M-M-RvaxPro

Change of marketing authorisation holder

- Change of tradename from “M‑M‑RVAXPRO” to “M‑M‑RvaxPro” throughout SPC.

- Correction to date of first authorisation (section 9).

Chemical formulas added to excipient names in section 6.1.

Section 6.5: deletion of the following pack sizes: "Powder in a vial (Type I glass) with a stopper (butyl rubber) and solvent in a pre filled syringe (Type I glass) with attached needle with plunger stopper (chlorobutyl rubber) and needle-shield (natural rubber) in a pack size of 1 and 10."

Section 8: deletion of corresponding EU numbers (EU/1/06/337/003-004)

• Section 1: Joint SPC now includes mention of the suspension for injection (vial) presentation (non-marketed)
• Section 4.4: Addition of headings on Traceability, Sodium, Potassium and Sorbitol
• Section 6.5: Joint SPC now includes pack sizes for both vial (non-marketed) and pre-filled syringe presentations
• Section 6.6: Updated details on reconstitution

Abbreviated HPRA details for reporting suspected adverse reactions; other editorial changes

Amended date of revision.

Addition of "Crying" as uncommon adverse reaction to section 4.8

Addition of "Crying" as uncommon adverse reaction to section 4.8

SANOFI PASTEUR MSD SNC

162, avenue Jean Jaurès

69007 Lyon

France

2.       QUALITATIVE AND QUANTITATIVE COMPOSITION

Added:

Excipients with known effect:

The vaccine contains 14.5 mg of sorbitol. See section 4.4.

For the full list of excipients, see section 6.1.

4.3              Contraindications

Deletion of 3 months changed to 1 month

• In section 2, added the particulars contained in the vaccine including excipients sorbitol
• In section 4.1, removed 12 months or older and replaced with from 12 months of age
• In section 4.3, extended pregnancy contraindication to include pregnancy should be avoided for 3 months following vaccination. Extended contraindication on children with tuberculosis
• In section 4.4, changed warning on sucrose to sorbitol
• In section 4.8, tabulated list of adverse reactions
• In section 4.9, replaced the paragraph with Administration of a higher than recommended dose of M-M-RVAXPRO was reported rarely and the adverse reaction profile was comparable to that observed with the recommended dose of M-M-RVAXPRO.
• In section 10, revised SPC date to 05/2011

• In section 2, added the particulars contained in the vaccine including excipients sorbitol
• In section 4.1, removed 12 months or older and replaced with 12 months of age
• In section 4.3, extended pregnancy contraindication to include pregnancy should be avoided for 3 months following vaccination. Extended contraindication on children with tuberculosis
• In section 4.4, changed warning on sucrose to sorbitol
• In section 4.8, tabulated list of adverse reactions
• In section 4.9, replaced the paragraph with Administration of a higher than recommended dose of M-M-RVAXPRO was reported rarely and the adverse reaction profile was comparable to that observed with the recommended dose of M-M-RVAXPRO.
• In section 10, revised SPC date to 05/2011

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

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

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.

Section 4.5: move second paragraph in first position. addition of a third paragraph

4.5    Interaction with other medicinal products and other forms of interaction

Use with other vaccines

Currently no specific studies have been conducted on the concomitant use of M‑M‑RVAXPRO and other vaccines. However, since M‑M‑RVAXPRO has been shown to have safety and immunogenicity profiles similar to the previous formulation of the combined measles, mumps, and rubella vaccine manufactured by Merck & Co., Inc., experience with this vaccine can be considered.

Published clinical data support concomitant administration of the previous formulation of the measles, mumps, and rubella vaccine manufactured by Merck & Co., Inc. with other childhood vaccinations, including DTaP (or DTwP), IPV (or OPV), HIB (Haemophilus influenzae type b), HIB-HBV (Haemophilus influenzae type b with Hepatitis B vaccine), and VAR (varicella). M‑M‑RVAXPRO should be given concomitantly at separate injection sites, or one month before or after administration of other live virus vaccines.

Based on clinical studies with the quadrivalent measles, mumps, rubella and varicella vaccine and with the previous formulation of the combined measles, mumps, and rubella vaccine manufactured by Merck & Co., Inc., M‑M‑RVAXPRO can be given simultaneously (but at separate injection sites) with Prevenar and/or hepatitis A vaccine. In these clinical studies, it was demonstrated that the immune responses were unaffected and that the overall safety profiles of the administered vaccines were similar.

Section 6.6
addition of instruction concerning the potential use of 2 needles

Reconstitution instructions

Inject the entire content of the syringe into the vial containing the powder. Gently agitate to mix thoroughly. Withdraw the entire content of the reconstituted vaccine vial into the same syringe and inject the entire volume.

If two needles are provided: use one needle to reconstitute the vaccine and the other for its administration to the person to be vaccinated.

The reconstituted vaccine must not be used if any particulate matter is noted or if the appearance of the solvent or powder or of the reconstituted vaccine differs from that described above.

Section 4.8: Revision of format of information to reflect data from clinical trials and post marketing experience.

Section 10: Date changed to 20/06/2008