Rho(D) Immune Globulin (Monograph)

Brand names: HyperRHO S/D Full Dose, HyperRHO S/D Mini-Dose, MICRhoGAM, RhoGAM, Rhophylac, WinRho SDF
Drug class: Antitoxins and Immune Globulins
ATC class: J06BB01
VA class: IM500

Medically reviewed by Drugs.com on Apr 20, 2023. Written by ASHP.

Introduction

Specific immune globulin. Rh_o(D) immune globulin (Rh_o(D) IG) contains anti-Rh_o(D) antibody to RBC antigen Rh_o(D) and is prepared from plasma of Rh_o(D)-negative donors immunized with Rh_o(D)-positive RBCs.

Uses for Rho(D) Immune Globulin

Suppression of Rh Isoimmunization

Used IM or IV to suppress the active antibody response and formation of anti-Rh_o(D) antibodies (i.e., Rh isoimmunization) in Rh_o(D)-negative women who have been exposed to Rh_o(D)-positive blood as the result of pregnancy or other obstetric conditions (e.g., spontaneous or induced abortion, trauma, threatened abortion, ectopic pregnancy, amniocentesis, chorionic villus sampling, pregnancy termination, external cephalic version); prevention of Rh isoimmunization decreases the likelihood of hemolytic disease of the newborn (erythroblastosis fetalis) in a future pregnancy with an Rh_o(D)-positive fetus.

ACOG recommends that Rh_o(D)-negative women who have not been sensitized to Rh_o(D) antigen receive Rh_o(D) IG at approximately 28 weeks of gestation for routine antenatal prophylaxis (unless father of the fetus is Rh_o(D)-negative), after delivery of an Rh_o(D)-positive infant, after a first-trimester pregnancy loss, and after invasive obstetric procedures (e.g., amniocentesis, chorionic villus sampling, fetal blood sampling). ACOG states use following threatened abortion, second- or third-trimester antenatal bleeding, abdominal trauma, or external cephalic version should be considered based on expert opinion and consensus, but evidence generally lacking for these conditions.

Also used IM or IV to suppress Rh isoimmunization in Rh_o(D)-negative individuals following transfusion of Rh_o(D)-positive blood or blood components containing Rh_o(D)-positive RBCs (e.g., RBCs, platelets, granulocytes). One manufacturer states to consider exchange transfusion prior to administration of Rh_o(D) IG if the transfused Rh_o(D)-positive blood represents >20% of the total circulating RBCs.

Idiopathic Thrombocytopenic Purpura (ITP)

Used IV for the treatment of ITP in Rh_o(D)-positive, nonsplenectomized patients to increase platelet counts and prevent excessive hemorrhage; WinRho SDF is FDA-labeled for use in adults with chronic ITP, children with acute or chronic ITP, and adults and children with ITP secondary to HIV infection, while Rhophylac is labeled for use in adults with chronic ITP.

In patients in whom a response to Rh_o(D) IG is obtained, the rise in platelet count is generally rapid (1–3 days) and transient (usually lasting about 1 month).

Safety and efficacy for the treatment of ITP in Rh_o(D)-negative or splenectomized individuals or for the treatment of thrombocytopenia not related to ITP not established.

Other therapies (i.e., corticosteroids, immune globulin IV [IGIV]) generally are preferred for treatment of ITP because of the risk of hemolysis associated with Rh_o(D) IG (see Hemolysis under Cautions); however, Rh_o(D) IG may be used in carefully selected patients.

Initial treatment of choice for ITP secondary to HIV infection is effective viral suppression with highly active antiretroviral therapy; if additional treatment is indicated, some experts suggest corticosteroids, IGIV, or Rh_o(D) IG may be used.

Related/similar drugs

Nplate, prednisone, triamcinolone, dexamethasone, Decadron, RhoGAM, Promacta

Rho(D) Immune Globulin Dosage and Administration

Administration

Administer HyperRHO, MICRhoGAM, and RhoGAM by IM injection; do not administer IV. Administer Rhophylac and WinRho SDF by IM or IV injection.

Rh_o(D) IG may be administered IM or IV for suppression of Rh isoimmunization. Rh_o(D) IG must be administered IV for the treatment of ITP.

Monitor patient for ≥20 minutes after administration of Rh_o(D) IG for suppression of Rh isoimmunization. Closely monitor patients with ITP for ≥8 hours (see Hemolysis under Cautions).

For suppression of Rh isoimmunization related to an Rh-incompatible pregnancy, administer Rh_o(D) IG to the mother; do not administer to the infant.

Prior to administration, perform appropriate laboratory tests to assess Rh status of the patient. Prior to antepartum or postpartum administration for suppression of Rh isoimmunization, determine whether recipient has been sensitized to Rh_o(D) antigens.

Rhophylac, WinRho SDF: Allow drug to reach room temperature prior to administration.

IM Administration

Preparations of Rh_o(D) IG that may be administered IM for suppression of Rh isoimmunization include HyperRHO, MICRhoGAM, RhoGAM, Rhophylac, and WinRho SDF.

Administer preferably into the deltoid muscle of the upper arm or lateral thigh muscle. Do not routinely use gluteal region because of the risk of injury to the sciatic nerve; if the gluteal region is used, use only the upper outer quadrant of the gluteal muscle.

Rhophylac: When dose is >5 mL (3750 units or 750 mcg), divide and inject into different muscle sites.

Consult manufacturer's prescribing information for specific procedures and techniques for IM administration. Although some manufacturers recommend that aspiration (i.e., pulling back on the syringe plunger after needle insertion and before injection) be performed to ensure that a blood vessel has not been entered, the US Public Health Service Advisory Committee on Immunization Practices (ACIP) states this procedure is not required because large blood vessels are not present at recommended IM injection sites.

IV Administration

For solution compatibility information, see Compatibility under Stability.

Preparations of Rh_o(D) IG that may be administered IV for suppression of Rh isoimmunization include Rhophylac and WinRho SDF. For the treatment of ITP, Rhophylac and WinRho SDF must be administered IV.

Commercially available Rh_o(D) IG can be administered as supplied with no dilution necessary. If dilution of WinRho SDF is preferred, use 0.9% sodium chloride injection as diluent; do not use 5% dextrose injection or any other diluent.

Do not mix with other drugs.

Rate of Administration

Rhophylac: 2 mL per 15–60 seconds.

WinRho SDF: Administer over 3–5 minutes when used for treatment of ITP, or at a rate of 2 mL per 5–15 seconds for suppression of Rh isoimmunization.

Dosage

Potency of Rh_o(D) IG is expressed in terms of international units (IU, units); potency established relative to the US, WHO, and European Pharmacopoeia Anti-D Reference Standard.

Dose previously expressed in mcg; 1 mcg equals 5 units.

A single 1500-unit (300-mcg) dose of Rh_o(D) IG (i.e., prefilled syringes of HyperRHO S/D Full Dose, RhoGAM, or Rhophylac) contains enough anti-Rh_o(D) to suppress the immunization potential of 15 mL of Rh_o(D)-positive RBCs.

A single 250-unit (50-mcg) dose of Rh_o(D) IG (i.e., prefilled syringes of HyperRHO S/D Mini-Dose or MICRhoGAM) contains enough anti-Rh_o(D) to suppress the immunization potential of 2.5 mL of Rh_o(D)-positive RBCs.

A single-dose vial of WinRho SDF containing 1500 units (300 mcg) of Rh_o(D) IG contains enough anti-Rh_o(D) to suppress the immunization potential of 17 mL of Rh_o(D)-positive RBCs.

Pediatric Patients

Idiopathic Thrombocytopenic Purpura (ITP)

Individualize dosage based on clinical response (i.e., platelet count, RBC count, hemoglobin, reticulocyte count).

Platelet count of 50,000/mm³ generally is considered a satisfactory response; treatment rarely indicated in patients with platelet count >50,000/mm³.

IV

WinRho SDF: Initially, 250 units/kg (50 mcg/kg) as a single injection or in 2 divided doses given on separate days. For patients with hemoglobin <10 g/dL, reduce initial dose to 125–200 units/kg (25–40 mcg/kg) to minimize risk of increasing severity of anemia. If subsequent therapy needed in patients with adequate response to the initial dose, maintenance dose of 125–300 units/kg (25–60 mcg/kg) is recommended; however, individualize based on platelet count and hemoglobin concentration. For patients with an inadequate response to the initial dose, subsequent dose is based on hemoglobin. If hemoglobin is >10 g/dL, maintenance dose is 250–300 units/kg (50–60 mcg/kg); if hemoglobin is 8–10 g/dL, maintenance dose is 125–200 units/kg (25–40 mcg/kg). (See Hemolysis under Cautions.)

Adults

Suppression of Rh Isoimmunization Related to Rh-incompatible Pregnancy

Routine Antepartum Prophylaxis

For routine prophylaxis in an unsensitized Rh_o(D)-negative woman, administer recommended dose of Rh_o(D) IG at approximately 28 weeks of gestation; give a second dose after delivery if neonate is Rh_o(D)-positive.

If delivery does not occur within 12 weeks after the standard antepartum dose, a second antepartum dose has been recommended to maintain adequate levels of passively acquired anti-Rh_o(D).

If Rh_o(D) IG is administered early in pregnancy for any reason, give additional antepartum doses at 12-week intervals to maintain adequate levels of anti-Rh_o(D) throughout the pregnancy.

IM

HyperRHO S/D Full Dose, RhoGAM: 1500 units (300 mcg) at about 26–28 weeks of gestation.

WinRho SDF, Rhophylac: 1500 units (300 mcg) at about 28–30 weeks of gestation.

IV

WinRho SDF, Rhophylac: 1500 units (300 mcg) at about 28–30 weeks of gestation.

Postpartum Prophylaxis

Administer recommended dose to unsensitized Rh_o(D)-negative woman as soon as possible (within 72 hours) after delivery of an Rh_o(D)-positive infant. Administer even if Rh_o(D) status of infant is not known at 72 hours. May be less effective if administered >72 hours after delivery; if >72 hours have elapsed, administer Rh_o(D) IG as soon as possible, up to 28 days after delivery.

Withhold postpartum dose if an antepartum dose was administered in the preceding 3 weeks, provided a large fetal-maternal hemorrhage has not occurred.

The usual postpartum dosage must be increased whenever a large fetal-maternal hemorrhage occurs during delivery. (See Excessive Fetal-Maternal Hemorrhage under Dosage and Administration.)

IM

HyperRHO S/D Full Dose, RhoGAM, Rhophylac: 1500 units (300 mcg) after delivery.

WinRho SDF: 600 units (120 mcg) after delivery.

IV

Rhophylac: 1500 units (300 mcg) after delivery.

WinRho SDF: 600 units (120 mcg) after delivery.

Termination of Pregnancy

Administer recommended dose to unsensitized Rh_o(D)-negative woman within 72 hours after termination of pregnancy.

The usual dosage administered following termination of pregnancy must be increased if a large fetal-maternal hemorrhage has occurred. (See Excessive Fetal-Maternal Hemorrhage under Dosage and Administration.)

IM

HyperRHO S/D Mini-Dose, MICRhoGAM: 250 units (50 mcg) as soon as possible after a spontaneous or induced abortion occurring up to and including 12 weeks of gestation. May use full-dose preparations if minidose preparations not available.

HyperRHO S/D Full Dose, RhoGAM: 1500 units (300 mcg) after a spontaneous or induced abortion occurring beyond 12 weeks of gestation.

Rhophylac: 1500 units (300 mcg) after a spontaneous or induced abortion.

WinRho SDF: 600 units (120 mcg) after abortion.

IV

Rhophylac: 1500 units (300 mcg) after a spontaneous or induced abortion.

WinRho SDF: 600 units (120 mcg) after abortion.

Other Obstetric Procedures or Complications During Pregnancy

Administer recommended dose to unsensitized Rh_o(D)-negative woman within 72 hours after the obstetric complication or procedure.

The usual dosage administered following an obstetric procedure or complication must be increased if a large fetal-maternal hemorrhage has occurred. (See Excessive Fetal-Maternal Hemorrhage under Dosage and Administration.)

If the complication or procedure occurs early in the pregnancy (before 26–28 weeks of gestation), administer additional antepartum doses (e.g., at 12-week intervals) to maintain adequate level of passively acquired anti-Rh_o(D) throughout the pregnancy. Also administer a full postpartum dose of Rh_o(D) IG to the mother if the infant is Rh_o(D)-positive.

If delivery occurs within 3 weeks after an antepartum dose, postpartum dose may be withheld unless a large fetal-maternal hemorrhage has occurred.

IM

HyperRHO S/D Full Dose: 1500 units (300 mcg) after threatened abortion at any stage of gestation, amniocentesis, or abdominal trauma.

RhoGAM: 1500 units (300 mcg) after threatened abortion beyond 12 weeks of gestation, amniocentesis, percutaneous umbilical blood sampling, chorionic villus sampling, abdominal trauma, or obstetric manipulation.

MICRhoGAM: 250 units (50 mcg) after threatened abortion occurring at or before 12 weeks of gestation. May use full-dose preparation if minidose preparation not available.

Rhophylac: 1500 units (300 mcg) after obstetric complications (e.g., threatened abortion, ectopic pregnancy or hydatidiform mole, transplacental hemorrhage resulting from antepartum hemorrhage), invasive procedures during pregnancy (e.g., amniocentesis, chorionic biopsy), obstetric manipulative procedures (e.g., external version), or abdominal trauma during pregnancy.

WinRho SDF: 1500 units (300 mcg) immediately after threatened abortion at any stage of gestation; 1500 units (300 mcg) immediately after amniocentesis or chorionic villus sampling in a pregnancy up to 34 weeks of gestation; 600 units (120 mcg) within 72 hours of amniocentesis or other obstetrical manipulation in a pregnancy beyond 34 weeks of gestation.

IV

Rhophylac: 1500 units (300 mcg) after obstetric complications (e.g., threatened abortion, ectopic pregnancy or hydatidiform mole, transplacental hemorrhage resulting from antepartum hemorrhage), invasive procedures during pregnancy (e.g., amniocentesis, chorionic biopsy), obstetric manipulative procedures (e.g., external version), or abdominal trauma during pregnancy.

WinRho SDF: 1500 units (300 mcg) immediately after threatened abortion at any stage of gestation; 1500 units (300 mcg) immediately after amniocentesis or chorionic villus sampling in a pregnancy up to 34 weeks of gestation; 600 units (120 mcg) within 72 hours of amniocentesis or other obstetrical manipulation in a pregnancy beyond 34 weeks of gestation.

Excessive Fetal-Maternal Hemorrhage

The usual dosage of Rh_o(D) IG administered postpartum, after termination of pregnancy, or after other obstetric procedures or complications must be increased if a large fetal-maternal hemorrhage occurs.

If a large fetal-maternal hemorrhage (>30 mL of whole blood or 15 mL of packed RBCs) is suspected, use an approved laboratory procedure to estimate the number of fetal Rh_o(D)-positive RBCs in the maternal circulation and to calculate the RBC volume of the hemorrhage.

Administer entire dose within 72 hours of the event.

IM

HyperRHO S/D Full Dose: If a large fetal-maternal hemorrhage (>15 mL RBCs) occurs, determine the number of prefilled syringes (each syringe contains 1500 units [300 mcg]) needed by dividing the RBC volume of the hemorrhage by 15 mL; if the calculated dose results in a fraction of a prefilled syringe, administer the next whole number of syringes. Administer multiple doses at the same time (at different sites) or at spaced intervals, provided the entire dose is administered within 72 hours.

RhoGAM: Multiple doses required if a large fetal-maternal hemorrhage (>15 mL RBCs) occurs. Consider administering more than 100 units (20 mcg) of RhoGAM per 1 mL of Rh_o(D)-positive RBCs whenever such hemorrhage is suspected or documented. Administer multiple doses at the same time (at different sites) or at spaced intervals, provided the entire dose is administered within 72 hours.

Rhophylac: If a large fetal-maternal hemorrhage (>15 mL RBCs) occurs or is suspected, administer usual 1500-unit (300-mcg) dose plus an additional 100 units (20 mcg) per mL of fetal RBCs in excess of 15 mL if bleeding is quantified or an additional 1500 units (300 mcg) if excess bleeding cannot be quantified. Administer large doses (>5 mL [3750 units or 750 mcg]) as divided doses at different sites.

WinRho SDF: Following massive fetal hemorrhage, administer 60 units (12 mcg) per mL of Rh_o(D)-positive blood or 120 units (24 mcg) per mL of Rh_o(D)-positive RBCs. Administer 6000 units (1200 mcg) every 12 hours until total dose given.

IV

Rhophylac: If a large fetal-maternal hemorrhage (>15 mL RBCs) occurs or is suspected, administer usual 1500-unit (300-mcg) dose plus an additional 100 units (20 mcg) per mL of fetal RBCs in excess of 15 mL if bleeding is quantified or an additional 1500 units (300 mcg) if excess bleeding cannot be quantified.

WinRho SDF: Following massive fetal hemorrhage, administer 45 units (9 mcg) per mL of Rh_o(D)-positive blood or 90 units (18 mcg) per mL of Rh_o(D)-positive RBCs. Administer 3000 units (600 mcg) every 8 hours until total dose given.

Suppression of Rh Isoimmunization Following Transfusion of Rh-incompatible Blood or Blood Products

Dosage depends on volume of Rh_o(D)-positive blood or Rh_o(D)-positive packed RBCs transfused. Calculate the volume of RBCs transfused by multiplying the volume of Rh_o(D)-positive whole blood administered by the hematocrit of the donor.

Administer entire dose within 72 hours of exposure.

IM

HyperRHO S/D Full Dose: Determine the number of prefilled syringes (each syringe contains 1500 units [300 mcg]) needed by dividing the RBC volume transfused by 15 mL; if the calculated dose results in a fraction of a prefilled syringe, administer the next whole number of syringes. If multiple syringes are required, the total dose may be given at the same time (at different sites) or at spaced intervals, provided entire dose is administered within 72 hours of exposure.

MICRhoGAM: 250 units (50 mcg) following exposure to <2.5 mL of Rh_o(D)-positive RBCs.

RhoGAM: 1500 units (300 mcg) following exposure to 2.5–15 mL of Rh_o(D)-positive RBCs. Additional dose(s) needed for exposure to >15 mL of Rh_o(D)-positive RBCs; administer 100 units (20 mcg) per mL of RBCs. If the calculated dose results in a fraction of a prefilled syringe, inject the entire contents of the syringe. May administer multiple doses at the same time (at different sites) or at spaced intervals, provided entire dose is administered within 72 hours of exposure.

Rhophylac: 100 units (20 mcg) per 2 mL of Rh_o(D)-positive blood or per 1 mL of Rh_o(D)-positive erythrocyte concentrate. Administer large doses (>5 mL [3750 units or 750 mcg]) as divided doses at different sites.

WinRho SDF: 60 units (12 mcg) per mL of Rh_o(D)-positive blood or 120 units (24 mcg) per mL of Rh_o(D)-positive RBCs. Administer 6000 units (1200 mcg) every 12 hours until total dose given.

IV

Rhophylac: 100 units (20 mcg) per 2 mL of Rh_o(D)-positive blood or per 1 mL of Rh_o(D)-positive erythrocyte concentrate.

WinRho SDF: 45 units (9 mcg) per mL of Rh_o(D)-positive blood or 90 units (18 mcg) per mL of Rh_o(D)-positive RBCs. Administer 3000 units (600 mcg) every 8 hours until total dose given.

Idiopathic Thrombocytopenic Purpura (ITP)

Individualize dosage based on clinical response (i.e., platelet count, RBC count, hemoglobin, reticulocyte count).

Platelet count of 50,000/mm³ generally is considered a satisfactory response; treatment rarely indicated in patients with platelet count >50,000/mm³.

IV

Rhophylac: 250 units/kg (50 mcg/kg). For information on use in patients with anemia, see Hemolysis under Cautions.

WinRho SDF: Initially, 250 units/kg (50 mcg/kg) as a single injection or in 2 divided doses given on separate days. For patients with hemoglobin <10 g/dL, reduce initial dose to 125–200 units/kg (25–40 mcg/kg) to minimize risk of increasing severity of anemia. If subsequent therapy needed in patients with adequate response to the initial dose, maintenance dose of 125–300 units/kg (25–60 mcg/kg) is recommended; however, individualize based on platelet count and hemoglobin concentration. For patients with an inadequate response to the initial dose, subsequent dose is based on hemoglobin. If hemoglobin >10 g/dL, maintenance dose is 250–300 units/kg (50–60 mcg/kg); if hemoglobin is 8–10 g/dL, maintenance dose is 125–200 units/kg (25–40 mcg/kg). (See Hemolysis under Cautions.)

Special Populations

Hepatic Impairment

No specific dosage recommendations.

Renal Impairment

WinRho SDF: Administer at minimum rate of infusion.

Geriatric Patients

WinRho SDF: Select dosage with caution (generally starting at the low end of the dosing range) because of age-related decreases in hepatic, renal, and/or cardiac function, and concomitant disease and drug therapy.

Cautions for Rho(D) Immune Globulin

Contraindications

• Known anaphylactic or severe systemic reactions to immune globulins.

• When used for the suppression of Rh isoimmunization, do not administer to the infant or to Rh_o(D)-positive individuals.

• IgA-deficient patients with antibodies to IgA and history of hypersensitivity. (See Selective IgA Deficiency under Cautions.)

• WinRho SDF: Autoimmune hemolytic anemia, preexisting hemolysis, or high risk for hemolysis.

Warnings/Precautions

Warnings

Hemolysis

Intravascular hemolysis, including some fatalities, reported in patients receiving Rh_o(D) IG for ITP. (See Boxed Warning.) Serious complications (e.g., severe anemia, acute renal insufficiency or failure, multiorgan failure including ARDS, disseminated intravascular coagulation [DIC]) may occur.

Closely monitor patients with ITP in a healthcare setting for ≥8 hours after administration. Perform dipstick urinalysis at baseline and after administration at 2 hours, 4 hours, and just prior to the end of monitoring period. Monitor for signs and symptoms of intravascular hemolysis (e.g., back pain, shaking chills, fever, discolored urine, hemoglobinuria, hematuria).

If necessary, perform appropriate confirmatory tests (e.g., CBCs, plasma hemoglobin, haptoglobin, urine dipstick, renal function tests [e.g., BUN, S_cr], LDH, direct and indirect bilirubin, specific tests for DIC [e.g., D-dimer, fibrin degradation products, fibrin split products]).

If transfusion needed, use Rh_o(D)-negative packed RBCs to avoid exacerbation of the ongoing hemolysis.

Administration of Rh_o(D) IG to Rh_o(D)-positive individuals for the treatment of ITP expected to result in extravascular destruction of Rh_o(D)-positive RBCs (via reticuloendothelial system) and a decrease in hemoglobin concentration.

WinRho SDF: When used for the treatment of ITP, reduce dose in individuals with hemoglobulin <10 g/dL. Use alternative treatments in individuals with hemoglobulin <8 g/dL. (See Idiopathic Thrombocytopenic Purpura [ITP] under Dosage and Administration.) Prior to administration, assess patient's risk of hemolysis with appropriate laboratory tests (e.g., blood type, blood cell count, reticulocyte count, direct antiglobulin test [DAT], dipstick urinalysis); if there is evidence or risk of hemolysis, alternative treatments to Rh_o(D) IG advised. (See Contraindications under Cautions.)

Rhophylac: Safety in the treatment of ITP not established in patients with preexisting anemia. Weigh potential benefits against the risk of increasing the severity of anemia.

Patients receiving Rh_o(D) IG for suppression of Rh isoimmunization following an Rh-incompatible transfusion may exhibit signs or symptoms of hemolysis; monitor for clinical or laboratory evidence of hemolysis.

Sensitivity Reactions

Hypersensitivity

Systemic allergic reactions reported rarely. If signs of hypersensitivity including generalized urticaria, tightness of the chest, wheezing, hypotension, or anaphylaxis occur, discontinue immediately and institute appropriate therapy (e.g., epinephrine) as indicated.

Selective IgA Deficiency

Rh_o(D) IG preparations may contain trace or small quantities of IgA.

Use with caution in individuals with selective IgA deficiency; these individuals may have antibodies to IgA or may develop such antibodies following administration of Rh_o(D) IG. Potential for severe hypersensitivity reactions (e.g., anaphylaxis) to IgA in such patients. (See Contraindications under Cautions.)

Other Warnings/Precautions

Renal Effects

Renal dysfunction and/or acute renal failure reported in patients receiving IV immune globulins.

Assess renal function (including BUN and S_cr) before initiating Rh_o(D) IG; ensure patient is not volume depleted.

Manufacturer of WinRho SDF states to use slowest possible infusion rate in patients at risk for renal dysfunction/failure (e.g., those with diabetes mellitus, age >65 years, volume depletion, sepsis, paraproteinemia, concomitant use of known nephrotoxic drugs) or with any renal impairment. Monitor renal function and urine output periodically in these patients.

Risk of Transmissible Agents in Plasma-derived Preparations

Because Rh_o(D) IG is prepared from pooled human plasma, it is a potential vehicle for transmission of human viruses, including the causative agents of viral hepatitis and HIV infection, and theoretically may carry a risk of transmitting the causative agent of Creutzfeldt-Jakob disease (CJD).

Improved donor screening, viral-inactivation procedures (e.g., solvent/detergent treatment), and filtration procedures have reduced, but not completely eliminated, risk of pathogen transmission with plasma-derived preparations.

The manufacturing process for Rh_o(D) IG includes a solvent/detergent inactivation process and a filtering procedure to remove both enveloped and nonenveloped viruses.

Despite these measures, there is still a possibility of disease transmission from plasma-derived preparations of Rh_o(D) IG. Report any infection believed to have been transmitted by Rh_o(D) IG to the manufacturer.

Blood Glucose Testing

Rh_o(D) IG preparations that contain maltose (WinRho SDF) may cause falsely elevated results in blood glucose determinations that use nonspecific methods based on glucose dehydrogenase pyrroloquinolinequinone (GDH-PQQ) or glucose-dye oxidoreductase. (See Specific Drugs and Laboratory Tests under Interactions.)

Thromboembolic Events

Thromboembolic events, sometimes fatal, reported in patients receiving Rh_o(D) IG.

Patients at risk include those with history of atherosclerosis, multiple cardiovascular risk factors, advanced age, impaired cardiac output, coagulation disorders, prolonged periods of immobilization, and/or known or suspected hyperviscosity. Manufacturer of WinRho SDF states to use slowest possible infusion rate in such patients.

Consider baseline assessment of blood viscosity in patients at risk for hyperviscosity (e.g., those with cryoglobulins, fasting chylomicronemia or markedly high triglycerides, or monoclonal gammopathies).

Transfusion-related Acute Lung Injury

Transfusion-related acute lung injury (TRALI; noncardiogenic pulmonary edema) reported in patients receiving IV immune globulins, including Rh_o(D) IG (WinRho SDF). Typically occurs within 1–6 hours following administration of blood product and is characterized by severe respiratory distress, pulmonary edema, hypoxemia, normal left ventricular function, and fever.

Monitor for adverse pulmonary effects. If TRALI is suspected, perform appropriate tests to determine whether anti-neutrophil and anti-HLA antibodies are present in product or patient serum.

Manage using oxygen therapy and adequate ventilatory support.

Improper Storage and Handling

Improper storage or handling of immune globulins may affect efficacy.

Do not administer Rh_o(D) IG that has been mishandled or has not been stored at the recommended temperature. (See Storage under Stability.)

Inspect all immune globulins upon delivery and monitor during storage to ensure that the appropriate temperature is maintained. If there are concerns about mishandling, contact the manufacturer or state or local health departments for guidance on whether Rh_o(D) IG is usable.

Specific Populations

Pregnancy

Category C.

Rh_o(D) IG not evaluated systematically in pregnant women with ITP; corticosteroids or IGIV generally recommended.

Lactation

Used in nursing women for suppression of Rh isoimmunization; no adverse effects expected during breastfeeding.

Rh_o(D) IG not evaluated in nursing women with ITP.

Not known whether distributed into human milk; use caution.

Pediatric Use

HyperRHO S/D Full Dose, HyperRHO S/D Mini-Dose: Safety and efficacy not established in pediatric patients.

Rhophylac: Safety and efficacy not established for suppression of Rh isoimmunization in pediatric patients given an incompatible transfusion. Weigh the potential risks against the benefits, particularly in girls whose later pregnancies may be affected if Rh isoimmunization occurs.

WinRho SDF: Used in children for the treatment of acute or chronic ITP or ITP secondary to HIV infection.

Geriatric Use

Rhophylac: When used for the treatment of ITP, no substantial differences in safety and efficacy relative to younger adults. Has not been evaluated for the suppression of Rh isoimmunization following incompatible transfusions in geriatric patients ≥65 years of age.

WinRho SDF: Insufficient experience in patients ≥65 years of age to determine whether they respond differently than younger adults. During postmarketing experience, increased risk of serious complications from intravascular hemolysis observed in geriatric patients >65 years of age with comorbid conditions (e.g., cardiorespiratory compromise, renal insufficiency or failure, prothrombotic conditions).

Common Adverse Effects

Chills, fever or increased body temperature, headache, nausea, dizziness, mild hemolysis (increased bilirubin, decreased hemoglobin), injection-site reactions (e.g., swelling, induration, erythema, mild pain or warmth), rash, body aches, malaise.

Drug Interactions

Live Vaccines

Antibodies present in immune globulin preparations may interfere with the immune response to measles, mumps, and rubella virus vaccine live (MMR), varicella virus vaccine live, and fixed combination of MMR and varicella vaccine (MMRV); no evidence of interference with the immune response to influenza virus vaccine live intranasal, rotavirus vaccine live oral, yellow fever virus vaccine live, typhoid vaccine live oral, or zoster vaccine live. (See Specific Drugs and Laboratory Tests under Interactions.)

Postpartum administration of Rh_o(D) IG has not been shown to reduce the response to rubella vaccine RA27/3 strain. Rubella and varicella immunity are important in women of childbearing potential. The ACIP recommends administering the appropriate vaccine immediately after delivery in women susceptible to rubella and/or varicella; do not delay administration because the woman received antepartum or postpartum Rh_o(D) IG. If possible, perform serologic tests ≥3 months after vaccination to ensure immunity to rubella and, if necessary, to measles.

Inactivated Vaccines and Toxoids

Immune globulin preparations not expected to have a clinically important effect on immune responses to inactivated vaccines or toxoids; inactivated vaccines, recombinant vaccines, polysaccharide vaccines, and toxoids may be administered simultaneously with (using different syringes and different injection sites) or at any interval before or after Rh_o(D) IG.

Specific Drugs and Laboratory Tests

Rho(D) Immune Globulin Pharmacokinetics

Absorption

Bioavailability

Following IM administration of Rh_o(D) IG, peak serum concentrations are achieved in 2–7 days.

Following IV administration of Rh_o(D) IG, peak serum concentrations are achieved in 30 minutes.

Rhophylac: Bioavailability of Rh_o(D) IG administered IM is approximately 69% of Rh_o(D) IG administered IV.

Distribution

Extent

Not known whether distributed into milk.

Elimination

Half-life

IM administration: 18–31 days.

IV administration: Approximately 16–24 days.

Stability

Storage

Parenteral

Injection

2–8°C. Do not freeze.

Store Rhophylac in the original carton to protect product from light.

Compatibility

Parenteral

Solution Compatibility (WinRhoSDF)1

Actions

• Contains anti-Rh_o(D) antibody to the RBC antigen Rh_o(D); used to provide temporary passive immunity in Rh_o(D)-negative individuals exposed to Rh_o(D)-positive blood from a pregnancy (when fetus is Rh_o[D]-positive) or from an Rh_o(D)-positive blood transfusion.

• Mechanism by which Rh_o(D) IG suppresses anti-Rh_o(D) not fully elucidated; anti-Rh_o(D) antibody may bind to Rh_o(D) antigen thus preventing the primary immune response to Rh_o(D) and production of anti-Rh_o(D).

• Mechanism by which Rh_o(D) IG increases platelet counts in the treatment of ITP not fully elucidated; administration of Rh_o(D) IG to Rh_o(D)-positive individuals results in formation of anti-Rh_o(D)-coated RBC complexes that may saturate Fc receptors and decrease Fc-mediated phagocytosis of antibody-coated platelets.

Advice to Patients

• Instruct patients being treated for ITP to read the patient information leaflet prior to each treatment.

• When using RhoGAM, importance of retaining the patient identification card and of presenting this card to healthcare providers.

• Instruct patients receiving Rh_o(D) IG for the treatment of ITP to immediately report signs or symptoms of hemolysis (e.g., back pain, shaking chills, fever, discolored urine, decreased urine output, swelling, shortness of breath) to their clinician.

• Importance of patients understanding potential risks (e.g., hypersensitivity reactions, possible transmission of infectious agents) and benefits of therapy.

• Importance of reporting viral infections (e.g., hepatitis, HIV) to clinician.

• Instruct pregnant women receiving an antepartum dose of Rh_o(D) IG of the need for a second dose at delivery if the infant is Rh_o(D)-positive.

• Importance of notifying clinician if signs and symptoms of a hypersensitivity reaction (i.e., generalized urticaria, tightness of the chest, wheezing, hypotension, anaphylaxis) occur.

• Advise patients with selective IgA deficiency that Rh_o(D) IG contains trace amounts of IgA and potentially could result in life-threatening allergic reactions if used in patients who have developed antibodies to IgA.

• Advise patients receiving WinRho SDF that this preparation contains maltose and may cause falsely elevated glucose readings when blood glucose monitoring systems based on GDH-PQQ or glucose-dye oxidoreductase are used; importance of using glucose-specific test methods not affected by maltose.

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including recent vaccinations (e.g., mumps, measles, rubella, varicella) and prescription and OTC drugs, as well as any concomitant illnesses.

• Importance of informing patients of other important precautionary information. (See Cautions.)

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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