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. |
| Molecular Weight | 65000 |
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 | Data not available; risk cannot be excluded. Based on animal studies, there may be a risk of fetal harm. Use only if potential benefit justifies risk. |
| 2nd trimester | Data not available; risk cannot be excluded. Based on animal studies, there may be a risk of fetal harm. Use only if potential benefit justifies risk. |
| 3rd trimester | Data not available; risk cannot be excluded. Based on animal studies, there may be a risk of fetal harm. Use only if potential benefit justifies risk. |
Clinical note
Comprehensive clinical and safety monograph for WINREVAIR (WINREVAIR).
| Placental transfer | Based on molecular weight (approximately 65 kDa) and protein structure, placental transfer is expected to be limited, but there are no human data. Animal studies show minimal transfer. |
| Breastfeeding | It is unknown if WINREVAIR is excreted in human milk. A risk to the breastfed infant cannot be excluded. Decision to breastfeed during therapy should consider the mother's clinical need, the drug's potential for adverse effects on the infant, and the benefits of breastfeeding. |
■ 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 |
Hypersensitivity to the active substance or to any of the excipientsPregnancy (due to teratogenicity observed in animal studies)
| Precautions | Embryofetal toxicity, Cardiovascular effects including hypotension, bradycardia, and syncope, Hypersensitivity reactions including anaphylaxis, Risk of infection if administered with live vaccines |
| Food/Dietary | Grapefruit and grapefruit juice are contraindicated as they may increase sotatercept exposure. No specific food restrictions otherwise. Avoid alcohol due to potential hepatotoxicity. |
Loading safety data…
| Lactation Rating | L4 (Possibly Hazardous) - No data on human milk levels; potential for serious adverse reactions in the infant. |
| 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. |
| 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. |
| Clinical Pearls | WINREVAIR (sotatercept) is an activin signaling inhibitor approved for pulmonary arterial hypertension (WHO Group I). Administer subcutaneously every 3 weeks. Monitor hemoglobin and hematocrit due to risk of erythrocytosis; consider phlebotomy if HCT >56%. Avoid initiating in patients with severe renal impairment (eGFR <30 mL/min) or hepatic impairment. Concomitant use with anticoagulants may increase bleeding risk. Do not coadminister with other activin receptor fusion proteins. |
| Patient Advice | Inject exactly as prescribed every 3 weeks; do not miss doses. · Rotate injection sites to reduce lipohypertrophy or skin reactions. · Report symptoms of excess red blood cells (headache, dizziness, blurred vision). · Avoid grapefruit and grapefruit juice during treatment. · Inform all healthcare providers you are taking WINREVAIR before any surgery or procedure. |