Human Rho(D) immune globulin

Identification

Name
Human Rho(D) immune globulin
Accession Number
DB11597
Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Polyclonal antibody (pAb)
Description

Human Rho(D) immune globulin is a medicine given by intramuscular or intravenous injection that is used to prevent the immunological condition known as Rh disease (or hemolytic disease of newborn). Rho (D) immune globulin is available as a sterile, lyophilized or liquid gamma globulin (IgG) fraction containing antibodies to the Rh0 (D) antigen (D antigen) under the name Rhophylac (IM/IV). Immune globullin was purified via ion-exchange chromatography method and prepared from pools of human plasma, where the donors are Rho (D)-negative donors who have been immunized with Rho(D)-positive RBCs. It was approved by FDA as treatment for suppression of rhesus (Rh) isoimmunization or chronic immune thrombocytopenic purpura (ITP) in adults.

Protein chemical formula
Not Available
Protein average weight
Not Available
Sequences
Not Available
Synonyms
  • Anti-D (RH) immunoglobulin (human)
  • Anti-D immunoglobulin
  • Anti-D immunoglobulins
  • Human anti-D immunoglobulin
  • IGG, Rho (D)
  • Immunoglobulin human anti-RH
  • Rh0(D) Immune Globulin Intravenous (Human)
  • Rho (D) immune globulin,human
  • Rho D immune globulin human
  • Rho(D) immune globulin (human)
  • Rho(D) immune globulin human
  • Rho(D) immune globulin IM human
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Hyp Rho D Inj 16.5%LiquidIntramuscularCutter Med & Biol, Division Of Miles Canada Ltd.1979-12-311998-09-25Canada
Hyperrho S/d Full DoseSolution1500 [iU]/1IntramuscularGRIFOLS USA, LLC1996-08-14Not applicableUs
Hyperrho S/d Mini-doseSolution250 [iU]/1IntramuscularGRIFOLS USA, LLC1996-08-14Not applicableUs
MICRhoGAM Ultra-Filtered PLUSInjection, solution50 ug/1IntramuscularKedrion Melville Inc.2007-03-09Not applicableUs
RhoGAM Ultra-Filtered PLUSInjection, solution300 ug/1IntramuscularKedrion Melville Inc.2007-03-09Not applicableUs
RhophylacSolution1500 [iU]/2mLIntramuscular; IntravenousCsl Behring Ag2009-01-06Not applicableUs
WinRho SDFKit5000 unitIntramuscular; IntravenousAptevo Biotherapeutics Llc1998-01-282016-07-15Canada
WinRho SDFKit1500 unitIntramuscular; IntravenousAptevo Biotherapeutics Llc1996-08-282016-07-15Canada
WinRho SDFKit600 unitIntramuscular; IntravenousAptevo Biotherapeutics Llc1997-01-102016-07-15Canada
WinRho SDFSolution15000 unitIntramuscular; IntravenousSaol Therapeutics Research LimitedNot applicableNot applicableCanada
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Winrho Sd Kit InjHuman Rho(D) immune globulin (120 mcg) + Sodium chloride (0.9 %)KitIntramuscular; IntravenousRh Pharmaceuticals Inc.1993-12-311997-07-22Canada
Winrho Sd Kit Inj.Human Rho(D) immune globulin (300 mcg) + Sodium chloride (.9 %)KitIntramuscular; IntravenousRh Pharmaceuticals Inc.1993-12-311997-07-22Canada
Categories
UNII
48W7181FLP
CAS number
Not Available

Pharmacology

Indication

Indicated for suppression of rhesus (Rh) isoimmunization in nonsensitized Rho (D)-negative women with an Rh-incompatible pregnancy, or in Rho (D)-negative individuals transfused with Rh0(D)-positive red blood cells (RBCs) or blood components containing Rh0(D)-positive RBCs. Also indicated in Rh0(D)-positive, non-splenectomized adult patients with chronic immune thrombocytopenic purpura (ITP) to raise platelet counts.

Associated Conditions
Associated Therapies
Pharmacodynamics

15000 international unit (IU) contains sufficient anti-Rho (D) to effectively suppress the immunizing potential of approximately 17mL of Rho (D) (D-positive) red blood cells 12. Human Rho(D) immune globulin therapy prevents immunization to Rho (D)-positive red blood cells (RBC) by inducing antibody-mediated immunosuppression (AMIS) effectively clearing Rho-positive RBCs by rapidly binding to them. This prevents Rho-negative mothers to produce alloantibodies to paternally inherited RhD antigen expressed on fetal erythrocytes and cause haemolytic diseases of the newborn. Rho immune globulin increase platelet counts and reduce bleeding in Rho-positive patients with ITP by inhibiting autoantibody-mediated platelet clearance.

Mechanism of action

The mechanism of action of Rho(D) immune globulin therapy is unclear. It is suggested that Rho immune globulin predominantly prevents the antibody response during incompatible pregnancy by accelerating the phagocytosis of RBC's and clearance from the circulation before the recognition by the immune system. IgG-opsonized RBCs may interact with activating IgG receptors (FcγRs) on effector cells and elicit phagocytosis via mononuclear phagocytic system, primarily by macrophages. IgG may also stimulate complement activation on the RBC surface, followed by RBC lysis or complement receptor-mediated phagocytosis but to smaller extent 4. Rho-specific IgG may inhibit the late stages of B cell activation by being internalized with Rho antigen by B cells, which alters the antigen processing and presentation. In response to the IgG-antigen complex formation, the immune globulin enhances the presentation of specific peptides and proliferation of epitope-specific T cells 4. Therapeutic efficacy of Rho (D) immune globulin in chronic immune thrombocytopenic purpura (ITP) may be explained by FcR blockade as well as the increase in the platelet count by substituting antibody-coated RBCs for antibodycoated platelets 2. In vitro studies of cytokine expression in human monocytes and granulocytes exposed to anti-D coated red blood cells have demonstrated enhanced secretion of interleukin 1 receptor antagonist resulting in down-regulation of FcγR mediated phagocytosis. Murine models show that RBC-specific antibodies can increase platelet counts by down-regulating FcγRIIIa on splenic macrophage, which is an opposing effect as predicted in intravenous Rho IgG 3.

TargetActionsOrganism
ARhesus blood group D antigen
antibody
Humans
Additional Data Available
Adverse Effects

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Additional Data Available
Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Additional Data Available
Blackbox Warnings

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Absorption

In patients undergoing therapy for Rh isoimmunization suppression, Rho(D) immune globulin titers were detected in all women up to at least 9 weeks following either intravenous or intramuscular administration. Following intravenous administration of a single 1500 IU (300 mcg) dose, peak serum levels of Rh0(D) immune globulin ranged from 62 to 84 ng/mL after first day. The levels ranged from 7 to 46 ng/mL and were achieved between 2 and 7 days following intramuscular injection. The absolute bioavailability achieved following IM administration is 69%.

Volume of distribution

A single dose of 300ug Rho(D) Immune Globulin through intramuscular injection displays a Vd of 8.59L 13.

Protein binding
Not Available
Metabolism

Rho (D) immune globulin is expected to undergo nonspecific catabolism.

Route of elimination

Human immune globulin and the fragments can be detected in feces and urine.

Half life

The half life is 16 ± 4 days following IV administration and 18 ± 5 days following IM administration.

Clearance

Mean systemic clearance following IV administration is 0.20 ±0.03 mL/min. Mean apparent clearance following IM administration is 0.29 ± 0.12 mL/min.

Toxicity

Most serious adverse reactions in patients with ITP include intravascular hemolysis, anemia, acute renal insufficiency, and death. In patients treated for Rh isoimmunization suppression, common adverse effects include nausea, dizziness, headache, pain at injection site and malaise. Common adverse effects in patients with ITP include chills, pyrexia, mild extravascular hemolysis and headache.

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Not Available
Food Interactions
Not Available

References

General References
  1. Cheung E, Liebman HA: Anti-RhD immunoglobulin in the treatment of immune thrombocytopenia. Biologics. 2009;3:57-62. Epub 2009 Jul 13. [PubMed:19707396]
  2. Bussel JB, Graziano JN, Kimberly RP, Pahwa S, Aledort LM: Intravenous anti-D treatment of immune thrombocytopenic purpura: analysis of efficacy, toxicity, and mechanism of effect. Blood. 1991 May 1;77(9):1884-93. [PubMed:1850307]
  3. Crowther CA, Keirse MJ: Anti-D administration in pregnancy for preventing rhesus alloimmunisation. Cochrane Database Syst Rev. 2000;(2):CD000020. [PubMed:10796088]
  4. Brinc D, Lazarus AH: Mechanisms of anti-D action in the prevention of hemolytic disease of the fetus and newborn. Hematology Am Soc Hematol Educ Program. 2009:185-91. doi: 10.1182/asheducation-2009.1.185. [PubMed:20008198]
  5. Brinc D, Le-Tien H, Crow AR, Freedman J, Lazarus AH: IgG-mediated immunosuppression is not dependent on erythrocyte clearance or immunological evasion: implications for the mechanism of action of anti-D in the prevention of haemolytic disease of the newborn? Br J Haematol. 2007 Oct;139(2):275-9. [PubMed:17897303]
  6. Bichler J, Schondorfer G, Pabst G, Andresen I: Pharmacokinetics of anti-D IgG in pregnant RhD-negative women. BJOG. 2003 Jan;110(1):39-45. [PubMed:12504934]
  7. Poortmans JR, Jeanloz RW: Urinary excretion of immunoglobulins and their subunits in human subjects before and after exercise. Med Sci Sports Exerc. 1993 Feb;25(2):171-8. [PubMed:8450718]
  8. Haneberg B, Endresen C: Fragments of immunoglobulins in human faeces. Acta Pathol Microbiol Scand C. 1976 Feb;84(1):31-6. [PubMed:1266624]
  9. Haneberg B, Aarskog D: Human faecal immunoglobulins in healthy infants and children, and in some with diseases affecting the intestinal tract or the immune system. Clin Exp Immunol. 1975 Nov;22(2):210-22. [PubMed:813931]
  10. Arend WP, Silverblatt FJ: Serum disappearance and catabolism of homologous immunoglobulin fragments in rats. Clin Exp Immunol. 1975 Dec;22(3):502-13. [PubMed:1225487]
  11. Rhophylac Summary of Basis for Approval [Link]
  12. WinRho Product information [Link]
  13. RhoGam (Rho(D) Immune Globulin intramuscular injection) product information [Link]
External Links
PubChem Substance
347911208
RxNav
1789837
Wikipedia
Rho(D)_immune_globulin
AHFS Codes
  • 80:04.00 — Serums
FDA label
Download (513 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentHealthy Volunteers1
2CompletedNot AvailableHealthy Volunteers1
Not AvailableCompletedTreatmentDengue Fever1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
LiquidIntramuscular
SolutionIntramuscular1500 [iU]/1
SolutionIntramuscular250 [iU]/1
Injection, solutionIntramuscular50 ug/1
Injection, solutionIntramuscular300 ug/1
SolutionIntramuscular; Intravenous1500 [iU]/2mL
KitIntramuscular; Intravenous
KitIntramuscular; Intravenous1500 unit
KitIntramuscular; Intravenous5000 unit
KitIntramuscular; Intravenous600 unit
SolutionIntramuscular; Intravenous1500 unit
SolutionIntramuscular; Intravenous15000 unit
SolutionIntramuscular; Intravenous2500 unit
SolutionIntramuscular; Intravenous5000 unit
SolutionIntramuscular; Intravenous600 unit
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
Not Available

Taxonomy

Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Peptides
Alternative Parents
Not Available
Substituents
Not Available
Molecular Framework
Not Available
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antibody
General Function
Ammonium transmembrane transporter activity
Specific Function
Not Available
Gene Name
RHD
Uniprot ID
A6PZ59
Uniprot Name
Rhesus blood group D antigen
Molecular Weight
45275.06 Da

Drug created on May 20, 2016 13:42 / Updated on May 28, 2020 00:58

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