Rotavirus Medication

In most cases, no medication is required. Instead, attention should be directed to appropriate fluid intake. Antiemetic and antidiarrheal medications have some risks for children in the age group typically affected by rotavirus and should be avoided if possible. Some recent studies have used antidiarrheals in children with success, but this practice is not widely accepted.^{[14, 15]} Antidiarrheals are generally only recommended in cases of excessive or significantly prolonged diarrhea in which no other etiology has been determined.^[16] Antiemetics have also been used with some success for vomiting in children with gastroenteritis.^{[17, 18]} Antibiotics are not indicated if rotavirus gastroenteritis is suspected.^[19]

A rotavirus vaccine (RotaShield) was released for general use in 1998-1999. Despite promising initial results, RotaShield was withdrawn from the market in 1999 because of a causal relationship between the vaccine and several cases of intussusception. The risk was observed 3-14 days following administration of the first dose of the RotaShield vaccine in infants older than 3 months.

In February 2006, the United States Food and Drug Administration (FDA) approved RotaTeq. RotaTeq administration has been recommended for children as 3 separate oral doses at ages 2, 4, and 6 months.^{[3, 20]} In April 2008, the FDA approved Rotarix, another oral vaccine, for prevention of rotavirus gastroenteritis. Rotarix administration is currently recommended as 2 separate doses to patients at ages 2 and 4 months.^{[3, 20]} Rotarix was efficacious in a large study showing that it protected patients against severe rotavirus gastroenteritis as well as decreasing the rate of severe diarrhea or gastroenteritis of any cause.^[21]

Following the introduction of the rotavirus vaccine in 2006, a substantial decrease in hospitalization for diarrhea in children younger than 5 years has been observed.^[22]

US Centers for Disease Control and Prevention (CDC) researchers analyzed hospital admission rates for rotavirus-related diarrhea and other measures of healthcare utilization. Results were compared with 5 years of data before 2006 (ie, before the introduction of the rotavirus vaccine). During 2007-2008, hospitalization rates for rotavirus-associated diarrhea decreased by 75% and hospitalizations for diarrhea of any cause by 33% compared with the preceding 5-year period. Diarrhea-related incidence also decreased among age-matched unvaccinated children. The study estimated a $278 million reduction in hospital costs related to lower diarrhea-related admissions.^[22]

The minimum recommended age for the first dose of either RotaTeq or Rotarix vaccine is 6 weeks while the maximum age for the first dose of each is 14 weeks and 6 days.^{[3, 20]} The minimum time recommended between each dose of either vaccine is 4 weeks, and the maximum age for the final vaccine dose is 8 months and 0 days.^{[3, 20]} No maximum time between doses is specified by the Advisory Committee on Immunization Practices (ACIP).^[3]

Either rotavirus vaccine can be given before, simultaneously, or after patient receipt of any blood product including those with antibodies.^[3] In addition, a study involving 484 infants between the ages of 6-12 weeks were randomized to receive either Rotarix concurrently with their 2-, 4-, and 6-month vaccines or Rotarix separately at ages 3 and 5 months.^[23] The 2-, 4-, and 6-month vaccines were Haemophilus influenzae type b conjugate vaccine, 7-valent pneumococcal conjugate vaccine, and combined diphtheria-tetanus-acellular pertussis-hepatitis B-poliovirus vaccine. Serum antibodies were drawn one month after the third dose of the above vaccines, and it was determined that the antibody response was similar to all of the antigens in both study groups.^[23]

Currently, ACIP, World Health Organization (WHO) (supported also by a large Cochrane Review), and American Academy of Pediatrics (AAP) recommend proper administration and usage of the vaccinations.^{[3, 20, 24, 25]} ACIP and AAP recommend that the vaccination be completed using the same product.^{[3, 20]} However, if it is unknown which product was initially administered, the patient's vaccination series should still be completed with whichever vaccine is available.^{[3, 20]} ACIP and AAP do not directly state a preference for either RotaTeq or Rotarix.^{[3, 20]} Owing to the use of different clinical scales defining severe rotavirus gastroenteritis in the trials of RotaTeq and Rotarix, a direct comparison of effectiveness currently cannot be made between the 2 vaccines.^{[20, 26]}

Other vaccines may eventually be released in the United States, although a definitive date has not yet been set. In addition, side effects, such as intussusception, will be closely monitored for both RotaTeq and Rotarix and any other future rotavirus vaccines. Between February 3, 2006, to January 31, 2007, 28 cases of intussusception after RotaTeq administration have been reported to the US Food and Drug Administration (FDA).^[27] However, this number does not exceed the basal expected number of cases of intussusception in the general population. The cases have developed after the first, second, or third dose of RotaTeq. Fortunately, no deaths were reported, but 16 of the 28 case patients required hospitalization and surgery, while the other 12 patients were treated with a contrast or air enema.

A study involving more than 63,000 patients who received Rotarix versus placebo at ages 2 and 4 months showed a decreased risk of intussusception for those patients receiving Rotarix.^[21] The intussusception data were determined over a 31-day observation period (inpatient or outpatient) after each dose of the Rotarix vaccine, and this also included a 100-day surveillance period for all serious adverse events.^[21] Although more patients who received Rotarix were observed to have seizures or pneumonia-related deaths, this link has not been directly established to Rotarix.^{[21, 4]} In addition, the FDA is requiring the Rotarix manufacturer to report data on postmarketing safety that involves more than 40,000 patients.^[4]

Some studies from outside the United States have indicated a small but short-term increase in risks of developing intussusception following rotavirus vaccination. A study involving 615 patients over 69 hospitals in Mexico and Brazil reported an increased risk in intussusception with Rotarix in approximately 1 in 51,000-68,000 vaccinated infants.^[28] This increased risk was seen in Mexico on days 1 to 7 after administration of the first dose of Rotarix, and this increase was also seen to a lesser extent in Brazil on days 1 to 7 after the administration of the second dose of Rotarix.^[28] Another study from Australia showed an increased risk of intussusception within the first 3 weeks of receiving either RotaTeq or Rotarix in infants aged 1 month to less than 3 months, but they did not report an overall increase in the number of intussusception cases in infants aged 1-9 months after receiving the vaccine.^[29]

Conversely, studies within the United States have not shown similar results to the aforementioned Mexico/Brazil^[28] and Australian^[29] studies.^{[30, 31]} In addition, a serial cross-sectional analysis of American hospitals 4 years before vaccine reintroduction (1997, 2000, 2003, and 2006) and 1 year after vaccine reintroduction (2009) did not demonstrate an increase in the number of discharged patients younger than 1 year with a diagnosis of intussusception.^[32] Another study involving 14 Latin American countries that currently use either Rotarix or RotaTeq compared the overall risk-and-benefit ratio of the vaccinations.^[33] The authors of this study concluded that the benefits of the vaccination were clinically significant and easily outweighed the risks, including that of intussusception.^[33]

In June 2007, the FDA also revised the RotaTeq Adverse Reactions and Post-Marketing sections of the label to include Kawasaki disease, as 6 cases of Kawasaki disease were reported in the phase 3 clinical trial of RotaTeq.^[34] Five of the cases occurred in patients who received RotaTeq, while the other case was reported in a patient who received the placebo. Kawasaki disease has also been reported with Rotarix administration. In clinical trials, 17 cases of Kawasaki disease have been reported in those who received Rotarix, while 9 cases were reported in patients who received a placebo.^[3]

The risks versus benefits of the available vaccines need to be evaluated for each individual patient. Based upon the current available data, it is generally accepted that the benefits of the vaccines significantly outweigh the risks of the vaccines including that of intussusception.^{[28, 35, 36, 33]} With the introduction of RotaTeq and Rotarix, a significant amount of data have demonstrated the efficacy of the vaccines and overall decline of the rotavirus season not only in the United States but globally as well.^{[7, 9, 37, 38, 39, 40, 41]} This has also lead to reduced use of resources and a significantly decreased need for hospitalizations and outpatient or emergency department visits.^{[7, 42, 43]}

Although more research is necessary, nitazoxanide was shown to reduce rotavirus diarrhea and gastroenteritis in a small study of 38 patients between the ages of 5 months to 7 years.^[44] Time to resolution of illness was 31 hours for the group who received nitazoxanide compared with 75 hours for the placebo group. Nitazoxanide is currently approved by the FDA for treatment of diarrhea in children and adults with diarrhea from Giardia or Cryptosporidium.

Class Summary

Elicit active immunization to increase resistance to infection. Vaccines consist of microorganisms or cellular components, which act as antigens. Administration of the vaccine stimulates the production of antibodies with specific protective properties.

Rotavirus vaccine (RotaTeq, Rotarix)

Currently, 2 orally administered live-virus vaccines are marketed in the United States. Each is indicated to prevent rotavirus gastroenteritis, a major cause of severe diarrhea in infants.

RotaTeq is a pentavalent vaccine that contains 5 live reassortant rotaviruses and is administered as a 3-dose regimen against G1, G2, G3, and G4 serotypes, the 4 most common rotavirus group A serotypes. Also contains attachment protein P1A (genotype P[8]).

Rotarix protects against rotavirus gastroenteritis caused by G1, G3, G4, and G9 strains and is administered as a 2-dose series in infants between ages 6 and 24 wk.

Clinical trials found that each vaccine prevented 74-78% of all rotavirus gastroenteritis cases, nearly all severe rotavirus gastroenteritis cases, and nearly all hospitalizations due to rotavirus.