Rho(D) Immune Globulin

Class: Serums
ATC Class: J06BB01
VA Class: IM500
Brands: HyperRHO S/D, MICRhoGAM, RhoGAM, Rhophylac, WinRho SDF

Warning(s)

Special Alerts:

[Posted 03/10/2010] Cangene, Baxter and FDA notified healthcare professionals that cases of intravascular hemolysis (IVH) and its complications, including fatalities, have been reported in patients treated for immune thrombocytopenic purpura (ITP) with Rho(D) Immune Globulin IV -[Human] (WinRho SDF). IVH can lead to clinically compromising anemia and multi-system organ failure including acute respiratory distress syndrome. Serious complications including severe anemia, acute renal insufficiency, renal failure and disseminated intravascular coagulation have also been reported. Fatal outcomes associated with IVH and its complications have occurred most frequently in patients of advanced age (age over 65) with co-morbid conditions.

The Boxed Warning informs healthcare professionals that:

  • Patients should be closely monitored in a health care setting for at least eight hours after administration.

  • A dipstick urinalysis should be performed at baseline, 2 hours, 4 hours after administration and prior to the end of the monitoring period.

  • Patients should be alerted to and monitor for signs and symptoms of IVH, including back pain, shaking chills, fever, and discolored urine or hematuria. Absence of these signs and/or symptoms of IVH within eight hours do not indicate IVH cannot occur subsequently.

  • If signs and/or symptoms of IVH are present or if IVH is suspected after Rho(D) Immune Globulin IV -[Human] administration, post-treatment laboratory tests should be performed including plasma hemoglobin, urinalysis, haptoglobin, LDH and plasma bilirubin (direct and indirect).

For more information visit the FDA website at: and .

Introduction

Specific immune globulin.1 14 15 16 23 25 Rho(D) immune globulin (Rho(D) IG) contains anti-Rho(D) antibody to RBC antigen Rho(D) prepared from plasma of Rho(D)-negative donors immunized with Rho(D)-positive RBCs.1 14 15 16 23 f m

Uses for Rho(D) Immune Globulin

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Suppression of Rh Isoimmunization

Used to suppress the active antibody response and formation of anti-Rho(D) antibodies (i.e., isoimmunization) in Rho(D)-negative women who have been exposed to Rho(D)-positive blood as the result of pregnancy, other obstetric conditions, or transfusion of Rho(D)-positive blood or blood components to decrease the likelihood of hemolytic disease of the newborn (erythroblastosis fetalis) in the present or a future pregnancy.14 15 16 25 b j

Rh isoimmunization can occur if sufficient number of RBCs from an Rho(D)-positive fetus gain access to its Rho(D)-negative mother's circulation.j n Fetomaternal hemorrhage of sufficient magnitude to cause Rh isoimmunization occurs most commonly at delivery.j n Spontaneous antenatal fetomaternal hemorrhage also can result in Rh isoimmunization; most of these hemorrhages occur in the third trimester.j n Certain clinical events (e.g., abortion, threatened abortion, ectopic pregnancy) and procedures (e.g., amniocentesis, chorionic villus sampling, external cephalic version) may lead to fetomaternal hemorrhage and maternal Rh isoimmunization.j n

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American College of Obstetricians and Gynecologists (ACOG) recommends that Rho(D)-negative women who have not been sensitized to Rho(D) antigen receive Rho(D) IG at approximately 28 weeks of gestation (unless father of the baby is Rho(D)-negative), after delivery of an Rho(D)-positive infant, after a first-trimester pregnancy loss, and after invasive procedures (e.g., amniocentesis, chorionic villus sampling).n Consider Rho(D) IG in women with threatened abortion, second- or third-trimester antenatal bleeding, abdominal trauma, and in those undergoing external cephalic version.n

Used to suppress the active antibody response and formation of anti-Rho(D) antibodies (i.e., isoimmunization) in Rho(D)-negative female children and women following transfusion of Rho(D)-positive blood or blood components containing Rho(D)-positive RBCs provided the transfused Rho(D)-positive blood represents <20% of the total circulating RBCs.b c e f Consider exchange transfusion prior to administration of Rho(D) IG if the transfused Rho(D)-positive blood represents >20% of the total circulating RBCs.f

Passively acquired anti-Rho(D) antibodies usually are undetectable 6 months after administration of Rho(D) IG; administration of the IG after one pregnancy or transfusion does not suppress formation of anti-Rho(D) following a subsequent exposure to Rho(D)-positive blood.a

Idiopathic Thrombocytopenic Purpura (ITP)

Rho(D) IGIV is used to increase platelet counts and to prevent excessive hemorrhage in adults with chronic ITP, children with acute or chronic ITP, and adults and children with ITP secondary to HIV infection1 2 3 4 5 6 7 8 9 10 11 12 13 (designated an orphan drug by FDA for this use).12

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

Efficacy established only in nonsplenectomized, Rho(D)-positive adults and children;1 2 3 4 5 7 f safety and efficacy for the treatment of ITP in other patient groups (i.e., Rho[D]-negative individuals, splenectomized individuals) or for the treatment of patients with thrombocytopenia not related to ITP not established.1 2 3 7 f

Rho(D) Immune Globulin Dosage and Administration

Administration

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Administer Rho(D) IGIM (HyperRHO, MICRhoGAM, RhoGAM) by IM injection; do not administer IV.c d e

Administer Rho(D) IGIV (Rhophylac, WinRho SDF) by IM or IV injection.b f

Rho(D) IG may be administered IM or IV for suppression of Rh isoimmunization.b c d e f

Rho(D) IG must be administered IV for the treatment of ITP.b f

Monitor patient for at least 20 minutes after administration.e

IM Administration

HyperRHO, MICRhoGAM, RhoGAM, Rhophylac, WinRho SDF: Administer by IM injection for suppression of Rh isoimmunization.b c d e f

Administer preferably into the deltoid muscle of the upper arm or anterolateral aspects of the upper thigh.14 15 b Avoid the central 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.14 15 b

When dose is >5 mL, divide and inject into several muscle sites to reduce local discomfort.f

Allow drug to reach room temperature before administration.f

Rho(D) IG is administered to the mother; do not administer to the infant.b c e f

IV Administration

Rhophylac and WinRho SDF: Administer by IV injection for the treatment of ITP.b f May be administered by IV injection for suppression of Rh isoimmunization.b f

When used for suppression of Rh isoimmunization, Rho(D) IG is administered to the mother; do not administer to the infant.b f

Allow drug to reach room temperature before administration.f

Do not mix with other drugs.b

Rate of Administration

Rhophylac: 2 mL per 15–60 seconds.f

WinRho SDF: Administer over 3–5 minutes.1

Dosage

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Potency of Rho(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.1 25 e f

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

A single 1500-unit (300-mcg) dose of Rho(D) IG contains enough anti-Rh o(D) to suppress the immunization potential of 15 mL of Rho(D)-positive RBCs.14 16 A single 250-unit (50-mcg) dose of Rho(D) IG contains enough anti-Rho(D) to suppress the immunization potential of 2.5 mL of Rho(D)-positive RBCs.15 16

Pediatric Patients

Idiopathic Thrombocytopenic Purpura (ITP)

Confirm that the patient is Rho(D)-positive prior to initiating therapy.b

Individualize the dosage based on clinical status (i.e., platelet count, RBC count, hemoglobin, reticulocyte count).1

IV

Rhophylac: 250 units/kg (50 mcg/kg).f For information on use of this agent in patients with anemia, see Hematologic Effects under Cautions.

WinRho SDF: Initially, 250 units/kg (50 mcg/kg) as a single injection or in 2 divided doses given on separate days.1 For patients with hemoglobin <10 g/dL, reduce dose to 125–200 units/kg (25–40 mcg/kg) to minimize the risk of increasing the severity of anemia.1 If subsequent therapy needed in patients with adequate response to the initial dose, maintenance dose is 125–300 units/kg (25–60 mcg/kg).1 For patients with an inadequate response to the initial dose, subsequent dose is based on hemoglobin.1 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).1 (See Hematologic Effects under Cautions.)

Adults

Suppression of Rh Isoimmunization

Rho(D) IG is used in unsensitized Rho(D)-negative women.b c d e f Prior to administration, determine whether recipient has been sensitized to Rho(D) antigens.j

Routine Antepartum Prophylaxis
IM

HyperRHO S/D Full Dose, RhoGAM: 1500 units (300 mcg) at about 28 weeks gestation.14 16

IM or IV

WinRho SDF, Rhophylac: 1500 units (300 mcg) at about 28 weeks gestation.1 25

Full-term Delivery (Postpartum)

Dosage depends on the magnitude of fetomaternal hemorrhage.14 16 b f Additional doses needed whenever a large fetal-maternal hemorrhage occurs during delivery.14 16 b e

IM

HyperRHO S/D Full Dose, RhoGAM: 1500 units (300 mcg) as soon as possible after delivery of an Rho(D)-positive infant, usually no later than 72 hours after delivery.14 16 Withhold postpartum dose if women received a dose in the preceding 3 weeks provided the women was not exposed to >15 mL of RBCs.e

If a large fetal-maternal hemorrhage (>15 mL RBCs) occurs, additional doses needed based on the extent of hemorrhage.14 e For HyperRHO S/D Full Dose, use an appropriate laboratory procedure to estimate the number of fetal Rh-positive RBC in maternal circulation and to calculate the RBC volume of the hemorrhage.14 Determine the number of HyperRHO Full Dose prefilled syringes (each syringe contains 1500 units [300 mcg]) needed by dividing the RBC volume of the hemorrhage by 15; if the calculated dose results in a fraction of a prefilled syringe, administer the next whole number of syringes.c

May be less effective if administered >72 hours after delivery.14 16 e

IM or IV

Rhophylac: 1500 units (300 mcg) within 72 hours of delivery of an Rho(D)-positive infant.25 f If a large fetal-maternal hemorrhage (>15 mL RBCs) occurs or is suspected, give an additional 100 units (20 mcg) per mL of fetal RBCs >15 mL if bleeding is quantified; if excess transplacental bleeding cannot be quantified, give an additional 1500 units (300 mcg) dose.f

WinRho SDF: 600 units (120 mcg) as soon as possible after delivery of an Rho(D)-positive infant, usually no later than 72 hours after delivery.1 Administer even if the Rh status of the infant is not known at 72 hours.1 If >72 hours have elapsed, administer as soon as possible up to 28 days after delivery.1 In the event of massive fetal hemorrhage, additional doses of WinRho SDF are administered using the dosage recommended for transfusion of Rho(D)-positive blood or blood products.b (See Transfusion of Blood or Blood Products under Dosage and Administration.)

May be less effective if administered >72 hours after delivery.14 16 f

Termination of Pregnancy
IM

HyperRHO S/D Mini-Dose, MICRhoGAM: 250 units (50 mcg) as soon as possible (preferably within 3 hours, usually no later than 72 hours) after a spontaneous or induced abortion occurring in a pregnancy up to and including 12 weeks of gestation.d e

HyperRHO S/D Full Dose, RhoGAM: 1500 units (300 mcg) within 72 hours of a spontaneous or induced abortion or ruptured tubal pregnancy in a pregnancy beyond 12 weeks of gestation.14 16

IM or IV

Rhophylac: 1500 units (300 mcg) within 72 hours of a miscarriage, abortion, ectopic pregnancy, or hydatidiform mole.f

WinRho SDF: 600 units (120 mcg) within 72 hours of an abortion.1

Other Obstetric Procedures or Complications During Pregnancy
IM

HyperRHO S/D Full Dose, RhoGAM: 1500 units (300 mcg) within 72 hours of amniocentesis, percutaneous umbilical blood sampling, chorionic villus sampling, abdominal trauma, obstetric manipulation, or threatened pregnancy loss in a pregnancy beyond 12 weeks gestation.14 e

If Rho(D) IG is administered early in the pregnancy, essential to give additional doses every 12 weeks to maintain adequate titers of anti-Rho(D).14 16 If delivery occurs within 3 weeks after an antepartum dose, withhold the postpartum dose (unless mother was exposed to >15 mL of RBCs).14 16

IM or IV

Rhophylac: 1500 units (300 mcg) within 72 hours of amniocentesis, chorionic villus sampling, abdominal trauma, obstetric manipulation, transplacental hemorrhage, or threatened pregnancy loss.f

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

If Rho(D) IG is administered early in the pregnancy, essential to give additional doses every 12 weeks to maintain adequate titers of anti-Rho(D).b e If delivery occurs within 3 weeks after an antepartum dose, withhold the postpartum dose (unless mother was exposed to >15 mL of RBCs).14 16

Transfusion of Blood or Blood Products

Dosage depends on volume of blood products transfused.b c e f

IM

HyperRHO S/D Full Dose: Calculate the volume of RBCs transfused by multiplying the volume of Rho(D)-positive whole blood administered by the hematocrit of the donor.14 Determine the number of HyperRHO S/D Full Dose prefilled syringes (each syringe contains 1500 units [300 mcg]) needed by dividing the RBC volume transfused by 15; if the calculated dose results in a fraction of a prefilled syringe, administer the next whole number of syringes.c Ensure that the total dose is administered within 72 hours.14

MICRhoGAM: 250 units (50 mcg) within 72 hours of exposure to <2.5 mL of Rh-positive RBCs.e

RhoGAM: 1500 units (300 mcg) within 72 hours of exposure to 2.5–15 mL of Rh-positive RBCs.e Additional dose(s) needed for exposure to >15 mL of Rh-positive RBCs; administer 20 mcg per mL of RBCs.e Ensure that the total dose is administered within 72 hours.e

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

IM or IV

Rhophylac: 100 units (20 mcg) per 2 mL of Rh-positive blood or per 1 mL of Rh-positive erythrocyte concentrate.25 Administer within 72 hours of exposure.f

IV

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

Idiopathic Thrombocytopenic Purpura (ITP)

Confirm that the patient is Rho(D)-positive prior to initiating therapy.b

Individualize the dosage based on clinical status (i.e., platelet count, RBC count, hemoglobin, reticulocyte count).1

IV

Rhophylac: 250 units/kg (50 mcg/kg).f For information on use of this agent in patients with anemia, see Hematologic Effects under Cautions.

WinRho SDF: Initially, 250 units/kg (50 mcg/kg) as a single injection or in 2 divided doses given on separate days.1 For patients with hemoglobin <10 g/dL, reduce dose to 125–200 units/kg (25–40 mcg/kg) to minimize the risk of increasing the severity of anemia.1 If subsequent therapy needed in patients with adequate response to the initial dose, maintenance dose is 125–300 units/kg (25–60 mcg/kg).1 For patients with an inadequate response to the initial dose, subsequent dose is based on hemoglobin.1 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).1 (See Hematologic Effects under Cautions.)

Special Populations

Hepatic Impairment

No specific dosage recommendations.b c d e f

Renal Impairment

No specific dosage recommendations.b c d e f

Cautions for Rho(D) Immune Globulin

Contraindications

  • History of anaphylactic or severe systemic reactions to immune globulins.1 f 16 25

  • When used for the suppression of Rh isoimmunization, do not administer to the infant.b

  • MICRhoGAM, RhoGAM: Rh-positive individuals.e

  • IgA deficiency.b (See Selective IgA Deficiency under Cautions.)

Warnings/Precautions

Warnings

Hematologic Effects

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Intravascular hemolysis, including some fatalities, reported in patients receiving Rho(D) IGIV for ITP.1 26 f Serious complications of intravascular hemolysis (e.g., acute onset or exacerbation of anemia, acute onset or exacerbation of renal insufficiency, disseminated intravascular coagulation) have occurred.1 26 f Monitor for signs and symptoms of intravascular hemolysis (e.g., back pain, shaking chills, fever, discolored urine), clinically compromising anemia, acute renal insufficiency, disseminated intravascular coagulation and, if necessary, perform confirmatory laboratory tests.1 26 e f If transfusion needed, use Rho(D)-negative packed red blood cells (PRBCs) to avoid exacerbation of the ongoing hemolysis.b f

Administration of Rho(D) IGIV to Rho(D)-positive individuals for the treatment of ITP expected to result in Rho(D)-positive RBC destruction and a decrease in hemoglobin concentration.1 2 3 4 5 6 7 8 10 13 f

WinRho SDF: When used for the treatment of ITP, reduce dose in individuals with hemoglobulin <10 g/dL.b Extreme caution advised in individuals with hemoglobulin <8 g/dL.b (See Idiopathic Thrombocytopenic Purpura (ITP) under Dosage and Administration.)

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

Bleeding may occur following IM administration in individuals with thrombocytopenia or other bleeding disorders.c d

Risk of Transmissible Agents in Plasma-derived Preparations

Because Rho(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).b c d e f

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

The manufacturing process for Rho(D) IG includes a solvent/detergent inactivation process and a filtering procedure to remove both enveloped and non-enveloped viruses.b c d e f

Because no purification method has been shown to be totally effective in removing the risk of viral infectivity from plasma-derived preparations and because new blood-borne viruses or other disease agents may emerge that may not be inactivated by the manufacturing process or the chemical (solvent/detergent) treatment procedures currently used, Rho(D) IG should be administered only when a benefit is expected.b c d e f

Report any infection believed to have been transmitted by Rho(D) IG to the manufacturer.b c d e f

Blood Glucose Testing

Rho(D) IGIV 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.b (See Specific Drugs and Laboratory Tests under Interactions.)

Sensitivity Reactions

Hypersensitivity

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

Selective IgA Deficiency

Rho(D) IG preparations contain trace or small quantities of IgA.1 16 25 f

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

General Precautions

Renal Effects

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Renal dysfunction and/or acute renal failure reported in patients receiving IGIV.b i These effects occur most frequently with IGIV preparations stabilized with sucrose.b i

Rho(D) IGIV does not contain sucrose as a stabilizer.b f

Assess renal function prior to administration of Rho(D) IGIV and at appropriate intervals during therapy, especially in those at risk of acute renal failure.b i If renal dysfunction occurs, consider reducing the infusion rate or discontinuing the drug.b

Specific Populations

Pregnancy

Category C.b c d e f

Rhophylac: Not evaluated in pregnant women with ITP.f

Lactation

Not distributed into milk;a no adverse effects are expected during breast feeding.25

Pediatric Use

For suppression of Rh isoimmunization related to pregnancy, do not administer Rho(D) IG to the infant.1 14 15 16 25 d f

HyperRHO S/D Full Dose, HyperRHO S/D Mini-Dose: Safety and efficacy not established in pediatric patients.14 15

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

WinRho SDF: Used in children for the treatment of acute or chronic ITP or ITP secondary to HIV infection.1

Geriatric Use

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

Common Adverse Effects

Chills, pyrexia, headache, nausea, dizziness, mild extravascular hemolysis (increased bilirubin, decreased hemoglobin).b c d e f

Interactions for Rho(D) Immune Globulin

Live Vaccine

Antibodies present in immune globulin preparations may interfere with the immune response to measles virus vaccine live, mumps virus vaccine live, rubella virus vaccine live, and varicella virus vaccines live;b c d e f no evidence of interference with the immune response to yellow fever virus vaccine live or typhoid vaccine live oral.24 k (See Specific Drugs and Laboratory Tests under Interactions.)

Postpartum administration of Rho(D) IG has not been shown to reduce the response to rubella vaccine RA27/3 strain.k Rubella and varicella immunity are important in women of childbearing potential.k The Advisory Committee on Immunization Practices (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 Rho(D) IG.k Perform serologic tests ≥3 months after vaccination to determine if seroconversion occurred.k

Inactivated Vaccine and Toxoids

ACIP states that administration of inactivated vaccines and toxoids simultaneously with (at different sites) or at any interval before or after administration of immune globulin preparations should not have a clinically important effect on the immune response to the vaccines or toxoids.k

Specific Drugs and Laboratory Tests

Drug or Test

Interaction

Comments

Measles, mumps, rubella, varicella vaccine live

Antibodies in Rho(D) IG may interfere with the immune response to these live virus vaccines1 14 15 22 24 f

Rubella: No evidence that Rho(D) IG interferes with immune response to the vaccinek

ACIP recommends administering the appropriate vaccine immediately after deliveryk (See Live Vaccine under Interactions.)

Manufacturers recommend deferring administration of these live virus vaccines for ≥3 months following administration of Rho(D) IG1 14 15 25

Tests, antibody screening

Possible positive antibody screening test from the presence of passively acquired anti-D in the maternal blood streame f

Tests, blood glucose (based on GDH-PQQ or glucose-dye oxidoreductase)

Maltose-containing Rho(D) IG preparations (e.g., WinRho SDF): Potential for falsely elevated blood glucose test resultsb

Use test methods not affected by maltose in patients receiving maltose-containing Rho(D) IG preparations b

Tests, blood typing

May affect blood typing test results in the mother and the infante f

Tests, immunohematology (Coombs’ test)

Passively transferred blood group antibodies (e.g., anti-A, anti-B, anti-C, anti-E) may result in positive direct and indirect antiglobulin (Coombs’) test resultsb

Interpret test results in the context of the patient’s underlying clinical condition and other laboratory resultsb

Typhoid vaccine live

No evidence that Rho(D) IG interferes with immune response to the vaccinek

Vaccine may be given simultaneously with or at any interval before or after Rho(D) IGk

Yellow fever virus vaccine

No evidence that Rho(D) IG interferes with immune response to the vaccinek

Vaccine may be given simultaneously with or at any interval before or after Rho(D) IGk

Rho(D) Immune Globulin Pharmacokinetics

Absorption

Bioavailability

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

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

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

Distribution

Extent

Not distributed into milk.a

Elimination

Half-life

IM administration: 18–31 days.b e f

IV administration: 24 days.b

Stability

Storage

Parenteral

Injection

2–8°C.b c d e f Do not freeze.b c d e f

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

Actions

  • Contains anti-Rho(D) antibody to the RBC cell antigen Rho(D); used to provide temporary passive immunity in Rho(D)-negative individuals exposed to Rho-positive blood from a pregnancy (when fetus is Rho(D)-positive) or from an Rho(D)-positive blood transfusion.1 14 15 16

  • Mechanism by which Rho(D) IG suppresses anti-Rho(D) not fully elucidated;1 14 15 16 25 anti-Rho(D) antibody may bind to Rho(D) antigen thus preventing the primary immune response to Rho(D) and production of anti-Rho(D).a

  • Mechanism by which Rho(D) IG increases platelet counts in the treatment of ITP not fully elucidated;1 2 3 7 20 21 b administration of Rho(D) IG to Rho(D)-positive individuals results in formation of anti-Rho(D)-coated RBC complexes that may saturate Fc receptors and decrease Fc-mediated phagocytosis of antibody-coated platelets.1 2 3 4 7 20 21

Advice to Patients

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

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

  • Importance of retaining the patient identification card with the record of Rho(D) IG administration and of presenting this card to healthcare providers.e

  • Instruct patients receiving Rho(D) IGIV for the treatment of ITP to immediately report symptoms of back pain, shaking chills, fever, discolored urine, decreased urine output, swelling, and/or shortness of breath to their clinician.b f g

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

  • Instruct pregnant women receiving Rho(D) IG at gestation week 28 of the need for a second dose at delivery if the baby’s blood type is Rh-positive.f h

  • Importance of notifying clinician if signs and symptoms of a hypersensitivity reaction (i.e., generalized urticaria, tightness of the chest, wheezing, hypotension, and anaphylaxis) occur.16 f

  • Advise patients with selective IgA deficiency that Rho(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.1 16 25 f

  • 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.b

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.b c d e f

  • 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.b c d e f g

  • Importance of informing patients of other important precautionary information.b c d e f (See Cautions.)

Preparations

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

Rho(D) Immune Globulin IM

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for IM use only

250 units (50 mcg)

HyperRHO S/D Mini-Dose (solvent/detergent-inactivated and virus filtered and with glycine 0.21–0.32 M; available in single- dose prefilled syringes)

Talecris

MICRhoGAM (virus filtered and with glycine 15 mg/mL; available in single-dose prefilled syringes)

Ortho-Clinical Diagnostics

1500 units (300 mcg)

HyperRHO S/D Full Dose (solvent/detergent-inactivated and virus filtered and with glycine 0.21–0.32 M; available in single-dose prefilled syringes)

Talecris

RhoGAM (virus filtered and with glycine 15 mg/mL; available in single-dose prefilled syringes)

Ortho-Clinical Diagnostics

Rho(D) Immune Globulin IV

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection

600 units (120 mcg)

WinRho SDF (solvent/detergent-inactivated and virus filtered)

Baxter

1500 units (300 mcg)

WinRho SDF (solvent/detergent-inactivated and virus filtered)

Baxter

Rhophylac (solvent/detergent-inactivated and virus filtered and with glycine 20 mg/mL; available in single-dose prefilled syringes)

CLS Behring

2500 units (500 mcg)

WinRho SDF (solvent/detergent-inactivated and virus filtered)

Baxter

5000 units (1000 mcg)

WinRho SDF (solvent/detergent-inactivated and virus filtered)

Baxter

15,000 units (3000 mcg)

WinRho SDF (solvent/detergent-inactivated and virus filtered)

Baxter

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions April 1, 2010. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Baxter. WinRho SDF (Rho [D] immune globulin intravenous [human]) prescribing information. Westlake Village, CA; 2004 Oct.

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a. AHFS Drug Information 2007. McEvoy GK, ed. Rho [D] Immune Globulin. Bethesda, MD: American Society of Health-System Pharmacists; 2007:3313-19.

b. Baxter. WinRho SDF (Rho [D] immune globulin intravenous [human]) prescribing information. Westlake Village, CA; 2006 Apr.

c. Talecris. HyperRHO S/D Full Dose (Rho [D] immune globulin [human]) prescribing information. Research Triangle Park, NC; 2007 Jun.

d. Talecris. HyperRHO S/D Mini-Dose (Rho [D] immune globulin [human]) prescribing information. Research Triangle Park, NC; 2007 Jun.

e. Ortho-Clinical Diagnostics. Rho-GAM (Rho [D] immune globulin [human]) ultra-filtered and MICRhoGAM (Rho [D] immune globulin [human]) ultra-filtered prescribing information. Raritan, NJ; 2007 Mar.

f. CSL Behring. Rhophylac (Rho [D] immune globulin intravenous [human]) prescribing information. Kankakee, IL; 2007 Mar.

g. Baxter. WinRho SDF (Rho [D] immune globulin intravenous [human]) patient information. Westlake Village, CA; 2006 Apr.

h. Talecris. HyperRho SD (Rho (D) immune globulin) patient information. Research Triangle Park, NC; 2007 Jun.

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j. American College of Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins. Management of alloimmunization druing pregnancy. Practice Bulletin No. 75. Washington, DC: American College of Obstetricians and Gynecologists; 2006 Aug.

k. Centers for Disease Control and Prevention. General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2006; 55(RR-15):1-47.

l. Beardsley DS. ITP in the 21st Century. Hematology Am Soc Hematol Educ Program. 2006; 402-7.

m. Kumar S. Universal RDH genotyping in fetuses. BMJ. 2008; 336:783-4. [PubMed 18390495]

n. American College of Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins. Prevention of Rh D alloimmunization. Practice Bulletin No. 4. Washington, DC: American College of Obstetricians and Gynecologists;1999 May.

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