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Rho(D) Immune Globulin

Pronunciation

(ar aych oh (dee) i MYUN GLOB yoo lin)

Index Terms

  • Anti-D Immunoglobulin
  • RhIG
  • Rho(D) Immune Globulin (Human)
  • RhoIGIV
  • RhoIVIM

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Injection:

WinRho SDF: 2500 units/2.2 mL (2.2 mL); 5000 units/4.4 mL (4.4 mL); 1500 units/1.3 mL (1.3 mL); 15,000 units/13 mL (13 mL)

Solution, Injection [preservative free]:

WinRho SDF: 2500 units/2.2 mL (2.2 mL); 5000 units/4.4 mL (4.4 mL); 1500 units/1.3 mL (1.3 mL); 15,000 units/13 mL (13 mL) [contains polysorbate 80]

Solution Prefilled Syringe, Injection [preservative free]:

Rhophylac: 1500 units/2 mL (2 mL)

Solution Prefilled Syringe, Intramuscular:

HyperRHO S/D: 250 units (1 ea [DSC])

Solution Prefilled Syringe, Intramuscular [preservative free]:

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

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

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

Brand Names: U.S.

  • HyperRHO S/D
  • MICRhoGAM Ultra-Filtered Plus
  • RhoGAM Ultra-Filtered Plus
  • Rhophylac
  • WinRho SDF

Pharmacologic Category

  • Blood Product Derivative
  • Immune Globulin

Pharmacology

Rh suppression: Not completely characterized; prevents isoimmunization by suppressing the immune response and antibody formation by Rho(D)-negative individuals to Rho(D)-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: Not completely characterized; Rho(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.

Distribution

Vd: 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: 2 to 7 days (IM); WinRho SDF: ≤2 hours (IV), 5 to 10 days (IM)

Duration of Action

Suppression of Rh isoimmunization: Rhophylac 300 mcg dose: Rho(D) immune globulin titers detected up to and 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 Rho (D) positive nonsplenectomized adults with chronic ITP.

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

Pregnancy and other obstetric conditions:

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

HyperRHO S/D Full Dose: For antepartum prophylaxis at ~28 weeks gestation; for administration within 72 hours of birth for the prevention of hemolytic disease of the newborn; for administration within 72 hours of spontaneous or induced abortion, ruptured tubal pregnancy, amniocentesis or abdominal trauma.

HyperRHO S/D Mini Dose: For administration within 3 hours (or as soon as possible) of spontaneous or induced abortion up to 12 weeks' gestation.

MICRhoGAM Ultra-Filtered Plus: For administration within 72 hours of actual or threatened termination of pregnancy (spontaneous or induced) up to and including 12 weeks' gestation.

RhoGAM Ultra-Filtered Plus: For antepartum prophylaxis at 26 to 28 weeks' gestation; for administration within 72 hours of birth for prevention of hemolytic disease of the newborn; for administration within 72 hours of amniocentesis, chorionic villus sampling (CVS), percutaneous umbilical blood sampling (PUBS), abdominal trauma or obstetrical manipulation, ectopic pregnancy, threatened pregnancy loss after 12 weeks' gestation (with continuation of pregnancy), pregnancy termination (spontaneous or induced) after 12 weeks' gestation.

Rhophylac: For antepartum prophylaxis at 28 to 30 weeks' gestation; for administration within 72 hours of birth for the prevention of hemolytic disease of the newborn; for administration within 72 hours of obstetric complications including miscarriage, abortion, threatened abortion, ectopic pregnancy or hydatiform mole, transplacental hemorrhage resulting from antepartum hemorrhage; for administration within 72 hours of invasive procedures during pregnancy including amniocentesis, chorionic biopsy, or obstetric manipulative procedures such as external version or abdominal trauma.

WinRho SDF: For antepartum prophylaxis at 28 weeks' gestation; for administration within 72 hours of birth for the prevention of hemolytic disease of the newborn; for administration following obstetric complications including miscarriage, abortion, threatened abortion, ectopic pregnancy or hydatiform mole, transplacental hemorrhage resulting from antepartum hemorrhage; for administration 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: To prevent isoimmunization in Rho(D) negative individuals who have been transfused with Rho(D) positive red blood cells or blood components containing red blood cells.

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: Use in Rh-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: 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; autoimmune hemolytic anemia; preexisting hemolysis or at high risk for hemolysis; suppression of Rho(D) isoimmunization in infants.

WinRho SDF Canadian labeling: Additional contraindications (not in US labeling): All uses: Use in IgA-deficient patients; hypersensitivity to Rho(D) immune globulin or any component of the formulation.

Rh Immunization prophylaxis: Use in Rho(D)-positive women; Rho(D) negative women who are Rh immunized.

Immune thrombocytopenia (ITP): Rho(D)-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.

Dosing: Adult

Note: Rho(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-Rho(D) standard where 1 mcg = 5 international units

Immune thrombocytopenia (ITP):

Rhophylac: IV: 50 mcg/kg

WinRho SDF: IV:

Initial: 50 mcg/kg as a single injection, or can be given as a divided dose on separate days. If hemoglobin is <10 g/dL: Dose should be reduced to 25 to 40 mcg/kg.

Subsequent dosing: 25 to 60 mcg/kg can be used if required to increase platelet count; frequency of dosing is dependent upon clinical response

Maintenance dosing if patient did respond to initial dosing: 25 to 60 mcg/kg based on platelet count and hemoglobin concentration

Maintenance dosing if patient did not respond to initial dosing:

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

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

Hemoglobin >10 g/dL: Redose between 50 to 60 mcg/kg

Rho(D) suppression: Note: In general, a 300 mcg dose will suppress the immune response to a fetal-maternal hemorrhage with ≤15 mL of Rh-positive RBC. If exposure to >15 mL of Rh-positive RBC 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 (ACOG 1999). 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 (ACOG 1999).

Pregnancy prophylaxis: Note: if antepartum prophylaxis is indicated, the mother may also need a postpartum dose if the infant is Rh-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. If the first dose is administered early in pregnancy, administer every 12 weeks to ensure adequate levels of passively acquired anti-D.

Postpartum prophylaxis:

HyperRHO S/D Full Dose: IM: 300 mcg provides sufficient antibody if volume of Rh-positive RBC exposure is ≤15 mL. If exposure to >15 mL of Rh-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 Rh-positive RBC exposure is ≤15 mL. If exposure to >15 mL of Rh-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 Rh-positive RBC exposure is ≤15 mL. If exposure to >15 mL of Rh-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 Rh-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 Rh-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 Rh-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 Rh-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 Rh-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 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 complications occurring at ≥13 weeks' gestation. If exposure to >15 mL of Rh-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 Rh-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 Rh-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.

RhoGAM: IM: 300 mcg within 72 hours following spontaneous or induced termination occurring ≥13 weeks' gestation. If exposure to >15 mL of Rh-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 Rh-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 Rh-positive RBC is suspected, an appropriate dose should be calculated (see dosing for excessive fetomaternal hemorrhage).

RhoGAM: IM: 300 mcg within 72 hours following threatened loss ≥13 weeks' gestation. If exposure to >15 mL of Rh-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 Rh-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 Rh-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 Rh-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 Rh-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 Rh-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.

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 Rho(D) positive whole blood: 9 mcg/mL blood

Exposure to Rho(D) 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 Rho(D) positive whole blood: 12 mcg/mL blood

Exposure to Rho(D) positive red blood cells: 24 mcg/mL cells

HyperRHO S/D Full Dose: IM: Multiply the volume of Rh-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 Rh-positive red blood cell exposure: 50 mcg. Administer within 72 hours after an incompatible transfusion.

RhoGAM: IM:

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

>15 mL Rh-positive red blood cell exposure: 20 mcg per mL of Rh-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.

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

Immune thrombocytopenia (ITP): Children and Adolescents: WinRho SDF: Refer to adult dosing.

Dosing: Renal Impairment

There are no dosage adjustments provided in the manufacturer’s labeling.

Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer’s labeling.

Reconstitution

Rhophylac: Bring prefilled syringe to room temperature before use.

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

Administration

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

HyperRHO S/D Full Dose, HyperRHO S/D Mini Dose, MICRhoGAM Ultra-Filtered Plus and RhoGAM Ultra-Filtered Plus are for IM administration only.

Rhophylac and WinRho SDF may be administered IM or IV (based on indication). 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.

IM: Administer into the deltoid muscle of the upper arm or anterolateral aspect of the upper thigh; avoid gluteal region due to risk of sciatic nerve injury. If large doses (>5 mL) are needed, administration in divided doses at different sites is recommended. HyperRHO S/D, MICRhoGAM Ultra-Filtered Plus and RhoGAM Ultra-Filtered Plus should not be administered intravenously.

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 rhesus (Rh) 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: Store at 2°C to 8°C (35°F to 46°F); do not freeze. Protect from light.

Drug Interactions

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: Influenza Virus Vaccine (Live/Attenuated); Rotavirus Vaccine; Yellow Fever Vaccine; Zoster Vaccine. Consider therapy modification

Test Interactions

Rho(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, Rho(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

Frequency not defined.

Cardiovascular: Hyper-/hypotension, pallor, vasodilation

Central nervous system: Chills, dizziness, fever, headache, malaise, somnolence

Dermatologic: Pruritus, rash

Gastrointestinal: Abdominal pain, diarrhea, nausea, vomiting

Hematologic: Haptoglobin decreased, hemoglobin decreased (patients with ITP), intravascular hemolysis (patients with ITP)

Hepatic: Bilirubin increased, LDH increased

Local: Injection site reaction: Discomfort, induration, mild pain, redness, swelling

Neuromuscular & skeletal: Arthralgia, back pain, hyperkinesia, myalgia, weakness

Renal: Acute renal insufficiency

Miscellaneous: Anaphylaxis, diaphoresis, infusion-related reactions, positive anti-C antibody test (transient), shivering

Postmarketing and/or case reports: Anemia (clinically-compromising), anuria, ARDS, cardiac arrest, cardiac failure, chest pain, chromaturia, DIC, edema, erythema, fatigue, hematuria, hemoglobinemia, hemoglobinuria (transient in patients with ITP), hyperhidrosis, hypersensitivity, injection site irritation, jaundice, myocardial infarction, muscle spasm, nausea, pain in extremities, renal failure, renal impairment, tachycardia, transfusion-related acute lung injury

ALERT: U.S. Boxed Warning

Intravascular hemolysis in immune thrombocytopenic purpura (WinRho SDF, Rophylac):

Intravascular hemolysis leading to death has been reported in Rho(D)-positive patients treated for immune thrombocytopenic purpura (ITP) with Rho(D) immune globulin.

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

Serious complications, including severe anemia, acute renal insufficiency, renal failure, and disseminated intravascular coagulation (DIC), have also been reported.

Closely monitor patients treated for signs and symptoms of hemolysis in a health care setting for at least 8 hours after administration. Perform a dipstick urinalysis at baseline, 2 and 4 hours after administration, and prior to the end of the monitoring period. 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 intravascular hemolysis cannot occur subsequently. If signs and/or symptoms of intravascular hemolysis are present or suspected after administration, perform posttreatment laboratory tests, including plasma hemoglobin (Hb), haptoglobin, lactate dehydrogenase (LDH), and plasma bilirubin (direct and indirect).

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 known 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 Rho(D)-positive patients treated with intravenous (IV) Rho(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 Rho(D) immune globulin does not preclude the possibility of IVH. Transfuse patients with hemolysis and clinically compromising anemia after receiving Rho(D) immune globulin; use Rho(D)-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, osmotic nephropathy, and death may occur with IGIV products. Use with caution and administer at the minimum infusion rate possible in patients at risk for renal disease (eg, diabetes mellitus, >65 years of age, volume depletion, sepsis, paraproteinemia, concomitant use of nephrotoxic medications); 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 or cardiovascular and/or thrombotic risk factors or patients with known/suspected hyperviscosity. Consider a baseline assessment of blood viscosity in patients at risk for hyperviscosity. Administer at the minimum practical infusion rate.

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): Appropriate use: Safety and efficacy of WinRho not established in Rho(D) negative, non-ITP thrombocytopenia, or splenectomized patients; safety and efficacy of Rhophylac not established in patients with preexisting anemia; may increase the severity of preexisting anemia. Dose adjustment may be required with decreased hemoglobin. Do not administer IM or SubQ; administer dose IV only. Although Rho(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 Rho(D) positive and require treatment, or in adults when corticosteroids are contraindicated (Neunert 2011).

• Renal impairment: Use with caution in patients with renal impairment or those at risk for renal disease (eg, diabetes mellitus, advanced age [>65 years], volume depletion, sepsis, paraproteinemia, concomitant use of nephrotoxic medications). In patients at risk of renal dysfunction, ensure adequate hydration prior to administration; administer at the minimum practical infusion rate.

• Rho(D) suppression: For use in the mother; do not administer to the neonate. If Rho(D) antibodies are already present in the mother, use of the Rho(D) immune globulin is not beneficial. In addition, if the father is known to be Rho(D) 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 1999).

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.

• 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 Risk Factor

C

Pregnancy Considerations

Animal reproduction studies have not been conducted.

Rho(D) immune globulin (RhIG) is administered to pregnant women to prevent alloimmunization of Rho(D) negative mothers who may potentially have a fetus who is Rho(D) 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 pregnant women who are Rho(D) negative and who are not already Rho(D) alloimmunized at ~28 weeks gestation (unless the father is known to be Rho(D) negative), within 72 hours of delivery of an Rho(D) positive infant, after a first trimester pregnancy loss, or after invasive procedures such as amniocentesis, chorionic villus sampling (CVS), or fetal blood sampling (ACOG 1999). Available evidence suggests that Rho(D) immune globulin administration during pregnancy does not harm the fetus or affect future pregnancies.

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

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience fatigue or injection site pain or irritation. Have patient report immediately to prescriber signs of severe cerebrovascular disease (change in strength on one side is greater than the other, trouble speaking or thinking, change in balance, or change in eyesight), signs of DVT (edema, warmth, numbness, change in color, or pain in the extremities), back pain, tremors, abdominal pain, blood in urine, dark urine, jaundice, urinary retention, change in amount of urine passed, tachycardia, nausea, vomiting, shortness of breath, excessive weight gain, swelling of arms or legs, loss of strength and energy, angina, chills, coughing up blood, severe dizziness, passing out, severe headache, fast breathing, pale skin, bruising, bleeding (HCAHPS).

• Educate patient about signs of a significant reaction (eg, 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. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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