Rotateq 2 ml Solution

RotaTeq is an oral pentavalent vaccine indicated for the prevention of rotavirus gastroenteritis in infants and children caused by the serotypes G1, G2, G3, G4 and G- serotypes that contain P1A[8] (e.g. G9). RotaTeq may be administered as early as 6 weeks of age.

FOR ORAL USE ONLY. NOT FOR INJECTION.

Paediatric Use

RotaTeq has been shown to be generally well tolerated and highly efficacious in preventing rotavirus gastroenteritis when administered to infants 6 weeks through 32 weeks of age. Safety and efficacy have not been established in infants < 6 weeks of age.

Posology

The vaccination series consists of 3 ready-to-use liquid doses of RotaTeq administered orally to infants. The first dose of RotaTeq should be administered at 6 to 12 weeks of age; the subsequent doses should be administered at a minimum interval of 4 weeks between each dose. There are no restrictions on the infantu2019s consumption of food or liquid, including breast milk, either before or after vaccination with RotaTeq. RotaTeq may be given to pre-term infants according to their chronological age. If for any reason an incomplete dose is administered (e.g. infant spits or regurgitates the vaccine), a replacement dose is not recommended, since such dosing was not studied in the clinical trials. The infant should continue to receive any remaining doses in the recommended series.

Hypersensitivity to any component of the vaccine

Individuals who develop symptoms suggestive of hypersensitivity after receiving a dose of RotaTeq should not receive further doses of RotaTeq.

Individuals with Severe Combined Immunodeficiency Disease (SCID).

Cases of gastroenteritis associated with vaccine virus have been reported post-marketing in infants with severe combined immunodeficiency (SCID).

Adequate treatment provisions, including epinephrine injection (1:1 000), should be available for immediate use should an anaphylactic reaction occur.

No safety or efficacy data are available from clinical trials regarding the administration of RotaTeq to:

• Immunocompromised patients such as
  • individuals with malignancies or who are otherwise immunocompromised
  • individuals receiving immunosuppressive therapy
• Individuals infected with HIV or
• Individuals who have received a blood transfusion or blood products, including immunoglobulins, within 42 days.

There are insufficient data from the clinical trials to support administration of RotaTeq to infants with indeterminate HIV status who are born to mothers with HIV/AIDS.

No faecal shedding of vaccine strains was seen in a small subset of infants with serious medical conditions (e.g. cystic fibrosis, failure to thrive, cancer, congenital heart disease and neutropenia) that were diagnosed after enrollment in the study. Healthcare providers may want to consider these data when assessing the benefits and potential risks of administering RotaTeq to infants with serious medical conditions while keeping in mind nearly all children are infected with naturally occurring rotavirus by age 5 years.

In clinical trials, RotaTeq was not administered to infants known to have immunodeficient household members. In these trials, RotaTeq was shed in the stools of 8,9 % of vaccine recipients almost exclusively in the week after dose 1 and in only one vaccine recipient (0,3 %) after dose 3. Transmission of vaccine virus strains to non-vaccinated contacts has been observed post-marketing. Therefore, RotaTeq should be administered with caution to individuals with immunodeficient close contacts such as: Individuals with malignancies or who are otherwise immunocompromised; or individuals receiving immunosuppressive therapy. However, because nearly all children are infected with naturally occurring rotavirus by the age of 5 years, vaccination of infants may decrease the risk of exposure of immunodeficient household contacts to naturally occurring rotavirus. The healthcare provider should assess the potential risks and benefits of administering RotaTeq to infants known to have immunodeficient close contacts.

Infants with active gastrointestinal illness, chronic diarrhoea or growth retardation or a history of congenital abdominal disorders or intussusception were not to be included in the clinical studies. Administration of RotaTeq may be considered with caution in such infants when, in the opinion of the physician, withholding the vaccine entails a greater risk.

In worldwide post-marketing surveillance, cases of intussusception have been reported in temporal association with RotaTeq. (See u201cSIDE EFFECTS, Post-Marketing Reportsu201d.)

Any acute infection or febrile illness may be reason for delaying use of RotaTeq except when, in the opinion of the physician, withholding the vaccine entails a greater risk. Low-grade fever itself and mild upper respiratory infection are not contraindications to vaccination with RotaTeq.

As with any vaccine, vaccination with RotaTeq may not result in complete protection in all recipients. The clinical studies were not designed to assess the level of protection provided by only 1 or 2 doses of RotaTeq. Post hoc analyses of data from a large clinical study suggest that RotaTeq provides protection against hospitalisations and emergency department visits for rotavirus gastroenteritis during administration of the 3-dose vaccination series starting from 14 days post-dose 1.

No clinical data are available for RotaTeq when administered after exposure to rotavirus.

Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this vaccine.

Concomitant administration of oral poliovirus vaccine (OPV) may reduce some immune responses to rotavirus vaccine; however, there is evidence that a high level of efficacy against severe rotavirus gastroenteritis is maintained (see u201cPHARMACOLOGICAL ACTION, Studies with Other Vaccinesu201d and u201cDOSAGE AND DIRECTIONS FOR USE, Use with Other Vaccinesu201d).

RotaTeq is a paediatric vaccine and is not indicated for use in adults. There have been no adequate, well-controlled studies in women or animals. Information on the safety of the vaccine when used during lactation is not available.

71 725 infants were evaluated in 3 placebo-controlled clinical trials including 36 165 infants who received RotaTeq and 35 560 infants who received placebo. Parents/guardians were contacted on days 7, 14 and 42 after each dose regarding intussusception and any other serious adverse events. The vaccine is generally well tolerated. In the large-scale (34 837 vaccine recipients and 34 788 placebo recipients), placebo-controlled Rotavirus Efficacy and Safety Trial (REST), RotaTeq did not increase the risk of intussusception relative to placebo (see Table 3). Active surveillance was employed to identify potential cases of intussusception at days 7, 14 and 42 after each dose and every 6 weeks thereafter for 1 year after dose one. There were no confirmed cases of intussusception during the 42-day period after dose one, and there was no clustering of cases among vaccine recipients at any time period after any dose. Following the 1-year safety follow-up period, 4 cases of intussusception were reported in children who had received placebo during the study.

Table 3 Confirmed Cases of Intussusception in Recipients of RotaTeq as Compared with Placebo Recipients during REST

RotaTeq (n=34 837) Placebo (n=34 788) Confirmed intussusception cases within 42 days after each dose 6 5 Relative Risk (95 % CI) u2020 1,6 (0,4; 6,4) -- Confirmed intussusception cases within 365 days after dose one 13 15 Relative Risk (95 % CI) 0,9 (0,4; 1,9) -- u2020Relative Risk and 95 % Confidence Interval based upon group sequential design stopping criteria employed in REST

Kawasakiu2019s disease was reported in the phase III clinical trials in < 0,1 % (5/36 150) of vaccine recipients and < 0,1 % (1/35 536) of placebo recipients within 42 days of any dose (not statistically significant).

In 11 711 infants (6 138 recipients of RotaTeq) from the 3 studies, a Vaccination Report Card was used by parents/guardians to record the childu2019s temperature and any episodes of diarrhoea and vomiting on a daily basis during the first week following each vaccination. Table 4 summarises the frequencies of these adverse events, regardless of cause.

Table 4 Adverse Experiences of Special Clinical Interest within the First Week after the First Dose

Adverse Event First Dose RotaTeq Placebo Elevated Temperature (u2265 100,5 u00b0F [38,1 u00b0C] rectal equivalent) 17,1 % 16,2 % Vomiting 6,7 % 5,4 % Diarrhoea 10,4 % 9,1 %

Parents/guardians of the 11 711 infants were also asked to report the presence of other events on the Vaccination Report Card for 42 days after each dose. The following vaccine-related adverse experiences were observed among recipients of RotaTeq at a frequency at least 0,3 % greater than that observed among placebo recipients.

Very Common (u2265 1/10); Common (u2265 1/100, < 1/10); Uncommon (u2265 1/1 000, < 1/100); Rare (u2265 1/10 000, < 1/1 000); Very Rare (< 1/10 000)

Infections and infestations Uncommon: Nasopharyngitis (0,6 % vaccine recipients, 0,3 % placebo recipients) Gastrointestinal disorders Very Common: Diarrhoea (17,6 % vaccine recipients, 15,1 % placebo recipients), vomiting (10,1 % vaccine recipients, 8,2 % placebo recipients) General disorders and administration site conditions Very Common: Pyrexia (20,9 % vaccine recipients, 18,7 % placebo recipients).

Other Adverse Events

Otitis media and bronchospasm occurred in more vaccine than placebo recipients (14,5 % versus 13,0 % and 1,1 % versus 0,7 %, respectively) overall; however, among cases that were considered to be vaccine-related in the opinion of the study investigator, the incidence was the same for vaccine and placebo recipients for otitis media (0,3 %) and bronchospasm (< 0,1 %).

Administration of other licensed vaccines was permitted in all studies. The safety of RotaTeq when administered concomitantly with pre-specified licensed vaccines including Haemophilus influenzae type b and hepatitis B vaccine, diphtheria and tetanus toxoids and acellular pertussis (DTaP) vaccine, inactivated poliovirus vaccine (IPV), pneumococcal conjugate vaccine and hexavalent vaccines was evaluated in all 3 phase III placebo-controlled studies. In subsequent controlled studies, the safety and immunogenicity of RotaTeq when administered concomitantly with oral poliovirus vaccine, meningococcal group C conjugate vaccine or hexavalent vaccine were evaluated. In all these studies, concomitant use with these vaccines was well tolerated; the frequency of adverse experiences observed was generally similar to that seen in the control group.

There have been reports of administration of higher than recommended doses of RotaTeq. In general, the adverse event profile reported with overdose was comparable to that observed with recommended doses of RotaTeq.