Severity of Adverse Reactiona

Dose Modification for BRAFTOVI

New Primary Malignancies [see Warnings and Precautions (5.1)]

Non-Cutaneous RAS Mutation-positiveMalignanciesPermanently discontinue BRAFTOVI.

Uveitis [see Warnings and Precautions (5.4)]

Grade 1-3 If Grade 1 or 2 does not respond to specific ocular therapy, or for Grade 3uveitis, withhold BRAFTOVI for up to 6 weeks.

 If improved, resume at same or reduced dose.

 If not improved, permanently discontinue BRAFTOVI.

 Grade 4 Permanently discontinue BRAFTOVI.

QTc Prolongation [see Warnings and Precautions (5.5)]

QTcF greater than 500 ms and

less than or equal to 60 msincrease from baselineWithhold BRAFTOVI until QTcF less than or equal to 500 ms. Resume at

reduced dose.

If more than one recurrence, permanently discontinue BRAFTOVI.

QTcF greater than 500 ms and

greater than 60 ms increase

from baseline

Permanently discontinue BRAFTOVI.

Hepatotoxicity

 Grade 2 AST or ALT

increased

Maintain BRAFTOVI dose.

 If no improvement within 4 weeks, withhold BRAFTOVI until

improves to Grade 0-1 or to pretreatment/baseline levels and then

resume at same dose.

 Grade 3 or 4 AST or ALT

increased

See Other Adverse Reactions.

Dermatologic

 Grade 2 If no improvement within 2 weeks, withhold BRAFTOVI until Grade 0-1.

Resume at same dose.

 Grade 3 Withhold BRAFTOVI until Grade 0-1. Resume at same dose if first

occurrence or reduce dose if recurrent.

 Grade 4 Permanently discontinue BRAFTOVI.

Other Adverse Reactions (including Hemorrhage [see Warnings and Precautions (5.3)])b

 Recurrent Grade 2 or

 First occurrence of any Grade 3

Withhold BRAFTOVI for up to 4 weeks.

 If improves to Grade 0-1 or to pretreatment/baseline level, resume

at reduced dose.

 If no improvement, permanently discontinue BRAFTOVI.

 First occurrence of any Grade 4 Permanently discontinue BRAFTOVI or

Withhold BRAFTOVI for up to 4 weeks.

 If improves to Grade 0-1 or to pretreatment/baseline level, then

resume at reduced dose.

 If no improvement, permanently discontinue BRAFTOVI.

 Recurrent Grade 3 Consider permanently discontinuing BRAFTOVI.

 Recurrent Grade 4 Permanently discontinue BRAFTOVI. 

aNational Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. b Dose modification of BRAFTOVI when administered with binimetinib is not recommended for new primary cutaneous malignancies; ocular

events other than uveitis, iritis, and iridocyclitis; interstitial lung disease/pneumonitis; cardiac dysfunction; creatine phosphokinase (CPK)elevation; rhabdomyolysis; and venous thromboembolism.

Refer to the binimetinib prescribing information for dose modifications for adverse reactions associated withbinimetinib. 

2.4 Dose Modifications for Coadministration of Strong or Moderate CYP3A4 InhibitorsAvoid concurrent use of strong or moderate CYP3A4 inhibitors during treatment with BRAFTOVI. If