a The only grade 4 laboratory abnormality was 1 patient with grade 4 thrombocytopenia
7 DRUG INTERACTIONS
Drug interaction studies with inhibitors, inducers or substrates of CYP enzymes and transporters have not been conducted with TAGRISSO.
7.1 Effect of Other Drugs on Osimertinib
Strong CYP3A Inhibitors
Avoid concomitant administration of TAGRISSO with strong CYP3A inhibitors, including macrolide antibiotics (e.g., telithromycin), antifungals (e.g., itraconazole), antivirals (e.g., ritonavir), nefazodone, as concomitant use of strong CYP3A inhibitors may increase osimertinib plasma concentrations. If no other alternative exists, monitor patients more closely for adverse reactions of TAGRISSO [see Dosage and Administrations (2.4) and Clinical Pharmacology (12.3)].
Strong CYP3A Inducers
Avoid concomitant administration of TAGRISSO with strong CYP3A inducers (e.g., phenytoin, rifampicin, carbamazepine, St. John’s Wort) as strong CYP3A inducers may decrease osimertinib plasma concentrations [see Clinical Pharmacology (12.3)].
7.2 Effect of Osimertinib on Other Drugs
Avoid concomitant administration of TAGRISSO with drugs that are sensitive substrates of CYP3A, breast cancer resistance protein (BCRP), or CYP1A2 with narrow therapeutic indices, including but not limited to fentanyl, cyclosporine, quinidine, ergot alkaloids, phenytoin, carbamazepine, as osimertinib may increase or decrease plasma concentrations of these drugs [see Clinical Pharmacology (12.3)].
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
Based on data from animal studies and its mechanism of action, TAGRISSO can cause fetal harm when administered to a pregnant woman. There are no available data on TAGRISSO use in pregnant women. Administration of osimertinib to pregnant rats was associated with embryolethality and reduced fetal growth at plasma exposures 1.5 times the exposure at the recommended human dose [see Data]. Advise pregnant women of the potential risk to a fetus.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically-recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Data
Animal Data
When administered to pregnant rats prior to embryonic implantation through the end of organogenesis (gestation days 2-20) at a dose of 20 mg/kg/day, which produced plasma exposures of approximately 1.5 times the clinical exposure, osimertinib caused post-implantation loss and early embryonic death. When administered to pregnant rats from implantation through the closure of the hard palate (gestation days 6 to 16) at doses of 1 mg/kg/day and above (0.1-times the AUC observed in patients at the recommended dose of 80 mg), an equivocal increase in the rate of fetal malformations and variations was observed in treated litters relative to those of concurrent controls. When administered to pregnant dams at doses of 30 mg/kg/day during organogenesis through lactation Day 6, osimertinib caused an increase in total litter loss and postnatal death. At a dose of 20 mg/kg/day, osimertinib administration during the same period resulted in increased postnatal death as well as a slight reduction in mean pup weight at birth that increased in magnit