TAGRISSO (osimertinib)

TAGRISSO is an EGFR TKI indicated as a monotherapy for:

Prescribing information

Warnings and precautions


  • Hypersensitivity to the active substance or to any of the excipients
  • St. John's Wort should not be used together with TAGRISSO

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)
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.
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.
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. 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.
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 of the SmPC. 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 percentage points 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 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 or worsening: eye
inflammation, lacrimation, light sensitivity, blurred vision, eye pain and/or
red eye should be referred promptly to an ophthalmology specialist.

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.

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