MP 5.01.10

Immune Prophylaxis for Respiratory Syncytial Virus

---

Medical Policy
Section Prescription Drug	Original Policy Date 3/15/99	Last Review Status/Date Reviewed with literature search/10:2009
Issue 10:2009		Return to Medical Policy Index

---

Disclaimer

Our medical policies are designed for informational purposes only and are not an authorization, or an explanation of benefits, or a contract.  Receipt of benefits is subject to satisfaction of all terms and conditions of the coverage.  Medical technology is constantly changing, and we reserve the right to review and update our policies periodically.

---

Respiratory syncytial virus (RSV) is the most common cause of lower respiratory infections in children. Those at highest risk include those less than 2 years old with prematurity, chronic lung disease (CLD, [formerly known as bronchopulmonary dysplasia]), congenital heart disease or multiple congenital anomalies. Immune prophylaxis against RSV is a prevention strategy to reduce the incidence of infection and its associated morbidity in high-risk infants.

Background/Overview

RSV Infections typically occur in the winter months, starting from October to December and ending from March to May. Considerable variation in the timing of community outbreaks is observed year to year. According to the Centers for Disease Control and Prevention (CDC), onset of the RSV season occurs when the median percentage of specimens testing positive for RSV is 10% higher over a 2-week period. In the U.S., RSV is associated with approximately 90,000 pediatric hospitalizations annually and 450 deaths.
The following table summarizes the immune prophylaxis therapies for RSV:

Drug Bradn Name Manufacturer FDA approval date	Route(s) of Administration Dose range	FDA Approved Indications
Respiratory Syncytial Virus Immune Globulin Intravenous (Human) (RSV-IGIV) (RespiGam®) MedImmune FDA approved 1993 No longer available	IV infusion 1.5mL/kg/hr for 15 minutes; if clinical condition does not contraindicate increase rate to 3.6mL/kg/hour	For the prevention of serious lower respiratory tract infection caused by RSV in children under 24 months of age with chronic lung disease [bronchopulmonary dysplasia (BPD)] or a history of premature birth (≤ 35 weeks gestation).
palivizumab (Synagis® ) MedImmune FDA approved 1998	Intramuscular injection 15mg/kg	For the prevention of serious lower respiratory tract infection caused by RSV in pediatric patients at high risk of RSV. Safety and efficacy were established in infants with chronic lung disease [bronchopulmonary dysplasia (BPD)], infants with a history of premature birth (≤ 35 weeks gestational age) and children with hemodynamically significant congenital heart disease.

As of May 2009, RespiGam is no longer available.

This policy does not address therapies to treat RSV infection.

---

Policy

Monthly administration of immune prophylaxis for respiratory syncytial virus during the RSV season with palivizumab may be considered medically necessary in the following infants and children based on the current guidelines from the American Academy of Pediatrics:

1. Infants with chronic lung disease (CLD, [formerly known as bronchopulmonary dysplasia]). Infants and children younger than 24 months of age who receive medical therapy (supplemental oxygen, bronchodilator, diuretic or chronic corticosteroid therapy) for chronic lung disease within 6 months before the start of the RSV season.
2. Infants born before 32 weeks’ gestation (31 weeks, 6 days or less). Infants in this category may benefit from RSV prophylaxis, even if they do not have CLD. For these infants, major risk factors to consider include gestational age and chronologic age at the start of the RSV season. Infants born at 28 weeks of gestation or earlier (up to and including 28 weeks, 6 days) may benefit from prophylaxis during the RSV season, whenever that occurs during the first 12 months of life. Infants born at 29 to 32 weeks of gestation may benefit most from prophylaxis if younger than 6 months of age at the start of the RSV season. In this setting, 32 weeks’ gestation refers to an infant born before the 32nd week of gestation (31 weeks, 6 days or less).
3. Infants born at 32 to less than 35 weeks’ gestation (defined as 32 weeks, 0 days through 34 weeks, 6 days). Infants younger than 3 months of age at the start of or born during RSV season, or who are likely to have an increased risk of exposure to RSV when at least one of the following risk factors is present:
   • Infant attends child care, defined as a home or facility where care is provided for any number of infants or young toddlers in the child care facility; or
   • Infant has a sibling younger than 5 years of age.
     Infants in this gestational age category should receive prophylaxis only until they reach 3 months of age, maximum of 3 monthly doses.
4. Infants with congenital abnormalities of the airway or neuromuscular disease. Infants born before 35 weeks of gestation who have either congenital abnormalities of the airway or a neuromuscular condition that compromises handling of respiratory secretions.
5. Infants and children with congenital heart disease. Children who are 24 months of age or younger with hemodynamically significant cyanotic or acyanotic congenital heart disease may benefit from palivizumab prophylaxis. Decisions regarding prophylaxis with palivizumab in children with congenital heart disease should be made on the basis of the degree of physiologic cardiovascular compromise. Children younger than 24 months of age with congenital heart disease who are most likely to benefit from immunoprophylaxis include:
   • Infants who are receiving medication to control congestive heart failure;
   • Infants with moderate to severe pulmonary hypertension;
   • Infants with cyanotic heart disease.
     

After surgical procedures that use cardiopulmonary bypass, for children who still require prophylaxis, a postoperative dose of palivizumab may be considered medically necessary as soon as the patient is medically stable.

Immunoprophylaxis for respiratory syncytial virus is considered not medically necessary in:

• Infants and children with hemodynamically insignificant heart disease (eg, 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 for the condition.
  

Other indications for immune prophylaxis for respiratory syncytial virus are considered investigational including, but not limited to, immunocompromised children; patients with cystic fibrosis; or for use in controlling outbreaks of health care-associated disease.

---

Policy Guidelines

Chronic lung disease (CLD, [formerly known as bronchopulmonary dysplasia]) is a general term for long-term respiratory problems in premature infants. CLD results from lung injury to newborns who must use a mechanical ventilator and extra oxygen for breathing. With injury, the lung tissues become inflamed and scarring can result. Some of the causes of the lung injury include the following: prematurity, low amounts of surfactant, oxygen use, mechanical ventilation. Risk factors for developing CLD include: birth at less that 34 weeks’ gestation, birth weight less than 2,000 grams (4 pounds 6.5 ounces), hyaline membrane disease, pulmonary interstitial emphysema (PIE), patent ductus arterioisus (PDA), Causasian, male infants, maternal womb infection (chorioamnionitis) and family history of asthma.

Hospitalized infants who qualify for prophylaxis during the RSV season should receive the first dose of palivizumab 48 to 72 hours before discharge or promptly after discharge.

If an infant or child, who is receiving palivizumab immunoprophylaxis, experiences a breakthrough RSV infection, they should continue monthly prophylaxis until a maximum of 5 doses for infants with congenital heart disease, chronic lung disease (CLD, [formerly known as bronchopulmonary dysplasia]), or preterm birth before 32 weeks’ gestation. 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.

Infants who qualify for prophylaxis in the 32 to 35 weeks' gestation age group should receive prophylaxis only until they reach 90 days of age or a maximum of 3 doses (whichever comes first).

RSV is known to be transmitted in the hospital setting and to cause serious disease in high-risk infants. Among hospitalized infants, the major means to reduce RSV transmission is strict observance of infection control practices, including prompt initiation of precautions for RSV-infected infants. If an RSV outbreak occurs in a high-risk unit (e.g., pediatric or neonatal intensive care unit or stem cell transplantation unit), primary emphasis should be placed on proper infection control practices, especially hand hygiene. No data exist to support palivizumab use in controlling outbreaks of health care-associated disease, and palivizumab use is not recommended for this purpose.

Palivizumab does not interfere with response to vaccines.

Infants, especially high-risk infants, never should be exposed to tobacco smoke. In published studies, passive household exposure to tobacco smoke has not been associated with an increased risk of RSV hospitalization on a consistent basis. However, exposure to tobacco smoke is a known risk factor for many adverse health related outcomes. Exposure to tobacco smoke can be controlled by the family of an infant at increased risk of RSV disease, and preventive measures will be less costly than palivizumab prophylaxis.

In contrast to the well-documented beneficial effect of breastfeeding against many viral illnesses, existing data are conflicting regarding the specific protective effect of breastfeeding against RSV infection. Breastfeeding should be encouraged for all infants in accordance with recommendations of the American Academy of Pediatrics. High-risk infants should be kept away from crowds and from situations in which exposure to infected people cannot be controlled. Participation in group 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. In addition, all high-risk infants 6 months of age and older and their contacts should receive influenza vaccine as well as other recommended age-appropriate immunizations.

Initiation and Termination of Immunoprophylaxis

In the temperate climates of North America, peak RSV activity typically occurs between November and March, whereas in equatorial countries, RSV seasonality patterns vary and may occur throughout the year. The inevitability of the RSV season is predictable, but the severity of the season, the time of onset, the peak of activity, and the end of the season cannot be predicted precisely. Substantial variation in timing of community outbreaks of RSV disease from year to year exists in the same community and between communities in the same year, even in the same region. These variations occur within the overall pattern of RSV outbreaks, usually beginning in November or December, peaking in January or February, and ending by the end of March or sometime in April. Communities in the southern United States, particularly some communities in the state of Florida, tend to experience the earliest onset of RSV activity. In recent years, the national median duration of the RSV season has been 17 weeks or less. Results from clinical trials indicate that palivizumab trough serum concentrations more than 30 days after the fifth dose will be well above the protective concentration for most infants. Five monthly doses of palivizumab will provide more than 20 weeks of protective serum antibody concentration. In the continental United States, a total of 5 monthly doses for infants and young children with congenital heart disease or chronic lung disease of prematurity or preterm birth before 32 weeks’ gestation (31 weeks, 6 days) will provide an optimal balance of benefit and cost, even with variation in season onset and end.

Initiation of immunoprophylaxis in November and continuation for a total of 5 monthly doses will provide protection into April and is recommended for most areas of the United States. If prophylaxis is initiated in October, the fifth and final dose should be administered in February.

Data from the Centers for Disease Control and Prevention (CDC) have identified variations in the onset and offset of the RSV season in the state of Florida that should affect the timing of palivizumab administration. Northwest Florida has an onset in mid-November, which is consistent with other areas of the United States. In north central and southwest Florida, the onset of RSV season typically is late September to early October. The RSV season in southeast Florida (Miami-Dade County) typically has its onset in July. Despite varied onsets, the RSV season is of equal duration in the different regions of Florida. Children who receive palivizumab prophylaxis for the entire RSV season should receive palivizumab only during the 5 months following the onset of RSV season in their region (maximum of 5 doses), which should provide coverage during the peak of the season, when prophylaxis is most effective.

In July 2004, the FDA approved a new liquid formulation of Synagis, supplied as a sterile solution ready for injection, thus providing improved convenience for administration. It is anticipated that this formulation will be used in the physician office setting.

---

Benefit Application
BlueCard/National Account Issues

This policy may be superseded by state or federal mandates that require coverage of FDA-labeled indications of drugs, and thus these items may be assessed only on the basis of their medical necessity.

---

Rationale

Several randomized clinical trials have demonstrated the success of immune prophylaxis of respiratory syncytial virus (RSV). In 1997, the PREVENT Study Group reported on a trial that randomized 510 infants with prematurity or chronic lung disease to receive either placebo or RSV-IVIg infusions monthly for 5 months. The authors reported a 41% reduction in hospitalization due to RSV infection, and reductions in other measures of severity of RSV infection when it did occur. (1) In 1998, the Impact RSV Study Group reported similar results with palivizumab. (2) There was a 55% reduction in hospitalization and similar reductions in other measures of RSV severity in breakthrough infections. It is anticipated that palivizumab will be preferred over the intravenous (IV) immunoglobulin product due to the convenience of intramuscular (IM) administration, safety concerns regarding immunoglobulin pooled from multiple donors, and the unlimited supply of a bioengineered product.

In 1998, the American Academy of Pediatrics (AAP) published revised guidelines regarding the use of RSV-IVIg or palivizumab for RSV immune prophylaxis, which focused on infants with chronic lung disease and preterm infants. (3) In 2003, the AAP Red Book, which summarizes immunization recommendations and the AAP policy statement on the prevention of RSV added indications for children with hemodynamically significant heart disease. (4, 5)

Immune prophylaxis has also been suggested for patients 24 months of age or younger with congenital heart disease (CHD). The AAP guidelines note that children with cyanotic CHD who received RSV-IVIg and underwent cardiac surgery appeared to experience an increased surgical mortality rate. Therefore, according to the AAP guidelines, RSV-IVIg is contraindicated in children with cyanotic CHD. The AAP guidelines indicate the use of palivizumab in children with CHD should be based on the degree of cardiovascular compromise. Infants younger than 12 months with CHD may benefit from palivizumab if they are receiving medication for congestive heart failure, have moderate-to-severe pulmonary hypertension, or have cyanotic heart disease.

The 2003 recommendation by the AAP is based on the results of a double-blind, placebo-controlled randomized trial of 1,287 children with hemodynamically significant CHD. A total of 9.7% of the placebo group required hospitalization compared to 5.3% of the treatment group. (6, 7)

The use of RSV-IVIg or palivizumab in patients with documented immunodeficiencies has also been suggested. The AAP guidelines note, 'Palivizumab or RSV-IVIg 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 immune globulin intravenous monthly, physicians may consider substituting RSV-IVIg during the RSV season.'

Immunocompromised patients undergoing stem-cell transplantation are also at risk for potentially lethal respiratory viral infections. Cortez and colleagues studied whether RSV-IVIg provided sufficient RSV immune prophylaxis to prevent RSV pneumonia in 54 patients undergoing stem cell transplantation. (8) The authors reported a low incidence of RSV infection in the 54 RSV-IVIg patients, as well as in 31 patients not enrolled in the study and could not determine the preventive effect of RSV-IVIg. No other studies evaluating RSV immune prophylaxis in patients undergoing stem-cell transplantation were identified.

The RSV season typically occurs from November to April. Within the U.S., the inevitability of the RSV season is predicable, but the severity of the season and time of onset are variable from year to year and also between geographic areas within a given year. This has led to requests for either earlier or later immunoprophylaxis, or greater than 5 monthly doses. Nevertheless, as pointed out by Meissner and colleagues from the Centers of Disease Control and Prevention, “…this yearly and regional variation still occurs within the overall pattern of RSV outbreaks, usually beginning in November or December, peaking in January or February, and ending by March. Communities in the southern region tend to experience the earliest onset of RSV activity, and midwestern states tend to experience the latest onset, but community to community variation in timing precludes using either national or regional data to precisely predict individual community RSV outbreaks. The duration of the season for western and northeast regions typically occurs between that noted in the South and the Midwest.” The authors point out that the recommendation for 5 monthly doses is derived from the randomized studies of pavilizumab. A serum pavilizumab concentration of >30 μg/mL is the target level for protection, and in randomized studies the trough level of pavilizumab exceeded 30 μg/mL for at least 30 days after the fifth dose. This indicates that 5 monthly doses will provide substantially more than 20 weeks of protective serum antibody levels, covering most of the RSV season even with variation in season onset and end. (9)

2006–2007 Update

The policy was updated with a literature search using MEDLINE from September 2005 through July 2007. None of the articles identified lead to a change in the policy statements above. The focus of many of the reports has been on measuring changes in hospitalization rates following use of palivizumab in those patients at risk of developing RSV infections. As one example, Mitchell reported that RSV hospitalization was significantly reduced from 7.3% to 3.0% in high-risk infants eligible for palivizumab (odds ratio 2.53). (10) No new publications were identified related to use of RSV-IVIg. Recent AAP recommendations are included in a clinical practice guideline on bronchiolitis and the 2006 Red Book. (11, 12) The current policy statements agree with these AAP recommendations concerning prophylaxis.

2008-2009 Update

A search of the MEDLINE database was performed for the period August 2007 through August 2009.
The literature search identified professional society guidelines, two systematic reviews and a registry database review.

The American Academy of Pediatrics (AAP) has updated their guidelines regarding the use of immune prophylaxis for respiratory syncytial virus (RSV). The updated guidelines were published in the new AAP Red Book 2009 in the chapter on RSV. (13) The following is a summary, provided by the AAP, of the major changes to the guidelines:

 

1. 'Recommendations for initiation and termination of prophylaxis are modified to reflect current CDC descriptions of RSV seasonality in different geographic locations within the United States.
2. The recommendations remain unchanged for infants with congenital heart disease, chronic lung disease of prematurity and birth before 32 weeks' gestation.
3. Regardless of the month when the first dose is administered, the recommendation for a maximum number of 5 doses for all geographic areas is emphasized for infants with hemodynamically significant congenital heart disease, chronic lung disease of prematurity or birth before 32 weeks' gestation and for a maximum number of 3 doses for infants with a gestational age of 32 to 35 weeks without hemodynamically significant congenital heart disease or chronic lung disease.
4. Risk factors for severe RSV lower respiratory tract disease among infants born between 32 to 35 weeks' gestation have been modified to include only:
   a. Infant attends child care
   b. Siblings living in the household are less than 5 years of age
5. Infants 32 to 35 weeks' gestation age who are born within the 3 months before the onset of RSV season and throughout the RSV season will qualify for prophylaxis if they have at least one risk factor. Earlier recommendations required 2 of 5 risk factors.
6. Infants who qualify for prophylaxis in the 32 to 35 weeks' gestation age group should receive prophylaxis only until they reach 90 days of age or a maximum of 3 doses (whichever comes first). This is a change from the previous recommendation for 5 months of prophylaxis.
7. The AAP's definition of gestational age is used throughout this document. For example, 32 to 35 weeks' gestation is defined as 32 weeks, 0 days through 34 weeks, 6 days.”
   

In August 2009, the American Academy of Pediatrics (AAP) released a policy statement (including references and evidence grading) that supported their revised indications for the use of palivizumab for the prevention of respiratory syncytial virus infections. (14)

In commenting on their 2009 recommendations, the AAP position paper indicates, 'they [the 2009 AAP recommendations] specifically target infants in this [32 to less than 35 weeks' gestational age] with consistently identified risk factors for RSV hospitalization during the period of greatest risk, which is the first 3 months of life.”

A systematic review was conducted in the United Kingdom (15) to evaluate the effectiveness of palivizumab for the prevention of respiratory syncytial virus (RSV) in children. Two randomized controlled trials (RCTs) were identified. Prophylaxis with palivizumab for preterm infants without chronic lung disease (CLD) or children with CLD resulted in a 55% reduction in RSV hospital admission; 4.8% (48/1002) in the palivizumab group and 10.6% (53/500) in the no prophylaxis group. Prophylaxis with palivizumab was associated with a 45% reduction in hospitalization rate for RSV among children with congenital heart disease (CHD). Hospitalization rates for RSV were 5.3% (34/639) in the palivizumab group and 9.7% (63/648) in the no prophylaxis group. The authors concluded, prophylaxis with palivizumab is clinically effective for the reducing the risk of serious lower respiratory tract infection caused by RSV infection and requiring hospitalization in high-risk children.

Cohen et al. (16) evaluated the characteristics of patients (n =19,548) enrolled in The Palivizumab Outcomes Registry with congenital heart disease (CHD) over the four RSV seasons. The Palivizumab Outcomes Registry prospectively collected data on patients who received respiratory syncytial virus (RSV) prophylaxis with palivizumab during the 2000-2004 RSV seasons. The percentage of registry subjects with CHD increased from 4.8% (102/2116) in the first season to 11.4% (688/6050) in the last season. Across all four seasons, 1500 subjects with CHD were enrolled; 71% of whom had acyanotic CHD. The proportion with cyanotic CHD increased from 19.6% (20/102) in the 2000-2001 season to 37.5% (258/688) in the 2003-2004 season, while the proportion of all CHD in the registry more than doubled during this time. The cumulative RSV hospitalization rate was 1.9% among patients with CHD who received prophylaxis. Among subjects with cyanotic and acyanotic CHD, hospitalization rates were 2.6% and 1.6%, respectively. The authors concluded,…” the prospective data collected in the Palivizumab Outcomes Registry provides the largest published dataset available on infants with CHD receiving palivizumab; shows low hospitalization rates, use consistent with prelicensure clinical trial data and the revised American Academy of Pediatrics guidelines.”

A review article (17), discusses the development of a second- generation humanized monoclonal antibody (mAb), motavizumab, which is currently under study in phase III clinical trials and most recently, a third generation mAb, Numax-YTE.

Clinical Input Received through Physician Specialty Societies and Academic Medical Centers

In response to requests, input was received through three Physician Specialty Societies (seven responders) while this policy was under review. While the various Physician Specialty Societies and Academic Medical Centers may collaborate with and make recommendations during this process, through the provision of appropriate reviewers, input does not represent an endorsement or position statement by the Physician Specialty Society or Academic Medical Centers, unless otherwise noted. Most of the inputs received supported the 2009 AAP guidelines.

Summary
This policy supports the 2009 AAP recommendations. The policy statements have been revised to reflect these conclusions.

Technology Assessments, Guidelines, Position Statements
In 2003, the American Academy of Pediatrics (AAP) released a policy statement with revised indications for the use of palivizumab and respiratory syncytial virus immune globulin intravenous for the prevention of respiratory syncytial virus infections.(5)

In June 2009, the American Academy of Pediatrics (AAP) released updated guidelines regarding the use of immune prophylaxis for respiratory syncytial virus (RSV). (13) The updated guidelines were published in the new AAP Red Book 2009 in the chapter on RSV.

In August 2009, the American Academy of Pediatrics (AAP) released a policy statement (including references and evidence grading) with revised indications for the use of palivizumab for the prevention of respiratory syncytial virus infections. (14)

In 2008, Department of Public Health and Epidemiology, University of Birmingham,
Birmingham, UK, released a Health Technology Assessment, Immunoprophylaxis against respiratory syncytial virus (RSV) with palivizumab in children. (15) The authors concluded prophylaxis with palivizumab is clinically effective for reducing the risk of serious lower respiratory tract infection caused by RSV infection and requiring hospitalization in high-risk children.

References:

1. The PREVENT Study Group. Reduction of respiratory syncytial virus hospitalization among premature infants and infants with bronchopulmonary dysplasia using respiratory syncytial virus immune globulin prophylaxis. Pediatrics 1997; 99(1):93-9.
2. 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(3 pt 1):531-7.
3. American Academy of Pediatrics. Prevention of respiratory syncytial virus infections: indications for the use of palivizumab and update on the use of RSV-IGIV. Pediatrics 1998; 102(5):1211-6.
4. 2003 Red Book. Report of the Committee on Infectious Diseases. Elk Grove Village, IL, American Academy of Pediatrics, 2003. pp 523-8.
5. American Academy of Pediatrics Committee on Infectious Diseases and 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. Pediatrics 2003; 112(6 Pt 1):1442-6. Accessed May 2009.
6. Sondheimer HM, Cabalka AK, Feltes TF et al. Palivizumab (PV) reduces hospitalization due to respiratory syncytial virus in young children with serious congenital heart disease. Pediatr Cardiol 2002; 23(6):664.
7. Feltes TF, Cabalka AK, Meissner HC et al. Palivizumab prophylaxis reduces hospitalization due to respiratory syncytial virus in young children with hemodynamically significant congenital heart disease. J Pediatr 2003; 143(4):532-40.
8. Cortez K, Murphy BR, Almeida KN et al. Immune-globulin prophylaxis of respiratory syncytial virus infection in patients undergoing stem-cell transplantation. J Infect Dis 2002; 186(6):834-8.
9. Meissner HC, Anderson LJ, Pickering LK. Annual variation in respiratory syncytial virus season and decisions regarding immunoprophylaxis with palivizumab. Pediatrics 2004; 114(4):1082-4.
10. Mitchell I, Tough S, Gillis L et al. Beyond randomized controlled trials: a ”real life” experience of respiratory syncytial virus infection prevention in infancy with and without palivizumab. Pediatr Pulmonol 2006; 41(12):1167-74.
11. Subcommittee on Diagnosis and Management of Bronchiolitis. Diagnosis and managment of bronchiolitis. Pediatrics 2006; 118:1774-93.
12. American Academy of Pediatrics. Respiratory Syncytial Virus. Pickering LK, Baker CJ, Long SS et al, eds. Red Book: 2006 Report of the committee on infectious diseases. 27th ed. Elk Grove Village, IL American Academy of Pediatrics; 2006:560-6.
13. American Academy of Pediatrics. Respiratory Syncytial Virus. Red Book: 2009 Report of the committee on infectious diseases. Available at: http://aapredbook.aappublications.org/cgi/content/full/2009/1/3.110?ck=nck.
14. American Academy of Pediatrics. Committee on Infectious Diseases. Policy statement- modified recommendations for use of palivizumab for prevention of respiratory syncytial virus infections. Pediatrics 2009 Sept 7 [Epub ahead of print]. Accessible at: http://pediatrics.aappublications.org/cgi/reprint/peds.2009-2345v1?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=palivizumab&andorexactfulltext=and&searchid=
    1&FIRSTINDEX=0&sortspec=relevance&resourcetype=HWCIT
15. Wang D, Cummins C, Bayliss S et al. Immunoprophylaxis against respiratory syncytial virus (RSV) with palivizumab in children: a systematic review and economic evaluation. Health Technol Assess 2008; 12(36):iii, ix-x, 1-86.
16. Cohen SA, Zanni R, Cohen A et al.; Palivizumab Outcomes Registry Group. Palivizumab use in subjects with congenital heart disease: results from the 2000-2004 Palivizumab Outcomes Registry. Pediatr Cardiol 2008; 29(2):382-7.
17. Wu H, Pfarr DS, Losonsky GA et al. Immunoprophylaxis of RSV infection: advancing from RSV-IGIV to palivizumab and motavizumab. Curr Top Microbiol Immunol 2008; 317:103-2

 

 

Codes	Number	Description
CPT	90378	Respiratory syncytial virus immune globulin for intramuscular use, 50 mg, each
	90379	Respiratory syncytial virus immune globulin, human, for intravenous use
	96365	Intravenous infusion, for therapy, prophylaxis, or diagnosis (specify substance or drug); initial, up to 1 hour
	96366	Each additional hour (list separately in addition to code for primary procedure)
	96372	Therapeutic, prophylactic, or diagnostic injection (specify substance or drug); subcutaneous or intramuscular
ICD-9 Procedure	99.29	Injection or infusion of other therapeutic or prophylactic substance
ICD-9 Diagnosis	396	Diseases of mitral and aortic valves (code range)
	417	Other disease of pulmonary circulation (code range)
	424	Other diseases of endocardium (code range)
	425	Cardiomyopathy (code range)
	428	Heart failure (code range)
	491	Chronic bronchitis (code range)
	745	Bulbus cordis anomalies and anomalies of cardiac septal closure (code range)
	746	Other congenital anomalies of the heart (code range)
	747	other congenital anomalies of the circulatory system (code range)
	765.2	Weeks of gestation (5th digit indicates specific weeks of gestation)
	V07.2	Prophylactic immunotherapy
	V46.2	Supplemental oxygen
HCPCS	J1565	Injection, respiratory syncytial virus immune globulin, intravenous, 50mg (i.e., RespiGam)
Type of Service	Prescription Drug
Place of Service	Outpatient

 

---

Index
Palivizumab
RespiGam
Respiratory Syncytial Virus
RSV-IVIg
Synagis

---

 

Policy History

Date	Action	Reason
03/15/99	Add to Prescription Drug Section	New policy
11/10/99	Replace policy	New CPT code; policy unchanged
02/15/02	Replace policy	Policy updated with new references; policy statement unchanged
10/09/03	Replace policy	Policy revised; added indication for palivizumab for infants with hemodynamically significant heart disease and for those born between 32 and 35 weeks’ gestation with additional high risk factors. Policy based on AAP guidelines.
11/09/04	Replace policy	Literature review update for the period between June 2003 and September 2004; references added. RSV immune prophylaxis in stem-cell transplantation added to the investigational policy statement.
09/27/05	Replace policy	Policy updated with literature review; no change in policy statement. Information added regarding new liquid formulation of Synagis to Policy Guidelines section. Reference 9 added, discussing length and variation of RSV season.
12/14/05	Replace policy-coding update only	CPT coding updated
09/18/07	Replace policy	Policy updated with literature search through July 2007; treatment is considered investigational for children over 2 years of age. No changes in policy statements. Reference numbers 10–12 added.
12/13/07	Replace policy-correction only	Language “treatment…over 2 years of age” added to 9/18/07 policy history.
10/06/09	Replace policy	Policy updated with literature search from August 2007 through August 2009; clinical input reviewed; The policy statement has been modified to reflect the 2009 AAP; new reference numbers 13-17 added.