Tagrisso

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ANNEX I

SUMMARY OF PRODUCT CHARACTERISTICS



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This medicinal product is subject to additional monitoring. This will allow quick identification of 
new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 
See section 4.8 for how to report adverse reactions.

1. NAME OF THE MEDICINAL PRODUCT

TAGRISSO 40 mg film-coated tablets
TAGRISSO 80 mg film-coated tablets

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

TAGRISSO 40 mg tablets
Each tablet contains 40 mg osimertinib (as mesylate).

TAGRISSO 80 mg tablets
Each tablet contains 80 mg osimertinib (as mesylate).

Excipient with known effect

This medicine contains 0.3 mg sodium per 40 mg tablet and 0.6 mg sodium per 80 mg tablet.

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Film-coated tablet (tablet).

TAGRISSO 40 mg tablets
Beige, 9 mm, round, biconvex tablet, debossed with “AZ” and “40” on one side and plain on the 
reverse.

TAGRISSO 80 mg tablets
Beige, 7.25 x 14.5 mm, oval, biconvex tablet, debossed with “AZ” and “80” on one side and plain on 
the reverse.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

TAGRISSO as monotherapy is indicated for:

 the first-line treatment of adult patients with locally advanced or metastatic non-small cell lung 

cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) mutations.

 the treatment of adult patients with locally advanced or metastatic EGFR T790M mutation-positive 
NSCLC.



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4.2 Posology and method of administration

Treatment with TAGRISSO should be initiated by a physician experienced in the use of anticancer 
therapies. 

When considering the use of TAGRISSO, EGFR mutation status in tumour or plasma specimens 
should be determined using a validated test method (see section 4.4).

Posology
The recommended dose is 80 mg osimertinib once a day until disease progression or unacceptable 
toxicity.

If a dose of TAGRISSO is missed, the dose should be made up unless the next dose is due within 12 
hours.

TAGRISSO can be taken with or without food at the same time each day.

Dose adjustments
Dosing interruption and/or dose reduction may be required based on individual safety and tolerability. 
If dose reduction is necessary, then the dose should be reduced to 40 mg taken once daily.

Dose reduction guidelines for adverse reactions toxicities are provided in Table 1.

Table 1. Recommended dose modifications for TAGRISSO 

Target 
organ Adverse reactiona Dose modification
Pulmonary ILD/Pneumonitis Discontinue TAGRISSO (see Section 4.4)
Cardiac QTc interval greater than 500 msec 

on at least 2 separate ECGs
Withhold TAGRISSO until QTc interval is 
less than 481 msec or recovery to baseline if 
baseline QTc is greater than or equal to 481 
msec, then restart at a reduced dose (40 mg)

QTc interval prolongation with 
signs/symptoms of serious 
arrhythmia

Permanently discontinue TAGRISSO

Other Grade 3 or higher adverse reaction Withhold TAGRISSO for up to 3 weeks
If Grade 3 or higher adverse 
reaction improves to Grade 0-2 after 
withholding of TAGRISSO for up 
to 3 weeks 

TAGRISSO may be restarted at the same dose 
(80 mg) or a lower dose (40 mg)

Grade 3 or higher adverse reaction 
that does not improve to Grade 0-2 
after withholding for up to 3 weeks 

Permanently discontinue TAGRISSO

a Note: The intensity of clinical adverse events graded by the National Cancer Institute (NCI) Common Terminology 
Criteria for Adverse Events (CTCAE) version 4.0.

ECGs: Electrocardiograms; QTc: QT interval corrected for heart rate

Special populations
No dosage adjustment is required due to patient age, body weight, gender, ethnicity and smoking 
status (see section 5.2).

Hepatic impairment
Based on clinical studies, no dose adjustments are necessary in patients with mild hepatic impairment
(Child Pugh A) or moderate hepatic impairment (Child Pugh B). Similarly, based on population 
pharmacokinetic analysis, no dose adjustment is recommended in patients with mild hepatic 



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impairment (total bilirubin ≤upper limit of normal (ULN) and aspartate aminotransferase (AST) 
>ULN or total bilirubin >1.0 to 1.5x ULN and any AST) or moderate hepatic impairment (total 
bilirubin between 1.5 to 3 times ULN and any AST). The safety and efficacy of this medicinal product 
has not been established in patients with severe hepatic impairment. Until additional data become 
available, use in patients with severe hepatic impairment is not recommended (see section 5.2).

Renal impairment
Based on clinical studies and population PK analysis, no dose adjustments are necessary in patients 
with mild, moderate, or severe renal impairment. The safety and efficacy of this medicinal product 
has not been established in patients with end-stage renal disease [creatinine clearance (CLcr) less than
15 mL/min, calculated by the Cockcroft and Gault equation], or on dialysis. Caution should be 
exercised when treating patients with severe and end-stage renal impairment (see section 5.2).

Paediatric population
The safety and efficacy of TAGRISSO in children or adolescents aged less than 18 years have not 
been established. No data are available.

Method of administration
This medicinal product is for oral use. The tablet should be swallowed whole with water and it should 
not be crushed, split or chewed.

If the patient is unable to swallow the tablet, the tablet may first be dispersed in 50 mL of 
non-carbonated water. It should be dropped in the water, without crushing, stirred until dispersed and 
immediately swallowed. An additional half a glass of water should be added to ensure that no residue 
remains and then immediately swallowed. No other liquids should be added.

If administration via nasogastric tube is required, the same process as above should be followed but 
using volumes of 15 mL for the initial dispersion and 15 mL for the residue rinses. The resulting 
30 mL of liquid should be administered as per the naso-gastric tube manufacturer’s instructions with 
appropriate water flushes. The dispersion and residues should be administered within 30 minutes of 
the addition of the tablets to water.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

St. John’s Wort should not be used together with TAGRISSO (see section 4.5).

4.4 Special warnings and precautions for use

Assessment of EGFR mutation status
When considering the use of TAGRISSO as a treatment for locally advanced or metastatic NSCLC, it 
is important that the EGFR mutation positive status is determined. A validated test should be 
performed using either tumour DNA derived from a tissue sample or circulating tumour DNA 
(ctDNA) obtained from a plasma sample.

Only robust, reliable and sensitive tests with demonstrated utility for the determination of EGFR 
mutation status of tumour derived DNA (from a tissue or a plasma sample) should be used.

Positive determination of EGFR mutation status using either a tissue-based or plasma-based test 
indicates eligibility for treatment with TAGRISSO. However, if a plasma-based ctDNA test is used 
and the result is negative, it is advisable to follow-up with a tissue test wherever possible due to the 
potential for false negative results using a plasma-based test.

Interstitial Lung Disease (ILD)



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Severe, life-threatening or fatal Interstitial Lung Disease (ILD) or ILD-like adverse reactions (e.g. 
pneumonitis) have been observed in patients treated with TAGRISSO in clinical studies. Most cases 
improved or resolved with interruption of treatment. Patients with a past medical history of ILD, 
drug-induced ILD, radiation pneumonitis that required steroid treatment, or any evidence of clinically 
active ILD were excluded from clinical studies (see section 4.8).

Interstitial Lung Disease (ILD) or ILD-like adverse reactions (e.g. pneumonitis) were reported in 
3.9% and were fatal in 0.4% of the 1142 patients who received TAGRISSO in FLAURA and AURA 
studies. The incidence of ILD was 10.4% in patients of Japanese ethnicity, 1.8% in patients of Asian 
ethnicity and 2.8% in non-Asian patients (see section 4.8).

Careful assessment of all patients with an acute onset and/or unexplained worsening of pulmonary 
symptoms (dyspnoea, cough, fever) should be performed to exclude ILD. Treatment with this 
medicinal product should be interrupted pending investigation of these symptoms. If ILD is 
diagnosed, TAGRISSO should be discontinued and appropriate treatment initiated as necessary.
Reintroduction of TAGRISSO should be considered only after careful consideration of the individual 
patient’s benefits and risk.

Stevens-Johnson syndrome
Case reports of Stevens-Johnson syndrome (SJS) have been reported rarely in association with 
TAGRISSO treatment.  Before initiating treatment, patients should be advised of signs and symptoms 
of SJS.  If signs and symptoms suggestive of SJS appear, TAGRISSO should be interrupted or 
discontinued immediately.

QTc interval prolongation
QTc interval prolongation occurs in patients treated with TAGRISSO. QTc interval prolongation may 
lead to an increased risk for ventricular tachyarrhythmias (e.g. torsade de pointes) or sudden death. No 
arrhythmic events were reported in FLAURA or AURA studies (see section 4.8). Patients with 
clinically important abnormalities in rhythm and conduction as measured by resting electrocardiogram 
(ECG) (e.g. QTc interval greater than 470 ms) were excluded from these studies (see section 4.8).

When possible, the use of osimertinib in patients with congenital long QT syndrome should be 
avoided. Periodic monitoring with electrocardiograms (ECGs) and electrolytes should be considered 
in patients with congestive heart failure, electrolyte abnormalities, or those who are taking medicinal 
products that are known to prolong the QTc interval. Treatment should be withheld in patients who 
develop a QTc interval greater than 500 msec on at least 2 separate ECGs until the QTc interval is less 
than 481 msec or recovery to baseline if the QTc interval is greater than or equal to 481 msec, then 
resume TAGRISSO at a reduced dose as described in Table 1. Osimertinib should be permanently 
discontinued in patients who develop QTc interval prolongation in combination with any of the 
following: Torsade de pointes, polymorphic ventricular tachycardia, signs/symptoms of serious 
arrhythmia.

Changes in cardiac contractility
Across clinical trials, Left Ventricular Ejection Fraction (LVEF) decreases greater than or equal to 
10% and a drop to less than 50% occurred in 3.9% (35/908) of patients treated with TAGRISSO who 
had baseline and at least one follow-up LVEF assessment. In patients with cardiac risk factors and 
those with conditions that can affect LVEF, cardiac monitoring, including an assessment of LVEF at 
baseline and during treatment, should be considered. In patients who develop relevant cardiac 
signs/symptoms during treatment, cardiac monitoring including LVEF assessment should be 
considered.

Keratitis
Keratitis was reported in 0.7% (n=8) of the 1142 patients treated with TAGRISSO in the FLAURA 
and AURA studies. Patients presenting with signs and symptoms suggestive of keratitis such as acute 



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or worsening: eye inflammation, lacrimation, light sensitivity, blurred vision, eye pain and/or red eye 
should be referred promptly to an ophthalmology specialist (see section 4.2 Table 1).

Age and body weight
Elderly patients (>65 years) or patients with low body weight (<50 kg) may be at increased risk of 
developing adverse events of Grade 3 or higher. Close monitoring is recommended in these patients 
(see section 4.8).

Sodium
This medicine contains < 1 mmol sodium (23 mg) per 40 mg or 80 mg tablet, that is to say essentially 
“sodium-free”.

4.5 Interaction with other medicinal products and other forms of interaction

Pharmacokinetic interactions
Strong CYP3A4 inducers can decrease the exposure of osimertinib. Osimertinib may increase the 
exposure of breast cancer resistant protein (BCRP) and P-glycoprotein (P-gp) substrates.

Active substances that may increase osimertinib plasma concentrations
In vitro studies have demonstrated that the Phase I metabolism of osimertinib is predominantly via 
CYP3A4 and CYP3A5. In a clinical pharmacokinetic study in patients, co-administration with 
200 mg itraconazole twice daily (a strong CYP3A4 inhibitor) had no clinically significant effect on 
the exposure of osimertinib (area under the curve (AUC) increased by 24% and Cmax decreased by 
20%). Therefore, CYP3A4 inhibitors are not likely to affect the exposure of osimertinib. Further 
catalyzing enzymes have not been identified.

Active substances that may decrease osimertinib plasma concentrations
In a clinical pharmacokinetic study in patients, the steady-state AUC of osimertinib was reduced by 
78% when co-administered with rifampicin (600 mg daily for 21 days). Similarly, the exposure to 
metabolite AZ5104 decreased by 82% for the AUC and 78% for Cmax. It is recommended that 
concomitant use of strong CYP3A inducers (e.g. Phenytoin, rifampicin and carbamazepine) with 
TAGRISSO should be avoided. Moderate CYP3A4 inducers (e.g. bosentan, efavirenz, etravirine, 
modafinil) may also decrease osimertinib exposure and should be used with caution, or avoided when 
possible. There are no clinical data available to recommend a dose adjustment of TAGRISSO. 
Concomitant use of St. John’s Wort is contraindicated (see section 4.3).

Effect of gastric acid reducing active substances on osimertinib
In a clinical pharmacokinetic study, co-administration of omeprazole did not result in clinically 
relevant changes in osimertinib exposures. Gastric pH modifying agents can be concomitantly used 
with TAGRISSO without any restrictions.

Active substances whose plasma concentrations may be altered by TAGRISSO
Based on in vitro studies, osimertinib is a competitive inhibitor of BCRP transporters.

In a clinical PK study, co-administration of TAGRISSO with rosuvastatin (sensitive BCRP substrate) 
increased the AUC and Cmax of rosuvastatin by 35% and 72%, respectively. Patients taking 
concomitant medications with disposition dependent upon BCRP and with narrow therapeutic index 
should be closely monitored for signs of changed tolerability of the concomitant medication as a result 
of increased exposure whilst receiving TAGRISSO (see section 5.2).

In a clinical PK study, co-administration of TAGRISSO with simvastatin (sensitive CYP3A4 
substrate) decreased the AUC and Cmax of simvastatin by 9% and 23% respectively. These changes are 
small and not likely to be of clinical significance. Clinical PK interactions with CYP3A4 substrates 
are unlikely. A risk for decreased exposure of hormonal contraceptives cannot be excluded.



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In a clinical Pregnane X Receptor (PXR) interaction study, co-administration of TAGRISSO with 
fexofenadine (P-gp substrate) increased the AUC and Cmax of fexofenadine by 56% (90% CI 35, 79) 
and 76% (90% CI 49, 108) after a single dose and 27% (90% CI 11, 46) and 25% (90% CI 6, 48) at 
steady state, respectively. Patients taking concomitant medications with disposition dependent upon 
P-gp and with narrow therapeutic index (e.g. digoxin, dabigatran, aliskiren) should be closely 
monitored for signs of changed tolerability as a result of increased exposure of the concomitant 
medication whilst receiving TAGRISSO (see section 5.2). 

4.6 Fertility, pregnancy and lactation

Contraception in males and females
Women of childbearing potential should be advised to avoid becoming pregnant while receiving 
TAGRISSO. Patients should be advised to use effective contraception for the following periods after 
completion of treatment with this medicinal product: at least 2 months for females and 4 months for 
males. A risk for decreased exposure of hormonal contraceptives cannot be excluded.

Pregnancy
There are no or limited amount of data from the use of osimertinib in pregnant women. Studies in 
animals have shown reproductive toxicity (embryolethality, reduced foetal growth, and neonatal 
death, see section 5.3). Based on its mechanism of action and preclinical data, osimertinib may cause 
foetal harm when administered to a pregnant woman. TAGRISSO should not be used during 
pregnancy unless the clinical condition of the woman requires treatment with osimertinib.

Breast-feeding
It is not known whether osimertinib or its metabolites are excreted in human milk. There is 
insufficient information on the excretion of osimertinib or its metabolites in animal milk. However, 
osimertinib and its metabolites were detected in the suckling pups and there were adverse effects on 
pup growth and survival (see section 5.3). A risk to the suckling child cannot be excluded. 
Breast-feeding should be discontinued during treatment with TAGRISSO.

Fertility
There are no data on the effect of TAGRISSO on human fertility. Results from animal studies have 
shown that osimertinib has effects on male and female reproductive organs and could impair fertility 
(see section 5.3).

4.7 Effects on ability to drive and use machines

TAGRISSO has no or negligible influence on the ability to drive and use machines.

4.8 Undesirable effects

Summary of the safety profile

Studies in EGFR mutation-positive NSCLC patients
The data described below reflect exposure to TAGRISSO in 1142 patients with EGFR mutation-
positive non-small cell lung cancer. These patients received TAGRISSO at a dose of 80 mg daily in 
two randomised Phase 3 studies (FLAURA, first line and AURA3, second line only), two single-arm 
studies (AURAex and AURA2, second line or greater) and one Phase 1 study (AURA1, first-line or 
greater) (see section 5.1). Most adverse reactions were Grade 1 or 2 in severity. The most commonly 
reported adverse drug reactions (ADRs) were diarrhoea (49%) and rash (47%). Grade 3 and Grade 4 
adverse reactions across both studies were 9.7% and 0.9%, respectively. In patients treated with 
TAGRISSO 80 mg once daily, dose reductions due to adverse reactions occurred in 2.1% of the 
patients. Discontinuation due to adverse reactions was 4.3%.



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Patients with a medical history of ILD, drug-induced ILD, radiation pneumonitis that required steroid 
treatment, or any evidence of clinically active ILD were excluded from clinical studies. Patients with 
clinically important abnormalities in rhythm and conduction as measured by resting electrocardiogram 
(ECG) (e.g. QTc interval greater than 470 ms) were excluded from these studies. Patients were 
evaluated for LVEF at screening and every 12 weeks thereafter.

Tabulated list of adverse reactions
Adverse reactions have been assigned to the frequency categories in Table 2 where possible based on 
the incidence of comparable adverse event reports in a pooled dataset from the 1142 EGFR mutation 
positive NSCLC patients who received TAGRISSO at a dose of 80 mg daily in the FLAURA, 
AURA3, AURAex, AURA 2 and AURA1 studies. 

Adverse reactions are listed according to system organ class (SOC) in MedDRA. Within each system 
organ class, the adverse drug reactions are ranked by frequency, with the most frequent reactions first. 
Within each frequency grouping, adverse drug reactions are presented in order of decreasing 
seriousness. In addition, the corresponding frequency category for each adverse reaction is based on 
the CIOMS III convention and is defined as: very common (≥1/10); common (≥1/100 to <1/10); 
uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); not known 
(cannot be estimated from available data). 

Table 2. Adverse reactions reported in FLAURA and AURA studiesa

MedDRA SOC MedDRA term CIOMS descriptor/ 
overall frequency (all 
CTCAE grades)b

Frequency of 
CTCAE grade 3 or 
higher

Respiratory, 
thoracic and 
mediastinal 
disorders

Interstitial lung diseasec Common (3.9%)d 1.5%

Gastrointestinal 
disorders

Diarrhoea Very common (49%) 1.2%

Stomatitis Very common (20%) 0.2%

Eye disorders Keratitise Uncommon (0.7%) 0.1%

Skin and 
subcutaneous tissue 
disorders

Rashf Very common (47%) 0.9%

Dry sking Very common (33%) 0.1%

Paronychiah Very common (31%) 0.3%
Pruritusi Very common (17%) 0.1%

Erythema multiformej Uncommon (0.35%) 0

Stevens-Johnson 
syndromek

Rare (0.02%)



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MedDRA SOC MedDRA term CIOMS descriptor/ 
overall frequency (all 
CTCAE grades)b

Frequency of 
CTCAE grade 3 or 
higher

Investigations QTc interval 
prolongationl

Uncommon (0.9%)

(Findings based on 
test results presented 
as CTCAE grade 
shifts)

Platelet count decreasedm Very common (54%) 1.6%

Leucocytes decreasedm Very common (68%) 1.5%

Lymphocytes decreasedm Very common (67%) 7.2%

Neutrophils decreasedm Very common (35%) 4.1%

a Data is cumulative from FLAURA and AURA (AURA3, AURAex, AURA 2 and AURA1) studies; only events for 
patients receiving at least one dose of TAGRISSO as their randomised treatment are summarised.

b National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0.
c Includes cases reported within the clustered terms: Interstitial lung disease, pneumonitis.
d 5 CTCAE grade 5 events (fatal) were reported.
e Includes cases reported within the clustered terms: Keratitis, punctate keratitis, corneal erosion, corneal epithelium 

defect.
f Includes cases reported within the clustered terms for rash AEs: Rash, rash generalised, rash erythematous, rash macular, 

rash maculo-papular, rash papular, rash pustular, rash pruritic, rash vesicular, rash follicular, erythema, folliculitis, acne, 
dermatitis, dermatitis acneiform, drug eruption, skin erosion.

g Includes cases reported within the clustered terms: Dry skin, skin fissures, xerosis, eczema, xeroderma.
h Includes cases reported within the clustered terms: Nail bed disorder, nail bed inflammation, nail bed infection, nail 

discolouration, nail pigmentation, nail disorder, nail toxicity, nail dystrophy, nail infection, nail ridging, onychalgia,
onychoclasis, onycholysis, onychomadesis, onychomalacia, paronychia.

i Includes cases reported within the clustered terms: pruritus, pruritus generalised, eyelid pruritus.
j Four of the 1142 patients in the AURA and FLAURA studies reported erythema multiforme. Post-marketing reports of 

erythema multiforme have also been received, including 7 reports from a post-marketing surveillance study (N=3578).
k One event was reported in a post-marketing study, and the frequency has been derived from the FLAURA and AURA 

studies and the post-marketing study (N=4720).
l Represents the incidence of patients who had a QTcF prolongation >500msec.
m Represents the incidence of laboratory findings, not of reported adverse events.

Safety findings in the single-arm Phase 2 AURAex and AURA2 studies were generally consistent 
with those observed in the AURA3 TAGRISSO arm. No additional or unexpected toxicity has been 
observed and adverse events have been aligned in type, severity and frequency.

Description of selected adverse reactions

Interstitial lung disease (ILD)
In the FLAURA and AURA studies, the incidence of ILD was 10.4% in patients of Japanese 
ethnicity, 1.8% in patients of non-Japanese Asian ethnicity and 2.8% in non-Asian patients. The 
median time to onset of ILD or ILD-like adverse reactions was 85 days (see section 4.4).

QTc interval prolongation
Of the 1142 patients in FLAURA and AURA studies treated with TAGRISSO 80 mg, 0.9% of 
patients (n=10) were found to have a QTc greater than 500 msec, and 3.6% of patients (n=41) had an 
increase from baseline QTc greater than 60 msec. A pharmacokinetic/pharmacodynamic analysis with 
TAGRISSO predicted a concentration-dependent increase in QTc interval prolongation. No QTc-
related arrhythmias were reported in the FLAURA or AURA studies (see sections 4.4 and 5.1).



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Gastrointestinal effects
In the FLAURA and AURA studies, diarrhoea was reported in 49% of patients of which 39% were 
Grade 1 events, 8.0% Grade 2 and 1.2% were Grade 3; no Grade 4 or 5 events were reported. Dose 
reduction was required in 0.2% of patients and dose interruption in 1.4%. One event (0.1%) led to 
discontinuation. In FLAURA and AURA3 the median time to onset was 19 days and 22 days, 
respectively, and the median duration of the Grade 2 events was 19 days and 6 days, respectively.

Haematological events
Early reductions in the median laboratory counts of leukocytes, lymphocytes, neutrophils and platelets 
have been observed in patients treated with TAGRISSO, which stabilised over time and then
remained above the lower limit of normal. Adverse events of leukopenia, lymphopenia, neutropenia 
and thrombocytopenia have been reported, most of which were mild or moderate in severity and did 
not lead to dose interruptions.

Elderly
In FLAURA and AURA3 (N=1142), 43% of patients were 65 years of age and older, and 13% were 
75 years of age and older. Compared with younger subjects (<65), more subjects ≥65 years old had 
reported adverse reactions that led to study drug dose modifications (interruptions or reductions) 
(13.4% versus 7.6%). The types of adverse events reported were similar regardless of age. Older 
patients reported more Grade 3 or higher adverse reactions compared to younger patients (13.4% 
versus 9.3%). No overall differences in efficacy were observed between these subjects and younger 
subjects. A consistent pattern in safety and efficacy results was observed in the analysis of AURA 
Phase 2 studies.

Low body weight
Patients receiving TAGRISSO 80 mg with low body weight (<50 kg) reported higher frequencies of 
Grade ≥3 adverse events (52% versus 35%) and QTc prolongation (14% versus 4%) than patients 
with higher body weight (≥50 kg).

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V.

4.9 Overdose

In TAGRISSO clinical trials a limited number of patients were treated with daily doses of up to 
240 mg without dose limiting toxicities. In these studies, patients who were treated with TAGRISSO 
daily doses of 160 mg and 240 mg experienced an increase in the frequency and severity of a number 
of typical EGFR TKI-induced AEs (primarily diarrhoea and skin rash) compared to the 80 mg dose. 
There is limited experience with accidental overdoses in humans. All cases were isolated incidents of 
patients taking an additional daily dose of TAGRISSO in error, without any resulting clinical 
consequences.

There is no specific treatment in the event of TAGRISSO overdose. In case of suspected overdose, 
TAGRISSO should be withheld and symptomatic treatment initiated.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: antineoplastic agents, protein kinase inhibitors; ATC code: L01XE35.

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Mechanism of action
Osimertinib is a Tyrosine Kinase Inhibitor (TKI). It is an irreversible inhibitor of Epidermal Growth 
Factor Receptors (EGFRs) harboring sensitising-mutations (EGFRm) and TKI-resistance mutation 
T790M.

Pharmacodynamic effects
In vitro studies have demonstrated that osimertinib has high potency and inhibitory activity against 
EGFR across a range of all clinically relevant EGFR sensitising-mutant and T790M mutant non-small 
cell lung cancer (NSCLC) cell lines (apparent IC50s from 6 nM to 54 nM against phospho-EGFR). 
This leads to inhibition of cell growth, while showing significantly less activity against EGFR in 
wild-type cell lines (apparent IC50s from 480 nM to 1.8 μM against phospho-EGFR). In vivo oral 
administration of osimertinib lead to tumour shrinkage in both EGFRm and T790M NSCLC xenograft 
and transgenic mouse lung tumour models.

Cardiac electrophysiology
The QTc interval prolongation potential of TAGRISSO was assessed in 210 patients who received 
osimertinib 80 mg daily in AURA2. Serial ECGs were collected following a single dose and at 
steady-state to evaluate the effect of osimertinib on QTc intervals. A 
pharmacokinetic/pharmacodynamic analysis predicted a drug-related QTc interval prolongation at 
80 mg of 14 msec with an upper bound of 16 msec (90% CI).

Clinical efficacy and safety

Previously untreated EGFR mutation positive locally advanced or metastatic NSCLC – FLAURA
The efficacy and safety of TAGRISSO for the treatment of patients with EGFR mutation positive 
locally advanced, not amenable to curative surgery or radiotherapy, or metastatic NSCLC, who had 
not received previous systemic treatment for advanced disease, was demonstrated in a randomised, 
double-blind, active-controlled study (FLAURA). Patient tumour tissue samples were required to 
have one of the two common EGFR mutations known to be associated with EGFR TKI sensitivity 
(Ex19del or L858R), as identified by local or central testing. 

Patients were randomised 1:1 to receive either TAGRISSO (n=279, 80 mg orally once daily) or EGFR 
TKI comparator (n=277; gefitinib 250 mg orally once daily or erlotinib 150 mg orally once daily). 
Randomisation was stratified by EGFR mutation type (Ex19del or L858R) and ethnicity (Asian or 
non-Asian). Patients received study therapy until intolerance to therapy, or the investigator 
determined that the patient was no longer experiencing clinical benefit. For patients receiving EGFR 
TKI comparator, post-progression crossover to open-label TAGRISSO was permitted provided 
tumour samples tested positive for the T790M mutation. The primary efficacy end-point was 
progression-free survival (PFS) as assessed by investigator.

The baseline demographic and disease characteristics of the overall study population were: median 
age 64 years (range 26-93 years), ≥75 years old (14%), female (63%), White (36%), Asian (62%), 
never smokers (64%), World Health Organization (WHO) performance status of 0 or 1 (100%), 
metastatic bone disease (36%), extra-thoracic visceral metastases (35%), CNS metastases (21%, 
identified by CNS lesion site at baseline, medical history, and/or prior surgery, and/or prior 
radiotherapy to CNS metastases).

TAGRISSO demonstrated a clinically meaningful and statistically significant improvement in PFS 
compared to EGFR TKI comparator (median 18.9 months and 10.2 months, respectively, HR=0.46, 
95% CI: 0.37, 0.57; P<0.0001). Efficacy results from FLAURA by investigator assessment are 
summarised in Table 3, and the Kaplan-Meier curve for PFS is shown in Figure 1. The final analysis 
of overall survival (OS, 58% maturity) demonstrated a statistically significant improvement with an
HR of 0.799 (95.05% CI: 0.641, 0.997) and a clinically meaningful longer median survival time in 



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patients randomized to TAGRISSO compared to EGFR TKI comparator (Table 3 and Figure 2). A 
greater proportion of patients treated with TAGRISSO were alive at 12, 18, 24 and 36 months (89%, 
81%, 74% and 54% respectively) compared to patients treated with EGFR TKI comparator (83%, 
71%, 59% and 44% respectively). Analysis of post-progression end–points demonstrated that the PFS 
benefit was preserved through subsequent lines of therapy.

Table 3. Efficacy results from FLAURA by investigator assessment

Efficacy Parameter TAGRISSO
(N=279)

EGFR TKI comparator  
(gefitinib or erlotinib)

(N=277)

Progression-Free Survival

Number of Events (62% maturity) 136 (49) 206 (74)

Median, Months (95% CI) 18.9 (15.2, 21.4) 10.2 (9.6, 11.1)

HR (95% CI) ; P-value 0.46 (0.37, 0.57); P < 0.0001

Overall Survival 

Number of deaths, (58% maturity) 155 (56) 166 (60)

Median OS in months (95% CI) 38.6 (34.5, 41.8) 31.8 (26.6, 36.0)

HR (95.05% CI); P-value 0.799 (0.641, 0.997); P=0.0462†

Objective Response Rate*1

Number of responses (n), Response Rate 
(95% CI)

223
80% (75, 85)

210
76% (70, 81)

Odds ratio (95% CI); P-value 1.3 (0.9, 1.9); P=0.2421

Duration of Response (DoR)*

Median, Months (95% CI) 17.2 (13.8, 22.0) 8.5 (7.3, 9.8)

Second PFS after start of first subsequent therapy (PFS2)



13

HR=Hazard Ratio; CI=Confidence Interval, NC=Not Calculable
PFS, ORR, DoR and PFS2 results based on RECIST investigator assessment
Based on unconfirmed response
Median follow-up time was 15.0 months for patients receiving TAGRISSO and 9.7 months for patients receiving EGFR TKI 
comparator
Median survival follow-up time was 35.8 months for patients receiving TAGRISSO and 27.0 months for patients receiving 
EGFR TKI comparator. 
PFS, ORR, DoR, PFS2, TFST and TSST results are from data cut-off 12 June 2017. OS results are from data cut-off 25 June 
2019.
A HR< 1 favours TAGRISSO, an Odds ratio of >1 favours TAGRISSO
† Adjusted for an interim analysis (25% maturity) a p-value < 0.0495 was required to achieve statistical significance
1 ORR results by Blinded Independent Central Review (BICR) were consistent with those reported via investigator 
assessment; ORR by BICR assessment was 78% (95% CI:73, 83) on TAGRISSO and 70% (95% CI:65, 76) on EGFR TKI 

comparator.

Number of patients with second progression 
(%)

73 (26) 106 (38)

Median PFS2, months (95% CI) NC (23.7, NC) 20.0 (18.0, NC)

HR (95% CI); P-value 0.58 (0.44, 0.78); P=0.0004

Time from randomisation to first subsequent treatment or death (TFST)

Number of patients who had first 
subsequent treatment or died (%)

115 (41) 175 (63)

Median TFST, months (95% CI) 23.5 (22.0, NC) 13.8 (12.3, 15.7)

HR (95% CI); P-value 0.51 (0.40, 0.64); P<0.0001

Time from randomisation to second subsequent treatment or death (TSST)

Number of patients who had second 
subsequent treatment or died (%)

75 (27) 110 (40)

Median TSST, months (95% CI) NC (NC, NC) 25.9 (20.0, NC)

HR (95% CI); P-value 0.60 (0.45, 0.80); P=0.0005



14

Figure 1. Kaplan-Meier Curves of Progression-Free Survival as assessed by investigator in
FLAURA 



15

Figure 2. Kaplan-Meier Curves of Overall Survival in FLAURA 

The PFS benefit of TAGRISSO compared to EGFR TKI comparator was consistent across all 
predefined subgroups analysed, including ethnicity, age, gender, smoking history, CNS metastases 
status at study entry and EGFR mutation type (Exon 19 deletion or L858R).

CNS metastases efficacy data in FLAURA study
Patients with CNS metastases not requiring steroids and with stable neurologic status for at least two 
weeks after completion of the definitive therapy and steroids were eligible to be randomised in the 
FLAURA study. Of 556 patients, 200 patients had available baseline brain scans. A BICR assessment 
of these scans resulted in a subgroup of 128/556 (23%) patients with CNS metastases and these data 
are summarised in Table 4. CNS efficacy by RECIST v1.1 in FLAURA demonstrated a statistically 
significant improvement in CNS PFS (HR=0.48, 95% CI 0.26, 0.86; P=0.014).

Table 4. CNS efficacy by BICR in patients with CNS metastases on a baseline brain scan in 
FLAURA 

Efficacy Parameter TAGRISSO
N=61

EGFR TKI comparator 
(gefitinib or erlotinib)

N=67
CNS Progression-free survival1

Number of Events (%) 18 (30) 30 (45)
Median, Months (95% CI) NC (16.5, NC) 13.9 (8.3, NC)
HR (95% CI); P-value 0.48 (0.26, 0.86); P=0.014

TAGRISSO (N=279)
Median 38.6 months

SoC (N=277)
Median 31.8 months

Hazard Ratio = 0.799
95.05% CI (0.641, 0.997)

P-value 0.0462

TAGRISSO
SoC

P
r
o
b
a
b
i
l
i
t
y
 
o
f
 
O
v
e
r
a
l
l
 
S
u
r
v
i
v
a
l

Time from randomisation (months)Number at risk

+ Censored patients.
The values at the base of the figure indicate number of subjects at risk.



16

CNS progression free and alive at 6 
months (%) (95% CI)

87 (74, 94) 71 (57, 81)

CNS progression free and alive at 12 
months (%) (95% CI)

77 (62, 86) 56 (42, 68)

HR=Hazard Ratio; CI=Confidence Interval, NC=Not Calculable
A HR< 1 favours TAGRISSO, an Odds ratio of >1 favours TAGRISSO
1 CNS PFS determined by RECIST v1.1by CNS BICR (CNS measurable and non-measurable lesions at baseline by 

BICR) n=61 for TAGRISSO and n=67 for EGFR TKI comparator; responses are unconfirmed

A pre-specified PFS subgroup based on CNS metastases status (identified by CNS lesion site at 
baseline, medical history, and/or prior surgery, and/or prior radiotherapy to CNS metastases) at study 
entry was performed in FLAURA and is shown in Figure 3. Irrespective of CNS lesion status at study 
entry, patients in the TAGRISSO arm demonstrated an efficacy benefit over those in the EGFR TKI 
comparator arm and there were fewer patients with new CNS lesions in the TAGRISSO arm 
compared to the EGFR TKI comparator arm (TAGRISSO, 11/279 [3.9%] compared to EGFR TKI 
comparator, 34/277 [12.3%]). In the subset of patients without CNS lesions at baseline, there were a 
lower number of new CNS lesions in the TAGRISSO arm compared to the EGFR TKI comparator 
arm (7/226 [3.1%] vs. 15/214 [7.0%], respectively).

Figure 3. Overall PFS by investigator assessment by CNS metastases status at study entry, 
Kaplan-Meier plot (full analysis set) in FLAURA 

Patient Reported Outcomes (PRO)

Patient-reported symptoms and health-related quality of life (HRQL) were electronically collected 
using the EORTC QLQ-C30 and its lung cancer module (EORTC QLQ-LC13). The LC13 was 
initially administered once a week for the first 6 weeks, then every 3 weeks before and after 
progression. The C30 was assessed every 6 weeks before and after progression. At baseline, no 
differences in patient reported symptoms, function or HRQL were observed between TAGRISSO and 
EGFR TKI comparator (gefitinib or erlotinib) arms. Compliance over the first 9 months was generally
high (≥70%) and similar in both arms.



17

Key lung cancer symptoms analysis
Data collected from baseline up to month 9 showed similar improvements in TAGRISSO and EGFR 
TKI comparator groups for the five pre-specified primary PRO symptoms (cough, dyspnoea, chest 
pain, fatigue, and appetite loss) with improvement in cough reaching the established clinically 
relevant cutoff. Up to month 9 there were no clinically meaningful differences in patient-reported 
symptoms between TAGRISSO and EGFR TKI comparator groups (as assessed by a difference of 
≥ 10 points).

HRQL and physical functioning improvement analysis
Both groups reported similar improvements in most functioning domains and global health 
status/HRQL, indicating that patients’ overall health status improved. Up to month 9, there were no 
clinically meaningful differences between the TAGRISSO and EGFR TKI comparator groups in 
functioning or HRQL. 

Pre-treated T790M positive NSCLC patients-AURA3
The efficacy and safety of TAGRISSO for the treatment of patients with locally advanced or 
metastatic T790M NSCLC whose disease has progressed on or after EGFR TKI therapy, was 
demonstrated in a randomised, open-label, active-controlled Phase 3 study (AURA3). All patients 
were required to have EGFR T790M mutation-positive NSCLC identified by the cobas EGFR 
mutation test performed in a central laboratory prior to randomisation. The T790M mutation status 
was also assessed using ctDNA extracted from a plasma sample taken during screening. The primary 
efficacy outcome was progression-free survival (PFS) as assessed by investigator. Additional efficacy 
outcome measures included ORR, DoR and overall survival (OS) as assessed by investigator.

Patients were randomised in a 2:1 (TAGRISSO: platinum-based doublet chemotherapy) ratio to 
receive TAGRISSO (n=279) or platinum-based doublet chemotherapy (n=140). Randomisation was 
stratified by ethnicity (Asian and non-Asian). Patients in the TAGRISSO arm received TAGRISSO 
80 mg orally once daily until intolerance to therapy, or the investigator determined that the patient 
was no longer experiencing clinical benefit. Chemotherapy consisted of pemetrexed 500 mg/m2 with 
carboplatin AUC5 or pemetrexed 500 mg/m2 with cisplatin 75 mg/m2 on Day 1 of every 21-day cycle 
for up to 6 cycles. Patients whose disease has not progressed after four cycles of platinum-based 
chemotherapy may receive pemetrexed maintenance therapy (pemetrexed 500 mg/m2 on Day 1 of 
every 21-day cycle). Subjects on the chemotherapy arm who had objective radiological progression 
(by the investigator and confirmed by independent central imaging review) were given the 
opportunity to begin treatment with TAGRISSO.

The baseline demographic and disease characteristics of the overall study population were: median 
age 62, ≥75 years old (15%), female (64%), white (32%), Asian (65%), never smoker (68%), WHO 
performance status 0 or 1 (100%). Fifty-four percent (54%) of patients had extra-thoracic visceral 
metastases, including 34% with CNS metastases (identified by CNS lesion site at baseline, medical 
history, and/or prior surgery, and/or prior radiotherapy to CNS metastases) and 23% with liver 
metastases. Forty-two percent (42%) of patients had metastatic bone disease.

AURA3 demonstrated a statistically significant improvement in PFS in the patients treated with 
TAGRISSO compared to chemotherapy. Efficacy results from AURA3 by investigator assessment are 
summarised in Table 5, and the Kaplan-Meier curve for PFS is shown in Figure 4. No statistically 
significant difference was observed between the treatment arms at the final OS analysis.



18

Table 5. Efficacy results from AURA3 by investigator assessment

Efficacy Parameter TAGRISSO
(N=279)

Chemotherapy
(Pemetrexed/Cisplatin or 
Pemetrexed/Carboplatin)

(N=140)

Progression-Free Survival

Number of Events (% maturity) 140 (50) 110 (79)

Median, Months (95% CI) 10.1 (8.3, 
12.3)

4.4 (4.2, 5.6)

HR (95% CI); P-value 0.30 (0.23,0.41); P<0.001

Overall Survival (OS)1

Number of Deaths (% maturity) 188 (67.4) 93 (66.4)

Median OS, Months (95% CI) 26.8 (23.5, 
31.5)

22.5 (20.2, 28.8)

HR (95.56% CI); P-value 0.87 (0.67, 1.13); P= 0.277

Objective Response Rate2

Number of responses, Response Rate (95% CI)
197

71% (65, 76)
44

31% (24, 40)

Odds ratio (95% CI); P-value 5.4 (3.5, 8.5); P <0.001

Duration of Response (DoR)2

Median, Months (95% CI) 9.7 (8.3, 11.6) 4.1 (3.0, 5.6)

HR=Hazard Ratio; CI=confidence interval; NC=non-calculable; OS=Overall Survival
All efficacy results based on RECIST investigator assessment
1The final analysis of OS was performed at 67% maturity. The CI for the HR has been adjusted for previous interim 
analyses. The OS analysis was not adjusted for the potentially confounding effects of crossover (99 [71%] patients on the 
chemotherapy arm received subsequent osimertinib treatment).
2 ORR and DoR results by investigator assessment were consistent with those reported via Blinded Independent Central 
Review (BICR); ORR by BICR assessment was 64.9% [95% CI: 59.0, 70.5] on osimertinib and 34.3 % [95% CI: 26.5, 42.8] 
on chemotherapy; DoR by BICR assessment was 11.2 months (95% CI: 8.3, NC) on osimertinib and 3.1 months 
(95% CI: 2.9, 4.3) on chemotherapy.



19

Figure 4. Kaplan-Meier curves of Progression-Free Survival as assessed by investigator in 
AURA3

A sensitivity analysis of PFS was conducted by a Blinded Independent Central Review (BICR) and 
showed a median PFS of 11.0 months with TAGRISSO compared with 4.2 months with 
chemotherapy. This analysis demonstrated a consistent treatment effect (HR 0.28; 95% CI: 0.20, 0.38) 
with that observed by investigator assessment.

Clinically meaningful improvements in PFS with HRs less than 0.50 in favour of patients receiving 
TAGRISSO compared to those receiving chemotherapy were consistently observed in all predefined 
subgroups analysed, including ethnicity, age, gender, smoking history and EGFR mutation (Exon 19 
deletion and L858R).

CNS metastases efficacy data in AURA3 study

Patients with asymptomatic, stable brain metastases not requiring steroids for at least 4 weeks prior to 
the start of study treatment were eligible to be randomised in the study. A BICR assessment of CNS 
efficacy by RECIST v1.1 in the subgroup of 116/419 (28%) patients identified to have CNS 
metastases on a baseline brain scan are summarised in Table 6.



20

Table 6. CNS efficacy by BICR in patients with CNS metastases on a baseline brain scan in 
AURA3

Efficacy Parameter TAGRISSO Chemotherapy

(Pemetrexed/Cisplatin or 
Pemetrexed/Carboplatin)

CNS Objective Response Rate1

CNS response rate % (n/N)

(95% CI)

70% (21/30)

(51, 85)

31% (5/16)

(11%, 59%)

Odds ratio (95% CI); P-value 5.1 (1.4, 21); P=0.015

CNS Duration of Response2

Median, Months (95% CI) 8.9 (4.3, NC) 5.7 (NC, NC)

CNS Disease control rate

CNS disease control rate
87% (65/75)

(77, 93)

68% (28/41)

(52, 82)

Odds ratio (95% CI); P-value 3 (1.2, 7.9); P=0.021

CNS Progression-free survival3 N=75 N=41

Number of Events (% maturity) 19 (25) 16 (39)

Median, Months (95% CI) 11.7 (10, NC) 5.6 (4.2, 9.7)

HR (95% CI); P-value 0.32 (0.15, 0.69); P=0.004

1 CNS Objective Response Rate and Duration of Response determined by RECIST v1.1 by CNS BICR in the 
evaluable for response population (CNS measurable lesions at baseline by BICR) n=30 for TAGRISSO and 
n=16 for Chemotherapy

2 Based on patients with response only; DoR defined as the time from the date of first documented response
(complete response or partial response) until progression or death event; DCR defined as the proportion of 
patients with response (complete response or partial response), or stable disease ≥ 6 weeks

3 CNS Progression Free Survival determined by RECIST v1.1 by CNS BICR in the full analysis set 
population (CNS measurable and non-measurable lesions at baseline by BICR) n=75 for TAGRISSO and 
n=41 for Chemotherapy
A HR<1 favours TAGRISSO

A pre-specified PFS subgroup analysis based on CNS metastases status at study entry was performed 
in AURA3 and is shown in Figure 5.



21

Figure 5. Overall PFS by investigator assessment by CNS metastases status at study entry, 
Kaplan-Meier plot (full analysis set) in AURA3

AURA3 demonstrated a statistically significant improvement in PFS for patients receiving 
TAGRISSO compared to those receiving chemotherapy irrespective of CNS metastases status at study 
entry.

Patient Reported Outcomes
Patient-reported symptoms and health-related quality of life (HRQL) were electronically collected 
using the EORTC QLQ-C30 and its lung cancer module (EORTC QLQ-LC13). The LC13 was 
initially administered once a week for the first 6 weeks, then every 3 weeks before and after 
progression. The C30 was assessed every 6 weeks before and after progression.

Key lung cancer symptoms analysis
TAGRISSO improved patient-reported lung cancer symptoms compared to chemotherapy by 
demonstrating a statistically significant difference in mean change from baseline versus chemotherapy 
during the overall time period from randomisation until 6 months for 5 pre-specified primary PRO 
symptoms (appetite loss, cough, chest pain, dyspnoea, and fatigue) as shown in Table 7.

Table 7. Mixed Model Repeated Measures – Key lung cancer symptoms - mean change from 
baseline in TAGRISSO patients compared with chemotherapy

Appetite Loss Cough Chest Pain Dyspnoea Fatigue

Arms TAGRISS
O

(279)

Chemo
-

therapy
(140)

TAGRISS
O

(279)

Chemo
-

therapy
(140)

TAGRISS
O

(279)

Chemo
-

therapy
(140)

TAGRISS
O

(279)

Chemo
-

therapy
(140)

TAGRISS
O

(279)

Chemo
-

therapy
(140)

N 239 97 228 113 228 113 228 113 239 97

Adj Mean -5.51 2.73 -12.22 -6.69 -5.15 0.22 -5.61 1.48 -5.68 4.71

Estimated 
Differenc
e 
(95%CI)

-8.24
(-12.88, 3.60)

-5.53
(-8.89, -2.17)

-5.36
(-8.20, -2.53)

-7.09
(-9.86, -4.33)

-10.39
(-14.55, -6.23)

p-value p <0.001 p=0.001 p<0.001 p<0.001 p<0.001



22

Adjusted mean and estimated differences obtained from a Mixed Model Repeated Measures (MMRM) analysis. The model included patient, 
treatment, visit, treatment-by-visit interaction, baseline symptom score, and baseline symptom score-by-visit interaction and used an 
unstructured covariance matrix.

HRQL and physical functioning improvement analysis
Patients on TAGRISSO had significantly greater chances of achieving a clinically meaningful 
improvement of greater than or equal to 10 points on the global health status and physical functioning 
of the EORTC-C30 questionnaire compared with chemotherapy during the study period Odds Ratio 
(OR) global health status: 2.11, (95% CI 1.24, 3.67, p=0.007); OR physical functioning 2.79 (95% 
CI 1.50, 5.46, p=0.002).

Pre-treated T790M positive NSCLC patients - AURAex and AURA2
Two single-arm, open-label clinical studies, AURAex (Phase 2 Extension cohort, (n=201)) and 
AURA2 (n=210) were conducted in patients with EGFR T790M mutation-positive lung cancer who 
have progressed on one or more prior systemic therapies, including an EGFR TKI. All patients were 
required to have EGFR T790M mutation-positive NSCLC identified by the cobas EGFR mutation test 
performed in a central laboratory prior to treatment. The T790M mutation status was also assessed 
retrospectively using ctDNA extracted from a plasma sample taken during screening. All patients 
received TAGRISSO at a dose of 80 mg once daily. The primary efficacy outcome measure of these 
two trials was ORR according to RECIST v1.1 as evaluated by a Blinded Independent Central Review 
(BICR). Secondary efficacy outcome measures included Duration of Response (DoR) and 
Progression-Free Survival (PFS).

Baseline characteristics of the overall study population (AURAex and AURA2) were as follows: 
median age 63 years, 13% of patients were ≥75 years old, female (68%), White (36%), Asian (60%). 
All patients received at least one prior line of therapy. Thirty-one percent (31%) (N=129) had 
received 1 prior line of therapy (EGFR-TKI treatment only), 69% (N=282) had received 2 or more 
prior lines. Seventy-two percent (72%) of patients were never smokers, 100% of patients had a World 
Health Organization (WHO) performance status of 0 or 1. Fifty-nine percent (59%) of patients had 
extra-thoracic visceral metastasis including 39% with CNS metastases (identified by CNS lesion site 
at baseline, medical history, and/or prior surgery and/or prior radiotherapy to CNS metastases) and 
29% with liver metastases. Forty-seven percent (47%) of patients had metastatic bone disease. The 
median duration of follow up for PFS was 12.6 months.

In the 411 pre-treated EGFR T790M mutation-positive patients, the total ORR by Blinded 
Independent Central Review (BICR) was 66% (95% CI: 61, 71). In patients with a confirmed 
response by BICR, the median DoR was 12.5 months (95% CI: 11.1, NE). The ORR by BICR in 
AURAex was 62% (95% CI: 55, 68) and 70% (95% CI: 63, 77) in AURA2. The median PFS was 
11.0 months 95% CI (9.6, 12.4).

Objective response rates by BICR above 50% were observed in all predefined subgroups analysed, 
including line of therapy, ethnicity, age and region.

In the evaluable for response population, 85% (223/262) had documentation of response at the time of 
the first scan (6 weeks); 94% (247/262) had documentation of response at the time of the second scan 
(12 weeks).

CNS metastases efficacy data in Phase 2 studies (AURAex and AURA2)
A BICR assessment of CNS efficacy by RECIST v 1.1 was performed in a subgroup of 50 (out of 
411) patients identified to have measurable CNS metastases on a baseline brain scan. A CNS ORR of 
54% (27/50 patients; 95% CI: 39.3, 68.2) was observed with 12% of these responses being complete 
responses.

Clinical studies have not been conducted in patients with de novo EGFR T790M mutation-positive 
NSCLC.



23

Paediatric population
The European Medicines Agency has waived the obligation to submit the results of studies with 
TAGRISSO in all subsets of the paediatric population in NSCLC (see section 4.2 for information on 
paediatric use).

5.2 Pharmacokinetic properties

Osimertinib pharmacokinetic parameters have been characterised in healthy subjects and NSCLC 
patients. Based on population pharmacokinetic analysis, osimertinib apparent plasma clearance is 
14.3 L/h, apparent volume of distribution is 918 L and terminal half-life of approximately 44 hours. 
The AUC and Cmax increased dose proportionally over 20 to 240 mg dose range. Administration of 
osimertinib once daily results in approximately 3 fold accumulation with steady-state exposures 
achieved by 15 days of dosing. At steady-state, circulating plasma concentrations are typically 
maintained within a 1.6 fold range over the 24-hour dosing interval.

Absorption
Following oral administration of TAGRISSO, peak plasma concentrations of osimertinib were 
achieved with a median (min-max) tmax of 6 (3-24) hours, with several peaks observed over the first 24 
hours in some patients. The absolute bioavailability of TAGRISSO is 70% (90% CI 67, 73). Based on 
a clinical pharmacokinetic study in patients at 80 mg, food does not alter osimertinib bioavailability to 
a clinically meaningful extent. (AUC increase by 6% (90% CI -5, 19) and Cmax decrease by 7% (90% 
CI -19, 6)). In healthy volunteers administered an 80 mg tablet where gastric pH was elevated by 
dosing of omeprazole for 5 days, osimertinib exposure was not affected (AUC and Cmax increase by 
7% and 2%, respectively) with the 90% CI for exposure ratio contained within the 80-125% limit.

Distribution
Population estimated mean volume of distribution at steady-state (Vss/F) of osimertinib is 918 L 
indicating extensive distribution into tissue. In vitro plasma protein binding of osimertinib is 94.7% 
(5.3% free). Osimertinib has also been demonstrated to bind covalently to rat and human plasma 
proteins, human serum albumin and rat and human hepatocytes.

Biotransformation
In vitro studies indicate that osimertinib is metabolised predominantly by CYP3A4, and CYP3A5. 
However, with current available data, alternative metabolic pathways cannot be fully ruled out. Based 
on in vitro studies, 2 pharmacologically active metabolites (AZ7550 and AZ5104) have subsequently 
been identified in the plasma of preclinical species and in humans after oral dosing with osimertinib; 
AZ7550 showed a similar pharmacological profile to TAGRISSO while AZ5104 showed greater 
potency across both mutant and wild-type EGFR. Both metabolites appeared slowly in plasma after 
administration of TAGRISSO to patients, with a median (min-max) tmax of 24 (4-72) and 24 (6-72) 
hours, respectively. In human plasma, parent osimertinib accounted for 0.8%, with the 2 metabolites 
contributing 0.08% and 0.07% of the total radioactivity with the majority of the radioactivity being 
covalently bound to plasma proteins. The geometric mean exposure of both AZ5104 and AZ7550, 
based on AUC, was approximately 10% each of the exposure of osimertinib at steady-state. 

The main metabolic pathway of osimertinib was oxidation and dealkylation. At least 12 components 
were observed in the pooled urine and faecal samples in humans with 5 components accounting for 
>1% of the dose of which unchanged osimertinib, AZ5104 and AZ7550, accounted for approximately 
1.9, 6.6 and 2.7% of the dose while a cysteinyl adduct (M21) and an unknown metabolite (M25) 
accounted for 1.5% and 1.9% of the dose, respectively.

Based on in vitro studies, osimertinib is a competitive inhibitor of CYP 3A4/5 but not CYP1A2, 2A6, 
2B6, 2C8, 2C9, 2C19, 2D6 and 2E1 at clinically relevant concentrations. Based on in vitro studies, 
osimertinib is not an inhibitor of UGT1A1 and UGT2B7 at clinically relevant concentrations 
hepatically. Intestinal inhibition of UGT1A1 is possible but the clinical impact is unknown.



24

Elimination
Following a single oral dose of 20 mg, 67.8% of the dose was recovered in faeces (1.2% as parent) 
while 14.2% of the administered dose (0.8% as parent) was found in urine by 84 days of sample 
collection. Unchanged osimertinib accounted for approximately 2% of the elimination with 0.8% in 
urine and 1.2% in faeces.

Interactions with transport proteins
In vitro studies have shown that osimertinib is not a substrate of OATP1B1 and OATP1B3. In vitro, 
osimertinib does not inhibit OAT1, OAT3, OATP1B1, OATP1B3, MATE1, OCT2 and MATE2K at 
clinically relevant concentrations. 

Effects of osimertinib on P-gp and BCRP
Based on in vitro studies, osimertinib is a substrate of P-gp and BCRP, but is unlikely to result in 
clinically relevant drug interactions with active substances by osimertinib at the clinical doses. Based 
on in vitro data, osimertinib is an inhibitor of BCRP and P-gp (see section 4.5).

Special populations
In a population based pharmacokinetic analyses (n=1367), no clinically significant relationships were 
identified between predicted steady-state exposure (AUCss) and patient’s age (range: 25 to 91 years), 
gender (65% female), ethnicity (including White, Asian, Japanese, Chinese and non-Asian-non-White 
patients), line of therapy and smoking status (n=34 current smokers, n=419 former smokers). 
Population PK analysis indicated that body weight was a significant covariate with a less than 20% 
change in osimertinib AUCss expected across a body weight range of 88 kg to 43 kg respectively 
(95% to 5% quantiles) when compared to the AUCss for the median body weight of 61 kg. Taking the 
extremes of body weight into consideration, from <43 kg to >88 kg, AZ5104 metabolite ratios ranged 
from 11.8% to 9.6% while for AZ7550 it ranged from 12.8% to 8.1%, respectively. Based on 
population PK analysis, serum albumin was identified as a significant covariate with a <30% change 
in osimertinib AUCss expected across the albumin range of 29 to 46 g/L respectively (95% to 5% 
quantiles) when compared to the AUCss for the median baseline albumin of 39 g/L. These exposure 
changes due to body weight or baseline albumin differences are not considered clinically relevant. 

Hepatic impairment
Osimertinib is eliminated mainly via the liver. In a clinical trial, patients with different types of 
advanced solid tumours and with mild hepatic impairment (Child Pugh A, mean score = 5.3, n=7) or 
moderate hepatic impairment (Child Pugh B, mean score = 8.2, n=5) had no increase in exposure 
compared to patients with normal hepatic function (n=10) after a single 80 mg dose of TAGRISSO.
The geometric mean ratio (90% CI) of osimertinib AUC and Cmax was 63.3% (47.3, 84.5) and 51.4% 
(36.6, 72.3) in patients with mild hepatic impairment and 68.4% (49.6, 94.2) and 60.7% (41.6, 88.6) 
in patients with moderate hepatic impairment; for the metabolite AZ5104 the AUC and Cmax were
66.5% (43.4, 101.9) and 66.3% (45.3, 96.9) in patients with mild hepatic impairment and 50.9% 
(31.7, 81.6) and 44.0% (28.9, 67.1) in patients with moderate hepatic impairment, compared to the 
exposure in patients with normal hepatic function. Based on population PK analysis, there was no 
relationship between markers of hepatic function (ALT, AST, bilirubin) and osimertinib exposure. 
The hepatic impairment marker serum albumin showed an effect on the PK of osimertinib. Clinical 
studies that were conducted excluded patients with AST or ALT >2.5x upper limit of normal (ULN), 
or if due to underlying malignancy, >5.0x ULN or with total bilirubin >1.5x ULN. Based on a 
pharmacokinetic analysis of 134 patients with mild hepatic impairment, 8 patients with moderate 
hepatic impairment and 1216 patients with normal hepatic function osimertinib exposures were 
similar. There are no data available on patients with severe hepatic impairment (see section 4.2).

Renal impairment
In a clinical trial, patients with severe renal impairment (CLcr 15 to less than 30 mL/min; n=7) 
compared to patients with normal renal function (CLcr greater than or equal to 90 mL/min; n=8) after 
a single 80 mg oral dose of TAGRISSO showed a 1.85-fold increase in AUC (90% CI; 0.94, 3.64) 



25

and a 1.19-fold increase in Cmax (90% CI: 0.69, 2.07). Furthermore, based on a population 
pharmacokinetic analysis of 593 patients with mild renal impairment (CLcr 60 to less than 
90 mL/min), 254 patients with moderate renal impairment (CLcr 30 to less than 60 mL/min), 5
patients with severe renal impairment (CLcr 15 to less than 30 mL/min) and 502 patients with normal 
renal function (greater than or equal to 90 mL/min), osimertinib exposures were similar. Patients with 
CLcr less than or equal to 10 mL/min were not included in the clinical trials.

5.3 Preclinical safety data

The main findings observed in repeat dose toxicity studies in rats and dogs comprised atrophic, 
inflammatory and/or degenerative changes affecting the epithelia of the cornea (accompanied by 
corneal translucencies and opacities in dogs at ophthalmology examination), GI tract (including 
tongue), skin, and male and female reproductive tracts with secondary changes in spleen. These 
findings occurred at plasma concentrations that were below those seen in patients at the 80 mg 
therapeutic dose. The findings present following 1 month of dosing were largely reversible within 1 
month of cessation of dosing with the exception of partial recovery for some of the corneal changes.

Osimertinib penetrated the intact blood-brain barrier of the cynomolgus monkey (i.v. dosing), rat and 
mouse (oral administration). 

Non-clinical data indicate that osimertinib and its metabolite (AZ5104) inhibit the h-ERG channel, 
and QTc prolonging effect cannot be excluded.

Carcinogenesis and mutagenesis
Carcinogenicity studies have not been performed with osimertinib. Osimertinib did not cause genetic 
damage in in vitro and in vivo assays.

Reproductive toxicity
Degenerative changes were present in the testes in rats and dogs exposed to osimertinib for ≥1 month 
and there was a reduction in male fertility in rats following exposure to osimertinib for 3 months. 
These findings were seen at clinically relevant plasma concentrations. Pathology findings in the testes
seen following 1 month dosing were reversible in rats; however, a definitive statement on reversibility 
of these lesions in dogs cannot be made.

Based on studies in animals, female fertility may be impaired by treatment with osimertinib. In repeat 
dose toxicity studies, an increased incidence of anoestrus, corpora lutea degeneration in the ovaries 
and epithelial thinning in the uterus and vagina were seen in rats exposed to osimertinib for ≥1 month 
at clinically relevant plasma concentrations. Findings in the ovaries seen following 1 month dosing 
were reversible. In a female fertility study in rats, administration of osimertinib at 20 mg/kg/day 
(approximately equal to the recommended daily clinical dose of 80 mg) had no effects on oestrus 
cycling or the number of females becoming pregnant, but caused early embryonic deaths. These 
findings showed evidence of reversibility following a 1 month off-dose.

In a modified embryofoetal development study in the rat, osimertinib caused embryolethality when 
administered to pregnant rats prior to embryonic implantation. These effects were seen at a maternally 
tolerated dose of 20 mg/kg where exposure was equivalent to the human exposure at the 
recommended dose of 80 mg daily (based on total AUC). Exposure at doses of 20 mg/kg and above 
during organogenesis caused reduced foetal weights but no adverse effects on external or visceral 
foetal morphology. When osimertinib was administered to pregnant female rats throughout gestation 
and then through early lactation, there was demonstrable exposure to osimertinib and its metabolites 
in suckling pups plus a reduction in pup survival and poor pup growth (at doses of 20 mg/kg and 
above).



26

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Tablet core
Mannitol
Microcrystalline cellulose
Low-substituted hydroxypropyl cellulose
Sodium stearyl fumarate

Tablet coating
Polyvinyl alcohol
Titanium dioxide (E 171)
Macrogol 3350
Talc
Yellow iron oxide (E 172)
Red iron oxide (E 172)
Black iron oxide (E 172)

6.2 Incompatibilities

Not applicable. 

6.3 Shelf life

3 years.

6.4 Special precautions for storage

This medicinal product does not require any special storage conditions.

6.5 Nature and contents of container

Al/Al perforated unit dose blisters. Cartons of 30 x 1 tablets (3 blisters).

Al/Al perforated unit dose blisters. Cartons of 28 x 1 tablets (4 blisters).

Not all pack sizes may be marketed.

6.6 Special precautions for disposal 

Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements.

7. MARKETING AUTHORISATION HOLDER

AstraZeneca AB
SE-151 85 Södertälje
Sweden



27

8. MARKETING AUTHORISATION NUMBER(S) 

EU/1/16/1086/001 40 mg 30 film-coated tablets
EU/1/16/1086/002 80 mg 30 film-coated tablets
EU/1/16/1086/003 40 mg 28 film-coated tablets
EU/1/16/1086/004 80 mg 28 film-coated tablets

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 2 February 2016
Date of latest renewal: 12 December 2016

10. DATE OF REVISION OF THE TEXT

Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu.

http://www.ema.europa.eu/


28

ANNEX II

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
AUTHORISATION

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 
EFFECTIVE USE OF THE MEDICINAL PRODUCT



29

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE

Name and address of the manufacturer responsible for batch release
AstraZeneca AB
Gärtunavägen
SE-151 85 Södertälje
SWEDEN

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE

Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2).

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
AUTHORISATION

 Periodic safety update reports (PSURs)

The requirements for submission of PSURs for this medicinal product are set out in the list of Union 
reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC and any 
subsequent updates published on the European medicines web-portal.

The marketing authorisation holder (MAH) shall submit the first PSUR for this product within 6 
months following authorisation.

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 
EFFECTIVE USE OF THE MEDICINAL PRODUCT

 Risk management plan (RMP)

The market authorisation holder (MAH) shall perform the required pharmacovigilance activities and 
interventions detailed in the agreed RMP presented in Module 1.8.2 of the marketing authorisation 
and any agreed subsequent updates of the RMP.
An updated RMP should be submitted:
 At the request of the European Medicines Agency;
 Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of an 
important (pharmacovigilance or risk minimisation) milestone being reached.



30

ANNEX III

LABELLING AND PACKAGE LEAFLET



31

A. LABELLING



32

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

CARTON

1. NAME OF THE MEDICINAL PRODUCT

TAGRISSO 40 mg film-coated tablets
osimertinib 

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each tablet contains 40 mg osimertinib (as mesylate).

3. LIST OF EXCIPIENTS

4. PHARMACEUTICAL FORM AND CONTENTS

30 x 1 film-coated tablets
28 x 1 film-coated tablets

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Oral use

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS



33

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements.

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

AstraZeneca AB
SE-151 85 Södertälje
Sweden

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/16/1086/001 40 mg 30 film-coated tablets
EU/1/16/1086/003 40 mg 28 film-coated tablets

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

Medicinal product subject to medical prescription.

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

tagrisso 40 mg

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC
SN
NN



34

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

CARTON

1. NAME OF THE MEDICINAL PRODUCT

TAGRISSO 80 mg film-coated tablets
osimertinib 

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each tablet contains 80 mg osimertinib (as mesylate).

3. LIST OF EXCIPIENTS

4. PHARMACEUTICAL FORM AND CONTENTS

30 x 1 film-coated tablets
28 x 1 film-coated tablets

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Oral use

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS



35

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements.

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

AstraZeneca AB
SE-151 85 Södertälje
Sweden

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/16/1086/002 80 mg 30 film-coated tablets
EU/1/16/1086/004 80 mg 28 film-coated tablets

13. BATCH NUMBER 

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

Medicinal product subject to medical prescription.

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

tagrisso 80 mg

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC
SN
NN



36

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

10 FILM-COATED TABLET BLISTERS (PERFORATED)
7 FILM-COATED TABLET BLISTERS (PERFORATED)

1. NAME OF THE MEDICINAL PRODUCT

TAGRISSO 40 mg tablets
osimertinib

2. NAME OF THE MARKETING AUTHORISATION HOLDER

AstraZeneca AB

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. OTHER



37

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

10 FILM-COATED TABLET BLISTERS (PERFORATED)
7 FILM-COATED TABLET BLISTERS (PERFORATED)

1. NAME OF THE MEDICINAL PRODUCT

TAGRISSO 80 mg tablets
osimertinib

2. NAME OF THE MARKETING AUTHORISATION HOLDER

AstraZeneca AB

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. OTHER



38

B. PACKAGE LEAFLET



39

Package leaflet: Information for the patient

TAGRISSO 40 mg film-coated tablets
TAGRISSO 80 mg film-coated tablets

osimertinib

This medicine is subject to additional monitoring. This will allow quick identification of new 
safety information. You can help by reporting any side effects you may get. See the end of section 4 
for how to report side effects.

Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you.
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor, pharmacist or nurse.
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours.
- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4.

What is in this leaflet

1. What TAGRISSO is and what it is used for
2. What you need to know before you take TAGRISSO
3. How to take TAGRISSO
4. Possible side effects 
5. How to store TAGRISSO
6. Contents of the pack and other information

1. What TAGRISSO is and what it is used for

TAGRISSO contains the active substance osimertinib, which belongs to a group of medicines called
protein kinase inhibitors which are used to treat cancer. TAGRISSO is used to treat adults with a type 
of lung cancer called ‘non-small cell lung cancer.’ If a test has shown that your cancer has certain 
changes (mutations) in a gene called ‘EGFR’ (epidermal growth factor receptor) and has spread to 
your other lung or other organs, your cancer is likely to respond to treatment with TAGRISSO. 
TAGRISSO can be prescribed for you:

 as the first medicine you receive for your cancer
or

 in certain circumstances if you have been treated for your cancer before with other protein kinase 
inhibitor medicines.

How TAGRISSO works

TAGRISSO works by blocking EGFR and may help to slow or stop your lung cancer from growing. 
It may also help to reduce the size of the tumour.

 If TAGRISSO is the first protein kinase inhibitor medicine you are receiving, it means that your 
cancer contains defects in the EGFR gene, for example ‘exon 19 deletions’ or ‘exon 21 
substitution mutations’.  

 If your cancer has progressed while you were being treated with other protein kinase inhibitor 
medicines, it means that your cancer contains a gene defect called ‘T790M’. Because of this 
defect, other protein kinase medicines may no longer work.



40

If you have any questions about how this medicine works or why this medicine has been prescribed 
for you, ask your doctor.

2. What you need to know before you take TAGRISSO

Do not take TAGRISSO if:
 you are allergic (hypersensitive) to osimertinib or any of the other ingredients of this medicine 

(listed in section 6).
 you are taking St. John’s Wort (Hypericum perforatum).

If you are not sure, talk to your doctor, pharmacist or nurse before taking TAGRISSO.

Warnings and precautions
Talk to your doctor, pharmacist or nurse before taking TAGRISSO if:
 you have suffered from inflammation of your lungs (a condition called ‘interstitial lung disease’).
 you have ever had heart problems – your doctor may want to keep a close eye on you.
 you have a history of eye problems.

If any of the above apply to you (or you are not sure), talk to your doctor, pharmacist or nurse before 
taking this medicine.

Tell your doctor straight away while taking this medicine if:
 you have sudden difficulty in breathing together with a cough or fever. 
 you have severe peeling of your skin.

See ‘Serious side effects’ in section 4 for more information.

Children and adolescents
TAGRISSO has not been studied in children or adolescents. Do not give this medicine to children or 
adolescents under the age of 18 years.

Other medicines and TAGRISSO
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. This includes herbal medicines and medicines obtained without a prescription. This is 
because TAGRISSO can affect the way some other medicines work. Also some other medicines can 
affect the way TAGRISSO works.

Tell your doctor before taking TAGRISSO if you are taking any of the following medicines:

The following medicines may reduce how well TAGRISSO works:
 Phenytoin, carbamazepine or phenobarbital – used for seizures or fits.
 Rifabutin or rifampicin – used for tuberculosis (TB).
 St. John’s Wort (Hypericum perforatum) – an herbal medicine used for depression.

TAGRISSO may affect how well the following medicines work and/or increase side effects of these 
medicines:
 Rosuvastatin – used to lower cholesterol.
 Oral hormonal contraceptive pill– used to prevent pregnancy. 
 Bosentan – used for high blood pressure in the lungs.
 Efavirenz and etravirine – used to treat HIV infections/AIDS.
 Modafinil – used for sleep disorders.
 Dabigatran – used to prevent blood clots.
 Digoxin – used for irregular heart beat or other heart problems.



41

 Aliskiren – used for high blood pressure.

If you are taking any of the medicines listed above, tell your doctor before taking TAGRISSO. 
Your doctor will discuss appropriate treatment options with you.

Pregnancy – information for women
 If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor for 

advice before taking this medicine. If you do become pregnant during treatment, tell your doctor 
straight away. Your doctor will decide with you whether you should carry on taking TAGRISSO.

 You should not become pregnant while taking this medicine. If you are able to become pregnant, 
you must use effective contraception. See ‘Contraception - information for women and men’ 
below. 

 If you plan to become pregnant after taking the last dose of this medicine, ask your doctor for 
advice. This is because some medicine may remain in your body, (see advice on contraception 
below).

Pregnancy – information for men
 If your partner becomes pregnant while you are taking this medicine, tell your doctor straight 

away.

Contraception – information for women and men
You must use effective contraception during treatment. 
 TAGRISSO may interfere with how well oral hormonal contraceptives work. Discuss with your 

doctor the most appropriate methods of contraception.
 TAGRISSO may pass into semen. Therefore, it is important that men also use effective 

contraception.

You must also do this after completing treatment with TAGRISSO:
 Women – keep using contraception for 2 months after. 
 Men – keep using contraception for 4 months after.

Breast-feeding
Do not breast-feed while taking this medicine. This is because it is not known if there is a risk to your 
baby.

Driving and using machines
TAGRISSO has no or no marked influence on the ability to drive and use machines.

Information on other ingredients in this medicine 
This medicine contains less than 1 mmol sodium (23 mg) per 40 mg or 80 mg tablet, that is to say 
essentially “sodium-free”.

3. How to take TAGRISSO

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure. 

How much to take
 The recommended dose is one 80 mg tablet each day.
 If necessary, your doctor may reduce your dose to one 40 mg tablet each day.

How to take



42

 TAGRISSO is taken by mouth. Swallow the tablet whole with water. Do not crush, split or chew 
the tablet.

 Take TAGRISSO every day at the same time.
 You can take this medicine with or without food.

If you have trouble swallowing the tablet, you can mix it in water: 
 Put the tablet in a glass.
 Add 50 mL (about two-thirds of a tumblerful) of still (non-fizzy) water – do not use any other 

liquids.
 Stir the water until the tablet breaks up into very small pieces - the tablet will not completely 

dissolve.
 Drink the liquid straight away.
 To make sure you have taken all of the medicine, rinse the glass thoroughly with another 50 mL 

of water and drink it.

If you take more TAGRISSO than you should
If you take more than your normal dose, contact your doctor or nearest hospital straight away.

If you forget to take TAGRISSO
If you forget a dose, take it as soon as you remember it. However, if it is less than 12 hours until your 
next dose is due, skip the missed dose. Take your next normal dose at its scheduled time.

If you stop taking TAGRISSO
Do not stop taking this medicine - talk to your doctor first. It is important to take this medicine every 
day, for as long as your doctor prescribes it for you. 

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Serious side effects
Tell your doctor straight away if you notice the following serious side effects:
 Sudden difficulty in breathing together with a cough or fever - this may be a sign of inflamed lungs 

(a condition called ‘interstitial lung disease’). Most cases can be treated but some cases have been 
fatal. Your doctor may wish to stop TAGRISSO if you get this side effect. This side effect is 
common: it may affect up to 1 in 10 people.

 If you develop watery eyes, sensitivity to light, eye pain, eye redness, or vision changes. This side 
effect is uncommon: it may affect up to 1 in 100 people.

 Stevens-Johnson syndrome, which can appear as reddish target-like macules or circular patches 
often with central blisters on the trunk, skin peeling, ulcers of mouth, throat, nose, genitals and 
eyes and be preceded by fever and flu-like symptoms. This side effect is rare: it may affect up to 1
in 1000 people. See also Section 2.

 Target lesions, which are skin reactions that look like rings (suggestive of Erythema multiforme). 
This side effect is uncommon: it may affect up to 1 in 100 people.

Tell your doctor straight away if you notice the serious side effects listed above.

Other side effects
Very common (may affect more than 1 in 10 people)
 Diarrhoea - this may come and go during treatment. Tell your doctor if your diarrhoea does not go 

away or becomes severe. 



43

 Skin and nail problems - signs may include pain, itching, dry skin, rash, redness around the 
fingernails. This is more likely in areas exposed to the sun. Using moisturisers regularly on your 
skin and nails can help with this. Tell your doctor if your skin or nail problems get worse.

 Stomatitis - inflammation of the inner lining of the mouth.
 Reduction in the number of white blood cells (leukocytes, lymphocytes or neutrophils).
 Reduction in the number of platelets in the blood.

Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. 
This includes any possible side effects not listed in this leaflet. You can also report side effects 
directly via the national reporting system listed in Appendix V. By reporting side effects you can help 
provide more information on the safety of this medicine.

5. How to store TAGRISSO

 Keep this medicine out of the sight and reach of children.
 Do not use this medicine after the expiry date (EXP) which is stated on the blister foil and carton. 

The expiry date refers to the last day of that month.
 This medicine does not require any special storage conditions.
 Do not use any pack that is damaged or shows signs of tampering.
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What TAGRISSO contains 
 The active substance is osimertinib (as mesylate). Each 40 mg film-coated tablet contains 40 mg of 

osimertinib. Each 80 mg film-coated tablet contains 80 mg of osimertinib.
 The other ingredients are mannitol, microcrystalline cellulose, low-substituted hydroxypropyl 

cellulose, sodium stearyl fumarate, polyvinyl alcohol, titanium dioxide, macrogol 3350, talc, 
yellow iron oxide, red iron oxide, black iron oxide (see section 2 “Information on other ingredients 
in this medicine”).

What TAGRISSO looks like and contents of the pack
TAGRISSO 40 mg is supplied as beige, film-coated, round and biconvex tablets, marked with “AZ” 
and “40” on one side, and plain on the other.

TAGRISSO 80 mg is supplied as beige, film-coated, oval and biconvex tablets, marked with “AZ” 
and “80” on one side, and plain on the other.

TAGRISSO is supplied in blisters containing 30 x 1 film-coated tablets, packed in cartons containing 
3 blisters of 10 tablets each. 

TAGRISSO is supplied in blisters containing 28 x 1 film-coated tablets, packed in cartons containing 
4 blisters of 7 tablets each. 

Marketing Authorisation Holder

AstraZeneca AB
SE-151 85 Södertälje
Sweden

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


44

Manufacturer

AstraZeneca AB
Gärtunavägen
SE-151 85 Södertälje
Sweden

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder.

België/Belgique/Belgien
AstraZeneca S.A./N.V.
Tel: +32 2 370 48 11

Lietuva
UAB AstraZeneca Lietuva
Tel: +370 5 2660550

България
АстраЗенека България ЕООД
Тел.: +359 24455000

Luxembourg/Luxemburg
AstraZeneca S.A./N.V.
Tél/Tel: +32 2 370 48 11

Česká republika
AstraZeneca Czech Republic s.r.o.
Tel: +420 222 807 111

Magyarország
AstraZeneca Kft.
Tel.: +36 1 883 6500

Danmark
AstraZeneca A/S
Tlf: +45 43 66 64 62

Malta
Associated Drug Co. Ltd
Tel: +356 2277 8000

Deutschland
AstraZeneca GmbH
Tel: +49 41 03 7080

Nederland
AstraZeneca BV
Tel: +31 79 363 2222

Eesti
AstraZeneca 
Tel: +372 6549 600

Norge
AstraZeneca AS
Tlf: +47 21 00 64 00

Ελλάδα
AstraZeneca A.E.
Τηλ: +30 210 6871500

Österreich
AstraZeneca Österreich GmbH
Tel: +43 1 711 31 0

España
AstraZeneca Farmacéutica Spain, S.A.
Tel: +34 91 301 91 00

Polska
AstraZeneca Pharma Poland Sp. z o.o.
Tel.: +48 22 245 73 00

France
AstraZeneca
Tél: +33 1 41 29 40 00

Portugal
AstraZeneca Produtos Farmacêuticos, Lda.
Tel: +351 21 434 61 00

Hrvatska
AstraZeneca d.o.o.
Tel: +385 1 4628 000

România
AstraZeneca Pharma SRL
Tel: +40 21 317 60 41

Ireland
AstraZeneca Pharmaceuticals (Ireland) 
DAC
Tel: +353 1609 7100

Slovenija
AstraZeneca UK Limited
Tel: +386 1 51 35 600



45

Ísland
Vistor hf.
Sími: +354 535 7000

Slovenská republika
AstraZeneca AB, o.z.
Tel: +421 2 5737 7777 

Italia
AstraZeneca S.p.A.
Tel: +39 02 9801 1

Suomi/Finland
AstraZeneca Oy
Puh/Tel: +358 10 23 010

Κύπρος
Αλέκτωρ Φαρµακευτική Λτδ
Τηλ: +357 22490305

Sverige
AstraZeneca AB
Tel: +46 8 553 26 000

Latvija
SIA AstraZeneca Latvija
Tel: +371 67377100

United Kingdom
AstraZeneca UK Ltd
Tel: +44 1582 836 836

This leaflet was last revised in

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu

http://www.ema.europa.eu/

	SUMMARY OF PRODUCT CHARACTERISTICS
	A.  MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET