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Revision as of 10:42, 16 February 2012 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Saving copy of the {{drugbox}} taken from revid 477153212 of page Rho(D)_immune_globulin for the Chem/Drugbox validation project (updated: '').  Latest revision as of 02:33, 15 December 2024 edit Scrooge Mcduc (talk | contribs)302 edits The statistic on untreated risk should not be portrayed as more reliable than it is. The originally cited article cites Zipursky which says "Walker, in 1971, reviewed a series of cases from his community" (and provides a citation to https://doi.org/10.1016/S0031-3955(16)30068-2 by Walker, who cites Gaffney's https://doi:10.1016/s0031-3955(16)30068-2 ), and mentions "similar observations in Manitoba Canada" citing PMID: 77714 by Bowman. 
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{{short description|Medication used to prevent RhD isoimmunization}}
{{ambox | text = This page contains a copy of the infobox ({{tl|drugbox}}) taken from revid of page ] with values updated to verified values.}}
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{{Drugbox
{{Redirect|Anti-D|the song|Anti-D (song)}}
| verifiedrevid = 464381669
{{Infobox drug
| Verifiedfields = changed
| verifiedrevid = 477162599
| image = | image =
<!-- Clinical data -->
| drug_name = Rho(D) immune globulin
| synonyms = Rh<sub>0</sub>(D) immune globulin, anti-D (Rh<sub>0</sub>) immunoglobulin, {{lang|la|immunoglobulinum humanum anti–D}}

| tradename = AntiD, Rhoclone, RhoGAM, ]:
<!--Clinical data-->
| Drugs.com = {{Drugs.com|monograph|rho-d-immune-globulin}}
| tradename =
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> | pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_US = <!-- A / B / C / D / X --> | pregnancy_US = <!-- A / B / C / D / X -->
| pregnancy_category = C | pregnancy_category = C
| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled--> | legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled -->
| legal_CA = <!-- Schedule I, II, III, IV, V, VI, VII, VIII --> | legal_CA = <!-- Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_UK = <!-- GSL, P, POM, CD, or Class A, B, C --> | legal_UK = <!-- GSL, P, POM, CD, or Class A, B, C -->
| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V --> | legal_US = <!-- Rx-only -->
| legal_status = | legal_status =
| routes_of_administration = intramuscular injection | routes_of_administration = Intramuscular injection
<!-- Identifiers -->

| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
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| CAS_number = | CAS_number =
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| PubChem = | PubChem =
| DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = | DrugBank = DB11597
| UNII = 48W7181FLP


<!--Chemical data--> <!-- Chemical data -->
}} }}
<!-- Definition and medical uses -->
'''Rh<sub>o</sub>(D) immune globulin''' ('''RhIG''') is a medication used to prevent ] in mothers who are ] and to treat ] (ITP) in people who are ].<ref name=AHFS2017/> It is often given both during and following ].<ref name=AHFS2017/> It may also be used when RhD-negative people are given RhD-positive blood.<ref name=AHFS2017/> It is given by ] or a ].<ref name=AHFS2017/> A single dose lasts 12 weeks.<ref name="AHFS2017">{{cite web|url=https://www.drugs.com/monograph/rho-d-immune-globulin.html|title=Rho(D) Immune Globulin|website=Drugs.com|publisher=The American Society of Health-System Pharmacists|archive-url=https://web.archive.org/web/20170109021739/https://www.drugs.com/monograph/rho-d-immune-globulin.html|archive-date=9 January 2017|url-status=live|access-date=8 January 2017}}</ref> It is made from ].<ref name="BNF69">{{cite book |title=British National Formulary: BNF 69 |date=2015 |publisher=British Medical Association |isbn=9780857111562 |edition=69 |page=871}}</ref>

<!-- Side effects and mechanism -->
Common side effects include ], headache, pain at the site of injection, and ].<ref name=AHFS2017/> Other side effects include ], ], and a very small risk of viral infections.<ref name=AHFS2017/> In those with ITP, the amount of red blood cell breakdown may be significant.<ref name=AHFS2017/> Use is safe with ].<ref name=AHFS2017/> Rho(D) immune globulin is made up of ] to the ] Rh<sub>o</sub>(D) present on some ].<ref name=AHFS2017/> It is believed to work by blocking a person's immune system from recognizing this antigen.<ref name=AHFS2017/>

<!-- Society and culture -->
Rh<sub>o</sub>(D) immune globulin came into medical use in the 1960s,<ref>{{cite book|url=https://books.google.com/books?id=WMsWpXjnWWYC&pg=PA251|title=Broadribb's Introductory Pediatric Nursing| vauthors = Hatfield NT |date=2007|publisher=Lippincott Williams & Wilkins|isbn=9780781777063|page=251|oclc=968617246|via=Google Books}}</ref> following the pioneering work of ]. In 1980, Gorman shared the ] for pioneering work on the ].<ref name=ABC2022>{{Cite news | vauthors = Probyn A |date=2022-11-01 |title=A vial of human serum, an ice box and an illegal flight: how an Australian doctor saved millions of babies' lives |language=en-AU |work=ABC News |url=https://www.abc.net.au/news/2022-11-02/john-gorman-rh-disease-treatment-millions-newborns-saved/101532694 |access-date=2022-11-02}}</ref>

RhIG is on the ].<ref name="WHO21st">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }}</ref><ref name="WHO22nd">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 22nd list (2021) | year = 2021 | hdl = 10665/345533 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2021.02 | hdl-access=free }}</ref>

==Medical uses==
=== Prevention of alloimmunization ===
==== Alloimmunization: mechanism, timing ====
]; the pink smudges are foetal-haemoglobin-containing red blood cells that have entered maternal circulation.]]
Even in normal pregnancies, a small number of fetal blood cells enters the maternal bloodstream (fetomaternal hemorrhage). If a mother is RhD negative, but the fetus is RhD positive, the mother's immune system may develop an immune response (develops ]) to the unfamiliar RhD antigens from the fetus. This process is called ''RhD alloimmunization''. Alloimmunization usually has minimal effect on the first such pregnancy; but, in a second such pregnancy, pre-existing maternal RhD IgG antibodies can cross the placenta in enough amounts to damage fetal red blood cells. This condition is called ] and can be fatal to the fetus.<ref name=":0"/>

The RhD status of the fetus is determined by genetic inheritance. In a pregnancy where the mother is RhD negative and the father is RhD positive, the probability of the fetus having RhD positive blood is dependent on whether the father is ] for RhD (i.e., both RhD alleles are present) or ] (i.e., only one RhD allele is present). If the father is homozygous, the fetus will necessarily be RhD positive, as the father will necessarily pass on a RhD positive allele. If the father is heterozygous, there is a 50% chance that the fetus will be RhD positive, as he will randomly pass on either the RhD positive allele or not.<ref name="Bowman_1988"/>{{rp|130}}. Not all Rh-negative patients are capable of being immunized to the RhD antigen, and mothers may only become immunized after many repeated pregnancies. The risk of ] (including due to RhD) significantly increases if the mother has had a past transfusion of Rh-positive blood. <ref name="Gaffney">{{cite journal| author=GAFFNEY PC| title=Hemolytic disease of the newborn. | journal=Pediatr Clin North Am | year= 1954 | volume= | issue= | pages= 283-302 | pmid=13155028 | doi=10.1016/s0031-3955(16)30068-2 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=13155028 }} </ref>

Exposure to fetal blood cells that can cause RhD alloimmunization can happen during normal pregnancy and delivery, miscarriage, amniocentesis, cordocentesis, chorionic villus sampling, external cephalic version, or trauma.<ref name=BNF69/><ref name=":0" /> 92% of women who develop an anti-D during pregnancy do so at or after 28 weeks gestation.<ref name="Roback 2008">{{cite book | vauthors = Roback J, Combs MR, Grossman B, Hillyer C |title=Technical Manual |date=2008 |publisher=American Association of Blood Banks (AABB) |location=Bethesda, MD |isbn=978-1-56395-260-9 |edition=16th}}</ref><ref name="Bowman_1988">{{cite journal | vauthors = Bowman JM | title = The prevention of Rh immunization | journal = Transfusion Medicine Reviews | volume = 2 | issue = 3 | pages = 129–150 | date = September 1988 | pmid = 2856526 | doi = 10.1016/S0887-7963(88)70039-5 }}</ref><ref name="D Alloimmunization. ACOG Practice Bulletin Number 4 1999">{{cite report | title = Prevention of Rh D Alloimmunization. | work = ACOG Practice Bulletin | issue = 4 | location = Washington, DC | publisher = American College of Obstetricians and Gynecologists | date = 1999 }}</ref>

In an RhD negative mother, RhIG can temporarily prevent sensitization of the maternal immune system to RhD ]s, with each 100 μg of anti-D being able to neutralize about 4 mL of fetal blood.<ref name=RCOG2002/> With the widespread use of RhIG, ] of the ] and ] has almost disappeared in the developed world. The risk that an RhD negative mother can be ] by a RhD positive fetus can be reduced from approximately 16% to less than 0.1% by the appropriate administration of RhIG.<ref name="Roback 2008"/><ref name="Bowman_1988"/><ref>{{cite journal | vauthors = Bowman JM | title = Controversies in Rh prophylaxis. Who needs Rh immune globulin and when should it be given? | journal = American Journal of Obstetrics and Gynecology | volume = 151 | issue = 3 | pages = 289–294 | date = February 1985 | pmid = 2982267 | doi = 10.1016/0002-9378(85)90288-1 }}</ref> In data collected from communities in Canada, without treatment as many as 14% of affected fetuses are stillborn, 30% of affected live births almost certainly fatal without treatment, and 30% with severe ] that untreated risks brain damage from ].<ref name=":0">{{cite journal | vauthors = | title = Practice Bulletin No. 181: Prevention of Rh D Alloimmunization | journal = Obstetrics and Gynecology | volume = 130 | issue = 2 | pages = e57–e70 | date = August 2017 | pmid = 28742673 | doi = 10.1097/AOG.0000000000002232 | s2cid = 26083215 }}</ref>
<ref name="Zipursky">{{cite journal| author=Zipursky A, Paul VK| title=The global burden of Rh disease. | journal=Arch Dis Child Fetal Neonatal Ed | year= 2011 | volume= 96 | issue= 2 | pages= F84-5 | pmid=21037283 | doi=10.1136/adc.2009.181172 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21037283 }} </ref>. Prior to effective transfusion therapy, the mortality rate of hemolytic disease was 70-80%, dropping to 30-50% with small transfusions and 13-33% for more aggressive transfusions before RhIg treatments were introduced. <ref name="Gaffney" />

==== Recommendations for use ====
The ] (ACOG) recommends that all RhD negative mothers, regardless of fetal blood type, receive RhIG at about 28 weeks gestation, and again shortly after delivery in the case of an RhD positive or RhD unknown baby.<ref>{{cite web |url = https://www.nice.org.uk/guidance/TA41/?c=91520 |title = Pregnancy - routine anti-D prophylaxis for RhD-negative women |publisher = ] |date = May 2002 |url-status = live |archive-url = https://web.archive.org/web/20080828175059/https://www.nice.org.uk/guidance/TA41/?c=91520 |archive-date = 2008-08-28 }}</ref> It should be given within 3 days of a potential exposure to Rh positive blood from the baby such as may occur during second and third trimester miscarriage, amniocentesis, cordocentesis, chorionic villus sampling, external cephalic version, trauma, or delivery (amounts detailed in the next section).<ref name=":0"/> It is given by intramuscular injection as part of modern routine ] care. Despite excellent results, the medication retains an FDA ] C.{{citation needed|date=December 2021}}

RhIG is recommended in the UK after antenatal pathological events that are likely to cause a feto–maternal hemorrhage. Applicable 'pathologic events' include accidents that may induce fetomaternal hemorrhage (motor vehicle accidents, falls, abdominal trauma), following obstetric/gynecologic procedures during pregnancy, and at the time of threatened- or spontaneous-/elective ]s, regardless of gestational age. RhIG is also recommended after normal delivery, with amounts detailed in the next section.<ref name=RCOG2002>{{cite web |url = https://www.rcog.org.uk/index.asp?PageID=1972 |title = Use of Anti-D Immunoglobulin for Rh Prophylaxis |publisher = ] |date = May 2002 |url-status = dead |archive-url = https://web.archive.org/web/20081230200349/https://www.rcog.org.uk/index.asp?PageID=1972 |archive-date = 2008-12-30 }}</ref>

There is insufficient evidence that the use of Rho(D) immune globulin after a spontaneous miscarriage is needed and a ] recommends that local practices be followed.<ref>{{cite journal | vauthors = Karanth L, Jaafar SH, Kanagasabai S, Nair NS, Barua A | title = Anti-D administration after spontaneous miscarriage for preventing Rhesus alloimmunisation | journal = The Cochrane Database of Systematic Reviews | volume = 2013 | issue = 3 | pages = CD009617 | date = March 2013 | pmid = 23543581 | doi = 10.1002/14651858.CD009617.pub2 | pmc = 11365588 }}</ref>

Rh immune globulin is composed of IgG antibodies and therefore is able to cross the placenta. In rare cases this can cause a baby to have a weakly positive ] (DAT) due to sensitization of fetal cells from mothers who have received multiple doses of RhIG. However, no treatment is necessary as the clinical course is benign.<ref name="Rudmann 2005">{{cite book | vauthors = Rudmann SV | year=2005 | title=Textbook of Blood Banking and Transfusion Medicine 2nd Edition | publisher=Elsevier Saunders | url=https://books.google.com/books?id=dXdISwJQJFIC&q=%22Textbook+of+Blood+Banking+and+Transfusion+Medicine%22 | pages=439–441| isbn=9780721603841 }}</ref>

==== Following delivery ====
Widespread use of RhIG started with postpartum administration, as delivery is the main source of significant fetomaternal hemorrhage.
A D-negative mother who is not alloimmunized to D should also receive an appropriate dose of RhIG after delivery of a D-positive infant. (In older recommendations, the Rh status of the infant is only known at delivery from testing of ].)<ref name="Bowman_1988"/> If the infant is D-positive, the mother should have a postpartum blood sample screened for fetomaternal hemorrhage in order to determine the appropriate dosage of RhIG to be administered. (The presence of residual anti-D from antepartum RhIG administration does not indicate ongoing protection from alloimmunization &ndash; repeat administration of RhIG is necessary.)<ref name=RCOG2002/>

The ] is a sensitive method to detect fetomaternal hemorrhage of 10 cc or more. This qualitative (not quantitative) test will be positive if fetal D-positive cells are present in the maternal sample, indicating a significantly large fetomaternal hemorrhage has occurred. A rosette test may be falsely positive if the mother is positive for the ] phenotype and falsely negative if the neonate is weak D. If the mother is positive for the weak D phenotype, the rosette test should not be used; instead, a quantitative test such as the ] or flow cytometry should be utilized. If the rosette test is negative, then a dose of 300 micrograms of RhIG is given (sufficient to prevent alloimmunization after delivery in 99% of cases).<ref name="Roback 2008"/><ref>{{cite book | vauthors = Klein H, Anstee DJ | chapter = Haemolytic Disease of the Fetus and Newborn. | title = Mollison's Blood Transfusion in Clinical Medicine. | edition = 11th | location = Oxford | publisher = Blackwell | date = 2005 | pages = 496–545 }}</ref> The RhIG dose suppresses the immune response to up to 30 cc of whole fetal blood (15 cc of red blood cells). If a fetomaternal hemorrhage in excess of 30 cc has occurred, additional testing is mandatory in order to determine the appropriate dosage of RhIG to prevent alloimmunization. A positive rosette test should be followed by a quantitative test such as the Kleihauer–Betke test or an alternative approach such as ]. See the article on Kleihauer–Betke test for details on how the volume of fetomaternal hemorrhage is calculated. The dosage of RhIG is calculated from the volume of fetal hemorrhage (in mL). Ex: 50 mL fetal hemorrhage / 30 mL = 1.667 (round up to 2) then add 1 = 3 vials of RhIG.{{citation needed|date=June 2020}}

Postpartum RhIG should be administered within 72 hours of delivery. If prophylaxis is delayed, the likelihood that alloimmunization will be prevented is decreased. However, ACOG still recommends that RhIG be administered because partial protection still occurs.<ref name="Roback 2008"/><ref name="D Alloimmunization. ACOG Practice Bulletin Number 4 1999"/> If the D-type of a newborn or stillborn is unknown or cannot be determined, RhIG should be administered.

===Immune thrombocytopenia===
Primary ] (ITP) is an acquired immune-mediated disorder characterized by isolated ], defined as a peripheral blood platelet count less than 100 x 10<sup>9</sup>/L, and the absence of any obvious initiating and/or underlying cause of the thrombocytopenia. Symptoms of ITP include abnormal bleeding and bruising due to the reduction in ].<ref name="International consensus report on t">{{cite journal | vauthors = Provan D, Stasi R, Newland AC, Blanchette VS, Bolton-Maggs P, Bussel JB, Chong BH, Cines DB, Gernsheimer TB, Godeau B, Grainger J, Greer I, Hunt BJ, Imbach PA, Lyons G, McMillan R, Rodeghiero F, Sanz MA, Tarantino M, Watson S, Young J, Kuter DJ | title = International consensus report on the investigation and management of primary immune thrombocytopenia | journal = Blood | volume = 115 | issue = 2 | pages = 168–186 | date = January 2010 | pmid = 19846889 | doi = 10.1182/blood-2009-06-225565 | doi-access = free }}</ref> Rh<sub>o</sub>(D) Immune Globulin Intravenous is indicated for use in non-splenectomized, Rh<sub>o</sub>(D)-positive children with chronic or acute ITP, adults with chronic ITP, and children and adults with ITP secondary to HIV infection. Anti-D must be administered via the intravenous route when used in clinical situations requiring an increase in platelet count. The mechanism of action of anti-D is not fully understood; however, after administration the anti-D coated red blood cell complexes saturate ] sites on ], resulting in preferential destruction of ] (RBCs), therefore sparing antibody-coated ].<ref name=":2">{{cite web | title = Winrho SDF prescribing information | url = http://www.winrho.com/pdfs/WinRho_SDF_Prescribing_Information.pdf | work = www.winrho.com }}</ref> Anti-D is recommended as a first-line therapy for ITP, along with corticosteroids and intravenous immune globulin (IVIG).<ref name="International consensus report on t"/><ref>{{cite journal | vauthors = Neunert C, Lim W, Crowther M, Cohen A, Solberg L, Crowther MA | title = The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia | journal = Blood | volume = 117 | issue = 16 | pages = 4190–4207 | date = April 2011 | pmid = 21325604 | doi = 10.1182/blood-2010-08-302984 | s2cid = 12375241 | doi-access = free }}</ref> ] in the US. There is a black box warning on WinRho SDF due to the risk of potentially fatal intravascular hemolysis when used in the treatment of ITP.<ref name=":2" /> Life-threatening ], ] failure, and ] (DIC) have occurred in people treated with WinRho SDF for ITP.{{citation needed|date=December 2021}}

== Contraindications ==
The following females are not candidates for RhIG:
* D-negative females whose fetus is known to be D-negative
* D-negative females who have been previously alloimmunized to D (they have already formed an anti-D alloantibody)
* Any D-positive females
* Women who test positive for one of the ] mutations by molecular testing should be considered RhD positive and not receive RhIG<ref name=":1">{{cite journal | vauthors = Haspel RL, Westhoff CM | title = How do I manage Rh typing in obstetric patients? | journal = Transfusion | volume = 55 | issue = 3 | pages = 470–474 | date = March 2015 | pmid = 25647404 | doi = 10.1111/trf.12995 | s2cid = 586699 }}</ref>
* Women who test positive for one of the partial D mutations (by molecular testing) should be treated as RhD negative and receive RhIG as clinically indicated<ref name=":1" />

==History==
The first Rho(D) immune globulin treatment "skymed" was introduced by ], a subsidiary holding of ], and was first administered on May 29, 1968, to Marianne Cummins in ], ].<ref>{{cite web | url = https://www.rhogam.com/pdfs/RhoGAM%20Prescribing%20Information.pdf | title = RhoGAM product label, includes clinical trial data and prescribing information | work = rhogam.com }}</ref>

In 1996, ZLB Bioplasma (part of ]) was given approval to sell Rhophylac in Europe. Effectiveness was demonstrated in a clinical trial in 2003 and in 2004 Rhophylac was approved in the United States.<ref>{{cite web | url = https://www.rhophylac.com/AboutHDN/evolution.asp | title = History of HDN Treatment | work = CSL Behring | archive-url = https://web.archive.org/web/20081121040322/https://www.rhophylac.com/AboutHDN/evolution.asp | archive-date=2008-11-21 }}</ref>

==Society and culture==
===Manufacturing and safety===
==== Human plasma ====
Conventional Rho(D) immune globulin is extracted from human ]. Excluding ], only people who are themselves Rho(D) negative can make the anti-D antibody. As a result, there is a limited pool of people from which to draw plasma that can contain the desired IgG. Special anti-D donation programs are set up to account for this rarity.<ref>{{cite web |title=Anti-D donor Steve Gansberg is just happy to help |url=https://www.lifeblood.com.au/news-and-stories/vital-reads/anti-d-donor-steve-gansberg-just-happy-help |website=Lifeblood.com.au |language=en |date=9 June 2022}}</ref> Volunteers are given an injection containing the D antigen in order to make their immune system start producing the antibody (alloimmunization) or to boost the amounts. Only those who have no ability to become pregnant may apply.<ref>{{cite web |title=Anti-D: Rh-negative Plasma Donation |url=https://www.cslplasma.com/anti-d |website=]}}</ref>

The most common way anti-D products are manufactured is by a form of the ] developed in the 1950s. Variations of the Cohn method developed in the 1950s may not completely clear aggregates of immunoglobulins, which can cause problems for patients if administered intravenously, and is a primary reason why most anti-Ds are for intramuscular use only. A non-Cohn manufacturing variation is ChromaPlus process approved by the ] (FDA) that is used to make Rhophylac.<ref>{{cite web | url = https://www.rhophylac.com/About/chromaplus.asp | title = ChromaPlus Manufacturing Process | archive-url = https://web.archive.org/web/20081121035457/https://www.rhophylac.com/About/chromaplus.asp | work = rhophylac.com | archive-date=2008-11-21 }}</ref> Rho(D) immune globulin may trigger an allergic reaction. Steps are taken in the plasma-donor screening process and the manufacturing process to eliminate bacterial and viral contamination, although a small, residual risk may remain for contamination with small viruses. There is also a theoretical possibility of transmission of the ] responsible for ], or of other, unknown infectious agents.<ref>{{cite web | url = https://www.jnj.com/innovations/new_features/RhoGAM.htm | title = RhoGAM Ultra-Filtered PLUS Rho(D) Immune Globulin (Human) Information Site | work = Johnson & Johnson Services, Inc. | archive-url = https://web.archive.org/web/20060311120204/https://www.jnj.com/innovations/new_features/RhoGAM.htm | archive-date=2006-03-11 }}</ref>

====Cell culture====
There has been continual attempts to produce a ] anti-D IgG formulation suitable for replacing the current polyclonal formulation.<ref>{{cite journal | vauthors = Béliard R | title = Monoclonal anti-D antibodies to prevent alloimmunization: lessons from clinical trials | journal = Transfusion Clinique et Biologique | volume = 13 | issue = 1–2 | pages = 58–64 | date = March 2006 | pmid = 16580863 | doi = 10.1016/j.tracli.2006.03.013 }}</ref> A monoclonal antibody can be produced without requiring human donors (and associated supply and disease risks) and would be more consistent from batch to batch.<ref name=:0/>

India has approved a monoclonal formulation called ''Rhoclone'' (Bharat Serums and Vaccines Ltd.),<ref>{{cite journal | vauthors = Chauhan AR, Nandanwar YS, Ramaiah A, Yelikar KA, Rashmi MD, Sachan R, Mayekar RV, Trivedi YN, Paradkar GV, Patole KP | title = A Multicenter, Randomized, Open-Label Trial Comparing the Efficacy and Safety of Monoclonal Anti-Rh (D) Immunoglobulin with Polyclonal Anti-Rh (D) Immunoglobulin for the Prevention of Maternal Rh-Isoimmunization | journal = Journal of Obstetrics and Gynaecology of India | volume = 69 | issue = 5 | pages = 420–425 | date = October 2019 | pmid = 31598044 | pmc = 6765035 | doi = 10.1007/s13224-019-01234-2 | doi-access = free }}</ref> made from ]. The country has also tested and recently marketed a ] version of Rhoclone expressed in ]s.<ref>{{cite journal | vauthors = Mayekar RV, Paradkar GV, Bhosale AA, Sachan R, Beeram S, Anand AR, Mundle SR, Trivedi Y, Md R, Patole KP, Sambarey PW, Daftary GV, John J, Divekar GH | title = Recombinant anti-D for prevention of maternal-foetal Rh(D) alloimmunization: a randomized multi-centre clinical trial | journal = Obstetrics & Gynecology Science | volume = 63 | issue = 3 | pages = 315–322 | date = May 2020 | pmid = 32489976 | pmc = 7231934 | doi = 10.5468/ogs.2020.63.3.315 | doi-access = free }}</ref> This recombinant formulation, Trinbelimab, marketed as AntiD, is also being evaluated in a large Real-world Prospective Study that aims to enroll 20,000 Rh-negative mothers.<ref>https://www.jsafog.com/abstractArticleContentBrowse/JSAFOG/6/15/5/34183/abstractArticle/Article</ref>

] and ] are two other formulations that have undergone some clinical trials. The former is a monoclonal IgG. The latter is a recombinant mixture of 25 IgGs.<ref name=:0/>

=== Routes of administration ===
RhIG can be administered by either intramuscular (IM) or intravenous (IV) injection, depending on the preparation.<ref>{{cite web | url=https://list.essentialmeds.org/medicines/460 | title=EEML - Electronic Essential Medicines List }}</ref> The IM-only preparation should never be administered IV due to the risk of complement system activation. Multiple IM doses should be given at different sites or at different times within the 72-hour window. Or, multiple IV doses can be administered according to the instructions in the package insert.{{citation needed|date=December 2021}}

===Names===
Rh<sub>o</sub>(D) immune globulin is also spelled Rh<sub>0</sub>(D) immune globulin (letter ] and digit ] are both widely attested; more at ]).

AntiD (Recombinant) and Rhoclone are the only Rh0(D) immune globulin marketed in the world. both manufactured by BSV Ltd. Rhophylac is manufactured by CSL Limited. RhoGAM and MICRhoGam are brand names of Kedrion Biopharma. Other brand names are BayRHo-D, Gamulin Rh, HypRho-D Mini-Dose, Mini-Gamulin Rh, Partobulin SDF (]), Rhesonativ (Octapharma), and RhesuGam (NBI). KamRho-D I.M. is a brand name of Kamada Ltd.

The United States ] rights for WinRho SDF (another brand name) were transferred from Baxter to the manufacturer, ], in 2010; they had been held by Baxter since 2005.<ref>{{cite news | author=Staff | title=Cangene assumes U.S. commercialization rights for WinRho SDF | date=5 May 2010 | work=] | location=United States | url=https://www.highbeam.com/doc/1G1-225162858.html | url-status=dead | archive-url=https://web.archive.org/web/20150329105804/https://www.highbeam.com/doc/1G1-225162858.html | archive-date=29 March 2015 | df=dmy-all | access-date=28 December 2014 }}</ref> Sales of WinRho fell every year under the agreement with Baxter, the supposition being that Baxter was favoring the sale of its own product over WinRho; according to one analyst, "WinRho was always an afterthought for a big company like Baxter."<ref>{{cite news | vauthors = Cash M | work=] | title=Cangene Corp. begins transformation project | date=16 June 2010 | url=https://www.highbeam.com/doc/1P3-2058879031.html | url-status=dead | archive-url=https://web.archive.org/web/20150329105801/https://www.highbeam.com/doc/1P3-2058879031.html | archive-date=29 March 2015 | df=dmy-all | access-date=28 December 2014 }}</ref>

== See also ==
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* ] &ndash; prolific anti-D donor

== References ==
{{reflist}}

== External links ==
* {{MeshName|Rho(D)+Immune+Globulin}}
* {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/rn/887269-77-4 | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Rho(D) Immune Globulin }}

{{Immune sera and immunoglobulins}}

{{portal bar|Medicine}}

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