RSV Management

Early Treatment of RSV

AGGRESSIVE MEDICAL INTERVENTION AND EARLY TREATMENT WITH VIRAZOLE® (RIBAVIRIN FOR INHALATION SOLUTION, USP) MAY REDUCE MORBIDITY FROM RSV DISEASE¹

• Virazole, a broad-spectrum antiviral with virustatic effects, inhibits RSV replication during the active replication phase.
• Achieves maximum antiviral effect when treatment is instituted within 3 days of onset of symptoms.

RSV TITER DURING LOWER RESPIRATORY TRACT (LTR) INFECTION²

TCID₅₀/ml=tissue culture infectious dose for 50% of the test units per milliliter.

Ribavirin should be administered as soon as an RSV diagnosis is confirmed -- preferably within 3 days of the onset of symptoms, before the viral load is at peak.

Adapted from McIntosh and Chanock²

Virazole® - Short-Term Benefits

IMPROVEMENT IN MEAN ARTERIAL OXYGEN PRESSURE IN INFANTS WITH UNDERLYING CARDIOPULMONARY DISEASE³

Based on mean duration of treatment 5 days
Adapted from Hall, et al.³

• Virazole® is the only antiviral agent approved for treatment of hospitalized infants and children with severe lower respiratory tract infections due to RSV
• Virazole® significantly improves arterial blood oxygenation, decreases illness severity, and decreases viral shedding³

RSV - Long-Term Impact

RSV BRONCHIOLITIS IN THE FIRST YEAR OF LIFE: IMPORTANT RISK FACTOR FOR ASTHMA DEVELOPMENT⁴

• The link between RSV bronchiolitis in infancy and bronchospastic airway disease later in life has been attributed to both a direct effect of the RSV infection upon bronchial tissue and an inherent genetic susceptibility to developing asthma⁵

RATES OF RECURRENT LOWER RESPIRATORY SYMPTOMS* IN INFANTS PREVIOUSLY HOSPITALIZED FOR AN INITIAL RSV INFECTION⁵

*Symptoms may include: dyspnea, chest wall retractions, rales, rhonchi, wheezing, and hyperinflation.

Virazole® - Long-Term Benefits

TWO-YEAR OUTCOME OF CHILDREN HOSPITALIZED WITH RSV LRT INFECTION AND ITS RELATION TO RIBAVIRIN (VIRAZOLE) TREATMENT¹⁴

AUTHORS: Fergie, et al. at Driscoll Children's Hospital in Corpus Christi, Texas

METHODS: Assessed the pulmonary health status at two years following hospital discharges of 30 VIRAZOLE-treated infants with RSV bronchiolitis (1994-1995 RSV season). Compared this status with 28 matched infants whose treatment at the same hospital excluded VIRAZOLE.

RESULTS: NUMBER OF PATIENTS CURRENTLY REQUIRING ASTHMA MEDICATIONS (SCHEDULED OR PRN)

CONCLUSION:

• Recurrent wheezing following RSV bronchiolitis has been associated with initial IgE response
• VIRAZOLE has been associated with a decrease in the development of RSV-specific IgE
• These results suggest a possible association between the use of VIRAZOLE and a decrease in the development of reactive airway disease after RSV infection

PROSPECTIVE (7-YEAR) FOLLOW-UP AND PULMONARY FUNCTIONS FROM PLACEBO-CONTROLLED RANDOMIZED TRIAL IN RSV BRONCHIOLITIS¹⁶

AUTHORS: Rodriguez, et al. at the Children's National Medical Center, Washington, D.C.

METHODS: Previously healthy, preterm infants and infants with chronic pulmonary disease were assessed for the prevalence of subsequent reactive airway disease (RAD) for up to 7 years

RESULTS: PULMONARY FUNCTION TESTS (PFTs)

• Following methacholine challenge, there was significantly less airway reactivity in VIRAZOLE-treated patients than in placebo patients (P=0.036)

CONCLUSION: Weighted severity scores suggest long-term beneficial effect of VIRAZOLE

Administration of Virazole®

DELIVERY SYSTEMS IN THE GENERAL PEDIATRIC WARD AND ICU: SMALL PARTICLE AEROSOL GENERATOR (SPAG^®-2)

• VIRAZOLE aerosol is delivered through an oxygen hood, oxygen tent, or face mask from the Small Particle Aerosol Generator (SPAG^®-2)

RECOMMENDED DOSING

• The standard treatment regimen is 20mg/mL given 18 hours per day for 3 to 7 days
• VIRAZOLE is part of a total treatment program that includes standard supportive respiratory care, correction of fluid imbalance, and nutritional management

Routine Procedures and Precautions

• Because VIRAZOLE is administered as an aerosol, direct exposure by the health professional should be avoided or minimized
• Pregnant women should be advised to avoid exposure to VIRAZOLE
• SPAG^® unit should be turned off 5 to 10 minutes prior to patient handling
• The use of a mask designed to block absorption of particles less than 1 micron in diameter provides added protection
• VIRAZOLE should be administered in well-ventilated rooms (at least six air changes per hour)

ADVERSE EVENTS PROFILE

Patients

• The most common adverse events attributed to VIRAZOLE given to infants include rash, mild bronchospasm and reversible skin irritation

Hospital staff

• Typical occupational exposure to VIRAZOLE, even without protective measures, results in undetectable or barely detectable amounts of drug in body fluid¹⁷
• Of 358 adverse events reported by 152 healthcare personnel exposed to VIRAZOLE, the most common were: headache (51% of reports), conjunctivitis (32%), rhinitis, nausea, rash, dizziness, pharyngitis, and lacrimation (10% to 20% each)
• Most signs and symptoms resolved themselves in minutes to hours

REFERENCES

1. Groothuis JR, Woodin KA, Katz R, et al.
Early ribavirin treatment of respiratory
syncytial viral infection in high-risk children. J
Pediatr. 1990;117:792-798.

2. McIntosh K, Chanock RM. Respiratory
syncytial virus. In: Fields BN, Knipe DM,
Chanock RM, et al, eds. Virology. 2nd ed.
New York, NY: Raven Press Ltd.;
1990:1045-1072.

3. Hall CB, McBride JT, Gala CL, Hildreth
SW, Schnabel KC. Ribavirin treatment of
respiratory syncytial viral infection in infants
with underlying cardiopulmonary disease.
JAMA. 1985;254:3047-3051.

4. Sigurs N, Bjarnason R, Sigurbergsson F,
Kjellman B, Bjorksten B. Asthma and
immunoglobulin E antibodies after respiratory
syncytial virus bronchiolitis: a prospective
cohort study with matched controls. Pediatrics.
1995;95(issue 4):500-505.

5. Long CE, McBride JT, Hall CB. Sequelae
of respiratory syncytial virus infections: a role
for intervention studies. Am J Respir Crit Care
Med. 1995;151:1678-1681.

6. Hall CB, Hall WJ, Gala CL, MaGill FB,
Leddy JP. Long-term prospective study in
children after respiratory syncytial virus
infection. J Pediatr. 1984;105:358-364.

7. Webb MSC, Henry RL, Milner AD, Stokes
GM, Swarbuck AS. Continuing respiratory
problems three and a half years after acute
viral bronchiolitis. Arch Dis Child.
1985;60:1064-1067.

8. Henry RL, Hodges IGC, Milner AD, Stokes
GM. Respiratory problems 2 years after acute
bronchiolitis in infancy. Arch Dis Child.
1983;58:713-716.

9. Gurwitz D, Mindorff C, Levinson H.
Increased evidence of bronchial reactivity in
children with a history of bronchiolitis. J
Pediatr. 1981;98:551-555.

10. Korppi M, Reijonen T, Poysa L,
Juntunen-Backman K. A 2- to 3-year outcome
after bronchiolitis. Am J Dis Child.
1993;147:628-631.

11. Sims DG, Downham MAPS, Gardner PS, Webb JKG, Weightmlan D. Study of 8-year-old children with a history of respiratory syncytial virus bronchiolitis in infancy . BMJ 1978;1:11-14.

12. Pullan CR, Hey EN. Wheezing, asthma,
and pulmonary dysfunction 10 years after
infection with respiratory syncytial virus in
infancy. BMJ. 1982;284:1665-1669.

13. Mok JYQ, Simpson H. Symptoms, atopy,
and bronchial reactivity after lower respiratory
infection in infancy. Arch Dis Child.
1984;59:299-305.

14. Fergie JE, Purcell K, Wanat DM, Seidel S. The effect of ribavirin on the two year outcome of children hospitalized with respiratory syncytial virus. Presented at the Annual Meeting of the Pediatric Academic Societies; May 4, 1998; New Orleans, LA.

15. Rosner IK, Welliver RC, Edelson PJ, Geraci-Ciardullo K, Sun M. Effect of ribavirin therapy on respiratory syncytial virus-specific IgE and IgA responses after infection. J Infect Dis. 1987;155:1043-1047.

16. Rodriguez WJ, Arrobio J, Fink R, Kim HW,
Milburn C. Prospective (7 yrs) follow up (FU)
and pulmonary functions (PFT) from a placebo
(P) controlled randomized trial of ribavirin (R)
in RSV bronchiolitis (B). Pediatr Res. May
1996. Abstract.

17. Linn WS, Gong H Jr, Anderson KR, Clark KW, Shamoo DA. Occupational exposures of health care workers to ribavirin aerosol: a pharmacokinetic study. Arch Environ Health. 1995;50(6).