Erleada Adverse Reactions

Summary of the safety profile: The most common adverse reactions are fatigue (26%), skin rash (26% of any grade and 6% Grade 3 or 4), hypertension (22%), hot flush (18%), arthralgia (17%), diarrhoea (16%), fall (13%), and weight decreased (13%). Other important adverse reactions include fractures (11%) and hypothyroidism (8%).
Tabulated list of adverse reactions: Adverse reactions observed during clinical studies are listed as follows 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 2.)

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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, dermatitis and rash vesicular. Adverse reactions of skin rash were reported for 26% of patients treated with apalutamide. Grade 3 skin rashes (defined as covering > 30% body surface area [BSA]) were reported with apalutamide treatment in 6% of patients.
The median days to onset of skin rash was 83 days. Seventy-eight percent of patients had resolution of rash with a median of 78 days to resolution. Medicinal products utilised included topical corticosteroids, oral anti-histamines, and 19% of patients received systemic corticosteroids. Among patients with skin rash, dose interruption occurred in 28% and dose reduction occurred in 14% (see Dosage & Administration). Skin rash recurred in 59% of patients who had dose interruption. Skin rash led to apalutamide treatment discontinuation in 7% of patients who experienced skin rash.
Falls and fractures: In Study ARN-509-003, fracture was reported for 11.7% of patients treated with apalitamode 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 apalutamide versus 9.0% of patients treated with placebo (see Precautions).
Ischaemic heart disease and ischaemic cerebrovascular disorders: In a randomised study (SPARTAN) of patients with nmCRPC, ischaemic heart disease occurred in 4% of patients treated with apalutamide and 3% of patients treated with placebo. In a randomised study (TITAN) in patients with mHSPC, ischaemic heart disease occurred in 4% of patients treated with apalutamide and 2% of patients treated with placebo. Across the SPARTAN and TITAN studies, 6 patients (0.5%) treated with apalutamide and 2 patients (0.2%) treated with placebo died from ischaemic heart disease (see Precautions).
In the SPARTAN study, with a median exposure of 32.9 months for apalutamide and 11.5 months for placebo, ischaemic cerebrovascular disorders occurred in 4% of patients treated with apalutamide and 1% of patients treated with placebo (see previously mentioned). In the TITAN study, ischaemic cerebrovascular disorders occurred in a similar proportion of patients in the apalutamide (1.5%) and placebo (1.5%) groups. Across the SPARTAN and TITAN studies, 2 patients (0.2%) treated with apalutamide and no patients treated with placebo died from an ischaemic cerebrovascular disorder (see Precautions).
Hypothyroidism: Hypothyroidism was reported for 8% of patients treated with apalutamide and 2% 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 30% of patients already receiving thyroid replacement therapy in the apalutamide arm and in 3% of patients in the placebo arm. In patients not receiving thyroid replacement therapy, hypothyroidism occurred in 7% of patients treated with apalutamide and in 2% 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.