Rotarix: anti-inflammatory drug caused by rotavirus

2021-06-10 10:45 PM

Rotarix has been demonstrated against rotavirus gastroenteritis of common strains such as G1P and uncommon strains of rotavirus such as G8P, which causes severe gastroenteritis, and G12P, which causes gastroenteritis of any degree.

Producer

GlaxoSmithKline.

Ingredient

One dose (1.5mL): not less than 106.0 CCID50 live attenuated human Rotavirus strain RIX4414.

Describe

The vaccine is in the form of a clear and colorless liquid.

Porcine Circovirus group 1 (PCV-1) was found in the Rotarix vaccine. PCV-1 is not known to cause disease in animals and does not infect or cause disease in humans. There is no evidence that the presence of PCV-1 poses any safety risk.

Pharmacotherapeutic group: virus vaccines, ATC code: J07BH01.

Pharmacodynamic properties

Protective effect

In clinical trials, efficacy was demonstrated against rotavirus gastroenteritis of common strains such as G1P[8], G2P[4], G3P[8], G4P[8] and G9P[edit] 8] and uncommon strains of rotavirus such as G8P[4] (causing severe gastroenteritis) and G12P[6] (causing gastroenteritis of any degree). All these strains are circulating the world.

Numerous clinical studies have been conducted in Europe, Latin America, Africa, and Asia to evaluate the protective efficacy of Rotarix against rotavirus causing severe and any gastroenteritis.
 
The severity of gastroenteritis is determined by the following two different criteria:
 
Vesikari 20 Scale, which assesses the overall clinical picture of rotavirus gastroenteritis taking into account the severity and duration of diarrhea and vomiting, the degree of high fever and dehydration, and the need for treatment. or

Clinical cases according to World Health Organization (WHO) standards.

Effective protection in Europe and Latin America

The vaccine's protective efficacy following two oral doses of Rotarix was observed in clinical studies conducted in Europe and Latin America during the 1st and 2nd year of age combined and demonstrated.

The effectiveness of the vaccine against severe gastroenteritis due to G2P strain rotavirus[4] was 38.6% (95% CI: <0.0; 84.2). The number of cases to estimate vaccine efficacy against G2P[4] is very small.

A meta-analysis of four efficacy studies showed efficacy against severe G2P-type rotavirus[4] (Vesikari score ≥11) of 71.4% (95% CI: 20.1; 91.1).

The degree of protective efficacy of the lyophilized form can be extrapolated to the suspension since the observed immune response following 2 doses of Rotarix Suspension is comparable to the immunological response following 2 doses of Rotarix Suspension. dose of Rotarix lyophilized.

Protective effect in Africa

A clinical study was conducted in Africa in more than 4,900 subjects receiving Rotarix at the age of 10 and 14 weeks (2 doses) or 6, 10, and 14 weeks (3 doses). The vaccine efficacy against severe rotavirus gastroenteritis during the first year of life was 61.2% (95% CI: 44.0; 73.2). The study did not evaluate the difference in effectiveness between the 2-dose and 3-dose immunization series.

Protective efficacy of vaccines against severe and any degree of gastroenteritis has been observed and demonstrated.

The effect lasts up to 3 years in Asia

A clinical study conducted in Asia (Hong Kong, Singapore, and Taiwan) in more than 10,000 subjects received different regimens of Rotarix (2.4 months of age; 3.4 months of age).

After 2 doses of Rotarix, the vaccine's protective effect observed until 3 years of age was demonstrated.

Immune response

In different clinical studies conducted in Europe, Latin America, and Asia, 1,957 neonates received freeze-dried Rotarix and 1006 infants received placebo according to different immunization regimens. Percentage of children who were initially seronegative for rotavirus (IgA antibody titer <20 U/mL (by ELISA) compared with serum anti-rotavirus IgA antibody titer ≥20 U/mL activity ranged from 77.9% to 100% and from 0% to 17.1% one or two months after the second dose of vaccine or placebo.

In three comparative clinical trials, the immune response induced by Rotarix suspension was comparable to that induced by lyophilized Rotarix.

In a clinical study conducted in Africa, the immune response was evaluated in 332 neonates receiving Rotarix (N=221) or placebo (N=111). 6, 10, and 14 weeks (3 doses). Percentage of children who were initially seronegative for rotavirus (IgA antibody titer <20 U/mL (by ELISA) compared with serum anti-rotavirus IgA antibody titer ≥20 U/mL per day) months after the last dose of vaccine or placebo were 58.4% and 22.5%, respectively.

Immune response in premature infants

In a clinical study in premature infants using the lyophilized form, Rotarix elicited an immune response; 85.7% of children achieved a serum anti-rotavirus IgA antibody titer ≥20 U/mL (by ELISA) one month after the second dose of vaccine.

Safe for children with acquired immunodeficiency syndrome (HIV)

In a clinical study, 100 children with acquired immunodeficiency syndrome (HIV) were assigned to either freeze-dried Rotarix or placebo. Safety data were similar between the Rotarix and placebo groups.

Excretion of vaccine virus in feces

The virus contained in the vaccine is excreted in the feces after oral administration and lasts an average of about 10 days, with a maximum on day 7. Virus antigen molecules detected by ELISA, in about 50% of stool samples after the first dose and approximately 4% of stool samples after the second dose. When tested for the presence of a live vaccine strain 17% of these stool samples were positive.

In two comparative controlled clinical trials, postvaccination virus excretion was comparable between Rotarix vaccine suspension and lyophilized form.

The actual effectiveness of vaccines

In observational studies, vaccine efficacy has been demonstrated against severe gastroenteritis leading to rotavirus hospitalization of common strains such as G1P[8], G2P[4], G3P[8 ], and G9P[8] as well as less common rotavirus strains such as G9P[4] and G9P[6]. All of these strains are circulating the world.

Results of matched case-control studies were conducted to evaluate the efficacy of Rotarix in preventing severe rotavirus gastroenteritis requiring hospitalization.

Effect on mortality

Impact studies of Rotarix conducted in Panama, Brazil, and Mexico showed a reduction in all-cause diarrhea mortality from 22% to 56% in children under 5 years of age, within 2 to 3 years of age. years after vaccination.

Impact on hospital admission rate

In a retrospective data study in Belgium conducted in children 5 years of age and younger, the direct and indirect effects of oral Rotarix vaccine on rotavirus-related hospitalizations ranged from 64 % (95% CI: 49; 76) to 80% (95% CI: 77; 83) after 2 years of vaccination. Similar studies in Brazil, Australia, and El Salvador also showed a 45 to 88% reduction in hospital admissions.

Furthermore, two studies of hospital admissions for all-cause diarrhea conducted in Latin America showed a 38 to 40% reduction in hospitalizations after 4 years of vaccination.

NOTE: Studies on the effects of vaccines have established a temporal association, not a cause-and-effect relationship between disease and vaccination.

Preclinical safety data

Preclinical safety data do not indicate a hazard to humans based on studies with repeated toxic doses.

Pharmacokinetics

No pharmacokinetic evaluation is required for vaccines.

Indications and uses

Rotarix is ​​indicated for the prevention of gastroenteritis caused by rotavirus.

Dosage and Administration

Dosage

The oral vaccine regimen consists of 2 doses. The first dose can be given from 6 weeks of age. The interval between doses is at least 4 weeks. Oral vaccination should be completed up to 24 weeks of age.

Rotarix can be used for premature infants at the same dose.

In clinical trials, spitting or spitting up was rarely observed, in which case no replacement dose was required. However, if the child spits up or spits up most of the vaccine taken in, a single replacement dose may be given in the same dose of the vaccine.

It should be emphasized that children who have received the first dose of Rotarix should receive a second dose of Rotarix as well.

Rotarix should not be given to children over 24 weeks of age.

How to use

Rotarix is ​​for oral use only.

Under no circumstances should Rotarix be injected.

Do not restrict your baby's food or water, including breast milk, before or after the vaccine.

Evidence from clinical trials suggests that breastfeeding does not reduce protection against gastroenteritis caused by rotavirus produced by Rotarix. Therefore, breastfeeding should be continued while the vaccine is being administered.

User manual

The vaccine is in the form of a clear, colorless liquid, free of foreign particles, intended for oral administration.

The vaccine is used immediately (no reconstitution or dilution required).

Vaccines intended for oral administration must not be mixed with any other vaccine or solution.

The vaccine should be visually inspected for any foreign particles and/or abnormalities. Discard vaccine if abnormalities are found.

Unused vaccines or waste should be disposed of according to local requirements.

Warning

To ensure good clinical practice before vaccination, a medical history (particularly prior vaccination and adverse events) should be checked and a physical examination is required.

As with other vaccines, the use of Rotarix should be postponed in children with severe, acute illness with fever. However, it is not contraindicated for children with mild infections such as colds.

The use of Rotarix should be postponed in children with diarrhea or vomiting.

There are no data on the safety and efficacy of Rotarix in children with gastrointestinal disease. Rotarix may be considered with caution in these children if the doctor thinks that not using the vaccine may pose a higher risk.

The risk of intussusception was evaluated in a large safety clinical trial (including 63,225 infants) in Latin America and Finland. This trial showed no increased risk of intussusception with Rotarix compared with placebo.

However, post-marketing safety studies showed an increase in intussusception following vaccination, mostly within 7 days of the first dose, and for the second dose, the risk was less. The total number of cases of intussusception is still very rare. It is not well established whether Rotarix affects the overall incidence of intussusception.

Health care professionals should watch for signs of intussusception (severe abdominal pain, persistent vomiting, bloody stools, abdominal distention, and/or high fever). When experiencing the above symptoms, parents or caregivers should immediately notify the medical staff.

The administration of Rotarix to immunocompromised children, including those undergoing immunosuppressive therapy, should be carefully weighed against the risks and benefits of use.

Elimination of vaccine virus in feces follows oral administration and lasts on average about 10 days with a peak of excretion on day 7.

In clinical trials, the transmission of discarded vaccine viruses from vaccinated subjects to seronegative contacts was observed without any clinical symptoms. which. Rotarix should be administered with caution to children who are in close contact with immunocompromised individuals, such as those with malignancies or other immunocompromised cases or on immunosuppressive therapy. Careful hygiene should be taken when handling a child who has just been vaccinated (including washing hands) when changing diapers.

As with other vaccines, a protective immune response may not be achieved in all vaccinated children.

The extent of Rotarix protection against non-circulatory strains of rotavirus in clinical trials is unknown.

Rotarix does not protect children against gastroenteritis caused by agents other than Rotavirus.

Under no circumstances should Rotarix be injected.

Effects on ability to drive and use machines

Not suitable as Rotarix is ​​not intended for use by adults.

Overdose

Several cases of overdose have been reported. Overall, the adverse event profile reported in these cases was similar to that observed following the use of the recommended dose of Rotarix.

Contraindications

Hypersensitivity to the vaccine or any of the excipients.

Hypersensitivity following previous use of rotavirus vaccine.

History of intussusception.

The patient has a congenital malformation of the gastrointestinal tract as a possible cause of intussusception.

The patient has a severe combined immune disorder (SCID disease).

The use of Rotarix should be postponed in patients with an acute high fever. Not contraindicated for use in patients with mild infections.

Postpone Rotarix in patients with vomiting or diarrhea.

Use in pregnant and lactating women

Rotarix is ​​not intended for adult use. Therefore, there are no data on human use of the vaccine during pregnancy or lactation and no animal reproduction studies have been conducted.

Interactive

Rotarix can be used at the same time as any monovalent or combination vaccine [such as six-component vaccine (DTPa-HBV-IPV/Hib)]: diphtheria - tetanus - pertussis vaccine whole cell (DTPw), diphtheria-tetanus - acellular pertussis (DTPa), Haemophilus influenzae type b (Hib) vaccine, inactivated polio vaccine (IPV), hepatitis B vaccine ( HBV), pneumococcal conjugate vaccine, and group C serogroup C meningococcal conjugate vaccine. Clinical studies have demonstrated the immune response and safety of concomitant vaccines. with Rotarix unaffected.

Concomitant administration of Rotarix and oral poliovirus vaccine (OPV) did not affect the immune response to polio antigen. Although co-administration with OPV may slightly attenuate the immune response to the rotavirus vaccine, clinical protection against severe rotavirus gastroenteritis is maintained.

Incompatibility

This vaccine should not be mixed with other medicinal products.

Side effects

Clinical trial data

The frequency classification is as follows: Very common ≥1/10, Common ≥1/100 and <1/10, Uncommon ≥1/1000 and <1/100, Rare ≥1/10,000 and <1/1000, Very rare <1/10,000.

The safety results presented below are based on data from clinical trials conducted with Rotarix freeze-dried vaccine or suspension.

In a total of 4 clinical trials, nearly 3,800 doses of Rotarix suspension were administered to nearly 1900 children. These trials have shown that the safety of the suspension vaccine is comparable to that of the lyophilized vaccine.

In a total of 23 clinical trials, approximately 106,000 doses of Rotarix (either lyophilized or suspension) were administered to nearly 51,000 infants.

In 3 placebo-controlled clinical trials, Rotarix was used alone (routine pediatric vaccine alternately indicated), incidence and severity of related reactions ( collected 8 days after vaccination), diarrhea, vomiting, anorexia, fever, irritability, and cough/runny nose were not significantly different in the Rotarix group compared with the placebo group. There was no increase in the incidence and severity of these reactions after the second dose.

In a meta-analysis of 17 placebo-controlled clinical trials including those where Rotarix was used in conjunction with routine childhood vaccines, the following adverse reactions were observed (collected). 31 days after vaccination) is likely related to vaccine use.

Digestive disorders

Common: diarrhea

Uncommon: flatulence, abdominal pain

Skin and subcutaneous tissue disorders

Uncommon: dermatitis

Systemic and local disorders

Common: irritation.

The risk of intussusception was assessed in a large safety trial conducted in Latin America and Finland with 63,225 participants. Results showed no evidence of an increased risk of intussusception in the Rotarix group compared with the placebo group, details are presented.

Safety in premature babies

In a clinical trial, 1009 infants received freeze-dried Rotarix or placebo (198 infants aged 27-30 weeks and 801 infants 31-36 weeks of age at birth). The first dose is used from 6 weeks postpartum. Serious adverse reactions were seen in 5.1% of subjects receiving Rotarix compared with 6.8% receiving placebo. Other adverse reactions in Rotarix and placebo-treated subjects were also reported at similar rates. No cases of intussusception were reported.

After-sales investigation

Digestive disorders.

Rare: bloody stools, vaccine-associated viral gastroenteritis in faeces in children with severe combined immune deficiency disease (SCID).

Very rare: intussusception.

Preservation

Store in the refrigerator (2-8 degrees Celsius). Do not freeze.

Store in original box to protect from light.

Presentation and packaging

Oral suspension: box of 1 ampoule of 1.5mL [1.5mL of oral suspension in an oral tube (class 1 I, Ph. Eur.) with a stopper piston (butyl rubber)].