Dacomitinib

VIZIMPRO is indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 L858R substitution mutations as detected by an FDA-approved test. VIZIMPRO is a kinase inhibitor indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 L858R substitution mutations as detected by an FDA-approved test.

Dacomitinib is an irreversible inhibitor of the kinase activity of the human EGFR family (EGFR/HER1, HER2, and HER4) and certain EGFR activating mutations (exon 19 deletion or the exon 21 L858R substitution mutation). In vitro dacomitinib also inhibited the activity of DDR1, EPHA6, LCK, DDR2, and MNK1 at clinically relevant concentrations. Dacomitinib demonstrated dose-dependent inhibition of EGFR and HER2 autophosphorylation and tumor growth in mice bearing subcutaneously implanted human tumor xenografts driven by HER family targets including mutated EGFR. Dacomitinib also exhibited antitumor activity in orally-dosed mice bearing intracranial human tumor xenografts driven by EGFR amplifications.

Recommended Dosage: 45 mg orally once daily with or without food. Patient Selection Select patients for the first-line treatment of metastatic NSCLC with VIZIMPRO based on the presence of an EGFR exon 19 deletion or exon 21 L858R substitution mutation in tumor specimens. Information on FDA-approved tests for the detection of EGFR mutations in NSCLC is available at: http://www.fda.gov/CompanionDiagnostics.

None. None.

• Interstitial Lung Disease (ILD): Permanently discontinue VIZIMPRO if ILD is confirmed. • Diarrhea: Withhold and reduce the dose of VIZIMPRO based on the severity. • Dermatologic Adverse Reactions: Withhold and reduce the dose of VIZIMPRO based on the severity. • Embryo-Fetal Toxicity: VIZIMPRO can cause fetal harm. Advise females of reproductive potential to use effective contraception.

The following adverse drug reactions are described elsewhere in the labeling: • Interstitial Lung Disease • Diarrhea • Dermatologic Adverse Reactions Most common adverse reactions (incidence >20%) are diarrhea, rash, paronychia, stomatitis, decreased appetite, dry skin, decreased weight, alopecia, cough, and pruritus.

• Proton Pump Inhibitors (PPIs): Avoid use with VIZIMPRO, use locally-acting antacids or H2-receptor antagonist, administer VIZIMPRO at least 6 hours before or 10 hours after H2-receptor antagonist. • CYP2D6 Substrates: Avoid concomitant use with VIZIMPRO where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.

Store at 20 °C to 25 °C (68 °F to 77 °F), excursions permitted between 15 °C to 30 °C (59 °F to 86 °F).