Brukinsa (Zanubrutinib)

BRUKINSA is a kinase inhibitor indicated for the treatment of adult patients with:

• Mantle cell lymphoma (MCL) who have received at least one prior therapy. (
  1.1 Mantle Cell Lymphoma

  BRUKINSA is indicated for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.

  This indication is approved under accelerated approval based on overall response rate

  [see Clinical Studies (14.1)]

  . Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
  )
  
  This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
• Waldenström's macroglobulinemia (WM). (
  1.2 Waldenström's Macroglobulinemia

  BRUKINSA is indicated for the treatment of adult patients with Waldenström's macroglobulinemia (WM)

  [see Clinical Studies (14.2)]

  .
  )
• Relapsed or refractory marginal zone lymphoma (MZL) who have received at least one anti–CD20-based regimen. (
  1.3 Marginal Zone Lymphoma

  BRUKINSA is indicated for the treatment of adult patients with relapsed or refractory marginal zone lymphoma (MZL) who have received at least one anti–CD20-based regimen.

  This indication is approved under accelerated approval based on overall response rate

  [see Clinical Studies (14.3)]

  . Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
  )
  
  This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
• Chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). (
  1.4 Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

  BRUKINSA is indicated for the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL)

  [see Clinical Studies (14.4)]

  .
  )
• Relapsed or refractory follicular lymphoma (FL), in combination with obinutuzumab, after two or more lines of systemic therapy. (
  1.5 Follicular Lymphoma

  BRUKINSA is indicated for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL), in combination with obinutuzumab, after two or more lines of systemic therapy.

  This indication is approved under accelerated approval based on response rate and durability of response

  [see Clinical Studies (14.5)]

  . Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
  )
  
  This indication is approved under accelerated approval based on response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

• Recommended dosage: 160 mg orally twice daily or 320 mg orally once daily with or without food; swallow whole with water.
• Tablets can be split in half as prescribed by the healthcare provider. (
  2.1 Recommended Dosage

  The recommended dosage of BRUKINSA for monotherapy or in combination with obinutuzumab is 160 mg taken orally twice daily or 320 mg taken orally once daily until disease progression or unacceptable toxicity.

  Capsule Administration Instructions

  • Administer BRUKINSA capsules with or without food
    [see Clinical Pharmacology (12.3)]
    . Advise patients to swallow capsules whole with water and not to open, break, or chew capsules.

  Tablet Administration Instructions

  • Administer BRUKINSA tablets with or without food

    [see Clinical Pharmacology (12.3)]

    . Advise patients to swallow tablets whole with water and not to chew or crush the tablets. The tablets can be split in half as prescribed by the healthcare provider.

  Missed Dose

  If a dose of BRUKINSA is missed, it should be taken as soon as possible on the same day with a return to the normal schedule the following day.
  )
• Reduce BRUKINSA dose in patients with severe hepatic impairment. (
  2.2 Dosage Modification for Use in Hepatic Impairment

  The recommended dosage of BRUKINSA for patients with severe hepatic impairment (Child-Pugh class C) is 80 mg orally twice daily; no dosage modification is recommended for patients with mild or moderate hepatic impairment (Child-Pugh class A or B)

  [see Use in Specific Populations (8.7)and Clinical Pharmacology (12.3)]

  .
  ,
  8.7 Hepatic Impairment

  Dosage modification of BRUKINSA is recommended in patients with severe hepatic impairment

  [see Dosage and Administration (2.2)]

  . The safety of BRUKINSA has not been evaluated in patients with severe hepatic impairment. No dosage modification is recommended in patients with mild to moderate hepatic impairment. Monitor for BRUKINSA adverse reactions in patients with hepatic impairment

  [see Clinical Pharmacology (12.3)]

  .
  )
• Advise patients not to open, break, or chew capsules. (
  2.1 Recommended Dosage

  The recommended dosage of BRUKINSA for monotherapy or in combination with obinutuzumab is 160 mg taken orally twice daily or 320 mg taken orally once daily until disease progression or unacceptable toxicity.

  Capsule Administration Instructions

  • Administer BRUKINSA capsules with or without food
    [see Clinical Pharmacology (12.3)]
    . Advise patients to swallow capsules whole with water and not to open, break, or chew capsules.

  Tablet Administration Instructions

  • Administer BRUKINSA tablets with or without food

    [see Clinical Pharmacology (12.3)]

    . Advise patients to swallow tablets whole with water and not to chew or crush the tablets. The tablets can be split in half as prescribed by the healthcare provider.

  Missed Dose

  If a dose of BRUKINSA is missed, it should be taken as soon as possible on the same day with a return to the normal schedule the following day.
  )
• Advise patients not to chew or crush tablets. (
  2.1 Recommended Dosage

  The recommended dosage of BRUKINSA for monotherapy or in combination with obinutuzumab is 160 mg taken orally twice daily or 320 mg taken orally once daily until disease progression or unacceptable toxicity.

  Capsule Administration Instructions

  • Administer BRUKINSA capsules with or without food
    [see Clinical Pharmacology (12.3)]
    . Advise patients to swallow capsules whole with water and not to open, break, or chew capsules.

  Tablet Administration Instructions

  • Administer BRUKINSA tablets with or without food

    [see Clinical Pharmacology (12.3)]

    . Advise patients to swallow tablets whole with water and not to chew or crush the tablets. The tablets can be split in half as prescribed by the healthcare provider.

  Missed Dose

  If a dose of BRUKINSA is missed, it should be taken as soon as possible on the same day with a return to the normal schedule the following day.
  )
• Manage toxicity using treatment interruption, dose reduction, or discontinuation. (
  2.4 Dosage Modifications for Adverse Reactions

  Recommended dosage modifications of BRUKINSA for Grade 3 or higher adverse reactions are provided in Table 2.

  Table 2: Recommended Dosage Modifications for Adverse Reaction

  Adverse Reaction	Adverse Reaction Occurrence	Dosage Modification (Starting Dose: 160 mg twice daily or 320 mg once daily)
  Hematological toxicities [see Warnings and Precautions (5.3)]
  Grade 3 or Grade 4 febrile neutropenia Platelet count decreased to 25,000-50,000/mm3with significant bleeding Neutrophil count decreased to <500/mm3(lasting more than 10 consecutive days) Platelet count decreased to <25,000/mm3(lasting more than 10 consecutive days)	First	Interrupt BRUKINSA Once toxicity has resolved to Grade 1 or lower or baseline: Resume at 160 mg twice daily or 320 mg once daily.
  	Second	Interrupt BRUKINSA Once toxicity has resolved to Grade 1 or lower or baseline: Resume at 80 mg twice daily or 160 mg once daily.
  	Third	Interrupt BRUKINSA Once toxicity has resolved to Grade 1 or lower or baseline: Resume at 80 mg once daily.
  	Fourth	Discontinue BRUKINSA
  Nonhematological toxicities [see Warnings and Precautions (5.5)and Adverse Reactions (6.1)]
  Severe or life-threatening nonhematological toxicitiesEvaluate the benefit-risk before resuming treatment at the same dosage for Grade 4 nonhematological toxicity.	First	Interrupt BRUKINSA Once toxicity has resolved to Grade 1 or lower or baseline: Resume at 160 mg twice daily or 320 mg once daily.
  	Second	Interrupt BRUKINSA Once toxicity has resolved to Grade 1 or lower or baseline: Resume at 80 mg twice daily or 160 mg once daily.
  	Third	Interrupt BRUKINSA Once toxicity has resolved to Grade 1 or lower or baseline: Resume at 80 mg once daily.
  	Fourth	Discontinue BRUKINSA

  Asymptomatic lymphocytosis in CLL and MCL should not be regarded as an adverse reaction, and these patients should continue taking BRUKINSA.

  Refer to the obinutuzumab prescribing information for management of obinutuzumab toxicities.
  )

Capsules: Each 80 mg capsule is a size 0, white to off-white opaque capsule marked with "ZANU 80" in black ink.

Tablets: 160 mg, blue, oval, film-coated tablets debossed with "zanu" on one side and functional scoring on the other side.

Lactation: Advise not to breastfeed. (