Brand name: Winrevair
Drug class: Respiratory Tract Agents, Miscellaneous

Medically reviewed by Drugs.com on Nov 10, 2024. Written by ASHP.

Introduction

Recombinant activin receptor type IIA-Fc (ActRIIA-Fc) fusion protein; activin signaling inhibitor.

Uses for Sotatercept-csrk

Pulmonary Arterial Hypertension

Treatment of adults with pulmonary arterial hypertension (PAH; WHO group 1 pulmonary hypertension) to increase exercise capacity, improve WHO functional class, and reduce the risk of clinical worsening events (designated an orphan drug by FDA for treatment of PAH).

Expert consensus guidelines recommend that all adult patients with symptomatic PAH be treated with established PAH-specific medications. Selection of drug therapy should be based on disease severity (WHO/NYHA class) in addition to comorbid conditions, concomitant medications, adverse effects, route of administration, costs, and patient preferences. Specific place in therapy for sotatercept not addressed in current guidelines. Likely to be useful in patients who do not respond adequately to established therapies.

Sotatercept-csrk Dosage and Administration

General

Pretreatment Screening

• Obtain hemoglobin and platelet count prior to initiating sotatercept; do not initiate if platelet count <50,000/mm³.

• Verify pregnancy status in females of reproductive potential.

Patient Monitoring

• Monitor hemoglobin and platelet counts before each dose for the first 5 doses, or longer if values are unstable; thereafter, monitor periodically.

• If overdose is suspected, monitor for erythrocytosis.

Administration

Sub-Q Administration

Administer via sub-Q injection once every 3 weeks. Intended for use under the guidance of a healthcare professional, but may be administered by patient or caregiver with appropriate training.

Available in kits containing 1 or 2 single-dose vials of sotatercept-csrk lyophilized powder for reconstitution, 1 or 2 prefilled syringes of sterile water for injection, a measuring syringe, a safety needle, vial adapters, and alcohol pads.

Preparation of a single dose may require 1 or 2 vials of drug, depending on injection volume; if 2 vials are required, use the 2-vial kit rather than 2 individual 1-vial kits.

Prior to reconstitution, remove injection kit from the refrigerator and wait 15 minutes to allow prefilled syringes and drug product to come to room temperature. Use provided prefilled syringes of sterile water for injection to reconstitute the product (one prefilled syringe per vial of drug); this provides a final concentration of 50 mg/mL. After injecting contents of the prefilled syringe into the vial, gently swirl the vial to reconstitute the drug; do not shake or vigorously agitate. Allow vial to stand for up to 3 minutes to allow bubbles to disappear. If 2 vials are required to prepare the dose, repeat above steps to prepare the second vial. Consult manufacturer labeling for additional information on reconstitution and preparation.

Administer sub-Q injections into the abdomen (≥2 inches away from the navel), upper thigh, or upper arm. Patients and caregivers should only administer into the abdomen or upper thigh. Do not administer into skin that is scarred, tender, or bruised.

If a dose is missed, administer as soon as possible; if not administered within 3 days of the scheduled date, adjust the dosing schedule to maintain 3-week dosing intervals.

Dosage

Adults

Pulmonary Arterial Hypertension

Sub-Q

Initially, 0.3 mg/kg once every 3 weeks; after verifying acceptable hemoglobin levels and platelet counts, increase to target dosage of 0.7 mg/kg every 3 weeks.

Dosage Modification for Toxicity

Monitor hemoglobin and platelet count before each dose for the first 5 doses (or longer if values are unstable), then periodically thereafter.

Delay treatment for at least 3 weeks if any of the following occur: hemoglobin increases >2 g/dL from the previous dose and is above the ULN; hemoglobin increases >4 g/dL from baseline; hemoglobin increases >2 g/dL above ULN; or platelet count decreases to <50,000/mm³. Recheck hemoglobin and platelet count prior to restarting treatment. If the treatment delay lasts >9 weeks, restart treatment at 0.3 mg/kg, and escalate to 0.7 mg/kg after verifying acceptable hemoglobin and platelet count.

Special Populations

Hepatic Impairment

No dosage recommendations at this time.

Renal Impairment

No dosage recommendations at this time.

Geriatric Patients

No dosage recommendations at this time.

Cautions for Sotatercept-csrk

Contraindications

• None.

Warnings/Precautions

Erythrocytosis

May increase hemoglobin levels; severe erythrocytosis may increase risk of hyperviscosity syndrome or thromboembolic events.

Monitor hemoglobin levels before each dose for the first 5 doses (or longer if values are unstable) and periodically thereafter. Consider need for treatment interruption if elevations in hemoglobin occur.

Severe Thrombocytopenia

May cause thrombocytopenia, leading to increased risk of bleeding. Thrombocytopenia more common among patients receiving concomitant prostacyclin infusions.

Do not initiate treatment if platelet count <50,000/mm³. Monitor platelet count before each dose for the first 5 doses (or longer if values are unstable) and periodically thereafter. Consider need for treatment interruption if decreases in platelet count occur.

Serious Bleeding

Serious bleeding (e.g., GI bleeding, intracranial hemorrhage) reported; events more common among patients with low platelet counts and patients who were receiving background therapy with prostacyclins and/or antithrombotic agents.

Advise patients of signs and symptoms of blood loss, and evaluate and treat any bleeding that occurs. Do not administer sotatercept-csrk if the patient is experiencing serious bleeding.

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm if administered to a pregnant woman, based on data from animal studies. Adverse developmental outcomes (increased embryofetal mortality, growth alterations, and structural variations) observed when sotatercept-csrk was administered to pregnant rats and rabbits during organogenesis.

Advise pregnant women of potential risk to a fetus. Verify pregnancy status in females of reproductive potential prior to starting treatment. Advise females of reproductive potential to use effective contraception during treatment and for at least 4 months after the final dose.

Impaired Fertility

May impair male and female fertility, based on data from animal studies. Advise patients on the potential effects on fertility.

Immunogenicity

Anti-sotatercept antibodies (including neutralizing antibodies) detected in patients treated with the drug. No effects on pharmacokinetics, pharmacodynamics, safety, or effectiveness.

Specific Populations

Pregnancy

May cause fetal harm based on animal data. No data in pregnant women. Adverse developmental outcomes (increased embryofetal mortality, growth alterations, and structural variations) observed in animals.

Pregnancy in patients with PAH associated with increased maternal and fetal morbidity and mortality, including spontaneous abortion, intrauterine growth restriction, and premature labor.

Advise pregnant women of the potential risk to a fetus. Verify pregnancy status in females of reproductive potential prior to starting therapy.

Lactation

No data on the presence of sotatercept in human breast milk. Effects on the breast-fed infant or on milk production unknown.

Breastfeeding not recommended during treatment or for 4 months after the final dose due to the potential for serious adverse reactions in the breast-fed infant.

Females and Males of Reproductive Potential

May cause fetal harm when administered to a pregnant woman. Verify pregnancy status in females of reproductive potential prior to starting treatment.

Advise females of reproductive potential to use effective contraception during treatment and for at least 4 months after the final dose.

Based on data from animal studies, sotatercept-csrk may impair male and female fertility.

Pediatric Use

Safety and efficacy not established.

Geriatric Use

No differences in efficacy observed between geriatric patients and younger adults. Bleeding adverse events more common among patients ≥65 years of age. Experience in patients ≥75 years of age insufficient to determine whether they respond differently than younger patients.

Hepatic Impairment

Effects of hepatic impairment on sotatercept pharmacokinetics not studied.

Renal Impairment

No clinically significant differences in pharmacokinetics observed based on mild to moderate renal impairment (eGFR 30–89 mL/minute) or end-stage kidney disease (eGFR <15 mL/minute) with dialysis. Severe renal impairment (eGFR 15–30 mL/minute) not expected to impact pharmacokinetics.

Common Adverse Effects

Most common adverse effects (≥10%): headache, epistaxis, rash, telangiectasia, diarrhea, dizziness, erythema.

Drug Interactions

No drug-drug interaction studies performed. Expected to be metabolized into small peptides via catabolic pathways.

Sotatercept-csrk Pharmacokinetics

Absorption

Bioavailability

66% following sub-Q administration.

Median time to peak plasma concentrations: approximately 7 days.

AUC and peak plasma concentrations increase proportionally with dose.

Steady state achieved after approximately 15 weeks.

Distribution

Extent

Not known if distributed in human milk.

Elimination

Metabolism

Expected to be metabolized into small peptides via catabolic pathways.

Half-life

Approximately 24 days.

Special Populations

No clinically significant differences observed based on age (18–81 years), sex, or race.

Clearance and central volume of distribution increase with increasing body weight; effect not clinically significant when administered using the recommended weight-based dosing.

Stability

Storage

Parenteral

Powder for Injection

Store at 2–8ºC in the original carton to protect from light; do not freeze. If needed, may store unopened kit at room temperature (up to 25ºC) for up to 24 hours.

Use reconstituted solution as soon as possible and no later than 4 hours after reconstitution.

Actions

• Activin signaling inhibitor; homodimeric recombinant fusion protein consisting of the extracellular domain of the human activin receptor type IIA (ActRIIA) linked to the human IgG₁ Fc domain.

• Distinct mechanism of action from other currently approved PAH treatments. Binds to activin A and other transforming growth factor beta (TGF-β) superfamily ligands, acting as an activin signaling inhibitor.

• Improves balance between pro-proliferative and anti-proliferative signaling and modulates vascular proliferation.

• Reduced inflammation and inhibited proliferation of endothelial and smooth muscle cells in diseased vasculature of rats, leading to thinner vessel walls, partial reversal of right ventricular remodeling, and improved hemodynamics.

Advice to Patients

• Advise patients to read the FDA-approved patient labeling (Patient Information and Instructions for Use).

• Provide training to the patient or caregiver regarding proper preparation and administration of sotatercept-csrk. Ensure that the patient or caregiver can properly reconstitute the medication, measure the correct amount according to the patient's prescription, select and prepare a proper injection site, and inject the medication subcutaneously.

• Advise patients to contact their clinician if they take more or less than the correct dose. Advise patients about signs and symptoms to monitor for and inform patients that additional laboratory tests may be required prior to the next scheduled dose to ensure that the next dose can be safely administered.

• Advise patients that if they miss the prescribed dose of sotatercept-csrk, they should take it within 3 days and maintain the original schedule for the next dose; if the missed dose is not taken within 3 days, instruct them to contact their clinician for guidance.

• Advise patients that sotatercept-csrk may raise hemoglobin to levels that increase the risk of thrombotic events. Inform patients that hemoglobin levels will be assessed before at least the first 5 doses and then periodically, as dosage may need to be adjusted.

• Advise patients that sotatercept-csrk may cause platelet counts to decrease, which could cause bleeding if severe. Inform patients that platelet count will be assessed before at least the first 5 doses and then periodically, as dosage may need to be adjusted.

• Inform patients of the possibility of serious bleeding, which is more likely to occur if they have low platelet counts or while on prostacyclin background therapy and/or antithrombotic agents. Advise patients to inform their clinician if signs and symptoms of bleeding occur.

• Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary and herbal supplements, as well as any concomitant illnesses.

• Advise women to inform their clinician if they are or plan to become pregnant. Advise females of reproductive potential to use effective contraception during sotatercept-csrk therapy and for at least 4 months after the final dose. Advise patients to contact their clinician if they become pregnant or if pregnancy is suspected during treatment with sotatercept-csrk. Exposure to sotatercept-csrk during pregnancy should be reported to the Merck Sharp & Dohme Adverse Event reporting line (1-877-888-4231).

• Advise women to inform their clinician if they plan to breast-feed. Advise patients not to breast-feed during treatment with sotatercept-csrk and for 4 months after the final dose.

• Advise females and males of reproductive potential that sotatercept-csrk may impair fertility.

• Advise patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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