Safety Profile for ROTARIX

There are two formulations of ROTARIX: a reconstituted lyophilized formulation and a liquid formulation. Safety data accrued with each formulation is relevant to the other because each contains the same live, attenuated rotavirus strain and is manufactured using a similar process.1

Clinical Trials Experience With Liquid Formulation1

  • The safety of the ROTARIX liquid formulation was evaluated in 3 randomized clinical studies. A total of 4223 infants received ROTARIX (liquid formulation, n=2507; reconstituted lyophilized formulation, n=1716)

Solicited Adverse Reactions Within 8 Days Following Doses 1 and 2 of ROTARIX (Liquid or Reconstituted Lyophilized Formulation), Study 10 Total Vaccinated Cohort

  Dose 1 Dose 2
  ROTARIX
(Liquid Formulation)
n=632		 ROTARIX
(Reconstituted
Lyophilized Formulation)
n=640		 ROTARIX
(Liquid Formulation)
n=607		 ROTARIX
(Reconstituted
Lyophilized Formulation)
n=609
Adverse Reactions Overall % G3 % Overall % G3 % Overall % G3 % Overall % G3 %
Fussiness/irritabilitya 70.9 9.2 71.6 8.8 72.5 13.7 70.1 11.8
Cough/runny noseb 27.2 0.5 28.1 1.3 36.9 3.8 36.5 3.6
Feverc 5.7 0.3 5.0 0.3 10.5 0.3 12.3 0.7
Loss of appetited 32.3 0.2 33.4 0.9 29.5 1.2 29.2 1.8
Vomitinge 17.4 2.8 16.4 3.4 13.7 4.0 12.8 3.3
Diarrheaf 6.2 0.2 5.6 0.8 5.6 0.5 4.3 0.3
  Dose 1
  ROTARIX
(Liquid Formulation)
n=632		 ROTARIX
(Reconstituted Lyophilized Formulation)
n=640
Adverse Reactions Overall
%		 G3
%		 Overall
%		 G3
%
Fussiness/irritabilitya 70.9 9.2 71.6 8.8
Cough/runny noseb 27.2 0.5 28.1 1.3
Feverc 5.7 0.3 5.0 0.3
Loss of appetited 32.3 0.2 33.4 0.9
Vomitinge 17.4 2.8 16.4 3.4
Diarrheaf 6.2 0.2 5.6 0.8
  Dose 2
  ROTARIX
(Liquid Formulation)
n=607		 ROTARIX
(Reconstituted Lyophilized Formulation)
n=609
Adverse Reactions Overall
%		 G3
%		 Overall
%		 G3
%
Fussiness/irritabilitya 72.5 13.7 70.1 11.8
Cough/runny noseb 36.9 3.8 36.5 3.6
Feverc 10.5 0.3 12.3 0.7
Loss of appetited 29.5 1.2 29.2 1.8
Vomitinge 13.7 4.0 12.8 3.3
Diarrheaf 5.6 0.5 4.3 0.3

G3=Grade 3.

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

n=Number of infants who received the specified dose.

  • a

    Overall: Defined as crying more than usual. Grade 3: Crying that could not be comforted/prevented normal activity.

  • b

    Grade 3 cough/runny nose: cough/runny nose that prevented daily activity.

  • c

    Overall: Defined as temperature ≥100.4°F (≥38.0°C). Grade 3: Defined as temperature >103.1°F (>39.5°C).

  • d

    Overall: Defined as eating less than usual. Grade 3: Defined as not eating at all.

  • e

    Overall: Defined as 1 or more episodes of forceful emptying of partially digested stomach contents ≥1 hour after feeding within a day. Grade 3: ≥3 episodes of vomiting/day.

  • f

    Overall: Defined as passage of 3 or more looser than normal stools within a day. Grade 3: ≥6 looser than normal stools/day.

Unsolicited Adverse Events1

  • Infants were monitored for unsolicited serious and non-SAEs that occurred in the 31-day period following vaccination. There were no notable differences in the occurrence and frequency of unsolicited adverse events between the groups

Serious Adverse Events1

  • During the entire course of the studies, SAEs occurred in 4.7% of recipients of ROTARIX liquid formulation (n=2507) as compared with 4.4% of ROTARIX reconstituted lyophilized formulation recipients (n=1716)

Intussusception1

 

  • Among participants, 2 intussusception cases were reported. One subject experienced intussusception 8 days after receiving the second dose of ROTARIX (reconstituted lyophilized formulation). The event was considered possibly related to ROTARIX. One subject from Study 9 experienced intussusception 133 days after receiving the second dose of ROTARIX (liquid formulation); the event was not considered related to ROTARIX. Both subjects were hospitalized, and the outcome of intussusception was reported as resolved

SAE=serious adverse events.

Clinical Trials Experience With Lyophilized Formulation

Solicited Adverse Reactions1

  • In 7 clinical studies, detailed safety information was collected by parents/guardians for 8 consecutive days following vaccination with ROTARIX
  • Solicited adverse reactions among recipients of ROTARIX and placebo occurred at similar rates

Solicited Adverse Reactions Within 8 Days Following Doses 1 and 2 of ROTARIX or Placebo (Total Vaccinated Cohort)1

  Dose 1 Dose 2
  ROTARIX
n=3284
%		 Placebo
n=2013
%		 ROTARIX
n=3201
%		 Placebo
n=1973
%
Fussiness/irritabilitya 52 52 42 42
Cough/runny noseb 28 30 31 33
Feverc 25 33 28 34
Loss of appetited 25 25 21 21
Vomiting 13 11 8 8
Diarrhea 4 3 3 3
  Dose 1
  ROTARIX
n=3284
%		 Placebo
n=2013
%
Fussiness/irritabilitya 52 52
Cough/runny noseb 28 30
Feverc 25 33
Loss of appetited 25 25
Vomiting 13 11
Diarrhea 4 3
  Dose 2
  ROTARIX
n=3201
%		 Placebo
n=1973
%
Fussiness/irritabilitya 42 42
Cough/runny noseb 31 33
Feverc 28 34
Loss of appetited 21 21
Vomiting 8 8
Diarrhea 3 3

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

n=number of infants for whom at least 1 symptom sheet was completed.

  • a

    Defined as crying more than usual.

  • b

    Data not collected in 1 of 7 studies. Dose 1: ROTARIX (n=2583); placebo (n=1897); Dose 2: ROTARIX (n=2522); placebo (n=1863).

  • c

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

  • d

    Defined as eating less than usual.

Unsolicited Adverse Reactions1

  • Infants were monitored for unsolicited serious and nonserious adverse events that occurred in the 31-day period following vaccination in 7 clinical studies (ROTARIX [n=5082]; placebo [n=2902])
  • The following adverse reactions occurred at a statistically higher incidence among recipients of ROTARIX compared with placebo: irritability (ROTARIX=11.4%, placebo=8.7%) and flatulence (ROTARIX=2.2%, placebo=1.3%)

Serious Adverse Reactions1

  • Infants were monitored for serious adverse events that occurred in the 31-day period following vaccination in 8 clinical studies. Serious adverse reactions 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

Deaths1

  • 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 (RR: 1.74, 95% CI: 0.76, 4.23)

Intussusception1

  • 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). 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

CI=confidence interval; RR=relative risk.

INDICATIONS & IMPORTANT SAFETY INFO

INDICATIONS

IMPORTANT SAFETY INFORMATION FOR ROTARIX

INDICATIONS

ROTARIX is a vaccine indicated for the prevention of rotavirus gastroenteritis caused by G1 and non-G1 types (G3, G4, and G9) when administered as a 2-dose series. ROTARIX is approved for use in infants 6 weeks and up to 24 weeks of age.

IMPORTANT SAFETY INFORMATION FOR ROTARIX

  • Contraindications for ROTARIX include a history of any of the following: hypersensitivity to the vaccine or any component of the vaccine; uncorrected congenital malformation of the gastrointestinal tract (such as Meckel’s diverticulum) that would predispose the infant to intussusception; intussusception (in postmarketing experience, intussusception resulting in death following a second dose has been reported following a history of intussusception after the first dose); or Severe Combined Immunodeficiency Disease (SCID)
  • The tip caps of the prefilled oral dosing applicators contain natural rubber latex, which may cause allergic reactions
  • Administration in infants suffering from acute diarrhea or vomiting should be delayed. Safety and effectiveness in infants with chronic gastrointestinal disorders have not been evaluated
  • Safety and effectiveness in infants with known primary or secondary immunodeficiencies, including infants with human immunodeficiency virus (HIV), infants on immunosuppressive therapy, or infants with malignant neoplasms affecting the bone marrow or lymphatic system have not been established
  • Rotavirus shedding in stool occurs after vaccination with peak excretion occurring around Day 7 after Dose 1. One clinical trial demonstrated that vaccinees transmit vaccine virus to healthy seronegative contacts. Caution is advised when considering whether to administer ROTARIX to individuals with immunodeficient close contacts
  • A study conducted after approval of ROTARIX showed an increased risk of intussusception in the 31 days after the first dose of ROTARIX, especially in the first 7 days. In other reports, an increased risk of intussusception has been observed within 7 days after dose 2
  • Safety and effectiveness of ROTARIX when administered after exposure to rotavirus have not been evaluated
  • In clinical studies, common (≥5%) solicited adverse reactions among recipients of ROTARIX included fussiness/irritability, cough/runny nose, fever, loss of appetite, and vomiting
  • Safety and effectiveness of ROTARIX in infants younger than 6 weeks or older than 24 weeks of age have not been evaluated
  • The effectiveness of ROTARIX in pre-term infants has not been established
  • Vaccination with ROTARIX may not result in protection in all vaccine recipients

 

Please see full Prescribing Information for ROTARIX.

References

  1. Prescribing Information for ROTARIX.