WinRho SDF - Drug Monograph

Introduction

WinRho SDF (Rhₒ(D) Immune Globulin Intravenous (Human)) is a sterile, freeze-dried preparation of immunoglobulin G (IgG) containing antibodies to the Rhₒ(D) antigen. It is derived from human plasma collected from screened donors and is used for the suppression of Rh isoimmunization in Rh-negative individuals and for the treatment of immune thrombocytopenic purpura (ITP).

Mechanism of Action

WinRho SDF works through two distinct mechanisms depending on its indication:

• Rh isoimmunization prevention: Binds to Rhₒ(D) positive red blood cells that may have entered the circulation of an Rh-negative individual, facilitating their clearance by the reticuloendothelial system before they can stimulate an immune response
• ITP treatment: Binds to Fcγ receptors on macrophages, blocking clearance of antibody-coated platelets, and may also modulate the immune response through anti-idiotypic antibodies

Indications

1. Suppression of Rh isoimmunization in: - Rh-negative women after delivery of an Rh-positive infant - Following obstetric complications (abortion, amniocentesis, chorionic villus sampling) - After transfusion of Rh-positive blood products to Rh-negative individuals

2. Treatment of immune thrombocytopenic purpura (ITP) in: - Non-splenectomized Rh-positive adults with chronic ITP - Children with acute or chronic ITP - Rh-positive children with chronic ITP

Dosage and Administration

• Postpartum: 300 mcg (1500 IU) IM or IV within 72 hours of delivery
• Antepartum: 300 mcg (1500 IU) at approximately 28 weeks gestation
• Following obstetric events: Dose varies based on estimated fetomaternal hemorrhage

• Initial dose: 50 mcg/kg (250 IU/kg) IV
• Maintenance: 25-60 mcg/kg (125-300 IU/kg) IV based on platelet response
• Dosing may be repeated as needed

• Reconstitute with 0.9% sodium chloride injection
• IV infusion: Administer over 3-5 minutes
• IM injection: Administer in deltoid muscle

Pharmacokinetics

• Absorption: Complete bioavailability when administered IV; slower absorption with IM administration
• Distribution: Distributes throughout vascular and extravascular spaces
• Metabolism: Catabolized similarly to endogenous IgG
• Elimination: Half-life approximately 23-26 days
• Onset of action: Platelet count increases typically seen within 1-2 days in ITP

Contraindications

1. History of severe systemic reaction to human immune globulin preparations 2. IgA-deficient patients with antibodies against IgA (due to trace IgA content) 3. Patients with hyperproliferative or selective immunoglobulin A deficiencies

Warnings and Precautions

1. Intravascular hemolysis: May occur in ITP patients, potentially leading to clinically compromising anemia 2. Renal dysfunction: Acute renal failure, osmotic nephrosis, and death have been reported with immune globulin products 3. Thrombotic events: Increased risk of thrombosis has been reported with immune globulin products 4. Aseptic meningitis syndrome: May occur within hours to two days following treatment 5. Transfusion-related acute lung injury (TRALI): Rare cases reported 6. Transmissible infectious agents: Theoretical risk despite manufacturing processes to reduce pathogens

Drug Interactions

1. Live virus vaccines: May interfere with immune response to vaccines (delay vaccination for 3 months post-treatment) 2. Other immunoglobulin preparations: May increase risk of adverse reactions 3. Blood products: May interfere with serological testing and crossmatching

Adverse Effects

• Headache
• Chills
• Fever
• Myalgia
• Fatigue
• Nausea

• Intravascular hemolysis
• Acute renal failure
• Anaphylaxis
• Thrombotic events
• Aseptic meningitis
• Transfusion-related acute lung injury

Monitoring Parameters

1. For Rh suppression: - Kleihauer-Betke test to quantify fetomaternal hemorrhage when indicated - hemoglobin/hematocrit monitoring

2. For ITP: - Platelet count before and after treatment - Hemoglobin/hematocrit (monitor for hemolysis) - Renal function (BUN, creatinine) - Signs/symptoms of intravascular hemolysis (hemoglobinuria, decreased haptoglobin) - Vital signs during infusion

3. General: - Signs of hypersensitivity reactions - Neurological symptoms (headache, meningismus)

Patient Education

1. Report any signs of allergic reaction (hives, itching, breathing difficulties) 2. Monitor for symptoms of hemolysis (dark urine, fever, chills, back pain) 3. Report symptoms of renal impairment (decreased urine output, edema) 4. Be aware of potential interference with live virus vaccines 5. Understand the purpose of treatment and expected outcomes 6. Report any unusual bleeding or bruising (for ITP patients) 7. Inform all healthcare providers about WinRho SDF treatment

References

1. WinRho SDF [package insert]. Winnipeg, MB: Cangene Corporation; 2021. 2. American College of Obstetricians and Gynecologists. Practice Bulletin No. 181: Prevention of Rh D Alloimmunization. Obstet Gynecol. 2017;130(2):e57-e70. 3. Provan D, Arnold DM, Bussel JB, et al. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood. 2019;133(11):e1-e40. 4. Moise KJ Jr. Management of rhesus alloimmunization in pregnancy. Obstet Gynecol. 2008;112(1):164-176. 5. Gaines AR. Disseminated intravascular coagulation associated with acute hemoglobinemia or hemoglobinuria following Rhₒ(D) immune globulin intravenous administration for immune thrombocytopenic purpura. Blood. 2005;106(5):1532-1537. 6. FDA. WinRho SDF label. Accessed [date]. Available from: https://www.fda.gov/vaccines-blood-biologics/winrho-sdf