Human Rho(D) immune globulin

Identification

Summary

Human Rho(D) immune globulin is a solution of antibodies used to prevent isoimmunization of Rho(D) negative patients exposed to Rho(D) positive blood in pregnancy or transfusion.

Brand Names

Hyperrho, Micrhogam, Rhogam, Rhophylac, Winrho

Generic Name

Human Rho(D) immune globulin

DrugBank Accession Number

DB11597

Background

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.

Type

Biotech

Groups

Approved, Investigational

Biologic Classification

Protein Based Therapies
Polyclonal antibody (pAb)

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

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.

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Associated Conditions

Chronic Immune thrombocytopenic purpura

Associated Therapies

Prophylaxis of Rhesus isoimmunization

Contraindications & Blackbox Warnings

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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.

Target	Actions	Organism
ARhesus blood group D antigen	antibody	Humans

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.

Adverse Effects

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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.

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.

Drug	Interaction
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Abciximab	The risk or severity of adverse effects can be increased when Abciximab is combined with Human Rho(D) immune globulin.
Adalimumab	The risk or severity of adverse effects can be increased when Adalimumab is combined with Human Rho(D) immune globulin.
Aducanumab	The risk or severity of adverse effects can be increased when Human Rho(D) immune globulin is combined with Aducanumab.
Alemtuzumab	The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Human Rho(D) immune globulin.
Alirocumab	The risk or severity of adverse effects can be increased when Alirocumab is combined with Human Rho(D) immune globulin.
Amivantamab	The risk or severity of adverse effects can be increased when Human Rho(D) immune globulin is combined with Amivantamab.
Anifrolumab	The risk or severity of adverse effects can be increased when Human Rho(D) immune globulin is combined with Anifrolumab.
Ansuvimab	The risk or severity of adverse effects can be increased when Human Rho(D) immune globulin is combined with Ansuvimab.
Anthrax immune globulin human	The risk or severity of adverse effects can be increased when Anthrax immune globulin human is combined with Human Rho(D) immune globulin.
Antilymphocyte immunoglobulin (horse)	The risk or severity of adverse effects can be increased when Antilymphocyte immunoglobulin (horse) is combined with Human Rho(D) immune globulin.

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Food Interactions

No interactions found.

Products

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Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Hyp Rho D Inj 16.5%	Liquid	16.5 %	Intramuscular	Cutter Med & Biol, Division Of Miles Canada Ltd.	1979-12-31	1998-09-25
Hyperrho S/d Full Dose	Solution	1500 unit / dose	Intramuscular	Grifols Therapeutics Llc	Not applicable	Not applicable
Hyperrho S/d Full Dose	Solution	1500 unit / dose	Intramuscular	Grifols Therapeutics Llc	Not applicable	Not applicable
Hyperrho S/d Full Dose	Solution	1500 [iU]/1	Intramuscular	GRIFOLS USA, LLC	1996-08-14	Not applicable
Hyperrho S/d Mini-dose	Solution	250 [iU]/1	Intramuscular	GRIFOLS USA, LLC	1996-08-14	Not applicable
MICRhoGAM Ultra-Filtered PLUS	Injection, solution	50 ug/1	Intramuscular	Kedrion Biopharma Inc	2007-03-09	Not applicable
RhoGAM Ultra-Filtered PLUS	Injection, solution	300 ug/1	Intramuscular	Kedrion Biopharma Inc	2007-03-09	Not applicable
Rhophylac	Solution	1500 [iU]/2mL	Intramuscular; Intravenous	Csl Behring Ag	2009-01-06	Not applicable
Winrho	Liquid	1500 [iU]/1mL	Intramuscular; Intravenous	Aptevo Biotherapeutics Llc	2016-07-01	Not applicable
Winrho	Liquid	5000 [iU]/1mL	Intramuscular; Intravenous	Aptevo Biotherapeutics Llc	2016-07-01	Not applicable

Mixture Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End	Region	Image
Winrho Sd Kit Inj	Human Rho(D) immune globulin (120 mcg / kit) + Sodium chloride (0.9 % / kit)	Kit	Intramuscular; Intravenous	Rh Pharmaceuticals Inc.	1993-12-31	1997-07-22
Winrho Sd Kit Inj.	Human Rho(D) immune globulin (300 mcg / kit) + Sodium chloride (.9 % / kit)	Kit	Intramuscular; Intravenous	Rh Pharmaceuticals Inc.	1993-12-31	1997-07-22

Unapproved/Other Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End	Region	Image
WIN RHO SDF 300 MCG FLAKON, 1 ADET	Human Rho(D) immune globulin (300 mcg)	Injection, solution	Intramuscular; Intravenous	RA İLAÇ SAN.VE TİC. A.Ş.	2020-08-14	Not applicable

Chemical Identifiers

UNII: 48W7181FLP
CAS number: Not Available

References

General References

Cheung E, Liebman HA: Anti-RhD immunoglobulin in the treatment of immune thrombocytopenia. Biologics. 2009;3:57-62. Epub 2009 Jul 13. [Article]
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. [Article]
Crowther CA, Keirse MJ: Anti-D administration in pregnancy for preventing rhesus alloimmunisation. Cochrane Database Syst Rev. 2000;(2):CD000020. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]
Haneberg B, Endresen C: Fragments of immunoglobulins in human faeces. Acta Pathol Microbiol Scand C. 1976 Feb;84(1):31-6. [Article]
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. [Article]
Arend WP, Silverblatt FJ: Serum disappearance and catabolism of homologous immunoglobulin fragments in rats. Clin Exp Immunol. 1975 Dec;22(3):502-13. [Article]
Rhophylac Summary of Basis for Approval [Link]
WinRho Product information [Link]
RhoGam (Rho(D) Immune Globulin intramuscular injection) product information [Link]

External Links

PubChem Substance: 347911208
RxNav: 1789837
Wikipedia: Rho(D)_immune_globulin

FDA label

Download (513 KB)

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
4	Recruiting	Prevention	Pregnancy Related	1
4	Terminated	Treatment	Hepatitis C Virus (HCV) Infection / Human Immunodeficiency Virus (HIV) Infections / Thrombocytopenia	1
3	Completed	Treatment	Localized, resectable Neuroblastoma (NB) / Localized, unresectable Neuroblastoma (NB) / Regional Neuroblastoma / Stage 4 Neuroblastoma / Stage 4S Neuroblastoma	1
2	Completed	Not Available	Healthy Subjects (HS)	1
1	Completed	Treatment	Healthy Subjects (HS)	1
Not Available	Completed	Treatment	Dengue Fever	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Injection, solution	Intramuscular	1500 IU/2ml
Powder, for solution	Intravenous
Liquid	Intramuscular	16.5 %
Injection	Intramuscular; Intravenous
Solution	Intramuscular	1500 [iU]/1
Solution	Intramuscular	1500 unit / dose
Injection	Intramuscular	1500 IU/dose
Solution	Intramuscular	250 [iU]/1
Injection, solution	Intramuscular	1500 iu
Injection, powder, for solution	Intramuscular	1250 U.I./2ML
Injection, solution	Intramuscular	1500 UI/2ML
Solution	Parenteral	300.000 mcg
Injection, powder, for solution	Intramuscular	200 MCG
Injection, solution	Intramuscular	100 mcg/2ml
Injection, solution	Intramuscular	300 MCG/2ML
Injection, powder, for solution	Intramuscular	300 mcg
Injection, powder, lyophilized, for solution	Intramuscular	300 mcg
Solution	Parenteral	1500 UI
Injection, solution	Intramuscular	50 ug/1
Injection, powder, for solution	Intramuscular
Injection, solution	Intramuscular
Injection, solution	Parenteral	625 IU/ml
Injection, solution	Intramuscular	625 IU/ml
Solution	Parenteral	300 mcg
Injection, solution	Intramuscular	300 mcg
Injection, solution	Intramuscular	300 ug/1
Injection, solution
Solution	Intramuscular; Intravenous	1500 [iU]/2mL
Solution	Intravenous	300.00 mcg
Injection	Intramuscular; Intravenous	300 mcg/2ml
Injection, solution	Intramuscular; Intravenous
Solution	Intramuscular; Intravenous	300 mcg
Solution	Intramuscular	1500 UI
Injection, solution	Intramuscular; Intravenous	300 mcg
Liquid	Intramuscular; Intravenous	1500 [iU]/1mL
Liquid	Intramuscular; Intravenous	15000 [iU]/1mL
Liquid	Intramuscular; Intravenous	2500 [iU]/1mL
Liquid	Intramuscular; Intravenous	5000 [iU]/1mL
Kit	Intramuscular; Intravenous
Injection	Intramuscular; Intravenous	1500 [iU]/1
Injection	Intramuscular; Intravenous	15000 [iU]/1
Injection	Intramuscular; Intravenous	2500 [iU]/1
Injection	Intramuscular; Intravenous	5000 [iU]/1
Injection, solution	Intramuscular; Intravenous	1500 [iU]/1.3mL
Injection, solution	Intramuscular; Intravenous	15000 [iU]/13mL
Injection, solution	Intramuscular; Intravenous	2500 [iU]/2.2mL
Injection, solution	Intramuscular; Intravenous	5000 [iU]/4.4mL
Kit	Intramuscular; Intravenous	1500 unit / kit
Kit	Intramuscular; Intravenous	5000 unit / kit
Kit	Intramuscular; Intravenous	600 unit / kit
Solution	Intramuscular; Intravenous	1500 unit / vial
Solution	Intramuscular; Intravenous	15000 unit / vial
Solution	Intramuscular; Intravenous	2500 unit / vial
Solution	Intramuscular; Intravenous	5000 unit / vial
Solution	Intramuscular; Intravenous	600 unit / vial

Prices