Winrevair 45mg Inj Kit (1 Vial)
It is used to treat high blood pressure in the lungs.
Drug Class
Pulmonary Hypertension Agent
Pharmacologic Class
Activin Receptor Type IIA (ActRIIA) Fc Fusion Protein
Pregnancy Category
Not available
FDA Approved
Mar 2024
DEA Schedule
Not Controlled
Overview
What is this medicine?
Winrevair (sotatercept) is an injectable medicine used to treat a serious lung condition called pulmonary arterial hypertension (PAH). It works by helping to rebalance certain signals in the blood vessels of your lungs, which can reduce the pressure in these vessels and make it easier for your heart to pump blood. This can improve your ability to exercise and reduce the risk of your condition worsening.
How to Use This Medicine
Proper Administration of This Medication
To ensure safe and effective use, follow your doctor's instructions and read all accompanying information carefully. This medication is administered via injection into the fatty tissue of the skin, typically on the top of the thigh or in the abdominal area. If you will be self-administering the injection, your doctor or nurse will provide guidance on the proper technique.
Preparation and Administration
1. Wash your hands before handling the medication.
2. The medication must be mixed before use. Follow the mixing instructions provided by your doctor.
3. Allow the medication to reach room temperature by leaving it at room temperature for 15 minutes. Do not heat the medication.
4. When preparing the medication, do not shake the vial.
5. Let the vial sit for up to 3 minutes to allow any large bubbles to dissipate.
6. Inspect the solution for clarity and color. The medication should be clear to slightly pearly and colorless to slightly yellow or slightly brown. Do not use the medication if it contains clumps, powder, particles, or large bubbles, or if the color has changed.
7. Use the medication within 4 hours of preparation.
8. Rotate the injection site with each dose to avoid tissue damage.
9. Avoid injecting into skin that is tender, damaged, bruised, sore, or has red patches.
10. Do not inject within 2 inches (5 cm) of the belly button.
11. Dispose of needles and other sharp objects in a designated disposal box. Do not reuse needles or other items. Follow local regulations for disposing of the box when it is full.
Storage and Disposal
Store the medication in a refrigerator at a temperature between 2°C and 8°C (36°F and 46°F). Do not freeze. Keep the medication in its original carton to protect it from light.
Missed Dose
If you miss a dose, take it as soon as you remember and resume your regular 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 and read all accompanying information carefully. This medication is administered via injection into the fatty tissue of the skin, typically on the top of the thigh or in the abdominal area. If you will be self-administering the injection, your doctor or nurse will provide guidance on the proper technique.
Preparation and Administration
1. Wash your hands before handling the medication.
2. The medication must be mixed before use. Follow the mixing instructions provided by your doctor.
3. Allow the medication to reach room temperature by leaving it at room temperature for 15 minutes. Do not heat the medication.
4. When preparing the medication, do not shake the vial.
5. Let the vial sit for up to 3 minutes to allow any large bubbles to dissipate.
6. Inspect the solution for clarity and color. The medication should be clear to slightly pearly and colorless to slightly yellow or slightly brown. Do not use the medication if it contains clumps, powder, particles, or large bubbles, or if the color has changed.
7. Use the medication within 4 hours of preparation.
8. Rotate the injection site with each dose to avoid tissue damage.
9. Avoid injecting into skin that is tender, damaged, bruised, sore, or has red patches.
10. Do not inject within 2 inches (5 cm) of the belly button.
11. Dispose of needles and other sharp objects in a designated disposal box. Do not reuse needles or other items. Follow local regulations for disposing of the box when it is full.
Storage and Disposal
Store the medication in a refrigerator at a temperature between 2°C and 8°C (36°F and 46°F). Do not freeze. Keep the medication in its original carton to protect it from light.
Missed Dose
If you miss a dose, take it as soon as you remember and resume your regular schedule. If you miss a dose by more than 3 days, consult your doctor for guidance on how to proceed.
Lifestyle & Tips
- Adhere strictly to the prescribed dosing schedule (every 3 weeks).
- Maintain regular follow-up appointments and blood tests as advised by your doctor.
- Continue with other prescribed PAH medications unless otherwise instructed.
- Report any new or worsening symptoms promptly to your healthcare provider.
- For females of reproductive potential, use effective contraception during treatment and for at least 4 months after the last dose.
- Avoid smoking and excessive alcohol consumption.
- Follow any dietary or fluid restrictions recommended by your doctor.
Available Forms & Alternatives
Dosing & Administration
Adult Dosing
Standard Dose:
Initial: 0.3 mg/kg subcutaneously every 3 weeks. May increase to 0.7 mg/kg subcutaneously every 3 weeks if tolerated and additional clinical benefit is needed.
Dose Range:
0.3 - 0.7 mg
Condition-Specific Dosing:
Pulmonary Arterial Hypertension (PAH):
0.3 mg/kg SC every 3 weeks, titrate to 0.7 mg/kg SC every 3 weeks based on tolerability and clinical response.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established
Adolescent:
Not established
Dose Adjustments
Renal Impairment:
Mild:
No dose adjustment needed
Moderate:
No dose adjustment needed
Severe:
No dose adjustment needed
Dialysis:
Not studied; use with caution
Hepatic Impairment:
Mild:
No dose adjustment needed
Moderate:
No dose adjustment needed
Severe:
Not studied; use with caution
Pharmacology
Mechanism of Action
Sotatercept is a recombinant fusion protein that acts as an activin receptor type IIA (ActRIIA) Fc fusion protein. It traps activins and growth differentiation factors (GDFs), which are ligands in the transforming growth factor-beta (TGF-β) superfamily. By binding to these ligands, sotatercept rebalances pro-proliferative and anti-proliferative signaling pathways in pulmonary arterial smooth muscle cells, leading to antiproliferative, anti-remodeling, and anti-inflammatory effects in the pulmonary vasculature. This ultimately reduces pulmonary vascular resistance and improves hemodynamics in patients with pulmonary arterial hypertension (PAH).
Pharmacokinetics
Absorption:
Bioavailability:
Not precisely quantified for SC administration of a biologic, but well absorbed.
Tmax:
Approximately 7 days
FoodEffect:
Not applicable (parenteral administration)
Distribution:
Vd:
Approximately 4.7 L
ProteinBinding:
Not applicable (biologic)
CnssPenetration:
Limited/No (large protein)
Elimination:
HalfLife:
Approximately 27 days
Clearance:
Approximately 0.12 L/day
ExcretionRoute:
Catabolism
Unchanged:
Not applicable (biologic)
Pharmacodynamics
OnsetOfAction:
Gradual (weeks to months)
PeakEffect:
Gradual (weeks to months)
DurationOfAction:
Prolonged (due to long half-life, allowing every 3-week dosing)
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 experience any of the following symptoms, contact your doctor or seek medical attention immediately:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble 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 enlarge
+ 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
Like all medications, this drug can cause side effects. Many people experience no side effects or only mild ones. If you experience any of the following side effects, or if they bother you or persist, contact your doctor or seek medical attention:
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 possible 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 experience any of the following symptoms, contact your doctor or seek medical attention immediately:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble 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 enlarge
+ 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
Like all medications, this drug can cause side effects. Many people experience no side effects or only mild ones. If you experience any of the following side effects, or if they bother you or persist, contact your doctor or seek medical attention:
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 possible 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:
- Headache, dizziness, blurred vision, or unusual fatigue (signs of high red blood cell count/erythrocytosis)
- Easy bruising, unusual bleeding (e.g., nosebleeds, gum bleeding), or pinpoint red spots on skin (signs of low platelet count/thrombocytopenia)
- Yellowing of skin or eyes (jaundice), dark urine, unexplained nausea, vomiting, or abdominal pain (signs of liver problems)
- Increased shortness of breath, swelling in legs/ankles, or chest pain (signs of worsening PAH)
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 complete medical history, including any health problems
Before starting, stopping, or changing the dose of any medication, including this one, consult with your doctor to ensure your safety.
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 complete medical history, including any health problems
Before starting, stopping, or changing the dose of any medication, including this one, consult with your doctor to ensure your safety.
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. If you experience any changes in weight, consult your doctor, as your dosage may need to be adjusted.
If you are 65 years or older, exercise caution when taking this medication, as the risk of bleeding may be higher in this age group.
This medication may also 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 cause harm to an unborn baby. To confirm you are not pregnant, a pregnancy test may be required before starting the medication. If you may become pregnant, it is essential to use birth control during treatment and for a specified period after the last dose, as advised by your doctor. If you do become pregnant while taking this medication, 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. If you experience any changes in weight, consult your doctor, as your dosage may need to be adjusted.
If you are 65 years or older, exercise caution when taking this medication, as the risk of bleeding may be higher in this age group.
This medication may also 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 cause harm to an unborn baby. To confirm you are not pregnant, a pregnancy test may be required before starting the medication. If you may become pregnant, it is essential to use birth control during treatment and for a specified period after the last dose, as advised by your doctor. If you do become pregnant while taking this medication, notify your doctor immediately.
Overdose Information
Overdose Symptoms:
- Symptoms of overdose are not well-characterized. High doses may exacerbate known adverse effects such as erythrocytosis or thrombocytopenia.
What to Do:
In case of suspected overdose, seek immediate medical attention. Management should be supportive and directed at treating symptoms. Call 1-800-222-1222 (Poison Control Center) for further guidance.
Drug Interactions
Monitoring
Baseline Monitoring
Liver Function Tests (ALT, AST, bilirubin)
Rationale: To establish baseline and monitor for potential hepatotoxicity.
Timing: Prior to initiation
Hemoglobin and Platelet Count
Rationale: To establish baseline and monitor for erythrocytosis and thrombocytopenia.
Timing: Prior to initiation
Pregnancy Test
Rationale: Sotatercept may cause embryo-fetal toxicity. For females of reproductive potential.
Timing: Prior to initiation
PAH Clinical Assessment (e.g., 6-minute walk distance, WHO functional class, hemodynamics)
Rationale: To establish baseline disease severity and assess treatment response.
Timing: Prior to initiation
Routine Monitoring
Hemoglobin and Platelet Count
Frequency: Prior to each dose for the first 5 doses, then periodically (e.g., every 3 months) thereafter.
Target: Maintain within normal limits or manage per clinical guidelines.
Action Threshold: For hemoglobin >16.5 g/dL (females) or >17.5 g/dL (males), consider dose reduction or therapeutic phlebotomy. For significant thrombocytopenia, consider dose interruption or reduction.
Liver Function Tests (ALT, AST, bilirubin)
Frequency: Periodically (e.g., every 3 months) or as clinically indicated.
Target: Maintain within normal limits.
Action Threshold: Elevations >3x ULN may require dose interruption or discontinuation.
PAH Clinical Assessment (e.g., 6-minute walk distance, WHO functional class, symptoms)
Frequency: Periodically (e.g., every 3-6 months) or as clinically indicated.
Target: Improvement or stabilization of PAH symptoms and functional capacity.
Action Threshold: Worsening symptoms or functional class may indicate need for re-evaluation of treatment.
Symptom Monitoring
- Signs of erythrocytosis (e.g., headache, dizziness, blurred vision, fatigue, plethora)
- Signs of bleeding or bruising (e.g., petechiae, epistaxis, gastrointestinal bleeding)
- Signs of liver injury (e.g., unexplained nausea, vomiting, abdominal pain, dark urine, jaundice)
- Signs of worsening PAH (e.g., increased dyspnea, fatigue, edema, syncope)
Special Patient Groups
Pregnancy
Sotatercept may cause embryo-fetal toxicity based on animal studies. Activin signaling is critical for embryonic and fetal development. Use during pregnancy is not recommended unless the potential benefit justifies the potential risk to the fetus. Females of reproductive potential should use effective contraception during treatment and for at least 4 months after the last dose.
Trimester-Specific Risks:
First Trimester:
Potential for major congenital malformations and early embryonic death based on animal data.
Second Trimester:
Potential for adverse developmental effects.
Third Trimester:
Potential for adverse developmental effects.
Lactation
It is unknown if sotatercept is excreted in human milk. Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended during treatment with sotatercept and for at least 4 months after the last dose.
Infant Risk:
Potential for serious adverse reactions (e.g., effects on growth and development due to its mechanism of action).
Pediatric Use
Safety and effectiveness in pediatric patients have not been established. Use is not recommended.
Geriatric Use
No overall differences in safety or effectiveness were observed between elderly patients (âĨ65 years) and younger patients. No specific dose adjustment is required based on age, but monitor for age-related comorbidities and potential for increased sensitivity to adverse effects.
Clinical Information
Clinical Pearls
- Sotatercept is a first-in-class activin signaling inhibitor for PAH, representing a novel therapeutic approach.
- It is administered subcutaneously every 3 weeks, which can improve patient adherence compared to daily oral medications.
- Requires careful monitoring for erythrocytosis (high red blood cell count) and thrombocytopenia (low platelet count) due to its mechanism of action.
- It is used in combination with other PAH therapies, not as monotherapy.
- Patients should be educated on the importance of contraception due to potential embryo-fetal toxicity.
Alternative Therapies
- Phosphodiesterase-5 (PDE5) inhibitors (e.g., sildenafil, tadalafil)
- Endothelin Receptor Antagonists (ERAs) (e.g., ambrisentan, bosentan, macitentan)
- Prostacyclin pathway agents (e.g., epoprostenol, treprostinil, iloprost, selexipag)
- Soluble Guanylate Cyclase (sGC) stimulators (e.g., riociguat)
Cost & Coverage
Average Cost:
Very high (specialty drug) per vial
Insurance Coverage:
Specialty Tier (requires prior authorization, often subject to step therapy)
General Drug Facts
If your symptoms or health condition do not improve or worsen over time, it is essential to contact your doctor for further evaluation and guidance. To ensure your safety and the effectiveness of your 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 is a good idea to consult with your pharmacist to see if this applies to your prescription. If you have any questions or concerns about your medication, do not hesitate to reach out to your doctor, nurse, pharmacist, or other healthcare provider for clarification and guidance. 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 detailed information about the overdose, including the name of the medication taken, the amount consumed, and the time it occurred.