Recommended Dose

The recommended dose is 160 mg STIVARGA (four 40 mg tablets) taken orally once daily for the first 21 days of each 28-day cycle. Continue treatment until disease progression or unacceptable toxicity.

Take STIVARGA at the same time each day. Swallow tablet whole with water after a low-fat meal that contains less than 600 calories and less than 30% fat [see Clinical Pharmacology (12.3)]. Do not take two doses of STIVARGA on the same day to make up for a missed dose from the previous day.

Dose Modifications

If dose modifications are required, reduce the dose in 40 mg (one tablet) increments; the lowest recommended daily dose of STIVARGA is 80 mg daily.

Interrupt STIVARGA for the following:

•

Grade 2 hand-foot skin reaction (HFSR) [palmar-plantar erythrodysesthesia syndrome (PPES)] that is recurrent or does not improve within 7 days despite dose reduction; interrupt therapy for a minimum of 7 days for Grade 3 HFSR

•

Symptomatic Grade 2 hypertension

•

Any Grade 3 or 4 adverse reaction

•

Worsening infection of any grade

Reduce the dose of STIVARGA to 120 mg:

•

For the first occurrence of Grade 2 HFSR of any duration

•

After recovery of any Grade 3 or 4 adverse reaction except infection

•

For Grade 3 aspartate aminotransferase (AST)/alanine aminotransferase (ALT) elevation, only resume if the potential benefit outweighs the risk of hepatotoxicity

Reduce the dose of STIVARGA to 80 mg:

•

For re-occurrence of Grade 2 HFSR at the 120 mg dose

•

After recovery of any Grade 3 or 4 adverse reaction at the 120 mg dose (except hepatotoxicity or infection)

Discontinue STIVARGA permanently for the following:

•

Failure to tolerate 80 mg dose

•

Any occurrence of AST or ALT more than 20 times the upper limit of normal (ULN)

•

Any occurrence of AST or ALT more than 3 times ULN with concurrent bilirubin more than 2 times ULN

•

Re-occurrence of AST or ALT more than 5 times ULN despite dose reduction to 120 mg

•

For any Grade 4 adverse reaction; only resume if the potential benefit outweighs the risks