Daconib 45

Non-small Cell Lung Cancer

Administer with or without food at the same time each day

Non-small Cell Lung Cancer Indicated for first-line treatment of patients with metastatic non-small 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 45 mg PO qDay Continue until disease progression or unacceptable toxicity occurs Hepatic impairment Mild or moderate (total bilirubin ?3x upper limit of normal [ULN] and any AST): No dosage adjustment necessary Severe (total bilirubin 3-10x ULN and any AST): Recommended dose not established

Renal impairment Mild or moderate (CrCl 30-89 mL/min estimated by Cockcroft-Gault equation): No dosage adjustment necessary Severe (CrCl <30 mL/min): Recommended dose not established

Irreversible kinase inhibitor 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) Also inhibited the activity of DDR1, EPHA6, LCK, DDR2, and MNK1 in vitro at clinically relevant concentrations Demonstrates dose-dependent inhibition of EGFR and HER2 autophosphorylation and tumor growth in mice bearing SC implanted human tumor xenografts driven by HER family targets including mutated EGFR; also, exhibits antitumor activity in orally dosed mice bearing intracranial human tumor xenografts driven by EGFR amplifications

Severe and fatal ILD/pneumonitis occurred; monitor for pulmonary symptoms indicative of ILD/pneumonitis; withhold treatment and promptly investigate for ILD in patients who present with worsening of respiratory symptoms, which may be indicative of ILD (eg, dyspnea, cough, fever); permanently discontinue treatment if ILD is confirmed Severe and fatal diarrhea occurred; promptly initiate antidiarrheal treatment (loperamide or diphenoxylate hydrochloride with atropine sulfate) for diarrhea

>10% (All Grades) Diarrhea (87%) Rash (69%) Paronychia (64%) Stomatitis (45%) Anemia (44%) Hypoalbuminemia (44%) Lymphopenia (42%) Increased ALT (40%) Hyperglycemia (36%) Increased AST (35%) Hypocalcemia (33%) Decreased appetite (31%) Dry skin (30%) Hypokalemia (29%) Decreased weight (26%) Hyponatremia (26%) Increased creatinine (24%) Alopecia (23%) Increased alkaline phosphatase (22%) Hypomagnesemia (22%) Pruritus (21%) Cough (21%) Nasal mucosal disorder (19%) Conjunctivitis (19%) Nausea (19%) Hyperbilirubinemia (16%) Palmar-plantar erythrodysesthesia syndrome (15%) Pain in extremity (14%) Dyspnea (13%) Constipation (13%) Asthenia (13%) Mouth ulceration (12%) Musculoskeletal pain (12%) Upper respiratory tract infection (12%) Dermatitis (11%) Insomnia (11%)

Pregnancy Based on findings from animal studies and its mechanism of action, fetal harm may occur when administered to a pregnant woman There are no available data on use in pregnant women Verify pregnancy status of females of reproductive potential prior to initiating treatment Advise females of reproductive potential to use effective contraception during treatment and for at least 17 days after final dose Animal data In animal reproduction studies, oral administration of dacomitinib to pregnant rats during organogenesis period resulted in an increased incidence of postimplantation loss and reduced fetal body weight at doses resulting in similar exposures seen at the 45-mg human dose Absence of EGFR signaling resulted in embryo lethality as well as postnatal death in animals Advise pregnant women of the potential risk to a fetus Lactation There is no information regarding presence of dacomitinib or its metabolites in human milk or their effects on breastfed infants or on milk production Because of potential for serious adverse reactions in breastfed infants, advise women not to breastfeed during treatment and for at least 17 days after last dose