Winrevair (sotatercept-csrk)

Monitor hemoglobin and platelet count before each dose of sotatercept-csrk 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 upper limit of normal (ULN); hemoglobin increases >4 g/dL from baseline; hemoglobin increases >2 g/dL above the 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.

Sotatercept-csrk is administered by subcutaneous injection once every 3 weeks. The drug is intended for use under the guidance of a healthcare professional, but may be administered by the patient or caregiver following appropriate training on reconstitution, preparation, and injection.

Sotatercept-csrk is 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. Store vials in the refrigerator at 2-8oC in the original carton until time of use; protect from light and do not freeze. Unopened kits should be stored in the refrigerator until ready to use, but can be stored out of the refrigerator (up to 25degreesC) for up to 24 hours if necessary.

Preparation of a single dose of sotatercept-csrk may require 1 or 2 vials of drug, depending on the patient's body weight; if 2 vials are required to prepare the dose, use the 2-vial kit rather than 2 individual 1-vial kits. Consult the manufacturer's labeling for detailed instructions on calculating the injection volume required for a given dose and selecting the appropriate kit type based on injection volume.

Prior to reconstitution, remove the injection kit from the refrigerator and wait 15 minutes to allow the prefilled syringes and drug product to come to room temperature. Use the provided prefilled syringes of sterile water for injection to reconstitute the product (one prefilled syringe per vial of drug); this will provide a final concentration of 50 mg/mL. After injecting the entire contents of the prefilled syringe into the vial, gently swirl the vial to reconstitute the drug; do not shake or vigorously agitate. Allow the vial to stand for up to 3 minutes to allow bubbles to disappear. Use the reconstituted solution as soon as possible, but no later than 4 hours after reconstitution. If the dose of sotatercept-csrk requires the use of 2 vials, repeat the same steps to prepare the second vial. Consult the manufacturer's labeling for detailed information on reconstitution and preparation of sotatercept-csrk.

Inject sotatercept-csrk subcutaneously into the abdomen (>=2 inches away from the navel), upper thigh, or upper arm. Patients and caregivers should only administer sotatercept-csrk into the abdomen or upper thigh. Do not administer into areas of skin that are scarred, tender, or bruised.

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

No dosing information is available for this tab.

No drug-drug interaction studies have been performed with sotatercept-csrk. The drug is expected to be metabolized into small peptides via catabolic pathways.

There are no contraindication interactions for this drug.

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Igg Antibodies And Derivatives/Efgartigimod-Alfa

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Efgartigimod-alfa binds to FcRn and may decrease systemic exposure of other ligands of FcRn, like immunoglobulins and IgG-based antibodies.(3)

CLINICAL EFFECTS: The effectiveness of medicines that bind to FcRn may be decreased.(3)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of efgartigimod-alfa states that efgartigimod-alfa should not be combined with long-term use of FcRn-binding medications. If the medication is essential for the patient, efgartigimod-alfa should be discontinued.(3)

DISCUSSION: Clinical drug interaction studies with efgartigimod-alfa have not been performed. Efgartigimod-alfa may decrease concentrations of compounds that bind to the human FcRn.(3)

Igg Antibodies And Derivatives/Nipocalimab-Aahu

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Nipocalimab-aahu binds to FcRn and may decrease systemic exposure of other ligands of FcRn, like immunoglobulins and IgG-based antibodies.(3)

CLINICAL EFFECTS: The effectiveness of medicines that bind to FcRn may be decreased.(3)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of nipocalimab-aahu states that nipocalimab-aahu should not be combined with long-term use of FcRn-binding medications. If the medication is essential for the patient, nipocalimab-aahu should be discontinued.(3)

DISCUSSION: Clinical drug interaction studies with nipocalimab-aahu have not been performed. Nipocalimab-aahu may decrease concentrations of compounds that bind to the human FcRn.(3)

Myelosuppressives; Immunomodulators/Sodium Iodide I 131

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Sodium iodide I 131 can cause depression of the hematopoetic system. Myelosuppressives and immunomodulators also suppress the immune system.(1)

CLINICAL EFFECTS: Concurrent use of sodium iodide I 131 with agents that cause bone marrow depression, including myelosuppressives or immunomodulators, may result in an enhanced risk of hematologic disorders, including anemia, blood dyscrasias, bone marrow depression, leukopenia, and thrombocytopenia. Bone marrow depression may increase the risk of serious infections and bleeding.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The US manufacturer of sodium iodide I 131 states that concurrent use with bone marrow depressants may enhance the depression of the hematopoetic system caused by large doses of sodium iodide I 131.(1) Sodium iodide I 131 causes a dose-dependent bone marrow suppression, including neutropenia or thrombocytopenia, in the 3 to 5 weeks following administration. Patients may be at increased risk of infections or bleeding during this time. Monitor complete blood counts within one month of therapy. If results indicate leukopenia or thrombocytopenia, dosimetry should be used to determine a safe sodium iodide I 131 activity.(1)

DISCUSSION: Hematologic disorders including death have been reported with sodium iodide I 131. The most common hematologic disorders reported include anemia, blood dyscrasias, bone marrow depression, leukopenia, and thrombocytopenia.(1)

Moderate Interaction: Assess the risk to the patient and take action as needed.

Igg Antibodies And Derivatives/Rozanolixizumab-Noli

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Rozanolixizumab-noli binds to FcRn and may decrease systemic exposure of other ligands of FcRn, like immunoglobulins and IgG-based antibodies.(3)

CLINICAL EFFECTS: The effectiveness of medications that bind to FcRn may be decreased.(3)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of rozanolixizumab-noli states that concurrent use with medications that bind to the human neonatal Fc receptor (FcRn) should be closely monitored for reduced effectiveness of these medications. If long-term use of such medications is essential for the patient, consider discontinuing rozanolixizumab-noli and use alternative therapies.(3)

DISCUSSION: Clinical drug interaction studies with rozanolixizumab-noli have not been performed. Rozanolixizumab-noli may decrease concentrations of compounds that bind to the human FcRn.(3)

*None.

• Lactation

• Erythrocytosis
• Hemorrhage
• Pregnancy
• Thrombocytopenic disorder

There are no moderate contraindications for this drug.

The most common adverse effects (>=10% in patients receiving sotatercept-csrk and 5% more than placebo) in clinical trials of sotatercept-csrk were infections, headache, epistaxis, rash, telangiectasia, diarrhea, increased hemoglobin, dizziness, gingival bleeding, and erythema.

More Frequent

• Infection

Rare or Very Rare

• Anaphylaxis
• Angioedema
• Gastrointestinal angiodysplasia
• Gastrointestinal hemorrhage
• Hypersensitivity drug reaction
• Intracranial bleeding
• Intrapulmonary right-to-left shunt
• Pericardial effusion

More Frequent

• Diarrhea
• Dizziness
• Epistaxis
• Erythema
• Gingival bleeding
• Headache disorder
• Skin rash
• Telangiectasia

Less Frequent

• Hypertension
• Increased hemoglobin
• Skin hypopigmentation
• Thrombocytopenic disorder

Rare or Very Rare

• Injection site sequelae

No enhanced messaging available.

The safety and efficacy of sotatercept-csrk have not been established in patients <18 years of age.

Based on data from animal studies, sotatercept may cause fetal harm if administered to a pregnant woman.

There are no available data on sotatercept use in pregnant women to inform a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. When sotatercept-csrk was administered to pregnant rats and rabbits during organogenesis, adverse developmental outcomes (increased embryofetal mortality, growth alterations, and structural variations) occurred at exposures 4- and 0.6-fold those occurring at the maximum recommended human dose, respectively.

There are risks to the mother and fetus associated with pulmonary arterial hypertension (PAH) in pregnancy. In patients with PAH, pregnancy is 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 sotatercept-csrk.

There are no data on the presence of sotatercept-csrk in human breast milk. The effects of sotatercept-csrk on the breast-fed infant or on milk production are not known. Because of the potential for serious adverse reactions in the breast-fed infant, breastfeeding is not recommended during sotatercept-csrk treatment or for 4 months after the final dose.

The manufacturer makes no specific dosage recommendations for geriatric patients.

A total of 99 patients >=65 years of age received sotatercept-csrk in clinical trials; no differences in efficacy were observed between geriatric patients and younger adults. Bleeding adverse events were more common among patients >=65 years of age, but there was no imbalance between age groups for any specific bleeding event. Experience in patients >=75 years of age is insufficient to determine whether they respond differently to sotatercept-csrk than younger patients.