2 TAGRISSO® (osimertinib) tablets, for oral use
statistically significant reduction in adverse reaction rates for TAGRISSO, or for the control arm,
for any adverse reaction listed in Tables 2 and 3.
Table 2. Adverse Reactions Occurring in ≥10% of Patients Receiving TAGRISSO in AURA3
Adverse Reaction TAGRISSO
Diarrhea 41 1. 1 11 1. 5
Nausea 16 0.7 49 3. 7
Stomatitis 15 0 15 1. 5
Constipation 14 0 35 0
Vomiting 11 0.4 20 2. 2
Rashb 34 0.7 5. 9 0
Dryskinc 23 0 4. 4 0
Nailtoxicityd 22 0 1. 5 0
Prurituse 13 0 5. 1 0
Metabolism and Nutrition Disorders
Decreasedappetite 18 1. 1 36 2. 9
Respiratory, Thoracic and Mediastinal Disorders
Cough 17 0 14 0
Musculoskeletal and Connective Tissue Disorders
Backpain 10 0.4 9 0.7
General Disorders and Administration Site Conditions
Fatiguef 22 1. 8 40 5. 1
NCI CTCAE v4.0.
a No grade 4 events were reported.
b Includes rash, rash generalized, rash erythematous, rash macular, rash maculo-papular, rash papular, rash
pustular, erythema, folliculitis, acne, dermatitis and acneform dermatitis.
c Includes dry skin, eczema, skin fissures, xerosis.
d Includes nail disorders, nail bed disorders, nail bed inflammation, nail bed tenderness, nail discoloration, nail
disorder, nail dystrophy, nail infection, nail ridging, nail toxicity, onychoclasis, onycholysis, onychomadesis,
e Includes pruritus, pruritus generalized, eyelid pruritus.
f Includes fatigue, asthenia.
Table 3. Common Laboratory Abnormalities (>20% for all NCI C TCAE Grades) in AURA3
Grade 3 or Grade
Grade 3 or
Leukopenia 61 1. 1 75 5. 3
Lymphopenia 63 8. 2 61 9. 9
Thrombocytopenia 46 0.7 48 7. 4
Neutropenia 27 2. 2 49 12
a Based on the number of patients with available follow-up laboratory data
AURA Extension and AURA2 Trials
The safety of TAGRISSO was evaluated in two single arm trials, AURA Extension (n=201) and
AURA2 (n=210). A total of 411 patients with EGFR 790M mutation-positive NSLC who received one
or more prior EGFR therapies including an EGFR TKI were treated with TAGRISSO (80 mg daily).
The majority of patients were heavily pretreated. Prior to enrollment, 68% of patients had received
at least 2 prior treatment regimens, 46% had received 3 or more prior lines of therapy, and 63%
had received prior platinum-based chemotherapy.
Median duration of exposure to TAGRISSO was 7. 7 months (range: <0.1 to 11. 6 months). The
toxicity profile of TAGRISSO observed in the AURA Extension and AURA2 trials was generally
consistent with the toxicity profile observed in the AURA3 trial. Four patients (1%) treated with
TAGRISSO developed fatal adverse reactions of ILD/pneumonitis. Discontinuation of therapy due
to adverse reactions occurred in 5.6% of patients treated with TAGRISSO. The most frequent
adverse reactions that led to discontinuation were ILD/pneumonitis.
DRUG IN TERAC TIONS
Effect of Other Drugs on Osimertinib
Strong CYP3A Inducers
Coadministering TAGRISSO with a strong CYP3A4 inducer decreased the exposure of osimertinib
compared to administering TAGRISSO alone [see Clinical Pharmacology ( 12. 3) in full Prescribing
Information]. Decreased osimertinib exposure may lead to reduced efficacy.
Avoid coadministering TAGRISSO with strong CYP3A inducers (e.g., phenytoin, rifampin,
carbamazepine, St. John’s Wort) [note: effect of St. John’s Wort varies widely and is preparation-dependent]. Increase the TAGRISSO dosage when coadministering with a strong CYP3A4
inducer if concurrent use is unavoidable [see Dosage and Administration ( 2. 4) in full Prescribing
Information]. No dose adjustments are required when TAGRISSO is used with moderate and/or
weak CYP3A inducers.
Effect of Osimertinib on Other Drugs
Coadministering TAGRISSO with a BCRP substrate increased the exposure of the BCRP substrate
compared to administering the BCRP substrate alone [see Clinical Pharmacology ( 12. 3) in full
Prescribing Information]. Increased BCRP substrate exposure may increase the risk of exposure-related toxicity.
Monitor for adverse reactions of the BCRP substrate (e.g., rosuvastatin, sulfasalazine, topotecan),
unless otherwise instructed in its approved labeling, when coadministered with TAGRISSO.
USE IN SPECIFIC POPULATIONS
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.
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 magnitude between
lactation days 4 and 6.
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) in full Prescribing Information]. 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.
Females and Males of Reproductive Potential
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) in full
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)
in full Prescribing Information].
Based on animal studies, TAGRISSO may impair fertility in females and males of reproductive
potential. The effects on female fertility showed a trend toward reversibility. It is not known whether
the effects on male fertility are reversible [see Nonclinical Toxicology ( 13. 1) in full Prescribing
The safety and effectiveness of TAGRISSO in pediatric patients have not been established.
Three hundred and forty-six (42%) of the 833 patients in AURA3 (n=279), AURA Extension (n=201),
AURA2 (n=210), and an expansion cohort in the first-in-human trial of osimertinib (AURA1, n=143)
were 65 years of age and older. No overall differences in effectiveness were observed based on
age. Exploratory analysis suggests a higher incidence of Grade 3 and 4 adverse reactions ( 9.8%
versus 6.8%) and more frequent dose modifications for adverse reactions ( 10.1% versus 6.0%) in
patients 65 years or older as compared to those younger than 65 years.
No dose adjustment is recommended in patients with mild, [creatinine clearance (CLcr)
60-89 mL/min, as estimated by the Cockcroft Gault method (C-G)] moderate, (CLcr 30-59 mL/min,
as estimated by C-G) or severe (CLcr 15-29 mL/min) renal impairment. There is no recommended
dose of TAGRISSO for patients with end-stage renal disease [see Clinical Pharmacology ( 12. 3) in
full Prescribing Information].
No dose adjustment is recommended in patients with mild hepatic impairment [total bilirubin less
than or equal to upper limit of normal (ULN) and AST greater than ULN or total bilirubin between
1.0 to 1. 5 times ULN and any AST] or moderate hepatic impairment (total bilirubin between 1. 5 to
3 times ULN and any AST). There is no recommended dose for TAGRISSO for patients with severe
hepatic impairment [see Clinical Pharmacology ( 12. 3) in full Prescribing Information].
Distributed by: AstraZeneca Pharmaceuticals LP, Wilmington, DE 19850
TAGRISSO is a registered trademark of the AstraZeneca group of companies.
Iss.03/17 3338004 4/17