Winrevair 60mg Inj Kit (2 Vials)
It is used to treat high blood pressure in the lungs.
Drug Class
Pulmonary Hypertension Agent
Pharmacologic Class
Activin Signaling Inhibitor; Ligand Trap
Pregnancy Category
Not assigned (Risk Summary available)
FDA Approved
Feb 2024
DEA Schedule
Not Controlled
Overview
What is this medicine?
Winrevair is an injectable medicine used to treat a rare lung condition called pulmonary arterial hypertension (PAH). It works by helping to improve the health of the blood vessels in your lungs, making it easier for your heart to pump blood and improving your ability to exercise.
How to Use This Medicine
Proper Administration of This Medication
To ensure safe and effective use, follow your doctor's instructions carefully. Read all provided information and adhere to the guidelines below.
This medication is administered via injection into the fatty tissue of the skin, typically on the top of the thigh or in the belly area. If you will be self-administering the injection, your doctor or nurse will provide personalized instruction on the proper technique.
Before use, wash your hands thoroughly. This medication requires mixing prior to administration. Follow the mixing instructions provided by your doctor.
To prepare the medication, allow the vial to reach room temperature by leaving it at room temperature for 15 minutes. Do not heat the medication. When mixing, avoid shaking the vial. Allow the vial to sit for up to 3 minutes to enable any large bubbles to dissipate.
Inspect the medication visually before use. The solution should be clear to slightly pearly in appearance. Do not use the medication if you notice any clumps, powder, particles, or large bubbles. The medication is colorless to slightly yellow or slightly brown in color. If you observe any change in color, do not use the medication.
Use the mixed medication within 4 hours of preparation. To minimize the risk of skin irritation, rotate the injection site with each administration. Avoid injecting into skin that is tender, damaged, bruised, sore, or exhibits red patches. Additionally, do not inject within 2 inches (5 cm) of the belly button.
Safe Disposal of Needles and Sharps
Dispose of used needles and sharps in a designated needle/sharp disposal box. Do not reuse needles or other items. When the disposal box is full, follow local regulations for proper disposal. If you have any questions or concerns, consult your doctor or pharmacist.
Storage and Disposal of This Medication
Store the medication in a refrigerator to maintain its potency. Do not freeze the medication. To protect the medication from light, store it in the original outer carton.
Missed Dose Instructions
If you miss a dose, take it as soon as you remember and resume your regular administration schedule. If you miss a dose by more than 3 days, consult your doctor for guidance on how to proceed.
To ensure safe and effective use, follow your doctor's instructions carefully. Read all provided information and adhere to the guidelines below.
This medication is administered via injection into the fatty tissue of the skin, typically on the top of the thigh or in the belly area. If you will be self-administering the injection, your doctor or nurse will provide personalized instruction on the proper technique.
Before use, wash your hands thoroughly. This medication requires mixing prior to administration. Follow the mixing instructions provided by your doctor.
To prepare the medication, allow the vial to reach room temperature by leaving it at room temperature for 15 minutes. Do not heat the medication. When mixing, avoid shaking the vial. Allow the vial to sit for up to 3 minutes to enable any large bubbles to dissipate.
Inspect the medication visually before use. The solution should be clear to slightly pearly in appearance. Do not use the medication if you notice any clumps, powder, particles, or large bubbles. The medication is colorless to slightly yellow or slightly brown in color. If you observe any change in color, do not use the medication.
Use the mixed medication within 4 hours of preparation. To minimize the risk of skin irritation, rotate the injection site with each administration. Avoid injecting into skin that is tender, damaged, bruised, sore, or exhibits red patches. Additionally, do not inject within 2 inches (5 cm) of the belly button.
Safe Disposal of Needles and Sharps
Dispose of used needles and sharps in a designated needle/sharp disposal box. Do not reuse needles or other items. When the disposal box is full, follow local regulations for proper disposal. If you have any questions or concerns, consult your doctor or pharmacist.
Storage and Disposal of This Medication
Store the medication in a refrigerator to maintain its potency. Do not freeze the medication. To protect the medication from light, store it in the original outer carton.
Missed Dose Instructions
If you miss a dose, take it as soon as you remember and resume your regular administration schedule. If you miss a dose by more than 3 days, consult your doctor for guidance on how to proceed.
Lifestyle & Tips
- Administer the injection exactly as prescribed by your doctor, typically every 3 weeks.
- Do not stop taking other PAH medications unless instructed by your doctor.
- Report any new or worsening symptoms to your healthcare provider promptly.
- Females of reproductive potential should use effective contraception during treatment and for at least 4 months after the last dose.
- Attend all scheduled blood tests and doctor appointments to monitor for side effects.
Available Forms & Alternatives
Dosing & Administration
Adult Dosing
Standard Dose:
Initial: 0.3 mg/kg subcutaneously every 3 weeks for 3 doses. Titration: If tolerated, increase to 0.7 mg/kg subcutaneously every 3 weeks. Max single dose: 120 mg.
Dose Range:
0.3 - 0.7 mg
Condition-Specific Dosing:
Pulmonary Arterial Hypertension (PAH):
Initial: 0.3 mg/kg SC every 3 weeks for 3 doses. Titration: If tolerated, increase to 0.7 mg/kg SC every 3 weeks. Max single dose: 120 mg.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established
Adolescent:
Not established
Dose Adjustments
Renal Impairment:
Mild:
No dose adjustment recommended.
Moderate:
No dose adjustment recommended.
Severe:
Not studied. Use with caution.
Dialysis:
Not studied. Use with caution.
Hepatic Impairment:
Mild:
No dose adjustment recommended.
Moderate:
No dose adjustment recommended.
Severe:
Not studied. Use with caution.
Pharmacology
Mechanism of Action
Sotatercept is a first-in-class activin receptor type IIA (ActRIIA)-Fc fusion protein. It acts as a ligand trap for members of the transforming growth factor (TGF)-beta superfamily, including activins and growth differentiation factors (GDFs), which are implicated in the pathogenesis of pulmonary arterial hypertension (PAH). By binding these ligands, sotatercept rebalances BMPR-II (bone morphogenetic protein receptor type II) signaling, which is often dysregulated in PAH. This leads to antiproliferative, anti-remodeling, and pro-apoptotic effects on pulmonary vascular cells, reducing pulmonary vascular resistance and improving exercise capacity.
Pharmacokinetics
Absorption:
Bioavailability:
63%
Tmax:
Median 7 days (after single SC dose)
FoodEffect:
Not applicable (parenteral administration)
Distribution:
Vd:
Central: 4.5 L; Peripheral: 2.9 L
ProteinBinding:
Not applicable (fusion protein)
CnssPenetration:
Limited (large protein)
Elimination:
HalfLife:
Mean 27 days
Clearance:
0.19 L/day (population mean)
ExcretionRoute:
Not specifically studied; likely via reticuloendothelial system (typical for biologics)
Unchanged:
Not applicable (biologic)
Pharmacodynamics
OnsetOfAction:
Not precisely defined; clinical effects observed within weeks to months.
PeakEffect:
Not precisely defined; sustained effects with chronic dosing.
DurationOfAction:
Approximately 3 weeks (based on dosing interval and half-life)
Safety & Warnings
Side Effects
Urgent Side Effects: Seek Medical Help Right Away
While rare, some people may experience severe and potentially life-threatening side effects when taking this medication. If you notice any of the following symptoms, contact your doctor or seek immediate medical attention:
Signs of an allergic reaction, such as:
+ Rash or hives
+ Itching or red, swollen, blistered, or peeling skin (with or without fever)
+ Wheezing or tightness in the chest or throat
+ Difficulty breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Signs of bleeding, including:
+ Vomiting or coughing up blood
+ Vomit that resembles coffee grounds
+ Blood in the urine
+ Black, red, or tarry stools
+ Bleeding from the gums
+ Abnormal vaginal bleeding
+ Unexplained bruises or bruises that increase in size
+ Uncontrollable bleeding
Neurological symptoms, such as:
+ Weakness on one side of the body
+ Difficulty speaking or thinking
+ Changes in balance
+ Drooping on one side of the face
+ Blurred vision
High levels of hemoglobin, which may increase the risk of blood clots. Seek medical help if you experience:
+ Chest pain or pressure
+ Coughing up blood
+ Shortness of breath
+ Swelling, warmth, numbness, color changes, or pain in a leg or arm
+ Difficulty speaking or swallowing
Other Possible Side Effects
Most people do not experience significant side effects, but some may occur. If you notice any of the following side effects or any other unusual symptoms, contact your doctor or seek medical help if they bother you or persist:
Dizziness or headache
Nosebleed
Spider veins (visible blood vessels on the skin that appear pink or red)
Diarrhea
* Redness
This is not an exhaustive list of potential side effects. If you have questions or concerns about side effects, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
While rare, some people may experience severe and potentially life-threatening side effects when taking this medication. If you notice any of the following symptoms, contact your doctor or seek immediate medical attention:
Signs of an allergic reaction, such as:
+ Rash or hives
+ Itching or red, swollen, blistered, or peeling skin (with or without fever)
+ Wheezing or tightness in the chest or throat
+ Difficulty breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Signs of bleeding, including:
+ Vomiting or coughing up blood
+ Vomit that resembles coffee grounds
+ Blood in the urine
+ Black, red, or tarry stools
+ Bleeding from the gums
+ Abnormal vaginal bleeding
+ Unexplained bruises or bruises that increase in size
+ Uncontrollable bleeding
Neurological symptoms, such as:
+ Weakness on one side of the body
+ Difficulty speaking or thinking
+ Changes in balance
+ Drooping on one side of the face
+ Blurred vision
High levels of hemoglobin, which may increase the risk of blood clots. Seek medical help if you experience:
+ Chest pain or pressure
+ Coughing up blood
+ Shortness of breath
+ Swelling, warmth, numbness, color changes, or pain in a leg or arm
+ Difficulty speaking or swallowing
Other Possible Side Effects
Most people do not experience significant side effects, but some may occur. If you notice any of the following side effects or any other unusual symptoms, contact your doctor or seek medical help if they bother you or persist:
Dizziness or headache
Nosebleed
Spider veins (visible blood vessels on the skin that appear pink or red)
Diarrhea
* Redness
This is not an exhaustive list of potential side effects. If you have questions or concerns about side effects, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Signs of increased red blood cells (erythrocytosis): headache, dizziness, blurred vision, shortness of breath.
- Signs of low platelets (thrombocytopenia): easy bruising, unusual bleeding (e.g., nosebleeds, bleeding gums, prolonged bleeding from cuts).
- Signs of high blood pressure: severe headache, blurred vision, chest pain, confusion.
- Signs of liver problems: yellowing of skin or eyes (jaundice), dark urine, severe stomach pain, nausea, vomiting.
- Worsening shortness of breath, swelling in legs/ankles, or other signs of PAH progression.
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances. Be sure to describe the allergic reaction and its symptoms.
Certain health conditions, such as bleeding problems or a low platelet count.
If you are breastfeeding or plan to breastfeed. Note that you should not breastfeed while taking this medication or for 4 months after your last dose.
This medication may interact with other medications or health conditions. Therefore, it is crucial to provide your doctor and pharmacist with a comprehensive list of:
All prescription and over-the-counter medications you are taking
Any natural products or vitamins you are using
Your health problems, including any medical conditions or concerns
Before starting, stopping, or changing the dose of any medication, including this one, consult with your doctor to ensure your safety. It is your responsibility to verify that it is safe to take this medication with all your other medications and health conditions.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances. Be sure to describe the allergic reaction and its symptoms.
Certain health conditions, such as bleeding problems or a low platelet count.
If you are breastfeeding or plan to breastfeed. Note that you should not breastfeed while taking this medication or for 4 months after your last dose.
This medication may interact with other medications or health conditions. Therefore, it is crucial to provide your doctor and pharmacist with a comprehensive list of:
All prescription and over-the-counter medications you are taking
Any natural products or vitamins you are using
Your health problems, including any medical conditions or concerns
Before starting, stopping, or changing the dose of any medication, including this one, consult with your doctor to ensure your safety. It is your responsibility to verify that it is safe to take this medication with all your other medications and health conditions.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication. Regular blood work and laboratory tests, as directed by your doctor, are crucial to monitor your condition.
As this medication may increase your risk of bleeding, it is vital to take precautions to avoid injury. To minimize this risk, use a soft-bristled toothbrush and an electric razor for shaving. Be cautious in your daily activities to prevent cuts and bruises.
If you experience any changes in your weight, consult your doctor, as your dosage may need to be adjusted. Elderly patients (65 years or older) should exercise extra caution when taking this medication, as the risk of bleeding may be higher in this age group.
This medication may affect fertility, potentially leading to difficulties in becoming pregnant or fathering a child. If you plan to conceive, discuss this with your doctor before initiating treatment.
Additionally, this medication can harm an unborn baby. To confirm you are not pregnant, a pregnancy test may be required before starting the medication. If you are of childbearing potential, it is essential to use effective birth control methods while taking this medication and for a specified period after the last dose. Your doctor will advise you on the duration of birth control use. If you become pregnant during or after treatment, notify your doctor immediately.
As this medication may increase your risk of bleeding, it is vital to take precautions to avoid injury. To minimize this risk, use a soft-bristled toothbrush and an electric razor for shaving. Be cautious in your daily activities to prevent cuts and bruises.
If you experience any changes in your weight, consult your doctor, as your dosage may need to be adjusted. Elderly patients (65 years or older) should exercise extra caution when taking this medication, as the risk of bleeding may be higher in this age group.
This medication may affect fertility, potentially leading to difficulties in becoming pregnant or fathering a child. If you plan to conceive, discuss this with your doctor before initiating treatment.
Additionally, this medication can harm an unborn baby. To confirm you are not pregnant, a pregnancy test may be required before starting the medication. If you are of childbearing potential, it is essential to use effective birth control methods while taking this medication and for a specified period after the last dose. Your doctor will advise you on the duration of birth control use. If you become pregnant during or after treatment, notify your doctor immediately.
Overdose Information
Overdose Symptoms:
- Symptoms of overdose are not well-established. Higher doses may increase the risk and severity of known adverse reactions such as erythrocytosis, thrombocytopenia, and hypertension.
What to Do:
In case of suspected overdose, seek immediate medical attention or call a poison control center (1-800-222-1222). Management should be supportive and directed at treating symptoms.
Drug Interactions
Monitoring
Baseline Monitoring
Hemoglobin
Rationale: To assess for erythrocytosis (increased red blood cell count), a common adverse reaction.
Timing: Prior to initiation of treatment.
Platelet count
Rationale: To assess for thrombocytopenia (decreased platelet count), an adverse reaction.
Timing: Prior to initiation of treatment.
Blood Pressure
Rationale: To assess for systemic hypertension, an adverse reaction.
Timing: Prior to initiation of treatment.
Liver Function Tests (LFTs)
Rationale: To assess for potential hepatic adverse reactions.
Timing: Prior to initiation of treatment.
Routine Monitoring
Hemoglobin
Frequency: Prior to each dose for the first 5 doses, then periodically (e.g., every 3 months) or as clinically indicated.
Target: Normal range; monitor for increases.
Action Threshold: If hemoglobin >16 g/dL (females) or >17 g/dL (males), consider dose reduction or temporary interruption. If >18 g/dL (females) or >19 g/dL (males), consider phlebotomy.
Platelet count
Frequency: Prior to each dose for the first 5 doses, then periodically (e.g., every 3 months) or as clinically indicated.
Target: Normal range; monitor for decreases.
Action Threshold: If platelet count <50 x 10^9/L, consider dose reduction or temporary interruption.
Blood Pressure
Frequency: Prior to each dose, then periodically or as clinically indicated.
Target: Normal range; monitor for increases.
Action Threshold: Manage hypertension according to clinical guidelines.
Signs/Symptoms of PAH progression
Frequency: Regularly at clinical visits.
Target: Stable or improved functional class, exercise capacity.
Action Threshold: Worsening symptoms may indicate need for re-evaluation of treatment.
Symptom Monitoring
- Dyspnea (shortness of breath)
- Fatigue
- Edema (swelling, especially in legs/ankles)
- Chest pain
- Syncope (fainting)
- Epistaxis (nosebleeds)
- Telangiectasia (spider veins)
- Headache
- Dizziness
Special Patient Groups
Pregnancy
WINREVAIRe may cause fetal harm when administered to a pregnant woman based on animal reproduction studies. Advise pregnant women of the potential risk to the fetus. For females of reproductive potential, use effective contraception during treatment and for at least 4 months after the last dose.
Trimester-Specific Risks:
First Trimester:
Potential for fetal harm based on animal data; human data lacking.
Second Trimester:
Potential for fetal harm based on animal data; human data lacking.
Third Trimester:
Potential for fetal harm based on animal data; human data lacking.
Lactation
There are no data on the presence of sotatercept in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for WINREVAIRe and any potential adverse effects on the breastfed infant from WINREVAIRe or from the underlying maternal condition.
Infant Risk:
Not available; potential unknown risk.
Pediatric Use
Safety and effectiveness in pediatric patients have not been established. Not indicated for pediatric use.
Geriatric Use
No overall differences in safety or effectiveness were observed between elderly (≥65 years) and younger patients. No dose adjustment is required based on age, but monitor for age-related comorbidities.
Clinical Information
Clinical Pearls
- Sotatercept is a novel, first-in-class agent for PAH, targeting the activin signaling pathway, which is distinct from other approved PAH therapies.
- It is administered subcutaneously every 3 weeks, which may improve patient adherence compared to daily oral medications.
- Close monitoring of hemoglobin and platelet counts is crucial due to the risk of erythrocytosis and thrombocytopenia.
- Patients should be educated on the signs and symptoms of erythrocytosis (e.g., headache, dizziness, blurred vision) and thrombocytopenia (e.g., easy bruising, bleeding).
- Sotatercept is intended to be added to existing PAH background therapy, not as monotherapy.
- Due to its long half-life, effects and potential adverse reactions may persist for several weeks after discontinuation.
Alternative Therapies
- Endothelin Receptor Antagonists (ERAs): Ambrisentan, Bosentan, Macitentan
- Phosphodiesterase-5 (PDE5) Inhibitors: Sildenafil, Tadalafil
- Soluble Guanylate Cyclase (sGC) Stimulators: Riociguat
- Prostacyclin Pathway Agents: Epoprostenol, Iloprost, Treprostinil, Selexipag
Cost & Coverage
Average Cost:
Highly variable, typically >$10,000 per vial/dose per vial
Insurance Coverage:
Specialty Tier; requires prior authorization and often step therapy for PAH.
General Drug Facts
If your symptoms or health issues persist or worsen, it is essential to contact your doctor promptly. To ensure safe and effective treatment, never share your medication with others or take someone else's medication. Some medications may come with an additional patient information leaflet, so it's a good idea to check with your pharmacist for more information. If you have any questions or concerns about this medication, don't hesitate to discuss them with your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. When seeking help, be prepared to provide details about the overdose, including the medication taken, the amount, and the time it occurred.