Pharmacology Update

Influenza Virus Vaccine Live, Intranasal (FluMist)

By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD

The FDA has approved the first nasally administered flu vaccine. This cold-adapted, temperature sensitive, attenuated, trivalent vaccine is manufactured by MedImmune Vaccine, Inc. and marketed by MedImmune and Wyeth under the name "FluMist." The nasal flu vaccine should be available this fall.

Indication

The vaccine is indicated for active immunization for the prevention of infection caused by influenza A and B. It is indicated for healthy children and adolescents 5-17 years of age and healthy adults 18-49 years of age. It is not indicated for children younger than 5 years of age or adults 50 years of age or older.1

Dosage

The recommended dose for children and adults aged 9-49 years is a single dose (0.5 mL) administered prior to exposure to influenza. For children 5-8 years, 2 doses are administered about 60 days apart (46-74 days). Approximately one-half of the dose (0.25 mL) is administered into each nostril.1 The 2003-2004 vaccine will contain A/New Caledonia/20/99 (H1N1), A/Panama/2007/99(H3N2) (A/Moscow/10/99-like), and B/Hong Kong/330/2001.1 The vaccine may be thawed in a refrigerator prior to administration but for no more than 24 hours.

Potential Advantages

The intranasal vaccine provides an alternative to the inactivated, parenterally administered vaccine.

Potential Disadvantages

The intranasal vaccine is not indicated in the very young (< 5 years of age) and the old (> 49 years of age). Two doses are required for children (5-8 years of age). In a large safety study, children < 5 years of age who received the nasal vaccine were found to have an increased rate of asthma and wheezing within 42 hours of vaccine administration.2 The vaccine should not be administered to individuals with chronic underlying medical conditions that may predispose them to severe influenza infection.3

Adverse events seen with intranasal flu vaccine were nasal congestion (7-11%) and fever (4%) in children, and score throat (10-15%) in adults.3 The vaccine requires storage in a non-frost-free freezer that maintains temperature of -15°C or less.

Comments

The first intranasal flu vaccine is a cold-adapted, temperature-sensitive, live attenuated vaccine. The cold-adaptive and temperature-sensitive process results in strains that replicate best at 25°C and are restricted in replication at 37°C. The phenotypes do not produce classic influenza viruses in animal models of human infections.1 Once administered, the attenuated viruses replicate in the nasopharynx and produce protective immunity. In 2 placebo-controlled trials in children (60-84 months of age) (n = 782), the vaccine had efficacy of about 87% based on cultured-confirmed influenza.1 The point estimates and 95% confidence interval were 87.4% (59.4%-97.9%) in one and 86.9% (70.8%-94.1%) in the other. In the Adult Effectiveness Study (n = 3637), the primary end point was reduction in the proportion of participants with one or more episodes of any febrile illness or, more specifically, severe febrile illness or febrile upper respiratory illness.1 No reduction in any febrile illness was observed, but a 19.5% (95% CI, 3-33.2%) reduction in severe febrile illness and a 23.7% (95% CI, 6.7-37.5%) reduction in febrile upper respiratory illness was noted.1 The intranasal vaccine was compared to an inactivated vaccine and placebo in a challenge study in 92 healthy adults. These volunteers were randomized to the 3 arms and then challenged with a previously susceptible wild-type influenza virus. Protective efficacy (based on laboratory-documented influenza) was 85% for the intranasal vaccine and 71% for the inactivated vaccine (not statistically different). Eighty percent of vaccine recipients shed at least one vaccine strain with a mean duration of 7.6 days. The public health significance is not clear. The probability of acquired transmitted virus is unlikely.1 The vaccine is generally well tolerated. The cost of the intranasal vaccine is $46 per dose. The cost of the inactivated influenza vaccine for the last season (02-03) was about $7 per dose.

Clinical Implications

The introduction of an intranasal influenza vaccine offers an alternative to the parenteral influenza vaccine, although at a much higher cost. It use is limited to use in the generally healthy population ages 5-49.

The vaccine is not indicated for those at highest risk, children younger than 5 years of age and adults older than 65 years of age.

Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; Asst. Clinical Professor of Medicine, University of California-San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Both are associate editors of Internal Medicine Alert.

References

1. FluMist Product Information. MedImmune Vaccine, Inc. June 2003.

2. FDA News. www.fda.gov/bbs/topics/NEWS/2003/NEW00913.html

3. Zangwill KM. Pediatr Infect Dis J. 2003;22(3):273-274.

4. Treanor JJ, et al. Vaccine. 2000;18:899-906.