Uncomplicated deep venous thrombosis(DVT) or pulmonary embolism (PE)Withhold MEKTOVI.

If improves to Grade 0-1, resume at a reduced dose.

If no improvement, permanently discontinue MEKTOVI.

Life threatening PE Permanently discontinue MEKTOVI.

Serous Retinopathy [see Warnings and Precautions (5.3)]

Symptomatic serous retinopathy/Retinalpigment epithelial detachmentsWithhold MEKTOVI for up to 10 days.

If improves and becomes asymptomatic, resume at same dose.

If not improved, resume at a lower dose level or permanentlydiscontinue MEKTOVI.

Retinal Vein Occlusion (RVO) [see Warnings and Precautions (5.3)]

Any Grade Permanently discontinue MEKTOVI.

Uveitis [see Warnings and Precautions (5.3)]Grade 1-3 If Grade 1 or 2 does not respond to specific ocular therapy, or for

Grade 3 uveitis, withhold MEKTOVI for up to 6 weeks.If improved, resume at same or reduced dose.

If not improved, permanently discontinue MEKTOVI.

Grade 4 Permanently discontinue MEKTOVI.

Interstitial Lung Disease [see Warnings and Precautions (5.4)]

Grade 2 Withhold MEKTOVI for up to 4 weeks.

If improved to Grade 0-1, resume at a reduced dose.

If not resolved within 4 weeks, permanently discontinueMEKTOVI.

Grade 3 or Grade 4 Permanently discontinue MEKTOVI.

Hepatotoxicity [see Warnings and Precautions (5.5)]

Grade 2 AST or ALT increased Maintain MEKTOVI dose.

If no improvement within 2 weeks, withhold MEKTOVI untilimproved to Grade 0-1 or to pretreatment/baseline levels and thenresume at the same dose.

Grade 3 or 4 AST or ALT increased See Other Adverse Reactions.

Rhabdomyolysis or Creatine Phosphokinase (CPK) elevations [see Warnings and Precautions (5.6)]

Grade 4 asymptomatic CPK elevation orAny Grade CPK elevation withsymptoms or with renal impairmentWithhold MEKTOVI dose for up to 4 weeks.

If improved to Grade 0-1 resume at a reduced dose.

If not resolved within 4 weeks, permanently discontinueMEKTOVI.

Dermatologic

Grade 2 If no improvement within 2 weeks, withhold MEKTOVI until Grade0-1. Resume at same dose if first occurrence or reduce dose if

recurrent.

Grade 3 Withhold MEKTOVI until Grade 0-1. Resume at same dose if firstoccurrence or reduce dose if recurrent.

Grade 4 Permanently discontinue MEKTOVI.

Other Adverse Reactions (including: Hemorrhage [see Warnings and Precautions (5.7)])bRecurrent Grade 2 or

First occurrence of any Grade 3

Withhold MEKTOVI for up to 4 weeks.

If improves to Grade 0-1 or to pretreatment/baseline levels,resume at reduced dose.

If no improvement, permanently discontinue MEKTOVI.

First occurrence of any Grade 4 Permanently discontinue MEKTOVI, orWithhold MEKTOVI for up to 4 weeks. 

 

Severity of Adverse Reactiona Dose Modification for MEKTOVIIf improves to Grade 0-1 or to pretreatment/baseline levels, thenresume at a reduced dose.

If no improvement, permanently discontinue MEKTOVI.

Recurrent Grade 3 Consider permanently discontinuing MEKTOVI.

Recurrent Grade 4 Permanently discontinue MEKTOVI. a National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.