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Generic Name: Palivizumab
Class: Monoclonal Antibodies
VA Class: AM800
CAS Number: 188039-54-5

Introduction

Antiviral; biosynthetic humanized form of a murine monoclonal antibody to the F surface glycoprotein of respiratory syncytial virus (RSV).1 2 3 4 5 6 7 8 50

Uses for Synagis

Respiratory Syncytial Virus (RSV) Infections

Prevention of serious RSV lower respiratory tract infections in infants at high risk for RSV disease.1 6 7 8 50 51

Recommended for infants <24 months of age who have chronic lung disease (e.g., bronchopulmonary dysplasia [BPD]), history of premature birth (gestational age ≤35 weeks), or hemodynamically significant congenital heart disease (CHD).1 6 7 8 50 51 May reduce severity of RSV infection and reduce frequency and duration of RSV-related hospitalizations in these high-risk infants.1 6 7 8 37 39 40 41 42 50 51

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Drug of choice when RSV prophylaxis is indicated.6 7 8 50

Need for and efficacy of palivizumab prophylaxis following institutional RSV outbreaks (e.g., in neonatal intensive care units) not studied to date; the major means of preventing RSV illness in such situations is strict observance of infection control practices.3 8 9

Safety and efficacy for treatment of established RSV disease not established.1 37 Do not use for treatment of RSV infection.1 8 50

Synagis Dosage and Administration

General

  • Administer first dose immediately prior to RSV season and additional doses once monthly throughout the season.1 3 8 In the northern hemisphere, RSV season typically commences in November and lasts through April, but may begin earlier or persist later in certain communities.1 3 8

  • AAP states that in most seasons and in most regions of the northern hemisphere, give first dose at beginning of November and the last dose at beginning of March; these 5 doses usually provide protection during the entire season.3 8 However, decisions about the specific duration of prophylaxis should be individualized according to the duration of the local RSV season.3 8

  • AAP recommends that clinicians consult local health departments or diagnostic virology laboratories or the CDC to determine the epidemiology of RSV in their area.8

  • If an infant receiving palivizumab prophylaxis becomes infected with RSV, continue giving the monthly prophylaxis doses for the duration of the RSV season.1 8 37

Administration

IM Administration

Administer IM,1 5 6 8 preferably in anterolateral aspect of the thigh.1 5 Avoid gluteal muscle because of risk of damage to sciatic nerve.1

Has been administered by IV infusion over 3–5 minutes in a limited number of infants,4 but manufacturer states the currently available formulation is intended for IM injection only.1 37

Administer immediately after withdrawal from vial.1 Vial is for single use only; discard any unused portion.1

Doses involving volumes >1 mL should be divided and injected IM at different sites.1

Dosage

Pediatric Patients

Respiratory Syncytial Virus (RSV) Infections
Prevention of RSV Lower Respiratory Tract Infections
IM

Infants at high risk for RSV disease: 15 mg/kg once monthly.1 6 8 50 Give first dose prior to beginning of RSV season and subsequent doses once monthly until end of season.1 6 8

Infants at high risk for RSV undergoing cardiopulmonary bypass: Give a supplemental 15-mg/kg dose as soon as possible after cardiopulmonary bypass (even if this is <1 month after the last dose).1 8 51 (See Plasma Concentrations under Pharmacokinetics.) Thereafter, give usual doses once monthly.1 8

Cautions for Synagis

Contraindications

  • History of a severe reaction to the drug or any ingredient in the formulation (e.g., murine protein).1 37

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity Reactions

Severe acute hypersensitivity reactions, including anaphylaxis, reported rarely.1

Dyspnea, cyanosis, respiratory failure, urticaria, pruritus, angioedema, hypotonia, and unresponsiveness also reported.1

If a severe hypersensitivity reaction occurs, discontinue palivizumab and initiate appropriate supportive care and therapy (e.g., epinephrine).1 Palivizumab may be continued with caution in patients who experience a milder reaction.1

General Precautions

Administration Precautions

For IM use only.1 Use caution in patients with thrombocytopenia or any coagulation disorder.1

Specific Populations

Pregnancy

Category C.1 Not indicated in adults; used only in pediatric patients who would not be of childbearing potential.1

Lactation

Not known whether distributed into milk.37 Not indicated in adults; used only in pediatric patients who would not be of lactating potential.1

Common Adverse Effects

Upper respiratory tract infection, otitis media, fever, rhinitis, hernia, elevated serum AST concentration.1

Interactions for Synagis

Formal studies have not been conducted to evaluate potential interactions between palivizumab and other drugs.1

Specific Drugs

Drug

Interaction

Bronchodilators

Not specifically studied, but no apparent increase in adverse effects when used concomitantly1

Corticosteroids

Not specifically studied, but no apparent increase in adverse effects when used concomitantly1

Vaccines

No evidence that palivizumab interferes with the immune response to vaccines;1 8 no apparent increase in adverse effects when given concomitantly with routine childhood vaccines1

Synagis Pharmacokinetics

Absorption

Bioavailability

Well absorbed following IM injection in infants.5 37

Plasma Concentrations

Concentrations >40 mcg/mL attained within 2 days after a single 15-mg/kg IM dose; peak concentrations attained within 5–7 days after a dose.5 37

Monthly 15-mg/kg IM doses usually adequate to maintain trough serum concentrations exceeding the ideal target throughout the dosing period (except in children undergoing cardiopulmonary bypass).4 5 Lower doses (i.e., 3 or 10 mg/kg IV, 5 or 10 mg/kg IM) result in inadequate trough concentrations.4 5

Surgical procedures involving cardiopulmonary bypass result in a mean 58% decrease in serum palivizumab concentrations.1 51 (See Dosage under Dosage and Administration.)

Elimination

Half-life

Pediatric patients ≤24 months of age (including patients ≤6 months of age born at ≤35 weeks’ gestation): 19–27 days.1 4 5

Stability

Storage

Parenteral

Injection

2–8°C in original container; do not freeze.1

Actions and Spectrum

  • A highly selective antiviral agent active only against RSV.1 2 3 4 5 6 7 8

  • Potent, RSV-neutralizing, monoclonal antibody that neutralizes and inhibits fusion of RSV,1 2 7 resulting in inhibition of viral replication.1

  • Active against both major strains of RSV (subgroup A and B).1 2 In vivo neutralizing activity of the drug was confirmed in a clinical trial in RSV-infected pediatric patients as evidenced by lower recovery of RSV from lower respiratory tract secretions in palivizumab-treated patients compared with placebo recipients.1 38

  • Evidence from animal studies indicates palivizumab does not interfere with in vivo development of a protective immune response to RSV.2

  • All clinical isolates of RSV subgroup A and B tested to date have been susceptible to palivizumab.1 2

  • Animal studies indicate that exposure of RSV to subinhibitory palivizumab concentrations does not enhance viral replication or pathology and does not promote emergence of resistant variants; palivizumab appeared to protect the animals against infection from subsequent RSV challenge despite systemic clearance of the drug.2 However, escape mutants (resistant viruses) have been associated with other monoclonal antibodies and the possibility that they could occur with palivizumab should be considered.8

Advice to Patients

  • Importance of continuing palivizumab prophylaxis in high-risk infants once monthly for the duration of the RSV season.1

  • Importance of contacting clinician if possible symptoms of a hypersensitivity reaction occur (e.g., dyspnea, cyanosis, respiratory failure, urticaria, pruritus, angioedema, hypotonia, unresponsiveness).1

  • Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal products, and any concomitant illnesses.

  • Importance of advising caregivers of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Palivizumab

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for IM use only

50 mg/0.5 mL

Synagis (preservative-free)

MedImmune, (also marketed by Ross)

100 mg/1 mL

Synagis (preservative-free)

MedImmune, (also marketed by Ross)

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions June 1, 2006. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. MedImmune, Inc. Synagis (palivizumab) for intramuscular administration prescribing information. Gaithersburg, MD; 2004 Jul 23.

2. Johnson S, Oliver C, Prince GA et al. Development of a humanized monoclonal antibody (MEDI-493) with potent in vitro and in vivo activity against respiratory syncytial virus. J Infect Dis. 1997; 176:1215-24. [PubMed 9359721]

3. Committee on Infectious Diseases, American Academy of Pediatrics. Red book: 2003 report of the Committee on Infectious Diseases. 26th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2003:523-8.

4. Subramanian KNS, Weisman LE, Rhodes T et al. Safety, tolerance and pharmacokinetics of a humanized monoclonal antibody to respiratory syncytial virus in premature infants and infants with bronchopulmonary dysplasia. Pediatr Infect Dis J. 1998; 17:110-15. [IDIS 401101] [PubMed 9493805]

5. Sáez-Llorens X, Casta˜no E, Null D et al. Safety and efficacy of intramuscular humanized monoclonal antibody to respiratory syncytial virus in premature infants with bronchopulmonary dysplasia. Pediatr Infect Dis J. 1998; 17:787-91. [IDIS 415465] [PubMed 9779762]

6. The Impact-RSV Study Group. Palivizumab, a humanized respiratory syncytial virus monoclonal antibody, reduces hospitalization from respiratory syncytial virus infection in high-risk infants. Pediatrics. 1998;102:531-7.

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