ( 6.1 )] .

The following clinically significant adverse reactions are described elsewhere in the labeling: Hemorrhage [see Warnings and Precautions ( 5.1 )] Infections [see Warnings and Precautions ( 5.2 )] Cardiac Arrhythmias, Cardiac Failure, and Sudden Death [see Warnings and Precautions ( 5.3 )] Hypertension [see Warnings and Precautions ( 5.4 )] Cytopenias [see Warnings and Precautions ( 5.5 )] Second Primary Malignancies [see Warnings and Precautions ( 5.6 )] Hepatotoxicity, including DILI [see Warning s and Precautions ( 5.7 )] Tumor Lysis Syndrome [see Warnings and Precautions ( 5.8 )] The most common (≥30%) adverse reactions in patients with B-cell malignancies are thrombocytopenia, diarrhea, fatigue, musculoskeletal pain, neutropenia, rash, anemia, bruising, and nausea ( 6 ). The most common (≥20%) adverse reactions in adult or pediatric patients with cGVHD are fatigue, anemia, bruising, diarrhea, thrombocytopenia, musculoskeletal pain, pyrexia, muscle spasms, stomatitis, hemorrhage, nausea, abdominal pain, pneumonia, and headache ( 6 ). To report SUSPECTED ADVERSE REACTIONS, contact AbbVie at 1-800-633-9110 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely variable conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared with rates of clinical trials of another drug and may not reflect the rates observed in practice.

Lactation : Advise not to breastfeed ( 8.2 ). Hepatic Impairment : Avoid use of IMBRUVICA in patients with severe hepatic impairment. In patients with mild or moderate impairment, reduce IMBRUVICA dose ( 2.4 , 8.6 ). 8.1 Pregnancy Risk Summary IMBRUVICA can cause fetal harm based on findings from animal studies. There are no available data on IMBRUVICA use in pregnant women to inform a drug-associated risk of major birth defects and miscarriage. In animal reproduction studies, administration of ibrutinib to pregnant rats and rabbits during the period of organogenesis at exposures up to 3-20 times the clinical dose of 420 mg daily produced embryofetal toxicity including structural abnormalities (see Data) . Advise pregnant women of the potential risk to a fetus. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data Ibrutinib was administered orally to pregnant rats during the period of organogenesis at doses of 10, 40 and 80 mg/kg/day.

Metabolism

Ibrutinib exposure increases with doses up to 840 mg (2 times the maximum approved recommended dosage) in patients with B-cell malignancies. The mean steady-state AUC (% coefficient of variation) observed in patients at 420 mg with CLL/SLL is 708 (71%) ng×h/mL, with WM is 707 (72%) ng×h/mL, and in adult patients with previously treated cGVHD is 1159 (50%) ng×h/mL.

There is no specific experience in the management of ibrutinib overdose in patients. One healthy subject experienced reversible Grade 4 hepatic enzyme increases (AST and ALT) after a dose of 1680 mg. Closely monitor patients who ingest more than the recommended dosage and provide appropriate supportive treatment.

• Nov 13, 2013NDANDA205552Pharmacyclics Llc
• Feb 16, 2018NDANDA210563Pharmacyclics Llc
• Aug 24, 2022NDANDA217003Pharmacyclics Llc

1. 1Death8,46611%
2. 2Off Label Use5,9427.5%
3. 3Fatigue4,7085.9%
4. 4Diarrhoea4,1525.2%
5. 5Atrial Fibrillation3,8664.9%
6. 6Pneumonia3,2374.1%
7. 7Contusion2,7923.5%
8. 8Incorrect Dose Administered2,7783.5%
9. 9Fall2,5023.1%
10. 10Asthenia2,3392.9%
11. 11Nausea2,2972.9%
12. 12Arthralgia2,1982.8%
13. 13Rash2,1392.7%
14. 14Haemorrhage1,9932.5%
15. 15Disease Progression1,9702.5%

The 10 most recently updated of 425 ClinicalTrials.gov registrations naming Ibrutinib as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• A Study of Nemtabrutinib (MK-1026) Versus Comparator (Investigator's Choice of Ibrutinib or Acalabrutinib) in First Line (1L) Chronic Lymphocytic Leukemia (CLL)/ Small Lymphocytic Lymphoma (SLL) (MK-1026-011/BELLWAVE-011)
  Recruiting · Phase 3 · Interventional · 1,200 enrolled · Merck Sharp & Dohme LLC
  NCT06136559updated 2026-06-12
• Ibrutinib and Rituximab in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma or Older Patients With Newly Diagnosed Mantle Cell Lymphoma
  Active not recruiting · Phase 2 · Interventional · 113 enrolled · M.D. Anderson Cancer Center
  NCT01880567updated 2026-06-12
• A Study of Nemtabrutinib (MK-1026) in Participants With Relapsed or Refractory Hematologic Malignancies (ARQ 531-101/MK-1026-001)
  Active not recruiting · Phase 1 · Phase 2 · Interventional · 190 enrolled · ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA)
  NCT03162536updated 2026-06-12
• Tisagenlecleucel in Adult Patients With Aggressive B-cell Non-Hodgkin Lymphoma
  Completed · Phase 3 · Interventional · 330 enrolled · Novartis Pharmaceuticals
  NCT03570892updated 2026-06-12
• Testing the Combination of Venetoclax and Rituximab, in Comparison to the Usual Treatment (Ibrutinib Plus Rituximab or Zanubrutinib Alone) for Waldenstrom's Macroglobulinemia/Lymphoplasmacytic Lymphoma
  Recruiting · Phase 2 · Interventional · 92 enrolled · National Cancer Institute (NCI)
  NCT04840602updated 2026-06-11
• A Study of Epcoritamab and Ibrutinib in People With Central Nervous System Lymphoma (CNSL)
  Recruiting · Phase 1 · Interventional · 26 enrolled · Memorial Sloan Kettering Cancer Center
  NCT07082868updated 2026-06-11
• Ibrutinib and Rituximab Compared With Fludarabine Phosphate, Cyclophosphamide, and Rituximab in Treating Patients With Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
  Active not recruiting · Phase 3 · Interventional · 529 enrolled · National Cancer Institute (NCI)
  NCT02048813updated 2026-06-11
• Ibrutinib After Intensive Induction in Treating Patients With Previously Untreated Mantle Cell Lymphoma
  Completed · Phase 2 · Interventional · 37 enrolled · Northwestern University
  NCT02242097updated 2026-06-10
• Lisocabtagene Maraleucel, Nivolumab and Ibrutinib for the Treatment of Richter's Transformation
  Active not recruiting · Phase 2 · Interventional · 9 enrolled · City of Hope Medical Center
  NCT05672173updated 2026-06-09
• A Study of Pirtobrutinib (LOXO-305) Versus Ibrutinib in Participants With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)
  Recruiting · Phase 3 · Interventional · 737 enrolled · Loxo Oncology, Inc.
  NCT05254743updated 2026-06-09

Frequently asked questions

How does Ibrutinib work?

Ibrutinib is a small-molecule inhibitor of Bruton’s tyrosine kinase (BTK). Ibrutinib forms a covalent bond with a cysteine residue in the BTK active site, leading to inhibition of BTK enzymatic activity.

What is Ibrutinib used for?

According to FDA labeling, Ibrutinib carries indications including: IMBRUVICA is a kinase inhibitor indicated for the treatment of: Adult patients with chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL) ( 1.1 ). Adult patients with chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL) with 17p deletion ( 1.2 ).. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Ibrutinib?

Ibrutinib is classified as Bruton's tyrosine kinase (BTK) inhibitors, Kinase Inhibitor, Protein Kinase Inhibitors, Cellular Proliferation Alteration.

What are the brand names for Ibrutinib?

Ibrutinib is marketed under brand names including Imbruvica.

What are the contraindications for Ibrutinib?

Ibrutinib labeling lists contraindications including: None None ( 4 ). Always consult the full prescribing information and a clinician.