Clinical Pharmacology Card
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