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change to mention age limited from 12 months to 9 months under some circumstancies
4.1 Therapeutic indications
M‑M‑RVAXPRO is indicated for simultaneous vaccination against measles, mumps, and rubella in individuals 12 months or older (see section 4.2).
M-M-RvaxProM‑M‑RVAXPRO can be administered to infants from 9 months of age under special circumstances. (see sections 4.2, 4.4 and 5.1)
For use in measles outbreaks, or for post-exposure vaccination, or, for use in previously unvaccinated children individuals older than 129 months who are in contact with susceptible pregnant women, and persons likely to be susceptible to mumps and rubella, see section 5.1.
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change to mention age limited from 12 months to 9 months under some circumstanciesPosology
4.2 Posology and method of administration
M‑M‑RVAXPRO is to be used on the basis of official recommendations.
Individuals 12 months of age or older:
Individuals 12 months or older should receive one dose at an elected date. A second dose may be administered at least 4 weeks after the first dose in accordance with official recommendation. The second dose is intended for individuals who did not respond to the first dose for any reason.
Infants less than 12 months of age:
Infants in their first year of life may not respond sufficiently to the measles component of the vaccine, due to the possible persistence of maternal measles antibodies and/or immaturity of the immune system.
Infants between 9 and 12 months of age:
Immunogenicity and safety data show that M-M-RVAXPRO can be administered to infants between 9 and 12 months of age, in accordance with official recommendations or when an early protection is considered necessary (e.g., day-care, outbreak situations, or travel to a region with high prevalence of measles). Such infants should be revaccinated at 12 to 15 months. An additional dose with a measles‑containing vaccine should be considered according to official recommendations (see sections 4.4 and 5.1).
- Infants between 6 months and less thanbelow 12 9 months of age:
No data on the efficacy and safety of M‑M‑RVAXPRO for use in children below 129 months of age are currently available (see section 5.1).
Infants between 6 months and less than 12 9 months of age vaccinated with a measles‑containing vaccine during measles outbreaks or for other reasons or vaccinated at that age in accordance with official recommendation may fail to respond to the vaccine due to the presence of circulating antibodies of maternal origin. Such infants should be revaccinated at 12 to 15 months followed by an additional dose with a measles‑containing vaccine according to the official recommendations.
Method of administration
The vaccine is to be injected intramuscularly (IM) or subcutaneously (SC).
The preferred injection sites are the anterolateral area of the thigh in younger children and the deltoid area in older children, adolescents, and adults.
The vaccine should be administered subcutaneously in patients with thrombocytopenia or any coagulation disorder.
Precautions to be taken before handling or administering the medicinal product
For instructions on reconstitution of the medicinal product before administration, see section 6.6.
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Addition of a new precaution
4.4 Special warnings and precautions for use
Infants from 9 to 12 months of age vaccinated with a measles‑containing vaccine during measles outbreaks or for other reasons may fail to respond to the vaccine due to the presence of circulating antibodies of maternal origin and/or immaturity of the immune system (see sections 4.2 and 5.1).
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change in format and addition of a paragraph for fertility
4.6 Fertility, pregnancy and lactation
4.6 Pregnancy and lactation
Pregnancy
Studies have not been conducted with M‑M‑RVAXPRO in pregnant women. It is not known whether M‑M‑RVAXPRO can cause foetal harm when administered to a pregnant woman or can affect reproduction capacity. Therefore, the vaccine should not be administered to pregnant females; furthermore, pregnancy should be avoided for 3 months following vaccination (see sections 4.3 and 4.4).
Fertility
Animal reproduction studies have not been conducted with M‑M‑RVAXPRO. M‑M‑RVAXPRO has not been evaluated for potential to impair fertility.
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update of section 5.1 to include data regarding the lower age
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Viral vaccine, ATC code J07BD52
Evaluation of immunogenicity and clinical efficacy
A comparative study in 1279 subjects who received M‑M‑RVAXPRO or the previous formulation (manufactured with human serum albumin) of the measles, mumps, and rubella vaccine manufactured by Merck & Co., Inc. demonstrated similar immunogenicity and safety between the 2 products.
Clinical studies of 284 triple seronegative children, 11 months to 7 years of age, demonstrated that the previous formulation of the measles, mumps, and rubella vaccine manufactured by Merck & Co., Inc. is highly immunogenic and generally well tolerated. In these studies, a single injection of the vaccine induced measles hemagglutination-inhibition (HI) antibodies in 95%, mumps neutralising antibodies in 96%, and rubella HI antibodies in 99% of susceptible persons.
Evaluation of immunogenicity in children from 9 to 12 months of age at the time of first dose
A clinical study was conducted with the quadrivalent measles, mumps, rubella and varicella vaccine manufactured by Merck & Co., Inc., administered with a 2-dose schedule, the doses being given 3 months apart in 1,620 healthy subjects from 9 to 12 months of age at the time of first dose. The safety profile post-dose 1 and 2 was generally comparable for all age cohorts.
In the Full Analysis Set (vaccinated subjects regardless of their antibody titre at baseline), high seroprotection rates of >99% were elicited to mumps and rubella post-dose 2, regardless of the age of the vaccinee at the first dose. After 2 doses, the seroprotection rates against measles were 98.1% when the first dose was given at 11 months compared to 98.9% when the first dose was given at 12 months (non-inferiority study objective met). After two doses, the seroprotection rates against measles were 94.6% when the first dose was given at 9 months compared to 98.9% when the first dose was given at 12 months (non-inferiority study objective not met).
The seroprotection rates to measles, mumps, and rubella for the Full Analysis Set are given in Table 1.
Table 1: Seroprotection Rates to Measles, Mumps, and Rubella 6 Weeks Post-Dose 1 and 6 Weeks Post-Dose 2 of the quadrivalent measles, mumps, rubella and varicella vaccine manufactured by Merck & Co., Inc. – Full Analysis Set
|
Valence (seropro
tection level)
|
Time point
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Dose 1 at 9 months / Dose 2 at 12 months
N = 527
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Dose 1 at 11 months / Dose 2 at 14 months
N = 480
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Dose 1 at 12 months / Dose 2 at 15 months
N = 466
|
|
Seroprotection ratesResponse rate
[95% CI]
|
Seroprotection ratesResponse rate
[95% CI]
|
Seroprotection ratesResponse rate
[95% CI]
|
|
Measles
(titre ≥255 mIU/mL)
|
Post-Dose 1
|
72.3%
[68.2; 76.1]
|
87.6%
[84.2; 90.4]
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90.6%
[87.6; 93.1]
|
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Post-Dose 2
|
94.6%
[92.3; 96.4]
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98.1%
[96.4; 99.1]
|
98.9%
[97.5; 99.6]
|
|
Mumps (titre ≥10 ELISA Ab units/mL)
|
Post-Dose 1
|
96.4%
[94.4; 97.8]
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98.7%
[97.3; 99.5]
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98.5%
[96.9; 99.4]
|
|
Post-Dose 2
|
99.2%
[98.0; 99.8]
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99.6%
[98.5; 99.9]
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99.3%
[98.1; 99.9]
|
|
Rubella (titre ≥10 IU/mL)
|
Post-Dose 1
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97.3%
[95.5; 98.5]
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98.7%
[97.3; 99.5]
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97.8%
[96.0; 98.9]
|
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Post-Dose 2
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99.4%
[98.3; 99.9]
|
99.4%
[98.1; 99.9]
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99.6%
[98.4; 99.9]
|
The post‑dose 2 geometric mean titres (GMTs) against mumps and rubella were comparable across all age categories, while the GMTs against measles were lower in subjects who received the first dose at 9 months of age as compared to subjects who received the first dose at 11 or 12 months of age.
A comparative study in 752 subjects who received M‑M‑RVAXPRO either by intramuscular route or subcutaneous route demonstrated a similar immunogenicity profile between both administration routes.
The efficacy of the components of the previous formulation of the measles, mumps, and rubella vaccine manufactured by Merck & Co., Inc. was established in a series of double‑blind controlled field trials, which demonstrated a high degree of protective efficacy afforded by the individual vaccine components. These studies also established that seroconversion in response to vaccination against measles, mumps, and rubella paralleled protection from these diseases.
Previously unvaccinated children individuals older than 912 months who are in contact with susceptible pregnant women should receive live attenuated rubella‑containing vaccine (such as M‑M‑RVAXPRO or a monovalent rubella vaccine) to reduce the risk of exposure of the pregnant woman.
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addition of a new sentece
10. DATE OF REVISION OF THE TEXT
Detailed information on this product is available on the website of the European Medicines Agency http://www.ema.europa.eu.
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