WINREVAIR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for WINREVAIR (WINREVAIR).
WINREVAIR is a monoclonal antibody that binds to activin A and inhibits activin signaling, thereby reducing pulmonary vascular resistance and improving exercise capacity in patients with pulmonary arterial hypertension.
| Metabolism | WINREVAIR is a monoclonal antibody that is degraded into small peptides and amino acids via general protein catabolism; no specific metabolic enzymes are involved. |
| Excretion | Approximately 98% of the dose is eliminated via the biliary/fecal route as unchanged drug, with minimal (<2%) renal excretion. |
| Half-life | Terminal elimination half-life is approximately 47 days (range 38–58 days), supporting a subcutaneous dosing interval of every 3 weeks. |
| Protein binding | Approximately 98% bound to plasma proteins, primarily to albumin and to a lesser extent alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution is approximately 0.3 L/kg, indicating limited extravascular distribution, consistent with a large molecule confined largely to the vascular space. |
| Bioavailability | Subcutaneous administration: Bioavailability is approximately 75% (relative to intravenous administration). |
| Onset of Action | Subcutaneous administration: Clinically significant reduction in pulmonary vascular resistance is observed within 2–4 weeks after the first dose. |
| Duration of Action | Duration of action is sustained over the 3-week dosing interval. Hemodynamic effects persist throughout the dosing period, but gradual loss of effect may occur if doses are missed. |
200 mg subcutaneous injection once weekly.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (eGFR >=30 mL/min/1.73 m²). Not studied in severe renal impairment (eGFR <30 mL/min/1.73 m²) or end-stage renal disease. Use caution if administered in these populations. |
| Liver impairment | Contraindicated in patients with Child-Pugh class B or C hepatic impairment. No dose adjustment required for Child-Pugh class A. |
| Pediatric use | Safety and effectiveness in pediatric patients have not been established. No pediatric dosing recommendations exist. |
| Geriatric use | No specific dose adjustment recommended. Clinical studies included patients aged 65 and older; no overall differences in safety or efficacy observed. Monitor renal function due to age-related decreased GFR. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for WINREVAIR (WINREVAIR).
| Breastfeeding | There are no data on the presence of sotatercept in human milk, effects on the breastfed infant, or effects on milk production. Sotatercept is a large protein molecule (MW ~76 kDa) and is expected to be present in milk at low levels. The M/P ratio is unknown. Due to the potential for serious adverse reactions in the breastfed infant, advise patients that breastfeeding is not recommended during treatment with WINREVAIR and for at least [duration not specified; likely 3-5 half-lives, half-life ~14-21 days] after the last dose. |
| Teratogenic Risk | WINREVAIR (sotatercept) is an activin receptor type IIA-Fc fusion protein. Based on its mechanism of action and animal studies, it is expected to cause fetal harm. In animal reproduction studies, administration of sotatercept to pregnant rabbits during organogenesis resulted in increased fetal malformations and embryolethality at exposures below the human clinical dose. Sotatercept should be avoided during pregnancy; if used, advise females of reproductive potential of the potential risk to the fetus. There are no adequate human data for first trimester risks; second and third trimester risks are unknown but likely include impaired fetal development due to interference with activin signaling. |
■ FDA Black Box Warning
Embryofetal toxicity: WINREVAIR may cause fetal harm when administered to pregnant women. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for at least 4 months after the last dose.
| Serious Effects |
["Pregnancy","Hypersensitivity to WINREVAIR or any of its excipients"]
| Precautions | ["Embryofetal toxicity","Cardiovascular effects including hypotension, bradycardia, and syncope","Hypersensitivity reactions including anaphylaxis","Risk of infection if administered with live vaccines"] |
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| Fetal Monitoring | For pregnant women exposed to WINREVAIR: Perform obstetric ultrasound to assess fetal anatomy and growth. Monitor for development of pulmonary hypertension worsening or complications. No specific maternal monitoring beyond standard prenatal care. For women of reproductive potential, confirm pregnancy status prior to initiation and advise use of effective contraception during treatment and for at least [duration not specified; likely 4 months] after the last dose. |
| Fertility Effects | Based on animal studies, WINREVAIR may impair female fertility. In female rabbits, ovulation was inhibited at doses resulting in exposures below the human clinical dose. Reversibility of these effects is unknown. No dedicated studies in male fertility; effects on spermatogenesis cannot be excluded. |