Vizimpro Adverse Reactions

Summary of safety profile: The median duration of treatment with VIZIMPRO across the pooled data set was 66.7 weeks.
The most common (>20%) adverse reactions in patients receiving dacomitinib were diarrhoea (88.6%), rash (79.2%), stomatitis (71.8%), nail disorder (65.5%), dry skin (33.3%), decreased appetite (31.8%), conjunctivitis (24.7%), weight decreased (24.3%), alopecia (23.1%), pruritus (22.4%), transaminases increased (22.0%), and nausea (20.4%).
Serious adverse reactions were reported in 6.7% of patients treated with dacomitinib. The most frequently (≥1%) reported serious adverse reactions in patients receiving dacomitinib were diarrhoea (2.0%), interstitial lung disease (1.2%), rash (1.2%), and decreased appetite (1.2%).
Adverse reactions leading to dose reductions were reported in 52.2% of patients treated with dacomitinib. The most frequently reported (>5%) reasons for dose reductions due to any adverse reactions in patients receiving dacomitinib were rash (32.2%), nail disorder (16.5%), and diarrhoea (7.5%).
Adverse reactions leading to permanent discontinuation were reported in 6.7% of patients treated with dacomitinib. The most common (>0.5%) reasons for permanent discontinuations associated with adverse reactions in patients receiving dacomitinib were: rash (2.4%), interstitial lung disease (2.0%), and diarrhoea (0.8%).
Tabulated list of adverse reactions: Table 4 presents adverse reactions for VIZIMPRO. Adverse reactions are listed according to system organ class (SOC). Within each SOC, the adverse reactions are ranked by frequency, with the most frequent reactions first, using the following convention: 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). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. (See Table 4.)

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Description of selected adverse reactions: Very common adverse reactions in patients occurring in at least 10% of patients in Study ARCHER 1050 are summarised by National Cancer Institute-Common Toxicity Criteria (NCI-CTC) Grade in Table 5. (See Table 5.)

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Interstitial lung disease (ILD)/Pneumonitis: ILD/pneumonitis adverse reactions were reported in 2.7% of patients receiving VIZIMPRO, and Grade ≥3 ILD/pneumonitis adverse reactions were reported in 0.8%, including a fatal event (0.4%) (see Precautions).
The median time to the first episode of any grade ILD/pneumonitis was 16 weeks and the median time to the worst episode of ILD/pneumonitis was 16 weeks in patients receiving dacomitinib. The median duration of any grade and Grade ≥3 ILD/pneumonitis was 13 weeks and 1.5 weeks, respectively (see Precautions).
Diarrhoea: Diarrhoea was the most frequently reported adverse reaction in patients receiving VIZIMPRO (88.6%) and Grade ≥3 diarrhoea adverse reactions were reported in 9.4% of patients. In a clinical study, one patient (0.4%) had a fatal outcome (see Precautions).
The median time to the first episode of any grade diarrhoea was 1 week and the median time to the worst episode of diarrhoea was 2 weeks in patients receiving dacomitinib. The median duration of any grade and Grade ≥3 diarrhoea was 20 weeks and 1 week, respectively (see Precautions).
Skin-related adverse reactions: Rash, erythematous and exfoliative skin condition adverse reactions were reported in 79.2% and 5.5%, respectively, of patients receiving VIZIMPRO. Skin-related adverse reactions were Grades 1 to 3. Grade 3 rash and erythematous skin condition adverse reactions were the most frequently reported Grade 3 adverse reactions (25.5%). Grade 3 exfoliative skin conditions were reported in 0.8% of patients (see Precautions).
The median time to the first episode of any grade rash and erythematous skin conditions was approximately 2 weeks and the median time to the worst episode of rash and erythematous skin conditions was 7 weeks in patients receiving dacomitinib. The median duration of any grade and Grade ≥3 rash and erythematous skin conditions was 53 weeks and 2 weeks, respectively. The median time to the first episode of any grade exfoliative skin conditions was 6 weeks and the median time to the worst episode of exfoliative skin conditions was 6 weeks. The median duration of any grade and Grade ≥3 exfoliative skin conditions was 10 weeks and approximately 2 weeks, respectively.
Transaminases increased: Transaminases increased (alanine aminotransferase increased, aspartate aminotransferase increased, transaminases increased) were reported in 22.0% of patients receiving VIZIMPRO and were Grades 1 to 3, with the majority Grade 1 (18.4%) (see Precautions).
The median time to the first episode of any grade of transaminases increased was approximately 12 weeks and the median time to the worst episode of transaminases increased was 12 weeks in patients receiving dacomitinib. The median duration of any grade and Grade ≥ 3 transaminases increased was 11 weeks and 1 week, respectively.