Rho(D) Immune Globulin

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Injection [preservative free]:

WinRho SDF: 1500 units (300 mcg) (1.3 mL); 2500 units (500 mcg) (2.2 mL); 5000 units (1000 mcg) (4.4 mL); 15,000 units (3000 mcg) (13 mL) [contains polysorbate 80]

Solution Prefilled Syringe, Injection [preservative free]:

Rhophylac: 1500 units (300 mcg) (2 mL)

Solution Prefilled Syringe, Intramuscular [preservative free]:

HyperRHO S/D: 250 units (50 mcg) (1 ea); 1500 units (300 mcg) (1 ea) [latex free]

MICRhoGAM Ultra-Filtered Plus: 250 units (50 mcg) (1 ea) [latex free, thimerosal free; contains polysorbate 80]

RhoGAM Ultra-Filtered Plus: 1500 units (300 mcg) (1 ea) [latex free, thimerosal free; contains polysorbate 80]

Pharmacology

Mechanism of Action

Rh suppression: Prevents isoimmunization by suppressing the immune response and antibody formation by RhD-negative individuals to RhD-positive red blood cells. When administered within 72 hours of a full-term delivery, the incidence of Rh isoimmunization decreases from 12% to 13% to 1% to 2%. The rate further decreases to <1% with administration at both 28 weeks' gestation and postpartum.

ITP: Rh_o(D) immune globulin is thought to form anti-D-coated red blood cell complexes which bind to macrophage Fc receptors within the reticuloendothelial system (RES); blocks or saturates the RES ability to clear antibody-coated cells, including platelets. Thus, platelets are spared from destruction.

Pharmacokinetics/Pharmacodynamics

Distribution

V_d: IM: RhoGAM Ultra Filtered Plus: 7.3 ± 1.5 L

Onset of Action

Onset of platelet increase: ITP: WinRho: Platelets should rise within 1 to 2 days; Peak effect: WinRho: In 7 to 14 days

Time to Peak

Plasma: RhoGAM Ultra Filtered Plus: 4 days (IM); Rhophylac: 1 day (IV), 2 to 7 days (IM); WinRho SDF: ≤2 hours (IV), 5 to 10 days (IM)

Duration of Action

Suppression of RhD isoimmunization: Rhophylac 300 mcg dose: Rh_o(D) immune globulin titers detected up to at least 9 weeks; WinRho SDF 120 mcg dose: ≤6 weeks; Treatment of ITP: 30 days (variable)

Half-Life Elimination

RhoGAM Ultra Filtered Plus: 30.9 ± 13.8 days (IM); Rhophylac: 16 ± 4 days (IV), 18 ± 5 days (IM); WinRho SDF: ~24 days (IV), ~30 days (IM)

Use: Labeled Indications

Immune thrombocytopenia (ITP):

Rhophylac: To increase platelet counts in RhD-positive nonsplenectomized adults with chronic ITP.

Safety and efficacy of Rhophylac have not been established in patients with preexisting anemia; may increase the severity of preexisting anemia.

WinRho SDF: To increase platelet counts in RhD-positive nonsplenectomized patients with the following conditions: acute ITP (children), chronic ITP (adults and children), or ITP secondary to HIV infection (adults and children).

Safety and efficacy of WinRho have not been established in RhD-negative, non-ITP causes of thrombocytopenia, or in previously splenectomized patients

Pregnancy and other obstetric conditions:

Prevention of RhD isoimmunization in an RhD-incompatible pregnancy. All products are for use in RhD-negative mothers who are not already sensitized to the RhD factor. An RhD-incompatible pregnancy is assumed if the fetus/baby is either RhD-positive or RhD unknown or if the father is either RhD-positive or RhD unknown. Use is not needed if the father or baby is conclusively RhD-negative. Product specific indications are as follows based on the above criteria:

HyperRHO S/D Full Dose: Antepartum and postpartum RhD prophylaxis for the prevention of hemolytic disease of the newborn; RhD prophylaxis following spontaneous or induced abortion, ruptured tubal pregnancy, amniocentesis or abdominal trauma.

HyperRHO S/D Mini Dose: RhD prophylaxis following spontaneous or induced abortion up to 12 weeks' gestation.

MICRhoGAM Ultra-Filtered Plus: RhD prophylaxis following actual or threatened termination of pregnancy (spontaneous or induced) up to and including 12 weeks' gestation.

RhoGAM Ultra-Filtered Plus: Antepartum RhD prophylaxis; postpartum RhD prophylaxis following delivery of an RhD-positive baby; RhD prophylaxis following amniocentesis, chorionic villus sampling (CVS), percutaneous umbilical blood sampling (PUBS), abdominal trauma or obstetrical manipulation, placenta previa, ectopic pregnancy, threatened pregnancy loss after 12 weeks' gestation (with continuation of pregnancy), pregnancy termination (spontaneous or induced) after 12 weeks' gestation.

Rhophylac, WinRho SDF: Routine antepartum and postpartum RhD prophylaxis; RhD prophylaxis in cases of obstetric complications including miscarriage, abortion, threatened abortion, ectopic pregnancy or hydatiform mole, transplacental hemorrhage resulting from antepartum hemorrhage; RhD prophylaxis following invasive procedures during pregnancy including amniocentesis, chorionic biopsy, or obstetric manipulative procedures such as external version or abdominal trauma.

Transfusion:

HyperRHO S/D Full Dose, MICRhoGAM Ultra-Filtered Plus, RhoGAM Ultra-Filtered Plus, Rhophylac, and WinRho SDF: Prevention or suppression of RhD isoimmunization in RhD-negative individuals who have been transfused with RhD-positive blood products, including red blood cells or blood components containing red blood cells (including platelet concentrates or granulocyte concentrates).

Contraindications

HyperRHO S/D Full Dose, HyperRHO S/D Mini Dose: There are no contraindications listed in the manufacturer's labeling.

MICRhoGAM Ultra-Filtered Plus, RhoGAM Ultra-Filtered Plus: Anaphylactic or severe systemic reaction to a previous dose of human immune globulin; use in RhD-positive individuals.

Rhophylac: Anaphylactic or severe systemic reaction to a previous dose of human immune globulin; use in IgA-deficient patients with antibodies to IgA and a history of hypersensitivity; administration to the neonate of a mother who received Rhophylac postpartum.

WinRho SDF: Hypersensitivity to Rh_o(D) immune globulin or any component of the formulation; known anaphylactic or severe systemic reaction to a previous dose of human immune globulin; use in IgA-deficient patients with antibodies to IgA; autoimmune hemolytic anemia with preexisting hemolysis or at high risk for hemolysis; suppression of RhD isoimmunization in infants.

WinRho SDF Canadian labeling: Additional contraindications (not in the US labeling): All uses: Use in IgA-deficient patients.

Rh Immunization prophylaxis: Use in RhD-positive women; RhD-negative women who are RhD immunized.

Immune thrombocytopenia (ITP): RhD-negative patients; splenectomized patients; ITP secondary to other conditions including leukemia, lymphoma, or active viral infections with EBV or HCV; elderly patients with underlying cardiac, renal, or hepatic comorbidities that would predispose them to acute hemolytic reactions (AHR) complications; autoimmune hemolytic anemia (Evan syndrome); systemic lupus erythematosus (SLE); antiphospholipid antibody syndrome.

Documentation of allergenic cross-reactivity for immune globulins is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Dosage and Administration

Dosing: Adult

Note: Rh_o(D) immune globulin is also referred to as anti-D immune globulin. Rh_o(D) immune globulin 300 mcg has traditionally been referred to as a “full dose”. Potency and dosing recommendations may also be expressed in international units by comparison to the WHO anti-Rh_o(D) standard where 1 mcg = 5 international units.

Immune thrombocytopenia (ITP):

Rhophylac: IV: 50 mcg/kg

WinRho SDF: IV:

Initial:

Hemoglobin ≥10 g/dL: 50 mcg/kg as a single injection, or can be given as 2 divided doses on separate days.

Hemoglobin 8 to <10 g/dL: 25 to 40 mcg/kg, as a single injection, or can be given as 2 divided doses on separate days.

Hemoglobin <8 g/dL: Alternative treatment should be used.

Maintenance: Note: Dosing frequency determined by clinical response in platelet counts, RBC, hemoglobin, and reticulocyte levels.

Hemoglobin ≥10 g/dL: 50 to 60 mcg/kg

Hemoglobin 8 to <10 g/dL: 25 to 40 mcg/kg

Hemoglobin <8 g/dL: Alternative treatment should be used.

RhD suppression: Note: In general, a 300 mcg dose will suppress the immune response to a fetal-maternal hemorrhage with ≤15 mL of RhD-positive RBC or ≤30 mL fetal whole blood. If exposure to >15 mL of RhD-positive fetal RBC or >30 mL fetal whole blood is suspected, an appropriate dose should be calculated. If the first dose is administered early in pregnancy, additional doses may be needed to ensure adequate levels of passively acquired anti-D at delivery. If delivery occurs within 3 weeks after the last antepartum dose, a postpartum dose may be withheld unless there is excessive fetal hemorrhage (ACOG 181 2017).

Pregnancy prophylaxis: Note: if antepartum prophylaxis is indicated, the mother may also need a postpartum dose if the infant is RhD-positive.

Antepartum prophylaxis:

HyperRHO S/D Full Dose: IM: 300 mcg at ~28 weeks’ gestation.

RhoGAM: IM: 300 mcg at 26 to 28 weeks' gestation; if delivery does not occur within 12 weeks after the dose, a second 300 mcg dose is recommended. If the first dose is prior to 26 weeks' gestation, administer every 12 weeks to ensure adequate levels of passively acquired anti-D. If delivery occurs within 3 weeks after the last antepartum dose, a postpartum dose may be withheld, but testing for fetal-maternal hemorrhage of >15 mL should be performed.

Rhophylac: IM, IV: 300 mcg at 28 to 30 weeks' gestation.

WinRho SDF: IM, IV: 300 mcg at 28 weeks' gestation.

Postpartum prophylaxis:

HyperRHO S/D Full Dose: IM: 300 mcg provides sufficient antibody if volume of RhD-positive RBC exposure is ≤15 mL. If exposure to >15 mL of RhD-positive RBC is suspected, an appropriate dose should be calculated (see dosing for excessive fetomaternal hemorrhage). The dose should be administered within 72 hours of delivery, but may provide some benefit if given later.

RhoGAM: IM: 300 mcg provides sufficient antibody if volume of RhD-positive RBC exposure is ≤15 mL. If exposure to >15 mL of RhD-positive RBC is suspected, an appropriate dose should be calculated. The dose should be administered within 72 hours of delivery.

Rhophylac: IM, IV: 300 mcg provides sufficient antibody if volume of RhD-positive RBC exposure is ≤15 mL. If exposure to >15 mL of RhD-positive RBC is suspected, an appropriate dose should be calculated (see dosing for excessive fetomaternal hemorrhage). The dose should be administered within 72 hours of delivery.

WinRho SDF: IM, IV: 120 mcg. The dose should be administered within 72 hours of delivery but may be given up to 28 days after delivery.

Other pregnancy/obstetric conditions:

Abdominal trauma:

HyperRHO S/D Full Dose: IM: 300 mcg following abdominal trauma in the second or third trimester. If exposure to >15 mL of RhD-positive RBC is suspected, an appropriate dose should be calculated (see dosing for excessive fetomaternal hemorrhage).

RhoGam: IM: 300 mcg within 72 hours following abdominal trauma or obstetrical manipulation occurring at ≥13 weeks' gestation. If exposure to >15 mL of RhD-positive RBC is suspected, an appropriate dose should be calculated.

Rhophylac: IV, IM: 300 mcg within 72 hours of complication. If exposure to >15 mL of RhD-positive RBC is suspected, an appropriate dose should be calculated (see dosing for excessive fetomaternal hemorrhage).

Amniocentesis:

HyperRHO S/D Full Dose: IM: 300 mcg at 15 to 18 weeks' gestation or during the third trimester. If exposure to >15 mL of Rh-positive RBC is suspected, an appropriate dose should be calculated (see dosing for excessive fetomaternal hemorrhage).

RhoGam: IM: 300 mcg within 72 hours of a procedure occurring at ≥13 weeks' gestation. If exposure to >15 mL of RhD-positive RBC is suspected, an appropriate dose should be calculated.

Rhophylac: IV, IM: 300 mcg within 72 hours of procedure. If exposure to >15 mL of RhD-positive RBC is suspected, an appropriate dose should be calculated (see dosing for excessive fetomaternal hemorrhage).

WinRho SDF: IV, IM: 300 mcg immediately after amniocentesis occurring before 34 weeks' gestation; repeat dose every 12 weeks during pregnancy. Administer 120 mcg within 72 hours of amniocentesis occurring after 34 weeks' gestation.

Ectopic pregnancy:

HyperRHO S/D Full Dose: IM: 300 mcg for complications occurring at ≥13 weeks' gestation. If exposure to >15 mL of RhD-positive RBC is suspected, an appropriate dose should be calculated (see dosing for excessive fetomaternal hemorrhage).

RhoGam: IM: 300 mcg within 72 hours of complications occurring at ≥13 weeks' gestation. If exposure to >15 mL of RhD-positive RBC is suspected, an appropriate dose should be calculated.

Rhophylac: IV, IM: 300 mcg within 72 hours of complication. If exposure to >15 mL of RhD-positive RBC is suspected, an appropriate dose should be calculated (see dosing for excessive fetomaternal hemorrhage).

Termination of pregnancy (spontaneous or induced):

HyperRHO S/D Mini Dose: IM: 50 mcg within 3 hours or as soon as possible following spontaneous or induced abortion occurring <13 weeks' gestation; administer within 72 hours of termination if prompt administration is not possible.

HyperRHO S/D Full Dose: IM: 300 mcg following miscarriage or abortion occurring ≥13 weeks' gestation. If exposure to >15 mL of RhD-positive RBC is suspected, an appropriate dose should be calculated (see dosing for excessive fetomaternal hemorrhage).

MICRhoGAM: IM: 50 mcg within 72 hours of actual or threatened termination occurring <13 weeks' gestation. Note: RhoGAM may be administered if MICRhoGAM is not available.

RhoGAM: IM: 300 mcg within 72 hours following spontaneous or induced termination occurring ≥13 weeks' gestation. If exposure to >15 mL of RhD-positive RBC is suspected, an appropriate dose should be calculated.

Rhophylac: IV, IM: 300 mcg within 72 hours of miscarriage or abortion. If exposure to >15 mL of RhD-positive RBC is suspected, an appropriate dose should be calculated (see dosing for excessive fetomaternal hemorrhage).

WinRho SDF: IV, IM: 120 mcg within 72 hours of abortion occurring after 34 weeks' gestation.

Threatened pregnancy loss with continuation of pregnancy:

HyperRHO S/D Full Dose: IM: 300 mcg following threatened loss at any time during pregnancy; administer as soon as possible. If exposure to >15 mL of RhD-positive RBC is suspected, an appropriate dose should be calculated (see dosing for excessive fetomaternal hemorrhage).

MICRhoGAM: IM: 50 mcg within 72 hours of threatened termination occurring <13 weeks' gestation. Note: RhoGAM may be administered if MICRhoGAM is not available.

RhoGAM: IM: 300 mcg within 72 hours following threatened loss ≥13 weeks' gestation. If exposure to >15 mL of RhD-positive RBC is suspected, an appropriate dose should be calculated.

Rhophylac: IV, IM: 300 mcg within 72 hours of threatened abortion. If exposure to >15 mL of RhD-positive RBC is suspected, an appropriate dose should be calculated (see dosing for excessive fetomaternal hemorrhage).

WinRho SDF: IV, IM: 300 mcg immediately following a threatened abortion occurring any time during pregnancy

Additional invasive/manipulative procedures or obstetric complications:

RhoGam: IM: 300 mcg within 72 hours of chorionic villus sampling or percutaneous umbilical blood sampling ≥13 weeks' gestation. If exposure to >15 mL of RhD-positive RBC is suspected, an appropriate dose should be calculated.

Rhophylac: IV, IM: 300 mcg within 72 hours of procedures such as chorionic biopsy or external version, or within 72 hours of complications such as hydatidiform mole, or transplacental hemorrhage resulting from antepartum hemorrhage. If exposure to >15 mL of RhD-positive RBC is suspected, an appropriate dose should be calculated (see dosing for excessive fetomaternal hemorrhage).

WinRho SDF: IV, IM: 300 mcg immediately after chorionic villus sampling before 34 weeks' gestation; repeat dose every 12 weeks during pregnancy. Administer 120 mcg within 72 hours of manipulation occurring after 34 weeks' gestation.

Dosing for excessive fetomaternal hemorrhage:

HyperRHO S/D Full Dose: IM: When exposure to >15 mL RhD-positive RBC or >30 mL whole blood is suspected, a fetal red cell count should be calculated. The fetal RBC volume is then divided by 15 mL, providing the number of 300 mcg doses (vials/syringes) to administer. If the dose calculated results in a fraction, round up to the next higher whole 300 mcg dose (vial/syringe).

Rhophylac: IV, IM: When exposure to >15 mL RhD-positive RBC, administer 300 mcg; in addition, administer 20 mcg per mL fetal RBC in excess of 15 mL if bleeding can be quantified or an additional 300 mcg if excess bleeding cannot be quantified. Total dose should be administered within 72 hours of complication.

Transfusion: Note: Actual dose is based upon volume of blood/blood product exposure.

HyperRHO S/D Full Dose: IM: Multiply the volume of RhD-positive whole blood administered by the hematocrit of the donor unit to equal the volume of RBCs transfused. The volume of RBCs is then divided by 15 mL, providing the number of 300 mcg doses (vials/syringes) to administer. If the dose calculated results in a fraction, round up to the next higher whole 300 mcg dose (vial/syringe). Administer as soon as possible and within 72 hours after an incompatible transfusion.

MICRhoGAM: IM: <2.5 mL of RhD-positive red blood cell exposure: 50 mcg. Administer within 72 hours after an incompatible transfusion.

RhoGAM: IM:

2.5 to 15 mL RhD-positive red blood cell exposure: 300 mcg. Administer within 72 hours after an incompatible transfusion.

>15 mL RhD-positive red blood cell exposure: 20 mcg per mL of RhD-positive red blood cell exposure. Multiple doses may be given at the same time or spaced at intervals; total dose must be given within 72 hours of exposure.

Rhophylac: IM, IV: 20 mcg per 2 mL transfused blood or 20 mcg per mL erythrocyte concentrate. Administer within 72 hours after an incompatible transfusion.

WinRho SDF: Administer within 72 hours after exposure of incompatible blood transfusion.

IV: Calculate dose as follows; administer 600 mcg every 8 hours until the total dose is administered:

Exposure to RhD-positive whole blood: 9 mcg/mL blood

Exposure to RhD-positive red blood cells: 18 mcg/mL cells

IM: Calculate dose as follows; administer 1,200 mcg every 12 hours until the total dose is administered:

Exposure to RhD-positive whole blood: 12 mcg/mL blood

Exposure to RhD- positive red blood cells: 24 mcg/mL cells

Dosing: Geriatric

Refer to adult dosing. Patients >65 years of age with a concurrent comorbid condition may be at increased risk of developing acute hemolytic reactions. Fatal outcomes associated with IVH have occurred most frequently in those >65 years. Use with caution; consider starting at lower doses.

Dosing: Pediatric

Note: Potency and dosing recommendations may also be expressed in units; 1 mcg = 5 units.

Immune thrombocytopenia (ITP), treatment: Note: Most newly diagnosed patients can be managed with a watch and wait approach. If treatment is necessary, Rh_o(D) immune globulin is recommended as first-line in Rh-positive, nonsplenectomized pediatric patients (Neunert 2011; Provan 2010):

Infants (limited data available), Children, and Adolescents:

Initial treatment: IV: 50 to 75 mcg/kg (250 to 375 units/kg) as a single dose (Provan 2010).

Serious or life-threatening bleeding: IV: 75 mcg/kg (375 units/kg) as a single dose in combination with platelet infusion(s) and corticosteroids (Provan 2010).

Product-specific dosing: WinRho SDF: Children and Adolescents <16 years:

Initial:

Hemoglobin <8 g/dL: Alternative therapy should be used.

Hemoglobin 8 to <10 g/dL: IV: 25 to 40 mcg/kg (125 to 200 units/kg) as single dose or divided into 2 doses given on separate days.

Hemoglobin ≥10 g/dL: IV: 50 mcg/kg (250 units/kg) as single dose or divided into 2 doses given on separate days.

Subsequent doses: Note: Dosing frequency determined by clinical response in platelet count, hemoglobin, red blood cell counts, and reticulocyte levels; platelet counts >50,000/mm³ rarely require treatment.

Hemoglobin <8 g/dL: Alternative therapy should be used.

Hemoglobin 8 to 10 g/dL: IV: 25 to 40 mcg/kg (125 to 200 units/kg).

Hemoglobin >10 g/dL: IV: 50 to 60 mcg/kg (250 to 300 units/kg).

Reconstitution

Rhophylac: Bring to room temperature before use.

WinRho SDF: ITP: May dilute in NS prior to IV administration if needed; do not dilute with D₅W. Bring to room temperature before use.

Administration

When used for the prevention of Rh isoimmunization in an RhD-incompatible pregnancy, the dose is administered to the mother, not the neonate.

Rhophylac and WinRho SDF may be administered IV or IM (based on indication); when used to treat ITP, administer by the IV route only (do not administer IM for ITP). Do not administer Rhophylac subcutaneously into the fatty tissue. There have been reports of lack of effect in patients with a BMI ≥30 kg/m² when Rhophylac was administered IM; administer Rhophylac IV if there is concern with reaching the muscle with IM administration.

HyperRHO S/D Full Dose, HyperRHO S/D Mini Dose, MICRhoGAM Ultra-Filtered Plus, and RhoGAM Ultra-Filtered Plus are for IM administration only; do not administer IV.

IM: Administer into the deltoid muscle of the upper arm or anterolateral aspect of the upper thigh. In general, avoid gluteal region due to risk of sciatic nerve injury. If the gluteal region must be used, administer into only the upper, outer quadrant. If large doses (>5 mL) are needed, administration in divided doses at different sites is recommended.

IV:

Rhophylac: ITP: Infuse at 2 mL per 15 to 60 seconds

WinRho SDF: Infuse at 2 mL per 5 to 15 seconds when used for the prevention of RhD isoimmunization or over 3 to 5 minutes when used for the treatment of ITP.

Storage

Store at 2°C to 8°C (35°F to 46°F); do not freeze.

Rhophylac, WinRho SDF: Store at 2°C to 8°C (35°F to 46°F); do not freeze. Protect from light.

Drug Interactions

Measles, Mumps, and Rubella Virus Vaccine: Rho(D) Immune Globulin may diminish the therapeutic effect of Measles, Mumps, and Rubella Virus Vaccine. Management: Do not delay administration of the measles, mumps, and rubella virus vaccine in women who have recently received Rho (D) immune globulin. If possible, women should be tested 3 or more months after vaccine administration to ensure immunity. Consider therapy modification

Measles, Mumps, Rubella, and Varicella Virus Vaccine: Rho(D) Immune Globulin may diminish the therapeutic effect of Measles, Mumps, Rubella, and Varicella Virus Vaccine. Management: Do not delay administration of the measles, mumps, rubella, and varicella virus vaccine in women who have recently received Rho (D) immune globulin. If possible, women should be tested 3 or more months after vaccine administration to ensure immunity. Consider therapy modification

Vaccines (Live): Immune Globulins may diminish the therapeutic effect of Vaccines (Live). Management: Consult full interaction monograph for dose interval recommendations. This interaction does not apply to oral Ty21a typhoid vaccine or others listed as exceptions. Exceptions: Adenovirus (Types 4, 7) Vaccine; Cholera Vaccine; Influenza Virus Vaccine (Live/Attenuated); Poliovirus Vaccine (Live/Bivalent/Oral); Poliovirus Vaccine (Live/Trivalent/Oral); Rotavirus Vaccine; Yellow Fever Vaccine; Zoster Vaccine (Live/Attenuated). Consider therapy modification

Varicella Virus Vaccine: Rho(D) Immune Globulin may diminish the therapeutic effect of Varicella Virus Vaccine. Management: Do not delay administration of the varicella virus vaccine in women who have recently received Rho (D) immune globulin. If possible, women should be tested 3 or more months after vaccine administration to ensure immunity. Consider therapy modification

Test Interactions

Rh_o(D) immune globulin may affect the results of blood typing, the antibody screening test, and the direct antiglobulin (Coombs’) test in the mother and neonate. Fetal-maternal hemorrhage may cause false blood-typing result in the mother; when there is any doubt to the patients' Rh type, Rh_o(D) immune globulin should be administered. WinRho SDF liquid contains maltose; may result in falsely elevated blood glucose levels with dehydrogenase pyrroloquinolinequinone or glucose-dye-oxidoreductase testing methods. WinRho SDF also contains trace amounts of anti-A, B, C and E; may alter Coombs’ tests. Rhophylac can contain antibodies to other Rh antigens (eg, anti-C antibodies), which might be detected by sensitive serological tests.

Adverse Reactions

>10%:

Central nervous system: Chills (5% to 35%), headache (11% to 14%)

Hepatic: Increased serum bilirubin (21%)

Neuromuscular & skeletal: Asthenia (3% to 11%)

Miscellaneous: Fever (5% to 31%)

1% to 10%:

Central nervous system: Dizziness (3% to 5%)

Infection: Infection (children: 5%)

Frequency not defined:

Cardiovascular: Hypertension, vasodilation

Central nervous system: Drowsiness, shivering

Dermatologic: Diaphoresis, pallor

Endocrine & metabolic: Decreased haptoglobins, increased lactate dehydrogenase

Gastrointestinal: Abdominal pain

Hematologic & oncologic: Decreased hemoglobin (patients with ITP)

Immunologic: Antibody development (positive anti-C antibody test)

Local: Discomfort at injection site, erythema at injection site, pain at injection site (mild)

Neuromuscular & skeletal: Hyperkinetic muscle activity

<1%, postmarketing, and/or case reports: Acute intravascular hemolysis (patients with ITP), acute myocardial infarction, acute respiratory distress syndrome, anaphylactic shock, anaphylaxis, anemia (clinically compromising), anuria, back pain, cardiac failure, chest pain, diarrhea, disseminated intravascular coagulation, dyspnea, edema, erythema of skin, fatigue, hematuria, hemoglobinemia, hemoglobinuria (transient in patients with ITP), hyperhidrosis, hypersensitivity reaction, hypotension, induration at injection site, itching at injection site, jaundice, limb pain, malaise, muscle spasm, myalgia, nausea, pain, pruritus, renal failure syndrome, renal insufficiency (can be acute), skin rash, swelling at injection site, tachycardia, transfusion-related acute lung injury, urine discoloration, vertigo, vomiting

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylactoid/hypersensitivity reactions: Severe hypersensitivity reactions may occur. Immediate treatment (including epinephrine 1 mg/mL) for anaphylactoid and/or hypersensitivity reactions should be available during use. Some products are specifically contraindicated in patients with a previous anaphylactic or severe systemic reaction to an immune globulin. If symptoms of allergic or early signs of hypersensitivity reactions occur, discontinue immediately and institute appropriate treatment.
• Anaphylaxis: Use with caution in patients with IgA deficiency, may contain trace amounts of IgA; patients with antibodies to IgA have a greater risk of developing potentially anaphylactic reactions. Some products are specifically contraindicated in patients with antibodies against IgA.
• Intravascular hemolysis: Rhophylac, WinRho SDF: [US Boxed Warning]: May cause fatal intravascular hemolysis (IVH) in RhD-positive patients treated with intravenous (IV) Rh_o(D) immune globulin for immune thrombocytopenia (ITP). IVH may result in clinically compromising anemia and multiorgan system failure including acute respiratory distress syndrome. Acute renal insufficiency, renal failure, severe anemia, and disseminated intravascular coagulation (DIC) have also been reported. Patients should be closely monitored for at least 8 hours after administration. Alert patients to and monitor them for back pain, shaking chills, fever, and discolored urine or hematuria. Absence of these signs and/or symptoms within 8 hours does not indicate IVH cannot occur subsequently. If signs and/or symptoms of intravascular hemolysis are present or suspected, perform post-treatment laboratory tests, including plasma hemoglobin, haptoglobin, LDH, and plasma bilirubin (direct and indirect). Previous administration of IV Rh_o(D) immune globulin does not preclude the possibility of IVH. Complications may occur more frequently in elderly patients with comorbid conditions and in patients with predisposing conditions. Use should be avoided in patients with preexisting hemolysis or a high risk of hemolysis (eg, positive direct antiglobulin test, elevated reticulocyte count). Transfuse patients with hemolysis and clinically compromising anemia after receiving Rh_o(D) immune globulin; use RhD-negative packed red blood cells.
• Pulmonary edema: Monitor for adverse pulmonary events including transfusion-related acute lung injury (TRALI); noncardiogenic pulmonary edema has been reported with intravenous immune globulin (IVIG) use. TRALI is characterized by severe respiratory distress, pulmonary edema, hypoxemia, and fever in the presence of normal left ventricular function and usually occurs within 1 to 6 hours after infusion; may be managed with oxygen and respiratory support
• Renal effects: Acute renal dysfunction/failure, acute tubular necrosis, osmotic nephropathy, proximal tubular nephropathy, and death may occur with IGIV products. Use with caution in patients with renal impairment or at risk for renal disease (eg, diabetes mellitus, >65 years of age, volume depletion, sepsis, paraproteinemia, concomitant use of nephrotoxic medications); administer at the minimum infusion rate possible and ensure adequate hydration prior to administration in these patients.
• Thrombotic events: Thrombotic events have been reported with administration of IVIG; use with caution in patients with a history of atherosclerosis, known/suspected hyperviscosity, advanced age, impaired cardiac output, prolonged immobilization, coagulation disorders, history of venous or arterial thrombosis, use of estrogens, indwelling central vascular catheters, or multiple cardiovascular risk factors. Consider a baseline assessment of blood viscosity in patients at risk for hyperviscosity. Administer at the minimum practical infusion rate in patients at risk for thrombotic events.

Disease-related concerns:

• Bleeding disorders: Use with caution in patients with thrombocytopenia or coagulation disorders; bleeding/hematoma may occur from IM administration.
• Immune globulin deficiency syndromes: Not for replacement therapy in immune globulin deficiency syndromes.
• Immune thrombocytopenia (ITP): Dose adjustment may be required with decreased hemoglobin. Although Rh_o(D) immune globulin is not the preferred pharmacologic agent for the management of ITP, a single dose may be used in non-splenectomized children who are RhD-positive and require treatment, or in adults when corticosteroids are contraindicated (Neunert 2011). Avoid use in patients with autoimmune hemolytic anemia; may exacerbate hemolysis (Provan 2010).
• RhD suppression: For use in the mother; do not administer to the neonate. If RhD antibodies are already present in the mother, use of the Rh_o(D) immune globulin is not beneficial. In addition, if paternity is certain and the father is confirmed to be RhD-negative, administration of the immune globulin is not needed. When treatment is indicated, administration should be within the time frame recommended. However, there may still be benefit if therapy is given as late as 28 days postpartum. The longer treatment is delayed, the less protection will be provided (ACOG 181 2017; Fung 2018).

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Dosage form specific issues:

• Human plasma: Product of human plasma; may potentially contain infectious agents which could transmit disease. Screening of donors, as well as testing and/or inactivation or removal of certain viruses, reduces the risk. Infections thought to be transmitted by this product should be reported to the manufacturer.
• Maltose: Some products may contain maltose, which may result in falsely elevated blood glucose readings. Avoid use in patients with an allergy to corn.
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.

Monitoring Parameters

Immune thrombocytopenia (ITP): Signs and symptoms of intravascular hemolysis (IVH), including anemia, renal insufficiency, back pain, shaking, chills, discolored urine, or hematuria; observe patient for 8 hours following administration. In addition, CBC (prior to therapy and 1 to 3 days after first infusion); differential and peripheral blood smear (prior to therapy), direct antiglobulin test and antibody screen (prior to therapy); reticulocyte count (prior to therapy); urinalysis (prior to therapy and 1 to 2 hours after treatment [product labeling specifies dipstick urinalysis at baseline and 2, and 4 hours prior to the end of the monitoring period]); serum creatinine and BUN (prior to therapy; monitor after therapy if post treatment hemoglobin decreases by >1 g/dL) (Despotovic 2012). For patients with suspected IVH, monitor plasma hemoglobin, haptoglobin, LDH, and plasma bilirubin (direct and indirect).

Pregnancy/obstetric conditions: Monitor for systemic reactions for 20 minutes after administration

Transfusion: Signs and symptoms of hemolytic reaction

Pregnancy

Pregnancy Considerations

Available evidence suggests that Rh_o(D) immune globulin administration during pregnancy does not harm the fetus or affect future pregnancies.

Rh_o(D) immune globulin (RhIG or anti-D immune globulin) is administered to pregnant females to prevent alloimmunization of RhD-negative mothers who may potentially have a fetus who is RhD-positive. Administration of the immune globulin prevents the mother from developing antibodies to the D antigen and the development of hemolytic anemia in the newborn. Current guidelines recommend administration of RhIG to all pregnant females who are RhD-negative and who are not already RhD alloimmunized at 28 weeks' gestation (unless paternity is certain and the father is documented to be RhD-negative); within 72 hours of delivery of an RhD-positive infant; after obstetric complications (such as a pregnancy loss, abdominal trauma, antenatal hemorrhage); or after invasive diagnostic procedures (such as amniocentesis or chorionic villus sampling). If RhIG not given within 72 hours of delivery or another sensitizing event, there may still be benefit if administered within 28 days (ACOG 181 2017; Fung 2018).

In pregnant women who require treatment for ITP, other agents are preferred. RhIG for this indication in pregnancy is limited to case reports and small studies (Neunert 2011).

Patient Education

What is this drug used for?

• It is used to treat Rh hemolytic disease.
• It is used to treat immune thrombocytopenia (ITP).
• It may be given to you for other reasons. Talk with the doctor.

Frequently reported side effects of this drug

• Fatigue
• Diarrhea
• Muscle pain
• Joint pain
• Injection site pain, redness, or swelling

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Blood clots like numbness or weakness on one side of the body; pain, redness, tenderness, warmth, or swelling in the arms or legs; change in color of an arm or leg; chest pain; shortness of breath; fast heartbeat; or coughing up blood.
• Kidney problems like unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain.
• Back pain
• Tremors
• Sore throat
• Abdominal pain
• Chills
• Dark urine
• Trouble urinating
• Swelling
• Yellow skin or eyes
• Nausea
• Vomiting
• Shortness of breath
• Sudden or excessive weight gain
• Swelling of arms or legs
• Severe loss of strength and energy
• Dizziness
• Passing out
• Severe headache
• Vision changes
• Pale skin
• Bruising
• Shivering
• Muscle spasm
• Bleeding
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.