Vaccine Information: M-M-R II

M-M-R II- measles virus strain enders’ attenuated edmonston live antigen, mumps virus strain b level jeryl lynn live antigen and rubella virus strain wistar ra 27/3 live antigen injection, powder, lyophilized, for suspension
Merck Sharp & Dohme LLC

1 INDICATIONS AND USAGE

M-M-R II is a vaccine indicated for active immunization for the prevention of measles, mumps, and rubella in individuals 12 months of age and older.

2 DOSAGE AND ADMINISTRATION

​ Intramuscular or Subcutaneous administration only.

2.1 Dose and Schedule

​ A single dose of M-M-R II is approximately 0.5 mL.

The first dose is administered at 12 to 15 months of age. A second dose is administered at 4 to 6 years of age.

The second dose may be administered prior to 4 years of age, provided that there is a minimum interval of one month between the doses of measles, mumps and rubella virus vaccine, live {1–2}.

Children who received an initial dose of measles, mumps and rubella vaccine prior to their first birthday should receive additional doses of vaccine at 12-15 months of age and at 4-6 years of age to complete the vaccination series [see Clinical Studies (14.2)].

For post-exposure prophylaxis for measles, administer a dose of M-M-R II vaccine within 72 hours after exposure.

2.2 Administration

Use a sterile syringe free of preservatives, antiseptics, and detergents for each injection and/or reconstitution of the vaccine because these substances may inactivate the live virus vaccine. To reconstitute, use only the diluent supplied with the vaccine since it is free of preservatives or other antiviral substances which might inactivate the vaccine.

Withdraw the entire volume of the supplied diluent from its vial and inject into lyophilized vaccine vial. Agitate to dissolve completely. Discard if the lyophilized vaccine cannot be dissolved.

​ Withdraw the entire volume of the reconstituted vaccine and inject the vaccine intramuscularly or subcutaneously.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Visually inspect the vaccine before and after reconstitution prior to administration. Before reconstitution, the lyophilized vaccine is a light yellow compact crystalline plug, when reconstituted, is a clear yellow liquid. Discard if particulate matter or discoloration are observed in the reconstituted vaccine.

To minimize loss of potency, administer M-M-R II as soon as possible after reconstitution. If not used immediately, the reconstituted vaccine may be stored between 36°F to 46°F (2°C to 8°C), protected from light, for up to 8 hours. Discard reconstituted vaccine if it is not used within 8 hours.

3 DOSAGE FORMS AND STRENGTHS

M-M-R II vaccine is a suspension for injection supplied as a single dose vial of lyophilized vaccine to be reconstituted using the accompanying sterile diluent [see Dosage and Administration (2.2) and How Supplied/Storage and Handling (16)]. A single dose after reconstitution is approximately 0.5 mL.

4 CONTRAINDICATIONS

4.1 Hypersensitivity

Do not administer M-M-R II vaccine to individuals with a history of hypersensitivity to any component of the vaccine (including gelatin) {3} or who have experienced a hypersensitivity reaction following administration of a previous dose of M-M-R II vaccine or any other measles, mumps and rubella-containing vaccine. Do not administer M-M-R II vaccine to individuals with a history of anaphylaxis to neomycin [see Description (11)].

4.2 Immunosuppression

Do not administer M-M-R II vaccine to individuals who are immunodeficient or immunosuppressed due to disease or medical therapy. Measles inclusion body encephalitis {4} (MIBE), pneumonitis {5} and death as a direct consequence of disseminated measles vaccine virus infection have been reported in immunocompromised individuals inadvertently vaccinated with measles-containing vaccine. In this population, disseminated mumps and rubella vaccine virus infection have also been reported.

4.3 Moderate or Severe Febrile Illness

Do not administer M-M-R II vaccine to individuals with an active febrile illness with fever >101.3°F (>38.5°C).

4.4 Active Untreated Tuberculosis

Do not administer M-M-R II vaccine to individuals with active untreated tuberculosis (TB).

4.5 Pregnancy

Do not administer M-M-R II to individuals who are pregnant or who are planning on becoming pregnant within the next month [see Use in Specific Populations (8.1) and Patient Counseling Information (17)].

5 WARNINGS AND PRECAUTIONS

5.1 Febrile Seizure

There is a risk of fever and associated febrile seizure in the first 2 weeks following immunization with M-M-R II vaccine. For children who have experienced a previous febrile seizure (from any cause) and those with a family history of febrile seizures there is a small increase in risk of febrile seizure following receipt of M-M-R II vaccine [see Adverse Reactions (6)].

5.2 Hypersensitivity to Eggs

Individuals with a history of anaphylactic, anaphylactoid, or other immediate reactions (e.g., hives, swelling of the mouth and throat, difficulty breathing, hypotension, or shock) subsequent to egg ingestion may be at an enhanced risk of immediate-type hypersensitivity reactions after receiving M-M-R II vaccine. The potential risks and known benefits should be evaluated before considering vaccination in these individuals.

5.3 Thrombocytopenia

Transient thrombocytopenia has been reported within 4-6 weeks following vaccination with measles, mumps and rubella vaccine. Carefully evaluate the potential risk and benefit of vaccination in children with thrombocytopenia or in those who experienced thrombocytopenia after vaccination with a previous dose of measles, mumps, and rubella vaccine {6–8} [see Adverse Reactions (6)].

5.4 Family History of Immunodeficiency

Vaccination should be deferred in individuals with a family history of congenital or hereditary immunodeficiency until the individual’s immune status has been evaluated and the individual has been found to be immunocompetent.

5.5 Immune Globulins and Transfusions

Immune Globulins (IG) and other blood products should not be given concurrently with M-M-R II [see Drug Interactions (7.2)]. These products may contain antibodies that interfere with vaccine virus replication and decrease the expected immune response.

The Advisory Committee on Immunization Practices (ACIP) has specific recommendations for intervals between administration of antibody containing products and live virus vaccines.

6 ADVERSE REACTIONS

The following adverse reactions include those identified during clinical trials or reported during post-approval use of M-M-R II vaccine or its individual components.

Body as a Whole

Panniculitis; atypical measles; fever; headache; dizziness; malaise; irritability.

Cardiovascular System

Vasculitis.

Digestive System

Pancreatitis; diarrhea; vomiting; parotitis; nausea.

Hematologic and Lymphatic Systems

Thrombocytopenia; purpura; regional lymphadenopathy; leukocytosis.

Immune System

Anaphylaxis, anaphylactoid reactions, angioedema (including peripheral or facial edema) and bronchial spasm.

Musculoskeletal System

Arthritis; arthralgia; myalgia.

Nervous System

Encephalitis; encephalopathy; measles inclusion body encephalitis (MIBE) subacute sclerosing panencephalitis (SSPE); Guillain-Barré Syndrome (GBS); acute disseminated encephalomyelitis (ADEM); transverse myelitis; febrile convulsions; afebrile convulsions or seizures; ataxia; polyneuritis; polyneuropathy; ocular palsies; paresthesia; syncope.

Respiratory System

Pneumonia; pneumonitis; sore throat; cough; rhinitis.

Skin

Stevens-Johnson syndrome; acute hemorrhagic edema of infancy; Henoch-Schönlein purpura; erythema multiforme; urticaria; rash; measles-like rash; pruritus; injection site reactions (pain, erythema, swelling and vesiculation).

Special Senses — Ear

Nerve deafness; otitis media.

Special Senses — Eye

Retinitis; optic neuritis; papillitis; conjunctivitis.

Urogenital System

Epididymitis; orchitis.

In a randomized open-label clinical trial (NCT00432523), conducted in France and Germany, 752 children 12 months through 18 months of age received M-M-R II concomitantly administered with VARIVAX at a separate site, by either the intramuscular (n=374) or subcutaneous (n=378) route. In the overall population, 55.3% were male and the median age was 13.2 months. Local and systemic solicited adverse reactions were recorded by parents or guardians using standardized diary cards. Local solicited reactions were recorded for 4 days after vaccination, and systemic solicited adverse reactions were recorded for 42 days after vaccination. In the event that a participant experienced a rash or a mumps-like illness, parents and/or guardians were instructed to contact the investigator for an examination as soon as possible and no later than 72 hours following onset of symptoms. The nature of any rash was characterized by principal investigator either as a measles-like, rubella-like, varicella-like or “other”. Study investigators reviewed the diary card with the participant or participant’s legal guardian 42 days vaccination to ensure consistency with protocol definitions. Table 1 below presents the frequency of solicited adverse reactions based on the final assessment by the study investigators.

Table 1: Proportion of Participants Reporting Solicited Adverse Reactions Following Vaccination with M-M-R II, Concomitantly Administered with VARIVAX, by the Intramuscular or Subcutaneous Route

	INTRAMUSCULAR N=374 %	SUBCUTANEOUS N=376 %
N=total number of participants in the group
* During the post vaccination monitoring period (0-42 days), 3 participants experienced a varicella-like injection-site rash at the M-M-R II injection site. All were reported in the subcutaneous group. † Intensity of injection site reaction: mild or ≤2.5 cm; moderate or >2.5 to ≤5.0 cm; severe or >5.0 cm. ‡ Intensity of pain: mild: awareness of symptom but easily tolerated; moderate: definitely acting like something is wrong; severe: extremely distressed or unable to do usual activities. § Testing to distinguish between rash caused by wild-type or vaccine virus was not performed. Reports of measles-, rubella-, and varicella-like rash included 3 reports of measles, 1 report of rubella, and 1 report of varicella, all with onset within 15 days post-vaccination. ¶ The percentage of fever is defined within the population who had valid temperature measurements. One participant in IM group and two participants in SC group did not have temperature measurements and were excluded from the denominator; resulting in N=373 and N=374, respectively. # In the IM Group 92.3% of fevers were documented using the rectal route of measurement and 7.7% of fevers were documented only by the axillary route of measurement. In the SC Group 89.6% of fevers were documented using the rectal route of measurement and 10.4% of fevers were documented only by the axillary route of measurement.
Solicited injection-site reactions at MMR injection-site (Days 0 to 4)*
Erythema †	10.4	16.2
Mild	8.8	13.0
Moderate	0.8	3.2
Severe	0	0
Missing	0.8	0
Pain ‡	7.0	7.2
Mild	5.1	5.9
Moderate	1.9	1.3
Severe	0	0
Swelling †	1.9	5.3
Mild	1.1	2.9
Moderate	0.5	1.1
Severe	0	0
Missing	0.3	1.3
Solicited systemic reactions (Days 0 to 42)
Measles-like rash §	2.9	2.7
Rubella-like rash §	2.7	2.7
Varicella-like rash §	0.5	3.2
Mumps-like illness	0	0.3
Fever (temperature ≥38.0°C)¶, #	66.5	66.8
38.0-38.5°C	20.4	22.2
>38.5-39.0°C	17.4	16.6
>39.0-39.5°C	14.2	13.4
>39.5-40.0°C	11.8	11.0
>40.0°C	2.7	3.7

Unsolicited adverse events that occurred within 42 days following vaccination were recorded using diary cards supplemented by medical review. Data on unsolicited adverse events were transcribed into the study database during an on-site visit at day 42. The rates and types of reported adverse events (AEs) across groups were similar and included common clinical events that are often reported in the evaluated populations. Serious adverse events occurred at rates of 0.3% and 1% in the intramuscular and subcutaneous groups, respectively. One moderate intensity case of otitis media occurred in a participant in the subcutaneous group was considered related to the study vaccination.