What are the warnings and precautions for Sotatercept-Winrevair?

In the clinical study of Sotatercept-Winrevair in the treatment of pulmonary arterial hypertension (PAH), warnings and precautions such as polycythemia, severe thrombocytopenia, severe bleeding, embryo-fetal toxicity, etc. appeared. Discontinue and resume at reduced dose upon recovery, or permanently discontinue based on severity.

1. Polycythemia: Soltercept may increase hemoglobin. Severe polycythemia may increase the risk of thromboembolic events or hyperviscosity syndrome. In clinical studies, 15% of patients taking WINREVAIR experienced moderate increases in Hgb (> 2 g/dL above ULN), while no increases above ULN ≥ 4 g/dL were observed. For the first 5 doses, monitor Hgb before each dose, if the value is unstable, monitor for a longer period of time, and then periodically thereafter to determine if dose adjustment is needed.

2. Severe thrombocytopenia: Soltercept may reduce platelet count. Severe thrombocytopenia may increase the risk of bleeding. In clinical studies, severe thrombocytopenia (platelet count < 50,000/mm3 [<50 x 109/L]) occurred in 3% of patients taking WINREVAIR. Thrombocytopenia is more common in patients receiving prostacyclin infusions.

Do not initiate treatment if platelet count< 50,000/mm3. For the first 5 doses, monitor platelets before each dose, longer if values u200bu200bare unstable, and periodically thereafter to determine if dose adjustments are needed.

3. Serious bleeding: In clinical studies, 4% of patients taking sotercept and 1% of patients taking placebo reported serious bleeding (such as gastrointestinal bleeding, intracranial bleeding). Patients with severe bleeding were more likely to be receiving background therapy with prostacyclin and/or antithrombotic drugs or to have low platelet counts. Inform patients of the signs and symptoms of blood loss. Assess and treat bleeding accordingly. Do not use sotercept if the patient is experiencing severe bleeding.

4. Embryotoxicity-Fetal Toxicity: According to findings from animal reproduction studies, Soltercept may cause harm to the fetus when used by pregnant women. In animal reproduction studies, administration of soltrecept to pregnant rats and rabbits during organogenesis resulted in adverse developmental outcomes, including in embryos- Increased fetal mortality, growth alterations, and structural variations at exposures 4 and 0.6 times the maximum recommended human dose (MRHD), respectively (based on area under the curve). Inform pregnant women of potential risks to the fetus. Advise females of reproductive potential to use an effective method of contraception during treatment with sotercept and for at least 4 months after the last dose.

5. Impairment of fertility: Based on animal studies, Soltrecept may damage both female and male fertility. Inform patients of the potential effects on fertility.

Reference materials:https://www.drugs.com/mtm/sotatercept.html