Rh o (D) Immune Globulin

( RhIG )

Pronunciation: i-MUNE GLOB-ue-lin
Class: Immune globulin

Trade Names

HyperRHO S/D Full-Dose
- Injection 15% to 18% protein

HyperRHO S/D Mini-Dose
- Injection 15% to 18% protein

MICRhoGAM
- Injection 250 units (50 mcg)

RhoGAM
- Injection 1,500 units (300 mcg)

Rhophylac
- Injection 1,500 units (300 mcg)

WinRho SDF
- Injection 1,500 units (300 mcg)
- Injection 2,500 units (500 mcg)
- Injection 5,000 units (1,000 mcg)
- Injection 15,000 units (3,000 mcg)

Pharmacology

By binding Rh o (D) antigen on RBCs, RhIG prevents production of anti-Rh o (D) (anti-D) antibodies in Rh o (D) antigen–negative patients. Prevention of Rh sensitization, in turn, prevents hemolytic disease of the fetus and newborn in subsequent Rh o (D) antigen–positive children.

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Pharmacokinetics

Absorption

MICRhoGAM , RhoGAM

C max is 54 ng/mL. T max is 4 days.

Rhophylac

Bioavailability is 69%; C max is 62 to 84 ng/mL after 1 day (IV); C max is 7 to 46 ng/mL between 2 and 7 days (IM).

WinRho SDF

C max (36 to 48 ng/mL) reached within 2 h of IV administration and C max (18 to 19 ng/mL) reached at 5 to 10 days after IM administration.

Distribution

MICRhoGAM , RhoGAM

Vd is 7.3 L.

Elimination

The half-life is approximately 30 days (IM).

MICRhoGAM , RhoGAM

Elimination half-life is 30.9 days; Cl is 150.4 mL/day.

Rhophylac

Mean systemic Cl is 0.2 mL/min and half-life is approximately 16 days (IV); mean apparent Cl is 0.29 mL/min and half-life is 18 days (IM).

WinRho SDF

Half-life is approximately 24 days (IV) and approximately 30 days (IM).

Indications and Usage

HyperRHO S/D Full-Dose

Prevention of Rh hemolytic disease of the newborn; suppression of Rh isoimmunization in nonsensitized Rh o (D)–negative women following spontaneous or induced abortion following ruptured tubal pregnancy, amniocentesis, or abdominal trauma; for prevention of isoimmunization in Rh o (D)–negative individuals who have been transfused with Rh o (D)–positive RBCs or blood components containing RBCs.

HyperRHO S/D Mini-Dose , MICRhoGAM

Prevent isoimmunization of Rh o (D)–negative women at the time of spontaneous or induced abortion of up to 12 weeks' gestation; for prevention of Rh immunization in Rh o (D)–negative individuals after incompatible transfusion of Rh-positive blood or blood products ( MICRhoGAM only).

RhoGAM

For administration to Rh-negative women not previously sensitized to the Rh o (D) factor after delivery of an Rh-positive baby irrespective of the ABO groups of the mother and baby, antepartum prophylaxis at 26 to 28 weeks' gestation, antepartum fetomaternal hemorrhage, amniocentesis, chorionic villus sampling (CVS), ectopic pregnancy, abdominal trauma, percutaneous umbilical sampling, other obstetrical manipulative procedure, or actual or threatened abortion; for prevention of Rh immunization in any Rh-negative person after incompatible transfusion of Rh-positive blood or blood products (eg, RBCs, platelet concentrates, granulocyte concentrates).

Rhophylac Immune thrombocytopenic purpura (ITP)

To raise platelet counts in Rh o (D)–positive, nonsplenectomized adult patients with chronic ITP.

Suppression of Rh isoimmunization Obstetric conditions

Suppression of Rh isoimmunization in nonsensitized Rh o (D)–negative women, including routine antepartum and postpartum Rh prophylaxis; Rh prophylaxis in case of obstetric complications (eg, miscarriage, abortion, threatened abortion, ectopic pregnancy or hydatidiform mole, transplacental hemorrhage resulting from antepartum hemorrhage); Rh prophylaxis in case of invasive procedures during pregnancy (eg, amniocentesis, chorionic biopsy or obstetric manipulative procedures [eg, external version], abdominal trauma).

Transfusion

Suppression of Rh isoimmunization in Rh o (D)–negative patients transfused with Rh o (D)–positive RBCs or blood components containing Rh o (D)–positive RBCs.

WinRho SDF ITP

Treatment of ITP must be given IV when an increase in platelet count occurs to prevent excessive hemorrhage in treating Rh o (D)–positive, nonsplenectomized children with chronic or acute ITP, nonsplenectomized adults with chronic ITP, or nonsplenectomized children and adults with ITP secondary to HIV infection.

Suppression of Rh isoimmunization Obstetric conditions

Suppression of Rh isoimmunization in nonsensitized Rh o (D)–negative women 72 h after spontaneous or induced abortions, amniocentesis, CVS, ruptured tubal pregnancy, abdominal trauma, or transplacental hemorrhage, or in the normal course of pregnancy unless the blood type of fetus or father is known to be Rh o (D) negative.

Transfusion

Suppression of Rh isoimmunization in Rh o (D)–negative female children and adults during their childbearing years who have been transfused with Rh o (D)–positive RBCs or blood components containing Rh o (D)–positive RBCs.

Contraindications

Hypersensitivity to any immune globulin or any of the product's components. Do not administer to an infant when used for suppression of Rh isoimmunization; persons deficient in immunoglobulin (IgA).

MICRhoGAM , RhoGAM

Rh-positive individuals.

WinRho SDF

Patients with preexisting hemolysis or who are at high risk for hemolysis; patients with autoimmune hemolytic anemia.

Dosage and Administration

HyperRHO S/D Full-Dose
Pregnancy and Other Obstetric Conditions Adults

IM

Postpartum prophylaxis

Administer 1 HyperRHO S/D Full-Dose syringe, preferably within 72 h of delivery. One full-dose syringe provides sufficient antibody to prevent Rh sensitization if the RBC volume that entered the circulation is 15 mL or less. If a large (more than 30 mL of whole blood or 15 mL of RBCs) fetomaternal hemorrhage is suspected, perform a fetal RBC count by an approved laboratory technique to determine the required immune globulin dose. The RBC volume of the fetomaternal hemorrhage is divided by 15 mL to obtain the number of full-dose syringes to be administered.

Antenatal prophylaxis

Administer 1 syringe (1,500 units) at approximately 26 to 28 weeks' gestation, followed by another full dose, preferably within 72 h following delivery, if the infant is Rh positive.

Threatened abortion

It is recommended that a full dose be given at any stage of gestation with continuation of pregnancy. If more than 15 mL of RBCs is suspected because of fetomaternal hemorrhage, the dose modification previously discussed in the Postpartum Prophylaxis section applies.

Miscarriage, abortion, or termination of ectopic pregnancy at or beyond 13 weeks' gestation

It is recommended that a full dose be given. If more than 15 mL of RBCs is suspected because of fetomaternal hemorrhage, the dose modification previously discussed in the Postpartum Prophylaxis section applies. If pregnancy is terminated prior to 13 weeks' gestation, a single-dose HyperRHO S/D Mini-Dose may be used instead of HyperRHO S/D Full-Dose .

Amniocentesis

Following amniocentesis at either 13 or 18 weeks' gestation or during the third trimester, or following abdominal trauma in the second or third trimester, obstetrical manipulation, CVS, or percutaneous blood sampling, it is recommended that a full dose be administered within 72 h of exposure. If there is a fetomaternal hemorrhage in excess of 15 mL of RBCs, the dose modification discussed previously in the Postpartum Prophylaxis section applies. If abdominal trauma, amniocentesis, or other adverse reaction requires giving HyperRHO S/D Full-Dose at 13 to 18 weeks' gestation, give another full dose at 26 to 28 wk. To maintain protection throughout pregnancy, the level of passively acquired anti-Rh o (D) should not fall below the level required to prevent immune response to Rh-positive red cells. Give a HyperRHO S/D Full-Dose within 72 h after delivery if the baby is Rh positive. If delivery occurs within 3 wk after the last dose, the postpartum dose may be withheld unless there is a fetomaternal hemorrhage in excess of 15 mL of RBCs.

Transfusion

The volume of Rh-positive whole blood given is multiplied by the hematocrit of the donor unit giving the volume of RBC transfused. The volume of RBCs is divided by 15 mL, which provides the number of syringes of HyperRHO S/D Full-Dose to be administered within 72 h.

MICRhoGAM and HyperRHO S/D Mini-Dose
Pregnancy and Other Obstetric Conditions Adults Actual or threatened termination of pregnancy (spontaneous or induced) up to 12 weeks' gestation

IM Administer 50 mcg within 72 h. RhoGAM may be administered if MICRhoGAM is not available.

Transfusion of Rh-incompatible blood or blood products ( MICRhoGAM only)

IM Less than 2.5 mL of Rh-positive RBCs: Administer 50 mcg of MICRhoGAM . RhoGAM may be administered if MICRhoGAM is not available.

RhoGAM
Pregnancy and Other Obstetric Conditions Adults Postpartum

IM If the newborn is Rh-positive, administer 300 mcg within 72 h of delivery. Additional doses are indicated when the patient has been exposed to more than 15 mL of Rh-positive RBCs. This may be determined by use of qualitative or quantitative tests for fetal-maternal hemorrhage.

Antepartum (prophylaxis at 26 to 28 weeks' gestation)

IM Administer 300 mcg within 72 h of suspected or proven exposure to Rh-positive RBCs resulting from amniocentesis, CVS, or percutaneous umbilical blood sampling, abdominal trauma or obstetrical manipulation, ectopic pregnancy, threatened pregnancy loss after 12 weeks' gestation with continuation of pregnancy; pregnancy termination (spontaneous or induced) beyond 12 weeks' gestation. If antepartum prophylaxis is indicated, it is essential that the mother receive a postpartum dose if the infant is Rh-positive. If RhoGAM is administered early in pregnancy (before 26 to 28 wk), there is an obligation to maintain a level of passively acquired anti-D by administration of RhoGAM at 12-wk intervals.

Transfusion

IM 300 mcg. Additional doses are indicated when the patient has been exposed to more than 15 mL of Rh-positive RBCs. Administer 20 mcg of RhoGAM per mL of Rh-positive RBC exposure. Multiple doses may be administered at the same time or at spaced intervals as long as the total dose is administered within 72 h of exposure.

Rhophylac
ITP Adults

IV 50 mcg/kg as a single injection. Administer at a rate of 2 mL per 15 to 60 sec.

Suppression of Rh Isoimmunization Rh-Incompatible Pregnancy Excessive Fetomaternal Hemorrhage (more than 15 mL) Adults

IM / IV Within 72 h of complications, 300 mcg plus 20 mcg per mL fetal RBCs in excess of 15 mL if excess transplacental bleeding is quantified, or an additional 300 mcg dose if excess transplacental bleeding cannot be quantified.

Other Obstetric Considerations Adults

IM / IV 300 mcg within 72 h of complications or invasive procedures. Dose must be increased if exposed to more than 15 mL of Rh o (D)-positive RBCs; in these cases, follow dosing guidelines for excessive fetomaternal hemorrhage.

Postpartum Prophylaxis Adults

IM / IV 300 mcg within 72 h of birth. Dose must be increased if exposed to more than 15 mL of Rh o (D)-positive RBCs; in these cases, follow dosing guidelines for excessive feto-maternal hemorrhage.

Routine Antepartum Prophylaxis Adults

IM / IV 300 mcg at weeks' 28 to 30 of gestation.

Transfusion Adults

IM / IV 200 mcg per 2 mL of transfused blood or per 1 mL of erythrocyte concentrate within 72 h of exposure.

WinRho SDF
ITP Adults and Children

IV Initial dose of 50 mcg/kg as a single injection. The initial dose may be given in 2 divided doses on separate days, if desired. If the Hgb level is less than 10 g/dL, reduce the dose to 25 to 40 mcg/kg. If subsequent treatment is needed to elevate platelet counts, an IV dose of 25 to 60 mcg/kg is recommended. If the patient responds to the initial dose with a satisfactory increase in platelets, the maintenance dosing, 25 to 60 mcg/kg, is individualized based on platelet and Hgb levels. If the patient does not respond to the initial dose, give a subsequent dose based on Hgb. If Hgb is between 8 and 10 g/dL, redose between 25 and 40 mcg/kg. If Hgb is more than 10 g/dL, redose between 50 and 60 mcg/kg. If the Hgb is less than 8 g/dL, alternative treatments should be used.

Suppression of Rh Isoimmunization Pregnancy

IM / IV 300 mcg at 28 weeks' gestation. If administered early in the pregnancy, administration at 12-wk intervals is recommended. A 120 mcg dose should be given as soon as possible after delivery of a confirmed Rh o (D)–positive baby and no later than 72 h after delivery. If the Rh status of the baby is not known at 72 h, administer to the mother at 72 h after delivery. If more than 72 h have elapsed, do not withhold, but administer as soon as possible up to 28 days after delivery.

Other Obstetric Considerations

IM / IV 120 mcg dose immediately (within 72 h) after abortion, amniocentesis, or any other manipulation late in pregnancy (after 34 weeks' gestation) associated with increased risk of Rh isoimmunization. Give a 300 mcg dose immediately after amniocentesis or after CVS (before 34 weeks' gestation). Repeat this dose every 12 wk while pregnant. In case of threatened abortion, give 300 mcg as soon as possible.

Adults and Children Transfusion

IM / IV If exposed to Rh o (D)–positive whole blood, give 9 mcg/mL of blood IV or 12 mcg/mL of blood IM. If exposed to Rh o (D)–positive RBCs, give 18 mcg/mL of cells IV or 24 mcg/mL of cells IM. Administer within 72 h after exposure.

General Advice

  • HyperRHO S/D Full-Dose
  • Do not inject IV. For IM use only, preferably in the anterolateral aspects of the upper thigh and the deltoid muscle of the upper arm.
  • Do not inject neonates.
  • The entire contents of a single-dose syringe may be injected into the patient.
  • If the dose consists of multiple syringes, the total volume can be given in divided doses at different sites at one time or the total dose may be divided and injected at intervals, provided the total dosage is given within 72 h of the fetomaternal hemorrhage or transfusion.
  • If more than 15 mL of D-positive fetal RBCs are present in the mother's circulation, more than a single syringe of HyperRHO S/D Full-Dose is required; failure to recognize this may result in an inadequate dose.
  • HyperRHO S/D Mini-Dose
  • Do not inject IV. For IM use only, preferably in the anterolateral aspects of the upper thigh and the deltoid muscle of the upper arm.
  • Administer only to women postabortion or postmiscarriage of up to 12 weeks' gestation.
  • MICRhoGAM , RhoGAM
  • Do not inject IV. For IM use only.
  • In the case of postpartum use, the products are intended for maternal administration only. Do not inject the newborn.
  • Rhophylac
  • Administer to ITP patients by the IV route only at a rate of 2 mL per 15 to 60 sec.
  • Administer IM or IV for suppression of Rh isoimmunization. If large doses (more than 5 mL) are required, administer in divided doses at different sites.
  • Bring to room temperature before use.
  • WinRHo SDF
  • IV: Inject rapidly over 3 to 5 min.
  • IM: Administer into the deltoid muscle of the upper arm or the anterolateral aspects of the upper thigh.
  • Administer separately from other drugs.

Storage/Stability

Store at 36° to 46°F. Do not freeze. Protect Rhophylac from light. Discard any unused portion.

Drug Interactions

Live virus vaccines (eg, measles, mumps, polio, rubella)

Immunoglobulin administration may transiently impair the efficacy of live attenuated virus vaccines such as measles, mumps, rubella, polio, and varicella. Ensure the immunizing health care provider is informed of recent therapy with Rh o (D) immune globulin IV so that appropriate measures can be taken. Do not give immunization with live vaccines within 3 mo after WinRho SDF administration.

Incompatibility

Do not coadminister RhIG IV with other products.

Laboratory Test Interactions

WinRho SDF contains maltose, which may give falsely high blood glucose levels when certain types of blood glucose testing systems are used (eg, glucose-dye-oxidoreductase method). Rh o (D) immune globulin may affect the results of blood typing, the antibody screening test, and the direct antiglobulin (Coombs) test. Antepartum administration of Rho(D) immune globulin to the mother can also affect these tests in the newborn. Rhophylac can contain antibodies to other Rh antigens (eg, anti-C antibodies), which might be detected by sensitive serological tests following administration. WinRho SDF contains trace amounts of anti-A, anti-B, anti-C, anti-E, and other blood group antibodies (eg, anti-Duffy, anti-Kidd antibodies) that may be detectable in direct and indirect antiglobulin (Coombs) tests obtained following RhIG administration. Interpretation of direct and indirect antiglobulin tests must be made in the context of the patient's underlying clinical condition and supporting laboratory data.

Adverse Reactions

Cardiovascular

Hypertension, hypotension, vasodilation (2% or less); cardiac arrest, cardiac failure, MI, tachycardia (postmarketing).

CNS

Headache (11%); asthenia, dizziness, hyperkinesia, malaise, somnolence (2% or less); fatigue, vertigo (postmarketing).

Dermatologic

Pruritus, rash, sweating (2% or less); erythema, hyperhydrosis (postmarketing).

GI

Abdominal pain, diarrhea, nausea, vomiting (2% or less); diarrhea (postmarketing).

Hematologic-Lymphatic

Extravascular hemolysis; anemia, DIC, hemoglobinemia, intravascular hemolysis, severe anemia (postmarketing).

Lab Tests

Bilirubin elevated (21%); creatinine elevated, decreased Hgb, haptoglobin decreased, LDH increased (2% or less).

Local

Pain at the injection site; induration, irritation, pruritis, swelling, warmth (postmarketing).

Musculoskeletal

Arthralgia, back pain, myalgia (2% or less); muscle spasm, pain in extremities (postmarketing).

Renal

Acute renal insufficiency; anuria, chromaturia, hemoglobinuria, hematuria, renal failure, renal impairment (postmarketing).

Respiratory

Acute respiratory distress syndrome, dyspnea, transfusion-related acute lung injury (postmarketing).

Miscellaneous

Chills (35%); pyrexia/increased body temperature (31%); pallor (2% or less); allergic or anaphylactic reactions, chest pain, edema (postmarketing).

Precautions

Warnings

WinRho SDF

Intravascular hemolysis leading to death has been reported in patients treated for ITP with WinRho SDF .

Intravascular hemolysis can lead to clinically compromising anemia and multisystem organ failure, including acute respiratory distress syndrome.

Serious complications, including severe anemia, acute renal insufficiency, renal failure, and DIC, have also been reported.

Closely monitor patients treated with WinRho SDF for ITP in a health care setting for at least 8 h after administration. If signs and/or symptoms of intravascular hemolysis are present or suspected after WinRho SDF administration, posttreatment laboratory tests should be performed, including plasma Hgb, haptoglobin, LDH, and plasma bilirubin (direct and indirect).


Monitor

When administering Rhophylac or WinRho SDF to ITP patients, monitor for signs and symptoms of clinically compromising anemia, DIC, intravascular hemolysis, and acute renal impairment. ITP patients presenting with signs and/or symptoms of intravascular hemolysis should have CBC (Hgb, platelets), hepatoglobin, plasma Hgb, urine dipstick, renal function, liver function, and DIC-specific tests (D-dimer or fibrin/fibrogen degradation products or fibrin split products) monitored. WinRho SDF contains maltose, which can cause falsely elevated glucose levels. Use a glucose-specific test or monitor blood glucose levels. Observe patients for at least 8 h after administration and perform a dipstick urinalysis at baseline, 2 and 4 h after administration, and prior to the end of the monitoring period. Monitor patients for pulmonary adverse reactions. Monitor renal function and urine output, including BUN and serum creatinine, before initial infusion and at appropriate intervals thereafter in patients at risk of developing acute renal failure. Consider baseline assessment of blood viscosity in patients at risk for hyperviscosity.


Pregnancy

Category C .

Lactation

Undetermined.

Children

For suppression of Rh isoimmunization in the mother, do not administer to infants. Safety and efficacy not established for Rhophylac .

Elderly

Fatal outcomes associated with intravascular hemolysis and its complications have occurred most frequently in elderly patients with comorbid conditions.

Renal Function

Renal impairment may occur in patients predisposed to acute renal failure or who have renal insufficiency.

Allergy

Allergic response, including anaphylactoid reactions, may occur.

Allergy history

Use with caution in patients with a history of systemic allergic reactions following administration of human immunoglobulin preparations.

Hematologic/Lymphatic

Bleeding complications may occur in patients with thrombocytopenia or other bleeding disorders. Use with extreme caution in patients with Hgb less than 8 g/dL.

IgA deficiency

Persons with specific IgA deficiency have increased potential for developing antibodies to IgA and could have anaphylactic reactions to subsequent administration of blood products containing IgA.

IM administration

As with other drugs administered by IM injection, give RhIG with caution to patients on anticoagulant therapy.

Infection

Because RhIG is made from human plasma, there is a risk of transmitting infectious agents (eg, viruses) and, theoretically, Creutzfeldt-Jakob disease.

Intravascular hemolysis

May occur. Serious complications, including severe anemia, acute renal insufficiency, renal failure, DIC, and acute respiratory distress syndrome, have been reported.

Maltose

WinRho SDF contains maltose, which has been shown to give false high blood glucose levels in certain types of blood glucose testing systems.

Rh isoimmunization suppression

Do not administer WinRho SDF to Rh o (D)–negative persons who are Rh immunized as evidenced by an indirect antiglobulin (Coombs) test revealing the presence of the anti-D antibody.

Thrombotic events

May occur following IV administration.

Transfusion

If ITP patients are to be transfused, Rh o (D)–negative RBCs should be used so as not to exacerbate ongoing hemolysis.

Transfusion-related lung injury

Noncardiogenic pulmonary edema may occur following IV treatment.

Overdosage

Symptoms

Chills, fever, headache, large Hgb decreases, risk of hemolytic reaction.

Patient Information

  • Instruct patient not to receive any live vaccines within 30 days before or 3 mo after administration of drug.
  • Explain how future Rh o (D)–positive infants will be protected.
  • Instruct patients to report the following symptoms to health care provider: abdominal pain, back pain, chills, decreased urine output, discolored urine, edema, fluid retention, lethargy, myalgia, shaking, shortness of breath, and sudden weight loss.
  • Inform patients that Rh o (D) immune globulin is made from human plasma and may contain infectious agents that can cause disease.
  • Inform patients of the early signs of allergic or hypersensitivity reactions, including anaphylaxis, chest tightness, hives, hypotension, and wheezing, and inform them to contact their health care provider immediately.

Copyright © 2009 Wolters Kluwer Health.

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