Brukinsa

Medical Editor: John P. Cunha, DO, FACOEP Last updated on RxList: 11/29/2021
Brukinsa Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

What Is Brukinsa?

Brukinsa (zanubrutinib) is a kinase inhibitor used to treat adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.

What Are Side Effects of Brukinsa?

Common side effects of Brukinsa include:

Dosage for Brukinsa

The recommended dose of Brukinsa is 160 mg orally twice daily or 320 mg orally once daily; swallow whole with water and with or without food.

Brukinsa In Children

Safety and effectiveness of Brukinsa in pediatric patients have not been established.

What Drugs, Substances, or Supplements Interact with Brukinsa?

Brukinsa may interact with other medicines such as:

  • itraconazole,
  • fluconazole,
  • clarithromycin,
  • erythromycin,
  • diltiazem,
  • rifampin,
  • efavirenz,
  • midazolam,
  • omeprazole, and
  • digoxin

Tell your doctor all medications and supplements you use.

Brukinsa During Pregnancy and Breastfeeding

Brukinsa is not recommended for use during pregnancy; it may harm a fetus. Pregnancy testing is recommended for females of reproductive potential prior to initiating Brukinsa therapy. Female patients of reproductive potential are advised to use effective contraception during treatment with Brukinsa and for at least 1 week following the last dose. It is unknown if Brukinsa passes into breast milk. Because of the potential for serious adverse reactions from Brukinsa in a breastfed child, breastfeeding is not recommended during treatment with Brukinsa and for at least two weeks following the last dose.

Additional Information

Our Brukinsa (zanubrutinib) Capsules, for Oral Use Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

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Brukinsa Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Zanubrutinib can cause serious or life-threatening side effects. Call your doctor at once if you have:

  • pounding heartbeats or fluttering in your chest;
  • chest discomfort;
  • a light-headed feeling, like you might pass out;
  • liver problems--right-sided upper stomach pain, vomiting, loss of appetite, yellowing of your skin or eyes, and not feeling well;
  • low platelets in your blood--easy bruising, unusual bleeding, purple or red spots under your skin;
  • low red blood cells--pale skin, weakness, unusual tiredness, feeling light-headed or short of breath, cold hands and feet, fast or irregular heartbeat;
  • low white blood cell counts--fever, mouth sores, skin sores, sore throat, cough, trouble breathing;
  • signs of bleeding inside your body--red or pink urine, bloody or tarry stools, coughing up blood or vomit that looks like coffee grounds, severe headache, vision problems, numbness or weakness on one side, trouble speaking or understanding what is said to you; or
  • signs of infection--fever, chills, redness or swelling, cough with mucus, feeling short of breath.

Your cancer treatments may be delayed or permanently discontinued if you have certain side effects.

Common side effects may include:

  • diarrhea;
  • low platelet or other blood cell counts;
  • easy bruising or bleeding;
  • rash; or
  • cold symptoms such as stuffy nose, sneezing, sore throat or cough.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Brukinsa (Zanubrutini Capsules)

Brukinsa Professional Information

SIDE EFFECTS

The following clinically significant adverse reactions are discussed in more detail in other sections of the labeling:

  • Hemorrhage [see WARNINGS AND PRECAUTIONS]
  • Infections [see WARNINGS AND PRECAUTIONS]
  • Cytopenias [see WARNINGS AND PRECAUTIONS]
  • Second Primary Malignancies [see WARNINGS AND PRECAUTIONS]
  • Cardiac Arrhythmias [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The data in the WARNINGS AND PRECAUTIONS reflect exposure to BRUKINSA in seven clinical trials, administered as a single agent at 160 mg twice daily in 662 patients, in patients with hematologic malignancies in clinical trials at 320 mg once daily in 105 patients, and at 40 mg to 160 mg once daily (0.125 to 0.5 times the recommended dosage) in 12 patients. Among 779 patients receiving BRUKINSA, 74% were exposed for at least 1 year, 55% were exposed for at least 2 years, and 16% were exposed for at least 3 years.

In this pooled safety population, the most common adverse reactions, including laboratory abnormalities, in ≥ 20% of patients who received BRUKINSA were neutrophil count decreased (56%), upper respiratory tract infection (49%), platelet count decreased (44%), rash (35%), hemorrhage (35%), musculoskeletal pain (30%), hemoglobin decreased (28%), bruising (25%), diarrhea (23%), pneumonia (22%), and cough (21%).

Mantle Cell Lymphoma (MCL)

The safety of BRUKINSA was evaluated in 118 patients with MCL who received at least one prior therapy in two single-arm clinical trials, BGB-3111-206 [NCT03206970] and BGB-3111- AU-003 [NCT02343120] [see Clinical Studies]. The median age of patients who received BRUKINSA in studies BGB-3111-206 and BGB-3111-AU-003 was 62 years (range: 34 to 86), 75% were male, 75% were Asian, 21% were White, and 94% had an ECOG performance status of 0 to 1. Patients had a median of 2 prior lines of therapy (range: 1 to 4). The BGB-3111-206 trial required a platelet count ≥ 75 x 109/L and an absolute neutrophil count ≥ 1 x 109/L independent of growth factor support, hepatic enzymes ≤ 2.5 x upper limit of normal, total bilirubin ≤ 1.5 x ULN. The BGB-3111-AU-003 trial required a platelet count ≥ 50 x 109/L and an absolute neutrophil count ≥ 1 x 109/L independent of growth factor support, hepatic enzymes ≤ 3 x upper limit of normal, total bilirubin ≤ 1.5 x ULN. Both trials required a CLcr ≥ 30 mL/min. Both trials excluded patients with prior allogeneic hematopoietic stem cell transplant, exposure to a BTK inhibitor, known infection with HIV, and serologic evidence of active hepatitis B or hepatitis C infection and patients requiring strong CYP3A inhibitors or strong CYP3A inducers. Patients received BRUKINSA 160 mg twice daily or 320 mg once daily. Among patients receiving BRUKINSA, 79% were exposed for 6 months or longer and 68% were exposed for greater than one year.

Fatal events within 30 days of the last dose of BRUKINSA occurred in 8 (7%) of 118 patients with MCL. Fatal cases included pneumonia in 2 patients and cerebral hemorrhage in one patient.

Serious adverse reactions were reported in 36 patients (31%). The most frequent serious adverse reactions that occurred were pneumonia (11%), and hemorrhage (5%).

Of the 118 patients with MCL treated with BRUKINSA, 8 (7%) patients discontinued treatment due to adverse reactions in the trials. The most frequent adverse reaction leading to treatment discontinuation was pneumonia (3.4%). One (0.8%) patient experienced an adverse reaction leading to dose reduction (hepatitis B).

Table 3 summarizes the adverse reactions in BGB-3111-206 and BGB-3111-AU-003.

Table 3: Adverse Reactions (≥ 10%) in Patients Receiving BRUKINSA in BGB-3111- 206 and BGB-3111-AU-003 Trials

Body System Adverse Reaction Percent of Patients
(N=118)
All Grades % Grade 3 or Higher %
Blood and lymphatic system disorders Neutropenia and Neutrophil count decreased 38 15
Thrombocytopenia and Platelet count decreased 27 5
Leukopenia and White blood count decreased 25 5
Anemia and Hemoglobin decreased 14 8
Infections and infestations Upper respiratory tract infection¶ 39 0
Pneumonia § 15 10^
Urinary tract infection 11 0.8
Skin and subcutaneous tissue disorders Rash || 36 0
Bruising * 14 0
Gastrointestinal disorders Diarrhea 23 0.8
Constipation 13 0
Vascular disorders Hypertension 12 3.4
Hemorrhage † 11 3.4^
Musculoskeletal and connective tissue disorders Musculoskeletal pain‡ 14 3.4
Metabolism and nutrition disorders Hypokalemia 14 1.7
Respiratory, thoracic and mediastinal disorders Cough 12 0
^ Includes fatal adverse reaction
* Bruising includes all related terms containing bruise, bruising, contusion, ecchymosis
† Hemorrhage includes all related terms containing hemorrhage, hematoma
‡ Musculoskeletal pain includes musculoskeletal pain, musculoskeletal discomfort, myalgia, back pain, arthralgia, arthritis
§ Pneumonia includes pneumonia, pneumonia fungal, pneumonia cryptococcal, pneumonia streptococcal, atypical pneumonia, lung infection, lower respiratory tract infection, lower respiratory tract infection bacterial, lower respiratory tract infection viral
o Rash includes all related terms containing rash
¶ Upper respiratory tract infection includes upper respiratory tract infection, upper respiratory tract infection viral

Other clinically significant adverse reactions that occurred in < 10% of patients with mantle cell lymphoma include major hemorrhage (defined as ≥ Grade 3 hemorrhage or CNS hemorrhage of any grade) (5%), hyperuricemia (6%) and headache (4.2%).

Table 4: Selected Laboratory Abnormalities* (> 20%) in Patients with MCL in Studies BGB-3111-206 and BGB-3111-AU-003

Laboratory Parameter Percent of Patients
(N=118)
All Grades (%) Grade 3 or 4 (%)
Neutrophils decreased 45 20
Platelets decreased 40 7
Hemoglobin decreased 27 6
Lymphocytosis † 41 16
Chemistry abnormalities
Blood uric acid increased 29 2.6
ALT increased 28 0.9
Bilirubin increased 24 0.9
* Based on laboratory measurements.
† Asymptomatic lymphocytosis is a known effect of BTK inhibition.

Waldenstrom's Macroglobulinemia (WM)

The safety of BRUKINSA was investigated in two cohorts of Study BGB-3111-302 (ASPEN). Cohort 1 included 199 patients with MYD88 mutation (MYD88MUT) WM, randomized to and treated with either BRUKINSA (101 patients) or ibrutinib (98 patients). The trial also included a non-randomized arm, Cohort 2, with 26 wild type MYD88 (MYD88WT) WM patients and 2 patients with unknown MYD88 status [see Clinical Studies].

Among patients who received BRUKINSA, 93% were exposed for 6 months or longer and 89% were exposed for greater than 1 year.

In Cohort 1 of the ASPEN study safety population (N=101), the median age of patients who received BRUKINSA was 70 years (45-87 years old); 67% were male, 86% were White, 4% were Asian and 10% were not reported (unknown race). In Cohort 2 of the ASPEN study safety population (N=28), the median age of patients who received BRUKINSA was 72 (39-87 years old); 50% were male and 96% were White, and 4% were not-reported (unknown race).

In Cohort 1, serious adverse reactions occurred in 44% of patients who received BRUKINSA. Serious adverse reactions in >2% of patients included influenza (3%), pneumonia (4%), neutropenia and neutrophil count decreased (3%), hemorrhage (4%), pyrexia (3%), and febrile neutropenia (3%). In Cohort 2, serious adverse reactions occurred in 39% of patients. Serious adverse reactions in > 2 patients included pneumonia (14%).

Permanent discontinuation of BRUKINSA due to an adverse reaction occurred in 2% of patients in Cohort 1 and included hemorrhage (1 patient) and neutropenia and neutrophil count decreased (1 patient); in Cohort 2, permanent discontinuation of BRUKINSA due to an adverse reaction occurred in 7% of patients and included subdural hemorrhage (1 patient) and diarrhea (1 patient).

Dosage interruptions of BRUKINSA due to an adverse reaction occurred in 32% of patients in Cohort 1 and in 29% in Cohort 2. Adverse reactions which required dosage interruption in > 2% of patients included neutropenia, vomiting, hemorrhage, thrombocytopenia, and pneumonia in Cohort 1. Adverse reactions leading to dosage interruption in >2 patients in Cohort 2 included pneumonia and pyrexia.

Dose reductions of BRUKINSA due to an adverse reaction occurred in 11% of patients in Cohort 1 and in 7% in Cohort 2. Adverse reactions which required dose reductions in > 2% of patients included neutropenia in Cohort 1. Adverse reaction leading to dose reduction occurred in 2 patients in Cohort 2 (each with one event: diarrhea and pneumonia).

Table 5 summarizes the adverse reactions in Cohort 1 in ASPEN.

Table 5: Adverse Reactions (≥ 10%) Occurring in Patients with WM Who Received BRUKINSA in Cohort 1

Body System Adverse Reaction BRUKINSA
(N=101)
Ibrutinib
(N=98)
All Grades (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%)
Infections and infestations Upper respiratory tract infection¶ 44 0 40 2
Pneumonia § 12 4 26 10
Urinary tract infection 11 0 13 2
Gastrointestinal disorders Diarrhea 22 3 34 2
Nausea 18 0 13 1
Constipation 16 0 7 0
Vomiting 12 0 14 1
General disorders and administration site conditions Fatigue# 31 1 25 1
Pyrexia 16 4 13 2
Edema peripheral 12 0 20 0
Skin and subcutaneous tissue disorders Bruising * 20 0 34 0
Rash 29 0 32 0
Pruritus 11 1 6 0
Musculoskeletal and connective tissue disorders Musculoskeletal pain ‡ 45 9 39 1
Muscle spasms 10 0 28 1
Nervous system disorders Headache 18 1 14 1
Dizziness 13 1 12 0
Respiratory, thoracic and mediastinal disorders Cough 16 0 18 0
Dyspnea 14 0 7 0
Vascular disorders Hemorrhage † 42 4 43 9
Hypertension 14 9 19 14
* Bruising includes all related terms containing “bruise,” “contusion,” or “ecchymosis”.
† Hemorrhage includes epistaxis, hematuria, conjunctival hemorrhage, hematoma, rectal hemorrhage, periorbital hemorrhage, mouth hemorrhage, post procedural hemorrhage, hemoptysis, skin hemorrhage, hemorrhoidal hemorrhage, ear hemorrhage, eye hemorrhage, hemorrhagic diathesis, periorbital hematoma, subdural hemorrhage, wound hemorrhage, gastric hemorrhage, lower gastrointestinal hemorrhage, spontaneous hematoma, traumatic hematoma, traumatic intracranial hemorrhage, tumor hemorrhage, retinal hemorrhage, hematochezia, diarrhea hemorrhagic, hemorrhage, melena, post procedural hematoma, subdural hematoma, anal hemorrhage, hemorrhagic disorder, pericardial hemorrhage, postmenopausal hemorrhage, stoma site hemorrhage and subarachnoid hemorrhage.
# Fatigue includes asthenia, fatigue, lethargy.
‡ Musculoskeletal pain includes back pain, arthralgia, pain in extremity, musculoskeletal pain, myalgia, bone pain, spinal pain, musculoskeletal chest pain, neck pain, arthritis and musculoskeletal discomfort.
§ Pneumonia includes lower respiratory tract infection, lung infiltration, pneumonia, pneumonia aspiration, pneumonia viral.
o Rash includes all related terms rash, maculo-papular rash, erythema, rash erythematous, drug eruption, dermatitis allergic, dermatitis atopic, rash pruritic, dermatitis, photodermatosis, dermatitis acneiform, stasis dermatitis, vasculitic rash, eyelid rash, urticaria, and skin toxicity.
¶ Upper respiratory tract infection includes upper respiratory tract infection, laryngitis, nasopharyngitis, sinusitis, rhinitis, viral upper respiratory tract infection, pharyngitis, rhinovirus infection, upper respiratory tract congestion.

Clinically relevant adverse reactions in <10% of patients who received BRUKINSA included localized infection, atrial fibrillation or atrial flutter, and hematuria.

Table 6 summarizes the laboratory abnormalities in ASPEN.

Table 6: Select Laboratory Abnormalities* (≥20%) That Worsened from Baseline in Patients with WM Who Received BRUKINSA in Cohort 1

Laboratory Abnormality BRUKINSA1 Ibrutinib1
All Grades (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%)
Hematologic Abnormalities
Neutrophils decreased 50 24 34 9
Platelets decreased 35 8 39 5
Hemoglobin decreased 20 7 20 7
Chemistry Abnormalities
Bilirubin increased 12 1.0 33 1.0
Calcium decreased 27 2.0 26 0
Creatinine increased 31 1.0 21 1.0
Glucose increased 45 2.3 33 2.3
Potassium increased 24 2.0 12 0
Urate increased 16 3.2 34 6
Phosphate decreased 20 3.1 18 0
* Based on laboratory measurements.
1The denominator used to calculate the rate varied from 86 to 101 based on the number of patients with a baseline value and at least one post-treatment value.

DRUG INTERACTIONS

Effect of Other Drugs on BRUKINSA

Table 7: Drug Interactions that Affect Zanubrutinib

Moderate and Strong CYP3A Inhibitors
Clinical Impact
  • Co-administration with a moderate or strong CYP3A inhibitor increases zanubrutinib Cmax and AUC [see CLINICAL PHARMACOLOGY] which may increase the risk of BRUKINSA toxicities.
Prevention or management
  • Reduce BRUKINSA dosage when co-administered with moderate or strong CYP3A inhibitors [see DOSAGE AND ADMINISTRATION].
Moderate and Strong CYP3A Inducers
Clinical Impact
  • Co-administration with a moderate or strong CYP3A inducer decreases zanubrutinib Cmax and AUC [see CLINICAL PHARMACOLOGY] which may reduce BRUKINSA efficacy.
Prevention or management
  • Avoid co-administration of BRUKINSA with moderate or strong CYP3A inducers [see DOSAGE AND ADMINISTRATION].

Read the entire FDA prescribing information for Brukinsa (Zanubrutini Capsules)

© Brukinsa Patient Information is supplied by Cerner Multum, Inc. and Brukinsa Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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