Rotarix

Rotarix is a vaccine used to prevent rotavirus in your baby. It comes in liquid form and is administered by a healthcare professional.

Rotarix comes in liquid form to be administered orally (by mouth) by a healthcare professional. It is administered using a prefilled applicator.

Common side effects include cough, runny nose, and fussiness.

Contact your doctor if you miss a booster dose or if you get behind schedule. Your child may not be protected from rotavirus if the doses aren't given within 10 weeks of each other. Be sure your child receives all recommended doses of this vaccine.

Rotavirus vaccine live is used to prevent infants and children from getting a rotavirus stomach infection. It works by causing your body to produce its own protection (antibodies) against the virus.

Rotavirus is a serious infection that causes diarrhea and vomiting. It may also cause severe dehydration in infants and children.

This vaccine is to be administered only by or under the supervision of your child's doctor.

Rotarix is available as a vial of lyophilized vaccine to be reconstituted with a liquid diluent in a prefilled oral applicator.

Each 1-mL dose contains a suspension of at least 106.0 median Cell Culture Infective Dose (CCID50) of live, attenuated human G1P[8] rotavirus after reconstitution.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a vaccine cannot be directly compared to rates in the clinical trials of another vaccine, and may not reflect the rates observed in practice. As with any vaccine, there is the possibility that broad use of Rotarix could reveal adverse reactions not observed in clinical trials.

Solicited and unsolicited adverse events, serious adverse events and cases of intussusception were collected in 7 clinical studies. Cases of intussusception and serious adverse events were collected in an additional large safety study. These 8 clinical studies evaluated a total of 71,209 infants who received Rotarix (N = 36,755) or placebo (N = 34,454). The racial distribution for these studies was as follows: Hispanic 73.4%, white 16.2%, black 1.0%, and other 9.4%; 51% were male.

Solicited Adverse Events: In 7 clinical studies, detailed safety information was collected by parents/guardians for 8 consecutive days following vaccination with Rotarix (i.e., day of vaccination and the next 7 days). A diary card was completed to record fussiness/irritability, cough/runny nose, the infant’s temperature, loss of appetite, vomiting, or diarrhea on a daily basis during the first week following each dose of Rotarix or placebo. Adverse events among recipients of Rotarix and placebo occurred at similar rates (Table 1).

Total vaccinated cohort = all vaccinated infants for whom safety data were available.

N = number of infants for whom at least one symptom sheet was completed.

aDefined as crying more than usual.

bData not collected in 1 of 7 studies; Dose 1: Rotarix N = 2,583; placebo N = 1,897; Dose 2: Rotarix N = 2,522; placebo N = 1,863.

cDefined as temperature ≥100.4°F (≥38.0°C) rectally or ≥99.5°F (≥37.5°C) orally.

dDefined as eating less than usual.

Unsolicited Adverse Events: Infants were monitored for unsolicited serious and non-serious adverse events that occurred in the 31-day period following vaccination in 7 clinical studies. The following adverse events occurred at a statistically higher incidence (95% CI of Relative Risk excluding 1) among recipients of Rotarix (N = 5,082) as compared with placebo recipients (N = 2,902): irritability (Rotarix 11.4%, placebo 8.7%) and flatulence (Rotarix 2.2%, placebo 1.3%).

Serious Adverse Events (SAEs): Infants were monitored for serious adverse events that occurred in the 31-day period following vaccination in 8 clinical studies. Serious adverse events occurred in 1.7% of recipients of Rotarix (N = 36,755) as compared with 1.9% of placebo recipients (N = 34,454). Among placebo recipients, diarrhea (placebo 0.07%, Rotarix 0.02%), dehydration (placebo 0.06%, Rotarix 0.02%), and gastroenteritis (placebo 0.3%, Rotarix 0.2%) occurred at a statistically higher incidence (95% CI of Relative Risk excluding 1) as compared with recipients of Rotarix.

Deaths: During the entire course of 8 clinical studies, there were 68 (0.19%) deaths following administration of Rotarix (N = 36,755) and 50 (0.15%) deaths following placebo administration (N = 34,454). The most commonly reported cause of death following vaccination was pneumonia, which was observed in 19 (0.05%) recipients of Rotarix and 10 (0.03%) placebo recipients (Relative Risk: 1.74, 95% CI: 0.76, 4.23).

Intussusception: In a controlled safety study conducted in Latin America and Finland, the risk of intussusception was evaluated in 63,225 infants (31,673 received Rotarix and 31,552 received placebo). Infants were monitored by active surveillance including independent, complementary methods (prospective hospital surveillance and parent reporting at scheduled study visits) to identify potential cases of intussusception within 31 days after vaccination and, in a subset of 20,169 infants (10,159 received Rotarix and 10,010 received placebo), up to one year after the first dose.

No increased risk of intussusception following administration of Rotarix was observed within a 31-day period following any dose, and rates were comparable to the placebo group after a median of 100 days (Table 2). In a subset of 20,169 infants (10,159 received Rotarix and 10,010 received placebo) followed up to one year after dose 1, there were 4 cases of intussusception with Rotarix compared with 14 cases of intussusception with placebo [Relative Risk: 0.28 (95% CI: 0.10, 0.81)]. All of the infants who developed intussusception recovered without sequelae.

 CI = Confidence Interval.

aMedian duration after dose 1 (follow-up visit at 30 to 90 days after dose 2).

Among vaccine recipients, there were no confirmed cases of intussusception within the 0- to 14-day period after the first dose (Table 3), which was the period of highest risk for the previously licensed oral live rhesus rotavirus-based vaccine.1

Kawasaki Disease: Kawasaki disease has been reported in 18 (0.035%) recipients of Rotarix and 9 (0.021%) placebo recipients from 16 completed or ongoing clinical trials. Of the 27 cases, 5 occurred following Rotarix in clinical trials that were either not placebo-controlled or 1:1 randomized. In placebo-controlled trials, Kawasaki disease was reported in 17 recipients of Rotarix and 9 placebo recipients [Relative Risk: 1.71 (95% CI: 0.71, 4.38)]. Three of the 27 cases were reported within 30 days post-vaccination: 2 cases (Rotarix = 1, placebo = 1) were from placebo-controlled trials [Relative Risk: 1.00 (95% CI: 0.01, 78.35)] and one case following Rotarix was from a non-placebo-controlled trial. Among recipients of Rotarix, the time of onset after study dose ranged 3 days to 19 months.

Postmarketing Experience

The risk of intussusception with Rotarix has been evaluated in a hospital-based Postmarketing Active Surveillance Study (PASS) in a birth cohort of infants in Mexico. An interim analysis of this study suggests an increased risk of intussusception in the 31-day period following administration of the first dose of Rotarix [Relative Risk: 1.8 (99% CI: 1.0, 3.1)]. In this study, within the 31-day period after the first dose, most cases of intussusception occurred in the first 7 days.

Applying the relative risk observed from the interim analysis of the PASS in Mexico to estimates of background rates of intussusception in the US would approximate 0 to 4 additional cases of intussusception hospitalizations per 100,000 vaccinated infants within the 31 days after the first dose. In the first year of life, the background rate of intussusception hospitalizations in the US is approximately 34 per 100,000 infants.2

Worldwide passive postmarketing surveillance data also suggest that most cases of intussusception reported following Rotarix occur in the 7-day period after the first dose.

The following adverse events have been reported since market introduction of Rotarix. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to vaccination with Rotarix.

Gastrointestinal Disorders: Intussusception (including death), hematochezia, gastroenteritis with vaccine viral shedding in infants with Severe Combined Immunodeficiency Disease (SCID).

Blood and Lymphatic System Disorders: Idiopathic thrombocytopenic purpura.

Vascular Disorders: Kawasaki disease.

General Disorders and Administration Site Conditions: Maladministration.

Efficacy Studies

The data demonstrating the efficacy of Rotarix in preventing rotavirus gastroenteritis come from 24,163 infants randomized in two placebo-controlled studies conducted in 17 countries in Europe and Latin America. In these studies, oral polio vaccine (OPV) was not coadministered; however, other routine childhood vaccines could be concomitantly administered. Breast-feeding was permitted in both studies.

A randomized, double-blind, placebo-controlled study was conducted in 6 European countries. A total of 3,994 infants were enrolled to receive Rotarix (n = 2,646) or placebo (n = 1,348). Vaccine or placebo was given to healthy infants as a 2-dose series with the first dose administered orally from 6 through 14 weeks of age followed by one additional dose administered at least 4 weeks after the first dose. The 2-dose series was completed by 24 weeks of age. For both vaccination groups, 98.3% of infants were white and 53% were male.

The clinical case definition of rotavirus gastroenteritis was an episode of diarrhea (passage of 3 or more loose or watery stools within a day), with or without vomiting, where rotavirus was identified in a stool sample. Severity of gastroenteritis was determined by a clinical scoring system, the Vesikari scale, assessing the duration and intensity of diarrhea and vomiting, the intensity of fever, use of rehydration therapy or hospitalization for each episode. Scores range from 0 to 20, where higher scores indicate greater severity. An episode of gastroenteritis with a score of 11 or greater was considered severe.5

The primary efficacy endpoint was prevention of any grade of severity of rotavirus gastroenteritis caused by naturally occurring rotavirus from 2 weeks after the second dose through one rotavirus season (according to protocol, ATP). Other efficacy evaluations included prevention of severe rotavirus gastroenteritis, as defined by the Vesikari scale, and reductions in hospitalizations due to rotavirus gastroenteritis and all cause gastroenteritis regardless of presumed etiology. Analyses were also done to evaluate the efficacy of Rotarix against rotavirus gastroenteritis among infants who received at least one vaccination (total vaccinated cohort, TVC).

Efficacy of Rotarix against any grade of severity of rotavirus gastroenteritis through one rotavirus season was 87.1% (95% CI: 79.6, 92.1); TVC efficacy was 87.3% (95% CI: 80.3, 92.0). Efficacy against severe rotavirus gastroenteritis through one rotavirus season was 95.8% (95% CI: 89.6, 98.7); TVC efficacy was 96.0% (95% CI: 90.2, 98.8) (Table 4). The protective effect of Rotarix against any grade of severity of rotavirus gastroenteritis observed immediately following dose 1 administration and prior to dose 2 was 89.8% (95% CI: 8.9, 99.8).

Efficacy of Rotarix in reducing hospitalizations for rotavirus gastroenteritis through one rotavirus season was 100% (95% CI: 81.8, 100); TVC efficacy was 100% (95% CI: 81.7, 100) (Table 4). Rotarix reduced hospitalizations for all cause gastroenteritis regardless of presumed etiology by 74.7% (95% CI: 45.5, 88.9).

RV GE = rotavirus gastroenteritis; CI = Confidence Interval.

aATP analysis includes all infants in the efficacy cohort who received two doses of vaccine according to randomization.

bTVC analysis includes all infants in the efficacy cohort who received at least one dose of vaccine or placebo.

cSevere gastroenteritis defined as ≥11 on the Vesikari scale.

dStatistically significant vs. placebo (P <0.001).

A randomized, double-blind, placebo-controlled study was conducted in 11 countries in Latin America and Finland. A total of 63,225 infants received Rotarix (n = 31,673) or placebo (n = 31,552). An efficacy subset of these infants consisting of 20,169 infants from Latin America received Rotarix (n = 10,159) or placebo (n = 10,010). Vaccine or placebo was given to healthy infants as a 2-dose series with the first dose administered orally from 6 through 13 weeks of age followed by one additional dose administered at least 4 weeks after the first dose. The 2-dose series was completed by the age of 24 weeks of age. For both vaccination groups, the racial distribution of the efficacy subset was as follows: Hispanic 85.8%, white 7.9%, black 1.1%, and other 5.2%; 51% were male.

The clinical case definition of severe rotavirus gastroenteritis was an episode of diarrhea (passage of 3 or more loose or watery stools within a day), with or without vomiting, where rotavirus was identified in a stool sample, requiring hospitalization and/or rehydration therapy equivalent to World Health Organization (WHO) plan B (oral rehydration therapy) or plan C (intravenous rehydration therapy) in a medical facility.

The primary efficacy endpoint was prevention of severe rotavirus gastroenteritis caused by naturally occurring rotavirus from 2 weeks after the second dose through one year (ATP). Analyses were done to evaluate the efficacy of Rotarix against severe rotavirus gastroenteritis among infants who received at least one vaccination (TVC). Reduction in hospitalizations due to rotavirus gastroenteritis was also evaluated (ATP).

Efficacy of Rotarix against severe rotavirus gastroenteritis through one year was 84.7% (95% CI: 71.7, 92.4); TVC efficacy was 81.1% (95% CI: 68.5, 89.3) (Table 5).

Efficacy of Rotarix in reducing hospitalizations for rotavirus gastroenteritis through one year was 85.0% (95% CI: 69.6, 93.5); TVC efficacy was 80.8% (95% CI: 65.7, 90.0) (Table 5).

RV GE = rotavirus gastroenteritis; CI = Confidence Interval.

aATP analysis includes all infants in the efficacy cohort who received two doses of vaccine according to randomization.

bTVC analysis includes all infants in the efficacy cohort who received at least one dose of vaccine or placebo.

cStatistically significant vs. placebo (P <0.001).

Efficacy Through Two Rotavirus Seasons

The efficacy of Rotarix persisting through two rotavirus seasons was evaluated in two studies.

In the European study, the efficacy of Rotarix against any grade of severity of rotavirus gastroenteritis through two rotavirus seasons was 78.9% (95% CI: 72.7, 83.8). Efficacy in preventing any grade of severity of rotavirus gastroenteritis cases occurring only during the second season post-vaccination was 71.9% (95% CI: 61.2, 79.8). The efficacy of Rotarix against severe rotavirus gastroenteritis through two rotavirus seasons was 90.4% (95% CI: 85.1, 94.1). Efficacy in preventing severe rotavirus gastroenteritis cases occurring only during the second season post-vaccination was 85.6% (95% CI: 75.8, 91.9).

The efficacy of Rotarix in reducing hospitalizations for rotavirus gastroenteritis through two rotavirus seasons was 96.0% (95% CI: 83.8, 99.5).

In the Latin American study, the efficacy of Rotarix against severe rotavirus gastroenteritis through two years was 80.5% (95% CI: 71.3, 87.1). Efficacy in preventing severe rotavirus gastroenteritis cases occurring only during the second year post-vaccination was 79.0% (95% CI: 66.4, 87.4). The efficacy of Rotarix in reducing hospitalizations for rotavirus gastroenteritis through two years was 83.0% (95% CI: 73.1, 89.7).

The efficacy of Rotarix beyond the second season post-vaccination was not evaluated.

Efficacy Against Specific Rotavirus Types

The type-specific efficacy against any grade of severity and severe rotavirus gastroenteritis caused by G1P[8], G3P[8], G4P[8], G9P[8], and combined non-G1 (G2, G3, G4, G9) types was statistically significant through one year. Additionally, type-specific efficacy against any grade of severity and severe rotavirus gastroenteritis caused by G1P[8], G2P[4], G3P[8], G4P[8], G9P[8], and combined non-G1 (G2, G3, G4, G9) types was statistically significant through two years (Table 6).

CI = Confidence Interval; NS = Not significant.

aStatistical analyses done by G type; if more than one rotavirus type was detected from a rotavirus gastroenteritis episode, the episode was counted in each of the detected rotavirus type categories.

bStatistically significant vs. placebo (P <0.05).

cThe P genotype was not typeable for one episode.

dP[8] genotype was not detected in one episode.

eTwo cases of G12P[8] were isolated in the second season (one in each group).

Rotarix is available as a vial of lyophilized vaccine, a prefilled oral applicator of liquid diluent (1 mL) with a plunger stopper, and a transfer adapter for reconstitution.

Supplied as:

NDC 58160-805-11 (package of 10)

Storage Before Reconstitution

• Vials: Store the vials of lyophilized Rotarix refrigerated at 2° to 8°C (36° to 46°F). Protect vials from light.
• Diluent: The diluent may be stored at a controlled room temperature 20° to 25°C (68° to 77°F). Do not freeze. Discard if the diluent has been frozen.

Storage After Reconstitution

Rotarix should be administered within 24 hours of reconstitution. It may be stored refrigerated at 2° to 8°C (36° to 46°F) or at room temperature up to 25°C (77°F), after reconstitution. Discard the reconstituted vaccine if not used within 24 hours in biological waste container. Do not freeze. Discard if the vaccine has been frozen.

Rotarix (rotavirus oral vaccine) contains up to five strains of rotavirus. It is made from both human and animal sources.

Infection with rotavirus can affect the digestive system of babies and young children, causing severe stomach or intestinal illness.

Rotarix vaccine is used to help prevent this disease in children.

Rotarix works by exposing your child to a small dose of the virus, which causes the body to develop immunity to the disease. This vaccine will not treat an active infection that has already developed in the body.

Rotarix is for use in children between the ages of 6 weeks and 24 weeks old. The first dose should be administered to infants beginning at 6 weeks of age. There should be an interval of at least 4 weeks between the first and second dose. The 2-dose series should be completed by 24 weeks of age.

Like any vaccine, Rotarix may not provide protection from disease in every person.

Applies to rotavirus vaccine: oral powder for reconstitution, oral suspension

General

The most common adverse events were irritability, cough, runny nose, fever, loss of appetite, diarrhea, and vomiting.[Ref]

Gastrointestinal

Very common (10% or more): Diarrhea (24.1%), vomiting (15.2%)
Common (1% to 10%): Flatulence, abdominal pain
Uncommon (0.1% to 1%): Hematochezia, gastroenteritis
Rare (less than 0.1%): Intussusception, frequent bowel movement
Postmarketing reports: Recurrent intussusception (including death), gastroenteritis with vaccine viral shedding in infants with Severe Combined Immunodeficiency Disease (SCID)[Ref]

Other

Very common (10% or more): Fever (28%), otitis media (14.5%)
Uncommon (0.1% to 1%): Death
Postmarketing reports: Maladministration, transmission of vaccine virus strains from vaccine recipient to non-vaccinated contacts[Ref]

Respiratory

Very common (10% or more): Cough/runny nose (31%)
Common (1% to 10%): Nasopharyngitis, bronchospasm
Uncommon (0.1% to 1%): Bronchiolitis, pneumonia
Rare (less than 0.1%): Apnea
Postmarketing reports: Apnea in very premature infants (28 weeks gestation or less)[Ref]

Psychiatric

Very common (10% or more): Fussiness/irritability (52%)[Ref]

Dermatologic

Uncommon (0.1% to 1%): Dermatitis
Rare (less than 0.1%): Urticaria, rash, eczema, dermatitis atopic
Postmarketing reports: Angioedema[Ref]

Metabolic

Very common (10% or more): Loss of appetite (25%)
Uncommon (0.1% to 1%): Gastroenteritis
Rare (less than 0.1%): Dehydration, weight gain poor[Ref]

Hypersensitivity

Postmarketing reports: Anaphylactic reaction[Ref]

Nervous system

Rare (less than 0.1%): Seizure, hypotonic-hyporesponsive episode, syncope-vasovagal[Ref]

Cardiovascular

Rare (less than 0.1%): Kawasaki disease[Ref]

Hematologic

Postmarketing reports: Idiopathic thrombocytopenic purpura[Ref]

Genitourinary

Uncommon (0.1% to 1%): Urinary tract infection[Ref]

Some side effects of Rotarix may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Animal studies have not been conducted. There are no controlled data in human pregnancy. AU TGA pregnancy category B2: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals are inadequate or may be lacking, but available data show no evidence of an increased occurrence of fetal damage. US FDA pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

This product is not indicated for women of childbearing age and should not be administered to pregnant females. AU TGA pregnancy category: B2 US FDA pregnancy category: C