Summary of the safety profile: The most common adverse reactions are fatigue (30%), skin rash (24% of any grade and 5% Grade 3 or 4), weight decreased (16%), arthralgia (16%), and fall (16%). Other important adverse reactions include fractures (12%) and hypothyroidism (8%).
Tabulated list of adverse reactions: Adverse reactions observed during clinical studies are listed below by frequency category. Frequency categories are defined as follows: 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) and not known (frequency cannot be estimated from the available data).
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. (See table.)
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Description of selected adverse reactions: Skin rash: Skin rash associated with ERLEADA was most commonly described as macular or maculo-papular. Skin rash included rash, rash maculo-papular, rash generalised, urticaria, rash pruritic, rash macular, conjunctivitis, erythema multiforme, rash papular, skin exfoliation, genital rash, rash erythematous, stomatitis, drug eruption, mouth ulceration, rash pustular, blister, papule, pemphigoid, skin erosion, and rash vesicular. Adverse reactions of skin rash were reported for 24% of patients treated with ERLEADA. Grade 3 skin rashes (defined as covering > 30% body surface area [BSA]) were reported with ERLEADA treatment in 5.2% of patients.
The median days to onset of skin rash was 82 days with a range of 1 to 994 days. Eighty-one percent of patients had resolution of rash with a median of 60 days to resolution. Medicinal products utilised included topical corticosteroids, systemic corticosteroids and oral anti-histamines. Among patients with skin rash, dose interruption occurred in 28% and dose reduction occurred in 12% (see Dosage & Administration). Skin rash recurred in approximately half of patients who were re-challenged. Skin rash led to ERLEADA treatment discontinuation in 9% of patients who experienced skin rash.
Falls and fractures: In Study ARN-509-003, fracture was reported for 11.7% of patients treated with ERLEADA and 6.5% of patients treated with placebo. Half of the patients experienced a fall within 7 days before the fracture event in both treatment groups. Falls were reported for 15.6% of patients treated with ERLEADA versus 9.0% of patients treated with placebo (see Precautions).
Hypothyroidism: Hypothyroidism was reported for 8.1% of patients treated with ERLEADA and 2.0% of patients treated with placebo based on assessments of thyroid-stimulating hormone (TSH) every 4 months. There were no grade 3 or 4 adverse events. Hypothyroidism occurred in 28% of patients already receiving thyroid replacement therapy in the ERLEADA arm and in 5.9% of patients in the placebo arm. In patients not receiving thyroid replacement therapy, hypothyroidism occurred in 5.7% of patients treated with ERLEADA and in 0.8% of patients treated with placebo. Thyroid replacement therapy, when clinically indicated, should be initiated or dose-adjusted (see Interactions).
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.