Pharmacology Update

Rotavirus Vaccine, Live, Oral, Pentavalent (Rota Teq®)

By William T. Elliott, MD, FACP, and James Chan, PhD, PharmD Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; Assistant Clinical Professor of Medicine, University of California, San Francisco; Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Drs. Chan and Elliott report no financial relationships to this field of study.

The FDA has approved a live, oral, vaccine for the prevention of rotavirus gastroenteritis in infants. An earlier vaccine approved for this indication (RotaShield®) was withdrawn in 1999 due to an increased risk of intussusception. In a large trial, of more than 70,000 children, risk of intussusception was not observed with the new vaccine. The new oral rotavirus vaccine will be marketed by Merck & Co., Inc. as Rota Teq®.

Indications

Rotavirus vaccine is indicated for the prevention of rotavirus gastroenteritis in infants and children (ages, 6-32 weeks) caused by serotypes G1, G2, and G4.1

Dosage

Rotavirus vaccine liquid is given orally, as 3 doses, starting at 6 to 12 weeks of age. The subsequent doses are given at 4 to 10 week intervals. The third dose should not be given after 32 weeks of age. There are no restrictions on food or liquid intake before or after the vaccine. Although the vaccine should not be mixed with other vaccines or solutions1 it may be co-administered with other commonly used infant vaccines. Oral polio vaccine was not permitted in the clinical trials. There are insufficient data regarding potential interference with pertussis vaccine.1

Potential Advantages

Rotavirus vaccine has been shown to reduce all grades of severity of gastroenteritis, hospitalization, and emergency department visits occurring 14 or more days after the third dose through the first rotavirus season post vaccination as well as any time after the first dose through the first season.1,2

Potential Disadvantages

The vaccine strains do not grow well in the intestine and there is generally no shedding in the stool. Therefore 3 doses are required to achieve sufficient titers.3 As with other vaccines, rotavirus vaccine does not provide complete protection in all recipients.

Comments

RotaTeq is an oral, live pentavalent (G1, G2, G3, G4 and P1[8]) WC3 human-bovine reassortant rotavirus vaccine. The parent strains were isolated from human and bovine hosts. Each reassortant virus contains a single gene encoding a major outer capsid protein from the most common human serotypes.2 In 3 placebo-controlled trials (n = 72,324), study participants who received 3 doses of rotavirus vaccine had a reduction in any grade of severity of gastroenteritis by about 72.5%-74%, reduction in severe gastroenteritis by 98%-100%, and reduction in hospitalization by 95.8% in the first rotavirus season. For participants who received at least one dose, reduction of severe gastroenteritis and hospitalization was 96.4%-100% and 94.7%, respectively. Gastroenteritis of any severity was reduced by about 60%. Gastroenteritis was defined as 3 or more watery or looser-than-normal stools within a 24-hour period or forceful vomiting along with the detection of rotavirus antigen.2 Severity was determined by a clinical scoring system taking into account the intensity and duration of symptoms of fever, vomiting, diarrhea, and behavioral changes. The frequency of adverse events such as elevated temperature, vomiting, diarrhea, and irritability were generally no different between the vaccine recipients and placebo recipients. Some adverse events had a higher incidence with the vaccine such as diarrhea (24.1% vs 21.3%), vomiting (15.2% vs 13.6%), otitis media (14.5% vs 13.0%), and nasopharyngitis (6.9% vs 5.8%). Seizure was reported in 33 of 36,150 vaccine recipients compared to 18 of 35,556 placebo recipients. The vaccine does not appear to increase the risk of intussusceptions based on clinical trials. This serious adverse event will be monitored in post-licensure studies.4 The wholesale cost of Rota Teq is $66.50 per dose. 

Clinical Implications

Rotavirus is the leading cause of childhood gastroenteritis and death. It accounts for about one-half million deaths and one third of hospitalizations worldwide.5 The Center of Disease Control and Prevention estimated that approximately 55,000 hospitalizations annually in the United States were due to rotavirus. Rota Teq appears to be a safe and effective vaccine.

References

1. RotaTeq Product Information. Merck & Co., Inc. February 2006.

2. Vesikari T, et al. Safety and efficacy of a pentavalent human-bovine (WC3) reassortant rotavirus vaccine. N Engl J Med. 2006;354:23-33.

3. Glass RI, Parashar UD. The promise of new rotavirus vaccines. N Engl J Med. 2006;354:75-77.

4. FDA News. www.fda.gov/bbs/topics/news/2006/NEW01307.html.

5. Parahar UD, et al. Global illness and deaths caused by rotavirus disease in children. Emerg Infect Dis. 2003;9: 565-572.