ude between lactation days 4 and 6.
8.2 Lactation
Risk Summary
There are no data on the presence of osimertinib in human milk, the effects of osimertinib on the breastfed infant or on milk production. Administration to rats during gestation and early lactation was associated with adverse effects, including reduced growth rates and neonatal death [see Use in Specific Populations (8.1)]. Because of the potential for serious adverse reactions in breastfed infants from osimertinib, advise a lactating woman not to breastfeed during treatment with TAGRISSO and for 2 weeks after the final dose.
8.3 Females and Males of Reproductive Potential
Contraception
Females
Advise females of reproductive potential to use effective contraception during treatment with TAGRISSO and for 6 weeks after the final dose [see Use in Specific Populations (8.1)].
Males
Advise male patients with female partners of reproductive potential to use effective contraception during and for 4 months following the final dose of TAGRISSO [see Nonclinical Toxicology (13.1)].
Infertility
Based on animal studies, TAGRISSO may impair fertility in females and males of reproductive potential. It is not known if the effects on fertility are reversible [see Nonclinical Toxicology (13.1)].
8.4 Pediatric Use
The safety and effectiveness of TAGRISSO in pediatric patients have not been established.
8.5 Geriatric Use
One hundred eighty-seven (45%) of the 411 patients in clinical trials of TAGRISSO were 65 years of age and older, and 54 patients (13%) were 75 years of age and older. No overall differences in effectiveness were observed based on age. Exploratory analysis suggest a higher incidence of Grade 3 and 4 adverse reactions (32% versus 25%) and more frequent dose modifications for adverse reactions (23% versus 17%) in patients 65 years or older as compared to those younger than 65 years.
8.6 Renal Impairment
No dedicated clinical studies have been conducted to eva luate the effect of renal impairment on the pharmacokinetics of osimertinib. Based on population pharmacokinetic analysis, no dose adjustment is recommended in patients with mild [creatinine clearance (CLcr) 60-89 mL/min] or moderate (CLcr 30-59 mL/min) renal impairment. There is no recommended dose of TAGRISSO for patients with severe renal impairment (CLcr <30 mL/min) or end-stage-renal disease [see Clinical Pharmacology (12.3)].
8.7 Hepatic Impairment
No dedicated clinical studies have been conducted to eva luate the effect of hepatic impairment on the pharmacokinetics of osimertinib. Based on population pharmacokinetic (PK) analysis, no dose adjustment is recommended in patients with mild hepatic impairment [total bilirubin <upper limit of normal (ULN) and AST between 1 to 1.5 times ULN or total bilirubin between 1.0 to 1.5 times ULN and any AST]. There is no recommended dose for TAGRISSO for patients with moderate or severe hepatic impairment [see Clinical Pharmacology (12.3)].
11 DESCRIPTION
Osimertinib is a kinase inhibitor for oral administration. The molecular formula for osimertinib mesylate is C28H33N7O2•CH4O3S, and the molecular weight is 596 g/mol. The chemical name is N-(2-{2-dimethylaminoethyl-methylamino}-4-methoxy-5-{[4-(1-methylindol-3-yl)pyrimidin-2-yl]amino}phenyl)prop-2-enamide mesylate salt. Osimertinib has the following structural formula (as osimertinib mesylate):
TAGRISSO tablets contain 40 or 80 mg of osimerti |
