TAGRISSO® (osimertinib)


Mechanism of Action Kinase inhibitor of the epidermal growth factor receptor (EGFR)
Pharmacodynamics (PD) QTc interval prolongation potential :  Maximum mean change from baseline = 16.2
Pharmacokinetics (PK) Dose-proportional increases in systemic exposure : 20 – 240 mg dose(i.e., 0.25 to 3 times the approved recommended dosage).

 Accumulation 3-fold following qd dosing.

 Plasma protein binding likely to be high based on  physiochemical properties

 Mean Terminal half-life  48 hours

 Primarily metabolized by CYP3A.          

Excretion : 68%  (feces), 14% (urine), 2% (unchanged)

High-fat, high-calorie meal enhanced the Cmax and AUC of osimertinib by 14% and 19% resp. vs. fasting

PK-PD Analysis Concentration-dependent QTc interval prolongation of 14 msec at 80 mg dose
Population PK No dose adjustment is recommended in patients with mild or moderate renal impairment  and mild hepatic impairment.
Special Populations No clinically significant differences in the PK based on age, sex, ethnicity, body weight, smoking status, mild or moderate renal impairment, or mild hepatic impairment

Effect of severe renal impairment, hemodialysis, or moderate to severe hepatic impairment on exposure unknown

Drug Interactions Avoid concomitant administration with strong CYP3A inhibitors or inducer

Source:  http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/208065s000lbl.pdf




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