Giotrif Adverse Reactions

Summary of the safety profile: The types of adverse reactions (ADRs) were generally associated with the EGFR inhibitory mode of action of afatinib. The summary of all ADRs is shown in Table 8 as follows. The most frequent ADRs were diarrhoea and skin related adverse events (see Precautions) as well as stomatitis and paronychia (see also Tables 9, 10 and 11). Overall, dose reduction (see Dosage & Administration) led to a lower frequency of common adverse reactions.
In patients treated with once daily GIOTRIF 40 mg, dose reductions due to ADRs occurred in 57% of the patients in LUX-Lung 3 trial and in 25% of the patients in the LUX-Lung 8 trial. Discontinuation due to ADRs diarrhoea and rash/acne was 1.3% and 0% in LUX-Lung 3 and 3.8% and 2.0% in LUX-Lung 8, respectively.
ILD-like adverse reactions were reported in 0.7% of afatinib treated patients. Bullous, blistering and exfoliative skin conditions have been reported including rare cases suggestive of Stevens-Johnson syndrome and toxic epidermal necrolysis although in these cases there were potential alternative aetiologies (see Precautions).
Tabulated list of adverse reactions: Table 8 summarises the frequencies of ADRs pooled from all NSCLC trials and from post-marketing experience with daily GIOTRIF doses of 40 mg or 50 mg as monotherapy. The following terms are used to rank the ADRs by frequency: 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). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. (See Table 8.)

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Description of selected adverse reactions: Very common ADRs in GIOTRIF-treated patients occurring in at least 10% of patients in trial LUX-Lung 3 and LUX Lung 7 are summarised by National Cancer Institute-Common Toxicity Criteria (NCI-CTC) Grade in Tables 9 and 10. (See Table 9 and Table 10.)

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Liver function test abnormalities: Liver function test abnormalities (including elevated ALT and AST) were observed in patients receiving GIOTRIF 40 mg. These elevations were mainly transient and did not lead to discontinuation. Grade 2 (> 2.5 to 5.0 times upper limit of normal (ULN)) ALT elevations occurred in < 8% of patients treated with this medicinal product. Grade 3 (> 5.0 to 20.0 times ULN) elevations occurred in <4% of patients treated with GIOTRIF (see Precautions).
Description of selected adverse reactions: Very common ADRs in GIOTRIF-treated patients occurring in at least 10% of patients in trial LUX-Lung 8 are summarised by National Cancer Institute-Common Toxicity Criteria (NCI-CTC) Grade in Table 11. (See Table 11.)

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Liver function test abnormalities: Liver function test abnormalities (including elevated ALT and AST) were observed in patients receiving GIOTRIF 40 mg. These elevations were mainly transient and did not lead to discontinuation. Grade 2 ALT elevations occurred in 1% and Grade 3 elevations occurred in 0.8% of patients treated with GIOTRIF (see Precautions).
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.