Winrevair (Sotatercept)
Activin signaling inhibitor for pulmonary arterial hypertension (PAH)
Winrevair (sotatercept) is a first-in-class activin signaling inhibitor used in combination with other medicines to treat pulmonary arterial hypertension (PAH) in adults. Given as a subcutaneous injection every three weeks, it targets the underlying vascular remodeling that causes PAH, improving exercise capacity and slowing disease progression. It requires regular blood monitoring for hemoglobin and platelet counts.
Quick Facts
Key Takeaways
- Winrevair is the first activin signaling inhibitor approved for pulmonary arterial hypertension, targeting the disease at a molecular level to reduce vascular remodeling in the lungs.
- It is always used in combination with other PAH therapies — never as monotherapy — and is administered as a subcutaneous injection once every three weeks.
- Regular blood tests are essential: hemoglobin levels may increase (raising blood clot risk) and platelet counts may decrease (raising bleeding risk).
- Winrevair is not recommended during pregnancy or breastfeeding. Effective contraception is required during treatment and for at least 4 months after the last dose.
- The medicine must be stored refrigerated (2–8 °C), reconstituted before use, and injected within 4 hours of preparation.
What Is Winrevair and What Is It Used For?
Quick answer: Winrevair (sotatercept) is a prescription medicine used together with other treatments for pulmonary arterial hypertension (PAH) in adults. It works on the underlying causes of PAH by reducing abnormal blood vessel thickening in the lungs.
Winrevair contains the active substance sotatercept, which belongs to a new class of medicines known as activin signaling inhibitors. It was developed to address a fundamental biological pathway involved in the development and progression of pulmonary arterial hypertension (PAH). PAH is a chronic, progressive condition characterized by abnormally high blood pressure in the pulmonary arteries — the blood vessels that carry blood from the right side of the heart to the lungs for oxygenation.
In patients with PAH, the walls of the pulmonary arteries become thickened and narrowed through a process called vascular remodeling. This narrowing forces the right side of the heart to work significantly harder to push blood through these constricted vessels. Over time, this increased workload can lead to right heart failure, which is the primary cause of death in PAH. Patients typically experience symptoms such as breathlessness (particularly during physical activity), fatigue, dizziness, chest pain, and swelling in the ankles or legs.
Sotatercept works by acting as a “ligand trap” for members of the transforming growth factor-beta (TGF-β) superfamily, specifically activins and certain growth differentiation factors. In PAH, there is an imbalance between growth-promoting and growth-inhibiting signals in the pulmonary vasculature. By neutralizing excess activin signaling, sotatercept helps restore this balance and reduces the pathological cell proliferation and vascular remodeling that drive PAH. This mechanism of action is distinct from and complementary to existing PAH therapies, which primarily target vasodilation (widening of blood vessels).
Clinical trials have demonstrated that when added to background PAH therapy, Winrevair significantly improves exercise capacity (as measured by the six-minute walk distance), reduces pulmonary vascular resistance, and lowers the risk of clinical worsening events including death, hospitalization for PAH, and disease progression. These benefits make it an important addition to the PAH treatment landscape, offering patients a therapy that addresses the disease process itself rather than just managing symptoms.
Winrevair is indicated for use in adult patients with PAH (WHO Functional Class II–III) in combination with other PAH-specific therapies. It is not intended for use as a standalone treatment. Your prescribing physician will determine whether Winrevair is appropriate for your specific clinical situation based on your diagnosis, disease severity, and current treatment regimen.
What Should You Know Before Taking Winrevair?
Quick answer: Do not use Winrevair if you are allergic to sotatercept or have repeatedly low platelet counts. Your doctor will monitor your blood regularly. Winrevair is not recommended during pregnancy or breastfeeding.
Contraindications
You must not use Winrevair if you are allergic to sotatercept or any of the other ingredients in this medicine. These include citric acid monohydrate, sodium citrate, polysorbate 80, sucrose, and water for injections. If you have experienced severe allergic reactions to any of these substances, inform your doctor before starting treatment.
Winrevair is also contraindicated if your platelet count has been very low on repeated occasions. Platelets are blood cells that help your blood clot, and persistently low platelet counts significantly increase the risk of serious bleeding. Your doctor will check your platelet levels before initiating therapy, and treatment will not be started if levels are critically low on multiple tests.
Warnings and Precautions
Winrevair can cause several important changes to your blood that require careful monitoring. Before and during treatment, speak with your doctor if you have any of the following conditions:
Winrevair may increase the risk of serious bleeding, especially when taken with certain other medications. Seek immediate medical attention if you experience: persistent headache, nausea, weakness, black or tarry stools, blood in stools, bright red blood when vomiting or coughing, persistent stomach cramps, severe back pain, or abnormally heavy menstrual bleeding.
Elevated hemoglobin levels: Winrevair can increase hemoglobin (a protein in red blood cells that carries oxygen) to above-normal levels. High hemoglobin increases the risk of blood clot formation, which can block blood vessels and lead to serious complications such as stroke, heart attack, or pulmonary embolism. Your doctor will check hemoglobin with regular blood tests before each dose for the first 5 doses (or longer if needed) and periodically throughout treatment.
Low platelet counts (thrombocytopenia): Treatment with Winrevair may reduce the number of platelets in your blood. Low platelet counts can cause you to bruise easily, bleed for a long time from cuts, and experience nosebleeds. Your doctor will monitor platelet counts before each dose for the first 5 doses (or longer if necessary) and regularly during ongoing therapy. If your platelet counts fall too low, your doctor may delay or discontinue treatment.
Pericardial effusion: Accumulation of fluid around the heart has been reported in patients taking Winrevair. While the frequency of this event is not fully established, your doctor will monitor for signs and symptoms of this condition.
Children and Adolescents
Winrevair should not be given to children or adolescents under 18 years of age. The safety and effectiveness of this medicine have not been established in the pediatric population. Clinical trials to date have only included adult patients.
Drug Interactions
Tell your doctor or pharmacist about all medicines you are currently taking, have recently taken, or might take. While no formal drug-drug interaction studies have identified specific problematic combinations, the risk of serious bleeding may be increased when Winrevair is used together with blood-thinning medicines (anticoagulants), antiplatelet agents, or nonsteroidal anti-inflammatory drugs (NSAIDs). Your doctor will carefully consider the overall bleeding risk when prescribing Winrevair alongside such medications.
Pregnancy and Breastfeeding
Winrevair may cause harm to an unborn baby. This medicine is not recommended during pregnancy. Effective contraception is required during treatment and for at least 4 months after the last dose. Contact your doctor immediately if you become pregnant or think you may be pregnant while using this medicine.
Your doctor will perform a pregnancy test before starting Winrevair. You must use effective contraception during treatment and for at least 4 months following your last dose. Discuss suitable contraceptive options with your doctor or pharmacist.
Breastfeeding: It is not known whether Winrevair passes into breast milk. Do not breastfeed during treatment and for at least 4 months after the last dose. Talk to your doctor about the best way to feed your baby during this time.
Fertility: Winrevair may impair fertility in both women and men. If you are planning to have children, discuss this with your doctor before starting treatment.
Driving and Operating Machinery
Winrevair is unlikely to affect your ability to drive or operate machinery. However, PAH itself can cause dizziness and fatigue, so exercise appropriate caution when performing these activities.
Winrevair contains less than 1 mmol (23 mg) sodium per dose, making it essentially sodium-free. It also contains polysorbate 80 (0.20 mg per mL of reconstituted solution), which may cause allergic reactions in sensitive individuals. Inform your doctor if you have any known allergies to these excipients.
What Is the Correct Dosage of Winrevair?
Quick answer: Winrevair is given as a subcutaneous injection every 3 weeks. Treatment starts at 0.3 mg/kg body weight and is increased to 0.7 mg/kg. Your dose is determined by your weight and blood test results.
Always use Winrevair exactly as your doctor, pharmacist, or nurse has instructed. Your dose depends on your body weight and the results of your blood tests. Your doctor will tell you exactly how much Winrevair to take and when to take it. Do not use Winrevair more often than prescribed.
Dosing Schedule
| Phase | Dose | Frequency | Notes |
|---|---|---|---|
| Starting dose | 0.3 mg/kg body weight | Once every 3 weeks | Blood tests required before each dose |
| Target dose | 0.7 mg/kg body weight | Once every 3 weeks | Dose increased based on tolerability |
Blood Monitoring
Your doctor will take blood tests before each dose for the first 5 doses, or longer if necessary, and regularly while you are taking Winrevair. These tests are essential for monitoring your hemoglobin levels and platelet counts, enabling your doctor to find the optimal dose for you. Based on these results, your doctor may adjust your dose, postpone treatment, or discontinue therapy.
How to Administer Winrevair
Winrevair is given as an injection just under the skin (subcutaneously). It is supplied as a powder that must be reconstituted with sterile water before injection. The approved injection sites are:
- Abdomen (stomach area): at least 5 cm (2 inches) from the navel
- Upper thigh
- Upper arm: only when administered by a healthcare professional
Choose a new injection site each time that is not tender, scarred, or bruised. If your doctor decides that you or your caregiver can administer injections at home, proper training in reconstitution and injection technique must be completed first. Do not attempt to inject Winrevair until your doctor has demonstrated the correct method.
Remove the kit from the refrigerator and wait 15 minutes for it to reach room temperature (cold medicine is more painful to inject). Attach the vial adapter, connect the pre-filled syringe of sterile water, and transfer all water into the vial. Gently swirl — do not shake — until fully dissolved (up to 2 minutes). The solution should be clear to opalescent and colorless to slightly brownish-yellow. Use the dosing syringe to draw up your prescribed volume. The final concentration after reconstitution is 50 mg/mL.
Missed Dose
If you miss your scheduled dose and it has been 3 days or fewer since you were supposed to take it, inject it immediately and then continue your original schedule for the next dose. If it has been more than 3 days, your injection schedule will need to be adjusted — contact your doctor or pharmacist for guidance.
Overdose
If you have used too much or too little Winrevair, contact your doctor or pharmacist immediately. Do not change your dose or stop taking Winrevair without consulting your doctor, as abrupt discontinuation may lead to worsening of PAH symptoms.
How Does Winrevair Interact with Other Drugs?
Quick answer: Winrevair may increase bleeding risk when used with anticoagulants, antiplatelet agents, or NSAIDs. Always tell your doctor about all medicines you are taking.
While formal drug-drug interaction studies specific to sotatercept are limited, the pharmacological profile of Winrevair — particularly its effect on platelet counts and hemoglobin levels — means that careful consideration is required when it is used alongside certain other medications. Your doctor will assess the overall risk-benefit balance when prescribing Winrevair in combination with other treatments.
| Drug Class | Examples | Interaction Risk | Clinical Significance |
|---|---|---|---|
| Anticoagulants | Warfarin, heparin, rivaroxaban, apixaban | Increased bleeding risk | Major — close monitoring required |
| Antiplatelet agents | Aspirin, clopidogrel, prasugrel | Increased bleeding risk | Major — use with caution |
| NSAIDs | Ibuprofen, naproxen, diclofenac | Increased bleeding risk | Moderate — avoid prolonged use |
| PAH therapies | Bosentan, ambrisentan, sildenafil, tadalafil, epoprostenol | No clinically significant interaction identified | Used in combination (intended use) |
| Erythropoiesis-stimulating agents | Epoetin alfa, darbepoetin alfa | Additive increase in hemoglobin | Major — hemoglobin monitoring essential |
It is important to note that Winrevair is specifically designed to be used in combination with background PAH therapies such as endothelin receptor antagonists (e.g., bosentan, ambrisentan), phosphodiesterase-5 inhibitors (e.g., sildenafil, tadalafil), and prostacyclin pathway agents. No clinically significant pharmacokinetic interactions have been identified with these standard PAH treatments.
Always inform your doctor about all medicines you are using, including over-the-counter medications, herbal supplements, and vitamins, as these may potentially affect your treatment or increase the risk of adverse effects.
What Are the Side Effects of Winrevair?
Quick answer: The most common side effects include headache, nosebleeds, spider veins, diarrhea, dizziness, rash, bleeding gums, and back pain. Serious effects include low platelet counts and elevated hemoglobin, which require regular blood monitoring.
Like all medicines, Winrevair can cause side effects, although not everyone will experience them. Some side effects are serious and require immediate medical attention, while others are more common and typically manageable. Your doctor will monitor you closely, especially during the initial phase of treatment.
Serious Side Effects
Contact your doctor or pharmacist immediately if you notice any of the following:
- Easy bruising, prolonged bleeding from cuts, or nosebleeds: These may be signs of low platelet counts (thrombocytopenia). Your blood tests will confirm this.
- Elevated hemoglobin levels: Detected through regular blood monitoring. May increase the risk of blood clots.
These serious side effects may affect more than 1 in 10 people treated with Winrevair.
Side Effect Frequency
Very Common
May affect more than 1 in 10 people
- Headache
- Nosebleeds (epistaxis)
- Spider veins or small blood vessels appearing as pink or red lines on the skin (telangiectasia)
- Diarrhea
- Dizziness
- Skin rash
- Bleeding gums
- Back pain
- Thrombocytopenia (low platelet count)
- Elevated hemoglobin levels
Common
May affect up to 1 in 10 people
- High blood pressure (hypertension)
- Skin redness (flushing)
- Itching at the injection site
- Urinary tract infection (kidneys, bladder, or urethra), which may cause lower back or abdominal pain and a burning sensation when urinating
Frequency Not Known
Reported in an unknown number of people
- Pericardial effusion (accumulation of fluid around the heart)
If you experience any side effects, including any not listed above, talk to your doctor, pharmacist, or nurse. You can also report suspected side effects to your national medicines regulatory authority to help continuously monitor the benefit-risk balance of this medicine.
How Should You Store Winrevair?
Quick answer: Store Winrevair in a refrigerator at 2–8 °C (36–46 °F). Do not freeze. Keep in original packaging to protect from light. Once reconstituted, use within 4 hours.
Proper storage of Winrevair is essential to ensure the medicine remains effective and safe for use. Follow these storage guidelines carefully:
- Temperature: Store in a refrigerator at 2–8 °C (36–46 °F). Do not freeze the medicine at any time, as freezing may damage the protein structure of sotatercept and render it ineffective.
- Light protection: Keep in the original packaging to protect from light. Sotatercept is light-sensitive and prolonged exposure to light may degrade the active ingredient.
- After reconstitution: Inject the medicine immediately after mixing the powder with the sterile water, or within a maximum of 4 hours. Discard any unused reconstituted solution after this time.
- Expiration: Do not use after the expiration date printed on the vial and carton (marked “EXP”). The expiration date refers to the last day of the indicated month.
- Keep out of reach: Store this medicine out of the sight and reach of children and pets.
- Disposal: Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. These measures help protect the environment.
Remove the kit from the refrigerator 15 minutes before preparation to allow it to reach room temperature. Cold medicine is more painful to inject. Do not use any other method to warm the medicine (such as a microwave or hot water).
What Does Winrevair Contain?
Quick answer: Each vial contains either 45 mg or 60 mg of sotatercept. After reconstitution, the solution contains 50 mg/mL. Inactive ingredients include citric acid, sodium citrate, polysorbate 80, and sucrose.
Active Ingredient
The active substance is sotatercept. Each vial contains either 45 mg or 60 mg of sotatercept as a lyophilized (freeze-dried) powder. After reconstitution with the provided sterile water for injections, the final concentration is 50 mg/mL.
Inactive Ingredients
The other ingredients are:
- In the powder: Citric acid monohydrate (E330), sodium citrate (E331), polysorbate 80 (E433), and sucrose
- In the solvent: Water for injections
Appearance and Pack Sizes
Winrevair consists of a white to off-white powder in a glass vial and a clear, colorless solvent (sterile water) in a pre-filled syringe. It is available in the following presentations:
| Strength | Solvent Volume | Deliverable Volume | Pack Contents |
|---|---|---|---|
| 45 mg (1-vial kit) | 1.0 mL | Up to 0.9 mL | 1 vial, 1 pre-filled syringe, 1 vial adapter, 1 dosing syringe, 1 needle, 4 alcohol swabs |
| 45 mg (2-vial kit) | 1.0 mL each | Up to 0.9 mL each | 2 vials, 2 pre-filled syringes, 2 vial adapters, 1 dosing syringe, 1 needle, 8 alcohol swabs |
| 60 mg (1-vial kit) | 1.3 mL | Up to 1.2 mL | 1 vial, 1 pre-filled syringe, 1 vial adapter, 1 dosing syringe, 1 needle, 4 alcohol swabs |
| 60 mg (2-vial kit) | 1.3 mL each | Up to 1.2 mL each | 2 vials, 2 pre-filled syringes, 2 vial adapters, 1 dosing syringe, 1 needle, 8 alcohol swabs |
The marketing authorization holder and manufacturer is Merck Sharp & Dohme B.V., Waarderweg 39, 2031 BN Haarlem, Netherlands. For further information, contact the local representative of the marketing authorization holder in your country.
Frequently Asked Questions About Winrevair
Winrevair (sotatercept) is used in combination with other medicines to treat pulmonary arterial hypertension (PAH) in adults. PAH is a type of high blood pressure in the blood vessels leading from the heart to the lungs. By targeting the underlying vascular remodeling process, Winrevair helps make it easier for the heart to pump blood to the lungs, slows disease progression, and can improve exercise capacity and reduce the need for hospitalization or lung transplantation.
Winrevair is given as a subcutaneous injection (under the skin) once every three weeks. It is supplied as a powder that must be mixed with sterile water before injection. Injection sites include the abdomen (at least 5 cm from the navel) or upper thigh. Healthcare providers may also use the upper arm. Treatment starts at 0.3 mg/kg body weight and is gradually increased to 0.7 mg/kg. You or your caregiver can be trained to administer injections at home.
Your doctor will perform blood tests to monitor hemoglobin levels and platelet counts before each dose for the first 5 doses (or longer if necessary) and regularly during ongoing treatment. Elevated hemoglobin increases the risk of blood clots, while low platelet counts increase the risk of bleeding. Based on these results, your doctor may adjust your dose, postpone treatment, or discontinue therapy entirely.
No. Winrevair is not recommended during pregnancy as it may harm the unborn baby. A pregnancy test should be performed before starting treatment. You must use effective contraception during treatment and for at least 4 months after the last dose. If you become pregnant or think you may be pregnant while using Winrevair, contact your doctor immediately. Breastfeeding is also not recommended during treatment and for at least 4 months after the last dose.
If you miss your scheduled dose and it has been 3 days or fewer since your missed dose, take it immediately and continue your original schedule for the next dose. If more than 3 days have passed, your injection schedule will need to be adjusted — contact your doctor or pharmacist for advice. Do not take a double dose to make up for a missed one, and do not stop using Winrevair without consulting your doctor.
Store Winrevair in a refrigerator at 2–8 °C (36–46 °F). Do not freeze. Keep in the original packaging to protect from light. Remove the kit from the refrigerator 15 minutes before use to reach room temperature. Once reconstituted (mixed), inject immediately or within 4 hours. Discard any unused reconstituted solution after 4 hours. Do not use after the expiration date on the vial and carton.
References
This article is based on the following peer-reviewed sources and official regulatory documents:
- European Medicines Agency (EMA). Winrevair (sotatercept) – Summary of Product Characteristics. EMA/CHMP. 2024. Available at: www.ema.europa.eu
- Hoeper MM, Badesch DB, Ghofrani HA, et al. Phase 3 Trial of Sotatercept for Treatment of Pulmonary Arterial Hypertension (STELLAR). New England Journal of Medicine. 2023;388(16):1478-1490. doi:10.1056/NEJMoa2213558
- Humbert M, Kovacs G, Hoeper MM, et al. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. European Heart Journal. 2022;43(38):3618-3731. doi:10.1093/eurheartj/ehac237
- U.S. Food and Drug Administration (FDA). Winrevair Prescribing Information. March 2024. Available at: www.fda.gov
- World Health Organization (WHO). Pulmonary Hypertension Fact Sheet. 2023. Available at: www.who.int
- Galiè N, Humbert M, Vachiery JL, et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. European Heart Journal. 2016;37(1):67-119.
- Sitbon O, Gomberg-Maitland M, Granton J, et al. Clinical trial design and new therapies for pulmonary arterial hypertension. European Respiratory Journal. 2019;53(1):1801908.
About Our Medical Editorial Team
This article has been written and reviewed by the iMedic Medical Editorial Team, comprising board-certified physicians with expertise in pulmonology, cardiology, and clinical pharmacology. Our team follows the GRADE evidence framework and adheres to international guidelines from the European Society of Cardiology (ESC), European Respiratory Society (ERS), and the World Health Organization (WHO).
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