Palivizumab

Last updated
Palivizumab
Monoclonal antibody
Type Whole antibody
Source Humanized (from mouse)
Target RSV protein F
Clinical data
Trade names Synagis
AHFS/Drugs.com Monograph
MedlinePlus a698034
License data
Routes of
administration 		Intramuscular
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only) [1]
  • UK: POM (Prescription only) [2]
  • US: ℞-only [3]
  • EU:Rx-only [4]
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Elimination half-life 18-20 days
Identifiers
CAS Number
DrugBank
ChemSpider
  • none
UNII
KEGG
ChEMBL
Chemical and physical data
Formula C6470H10056N1700O2008S50
Molar mass 145388.51 g·mol−1
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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. [2] [4] It is recommended for infants at high-risk for RSV due to conditions such as prematurity or other medical problems including heart or lung diseases. [2] [4]

Contents

The most common side effects include fever and rash. [2] [4]

Palivizumab is a 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%. [5] Palivizumab is dosed once a month via 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. [2] [6] [7]

Palivizumab targets the fusion protein of RSV, [8] inhibiting its entry into the cell and thereby preventing infection. Palivizumab was approved for medical use in 1998. [9]

Medical use

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: [2] [4] [10]

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 and other risk factors on RSV hospitalization rates, the mortality of children hospitalized with RSV infection, the effect of prophylaxis on wheezing, and palivizumab-resistant RSV isolates. [11]

RSV Prophylaxis

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, glucocorticoids, diuretics) within six months of the anticipated RSV season are recommended to use palivizumab as prophylaxis. [11] Taking palivizumab prophylactically decreases the number of RSV infections, decreases wheezing, and may decrease the rate of hospitalization attributed to RSV. [12] [13] There are few negative side effects reported. [13] 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. [13]

Since the risk of RSV decreases after the first year following birth, the use of palivizumab for children more than 12 months of age is generally not recommended with the exception of premature infants who need supplemental oxygen, bronchodilator therapy, or steroid therapy at the time of their second RSV season. [11]

RSV Prophylaxis Target Groups

Decisions regarding palivizumab prophylaxis for children in these groups should be made on a case-by-case basis. [11]

RSV Treatment

Because palivizumab is a passive antibody, it is ineffective in the treatment of RSV infection, and its administration is not recommended for this indication. [11] 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. [14] Larger RCTs will be required before palivizumab can be recommended as a treatment option. [15] 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. [11] Current studies are in progress to determine new treatments for RSV rather than solely prophylaxis. [16]

Contraindications

Contraindications for the use of palivizumab include hypersensitivity reactions upon exposure to palivizumab. Serious cases of anaphylaxis have been reported after exposure to palivizumab. Signs of hypersensitivity include hives, shortness of breath, hypotension, and unresponsiveness. No other contraindications for palivizumab have been reported. [17] Further studies are needed to determine if any drug-drug interactions exist as none have been conducted as of yet.

Side effects

Palivizumab use may cause side effects, which include, but are not limited to: [18]

Some more serious side effects include:

Pharmacology

Pharmacodynamics

Palivizumab has demonstrated a significantly higher affinity and potency in neutralizing both A and B subtypes of RSV when compared with RSV-IGIV. [19] Treatment with 2.5 mg/kg of palivizumab led to a serum concentration of 25-30 μg/mL in cotton rats and reduced RSV titers by 99% in their lungs. [20]

Mechanism of action

Palivizumab is a monoclonal antibody that targets the fusion (F) glycoprotein on the surface of RSV, and deactivates it. [21] The F protein is a membrane protein responsible for fusing the virus with its target cell and is highly conserved among subgroups of RSV. Deactivating the F protein prevents the virus from fusing with its target's cell membrane and prevents the virus from entering the host cell. [21] [22]

Pharmacokinetics

Absorption

A 2008 meta-analysis found that palivizumab absorption was quicker in the pediatric population compared to adults (ka = 1.01/day vs. ka = 0.373/day). The intramuscular bioavailability of this drug is approximately 70% in healthy young adults. [23] Current recommendation for RSV immunoprophylaxis is administration of 5 x 15 mg/kg doses of palivizumab to maintain body concentrations above 40 μg/mL. [24]

Distribution

The volume of distribution is approximately 4.1 liters. [23]

Clearance

Palivizumab has a drug clearance (CL) of approximately 198 ml/day. The half-life of this drug is approximately 20 days with three doses sustaining body concentrations that will last the entire RSV season (5 to 6 months). A 2008 meta-analysis estimated clearance in the pediatric population by considering maturation of CL and body weight which showed a significant reduction compared to adults. [23]

Society and Culture

Cost

Palivizumab is a relatively expensive medication, with a 100-mg vial ranging from $904 to $1866. [25] Multiple studies done by both the manufacturer and independent researchers to determine the cost-effectiveness of palivizumab have found conflicting results. The heterogeneity between these studies makes them difficult to compare. Given that there is no consensus about the cost-effectiveness of palivizumab, usage largely depends on the location of care and individual risk factors. [26] [21] [27]

A 2013 meta-analysis reported that palivizumab prophylaxis was a dominant strategy with an incremental cost-effectiveness ratio of $2,526,203 per quality-adjusted life-year (QALY). It also showed an incremental cost-effectiveness ratio for preterm infants between $5188 and $791,265 per QALY, from the payer perspective. [28] However, as previously stated, the cost-effectiveness of palivizumab is undecided, and this meta-analysis is only one example of society can benefit from palivizumab prophylaxis.

History

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. [29] 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 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. [30] Subsequent attempts to develop an attenuated live virus vaccine with optimal immune response and minimal reactogenicity have been unsuccessful. [31] Further research on animal subjects suggested that intravenously administered immunoglobulin with high RSV neutralizing activity can protect against RSV infection. [32] In 1995, the 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 premature birth. [33] 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. [34]

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). [34] It was developed over a 10-year period by MedImmune Inc. by combining human and mouse DNA. [35] 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. [20]

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Antiviral drugs are a class of medication used for treating viral infections. Most antivirals target specific viruses, while a broad-spectrum antiviral is effective against a wide range of viruses. Antiviral drugs are a class of antimicrobials, a larger group which also includes antibiotic, antifungal and antiparasitic drugs, or antiviral drugs based on monoclonal antibodies. Most antivirals are considered relatively harmless to the host, and therefore can be used to treat infections. They should be distinguished from virucides, which are not medication but deactivate or destroy virus particles, either inside or outside the body. Natural virucides are produced by some plants such as eucalyptus and Australian tea trees.

<span class="mw-page-title-main">Bronchiolitis</span> Blockage of the small airways in the lungs due to a viral infection

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<span class="mw-page-title-main">Respiratory syncytial virus</span> Species of a virus

Respiratory syncytial virus (RSV), also called human respiratory syncytial virus (hRSV) and human orthopneumovirus, is a contagious virus that causes infections of the respiratory tract. It is a negative-sense, single-stranded RNA virus. Its name is derived from the large cells known as syncytia that form when infected cells fuse.

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References

  1. ↑ https://www.tga.gov.au/resources/artg/231139
  2. 1 2 3 4 5 6 "Synagis 100 mg/ml solution for injection - Summary of Product Characteristics (SmPC)". (emc). 12 August 2020. Retrieved 20 August 2020.
  3. ↑ "Synagis- palivizumab injection, solution". DailyMed. 12 May 2017. Retrieved 20 August 2020.
  4. 1 2 3 4 5 6 7 8 "Synagis EPAR". European Medicines Agency (EMA). 17 September 2018. Retrieved 20 August 2020. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  5. ↑ "Prospective Study for the Use of Palivizumab (Synagis®) in High-risk Children in Germany". ClinicalTrials.gov. 2021.
  6. ↑ Borchers AT, Chang C, Gershwin ME, Gershwin LJ (December 2013). "Respiratory syncytial virus--a comprehensive review". Clinical Reviews in Allergy & Immunology. 45 (3): 331–379. doi:10.1007/s12016-013-8368-9. PMC   7090643 . PMID   23575961.
  7. ↑ CDC (2020-12-18). "Trends and Surveillance for RSV in the US". Centers for Disease Control and Prevention. Retrieved 2021-08-10.
  8. ↑ Levinson W (2004). Medical Microbiology and Immunology (8th ed.). Lange. p.  430. ISBN   9780071431996.
  9. ↑ Long SS, Pickering LK, Prober CG (2012). Principles and Practice of Pediatric Infectious Disease. Elsevier Health Sciences. p. 1502. ISBN   978-1437727029.
  10. ↑ Santos da Silva GN, Monti Atik D, Antunes Fernandes JL, de Freitas do Nascimento D, Fazolo T, Duarte de Souza AP, Baggio Gnoatto SC (July 2018). "Synthesis of three triterpene series and their activity against respiratory syncytial virus". Archiv der Pharmazie. 351 (8): e1800108. doi:10.1002/ardp.201800108. hdl: 10923/21468 . PMID   29999539. S2CID   51621538.
  11. 1 2 3 4 5 6 7 Brady MT, Byington CL, Davies HD, Edwards KM, Jackson MA, Maldonado YA, et al. (American Academy of Pediatrics Committee on Infectious Diseases; American Academy of Pediatrics Bronchiolitis Guidelines Committee.) (August 2014). "Updated guidance for palivizumab prophylaxis among infants and young children at increased risk of hospitalization for respiratory syncytial virus infection". Pediatrics. 134 (2): 415–420. doi: 10.1542/peds.2014-1665 . PMID   25070315.
  12. ↑ Andabaka T, Nickerson JW, Rojas-Reyes MX, Rueda JD, Bacic Vrca V, Barsic B (April 2013). "Monoclonal antibody for reducing the risk of respiratory syncytial virus infection in children". The Cochrane Database of Systematic Reviews (4): CD006602. doi:10.1002/14651858.cd006602.pub4. PMID   23633336.
  13. 1 2 3 Garegnani L, Styrmisdóttir L, Roson Rodriguez P, Escobar Liquitay CM, Esteban I, Franco JV (November 2021). Cochrane Acute Respiratory Infections Group (ed.). "Palivizumab for preventing severe respiratory syncytial virus (RSV) infection in children". The Cochrane Database of Systematic Reviews. 2021 (11): CD013757. doi:10.1002/14651858.CD013757.pub2. PMC   8594174 . PMID   34783356.
  14. ↑ Sanders SL, Agwan S, Hassan M, Bont LJ, Venekamp RP (October 2023). "Immunoglobulin treatment for hospitalised infants and young children with respiratory syncytial virus infection". The Cochrane Database of Systematic Reviews. 2023 (10): CD009417. doi:10.1002/14651858.CD009417.pub3. PMC  10591280. PMID   37870128.
  15. ↑ Hu J, Robinson JL (November 2010). "Treatment of respiratory syncytial virus with palivizumab: a systematic review". World Journal of Pediatrics. 6 (4): 296–300. doi:10.1007/s12519-010-0230-z. PMID   21080142. S2CID   22504710.
  16. ↑ Ferla S, Manganaro R, Benato S, Paulissen J, Neyts J, Jochmans D, et al. (April 2020). "Rational modifications, synthesis and biological evaluation of new potential antivirals for RSV designed to target the M2-1 protein" (PDF). Bioorganic & Medicinal Chemistry. 28 (8): 115401. doi:10.1016/j.bmc.2020.115401. PMID   32143992. S2CID   212622222.
  17. ↑ "Drugs@FDA: FDA-Approved Drugs". www.accessdata.fda.gov. Retrieved 28 July 2021.
  18. ↑ "Palivizumab Injection". MedlinePlus Drug Information. U.S. National Library of Medicine. Retrieved 2016-01-30.
  19. ↑ Wu H, Pfarr DS, Losonsky GA, Kiener PA (2008). "Immunoprophylaxis of RSV Infection: Advancing from RSV-IGIV to Palivizumab and Motavizumab". Human Antibody Therapeutics for Viral Disease. Current Topics in Microbiology and Immunology. Vol. 317. pp. 103–123. doi:10.1007/978-3-540-72146-8_4. ISBN   978-3-540-72144-4. PMID   17990791.
  20. 1 2 Resch B (September 2017). "Product review on the monoclonal antibody palivizumab for prevention of respiratory syncytial virus infection". Human Vaccines & Immunotherapeutics. 13 (9): 2138–2149. doi:10.1080/21645515.2017.1337614. PMC   5612471 . PMID   28605249.
  21. 1 2 3 Resch B (September 2017). "Product review on the monoclonal antibody palivizumab for prevention of respiratory syncytial virus infection". Human Vaccines & Immunotherapeutics. 13 (9): 2138–2149. doi:10.1080/21645515.2017.1337614. PMC   5612471 . PMID   28605249.
  22. ↑ McLellan JS, Ray WC, Peeples ME (2013). "Structure and Function of Respiratory Syncytial Virus Surface Glycoproteins". Challenges and Opportunities for Respiratory Syncytial Virus Vaccines. Current Topics in Microbiology and Immunology. Vol. 372. pp. 83–104. doi:10.1007/978-3-642-38919-1_4. ISBN   978-3-642-38918-4. PMC   4211642 . PMID   24362685.
  23. 1 2 3 Robbie GJ, Zhao L, Mondick J, Losonsky G, Roskos LK (September 2012). "Population pharmacokinetics of palivizumab, a humanized anti-respiratory syncytial virus monoclonal antibody, in adults and children". Antimicrobial Agents and Chemotherapy. 56 (9): 4927–4936. doi:10.1128/AAC.06446-11. PMC   3421858 . PMID   22802243.
  24. ↑ Reuter SE, Evans AM, Ward MB (January 2019). "Reducing Palivizumab Dose Requirements Through Rational Dose Regimen Design". CPT. 8 (1): 26–33. doi:10.1002/psp4.12364. PMC   6363066 . PMID   30426719.
  25. ↑ Mac S, Sumner A, Duchesne-Belanger S, Stirling R, Tunis M, Sander B (May 2019). "Cost-effectiveness of Palivizumab for Respiratory Syncytial Virus: A Systematic Review". Pediatrics. 143 (5): e20184064. doi: 10.1542/peds.2018-4064 . PMID   31040196.
  26. ↑ Andabaka T, Nickerson JW, Rojas-Reyes MX, Rueda JD, Bacic Vrca V, Barsic B (April 2013). "Monoclonal antibody for reducing the risk of respiratory syncytial virus infection in children". The Cochrane Database of Systematic Reviews (4): CD006602. doi:10.1002/14651858.cd006602.pub4. PMID   23633336.
  27. ↑ Barr R, Green CA, Sande CJ, Drysdale SB (2019-07-29). "Respiratory syncytial virus: diagnosis, prevention and management". Therapeutic Advances in Infectious Disease. 6: 2049936119865798. doi:10.1177/2049936119865798. PMC   6664627 . PMID   31384456.
  28. ↑ Mac S, Sumner A, Duchesne-Belanger S, Stirling R, Tunis M, Sander B (May 2019). "Cost-effectiveness of Palivizumab for Respiratory Syncytial Virus: A Systematic Review". Pediatrics. 143 (5): e20184064. doi: 10.1542/peds.2018-4064 . PMID   31040196.
  29. ↑ Shafique M, Zahoor MA, Arshad MI, Aslam B, Siddique AB, Rasool AH, Qamar MU, Usman M (2019-10-30). "Hurdles in Vaccine Development against Respiratory Syncytial Virus". In Resch B (ed.). The Burden of Respiratory Syncytial Virus Infection in the Young. IntechOpen. doi: 10.5772/intechopen.87126 . ISBN   978-1-78984-642-3 . Retrieved 2021-08-03.
  30. ↑ Kim HW, Canchola JG, Brandt CD, Pyles G, Chanock RM, Jensen K, Parrott RH (April 1969). "Respiratory syncytial virus disease in infants despite prior administration of antigenic inactivated vaccine". American Journal of Epidemiology. 89 (4): 422–434. doi:10.1093/oxfordjournals.aje.a120955. PMID   4305198.
  31. ↑ Karron RA, Buchholz UJ, Collins PL (2013). "Live-Attenuated Respiratory Syncytial Virus Vaccines". In Anderson L, Graham BS (eds.). Challenges and Opportunities for Respiratory Syncytial Virus Vaccines. Current Topics in Microbiology and Immunology. Vol. 372. Berlin, Heidelberg: Springer Berlin Heidelberg. pp. 259–284. doi:10.1007/978-3-642-38919-1_13. ISBN   978-3-642-38918-4. PMC   4794267 . PMID   24362694.
  32. ↑ Boukhvalova MS, Yim KC, Blanco J (2018-01-01). "Cotton rat model for testing vaccines and antivirals against respiratory syncytial virus". Antiviral Chemistry & Chemotherapy. 26: 2040206618770518. doi:10.1177/2040206618770518. PMC   5987903 . PMID   29768937.
  33. ↑ Pollack P, Groothuis JR (September 2002). "Development and use of palivizumab (Synagis): a passive immunoprophylactic agent for RSV". Journal of Infection and Chemotherapy. 8 (3): 201–206. doi:10.1007/s10156-002-0178-6. PMID   12373481. S2CID   39331984.
  34. 1 2 Dessain SK (2021). Human antibody therapeutics for viral disease. Berlin: Springer Verlag. ISBN   978-3-540-72146-8. OCLC   209988317.
  35. ↑ Johnson S, Oliver C, Prince GA, Hemming VG, Pfarr DS, Wang SC, et al. (November 1997). "Development of a humanized monoclonal antibody (MEDI-493) with potent in vitro and in vivo activity against respiratory syncytial virus". The Journal of Infectious Diseases. 176 (5): 1215–1224. doi: 10.1086/514115 . PMID   9359721.
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