Palivizumab: Difference between revisions
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=== Pharmacodynamics === |
=== Pharmacodynamics === |
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Palivizumab has demonstrated significantly higher affinity and potency in neutralizing both A and B subtypes of RSV when compared with RSV-IGIV. 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.<ref>{{Cite journal|last=Resch|first=Bernhard|date=2017-06-12|title=Product review on the monoclonal antibody palivizumab for prevention of respiratory syncytial virus infection|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5612471/|journal=Human Vaccines & Immunotherapeutics|volume=13|issue=9|pages=2138–2149|doi=10.1080/21645515.2017.1337614|issn=2164-5515|pmc=5612471|pmid=28605249}}</ref> |
Palivizumab has demonstrated significantly higher affinity and potency in neutralizing both A and B subtypes of RSV when compared with RSV-IGIV.<ref>{{Cite journal|last=Wu|first=H.|last2=Pfarr|first2=D. S.|last3=Losonsky|first3=G. A.|last4=Kiener|first4=P. A.|date=2008|title=Immunoprophylaxis of RSV infection: advancing from RSV-IGIV to palivizumab and motavizumab|url=https://pubmed.ncbi.nlm.nih.gov/17990791/|journal=Current Topics in Microbiology and Immunology|volume=317|pages=103–123|doi=10.1007/978-3-540-72146-8_4|issn=0070-217X|pmid=17990791}}</ref> 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.<ref>{{Cite journal|last=Resch|first=Bernhard|date=2017-06-12|title=Product review on the monoclonal antibody palivizumab for prevention of respiratory syncytial virus infection|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5612471/|journal=Human Vaccines & Immunotherapeutics|volume=13|issue=9|pages=2138–2149|doi=10.1080/21645515.2017.1337614|issn=2164-5515|pmc=5612471|pmid=28605249}}</ref> |
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== Side effects == |
== Side effects == |
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Revision as of 17:37, 29 July 2021
| 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 |
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| Pregnancy category |
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| Routes of administration | Intramuscular |
| ATC code | |
| Legal status | |
| Legal status | |
| Pharmacokinetic data | |
| Elimination half-life | 18-20 days |
| Identifiers | |
| CAS Number | |
| DrugBank | |
| ChemSpider |
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| UNII | |
| KEGG | |
| ChEMBL | |
| Chemical and physical data | |
| Formula | C6470H10056N1700O2008S50 |
| Molar mass | 145388.51 g·mol−1 |
  (what is this?) (verify) | |
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][3] It is recommended for infants that are high-risk because of prematurity or other medical problems such as congenital heart disease.[2][3]
The most common side effects include fever and rash.[2][3]
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%. Palivizumab is dosed once a month via intramuscular (IM) injection, to be administered throughout the duration of the RSV season.[2]
Palivizumab targets the fusion protein of RSV,[4] inhibiting its entry into the cell and thereby preventing infection. Palivizumab was approved for medical use in 1998.[5]
Medical use
Palivizumab is indicated for the prevention of serious lower respiratory tract disease requiring hospitalization caused by respiratory syncytial virus (RSV) in children at high risk for RSV disease:[2][3]
- children born at 35 weeks of gestation or less and less than six months of age at the onset of the RSV season;[3]
- children less than two years of age and requiring treatment for bronchopulmonary dysplasia within the last six months;[3]
- children less than two years of age and with haemodynamically significant congenital heart disease.[3]
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.[6]
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.[6]
Other potential target groups for palivizumab prophylaxis include:
- Infants younger than one year of age with hemodynamically significant congenital heart disease.
- Infants younger than one year of age with neuromuscular disorders impairing the ability to clear secretions from the upper airways or pulmonary abnormalities.
- Children younger than two years of age who are immunocompromised (e.g. those with severe combined immunodeficiency; those younger than two years of age who have undergone lung transplantation or hematopoietic stem cell transplantation) during the RSV season.
- Children with Down syndrome who have additional risk factors for lower respiratory tract infections.
- Alaska native and American Indian infants.
Decisions regarding palivizumab prophylaxis for children in these groups should be made on a case-by-case basis.[6]
Because palivizumab is a passive antibody, it is ineffective in treatment of RSV infection, and its administration is not recommended for this indication.[7]
Mechanism of Action
Palivizumab is a monoclonal antibody that targets the fusion (F) glycoprotein on the surface of RSV, and deactivates it.[8] 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.[8][9]
Pharmacodynamics
Palivizumab has demonstrated significantly higher affinity and potency in neutralizing both A and B subtypes of RSV when compared with RSV-IGIV.[10] 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.[11]
Side effects
Palivizumab use may cause side effects, which include, but are not limited to:[12]
Some more serious side effects include:
- Severe skin rash
- Itching
- Hives (urticaria)
- Difficulty breathing
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.[13]
Pharmacokinetics
Absorption
Based on a recent meta analysis, palivizumab absorption is quicker in pediatrics compared to adult populations (ka = 1.01/day vs. ka = 0.373/day). The intramuscular bioavailability of this drug is approximately 70% in healthy young adults.[14] Current recommendation for RSV immunoprophylaxis is administration of 5 x 15 mg/kg doses of palivizumab to maintain body concentrations above 40 μg/mL.[15]
Distribution
The volume of distribution is approximately 4.1 liters.[14]
Clearance
Palivizumab has a relatively low 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 recent meta analysis estimated clearance in pediatric population by considering maturation of CL and body weight which showed a significant reduction compared to adult populations.[14]
References
- ^ "Synagis 100 mg/ml solution for injection - Summary of Product Characteristics (SmPC)". (emc). 12 August 2020. Retrieved 20 August 2020.
- ^ a b c d e f "Synagis- palivizumab injection, solution". DailyMed. 12 May 2017. Retrieved 20 August 2020.
- ^ a b c d e f g h "Synagis EPAR". European Medicines Agency (EMA). Retrieved 20 August 2020. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
- ^ Levinson W (2004). Medical Microbiology and Immunology (8th ed.). Lange. p. 430.
- ^ Long SS, Pickering LK, Prober CG (2012). Principles and Practice of Pediatric Infectious Disease. Elsevier Health Sciences. p. 1502. ISBN 978-1437727029.
- ^ a b c Brady MT, Byington CL, Davies HD, Edwards KM, Jackson MA, 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): 415–20. doi:10.1542/peds.2014-1665. PMID 25070315.
- ^ Committee, Committee on Infectious Diseases and Bronchiolitis Guidelines (2014-08-01). "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. ISSN 0031-4005. PMID 25070315.
- ^ a b Resch, Bernhard (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. ISSN 2164-5515. PMC 5612471. PMID 28605249.
- ^ McLellan, Jason S.; Ray, William C.; Peeples, Mark E. (2013). "Structure and Function of RSV Surface Glycoproteins". Current topics in microbiology and immunology. 372: 83–104. doi:10.1007/978-3-642-38919-1_4. ISSN 0070-217X. PMC 4211642. PMID 24362685.
- ^ Wu, H.; Pfarr, D. S.; Losonsky, G. A.; Kiener, P. A. (2008). "Immunoprophylaxis of RSV infection: advancing from RSV-IGIV to palivizumab and motavizumab". Current Topics in Microbiology and Immunology. 317: 103–123. doi:10.1007/978-3-540-72146-8_4. ISSN 0070-217X. PMID 17990791.
- ^ Resch, Bernhard (2017-06-12). "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. ISSN 2164-5515. PMC 5612471. PMID 28605249.
- ^ "Palivizumab Injection". MedlinePlus Drug Information. U.S. National Library of Medicine. Retrieved 2016-01-30.
- ^ "Drugs@FDA: FDA-Approved Drugs". www.accessdata.fda.gov. Retrieved 28 July 2021.
{{cite web}}: CS1 maint: url-status (link) - ^ a b c Robbie, Gabriel J.; Zhao, Liang; Mondick, John; Losonsky, Genevieve; Roskos, Lorin K. (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. ISSN 0066-4804. PMC 3421858. PMID 22802243.
- ^ Reuter, Stephanie E.; Evans, Allan M.; Ward, Michael B. (2019). "Reducing Palivizumab Dose Requirements Through Rational Dose Regimen Design". CPT: Pharmacometrics & Systems Pharmacology. 8 (1): 26–33. doi:10.1002/psp4.12364. ISSN 2163-8306. PMC 6363066. PMID 30426719.
External links
- "Palivizumab". Drug Information Portal. U.S. National Library of Medicine.
