New Primary Malignancies [see Warnings and Precautions (5.1)] |
Non-Cutaneous RAS Mutation-positive Malignancies | Permanently discontinue BRAFTOVI. |
Cardiomyopathy [see Warnings and Precautions (5.3)] |
- •
- Symptomatic congestive heart failure or absolute decrease in LVEF of greater than 20% from baseline that is also below LLN
| Reduce BRAFTOVI by one dose level [see Dosage and Administration (2.3)]. - •
- If LVEF improves to at least institutional LLN and absolute decrease to less than or equal to 10% compared to baseline, continue BRAFTOVI at the reduced dose [see Dosage and Administration (2.3)].
- •
- If no improvement, withhold BRAFTOVI until improves to at least institutional LLN and absolute decrease to less than or equal to 10% compared to baseline and then resume at the reduced dose or reduce dose an additional dose level.
|
Hepatotoxicity [see Warnings and Precautions (5.4)] |
- •
- 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. |
Uveitis [see Warnings and Precautions (5.6)] |
- •
- Grade 1–3
| If Grade 1 or 2 does not respond to specific ocular therapy, or for Grade 3 uveitis, 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 (5.7)] |
- •
- QTcF greater than 500 ms and less than or equal to 60 ms increase from baseline
| Withhold 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. |
Dermatologic [other than Hand-foot Skin Reaction (HFSR)] [see Adverse Reactions (6.1)] |
- •
- 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)] and HFSR [see Adverse Reactions (6.1)]† |
- •
- 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. |