Winrevair Adverse Reactions

Summary of safety profile: The most frequently reported adverse reactions were headache (24.5%), epistaxis (22.1%), telangiectasia (16.6%), diarrhoea (15.3%), dizziness (14.7%), rash (12.3%), and thrombocytopenia (10.4%).
The most frequently reported serious adverse reactions were thrombocytopenia (<1%) and epistaxis (<1%).
The most common adverse reactions leading to discontinuation were epistaxis and telangiectasia.
Tabulated list of adverse reactions: The safety of sotatercept was evaluated in the pivotal study STELLAR, a placebo-controlled study of 163 patients with PAH treated with sotatercept (see Pharmacology: Pharmacodynamics under Actions). The median duration of treatment with sotatercept was 313 days.
The adverse reactions reported with sotatercept are listed in the table as follows by MedDRA system organ class and by frequency. Frequencies are defined as 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), and very rare (<1/10 000). (See Table 4.)

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Description of selected adverse reactions: Increased haemoglobin: In STELLAR, adverse reactions of increased Hgb ('haemoglobin increased' and 'polycythaemia') were reported in 8.6% of patients taking sotatercept. Based on laboratory data, moderate elevations in Hgb (>1.24 mmol/L (2 g/dL) above ULN) occurred in 15.3% of patients taking sotatercept. Increases in Hgb were managed by dose adjustments (see Dosage & Administration and Precautions).
Thrombocytopenia: Thrombocytopenia ('thrombocytopenia' and 'platelet count decreased') was reported in 10.4% of patients taking sotatercept. Severe reduction in platelet count <50 x 10⁹/L occurred in 2.5% of patients taking sotatercept. Thrombocytopenia was reported more frequently in patients also receiving prostacyclin infusion (21.5%) compared to patients not receiving prostacyclin infusion (3.1%). Thrombocytopenia was managed by dose adjustments (see Dosage & Administration and Precautions).
Telangiectasia: Telangiectasia was observed in 16.6% of patients taking sotatercept. The median time to onset was 18.6 weeks. Discontinuations of treatment due to telangiectasia were 1% in the sotatercept group.
Increased blood pressure: Increased blood pressure was reported in 4.3% of patients taking sotatercept. In patients taking sotatercept, mean systolic blood pressure increased from baseline by 2.2 mmHg and diastolic blood pressure increased by 4.9 mmHg at 24 weeks.
Elderly: With the exception of bleeding events (a collective group of adverse events of clinical interest), there were no differences in safety between the <65-year-old and ≥65-year-old subgroups. Bleeding events occurred more commonly in the older sotatercept subgroup (52% vs 31.9% in patients <65-year-old); however, there was no notable imbalance between age categories for any specific bleeding event. Serious bleeding occurred in 3.6% of patients <65-year-old and in 8.0% of patients ≥65-year-old taking sotatercept.
Long-term safety data: Long-term safety data are available from pooled phase 2 and phase 3 clinical studies (n=431). The median duration of exposure was 657 days. The safety profile was generally similar to that observed in the pivotal STELLAR study.
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.