Palivizumab: Difference between revisions

| pregnancy_AU = N

| ATC_suffix = BB16BD01

| legal_UK_comment = <ref name="Synagis SmPC">{{cite web | title=Synagis 100 mg/ml solution for injection - Summary of Product Characteristics (SmPC) | website=(emc) | date=12 August 2020 | url=https://www.medicines.org.uk/emc/product/6963/smpc | access-date=20 August 2020}}</ref>

'''Palivizumab''', sold under the brand name '''Synagis''', is a [[monoclonal antibody]] produced by [[recombinant DNA]] technology used to prevent severe disease caused by [[respiratory syncytial virus]] (RSV) infections.<ref name=":2">{{Cite web|title=Synagis 100 mg/1 ml solution for injection - Summary of Product Characteristics (SmPC)" - (emc)|url=https://www.medicines.org.uk/emc/product/12734/smpc#gref|access-date=2021-08-03|website=www.medicines.org.uk}}</ref><ref name="Synagis EPAR" /> It is recommended for infants at high-risk for RSV due to conditions such as [[Preterm birth|prematurity]] or other medical problems including heart or lung diseases.<ref name=":2Synagis SmPC" /><ref name="Synagis EPAR" />

The most common side effects include [[fever]] and [[rash]].<ref name=":2Synagis SmPC" /><ref name="Synagis EPAR">{{cite web | title=Synagis EPAR | website=[[European Medicines Agency]] (EMA) | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/synagis | access-date=20 August 2020}} Text was copied from this source which is ©copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref>

Palivizumab is a [[Humanized antibody|humanized]] monoclonal antibody (IgG) directed against an [[epitope]] in the A antigenic site of the F protein of RSV. In two [[phase III clinical trials]] in the pediatric population, palivizumab reduced the risk of hospitalization due to RSV infection by 55% and 45%.<ref>{{Cite webjournal|date=2021|title=Prospective Study for the Use of Palivizumab (Synagis®) in High-risk Children in Germany|url=https://clinicaltrials.gov/ct2/show/NCT01155193|url-status=live |website=ClinicalTrials.gov}}</ref> Palivizumab is dosed once a month via [[intramuscular injection|intramuscular (IM) injection]], to be administered throughout the duration of the RSV season, which in based on past trends has started in Mid-September to Mid-November.<ref name=":2Synagis SmPC" /><ref>{{cite journal | vauthors = Borchers AT, Chang C, Gershwin ME, Gershwin LJ | title = Respiratory syncytial virus--a comprehensive review | journal = Clinical Reviews in Allergy & Immunology | volume = 45 | issue = 3 | pages = 331–79331–379 | date = December 2013 | pmid = 23575961 | pmc = 7090643 | doi = 10.1007/s12016-013-8368-9 }}</ref><ref>{{Cite web|last=CDC|date=2020-12-18|title=Trends and Surveillance for RSV in the US.|url=https://www.cdc.gov/rsv/research/us-surveillance.html|access-date=2021-08-10|website=Centers for Disease Control and Prevention|language=en-us}}</ref>

Palivizumab targets the fusion protein of RSV,<ref>{{cite book | vauthors = Levinson W | title = Medical Microbiology and Immunology | url = https://archive.org/details/medicalmicrobiol00warr_0 | url-access = registration | edition = 8th | publisher = Lange | date = 2004 | page = [https://archive.org/details/medicalmicrobiol00warr_0/page/430 430] | isbn = 9780071431996 }}</ref> inhibiting its entry into the cell and thereby preventing infection. Palivizumab was approved for medical use in 1998.<ref>{{cite book | vauthors = Long SS, Pickering LK, Prober CG |title=Principles and Practice of Pediatric Infectious Disease |date=2012 |publisher=Elsevier Health Sciences |isbn=978-1437727029 |page=1502 |url=https://books.google.com/books?id=nQ7-o8JAH7kC&pg=PA1502|language=en}}</ref>

Palivizumab is indicated for the prevention of serious lower respiratory tract disease requiring hospitalization caused by the respiratory syncytial virus (RSV) in children at high risk for RSV disease:<ref name=":2Synagis SmPC" /><ref name="Synagis EPAR" /><ref>{{Citecite journal |last vauthors = Santos da Silva|first=Gloria N.|last2=GN, Monti Atik|first2=Diana|last3= D, Antunes Fernandes|first3=Jheini L.|last4=JL, de Freitas do Nascimento|first4=Deise|last5= D, Fazolo|first5=Tiago|last6= T, Duarte de Souza|first6=Ana Paula|last7=AP, Baggio Gnoatto SC |first7=Simone C.|date=2021|title = Synthesis of three triterpene series and their activity against respiratory syncytial virus |url=https://onlinelibrary.wiley.com/doi/10.1002/ardp.201800108| journal = Archiv der Pharmazie |language=en| volume = 351 | issue = 8 | pages =1800108 e1800108 | date = July 2018 | pmid = 29999539 | doi = 10.1002/ardp.201800108 | hdl-access = free | s2cid = 51621538 | hdl = 10923/21468 }}</ref>

The [[American Academy of Pediatrics]] has published guidelines for the use of palivizumab. The most recent updates to these recommendations are based on new information regarding RSV seasonality, palivizumab pharmacokinetics, the incidence of [[bronchiolitis]] hospitalizations, the effect of [[Gestational age (obstetrics)|gestational age]] and other risk factors on RSV hospitalization rates, the mortality of children hospitalized with RSV infection, the effect of [[Preventive healthcare|prophylaxis]] on wheezing, and palivizumab-resistant RSV isolates.<ref name="2014 Pediatrics">{{cite journal | vauthors = Brady MT, Byington CL, Davies HD, Edwards KM, Jackson MA, Maldonado YA, Murray DL, Orenstein WA, Rathore MH, Sawyer MH, Schutze GE, Willoughby RE, Zaoutis TE | display-authors = 6 | title = Updated guidance for palivizumab prophylaxis among infants and young children at increased risk of hospitalization for respiratory syncytial virus infection | journal = Pediatrics | volume = 134 | issue = 2 | pages = 415–20415–420 | date = August 2014 | pmid = 25070315 | doi = 10.1542/peds.2014-1665 | collaboration = American Academy of Pediatrics Committee on Infectious Diseases; American Academy of Pediatrics Bronchiolitis Guidelines Committee. | doi-access = free }}</ref>

All infants younger than one year who were born at <29 weeks (i.e. ≤28 weeks, 6 days) of gestation are recommended to use palivizumab. Infants younger than one year with [[bronchopulmonary dysplasia]] (i.e. who were born at <32 weeks gestation and required supplemental oxygen for the first 28 days after birth) and infants younger than two years with [[bronchopulmonary dysplasia]] who require medical therapy (e.g. supplemental oxygen, [[Glucocorticoid|glucocorticoids]], diuretics) within six months of the anticipated RSV season are recommended to use palivizumab as prophylaxis.<ref name="2014 Pediatrics" /> ATaking [[Cochranepalivizumab (organisation)|Cochraneprophylactically review]]decreases showsthe evidencenumber that palivizumabof RSV prophylaxisinfections, isdecreases effectivewheezing, atand reducingmay decrease the frequencyrate of hospitalization inattributed children withto RSV infection.<ref>{{cite journal | vauthors = Andabaka T, Nickerson JW, Rojas-Reyes MX, Rueda JD, Bacic Vrca V, Barsic B | title = Monoclonal antibody for reducing the risk of respiratory syncytial virus infection in children | journal = The Cochrane Database of Systematic Reviews | issue = 4 | pages = CD006602 | date = April 2013 | pmid = 23633336 | doi = 10.1002/14651858.cd006602.pub4 }}</ref><ref name="Garegnani_2021">{{cite journal | vauthors = Garegnani L, Styrmisdóttir L, Roson Rodriguez P, Escobar Liquitay CM, Esteban I, Franco JV | title = Palivizumab for preventing severe respiratory syncytial virus (RSV) infection in children | journal = The Cochrane Database of Systematic Reviews | volume = 2021 | issue = 11 | pages = CD013757 | date = November 2021 | pmid = 34783356 | pmc = 8594174 | doi = 10.1002/14651858.CD013757.pub2 | collaboration = Cochrane Acute Respiratory Infections Group }}</ref> There are few negative side effects reported.<ref name="Garegnani_2021" /> It is not clear if palivizumab is effective and safe for the other medical conditions that put them at a higher risk for serious cases of RSV such as deficiencies in their immune system.<ref name="Garegnani_2021" />

Because palivizumab is a passive antibody, it is ineffective in the treatment of RSV infection, and its administration is not recommended for this indication.<ref name="2014 Pediatrics" /> A 2019 (updated in 2023) Cochrane review found no differences in palivizumab and placebo on outcomes of mortality, length of hospital stay, and adverse events in infants and children aged up to 3 years old with RSV.<ref>{{cite journal | vauthors = Sanders SL, Agwan S, Hassan M, vanBont Driel MLLJ, Del MarVenekamp CBRP | title = Immunoglobulin treatment for hospitalised infants and young children with respiratory syncytial virus infection | journal = The Cochrane Database of Systematic Reviews | volume = 82023 | issue = 10 | pages = CD009417 | date = AugustOctober 20192023 | pmid = 3144662237870128 | pmc = 670860410591280 | doi = 10.1002/14651858.cd009417CD009417.pub2pub3 }}</ref> Larger RCTs will be required before palivizumab can be recommended as a treatment option.<ref>{{cite journal | vauthors = Hu J, Robinson JL | title = Treatment of respiratory syncytial virus with palivizumab: a systematic review | journal = World Journal of Pediatrics | volume = 6 | issue = 4 | pages = 296–300 | date = November 2010 | pmid = 21080142 | doi = 10.1007/s12519-010-0230-z | s2cid = 22504710 }}</ref> If an infant has an RSV infection despite the use of palivizumab during the RSV season, monthly doses of palivizumab may be discontinued for the rest of the RSV season due to the low risk of re-hospitalization.<ref name="2014 Pediatrics" /> Current studies are in progress to determine new treatments for RSV rather than solely prophylaxis. <ref>{{Citecite journal |last vauthors = Ferla|first=Salvatore|last2= S, Manganaro|first2=Roberto|last3= R, Benato|first3=Sara|last4= S, Paulissen|first4=Jasmine|last5= J, Neyts|first5=Johan|last6= J, Jochmans|first6=Dirk|last7= D, Brancale|first7=Andrea|last8= A, Bassetto M |first8=Marcella|date=2021| title = Rational modifications, synthesis and biological evaluation of new potential antivirals for RSV designed to target the M2-1 protein |url=https://linkinghub.elsevier.com/retrieve/pii/S0968089620302066| journal = Bioorganic & Medicinal Chemistry |language=en| volume = 28 | issue = 8 | pages = 115401 | date = April 2020 | pmid = 32143992 | doi = 10.1016/j.bmc.2020.115401 | s2cid = 212622222 | url = https://lirias.kuleuven.be/bitstream/123456789/652873/3/BMC_RSV_2020_main_Accepted.pdf }}</ref>

== Mechanism of ActionContraindications ==

==== CostMechanism of action ====

The disease burden of RSV in young infants and its global prevalence have prompted attempts for vaccine development. As of 2019, there was no approved vaccine for RSV prevention.<ref>{{Citationcite book |last vauthors = Shafique M, Zahoor MA, Arshad MI, Aslam B, Siddique AB, Rasool AH, Qamar MU, Usman M |first=Muhammad|title chapter =Hurdles in Vaccine Development against Respiratory Syncytial Virus|date=2019-10-30| chapter-url=https://www.intechopen.com/books/the-burden-of-respiratory-syncytial-virus-infection-in-the-young/hurdles-in-vaccine-development-against-respiratory-syncytial-virus|work title = The Burden of Respiratory Syncytial Virus Infection in the Young|editor-last veditors = Resch|editor-first=Bernhard B |publisher=IntechOpen|language=en|doi=10.5772/intechopen.87126|isbn=978-1-78984-642-3|access-date=2021-08-03|last2=Asif Zahoor|first2=Muhammad|last3=Imran Arshad|first3=Muhammad|last4=Aslam|first4=Bilal|last5=Baker Siddique|first5=Abu|last6=Hidayat Rasool|first6=Muhammad|last7=Usman Qamar|first7=Muhammad|last8=Usman|first8=Muhammad|doi-access=free}}</ref> A formalin-inactivated RSV vaccine (FIRSV) was studied in the 1960s. The immunized children who were exposed to the virus in the community developed an enhanced form of RSV disease presented by [[Wheeze|wheezing]], fever, and [[bronchopneumonia]]. This enhanced form of the disease led to 80% hospitalization in the recipients of FIRSV compared to 5% in the control group. Additionally, 2 fatalities occurred among the vaccine recipients upon reinfection in subsequent years.<ref>{{cite journal | vauthors = Kim HW, Canchola JG, Brandt CD, Pyles G, Chanock RM, Jensen K, Parrott RH | title = Respiratory syncytial virus disease in infants despite prior administration of antigenic inactivated vaccine | journal = American Journal of Epidemiology | volume = 89 | issue = 4 | pages = 422–34422–434 | date = April 1969 | pmid = 4305198 | doi = 10.1093/oxfordjournals.aje.a120955 }}</ref> Subsequent attempts to develop an attenuated live virus vaccine with optimal [[immune response]] and minimal [[reactogenicity]] have been unsuccessful.<ref name="pmid24362694">{{cite journalbook | vauthors = Karron RA, Buchholz UJ, Collins PL | titlechapter = Live-attenuatedAttenuated respiratoryRespiratory syncytialSyncytial virusVirus vaccinesVaccines | journalseries = Current Topics in Microbiology and Immunology | volumetitle = 372Challenges and Opportunities for Respiratory Syncytial Virus Vaccines | issuevolume = 372 | pages = 259–84259–284 | date = 2013 | pmid = 24362694 | pmc = 4794267 | doi = 10.1007/978-3-642-38919-1_13 | veditorspublisher = Anderson L, Graham BS |place=Berlin, Heidelberg|publisher=Springer Berlin Heidelberg | isbn = 978-3-642-38918-4 | veditors = Anderson L, Graham BS | place = Berlin, Heidelberg }}</ref> Further research on animal subjects suggested that intravenously administered immunoglobulin with high RSV neutralizing activity can protect against RSV infection.<ref>{{cite journal | vauthors = Boukhvalova MS, Yim KC, Blanco J | title = Cotton rat model for testing vaccines and antivirals against respiratory syncytial virus | journal = Antiviral Chemistry & Chemotherapy | volume = 26 | pages = 2040206618770518 | date = 2018-01-01 | pmid = 29768937 | pmc = 5987903 | doi = 10.1177/2040206618770518 }}</ref> In 1995, the [[Food and Drug Administration|U.S. Food and Drug Administration]] (FDA) approved the use of RespiGam (RSV-IGIV) for the prevention of serious lower respiratory tract infection caused by RSV in children younger than 24 months of age with [[bronchopulmonary dysplasia]] or a history of [[Preterm birth|premature birth]].<ref>{{cite journal | vauthors = Pollack P, Groothuis JR | title = Development and use of palivizumab (Synagis): a passive immunoprophylactic agent for RSV | journal = Journal of Infection and Chemotherapy | volume = 8 | issue = 3 | pages = 201–6201–206 | date = September 2002 | pmid = 12373481 | doi = 10.1007/s10156-002-0178-6 | s2cid = 39331984 }}</ref> The success of the RSV-IGIV demonstrated efficacy in immunoprophylaxis and prompted research into further technologies. Thus, Palivizumab was developed as an antibody that was found to be fifty times more potent than its predecessor. This antibody has been widely used for RSV since 1998 when it was approved. <ref name = "Dessain_2021">{{Cite book |url= https://www.worldcat.org/oclc/209988317 |title=Human antibody therapeutics for viral disease|date=2021|publisher=Springer Verlag|others=Scott K.vauthors = Dessain SK |isbn=978-3-540-72146-8|location=Berlin|oclc=209988317}}</ref>

Palivizumab, originally known as MEDI-493, was developed as an RSV immune prophylaxis tool that was easier to administer and more effective than the current tools of that time (the 1990s).<ref>{{Cite book|last=Dessain|first=Scottname K.|url=https://www.worldcat.org/oclc/209988317|title=Human antibody"Dessain_2021" therapeutics for viral disease|date=2021|publisher=Springer Verlag|others=|isbn=978-3-540-72146-8|location=Berlin|oclc=209988317}}</ref> It was developed over a 10-year period by MedImmune Inc. by combining human and mouse DNA.<ref>{{Citecite journal |last vauthors = Johnson|first=Syd|last2= S, Oliver|first2=Cynthia|last3= C, Prince|first3=Gregory A.|last4= GA, Hemming|first4=Val G.|last5= VG, Pfarr|first5=David S.|last6= DS, Wang|first6=Sheau‐Chiann|last7= SC, Dormitzer|first7=Melissa|last8= M, O'Grady|first8=John|last9= J, Koenig|first9=Scott|last10= S, Tamura|first10=James K.|last11= JK, Woods R, Bansal G, Couchenour D, Tsao E, Hall WC, Young JF |first11=Robert|date=1997| title = Development of a Humanizedhumanized Monoclonalmonoclonal Antibodyantibody (MEDI‐493MEDI-493) with Potentpotent Inin Vitrovitro and Inin Vivovivo Activityactivity against Respiratoryrespiratory Syncytialsyncytial virus Virus|url=https://academic.oup.com/jid/article-lookup/doi/10.1086/514115| journal = The Journal of Infectious Diseases |language=en| volume = 176 | issue = 5 | pages = 1215–1224 | date = November 1997 | pmid = 9359721 | doi = 10.1086/514115 |issn=0022 doi-1899access = free }}</ref> Specifically, antibody production was stimulated in a mouse model following immunization with RSV. The antibody-producing B cells were isolated from the mouse's spleen and fused with mouse myeloma cell lines. The antibodies were then humanized by cloning and sequencing the DNA from both the heavy and light chains of the monoclonal antibody. Overall, the monoclonal antibody is 95% similar to other human antibodies with the other 5% having DNA origins from the original mouse.<ref name="Resch 2138–2149"/>

[[Category:AbbVieDrugs brandsdeveloped by AbbVie]]

[[Category:AstraZenecaDrugs brandsdeveloped by AstraZeneca]]