• No dose modification for patients aged ≥65 years, or with mild-to-moderate impairment of kidney function or liver function¹
  • No dose modification is needed for patients with mild-to-moderate renal impairment (creatinine clearance (CrCl) ≥ 30 mL/min, estimated by Cockcroft-Gault).
  • No dose modification is needed for patients with mild (Child-Pugh class A) or moderate (Child-Pugh class B) hepatic impairment.
  • Patients with severe kidney impairment, patients requiring dialysis, and patients with severe hepatic impairment should be monitored for adverse reactions. Although the safety of BRUKINSA has not been evaluated in patients with severe hepatic impairment, there is no caution to avoid use in these patients; dose modification is recommended.
• Simple dose adjustment for co-administration with strong or moderate CYP3A inhibitors.
  Avoid co-administration with strong and moderate CYP3A inducers. Co-administration with mild CYP3A inducers should be done with caution¹
• For 3 to 7 days pre- and post-surgery, consider the benefit-risk of withholding BRUKINSA depending upon the type of surgery and the risk of bleeding¹

Recommended dose modification for Grade ≥3 adverse reactions¹

Starting dose	1st occurrence	2nd occurrence	3rd occurrence	4th occurrence
Start at a total dose of 320 mg (four 80 mg capsules)	Interrupt BRUKINSA treatment. Resume treatment once toxicity has returned to grade ≤1 or baseline			Discontinue
	No dose change	Reduce to a total dose of 160 mg	Reduce to a total dose of 80 mg
Take once daily am/pm	am/pm	am/pm	Once daily	Discontinue
OR
Take twice daily am pm	am pm	am pm	Once daily	Discontinue

Grade ≥3 adverse reactions

• Grade 3 or higher non-haematological toxicities
• Grade 3 febrile neutropenia
• Grade 3 thrombocytopenia with significant bleeding
• Grade 4 neutropenia (lasting more than 10 consecutive days)
• Grade 4 thrombocytopenia (lasting more than 10 consecutive days)

• Dose reduction across studies (N=1,550): 5%¹
• Treatment discontinuation across studies (N=1,550): 5%¹

The safety profile is based on pooled data from 1,550 patients with B-cell malignancies treated with BRUKINSA in clinical studies with a median duration of exposure of 34.41 months¹

Pooled data: treatment-emergent adverse reactions in ≥10% of patients with B-cell malignancies (N=1,550)*¹

• *Grades were evaluated based on the NCI-CTCAE version 4.03¹
• †<1% of patients with Grade 3 or higher adverse reactions.¹
• ‡Includes multiple adverse reaction terms.¹
• ¶Includes events with fatal outcome(s).¹