Palivizumab

Identification

Summary

Palivizumab is a monoclonal anti respiratory syncytial virus F protein antibody used to prevent serious sequelae caused by respiratory syncytial virus infection in pediatric patients.

Brand Names
Synagis
Generic Name
Palivizumab
DrugBank Accession Number
DB00110
Background

Humanized monoclonal antibody (IgG1k) produced by recombinant DNA technology, directed to an epitope in the A antigenic site of the F protein of respiratory syncytial virus (RSV). Synagis is a composite of human (95%) and murine (5%) antibody sequences. The human heavy chain sequence was derived from the constant domains of human IgG1 and the variable framework regions of the VH genes Cor (1) and Cess (2). The human lightchain sequence was derived from the constant domain of Ck and the variable framework regions of the VL gene K104 withJk-4. Palivizumab is expressed from a stable murine (mouse) myeloma cell line (NS0). Palivizumab is composed of to heavy chains (50.6 kDa each) and two light chains (27.6 kDa each), contains 1-2% carbohydrate by weight and has a molecular weight of 147.7 kDa +/- 1 kDa (MALDI-TOF)

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Protein Structure
Protein Chemical Formula
Not Available
Protein Average Weight
Not Available
Sequences
>VH region MEDI-493
QVTLRESGPALVKPTQTLTLTCTFSGFSLSTSGMSVGWIRQPPGKALEWLADIWWDDKKD
YNPSLKSRLTISKDTSKNQVVLKVTNMDPADTATYYCARSMITNWYFDVWGAGTTVTVSS
>VH Region
QVTLRESGPALVKPTQTLTLTCTFSGFSLSTSGMSVGWIRQPPGKALEWLADIWWDDKKD
YNPSLKSRLTISKDTSKNQVVLKVTNMDPADTATYYCARSMITNWYFDVWGAGTTVTVSS
Download FASTA Format
Synonyms
  • Palivizumab
External IDs
  • MEDI 493

Pharmacology

Indication

For prophylaxis of respiratory diseases casued by respiratory syncytial virus.

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Prevention ofSevere respiratory syncytial virus infection••••••••••••••••••••••••••••••• ••••• ••••••• •••••
Prevention ofSevere respiratory syncytial virus infection•••••••••••••••••••••••••••• •••• ••••••• •• •••••••••••
Prevention ofSevere respiratory syncytial virus infection••••••••••••••••••••• •••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Synagis exhibits neutralizing and fusion-inhibitory activity against Respiratory syncytial virus (RSV). These activities inhibit RSV replication or spread. Synagis is given to prevent the development of lower respiratory tract disease in pediatric patients.

Mechanism of action

Palivizumab binds to the fusion glycoprotein of RSV. This prevents its binding and uptake by host cellular receptors.

TargetActionsOrganism
AFusion glycoprotein F0Not AvailableHuman respiratory syncytial virus B (strain 18537)
ULow affinity immunoglobulin gamma Fc region receptor III-BNot AvailableHumans
UComplement C1r subcomponentNot AvailableHumans
UComplement C1q subcomponent subunit ANot AvailableHumans
UComplement C1q subcomponent subunit BNot AvailableHumans
UComplement C1q subcomponent subunit CNot AvailableHumans
ULow affinity immunoglobulin gamma Fc region receptor III-ANot AvailableHumans
UHigh affinity immunoglobulin gamma Fc receptor INot AvailableHumans
ULow affinity immunoglobulin gamma Fc region receptor II-bNot AvailableHumans
Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism

Most likely removed by opsonization via the reticuloendothelial system.

Route of elimination

Not Available

Half-life

18-20 days (in adults)

Clearance

Not Available

Adverse Effects
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Toxicity

Not Available

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.
DrugInteraction
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Palivizumab.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Palivizumab.
Adenovirus type 7 vaccine liveThe therapeutic efficacy of Adenovirus type 7 vaccine live can be decreased when used in combination with Palivizumab.
AducanumabThe risk or severity of adverse effects can be increased when Palivizumab is combined with Aducanumab.
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Palivizumab.
Food Interactions
No interactions found.

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
SynagisInjection, solution50 mg/0.5mLIntramuscularAstrazeneca Ab2016-09-08Not applicableEU flag
SynagisPowder, for solution100 mg / vialIntramuscularAbbvie2002-09-262018-01-31Canada flag
SynagisSolution100 mg / mLIntramuscularAstrazeneca Ab2016-11-03Not applicableCanada flag
SynagisInjection, solution100 mg/1mLIntramuscularMedImmune, LLC1998-06-19Not applicableUS flag
SynagisInjection, powder, for solution100 mgIntramuscularAstrazeneca Ab2016-09-08Not applicableEU flag

Categories

ATC Codes
J06BD01 — Palivizumab
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Peptides
Alternative Parents
Not Available
Substituents
Not Available
Molecular Framework
Not Available
External Descriptors
Not Available
Affected organisms
Not Available

Chemical Identifiers

UNII
DQ448MW7KS
CAS number
188039-54-5

References

General References
Not Available
PubChem Substance
46506637
RxNav
194279
ChEMBL
CHEMBL1201586
Therapeutic Targets Database
DAP000386
PharmGKB
PA164748781
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Palivizumab
FDA label
Download (36.1 KB)

Clinical Trials

Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package
PhaseStatusPurposeConditionsCountStart DateWhy Stopped100+ additional columns
Not AvailableCompletedNot AvailableRespiratory Syncytial Virus (RSV) Infection1somestatusstop reasonjust information to hide
4CompletedTreatmentLung Disorder1somestatusstop reasonjust information to hide
3Active Not RecruitingPreventionRespiratory Syncytial Virus (RSV) Infection1somestatusstop reasonjust information to hide
3CompletedPreventionRespiratory Syncytial Virus (RSV) Infection2somestatusstop reasonjust information to hide
3CompletedSupportive CareCancer1somestatusstop reasonjust information to hide

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Abbott Laboratories Ltd.
  • Medimmune Inc.
Dosage Forms
FormRouteStrength
Injection, powder, for solutionIntramuscular100 MG
Injection, powder, for solutionIntramuscular50 MG
Injection, solutionIntramuscular100 mg/1mL
Injection, solutionIntramuscular50 mg/0.5mL
Injection, solutionIntramuscular; Parenteral100 MG/ML
Powder, for solutionIntramuscular100 mg / vial
Powder, for solutionIntramuscular50 mg / vial
SolutionIntramuscular100 mg / mL
SolutionIntramuscular100.000 mg
SolutionIntramuscular50 mg / 0.5 mL
Injection, solutionIntramuscular
Injection, solutionIntramuscular100 ml
SolutionIntramuscular100 mg/ml
Injection, solutionIntramuscular50 mg/ml
SolutionIntramuscular50 mg
Injection, solutionIntramuscular100 mg/ml
Injection, powder, for solutionIntramuscular100 mg/mL
Injection, powder, lyophilized, for solutionIntramuscular50 mg
SolutionIntramuscular100 mg
SolutionIntramuscular10000000 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
CA2197684No2000-10-312015-08-09Canada flag

Properties

State
Liquid
Experimental Properties
PropertyValueSource
melting point (°C)61 °C (FAB fragment), 71 °C (whole mAb)Vermeer, A.W.P. & Norde, W., Biophys. J. 78:394-404 (2000)

Targets

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Kind
Protein
Organism
Human respiratory syncytial virus B (strain 18537)
Pharmacological action
Yes
General Function
Fusion glycoprotein F0 Inactive precursor that is cleaved at two sites by a furin-like protease to give rise to the mature F1 and F2 fusion glycoproteins.
Specific Function
Not Available
Gene Name
F
Uniprot ID
P13843
Uniprot Name
Fusion glycoprotein F0
Molecular Weight
63687.815 Da
References
  1. Huang K, Incognito L, Cheng X, Ulbrandt ND, Wu H: Respiratory syncytial virus-neutralizing monoclonal antibodies motavizumab and palivizumab inhibit fusion. J Virol. 2010 Aug;84(16):8132-40. doi: 10.1128/JVI.02699-09. Epub 2010 Jun 2. [Article]
  2. Wu H, Pfarr DS, Losonsky GA, Kiener PA: Immunoprophylaxis of RSV infection: advancing from RSV-IGIV to palivizumab and motavizumab. Curr Top Microbiol Immunol. 2008;317:103-23. [Article]
  3. Robinson KA, Odelola OA, Saldanha I, McKoy N: Palivizumab for prophylaxis against respiratory syncytial virus infection in children with cystic fibrosis. Cochrane Database Syst Rev. 2010 Feb 17;(2):CD007743. doi: 10.1002/14651858.CD007743.pub2. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Receptor for the Fc region of immunoglobulins gamma. Low affinity receptor. Binds complexed or aggregated IgG and also monomeric IgG. Contrary to III-A, is not capable to mediate antibody-dependent cytotoxicity and phagocytosis. May serve as a trap for immune complexes in the peripheral circulation which does not activate neutrophils
Specific Function
GPI anchor binding
Gene Name
FCGR3B
Uniprot ID
O75015
Uniprot Name
Low affinity immunoglobulin gamma Fc region receptor III-B
Molecular Weight
26242.67 Da
References
  1. Hiatt A, Bohorova N, Bohorov O, Goodman C, Kim D, Pauly MH, Velasco J, Whaley KJ, Piedra PA, Gilbert BE, Zeitlin L: Glycan variants of a respiratory syncytial virus antibody with enhanced effector function and in vivo efficacy. Proc Natl Acad Sci U S A. 2014 Apr 22;111(16):5992-7. doi: 10.1073/pnas.1402458111. Epub 2014 Apr 7. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
C1r B chain is a serine protease that combines with C1q and C1s to form C1, the first component of the classical pathway of the complement system
Specific Function
calcium ion binding
Gene Name
C1R
Uniprot ID
P00736
Uniprot Name
Complement C1r subcomponent
Molecular Weight
80118.04 Da
References
  1. Hiatt A, Bohorova N, Bohorov O, Goodman C, Kim D, Pauly MH, Velasco J, Whaley KJ, Piedra PA, Gilbert BE, Zeitlin L: Glycan variants of a respiratory syncytial virus antibody with enhanced effector function and in vivo efficacy. Proc Natl Acad Sci U S A. 2014 Apr 22;111(16):5992-7. doi: 10.1073/pnas.1402458111. Epub 2014 Apr 7. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
C1q associates with the proenzymes C1r and C1s to yield C1, the first component of the serum complement system. The collagen-like regions of C1q interact with the Ca(2+)-dependent C1r(2)C1s(2) proenzyme complex, and efficient activation of C1 takes place on interaction of the globular heads of C1q with the Fc regions of IgG or IgM antibody present in immune complexes
Specific Function
amyloid-beta binding
Gene Name
C1QA
Uniprot ID
P02745
Uniprot Name
Complement C1q subcomponent subunit A
Molecular Weight
26016.47 Da
References
  1. Hiatt A, Bohorova N, Bohorov O, Goodman C, Kim D, Pauly MH, Velasco J, Whaley KJ, Piedra PA, Gilbert BE, Zeitlin L: Glycan variants of a respiratory syncytial virus antibody with enhanced effector function and in vivo efficacy. Proc Natl Acad Sci U S A. 2014 Apr 22;111(16):5992-7. doi: 10.1073/pnas.1402458111. Epub 2014 Apr 7. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
C1q associates with the proenzymes C1r and C1s to yield C1, the first component of the serum complement system. The collagen-like regions of C1q interact with the Ca(2+)-dependent C1r(2)C1s(2) proenzyme complex, and efficient activation of C1 takes place on interaction of the globular heads of C1q with the Fc regions of IgG or IgM antibody present in immune complexes
Specific Function
Not Available
Gene Name
C1QB
Uniprot ID
P02746
Uniprot Name
Complement C1q subcomponent subunit B
Molecular Weight
26721.62 Da
References
  1. Hiatt A, Bohorova N, Bohorov O, Goodman C, Kim D, Pauly MH, Velasco J, Whaley KJ, Piedra PA, Gilbert BE, Zeitlin L: Glycan variants of a respiratory syncytial virus antibody with enhanced effector function and in vivo efficacy. Proc Natl Acad Sci U S A. 2014 Apr 22;111(16):5992-7. doi: 10.1073/pnas.1402458111. Epub 2014 Apr 7. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
C1q associates with the proenzymes C1r and C1s to yield C1, the first component of the serum complement system. The collagen-like regions of C1q interact with the Ca(2+)-dependent C1r(2)C1s(2) proenzyme complex, and efficient activation of C1 takes place on interaction of the globular heads of C1q with the Fc regions of IgG or IgM antibody present in immune complexes
Specific Function
Not Available
Gene Name
C1QC
Uniprot ID
P02747
Uniprot Name
Complement C1q subcomponent subunit C
Molecular Weight
25773.56 Da
References
  1. Hiatt A, Bohorova N, Bohorov O, Goodman C, Kim D, Pauly MH, Velasco J, Whaley KJ, Piedra PA, Gilbert BE, Zeitlin L: Glycan variants of a respiratory syncytial virus antibody with enhanced effector function and in vivo efficacy. Proc Natl Acad Sci U S A. 2014 Apr 22;111(16):5992-7. doi: 10.1073/pnas.1402458111. Epub 2014 Apr 7. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Receptor for the invariable Fc fragment of immunoglobulin gamma (IgG). Optimally activated upon binding of clustered antigen-IgG complexes displayed on cell surfaces, triggers lysis of antibody-coated cells, a process known as antibody-dependent cellular cytotoxicity (ADCC). Does not bind free monomeric IgG, thus avoiding inappropriate effector cell activation in the absence of antigenic trigger (PubMed:11711607, PubMed:21768335, PubMed:22023369, PubMed:24412922, PubMed:25786175, PubMed:25816339, PubMed:28652325, PubMed:8609432, PubMed:9242542). Mediates IgG effector functions on natural killer (NK) cells. Binds antigen-IgG complexes generated upon infection and triggers NK cell-dependent cytokine production and degranulation to limit viral load and propagation. Involved in the generation of memory-like adaptive NK cells capable to produce high amounts of IFNG and to efficiently eliminate virus-infected cells via ADCC (PubMed:24412922, PubMed:25786175). Regulates NK cell survival and proliferation, in particular by preventing NK cell progenitor apoptosis (PubMed:29967280, PubMed:9916693). Fc-binding subunit that associates with CD247 and/or FCER1G adapters to form functional signaling complexes. Following the engagement of antigen-IgG complexes, triggers phosphorylation of immunoreceptor tyrosine-based activation motif (ITAM)-containing adapters with subsequent activation of phosphatidylinositol 3-kinase signaling and sustained elevation of intracellular calcium that ultimately drive NK cell activation. The ITAM-dependent signaling coupled to receptor phosphorylation by PKC mediates robust intracellular calcium flux that leads to production of pro-inflammatory cytokines, whereas in the absence of receptor phosphorylation it mainly activates phosphatidylinositol 3-kinase signaling leading to cell degranulation (PubMed:1825220, PubMed:23024279, PubMed:2532305). Costimulates NK cells and trigger lysis of target cells independently of IgG binding (PubMed:10318937, PubMed:23006327). Mediates the antitumor activities of therapeutic antibodies. Upon ligation on monocytes triggers TNFA-dependent ADCC of IgG-coated tumor cells (PubMed:27670158). Mediates enhanced ADCC in response to afucosylated IgGs (PubMed:34485821)
Specific Function
IgG binding
Gene Name
FCGR3A
Uniprot ID
P08637
Uniprot Name
Low affinity immunoglobulin gamma Fc region receptor III-A
Molecular Weight
29088.895 Da
References
  1. Hiatt A, Bohorova N, Bohorov O, Goodman C, Kim D, Pauly MH, Velasco J, Whaley KJ, Piedra PA, Gilbert BE, Zeitlin L: Glycan variants of a respiratory syncytial virus antibody with enhanced effector function and in vivo efficacy. Proc Natl Acad Sci U S A. 2014 Apr 22;111(16):5992-7. doi: 10.1073/pnas.1402458111. Epub 2014 Apr 7. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
High affinity receptor for the Fc region of immunoglobulins gamma. Functions in both innate and adaptive immune responses. Mediates IgG effector functions on monocytes triggering antibody-dependent cellular cytotoxicity (ADCC) of virus-infected cells
Specific Function
high-affinity IgG receptor activity
Gene Name
FCGR1A
Uniprot ID
P12314
Uniprot Name
High affinity immunoglobulin gamma Fc receptor I
Molecular Weight
42631.525 Da
References
  1. Hiatt A, Bohorova N, Bohorov O, Goodman C, Kim D, Pauly MH, Velasco J, Whaley KJ, Piedra PA, Gilbert BE, Zeitlin L: Glycan variants of a respiratory syncytial virus antibody with enhanced effector function and in vivo efficacy. Proc Natl Acad Sci U S A. 2014 Apr 22;111(16):5992-7. doi: 10.1073/pnas.1402458111. Epub 2014 Apr 7. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Receptor for the Fc region of complexed or aggregated immunoglobulins gamma. Low affinity receptor. Involved in a variety of effector and regulatory functions such as phagocytosis of immune complexes and modulation of antibody production by B-cells. Binding to this receptor results in down-modulation of previous state of cell activation triggered via antigen receptors on B-cells (BCR), T-cells (TCR) or via another Fc receptor. Isoform IIB1 fails to mediate endocytosis or phagocytosis. Isoform IIB2 does not trigger phagocytosis
Specific Function
amyloid-beta binding
Gene Name
FCGR2B
Uniprot ID
P31994
Uniprot Name
Low affinity immunoglobulin gamma Fc region receptor II-b
Molecular Weight
34043.355 Da
References
  1. Hiatt A, Bohorova N, Bohorov O, Goodman C, Kim D, Pauly MH, Velasco J, Whaley KJ, Piedra PA, Gilbert BE, Zeitlin L: Glycan variants of a respiratory syncytial virus antibody with enhanced effector function and in vivo efficacy. Proc Natl Acad Sci U S A. 2014 Apr 22;111(16):5992-7. doi: 10.1073/pnas.1402458111. Epub 2014 Apr 7. [Article]

Drug created at June 13, 2005 13:24 / Updated at August 02, 2024 07:21