Tagrisso Special Precautions

Assessment of EGFR mutation status: When considering the use of TAGRISSO as an adjuvant therapy after tumour resection in patients with NSCLC, EGFR mutation positive status (exon 19 deletions or exon 21 (L858R) substitution mutations) indicates treatment eligibility. A validated test should be performed in a clinical laboratory using tumour tissue DNA from diagnostic tumour biopsy specimen or tumour tissue taken during surgery.
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 in a clinical laboratory using either tumour tissue DNA or circulating tumour DNA (ctDNA) obtained from a plasma sample.
Only robust, reliable and sensitive test(s) with demonstrated utility for the determination of EGFR mutation status should be used.
Positive determination of EGFR mutation status (exon 19 deletions or exon 21 (L858R) substitution mutations for first-line treatment or T790M mutations following progression on or after EGFR TKI therapy) 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): Interstitial Lung Disease (ILD) or ILD-like adverse reactions (e.g. pneumonitis) were reported in 3.7% and were fatal in 0.3% (n=5) of the 1479 patients who received TAGRISSO in ADAURA, FLAURA and AURA studies.
The incidence of ILD was 10.9% in patients of Japanese ethnicity, 1.6% in patients of non-Japanese Asian ethnicity and 2.5% in non-Asian patients. The median time to onset of ILD or ILD-like adverse reactions was 2.8 months.
Withhold TAGRISSO and promptly investigate for ILD in any patient who presents with worsening of respiratory symptoms which may be indicative of ILD (e.g. dyspnoea, cough and fever). Permanently discontinue TAGRISSO if ILD is confirmed.
Erythema multiforme and Stevens-Johnson syndrome: Case reports of Erythema multiforme (EM) and Stevens-Johnson syndrome (SJS) have been uncommonly and rarely reported, respectively, in association with TAGRISSO treatment. Before initiating treatment, patients should be advised of signs and symptoms of EM and SJS. If signs and symptoms suggestive of EM develop, close patient monitoring and drug interruption or discontinuation of TAGRISSO should be considered. If signs and symptoms suggestive of SJS appear, TAGRISSO should be interrupted or discontinued immediately.
QTc interval prolongation: When possible, avoid use of TAGRISSO in patients with congenital long QT syndrome (see Adverse Reactions). Consider periodic monitoring with electrocardiograms (ECGs) and electrolytes in patients with congestive heart failure, electrolyte abnormalities, or those who are taking medications that are known to prolong the QTc interval. Withhold TAGRISSO 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 10. Permanently discontinue TAGRISSO 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 3.2% (40/1233) of patients treated with TAGRISSO who had baseline and at least one follow-up LVEF assessment. In a placebo controlled trial (ADAURA), 1.6% (5/312) of patients treated with TAGRISSO and 1.5% (5/331) of patients treated with placebo experienced LVEF decreases greater than or equal to 10 percentage points and a drop to less than 50%.
Based on the available clinical trial data, a causal relationship between effects on changes in cardiac contractility and TAGRISSO has not been established. 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=10) of the 1479 patients treated with TAGRISSO in the ADAURA, 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 (see Dosage & Administration).
Aplastic Anaemia: Rare reports of aplastic anaemia have been reported in association with TAGRISSO treatment. Some cases had a fatal outcome. Before initiating treatment, patients should be advised of signs and symptoms of aplastic anaemia including but not limited to persistent fever, bruising, bleeding, pallor. If signs and symptoms suggestive of aplastic anaemia develop, close patient monitoring and drug interruption or discontinuation of TAGRISSO should be considered. TAGRISSO should be discontinued in patients with confirmed aplastic anaemia.
Effects on ability to drive and use machines: TAGRISSO has no or no marked influence on the ability to drive and use machines.