• Introduction
• Candidates for Synagis® or RespiGam®: 2003-2004 RSV Season
• Health Care Provider Information Sheet
• Adverse Effects
• Parent Information Sheet
• Author

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Based on our local RSV disease experience, FDA indications, and published study results, the following children would most likely will benefit from prophylaxis against serious RSV-lower respiratory tract illnesses:

• Infants who have conditions that adversely affect respiratory function and who have required medical therapy (e.g. oxygen, diuretics, corticosteroids, bronchodilators, mechanical ventilation, etc.) within the last 6 months and who are <2 years of age at the onset of the RSV season.
• Infants born at <28 weeks gestation who are <12 months at the onset of the RSV season.
• Infants born at 28-32 weeks gestation who are <6 months at the onset of the RSV season.
• Infants born at 32-35 weeks gestation who are <6 months old at the onset of the RSV season and have at least two risk factors (exposure to environmental air pollutants; child care attendance; school-aged siblings; congenital abnormalities of the airways; severe neuromuscular disease; persistent hospitalization on an inpatient ward; Native American Indian; severe social disarray such as homeless parents, illicit drug use, etc.).
• Infants <2 years of age at the onset of the RSV season with hemodynamically significant cyanotic or acyanotic congenital heart disease.

• The onset of the RSV season will be considered December 1, 2003. The initiation of Synagis® will occur December 1, 2003 depending on location in Washington state and evidence of early RSV disease.
• The end of the RSV season will be determined locally based on the week that RSV inpatient isolates represent 10% of the peak total weekly isolates.
• RSV-IGIV (RespiGam®) remains an option instead of palivizumab (Synagis®) in selected circumstances where a clinician decides that a polyclonal product offers a significant advantage to a selected candidate over a monoclonal product.

Administration of either RespiGam® or Synagis® to any patient should be a joint decision made by the parents and the primary care provider after consideration of the risks, benefits, and cost.

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Health Care Provider Information Sheet



Deccember, 2003
Prepared by Dr. Greg Redding and Dr. Dennis Mayock

Two medications are currently FDA-approved for the prevention of RSV lower respiratory tract disease in high risk infants and children. RespiGam® is a sterile human-derived immunoglobulin G liquid preparation containing neutralizing antibody to Respiratory Syncytial Virus (RSV). Synagis® is a humanized monoclonal antibody supplied as a sterile lyophilized powder.

Candidates for prophylaxis against RSV include:

• Infants who have conditions that adversely affect respiratory function and who have required medical therapy (e.g. oxygen, diuretics, corticosteroids, bronchodilators, mechanical ventilation, etc.) within the last 6 months and who are <2 years of age at the onset of the RSV season.
• Infants born at <28 weeks gestation who are <12 months at the onset of the RSV season.
• Infants born at 28-32 weeks gestation who are < 6 months at the onset of the RSV season.
• Infants born at 32-35 weeks gestation who are <6 months old at the onset of the RSV season and have at least two risk factors (exposure to environmental air pollutants; child care attendance; school-aged siblings; congenital abnormalities of the airways; severe neuromuscular disease; persistent hospitalization on an inpatient ward; Native American Indian; severe social disarray such as homeless parents, illicit drug use, etc.).
• Infants <2 years of age at the onset of the RSV season with hemodynamically significant cyanotic or acyanotic congenital heart disease.

Additional consensus considerations regarding RSV prevention during the 2003-2004 RSV season:

• The onset of the RSV season will be considered December 1, 2003.
• The end of the RSV season will be determined locally based on the week that RSV inpatient isolates represent 10% of the peak total weekly isolates.
• RSV-IGIV (RespiGam) remains an option instead of palivizumab (Synagis) in selected circumstances where a clinician decides that a polyclonal product offers a significant advantage to a selected candidate over a monoclonal product.
In a double-blind placebo-controlled multi-center clinical trial (Prevent Study, Pediatrics 1997;99:93-99), RespiGam® reduced RSV hospitalizations by 41%, RSV hospital days by 53%, RSV hospital days on oxygen therapy by 60%, and reduced all respiratory-related hospitalizations by 46% compared to the control group. On the basis of this data, the FDA approved its use in January 1996. In a double-blind placebo-controlled multi-center clinical trial (Impact Study, Pediatrics 1998;102:531-537), Synagis® reduced RSV hospitalizations by 55%. In infants with prematurity, but without BPD, the reduction in RSV hospitalization was 78%.

RespiGam® and Synagis® are neither indicated nor approved for treatment of RSV respiratory infections; only for the prevention of serious RSV infections. Neither drug will prevent RSV-related upper respiratory tract infections.

RespiGam® is administered intravenously on a monthly basis at a dose of 750 mg/kg (15 mL/kg per dose). Each intravenous administration is accomplished over a 3-4 hour period. During this time, vital signs and oxy-hemoglobin saturation are monitored to assure tolerance and safety of administration.

Synagis® is administered intramuscularly on a monthly basis at a dose of 15 mg/kg (0.15 mL/kg per dose).

RespiGam® is derived from pooled human plasma and screened for high titers of neutralizing antibodies against RSV. Plasma is processed using a precipitation procedure and solvent detergent procedure to specifically inactivate blood-borne viruses including HIV-1, HIV-2, Hepatitis B and Hepatitis C viruses. As with other gamma globulin preparations, it is possible that RespiGam® contains as yet unidentified blood-borne pathogens. RespiGam® contains no preservatives.

Synagis® is a humanized monoclonal antibody produced by recombinant DNA technology and contain 5% murine antibody sequences and 95% human antibody sequences. There is no risk of blood-borne transmission. Synagis® contains no preservatives.

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Adverse Effects

The side effects of RespiGam® include fever in 5% and respiratory distress in 2% of recipients due to fluid overload as a result of the volume delivered. The latter has been successfully managed by slowing the intravenous infusion and/or administering diuretic medication. Anaphylaxis occurs in <1% of patients receiving RespiGam®.

The side effects of Synagis® include local irritation (swelling, pain, erythema) at the injection site. No anaphylaxis has been reported due to Synagis®.

As with other immunoglobulin preparations, RespiGam® may interfere with immune responses to live virus vaccines, such as measles, mumps, and rubella. If such a vaccine is given during or within 10 months of RespiGam® infusions, re-immunization is recommended. Responses to non-live virus vaccines (e.g. DPT) are not influenced by RespiGam®.

Synagis® has no effect on immune responses to live virus vaccines.

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RSV Respiratory Infections and Prevention with Synagis® and RespiGam®

Parent Information Sheet


December, 2003
Prepared by Dr. Greg Redding and Dr. Dennis Mayock

Two medications are available to high risk infants for the prevention of serious RSV infection. Respiratory infections caused by viruses are common during the winter months. One particular virus, named Respiratory Syncytial Virus (abbreviated RSV), causes respiratory infections during the winter every year. RSV infections can cause upper respiratory infections, like a cold, or it can cause more serious lower respiratory infections, such as pneumonia. RSV infections are particularly severe in infants and young children with lung problems. Up to 50% of infants who are born prematurely or with lung conditions who become infected with RSV need to be hospitalized. RSV is a very common virus, 50% of children will be infected with RSV during their first year of life. By age 5 all children will have been infected with the virus at least once. When children become infected with a virus their bodies produce antibodies (proteins) to fight the infection.

One medication called RespiGam® is similar to standard immune globulins which are commonly used to help patients fight infections. The only difference is that this immune globulin contains high levels of RSV antibodies to help fight RSV infection. RespiGam® is made from blood (plasma) collected from many donors. The plasma is processed chemically to inactivate viruses that can be found in human plasma, such as HIV or hepatitis B and C viruses. These processes minimize the risk of patients acquiring a blood-borne virus, either known viruses such as HIV or hepatitis, or currently unknown viruses.

In research studies, RespiGam®, was shown to reduce the incidence of hospitalization for RSV infection in high risk infants by 41%. In children who were hospitalized for RSV infection, the length of hospitalization was reduced by 53%. RespiGam® also reduced the incidence of hospitalizations for non-RSV respiratory causes.

RespiGam® must be given by vein every month (usually for 5 months) during the RSV season. It is given slowly as an infusion which lasts 3-4 hours. The amount of fluid given to the child over this time is 15 mL/kg. Respiratory distress (breathing difficulties) was reported in 2% of the children receiving RespiGam®. These breathing difficulties were treated by slowing down the rate of infusion or by giving diuretics, medicines which help the child make more urine. Other side effects reported included vomiting and nausea, wheezing, and rash. Allergic reactions (low blood pressure, low blood oxygen levels, severe respiratory distress) to RespiGam® were rare. As with any medicine, unanticipated side effects can occur.

RespiGam® can interfere with some routine childhood vaccinations that are given during the first two years of childhood. If a child is vaccinated for measles, mumps, and German measles (rubella) within 10 months of receiving a RespiGam® infusion, the child should be revaccinated.

The second medication is called Synagis®. It is an antibody against respiratory syncytial virus that is made by recombinant DNA technology. This manufacturing process avoids the potential for blood-borne diseases. In research studies. Synagis® was shown to reduce the incidence of hospitalization for RSV infection in high risk infants by 55%. The length of RSV hospitalization was also reduced.

Synagis® is given by injection in the thigh muscle monthly during the RSV season. No significant adverse effects were found.

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Author


This document was created and prepared for this Web site by:

• Dennis E. Mayock, M.D.
  University of Washington School of Medicine Children's Hospital and Regional Medical Center
  Seattle, Washington



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