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## Complete Summary

#### GUIDELINE TITLE

Revised indications for the use of palivizumab and respiratory syncytial
virus immune globulin intravenous for the prevention of respiratory
syncytial virus infections.

#### BIBLIOGRAPHIC SOURCE(S)

Revised indications for the use of palivizumab and respiratory syncytial
virus immune globulin intravenous for the prevention of respiratory
syncytial virus infections. Pediatrics 2003 Dec;112(6 Pt 1):1442-6. \[5
references\]
[PubMed](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14654627)

#### GUIDELINE STATUS

This is the current release of the guideline.

American Academy of Pediatrics (AAP) Policies are reviewed every 3 years
by the authoring body, at which time a recommendation is made that the
policy be retired, revised, or reaffirmed without change. Until the
Board of Directors approves a revision or reaffirmation, or retires a
statement, the current policy remains in effect.

### COMPLETE SUMMARY CONTENT

 SCOPE\
 METHODOLOGY - including Rating Scheme and Cost Analysis\
 RECOMMENDATIONS\
 EVIDENCE SUPPORTING THE RECOMMENDATIONS\
 BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS\
 CONTRAINDICATIONS\
 QUALIFYING STATEMENTS\
 IMPLEMENTATION OF THE GUIDELINE\
 INSTITUTE OF MEDICINE (IOM) NATIONAL HEALTHCARE QUALITY REPORT
CATEGORIES\
 IDENTIFYING INFORMATION AND AVAILABILITY\
 DISCLAIMER

### SCOPE

#### DISEASE/CONDITION(S)

-   Severe lower respiratory tract infections caused by respiratory
    syncytial virus

-   Chronic lung disease (formerly called bronchopulmonary dysplasia)

-   Congenital heart disease

-   Preterm infants

#### GUIDELINE CATEGORY

Assessment of Therapeutic Effectiveness\
Prevention\
Treatment

#### CLINICAL SPECIALTY

Cardiology\
Family Practice\
Infectious Diseases\
Pediatrics\
Pulmonary Medicine

#### INTENDED USERS

Advanced Practice Nurses\
Nurses\
Physician Assistants\
Physicians\
Respiratory Care Practitioners

#### GUIDELINE OBJECTIVE(S)

-   To provide revised recommendations for administering respiratory
    syncytial virus (RSV) prophylaxis to infants and children with
    congenital heart disease, for identifying infants with a history of
    preterm birth and chronic lung disease who are most likely to
    benefit from immunoprophylaxis, and for reducing the risk of RSV
    exposure and infection in high-risk children

-   To update clinicians on the appropriate use of respiratory syncytial
    virus immune globulin intravenous (RSV-IGIV) and palivizumab on the
    basis of data from 5 clinical trials

#### TARGET POPULATION

Infants at high-risk for respiratory syncytial virus (RSV) infection

#### INTERVENTIONS AND PRACTICES CONSIDERED

1.  Respiratory Syncytial Virus Immune Globulin Intravenous (RSV-IGIV)
    (a polyclonal hyperimmune globulin prepared from donors selected for
    having high serum titers of RSV neutralizing antibody)

2.  Palivizumab (a humanized murine monoclonal anti-F glycoprotein
    immunoglobulin G1 antibody with neutralizing and fusion inhibitory
    activity against RSV)

#### MAJOR OUTCOMES CONSIDERED

-   Hospital admissions

-   Number of days of hospitalization

-   Respiratory tract disease severity

-   Cost associated with immunoprophylaxis intervention

### METHODOLOGY

#### METHODS USED TO COLLECT/SELECT EVIDENCE

Hand-searches of Published Literature (Primary Sources)\
Hand-searches of Published Literature (Secondary Sources)\
Searches of Electronic Databases

#### DESCRIPTION OF METHODS USED TO COLLECT/SELECT THE EVIDENCE

Not stated

#### NUMBER OF SOURCE DOCUMENTS

Not stated

#### METHODS USED TO ASSESS THE QUALITY AND STRENGTH OF THE EVIDENCE

Weighting According to a Rating Scheme (Scheme Given)

#### RATING SCHEME FOR THE STRENGTH OF THE EVIDENCE

**Evidence grade I**: evidence obtained from at least one properly
designed, randomized, controlled trial

**Evidence grade II-1**: evidence obtained from well-designed controlled
trials without randomization

**Evidence grade II-2**: evidence obtained from well-designed cohort or
case-control analytic studies, preferably from more than one center or
research group

**Evidence grade II-3**: evidence obtained from multiple time series
with or without the intervention, or dramatic results in uncontrolled
experiments

**Evidence grade III**: opinions of respected authorities, based on
clinical experience, descriptive studies, or reports of expert
committees

#### METHODS USED TO ANALYZE THE EVIDENCE

Systematic Review

#### DESCRIPTION OF THE METHODS USED TO ANALYZE THE EVIDENCE

Not stated

#### METHODS USED TO FORMULATE THE RECOMMENDATIONS

Expert Consensus

#### DESCRIPTION OF METHODS USED TO FORMULATE THE RECOMMENDATIONS

Not stated

#### RATING SCHEME FOR THE STRENGTH OF THE RECOMMENDATIONS

Not applicable

#### COST ANALYSIS

Several economic analyses of respiratory syncytial virus (RSV)
immunoprophylaxis have been published and reviewed. The primary benefit
of immunoprophylaxis with either agent is a decrease in the rate of
RSV-associated hospitalization. None of the 5 randomized, controlled
clinical trials have demonstrated a significant decrease in rate of
mortality attributable to RSV infection in infants who receive
prophylaxis. Most of the economic analyses fail to demonstrate overall
savings in health care dollars because of the high cost if all at-risk
children were to receive prophylaxis. Estimates of cost per
hospitalization prevented have been inconsistent because of considerable
variation in the baseline rate of hospitalization attributable to RSV in
different high-risk groups. Other considerations that will influence
results include the effect of prophylaxis on outpatient costs and a
resolution of the question of whether prevention of RSV infection in
infancy decreases wheezing and lower respiratory tract problems later in
childhood.

Factors other than degree of prematurity, congenital heart disease
(CHD), and chronic lung disease (CLD) that may influence the decision
regarding prophylaxis include presence of other underlying conditions
that predispose to respiratory complications (e.g., neurologic disease
in very low birth weight infants), number of young siblings, child care
center attendance, anticipation of cardiac surgery, and distance to and
availability of hospital care for severe respiratory illness. For many
infants who qualify for the approved indications, risk of
hospitalization for serious respiratory illness will be low, and the
cost and logistic difficulties associated with prophylaxis may outweigh
potential benefits.

#### METHOD OF GUIDELINE VALIDATION

Peer Review

#### DESCRIPTION OF METHOD OF GUIDELINE VALIDATION

Not stated

### RECOMMENDATIONS

#### MAJOR RECOMMENDATIONS

1.  Palivizumab or Respiratory Syncytial Virus Immune Globulin
    Intravenous (RSV-IGIV) prophylaxis should be considered for infants
    and children younger than 2 years of age with chronic lung disease
    (CLD) who have required medical therapy (supplemental oxygen,
    bronchodilator, diuretic, or corticosteroid therapy) for CLD within
    6 months before the anticipated start of the respiratory syncytial
    virus (RSV) season. Palivizumab is preferred over RSV-IGIV for most
    high-risk children because of its ease of administration, safety,
    and effectiveness. (**Evidence grade I**)

    -   Patients with more severe CLD may benefit from prophylaxis
        during a second RSV season if they continue to require medical
        therapy for pulmonary or cardiac dysfunction. Individual
        patients may benefit from decisions made in consultation with
        neonatologists, pediatric intensivists, pulmonologists, or
        infectious disease specialists. There are limited data regarding
        the effectiveness of palivizumab during the second year of life,
        although children with CLD or congenital heart disease (CHD) who
        require ongoing medical therapy may experience severe RSV
        infections.

2.  Infants born at 32 weeks´ gestation or earlier may benefit from RSV
    prophylaxis, even if they do not have CLD. For these infants, major
    risk factors to consider include their gestational age and
    chronologic age at the start of the RSV season. (**Evidence grade
    I**)

    -   Infants born at 28 weeks´ gestation or earlier may benefit from
        prophylaxis during their first RSV season whenever that occurs
        during the first 12 months of life. Infants born at 29 to 32
        weeks´ gestation may benefit most from prophylaxis up to 6
        months of age. For the purpose of this recommendation, 32 weeks´
        gestation refers to an infant born on or before the 32nd week of
        gestation (i.e., 32 weeks, 0 days). Once a child qualifies for
        initiation of prophylaxis at the start of the RSV season,
        administration should continue throughout the season and not
        stop at the point an infant reaches either 6 months or 12 months
        of age.

3.  Although palivizumab and RSV-IGIV have been shown to decrease the
    likelihood of hospitalization for infants born between 32 and 35
    weeks of gestation (i.e., between 32 weeks, 1 day and 35 weeks, 0
    days) (**Evidence** **grade I**), the cost of administering
    prophylaxis to this large group of infants must be considered
    carefully.

    -   Most experts recommend that prophylaxis be reserved for infants
        in this group who are at greatest risk of severe infection and
        who are younger than 6 months at the start of the RSV season.
        Epidemiologic data suggest that RSV infection is more likely to
        lead to hospitalization for these infants when the following
        risk factors are present: child care attendance, school-aged
        siblings, exposure to environmental air pollutants, congenital
        abnormalities of the airways, or severe neuromuscular disease.
        However, no single risk factor causes a very large increase in
        the rate of hospitalization, and the risk is additive as the
        number of risk factors for an individual infant increases.
        Therefore, prophylaxis should be considered for infants between
        32 and 35 weeks´ gestation only if 2 or more of these risk
        factors are present.

    -   Exposure to tobacco smoke is a risk factor that can be
        controlled by the family of an infant at increased risk of RSV
        disease, and tobacco smoke control measures will be far less
        costly than palivizumab prophylaxis. High-risk infants never
        should be exposed to tobacco smoke. High-risk infants should be
        kept away from crowds and from situations where exposure to
        infected individuals cannot be controlled.

    -   Participation in child care should be restricted during the RSV
        season for high-risk infants whenever feasible. Parents should
        be instructed on the importance of careful hand hygiene.

    -   All high-risk infants and their contacts should be immunized
        against influenza beginning at 6 months of age.

4.  Prophylaxis against RSV should be initiated just before the onset of
    the RSV season and terminated at the end of the RSV season. In most
    seasons and in most regions of the Northern Hemisphere, the first
    dose of palivizumab should be administered at the beginning of
    November and the last dose should be administered at the beginning
    of March, which will provide protection into April. (**Evidence
    grade III**)

    -   To understand the epidemiology of RSV in their area, physicians
        should consult with local health departments or diagnostic
        virology laboratories or the Centers for Disease Control and
        Prevention if such information is not available locally.
        Decisions about the specific duration of prophylaxis should be
        individualized according to the duration of the RSV season.
        Pediatricians may wish to use RSV hospitalization data from
        their own region to assist in the decision-making process.

5.  Children who are 24 months of age or younger with hemodynamically
    significant cyanotic and acyanotic CHD will benefit from 5 monthly
    intramuscular injections of palivizumab (15 mg/kg). (**Evidence
    grade I**)

    -   Decisions regarding prophylaxis with palivizumab in children
        with CHD should be made on the basis of the degree of
        physiologic cardiovascular compromise. Infants younger than 12
        months with CHD who are most likely to benefit from
        immunoprophylaxis include:

        a.  Infants who are receiving medication to control congestive
            heart failure (CHF)

        b.  Infants with moderate to severe pulmonary hypertension

        c.  Infants with cyanotic heart disease

    -   Because a mean decrease in palivizumab serum concentration of
        58% was observed after surgical procedures that use
        cardiopulmonary bypass, for children who still require
        prophylaxis, a postoperative dose of palivizumab (15 mg/kg)
        should be considered as soon as the patient is medically stable.

> The following groups of infants are not at increased risk from RSV and
> generally should not receive immunoprophylaxis:

-   Infants and children with hemodynamically insignificant heart
    disease (e.g., secundum atrial septal defect, small ventricular
    septal defect, pulmonic stenosis, uncomplicated aortic stenosis,
    mild coarctation of the aorta, and patent ductus arteriosus)

-   Infants with lesions adequately corrected by surgery unless they
    continue to require medication for congestive heart failure

-   Infants with mild cardiomyopathy who are not receiving medical
    therapy

> Dates for initiation and termination of prophylaxis should be based on
> the same considerations as for high-risk preterm infants. Unlike
> palivizumab, RSV-IGIV is contraindicated in children with cyanotic
> CHD.

6.  Palivizumab or RSV-IGIV prophylaxis has not been evaluated in
    randomized trials in immunocompromised children. Although specific
    recommendations for immunocompromised patients cannot be made,
    children with severe immunodeficiencies (e.g., severe combined
    immunodeficiency or severe acquired immunodeficiency syndrome) may
    benefit from prophylaxis. If these infants and children are
    receiving standard IGIV monthly, physicians may consider
    substitution of RSV-IGIV during the RSV season. (**Evidence grade
    III**)

7.  Because RSV-IGIV and palivizumab are not effective in the treatment
    of RSV disease, neither is licensed for this indication. (**Evidence
    grade I**)

8.  Limited studies suggest that some patients with cystic fibrosis may
    be at increased risk of RSV infection. However, there are
    insufficient data to determine the effectiveness of palivizumab use
    in this patient population.

9.  If an infant or child who is receiving immunoprophylaxis experiences
    a breakthrough RSV infection, prophylaxis should continue through
    the RSV season. (**Evidence grade III**)

    -   This recommendation is based on the observation that high-risk
        infants may be hospitalized more than once in the same season
        with RSV lower respiratory tract disease and the fact that more
        than one RSV strain often co-circulates in a community.

10. Physicians should arrange for drug administration within 6 hours
    after opening a vial, because this product does not contain a
    preservative.

11. Recommendations cannot be made regarding the use of palivizumab as a
    means of prevention of nosocomial RSV disease.

    -   RSV is known to be transmitted in the hospital setting and to
        cause serious disease in high-risk infants. In high-risk
        hospitalized infants, the major means to prevent RSV disease is
        strict observance of infection control practices, including the
        use of rapid means to identify and isolate RSV-infected infants.
        If an RSV outbreak is documented in a high-risk unit (e.g.,
        pediatric intensive care unit \[ICU\]), primary emphasis should
        be placed on proper infection control practices, especially hand
        hygiene.

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12. Palivizumab does not interfere with the response to vaccines.
    Infants and children receiving prophylaxis with RSV-IGIV should have
    immunization with measles-mumps-rubella and varicella vaccines
    deferred for 9 months after the last dose of RSV-IGIV.

    -   The use of RSV-IGIV should not alter primary immunization
        schedule for other recommended immunizations. Available data at
        this time do not support the need for supplemental doses of any
        of these routinely administered vaccines.

**[Definitions]{.underline}**:

**Evidence Grading**

**Evidence grade I**: evidence obtained from at least one properly
designed, randomized, controlled trial

**Evidence grade II-1**: evidence obtained from well-designed controlled
trials without randomization

**Evidence grade II-2**: evidence obtained from well-designed cohort or
case-control analytic studies, preferably from more than one center or
research group

**Evidence grade II-3**: evidence obtained from multiple time series
with or without the intervention, or dramatic results in uncontrolled
experiments

**Evidence grade III**: opinions of respected authorities, based on
clinical experience, descriptive studies, or reports of expert
committees

#### CLINICAL ALGORITHM(S)

None provided

### EVIDENCE SUPPORTING THE RECOMMENDATIONS

#### TYPE OF EVIDENCE SUPPORTING THE RECOMMENDATIONS

The type of evidence is identified and graded for each recommendation
(see \"Major Recommendations\").

### BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS

#### POTENTIAL BENEFITS

**Overall Benefits**

Prevention of severe lower respiratory tract infections caused by
respiratory syncytial virus (RSV) in high-risk infants, children younger
than 24 months with chronic lung disease (formerly called
bronchopulmonary dysplasia), and certain preterm infants

**Specific Benefits**

Palivizumab is preferred for most high-risk infants and children because
of ease of intramuscular administration. Monthly administration of
palivizumab during the RSV season results in a 45 to 55% decrease in the
rate of hospitalization attributable to RSV.

#### POTENTIAL HARMS

**Respiratory Syncytial Virus Immune Globulin Intravenous (RSV-IGIV)**

-   Volume overload

-   Interference with the immune response to some live-virus vaccines;
    therefore, immunization with measles-mumps-rubella and varicella
    vaccines should be deferred for 9 months after the last dose. The
    manufacturer has suggested an additional dose of vaccine to ensure
    adequate immune response to diphtheria and tetanus toxoids and
    acellular pertussis, *H influenzae* type b, and oral poliovirus
    vaccines; however, available data do not support the need for
    supplemental doses of routinely administered vaccines.

-   Mild decrease in oxygen saturation and fever

**Palivizumab**

Because a mean decrease in palivizumab serum concentration of 58% was
observed after surgical procedures that use cardiopulmonary bypass, for
children who still require prophylaxis, a postoperative dose of
palivizumab should be considered as soon as the patient is medically
stable.

### CONTRAINDICATIONS

#### CONTRAINDICATIONS

Respiratory syncytial virus immune globulin intravenous (RSV-IGIV) is
contraindicated in children with cyanotic congenital heart disease (CHD)

### QUALIFYING STATEMENTS

#### QUALIFYING STATEMENTS

The guidance in this report does not indicate an exclusive course of
treatment or serve as a standard of medical care. Variations, taking
into account individual circumstances, may be appropriate.

### IMPLEMENTATION OF THE GUIDELINE

#### DESCRIPTION OF IMPLEMENTATION STRATEGY

An implementation strategy was not provided.

### INSTITUTE OF MEDICINE (IOM) NATIONAL HEALTHCARE QUALITY REPORT CATEGORIES

#### IOM CARE NEED

Staying Healthy

#### IOM DOMAIN

Effectiveness

### IDENTIFYING INFORMATION AND AVAILABILITY

#### BIBLIOGRAPHIC SOURCE(S)

Revised indications for the use of palivizumab and respiratory syncytial
virus immune globulin intravenous for the prevention of respiratory
syncytial virus infections. Pediatrics 2003 Dec;112(6 Pt 1):1442-6. \[5
references\]
[PubMed](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14654627)

#### ADAPTATION

Not applicable: The guideline was not adapted from another source.

#### DATE RELEASED

2003 Dec

#### GUIDELINE DEVELOPER(S)

American Academy of Pediatrics - Medical Specialty Society

#### SOURCE(S) OF FUNDING

American Academy of Pediatrics

#### GUIDELINE COMMITTEE

Committee on Infectious Diseases, 2002-2003\
Committee on Fetus and Newborn, 2003-2004

#### COMPOSITION OF GROUP THAT AUTHORED THE GUIDELINE

*Committee on Infectious Diseases, 2002-2003*: Jon S. Abramson, MD
(*Chair*); Carol J. Baker, MD; Robert S. Baltimore, MD; Joseph A.
Bocchini Jr, MD; Sarah S. Long, MD; Julia A. McMillan, MD; H. Cody
Meissner, MD; Keith R. Powell, MD; Charles G. Prober, MD; Margaret B.
Rennels, MD; Thomas N. Saari, MD; Leonard B. Weiner, MD

*Liaisons*: Joanne Embree, MD, Canadian Paediatric Society; Marc A.
Fischer, MD, Centers for Disease Control and Prevention; Bruce G.
Gellin, MD, MPH, National Vaccine Program Office; Caroline B. Hall, MD,
Section on Infectious Disease; Martin C. Mahoney, MD, American Academy
of Family Physicians; Mamodikoe Makhene, MD, National Institutes of
Health; Walter A. Orenstein, MD, Centers for Disease Control and
Prevention; Douglas R. Pratt, MD, Food and Drug Administration; Jeffrey
R. Starke, MD, American Thoracic Society; Jack Swanson, MD, American
Academy of Pediatrics Practice Action Group

*Ex Officio*: Larry K. Pickering, MD *Red Book* Editor

*Consultant*: Edgar O. Ledbetter, MD

*Staff*: Martha Cook, MS

*Committee on Fetus and Newborn, 2003-2004*: Lillian Blackmon, MD
(*Chairperson*); Daniel G. Batton, MD; Edward F. Bell, MD; Susan E.
Denson, MD; William A. Engle, MD; William P. Kanto, Jr, MD; Gilbert I.
Martin, MD; Ann R. Stark, MD

*Liaisons*: Keith J. Barrington, MD, Canadian Paediatric Society; Tonse
Raju, MD, DCH, National Institutes of Health; Laura E. Riley, MD,
American College of Obstetricians and Gynecologists; Kay M. Tomashek,
MD, Centers for Disease Control and Prevention; Carol Wallman, MSN, RNC,
NNP, National Association of Neonatal Nurses

*Staff*: Jim Couto, MA

#### FINANCIAL DISCLOSURES/CONFLICTS OF INTEREST

Not stated

#### GUIDELINE STATUS

This is the current release of the guideline.

American Academy of Pediatrics (AAP) Policies are reviewed every 3 years
by the authoring body, at which time a recommendation is made that the
policy be retired, revised, or reaffirmed without change. Until the
Board of Directors approves a revision or reaffirmation, or retires a
statement, the current policy remains in effect.

#### GUIDELINE AVAILABILITY

Electronic copies: Available from the [American Academy of Pediatrics
(AAP) Policy Web
site](http://aappolicy.aappublications.org/cgi/content/full/pediatrics;112/6/1442).

Print copies: Available from American Academy of Pediatrics, 141
Northwest Point Blvd., P.O. Box 927, Elk Grove Village, IL 60009-0927.

#### AVAILABILITY OF COMPANION DOCUMENTS

The following is available:

-   Meissner HC, Long SS, and the Committee on Infectious Diseases and
    the Committee on Fetus and Newborn. Revised indications for the use
    of palivizumab and respiratory syncytial virus immune globulin
    intravenous for the prevention of respiratory syncytial virus
    infections. Technical report. Pediatrics 2003 Dec;112(6 Pt
    1):1447-52.

Electronic copies: Available from the [American Academy of Pediatrics
(AAP)](http://aappolicy.aappublications.org/cgi/content/full/pediatrics;112/6/1447)
Web site.

Print copies: Available from American Academy of Pediatrics, 141
Northwest Point Blvd., P.O. Box 927, Elk Grove Village, IL 60009-0927.

#### PATIENT RESOURCES

None available

#### NGC STATUS

This NGC summary was completed by ECRI on May 20, 2004. The information
was verified by the guideline developer on June 23, 2004.

#### COPYRIGHT STATEMENT

This NGC summary is based on the original guideline, which is subject to
the guideline developer\'s copyright restrictions. Please contact the
Permissions Editor, American Academy of Pediatrics (AAP), 141 Northwest
Point Blvd, Elk Grove Village, IL 60007.

### DISCLAIMER

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© 1998-2008 National Guideline Clearinghouse

Date Modified: 11/10/2008