Dacocent

• Metastatic non-small cell lung cancer

Dacomitinib 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.

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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.

Proton Pump Inhibitors (PPIs): Avoid use with DACOMITINIB; use locally-acting antacids or H2-receptor antagonist; administer DACOMITINIB at least 6 hours before or 10 hours after H2-receptor antagonistCYP2D6 Substrates: Avoid concomitant use with DACOMITINIB where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities

Most common adverse reactions (incidence >20%) are diarrhea, rash, paronychia, stomatitis, decreased appetite, dry skin, decreased weight, alopecia, cough, and pruritus.

Dacomitinib can cause fetal harm when administered to a pregnant woman. There is no information regarding the presence of dacomitinib or its metabolites in human milk or their effects on the breastfed infant or on milk production. Because of the potential for serious adverse reactions in breastfed infants from Dacomitinib, advise women not to breastfeed during treatment with Dacomitinib and for at least 17 days after the last dose.

Interstitial Lung Disease (ILD): Permanently discontinue Dacomitinib if ILD is confirmedDiarrhea: Withhold and reduce the dose of DACOMITINIB based on the severityDermatologic Adverse Reactions: Withhold and reduce the dose of DACOMITINIB based on the severityEmbryo-Fetal Toxicity: Dacomitinib can cause fetal harm. Advise females of reproductive potential to use effective contraception.

Pediatric Use: The safety and effectiveness of Dacomitinib in pediatrics have not been established.Renal Impairment: No dosage modification is recommended for patients with mild or moderate renal impairment (ClCr 30 to 89 mL/min estimated by Cockcroft-Gault). The recommended dose of Dacomitinib has not been established for patients with severe renal impairment (ClCr<30 mL/min)