Each year in the United States, respiratory syncytial virus (RSV) causes hospitalizations in 2% to 3% of infants in the first 12 months of life. Although RSV infection is largely self-limiting, certain populations may be at an increased risk for complications.
Palivizumab (Synagis) (MedImmune; Gaithersburg, MD) is a humanized monoclonal antibody that is produced by recombinant deoxyribonucleic acid (DNA) technology. Palivizumab (Synagis) was licensed in June 1998 by the US Food and Drug Administration (FDA) and "is indicated for the prevention of serious lower respiratory tract disease caused by RSV in children at high risk of RSV disease.” In the absence of a specific definition of “high risk” by the FDA, the American Academy of Pediatrics (AAP) has endeavored to provide pediatricians and other professional providers with more precise guidance for determining who is at increased risk since palivizumab (Synagis) was first licensed. The FDA label has subsequently been updated to better define the
appropriate pediatric population to receive palivizumab (Synagis).
Palivizumab (Synagis) is indicated for use in high-risk infants and children younger than 24 months of age with chronic lung disease (CLD) of prematurity, which is defined by the AAP as an individual with a gestational age less than 32 weeks, 0 days, who required more than 21% oxygen for at least the first 28 days after birth.
Infants with neuromuscular disease or congenital anomaly that impairs the ability to clear secretions from the upper airway because of ineffective cough are known to be at risk for a prolonged hospitalization related to lower respiratory tract infection and, therefore, may be considered for prophylaxis with palivizumab (Synagis) during the first year of life.
Among the patient-specific parameters, the AAP recommends the prophylactic use of palivizumab (Synagis) in selected individuals under 12 months of age who are born within 12 months of onset of the RSV season and have hemodynamically significant congenital heart disease (CHD). The recommendation suggests that prophylactic use of palivizumab (Synagis) should be administered for the following conditions:
- Acyanotic CHD in individuals who are receiving medication to control congestive heart failure and will require cardiac surgical procedures
- Moderate-to-severe pulmonary hypertension
- Cyanotic CHD, after consultation with a pediatric cardiologist
The AAP also recommends a postoperative dose of palivizumab (Synagis) for infants or children younger than 24 months who are currently receiving palivizumab (Synagis) and have undergone cardiac transplantation or a surgical procedure that uses cardiopulmonary bypass. This recommendation is based on evidence suggesting that there is a significant intraoperative loss of serum palivizumab (Synagis) levels.
The following groups of infants with CHD are not at increased risk of RSV infection 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 for the condition
- Children in the second year of life
The AAP has stated that routine use of palivizumab (Synagis) prophylaxis in patients with cystic fibrosis, including neonates diagnosed with cystic fibrosis by newborn screening, is not recommended unless other indications are present.
Palivizumab (Synagis) prophylaxis has not been evaluated in randomized trials in the immunosuppressed population; however, the AAP suggests that children with severe immunodeficiencies may benefit from immune prophylaxis.
Lastly, the AAP recommends prophylaxis with palivizumab (Synagis) for those born prematurely at less than 29 weeks gestational age.
There are limited data to suggest a slight increase in RSV hospitalization rates among children with Down syndrome. However, data are insufficient to justify a recommendation for routine use of prophylaxis with palivizumab (Synagis) in children with Down syndrome unless qualifying heart disease, CLD, airway clearance issues, or prematurity (<29 weeks, 0 days gestation) is present.
Hospitalization rates attributable to RSV decrease during the second RSV season for all children. A second season of palivizumab prophylaxis is recommended only for preterm infants born at <32 weeks, 0 days gestation who required at least 28 days of oxygen after birth and who continue to require supplemental oxygen, diuretics, or chronic systemic corticosteroid therapy, within 6 months of the start of the second RSV season.
If any infant or young child receiving monthly palivizumab prophylaxis experiences a breakthrough RSV hospitalization, monthly prophylaxis should be discontinued because of the extremely low likelihood of a second RSV hospitalization in the same season (<0.5%).
RSV SEASON AND IMMUNE PROPHYLAXIS
According to peer-reviewed literature, five monthly doses of palivizumab at 15 mg/kg per dose will provide more than 6 months (>24 weeks) of serum palivizumab concentrations above the desired level for most children; therefore, administration of more than five monthly doses is not recommended within the continental United States. For qualifying infants who require five doses, a dose beginning in November and continuation for a total of five monthly doses will provide protection for most infants through 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, which will provide protection for most infants through March. If prophylaxis is initiated in December, the fifth and final dose should be administered in April, which will provide protection for most infants through May.
Sporadic RSV infections occur throughout the year in most geographic locations. During times of low RSV prevalence (regardless of proportion of positive results), prophylaxis with palivizumab provides the least benefit because of the large number of children who must receive prophylaxis to prevent one RSV hospitalization.
Prophylaxis is not recommended for primary asthma prevention or to reduce subsequent episodes of wheezing.
Palivizumab prophylaxis is not recommended for prevention of health care–associated RSV disease.
