Winrevair 45mg Inj Kit (2 Vials)
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 is an injectable medicine used to treat a serious 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 for you to breathe.
How to Use This Medicine
Proper Use of This Medication
To use this medication correctly, follow your doctor's instructions and read all the information provided. 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 guidance on the proper technique.
Before use, wash your hands thoroughly. This medication requires mixing prior to administration, and you should follow the instructions provided by your doctor. To prepare the medication, allow the vial to come to room temperature for 15 minutes. Do not heat the medication. When mixing, do not shake the vial. Instead, let it sit for up to 3 minutes to allow any large bubbles to dissipate.
Inspect the medication before use. It should be clear to slightly pearly in appearance. Do not use the medication if you notice any clumps, powder, particles, or large bubbles in the solution. The medication is colorless to slightly yellow or slightly brown. If the solution changes color, do not use it. Use the medication within 4 hours of mixing.
When administering the injection, rotate the injection site with each dose. Avoid injecting into skin that is tender, damaged, bruised, sore, or has red patches. Do not inject within 2 inches (5 cm) of the belly button. After use, dispose of needles 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, consult your doctor or pharmacist.
Storage and Disposal
Store this medication in a refrigerator, but do not freeze it. 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 then return to your regular schedule. If you miss a dose by more than 3 days, contact your doctor for guidance on what to do next.
To use this medication correctly, follow your doctor's instructions and read all the information provided. 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 guidance on the proper technique.
Before use, wash your hands thoroughly. This medication requires mixing prior to administration, and you should follow the instructions provided by your doctor. To prepare the medication, allow the vial to come to room temperature for 15 minutes. Do not heat the medication. When mixing, do not shake the vial. Instead, let it sit for up to 3 minutes to allow any large bubbles to dissipate.
Inspect the medication before use. It should be clear to slightly pearly in appearance. Do not use the medication if you notice any clumps, powder, particles, or large bubbles in the solution. The medication is colorless to slightly yellow or slightly brown. If the solution changes color, do not use it. Use the medication within 4 hours of mixing.
When administering the injection, rotate the injection site with each dose. Avoid injecting into skin that is tender, damaged, bruised, sore, or has red patches. Do not inject within 2 inches (5 cm) of the belly button. After use, dispose of needles 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, consult your doctor or pharmacist.
Storage and Disposal
Store this medication in a refrigerator, but do not freeze it. 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 then return to your regular schedule. If you miss a dose by more than 3 days, contact your doctor for guidance on what to do next.
Lifestyle & Tips
- Administer the injection exactly as instructed by your healthcare provider.
- Do not stop taking Winrevair without talking to your doctor.
- Keep all appointments for blood tests and follow-up visits.
- Report any new or worsening symptoms to your doctor immediately.
- Females of reproductive potential must use effective contraception during treatment and for at least 4 months after the last dose.
Available Forms & Alternatives
Dosing & Administration
Adult Dosing
Standard Dose:
Initial 0.3 mg/kg subcutaneous (SC) every 3 weeks for 3 doses, then increase to 0.7 mg/kg SC 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, then 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 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 a ligand trap for members of the transforming growth factor (TGF)-beta superfamily, including activins. By binding to these ligands, sotatercept rebalances signaling through the bone morphogenetic protein receptor type II (BMPR2) pathway, which is dysregulated in pulmonary arterial hypertension (PAH). This rebalancing leads to antiproliferative and pro-apoptotic effects on pulmonary vascular cells, reducing pulmonary vascular remodeling and improving pulmonary hemodynamics.
Pharmacokinetics
Absorption:
Bioavailability:
Approximately 60-70% (subcutaneous)
Tmax:
Approximately 7 days (range 3-14 days)
FoodEffect:
Not applicable (subcutaneous administration)
Distribution:
Vd:
Approximately 4.6 L
ProteinBinding:
Not applicable (biologic)
CnssPenetration:
Limited
Elimination:
HalfLife:
Approximately 27 days
Clearance:
Approximately 0.12 L/day
ExcretionRoute:
Primarily via catabolism and subsequent renal excretion of metabolites
Unchanged:
Not applicable (biologic)
Pharmacodynamics
OnsetOfAction:
Clinical improvement observed within weeks to months
PeakEffect:
Not precisely defined for all clinical endpoints, but sustained effects seen with chronic dosing.
DurationOfAction:
Effects persist for several weeks after last dose due to long half-life.
Confidence:
Medium
Safety & Warnings
Side Effects
Urgent Side Effects: Seek Medical Help Right Away
Although rare, some people may experience severe and potentially life-threatening side effects while 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
+ 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 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 immediately 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. While many people may not experience any side effects or only minor ones, it's essential to discuss any concerns with your doctor. If you experience any of the following side effects or any other symptoms that bother you or persist, contact your doctor or seek medical help:
Dizziness or headache
Nosebleed
Spider veins (visible blood vessels on the skin that appear pink or red)
Diarrhea
* Redness
This list is not exhaustive, and you may experience other 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.
Although rare, some people may experience severe and potentially life-threatening side effects while 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
+ 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 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 immediately 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. While many people may not experience any side effects or only minor ones, it's essential to discuss any concerns with your doctor. If you experience any of the following side effects or any other symptoms that bother you or persist, contact your doctor or seek medical help:
Dizziness or headache
Nosebleed
Spider veins (visible blood vessels on the skin that appear pink or red)
Diarrhea
* Redness
This list is not exhaustive, and you may experience other 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:
- Unusual bleeding or bruising
- Yellowing of skin or eyes (jaundice)
- Dark urine
- Nausea, vomiting, or stomach pain
- Severe headache
- Dizziness or lightheadedness
- Vision changes
- New or worsening spider veins (telangiectasias)
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. Be cautious in your daily activities to prevent cuts and bruises.
If you experience any changes in weight, consult your doctor, as your dosage may need to be adjusted. Elderly patients (65 years and 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 starting the medication. Additionally, this drug may harm an unborn baby. To confirm you are not pregnant, a pregnancy test may be required before initiating treatment.
If you are of childbearing potential, it is crucial to use effective birth control methods while taking this medication and for a specified period after the last dose. Consult your doctor to determine the recommended duration of birth control. 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 weight, consult your doctor, as your dosage may need to be adjusted. Elderly patients (65 years and 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 starting the medication. Additionally, this drug may harm an unborn baby. To confirm you are not pregnant, a pregnancy test may be required before initiating treatment.
If you are of childbearing potential, it is crucial to use effective birth control methods while taking this medication and for a specified period after the last dose. Consult your doctor to determine the recommended duration of birth control. If you become pregnant during or after treatment, notify your doctor immediately.
Overdose Information
Overdose Symptoms:
- Symptoms of overdose are not well-established. May include exaggerated adverse effects such as erythrocytosis, thrombocytopenia, or liver enzyme elevations.
What to Do:
Seek immediate medical attention or call a poison control center (1-800-222-1222). Treatment should be supportive and directed at managing symptoms.
Drug Interactions
Monitoring
Baseline Monitoring
Hemoglobin
Rationale: To establish baseline and monitor for erythrocytosis.
Timing: Prior to initiation
Platelet count
Rationale: To establish baseline and monitor for thrombocytopenia.
Timing: Prior to initiation
Liver function tests (ALT, AST, bilirubin)
Rationale: To establish baseline and monitor for hepatotoxicity.
Timing: Prior to initiation
Blood pressure
Rationale: To establish baseline and monitor for systemic hypertension.
Timing: Prior to initiation
Pregnancy test
Rationale: Sotatercept may cause fetal harm; confirm negative status in females of reproductive potential.
Timing: Prior to initiation
Routine Monitoring
Hemoglobin
Frequency: Every 3 weeks for the first 5 doses, then every 3 months thereafter.
Target: Within normal limits
Action Threshold: Consider dose reduction or interruption if hemoglobin > 16 g/dL (females) or > 17 g/dL (males) or if clinically significant erythrocytosis develops.
Platelet count
Frequency: Every 3 weeks for the first 5 doses, then every 3 months thereafter.
Target: Within normal limits
Action Threshold: Consider dose reduction or interruption if platelet count < 50 x 10^9/L.
Liver function tests (ALT, AST, bilirubin)
Frequency: Every 3 weeks for the first 5 doses, then every 3 months thereafter.
Target: Within normal limits
Action Threshold: Consider dose reduction or interruption if transaminases > 3 x ULN or total bilirubin > 2 x ULN.
Blood pressure
Frequency: At each visit
Target: Individualized
Action Threshold: Monitor for systemic hypertension; manage as clinically indicated.
Symptom Monitoring
- Signs of bleeding (e.g., bruising, epistaxis, gastrointestinal bleeding)
- Symptoms of liver injury (e.g., fatigue, nausea, vomiting, right upper quadrant pain, dark urine, jaundice)
- Symptoms of systemic hypertension (e.g., headache, dizziness, blurred vision)
- Development or worsening of telangiectasias
Special Patient Groups
Pregnancy
Sotatercept may cause fetal harm when administered to a pregnant female. Based on animal studies, it can cause adverse developmental outcomes. 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 fetal harm based on animal data.
Second Trimester:
Potential for fetal harm based on animal data.
Third Trimester:
Potential for fetal harm based on animal data.
Lactation
It is not known whether sotatercept is excreted in human milk or if it affects the breastfed infant or milk production. Due to the potential for serious adverse reactions in a breastfed infant, advise females not to breastfeed during treatment and for 4 months after the last dose.
Infant Risk:
Risk unknown; potential for serious adverse reactions.
Pediatric Use
The safety and effectiveness of sotatercept in pediatric patients have not been established.
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 concomitant medications.
Clinical Information
Clinical Pearls
- Sotatercept is a first-in-class activin receptor type IIA (ActRIIA) Fc-fusion protein for PAH, representing a new therapeutic approach targeting the BMPR2 pathway.
- It is administered subcutaneously every 3 weeks, offering a convenient dosing schedule.
- Close monitoring of hemoglobin, platelet count, and liver function tests is crucial due to potential adverse effects like erythrocytosis, thrombocytopenia, and hepatotoxicity.
- Patients should be educated on the importance of contraception due to potential fetal harm.
- Winrevair is intended to be added to existing PAH background therapy.
Alternative Therapies
- Endothelin Receptor Antagonists (ERAs): e.g., ambrisentan, bosentan, macitentan
- Phosphodiesterase-5 (PDE5) Inhibitors: e.g., sildenafil, tadalafil
- Guanylate Cyclase Stimulators: e.g., riociguat
- Prostacyclin Analogues/Receptor Agonists: e.g., epoprostenol, treprostinil, iloprost, selexipag
- Calcium Channel Blockers (for responders to acute vasoreactivity testing): e.g., nifedipine, diltiazem, amlodipine
Cost & Coverage
Average Cost:
Not available (newly approved, high cost specialty drug) per vial
Insurance Coverage:
Specialty Tier, requires prior authorization and often step therapy
General Drug Facts
If your symptoms or health issues persist or worsen, it is essential to contact your doctor for further guidance. 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.