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    Other Disease Specific Immunoglobulins

    BOXED WARNING

    Anemia, hemolysis, hemolytic anemia, renal impairment, requires a specialized care setting

    WinRho SDF and Rhophylac are approved for intravenous use in patients with idiopathic thrombocytopenic purpura (ITP). Increased destruction of Rh0 [D]-positive red cells occurs after Rh0 [D] immune globulin administration, and this will produce decreased serum hemoglobin concentrations and associated clinical symptoms. Because of this, use with caution in patients with preexisting anemia. Patients with ITP who have a hemoglobin < 10 g/dl should receive a reduced dose of WinRho SDF in order to decrease the risk of worsening the severity of the anemia. Alternative treatments should be used in patients with ITP who have a hemoglobin level < 8 g/dl because the risk of the severity of anemia is increased. The safety of Rhophylac in the treatment of ITP has not been established in patients with pre-existing anemia; weigh the benefits of Rhophylac versus the potential risk of increasing the anemia severity. While most of the red cell destruction will occur in the spleen, there have been rare reports of acute hemoglobinuria consistent with intravascular hemolysis that have occurred during Rh0 [D] immune globulin administration to patients with ITP. WinRho SDF is contraindicated for use in patients with pre-existing hemolysis, patients at high risk for hemolysis, and in patients with autoimmune hemolytic anemia. Rh0[D]-positive patients with ITP should be monitored for signs and/or symptoms of intravascular hemolysis (IVH), clinically compromising hemolytic anemia, and renal impairment during treatment. IVH leading to death has been reported in patients treated for ITP with Rh0 [D] immune globulin. IVH can lead to clinically compromising anemia and multi-system organ failure including acute respiratory distress syndrome (ARDS). Serious complications, including severe anemia, acute renal impairment, renal failure, and disseminated intravascular coagulation (DIC) have also been reported. WinRho SDF and Rhophylac for ITP requires a specialized care setting; closely monitor patients in a health care setting for at least 8 hours after administration. Perform a dipstick urinalysis at baseline and at 2 hours, 4 hours, and 8 hours after administration. Monitor signs and symptoms of IVH including back pain, chills, fever, and hematuria. Absence of these signs and/or symptoms of IVH within 8 hours does not indicate that IVH cannot occur subsequently. If signs and/or symptoms of IVH are present or suspected after Rh0 [D] immune globulin administration, post-treatment laboratory tests should be performed including plasma hemoglobin, microscopic and dipstick urinalysis, haptoglobin, LDH, and plasma bilirubin (direct and indirect). Periodic monitoring of renal function and urine output is particularly important in patients judged to be at increased risk of developing acute renal failure. Assess renal function in all patients before initiation of Rh0 [D] immune globulin and at appropriate intervals thereafter for at-risk patients. Infusion of intravenous immune globulin at a minimal practical concentration and infusion rate is recommended for patients with renal insufficiency or for patients who are predisposed to acute renal failure. Receipt of intravenous immune globulin has been reported to produce renal dysfunction in these patients. Most reports of renal dysfunction have involved products that contain sucrose as a stabilizer. If renal dysfunction occurs, use clinical judgment to either decrease the infusion rate or stop the infusion.

    DEA CLASS

    Rx

    DESCRIPTION

    Parenteral IgG administered to females to decrease the risk of erythroblastosis fetalis following Rh0[D]-incompatible delivery, abortion, miscarriage, or trauma; one IV product also used for certain patients with ITP.

    COMMON BRAND NAMES

    HyperRHO S/D, MICRhoGAM, RhoGAM, Rhophylac, WinRho SDF

    HOW SUPPLIED

    HyperRHO S/D/MICRhoGAM/RhoGAM/Rhophylac/WinRho SDF Intramuscular Inj Sol: 250IU, 1500IU, 2500IU, 5000IU, 15000IU
    Rhophylac/WinRho SDF Intravenous Inj Sol: 1500IU, 2500IU, 5000IU, 15000IU

    DOSAGE & INDICATIONS

    For Rh isoimmunization prophylaxis in Rh0 [D]-negative patient and to ensure subsequent erythroblastosis fetalis prophylaxis in females with present and future pregnancies.
    NOTE: Never administer Rh0 [D] immune globulin to the neonate; administer to the mother only.
    NOTE: The woman must not be sensitized to the Rh0 [D] antigen. The immune globulin is used to prevent the formation of anti-Rh0 [D] antibody.
    NOTE: Rh0 [D] immune globulin prophylaxis for all obstetric indications is not indicated if either the father or the fetus is known to be Rh0 [D] negative. If the Rh status of the father and fetus are unknown, assume the fetus to be Rh0 [D] positive, and administer Rh0 [D] immune globulin to the mother.
    NOTE: Passively acquired anti-Rh0 [D] may be detected in maternal or neonatal blood if antibody screening tests are performed after Rh0 [D] immune globulin administration. The presence of passively acquired anti-Rh0 [D] does not preclude further antepartum or postpartum prophylaxis with Rh0 [D] immune globulin. A woman who had a large fetomaternal hemorrhage late in pregnancy or after delivery may test Rh positive even though she is really Rh negative. Administer Rh0 [D] immune globulin if there is any doubt about the mother's Rh type. A screening test to detect fetal red blood cells may be helpful.
    To reduce the risk of Rh isoimmunization antepartum and suppression of Rh isoimmunization postpartum following the delivery of a full-term infant.
    Intramuscular dosage (HyperRHO S/D Full dose only)
    Adult and adolescent females at least 16 years of age

    300 mcg (1500 international units) IM at 28 weeks gestation. Repeat the 300 mcg (1500 international units) IM dose within 72 hours of delivery of a confirmed Rh0 [D]-positive infant. If Rh status of the infant is unknown at 72 hours or > 72 hours have passed, do not withhold the dose. A dose of Rh0 [D] immune globulin after delivery is not needed if delivery is within 3 weeks of the last dose and no fetomaternal hemorrhage of greater than 15 ml of RBC has occurred.

    Intramuscular dosage (RhoGAM only)
    Adult and adolescent females

    300 mcg (1500 international units) IM at 26—28 weeks gestation. Repeat the 300 mcg (1500 international units) IM dose within 72 hours of delivery of a confirmed Rh0 [D]-positive infant. If Rh status of the infant is unknown at 72 hours or > 72 hours have passed, do not withhold the dose.

    Intravenous or Intramuscular dosage (WinRho SDF only)
     Adult and adolescent females

    300 mcg (1500 international units) IM or IV at 28 weeks gestation. If administered earlier in pregnancy, give at 12-week intervals during pregnancy to maintain sufficient levels of passively acquired anti-Rh0 [D] antibodies. A 120 mcg (600 international units) IM or IV dose should be given as soon as possible and preferably within 72 hours of delivery of a confirmed Rh0 [D]-positive infant. If Rh status of the infant is unknown at 72 hours or > 72 hours have passed, do not withhold the dose. Administer as soon as possible, up to 28 days after delivery.

    Intravenous or Intramuscular dosage (Rhophylac only)
    Adult and adolescent females

    300 mcg (1500 international units) IM or IV at 28—30 weeks gestation. Repeat the 300 mcg (1500 international units) IM or IV dose within 72 hours of delivery of a confirmed Rh0 [D]-positive infant. If Rh status of the infant is unknown at 72 hours or > 72 hours have passed, do not withhold the dose.

    Known or suspected massive fetomaternal hemorrhage ( > 15 ml fetal red blood cells or > 30 ml fetal whole blood).
    NOTE: One prefilled syringe of HyperRHO S/D Full-Dose, of Rhophylac, or of RhoGAM has at least 1500 international units of Rh0 [D] antibody and will suppress the immunizing potential of 15 ml of Rh0 [D] positive packed red blood cells or the equivalent of 30 ml of whole blood. One 300 mcg vial of WinRho SDF has at least 1500 international units of Rh0 [D] antibody and will suppress the immunizing potential of 17 ml of Rh0 [D] positive packed red blood cells.
    Intramuscular dosage (HyperRHO S/D Full dose only)

    NOTE: In order to determine the dosage of immune globulin required, perform a fetal red cell count by an approved laboratory technique such as the modified Kleihauer-Betke acid elution stain technique. If the calculated total dose or number of syringes needed is a fraction, round up to the closest full syringe size.

    Adult and adolescent females at least 16 years of age

    300 mcg (1500 international units) IM should be given for every 15 ml of fetal red blood cells (30 ml of fetal whole blood) present. Multiple syringes may be injected IM at the same time at different sites or at spaced intervals. The total dose should be administered within 72 hours of the exposure. Repeat the 300 mcg (1500 international units) IM dose within 72 hours of delivery of a confirmed Rh0 [D]-positive infant. If Rh status of the infant is unknown at 72 hours or > 72 hours have passed, do not withhold the dose.

    Intramuscular dosage (RhoGAM only)
    Adult and adolescent females

    300 mcg (1500 international units) IM should be given for every 15 ml of fetal red blood cells (30 ml of fetal whole blood) present. The total dose should be administered within 72 hours of the exposure.

    Intravenous or Intramuscular dosage (WinRho SDF only)
    Adult and adolescent females

    If a large fetal-maternal hemorrhage is suspected, give 9 mcg (45 international units) IV or 12 mcg (60 international units) IM for every ml of fetal whole blood. Administer at a frequency of 600 mcg (3000 international units) IV every 8 hours or 1200 mcg (6000 international units) IM every 12 hours until the total dose is administered. The total calculated dose should be administered within 72 hours of the exposure. A 120 mcg (600 international units) IM or IV dose should be given as soon as possible and preferably within 72 hours of delivery of a confirmed Rh0 [D]-positive infant. If Rh status of the infant is unknown at 72 hours or > 72 hours have passed, do not withhold the dose.

    Intravenous or Intramuscular dosage (Rhophylac only)

    NOTE: If possible, determine the number of fetal red blood cells in the maternal circulation. 
    NOTE: Intravenous administration is preferred.

    Adult and adolescent females

    If excess transplacental bleeding is measured, give 20 mcg (100 international units) IV or IM for every ml of fetal red blood cells. If testing for the number of fetal red blood cells in the maternal circulation is not feasible and an excessive fetomaternal hemorrhage cannot be excluded, give an additional 300 mcg (1500 international units) IV or IM, which will suppress the immunizing potential of 15 ml of Rh0 [D] positive packed red blood cells. The total calculated dose should be administered as soon as possible and within 72 hours of the exposure.

    During threatened abortion at any stage of gestation that results in the continuation of pregnancy.
    Intramuscular dosage (HyperRHO S/D Full dose only)
    Adult and adolescent females at least 16 years of age

    300 mcg (1500 international units) IM as soon as possible. If administered at 13—18 weeks gestation, give another 300 mcg (1500 international units) IM at 26—28 weeks. Repeat the 300 mcg (1500 international units) IM dose within 72 hours of delivery of a confirmed Rh0 [D]-positive infant. If Rh status of the infant is unknown at 72 hours or > 72 hours have passed, do not withhold the dose. A dose after delivery is not needed if delivery is within 3 weeks of the last dose and no fetomaternal hemorrhage of greater than 15 ml of RBC has occurred.

    Intramuscular dosage (RhoGAM only)
    Adult and adolescent females

    300 mcg (1500 international units) IM as soon as possible and within 72 hours of the event.

    Intravenous or Intramuscular dosage (Rhophylac only)
    Adult and adolescent females

    300 mcg (1500 international units) IM or IV as soon as possible and within 72 hours of the event.

    Intravenous or Intramuscular dosage (WinRho SDF only)
    Adult and adolescent females

    300 mcg (1500 international units) IM or IV as soon as possible and within 72 hours of the event. Repeat this dose at 12 week intervals during the pregnancy to maintain sufficient levels of passively acquired anti-Rh0 [D] antibodies. A 120 mcg (600 international units) IM or IV dose should be given as soon as possible and preferably within 72 hours of delivery of a confirmed Rh0 [D]-positive infant. If Rh status of the infant is unknown at 72 hours or > 72 hours have passed, do not withhold the dose.

    Following spontaneous abortion, induced termination of pregnancy, or ectopic pregnancy that occurs <= 12 weeks of gestation.
    NOTE: One prefilled syringe of HyperRHO S/D Mini-Dose or of MICRhoGAM has at least 250 international units of Rh0 [D] antibody and will suppress the immunizing potential of 2.5 ml of Rh0 [D] positive packed red blood cells or the equivalent of 5 ml of whole blood.
    Intramuscular dosage (HyperRHO S/D Mini-Dose and MICRhoGAM only)

    NOTE: The safety and efficacy of HyperRHO™ S/D Mini Dose in adolescents less than 16 years of age have not been established.

    Adult and adolescent females

    50 mcg (250 international units) IM as soon as possible. Give the dose within 3 hours of the spontaneous or surgical removal of aborted tissues, if possible, and within 72 hours of the exposure.

    Following spontaneous abortion, induced termination of pregnancy, or ruptured tubal pregnancy (ectopic pregnancy) that occurs at >= 13 weeks.
    Intramuscular dosage (HyperRHO S/D Full dose and RhoGAM only)

    NOTE: The safety and efficacy of HyperRHO S/D Full Dose in adolescents less than 16 years of age have not been established.

    Adult and adolescent females

    300 mcg (1500 international units) IM as soon as possible and within 72 hours of the event.

    Following spontaneous abortion, induced termination of pregnancy, ectopic pregnancy, hydatiform mole, or transplacental hemorrhage resulting from antepartum hemorrhage.
     Intravenous or Intramuscular dosage (Rhophylac only)
    Adult and adolescent females

    300 mcg (1500 international units) IM or IV as soon as possible and within 72 hours of the event.

    Following spontaneous abortion, induced termination of pregnancy, amniocentesis, chorionic villus sampling, abdominal trauma, ruptured tubal pregnancy, or percutaneous umbilical cord sampling occurring up to 34 weeks of gestation.
    Intravenous or Intramuscular dosage (WinRho SDF only)
    Adult and adolescent females

    300 mcg (1500 international units) IM or IV within 72 hours of the event. Repeat this dose at 12 week intervals during the pregnancy to maintain sufficient levels of passively acquired anti-Rh0 [D] antibodies. A 120 mcg (600 international units) IM or IV dose should be given as soon as possible and preferably within 72 hours of delivery of a confirmed Rh0 [D]-positive infant. If Rh status of the infant is unknown at 72 hours or > 72 hours have passed, do not withhold the dose.

    Following invasive procedures such as amniocentesis, chorionic biopsy (chorionic villus sampling), and percutaneous umbilical cord sampling or obstetric manipulative procedures such as external version and abdominal trauma.
    Intravenous/Intramuscular dosage (Rhophylac only)
    Adults and adolescent females

    300 mcg (1500 international units) IM or IV within 72 hours of the event.

    Intramuscular dosage (RhoGAM only)
    Adults and adolescent females

    300 mcg (1500 international units) IM as soon as possible and within 72 hours of the event.

    Following spontaneous abortion, induced termination of pregnancy, amniocentesis, chorionic villus sampling, abdominal trauma, ruptured tubal pregnancy, or percutaneous umbilical cord sampling occurring after 34 weeks of gestation.
    Intravenous/Intramuscular dosage (WinRho SDF only)
    Adults and adolescent females

    120 mcg (600 international units) IM or IV as soon as possible and within 72 hours of the event. A 120 mcg (600 international units) IM or IV dose should be given as soon as possible and preferably within 72 hours of delivery or a confirmed Rh0 [D]-positive infant. If Rh status of the infant is unknown at 72 hours or > 72 hours have passed, do not withhold the dose.

    Following amniocentesis during weeks 15—18 or during the third trimester or for abdominal trauma in the second or third trimester.
    Intramuscular dosage (HyperRHO S/D Full dose only)
    Adult and adolescent females at least 16 years of age

    300 mcg (1500 international units) IM as soon as possible and within 72 hours of the event. If administered because of abdominal trauma, amniocentesis, or other event at 13—18 weeks gestation, give another 300 mcg (1500 international units) IM at 26—28 weeks. Repeat the 300 mcg (1500 international units) IM dose within 72 hours of delivery of a confirmed Rh0 [D]-positive infant. If Rh status of the infant is unknown at 72 hours, or > 72 hours have passed, do not withhold the dose. A dose after delivery is not needed if delivery is within 3 weeks of the last dose and no fetomaternal hemorrhage of greater than 15 ml of RBC has occurred.

    For the suppression of Rh isoimmunization in Rh0 [D]-negative patients who are exposed to Rh0 [D]-positive red blood cells or Rh0 [D]-positive blood products secondary to blood transfusion.
    NOTE: One prefilled syringe of HyperRHO S/D Full-Dose, of Rhophylac, or of RhoGAM has at least 1500 international units of Rh0 [D] antibody and will suppress the immunizing potential of 15 ml of Rh0 [D] positive packed red blood cells or the equivalent of 30 ml of whole blood. One 300 mcg vial of WinRho SDF has at least 1500 international units of Rh0 [D] antibody and will suppress the immunizing potential of 17 ml of Rh0 [D] positive packed red blood cells.
    NOTE: The amount of incompatible blood transfusion should be determined by an approved assay such as the modified Kleihauer-Betke acid elution stain technique.
    NOTE: Rh immunization can occur after exposure to less than 1 ml of Rh-positive red blood cells.
    NOTE: Monitor patients by clinical and laboratory methods because of the risk for a hemolytic reaction.
    Intramuscular dosage (HyperRHO S/D Full dose and RhoGAM only)
    Adults

    300 mcg (1500 international units) IM should be given for every 15 ml of Rh0 [D]-positive red blood cells transfused. Multiple prefilled syringes may be injected IM at the same time at different sites or at spaced intervals. The total dose should be administered as soon as possible and within 72 hours of the exposure.

    Intramuscular dosage (MICRhoGAM only)
    Adults

    50 mcg (250 international units) IM should be given if less than 2.5 ml of Rh0 [D]-positive red blood cells were transfused. The total dose should be administered as soon as possible and within 72 hours of the exposure.

    Intravenous or Intramuscular dosage (WinRho SDF only)

    NOTE: Treatment should be given (without preceding exchange transfusion) only if the transfused Rh0 [D]-positive blood represents less than 20% of the total circulating red cells.

    Female adults in their childbearing years, adolescent females, and female children

    Give 18 mcg (90 international units) IV or 24 mcg (120 international units) IM for every ml of Rh0 [D]-positive red blood cells transfused. Administer at a frequency of 600 mcg (3000 international units) IV every 8 hours or 1200 mcg (6000 international units) IM every 12 hours until the total dose is administered. The total calculated dose should be administered within 72 hours of the exposure.

    Intravenous or Intramuscular dosage (Rhophylac only)

    NOTE: Treatment should be given (without preceding exchange transfusion) only if the transfused Rh0 [D]-positive blood represents less than 20% of the total circulating red cells. 

    Adults

    20 mcg (100 international units) IV or IM for every 2 ml of transfused blood or per 1 ml of erythrocyte concentrate. Administration should occur within 72 hours of the event.

    For the treatment of immune thrombocytopenia/idiopathic thrombocytopenic purpura (ITP) in non-splenectomized, Rh0 [D] antigen-positive patients.
    NOTE: Alternative treatments should be used in patients with hemoglobin concentrations less than 8 g/dl due to the risk of increasing the severity of anemia.
    In clinical situations requiring an increase in platelet counts to prevent excessive hemorrhage. Includes children with acute or chronic ITP, adults with chronic ITP, or children and adults with ITP secondary to HIV infection.
    NOTE: WinRho SDF has been designated an orphan drug by the FDA for this indication. Confirm that the patient is Rh0 [D] antigen-positive prior to initiating ITP treatment with Rh0 [D] immune globulin. If the calculated dose or number of vials needed is a fraction, round up to the closest full vial size.
    NOTE: If transfusion is necessary, use only Rh0 [D] negative red blood cells and platelet products to prevent exacerbation of ongoing hemolysis. Platelet products may contain up to 5 ml of red blood cells.
    NOTE: The intravenous route must be used for the treatment of ITP. Other routes have not been proven efficacious and could be dangerous (see Contraindications).
    Intravenous dosage (WinRho SDF only)
    Adults, Adolescents, and Children, initial dose

    50 mcg/kg (250 international units/kg) IV initially, as a single dose or in two divided doses on separate days. Patients with a hemoglobin level < 10 g/dl should receive an initial dose of 25—40 mcg/kg (125—200 international units/kg) IV. Alternative treatments should be used if the hemoglobin level is < 8 g/dl. In a small trial of adults and children, a dose of 75 mcg/kg IV as a single dose resulted in higher median day 1 platelet counts (43,000/mm3 vs 7500/mm3) and a longer duration of response (43 days vs. 21 days) as compared to the standard 50 mcg/kg IV dose, respectively.

    Adults, Adolescents, and Children, subsequent doses

    If subsequent therapy is required to elevate platelet counts and the patient had a satisfactory increase in platelets in response to the initial dose, a dose of 25—60 mcg/kg (125—300 international units/kg) IV is recommended. The dose prescribed will be dependent on the patient's clinical response and assessment of platelet counts, hemoglobin levels, red blood cell counts, and reticulocyte counts. If a patient did not respond to the initial dose, give a subsequent dose based on the hemoglobin concentration. Redose patients with hemoglobin levels 8—10 g/dl with 25—40 mcg/kg (125—200 international units/kg) IV. If the hemoglobin is > 10 g/dl, redose patients with 50—60 mcg/kg (250—300 international units/kg) IV. Alternative treatments should be used if the hemoglobin level is < 8 g/dl.

    To raise platelet counts in patients with chronic ITP.
    Intravenous dosage (Rhophylac only)
    Adults

    50 mcg/kg (250 international units/kg) IV; each syringe contains 1500 international units/2 ml; determine the volume needed, and administer 2 ml every 15—60 seconds until the needed volume is administered.

    MAXIMUM DOSAGE

    Adults

    The maximum amount depends on the indication.

    Elderly

    The maximum amount depends on the indication.

    Adolescents

    The maximum amount depends on the indication.

    Children

    The maximum amount depends on the indication.

    Infants

    Not recommended.

    Neonates

    Not recommended.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

    Renal Impairment

    Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

    ADMINISTRATION

    NOTE: Using the International (WHO) Reference, 1 mcg is equivalent to 5 international units. The traditional standard full dose is considered to be approximately 300 mcg (1500 international units).

    Injectable Administration

    HyperRHO S/D, MICRhoGAM, and RhoGAM are administered by the intramuscular route only; DO NOT inject intravenously.
    WinRho SDF and Rhophylac are administered intravenously for the treatment of immune thrombocytopenic purpura and may be administered intramuscularly or intravenously for suppression of Rh isoimmunization.
    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. The Rhophylac solution should be clear or slightly opalescent and colorless to pale yellow; do not use if the solution is cloudy, has deposits, or has been frozen.
    Reconstitution/Dilution of the WinRho SDF lyophilized powder:
    No reconstitution or dilution is necessary for BayRho-D (HyperRHO S/D) Mini-dose, BayRho-D (HyperRHO S/D) Full-dose, Rhophylac, MICRhoGAM, RhoGAM, or the liquid formulation of WinRho SDF.
    WinRho SDF lyophilized powder for IV use: If the product will be given intravenously, reconstitute the 600 international units or 1500 international units powder immediately before use with 2.5 ml of sterile diluent. Reconstitute the 5000 international units powder immediately before use with 8.5 ml of sterile diluent. Add the diluent to the vial by slowly injecting down the side wall of the vial. Gently swirl the vial until the powder is dissolved. Do not shake. Discard any unused diluent.
    WinRho SDF lyophilized powder for IM use: If the product will be given intramuscularly, reconstitute the 600 international units or 1500 international units powder immediately before use with 1.25 ml of sterile diluent. Reconstitute the 5000 international units powder immediately before use with 8.5 ml of sterile diluent. Add the diluent to the vial by slowly injecting down the side wall of the vial. Gently swirl the vial until the powder is dissolved. Do not shake. Discard any unused diluent.
    Reconstituted WinRho SDF lyophilized powder should be used promptly. If reconstituted product is not used immediately, it may be stored at room temperature for up to 12 hours; do not freeze. Discard the reconstituted lyophilized product if not used within 12 hours of reconstitution.

    Intravenous Administration

    Use aseptic technique.
    WinRho SDF: Bring the solution to room temperature before use. Remove the entire contents of the vial in order to obtain the labeled dosage. If partial vials are required for dosage calculation, withdraw the entire vial contents to ensure accurate calculation of the dosage requirement. If dilution is desired, ONLY use NS as the diluent. For immune thrombocytopenic purpura, infuse IV into a suitable vein over 3—5 minutes; closely monitor patients in a healthcare setting for at least 8 hours after administration. Also, perform a dipstick urinalysis to monitor for hematuria and hemoglobinuria at baseline and at 2, 4, and 8 hours after administration. For Rh isoimmunization suppression, infuse at a rate of 2 ml per 5—15 seconds. Administer separately from other IV drugs and fluids.
    Rhophylac: Bring the solution to room temperature before use. Ensure that the needle-free IV administration system is compatible with the tip of the Rhophylac glass syringe. For immune thrombocytopenic purpura, infuse at a rate of 2 ml per 15—60 seconds; closely monitor patients in a healthcare setting for at least 8 hours after administration. Also, perform a dipstick urinalysis to monitor for hematuria and hemoglobinuria at baseline and at 2, 4, and 8 hours after administration.

    Intramuscular Administration

    Rhophylac and WinRho SDF: Bring the solution to room temperature before use.
    If the calculated dose is > 5 ml, administer the total dose in divided doses at different sites at the same time. Alternatively, each vial or syringe may be administered at intervals, provided the entire calculated dose is administered within 72 hours of the fetomaternal hemorrhage or incompatible blood transfusion. Administer the entire calculated dose as soon as possible.
    Using aseptic technique, inject IM into the deltoid muscle of the upper arm or the anterolateral portion of the upper thigh. Do not use the gluteal muscle as a routine injection site due to the risk of sciatic nerve injury. If the gluteal region is used, injection should be made only into the upper, outer quadrant. Aspirate prior to injection to avoid injection into a blood vessel. If a vessel is penetrated, withdraw the needle and use a new syringe and needle at a different injection site.
    RhoGAM, MICRhoGAM, or Rhophylac: Observe patients for at least 20 minutes after administration.

    STORAGE

    HyperRHO S/D:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Do not freeze
    - Store between 36 to 46 degrees F
    MICRhoGAM:
    - Do not freeze
    - Refrigerate (between 36 and 46 degrees F)
    RhoGAM:
    - Do not freeze
    - Refrigerate (between 36 and 46 degrees F)
    Rhophylac:
    - Do not freeze
    - Protect from light
    - Store in original container
    - Store product in refrigerator (36 to 46 degrees F) for up to 36 months from date of manufacture
    WinRho SDF:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Do not freeze
    - Refrigerate (between 36 and 46 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    Anemia, hemolysis, hemolytic anemia, renal impairment, requires a specialized care setting

    WinRho SDF and Rhophylac are approved for intravenous use in patients with idiopathic thrombocytopenic purpura (ITP). Increased destruction of Rh0 [D]-positive red cells occurs after Rh0 [D] immune globulin administration, and this will produce decreased serum hemoglobin concentrations and associated clinical symptoms. Because of this, use with caution in patients with preexisting anemia. Patients with ITP who have a hemoglobin < 10 g/dl should receive a reduced dose of WinRho SDF in order to decrease the risk of worsening the severity of the anemia. Alternative treatments should be used in patients with ITP who have a hemoglobin level < 8 g/dl because the risk of the severity of anemia is increased. The safety of Rhophylac in the treatment of ITP has not been established in patients with pre-existing anemia; weigh the benefits of Rhophylac versus the potential risk of increasing the anemia severity. While most of the red cell destruction will occur in the spleen, there have been rare reports of acute hemoglobinuria consistent with intravascular hemolysis that have occurred during Rh0 [D] immune globulin administration to patients with ITP. WinRho SDF is contraindicated for use in patients with pre-existing hemolysis, patients at high risk for hemolysis, and in patients with autoimmune hemolytic anemia. Rh0[D]-positive patients with ITP should be monitored for signs and/or symptoms of intravascular hemolysis (IVH), clinically compromising hemolytic anemia, and renal impairment during treatment. IVH leading to death has been reported in patients treated for ITP with Rh0 [D] immune globulin. IVH can lead to clinically compromising anemia and multi-system organ failure including acute respiratory distress syndrome (ARDS). Serious complications, including severe anemia, acute renal impairment, renal failure, and disseminated intravascular coagulation (DIC) have also been reported. WinRho SDF and Rhophylac for ITP requires a specialized care setting; closely monitor patients in a health care setting for at least 8 hours after administration. Perform a dipstick urinalysis at baseline and at 2 hours, 4 hours, and 8 hours after administration. Monitor signs and symptoms of IVH including back pain, chills, fever, and hematuria. Absence of these signs and/or symptoms of IVH within 8 hours does not indicate that IVH cannot occur subsequently. If signs and/or symptoms of IVH are present or suspected after Rh0 [D] immune globulin administration, post-treatment laboratory tests should be performed including plasma hemoglobin, microscopic and dipstick urinalysis, haptoglobin, LDH, and plasma bilirubin (direct and indirect). Periodic monitoring of renal function and urine output is particularly important in patients judged to be at increased risk of developing acute renal failure. Assess renal function in all patients before initiation of Rh0 [D] immune globulin and at appropriate intervals thereafter for at-risk patients. Infusion of intravenous immune globulin at a minimal practical concentration and infusion rate is recommended for patients with renal insufficiency or for patients who are predisposed to acute renal failure. Receipt of intravenous immune globulin has been reported to produce renal dysfunction in these patients. Most reports of renal dysfunction have involved products that contain sucrose as a stabilizer. If renal dysfunction occurs, use clinical judgment to either decrease the infusion rate or stop the infusion.

    IgA deficiency

    WinRho SDF is contraindicated in patients who have IgA deficiency with antibodies against IgA.Patients with IgA deficiency often develop antibodies against IgA and are more likely to have anaphylactic or immune-mediated adverse reactions to pooled immunoglobulin products such as Rh0 [D] immune globulin. WinRho SDF contains approximately 5 mcg/ml of IgA, Rhophylac has less than 5 mcg/ml of IgA, and RhoGAM and MICRhoGAM typically contain less than 15 mcg per dose. The benefits of Rh0 [D] immune globulin must be carefully weighed against the potential risk of severe hypersensitivity reactions. The health care professional should have immediate availability of epinephrine (1:1000) injection and other agents used in the treatment of severe anaphylaxis in the event of a serious allergic reaction to Rh0 [D] immune globulin. Immediately stop the administration of Rh0 [D] immune globulin if allergic or anaphylactic-type symptoms occur.

    Anticoagulant therapy, coagulopathy, hemophilia, intramuscular administration, intravenous administration, thrombocytopenia, vitamin K deficiency

    HyperRHO S/D Full dose or Mini dose, RhoGAM, and MICRhoGAM are for intramuscular administration only; do not give these products via intravenous administration. Any condition such as thrombocytopenia, coagulopathy, or other bleeding disorder that contraindicates the use of intramuscular (IM) injections contraindicates the use of Rh0 [D] immune globulin that is given intramuscularly. Patients with thrombocytopenia, vitamin K deficiency, a coagulopathy (e.g., hemophilia) or receiving anticoagulant therapy should be monitored closely when given Rh0 [D] immune globulin by IM injection because bleeding can occur at the IM injection site. WinRho SDF and Rhophylac are the only Rh0 [D] immune globulin products that may be used via intravenous administration. WinRho SDF must be given intravenously for the treatment of idiopathic thrombocytopenic purpura (ITP) in patients with a spleen who are Rh0[D]-positive; do not give via intramuscular administration when used for ITP. The efficacy and safety of WinRho SDF for ITP has only been established when given by the intravenous route.

    Agammaglobulinemia, hypogammaglobulinemia

    Rh0 [D] immune globulin is not indicated for use as immunoglobulin replacement therapy for patients with immune globulin deficiency syndromes such as agammaglobulinemia or hypogammaglobulinemia. Also, intravenous use of WinRho SDF is only for patients with ITP who are Rh0 [D]-positive and have a spleen (see Mechanism of Action). The efficacy of the product in patients with ITP who have asplenia or who are Rh0 [D]-negative has not been established. Also, Rh0 [D]-negative patients who have anti-Rh0 [D] antibodies should not get Rh0 [D] immune globulin (see Mechanism of Action). The presence of anti-Rh0 [D] antibodies is detected by an indirect antiglobulin (Coombs') test.

    Pregnancy

    Rh0 [D] immune globulin is classified as pregnancy category C. Although this agent has not been well studied in pregnant women, some of the products are routinely given during pregnancy. The HyperRHO S/D Mini-Dose product is not indicated for use during pregnancy (see Dosage). Under ideal circumstances, when used to prevent Rh0 [D] isoimmunization from exposure to Rh0[D]-positive blood, Rh0 [D] immune globulin should only be administered to a non-sensitized Rh0 [D]-negative obstetric patient. If there is question about the mother's Rh type or if there is insufficient time to determine fetal Rh typing (as might occur in trauma during pregnancy), then Rh0 [D] immune globulin should be administered as indicated by the clinical situation. Rh0 [D] immune globulin would not be effective in preventing erythroblastosis fetalis in the Rh0 [D]-negative mother who has already formed anti-D IgG antibodies. However, Rh0 [D] negative women who have already been sensitized to the Rh0 [D] erythrocyte factor do not appear to have an increase in adverse reactions if administered the product as a result of unknown Rh status. There is no known obstetric indication for the use of Rh0 [D] immune globulin in women who are Rh0 [D]-positive, as these women are not at risk of isoimmunization from an Rh0 [D]-positive fetus.

    Children, infants, neonates

    The Rh0 [D] immune globulin is never to be administered to neonates, as the anti-D activity could precipitate a hemolytic episode if the infant is Rh0 [D]-positive. The safety and efficacy of HyperRHO S/D Mini Dose or Full Dose in infants, children, or adolescents less than 16 years of age have not been established.

    Breast-feeding

    Rh0 [D] immune globulin is is a immune globulin (IgG) rich in IgG antibodies. IgG is a normal component of breastmilk. Rh0 [D] immune globulin is frequently used in nursing mothers and no adverse effects have been reported in a breast-feeding infant. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    Diabetes mellitus

    Only glucose-specific testing methods such as glucose dehydrogenase nicotine-adenine dinucleotide, glucose oxidase- or glucose hexokinase-based tests are appropriate to determine serum glucose concentrations in patients such as those with diabetes mellitus who have received the liquid formulation of WinRho SDF. The liquid formulation of the immune globulin contains maltose, which can cause falsely elevated glucose readings on some testing systems such as glucose dehydrogenase pyrroloquinolinequinone (GDH-PQQ)-glucose monitoring systems. The interaction with glucose testing does not occur with the lyophilized powder formulation of WinRho SDF. Tell patients who get the liquid formulation to only use glucose-specific testing methods. Carefully review the product information of the blood glucose testing system including the information about the test strips. Contact the manufacturer of the testing system if any uncertainty exists about the appropriateness of the system in regard to maltose-containing parenteral products.

    Geriatric, hepatitis, infection, leukemia, lymphoma, systemic lupus erythematosus (SLE)

    Geriatric patients with comorbid conditions such as active infection (including hepatitis C virus (HCV)), hematological malignancies (including non-Hodgkin's lymphoma, Hodgkin's disease or chronic lymphocytic leukemia), and autoimmune disorders (systemic lupus erythematosus (SLE), antiphospholipid syndrome, and autoimmune hemolytic anemia) may be at an increased risk of developing acute hemolytic reactions to WinRho SDF such as intravascular hemolysis (IVH). Patients receiving doses of WinRho SDF in excess of 300 IU/kg of WinRho SDF may also be at an increased risk. Fatal outcomes associated with IVH have occurred most frequently in elderly patients with comorbid conditions. In general, caution should be used in dose selection for an elderly patient, with consideration given to starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

    ADVERSE REACTIONS

    Severe

    anaphylactoid reactions / Rapid / Incidence not known
    anaphylactic shock / Rapid / Incidence not known
    cardiac arrest / Early / Incidence not known
    myocardial infarction / Delayed / Incidence not known
    anuria / Delayed / Incidence not known
    acute respiratory distress syndrome (ARDS) / Early / Incidence not known
    oliguria / Early / Incidence not known
    renal failure (unspecified) / Delayed / Incidence not known
    disseminated intravascular coagulation (DIC) / Delayed / Incidence not known
    hemolytic-uremic syndrome / Delayed / Incidence not known
    heart failure / Delayed / Incidence not known
    pulmonary edema / Early / Incidence not known

    Moderate

    hyperbilirubinemia / Delayed / 21.4-21.4
    hypertension / Early / 2.0-2.0
    hypotension / Rapid / 2.0-2.0
    erythema / Early / Incidence not known
    peripheral vasodilation / Rapid / Incidence not known
    chest pain (unspecified) / Early / Incidence not known
    wheezing / Rapid / Incidence not known
    hematuria / Delayed / Incidence not known
    sinus tachycardia / Rapid / Incidence not known
    jaundice / Delayed / Incidence not known
    hemolysis / Early / Incidence not known
    prolonged bleeding time / Delayed / Incidence not known
    dyspnea / Early / Incidence not known
    anemia / Delayed / Incidence not known
    edema / Delayed / Incidence not known
    hypoxia / Early / Incidence not known

    Mild

    chills / Rapid / 8.0-34.7
    fever / Early / 6.0-30.6
    headache / Early / 11.0-11.2
    asthenia / Delayed / 4.0-4.0
    dizziness / Early / 4.0-4.0
    infection / Delayed / 3.0-3.0
    back pain / Delayed / 2.0-2.0
    vomiting / Early / 2.0-2.0
    pallor / Early / 2.0-2.0
    nausea / Early / 2.0-2.0
    abdominal pain / Early / 2.0-2.0
    hyperkinesis / Delayed / Incidence not known
    drowsiness / Early / Incidence not known
    diarrhea / Early / Incidence not known
    myalgia / Early / Incidence not known
    diaphoresis / Early / Incidence not known
    arthralgia / Delayed / Incidence not known
    injection site reaction / Rapid / Incidence not known
    rash (unspecified) / Early / Incidence not known
    pruritus / Rapid / Incidence not known
    urticaria / Rapid / Incidence not known
    weakness / Early / Incidence not known
    ecchymosis / Delayed / Incidence not known
    weight gain / Delayed / Incidence not known
    hyperhidrosis / Delayed / Incidence not known
    muscle cramps / Delayed / Incidence not known

    DRUG INTERACTIONS

    Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live: (Major) Do not give immune globulin including varicella zoster immune globulin concurrently with the varicella-zoster virus vaccine, live. Because of the potential inhibition of the immune response to vaccination by passively transferred antibodies, it is advisable not to give varicella-zoster virus vaccine, live to any patient who has received blood (except washed red blood cells), plasma transfusions, or immunoglobulins within the previous 5 months. After varicella vaccination, the CDC recommends that immune globulin products should not be given for 3 weeks, unless the benefit outweighs the risk; the manufacturer recommends waiting 2 months before administering immunoglobulins. In the case that IgG products are administered within 3 weeks of vaccination, the vaccinee should be either revaccinated at 5 months or tested for immunity and revaccinated if seronegative. Consult current CDC guidelines for recommendations. (Major) Rubella virus vaccine or Measles/mumps/rubella vaccines, MMR should not be given for at least 3 months following administration of immunoglobulins because antibodies in these products can neutralize the vaccine.
    Measles/Mumps/Rubella Vaccines, MMR: (Major) Rubella virus vaccine or Measles/mumps/rubella vaccines, MMR should not be given for at least 3 months following administration of immunoglobulins because antibodies in these products can neutralize the vaccine.
    Rotavirus Vaccine: (Major) Defer vaccination with live virus vaccines such as Rotavirus Vaccine until approximately 3 months after Rh0 [D] immune globulin administration. Inform the immunizing physician of recent therapy with Rh0 [D] immune globulin so that appropriate measures can be taken. The efficacy of live attenuated virus vaccines such as Rotavirus Vaccine may be impaired by Rh0 [D] immune globulin administration; revaccination may be necessary. The passive transfer of antibodies from the immune globulin may impair the efficacy of live attenuated virus vaccine.
    Rubella Virus Vaccine Live: (Major) Rubella virus vaccine or Measles/mumps/rubella vaccines, MMR should not be given for at least 3 months following administration of immunoglobulins because antibodies in these products can neutralize the vaccine.
    Tetanus Toxoid: (Moderate) Concomitant administration of immunoglobulins can decrease the immunological response to the DTP or Tdap vaccine. If concurrent tetanus immune globulin and/or diphtheria antitoxin is needed, administration should be at a separate site and with a separate needle from DTP or Tdap administration.
    Varicella-Zoster Virus Vaccine, Live: (Major) Do not give immune globulin including varicella zoster immune globulin concurrently with the varicella-zoster virus vaccine, live. Because of the potential inhibition of the immune response to vaccination by passively transferred antibodies, it is advisable not to give varicella-zoster virus vaccine, live to any patient who has received blood (except washed red blood cells), plasma transfusions, or immunoglobulins within the previous 5 months. After varicella vaccination, the CDC recommends that immune globulin products should not be given for 3 weeks, unless the benefit outweighs the risk; the manufacturer recommends waiting 2 months before administering immunoglobulins. In the case that IgG products are administered within 3 weeks of vaccination, the vaccinee should be either revaccinated at 5 months or tested for immunity and revaccinated if seronegative. Consult current CDC guidelines for recommendations.

    PREGNANCY AND LACTATION

    Pregnancy

    Rh0 [D] immune globulin is classified as pregnancy category C. Although this agent has not been well studied in pregnant women, some of the products are routinely given during pregnancy. The HyperRHO S/D Mini-Dose product is not indicated for use during pregnancy (see Dosage). Under ideal circumstances, when used to prevent Rh0 [D] isoimmunization from exposure to Rh0[D]-positive blood, Rh0 [D] immune globulin should only be administered to a non-sensitized Rh0 [D]-negative obstetric patient. If there is question about the mother's Rh type or if there is insufficient time to determine fetal Rh typing (as might occur in trauma during pregnancy), then Rh0 [D] immune globulin should be administered as indicated by the clinical situation. Rh0 [D] immune globulin would not be effective in preventing erythroblastosis fetalis in the Rh0 [D]-negative mother who has already formed anti-D IgG antibodies. However, Rh0 [D] negative women who have already been sensitized to the Rh0 [D] erythrocyte factor do not appear to have an increase in adverse reactions if administered the product as a result of unknown Rh status. There is no known obstetric indication for the use of Rh0 [D] immune globulin in women who are Rh0 [D]-positive, as these women are not at risk of isoimmunization from an Rh0 [D]-positive fetus.

    Rh0 [D] immune globulin is is a immune globulin (IgG) rich in IgG antibodies. IgG is a normal component of breastmilk. Rh0 [D] immune globulin is frequently used in nursing mothers and no adverse effects have been reported in a breast-feeding infant. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    MECHANISM OF ACTION

    Although the mechanism is not well understood, it is believed that the anti-Rh0[D] antibodies contained in Rh0 [D] immune globulin interact directly with the Rh0[D] antigens, thereby preventing the interaction between the antigens and the maternal immune system. Sensitization to Rh0[D]-positive blood is therefore less likely to occur. If Rh immunization has occurred, Rh0 [D] immune globulin is ineffective. Clinical studies indicate that administration of 300 mcg (1500 International Units) Rh0 [D] immune globulin within 72 hours after delivery of an Rh0[D]-positive infant by a Rh0[D]-negative mother decreases the incidence of active anti-Rh0 [D] production from 12—13% to 1—2%. When treatment is administered both antenatally at 28 weeks of gestation and postpartum, the Rh isoimmunization rate drops to around 0.1%. The appropriate use of Rh0 [D] immune globulin has reduced the prevalence of Rh isoimmunization in the U.S. and Canada by 96 percent since the 1940s.
     
    The actions of Rh0 [D] immune globulin in idiopathic thrombocytopenic purpura (ITP) are not well understood. Intravenous infusion of Rh0 [D] immune globulin into a Rh0 [D]-positive patient leads to antibody coating of circulating erythrocytes. These coated red cells are cleared primarily by the spleen. The immune-mediated clearance of these sensitized erythrocytes occupies the reticuloendothelial system (RES) and allows for the survival of antibody coated platelets. The primary mechanism of action of Rh0 [D] immune globulin appears to occur via immunologic blockade of Fc-receptors within the RES. Other immunomodulatory mechanisms may also play a role in Rh0 [D] immune globulin efficacy in ITP. After administration, Rh0 [D] immune globulin produces a 2—3 day delay in increasing the platelet count. The mean duration of response is about 30 days. Children with ITP tend to respond better than adults to Rh0 [D] immune globulin therapy. Repeated Rh0 [D] immune globulin infusions do not cure the disease but are used to maintain platelet counts at levels sufficient enough to provide adequate hemostasis ( > 30,000/mcl). Rh0 [D] immune globulin is not effective in splenectomized or Rh0 [D]-negative patients with ITP.

    PHARMACOKINETICS

    Rho [D] is administered via intravenous or intramuscular injection. The pharmacokinetics of Rh0 [D] immune globulin are not well described, but passively acquired anti-Rh0 [D] antibodies are not detectable 6 months after administration. If a Rh negative mother is exposed to Rh positive cells early in pregnancy, repeat doses of Rh0 [D] immune globulin may be needed (see Dosage). In order to maintain protection throughout pregnancy, the concentration of passively acquired anti-Rh0 [D] must not fall below the concentration necessary to prevent an immune response to Rh positive red cells.

    Intravenous Route

    Peak levels following IV administration occur within 2 hours. The calculated AUC is similar for both IV and IM administration. The liquid and lyophilized formulations of WinRho SDF given IV are bioequivalent. Similar pharmacokinetic parameters were obtained for both formulations when given intramuscularly. The mean peak concentrations occurred within 30 minutes of IV administration. The half-life of Rh0 [D] immune globulin is approximately 24 days after IV administration.

    Intramuscular Route

    Peak levels following IM administration occur within 5—10 days. The calculated AUC is similar for both IV and IM administration. Similar pharmacokinetic parameters were obtained for both the liquid and lyophilized formulations of WinRho SDF when given intramuscularly. The mean peak concentrations is within 2—4 days of IM administration. The half-life of Rh0 [D] immune globulin is approximately 30 days after IM administration.