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ProQuad

ProQuad® powder and solvent for suspension for injection

Manufacturer
Merck Sharp & Dohme (UK) Limited
Label last updated
05 Jan 2026
Source
Official SmPC ↗

Combined MMR and chickenpox vaccine for children from 12 months. Two of its four viruses are grown on human foetal cell lines, and the label states that no formal efficacy studies of the combination were ever performed.

78 findings, each with the section of the label it comes from.

Ingredients and materials

  • Measles virus Enders' Edmonston strain, live and attenuated, not less than 3.00 log10 TCID50 per 0.5 ml doses.2
  • Mumps virus Jeryl Lynn level B strain, live and attenuated, not less than 4.30 log10 TCID50s.2
  • Rubella virus Wistar RA 27/3 strain, live and attenuated, not less than 3.00 log10 TCID50s.2
  • Varicella virus Oka/Merck strain, live and attenuated, not less than 3.99 log10 plaque forming unitss.2
  • Measles and mumps are produced in chick embryo cells; rubella is produced in human diploid lung (WI-38) fibroblasts and varicella in human diploid (MRC-5) cells - two different cell lines originally derived from human foetal tissues.2
  • May contain traces of recombinant human albumin (rHA)s.2
  • Contains a trace amount of neomycin; hypersensitivity to it is a contraindications.2, 4.3
  • Powder excipients: sucrose, hydrolysed gelatin, sodium chloride, sorbitol (E420), monosodium glutamate, sodium phosphate, sodium bicarbonate, potassium phosphate, potassium chloride, Medium 199 with Hanks' salts, Minimum Essential Medium Eagle, neomycin, phenol red, hydrochloric acid and sodium hydroxide to adjust pH, and ureas.6.1
  • Solvent: water for injectionss.6.1
  • Contains 16 mg sorbitol per dose, and the additive effect of other sorbitol or fructose products plus dietary intake should be taken into accounts.2, 4.4
  • Declared essentially sodium-free and potassium-free, less than 1 mmol of each per doses.4.4

Manufacture, storage and handling

  • Shelf life 18 monthss.6.3
  • Store and transport refrigerated at 2C to 8C, do not freeze, store in the original package to protect from lights.6.3, 6.4
  • After reconstitution the vaccine should be used immediately; in-use stability has been demonstrated for only 30 minutes at 20C to 25C, and it must be discarded if not used within 30 minutess.6.3, 6.6
  • Only the supplied solvent may be used, because it is free of preservatives or other antiviral substances that might inactivate the vaccines.6.6
  • A separate sterile syringe and needle must be used for each individual to prevent transmission of infectious agents from one individual to another, and a new needle must be used for the injection after reconstitutions.6.6
  • Intramuscular or subcutaneous injection, into the anterolateral thigh in younger children and the deltoid in older children, adolescents and adultss.4.2
  • Must be given subcutaneously in people with thrombocytopenia or a coagulation disorders.4.2, 4.4
  • The vaccine should under no circumstances be injected intravascularlys.4.2
  • Must not be mixed in a syringe with other vaccines, and must not be mixed with other medicinal products; no compatibility studies exists.6.6, 6.2
  • Two doses: a second dose of ProQuad, or a second dose of a single varicella vaccine, is needed for optimal protection against chickenpox. At least one month must elapse between live viral vaccines, and the second dose is preferably given within three monthss.4.2

Safety findings

  • Licensed from 12 months, with use from 9 months only under special circumstances such as national schedules, outbreaks, or travel to an area with high measles prevalences.4.1, 4.2
  • Not indicated and not studied in children under 9 months of ages.4.2
  • Children under 12 months vaccinated with a measles-containing vaccine may fail to respond because of circulating maternal antibodies or immaturity of the immune systems.4.4
  • Contraindicated in blood dyscrasias, leukaemia, lymphomas of any type, or other malignant neoplasms affecting the haematopoietic and lymphatic systems.4.3
  • Contraindicated in current immunosuppressive therapy including high doses of corticosteroids, but not in people receiving topical or low-dose parenteral corticosteroidss.4.3
  • Contraindicated in severe humoral or cellular immunodeficiency, whether primary or acquired, including severe combined immunodeficiency, agammaglobulinemia, AIDS or symptomatic HIV infection, or an age-specific CD4+ T-lymphocyte percentage below 25 per cent under 12 months, below 20 per cent at 12 to 35 months and below 15 per cent at 36 to 59 monthss.4.3
  • Contraindicated in a family history of congenital or hereditary immunodeficiency unless the immune competence of the recipient is demonstrateds.4.3
  • Contraindicated in active untreated tuberculosis. Children under treatment for tuberculosis have not experienced exacerbation of the disease when immunised with live measles virus vaccine, but no studies have been reported on the effect of measles virus vaccines in children with untreated tuberculosiss.4.3
  • Contraindicated in pregnancy, and pregnancy should be avoided for 1 month after vaccinations.4.3, 4.6
  • Vaccination should be postponed during any illness with fever above 38.5Cs.4.3
  • In severely immunocompromised individuals inadvertently vaccinated with a measles-containing vaccine, measles inclusion body encephalitis, pneumonitis and fatal outcome as a direct consequence of disseminated measles vaccine virus infection have been reporteds.4.3, 4.4
  • An increased risk of febrile seizure was observed in the 5 to 12 day window after the first dose of quadrivalent MMRV vaccines compared with giving MMR and varicella vaccines at the same time but separatelys.4.4
  • A post-marketing observational study in children aged 12 to 60 months revealed an approximate two-fold increase in febrile seizure risk in the 5 to 12 day window after a first dose: 0.70 per 1,000 against 0.32 per 1,000 children, in 31,298 children in each groups.4.8
  • That suggests one additional case of febrile seizure per 2,600 children vaccinated with ProQuad compared with separate administration of the MMR and varicella vaccines. The finding was confirmed by a study sponsored by the US Centers for Disease Control and Prevention, and in the 30-day window after vaccination no increased risk was observeds.4.8
  • Due caution is advised in people with an individual or family history of convulsions or a history of cerebral injury, and the physician should be alert to the temperature elevation that may follow vaccinations.4.4
  • Salicylates should be avoided for 6 weeks after vaccination because Reye syndrome has been reported with salicylates during wild-type varicella infections.4.4
  • Vaccination may not result in protection in all recipients, and immunocompromised patients without a contraindication may not respond as well and may still acquire measles, mumps, rubella or varicella on contact despite vaccination, so they should be monitored carefully for signs of these diseasess.4.4
  • Excretion of small amounts of live attenuated rubella virus from the nose or throat has occurred in the majority of susceptible individuals 7 to 28 days after vaccination. There is no confirmed evidence it is transmitted to susceptible contacts, so transmission through close personal contact is accepted as a theoretical possibility but 'is not regarded as a significant risk'. Transmission of rubella vaccine virus to infants via breast milk has been documented without any evidence of clinical diseases.4.4
  • There are no reports of transmission of the Enders' Edmonston measles strain or the Jeryl Lynn mumps strain from vaccine recipients to susceptible contactss.4.4
  • Post-marketing experience suggests transmission of the Oka/Merck varicella vaccine virus, resulting in varicella infection including disseminated disease, may rarely occur between vaccine recipients - who may or may not develop a varicella-like rash - and contacts susceptible to varicella, including healthy people as well as high-risk individualss.4.4, 4.8
  • Vaccine recipients should try to avoid close association with high-risk individuals susceptible to varicella - immunocompromised people, pregnant women without a documented history of chickenpox or laboratory evidence of prior infection, and newborns of such mothers - for up to 6 weeks after vaccinations.4.4
  • Cases of thrombocytopenia have been reported in post-marketing experience after primary vaccination. Post-marketing experience with live MMR vaccine indicates that people with current thrombocytopenia may develop more severe thrombocytopenia after vaccination, and those who had thrombocytopenia after a first dose may develop it again with repeat doses. Serologic status may be evaluated to decide whether further doses are neededs.4.4
  • Encephalitis has been reported during post-marketing use of live attenuated measles, mumps, rubella and varicella vaccines, with fatal outcomes in a few cases especially in immunocompromised patients; vaccinees or parents should seek prompt medical attention for symptoms such as loss or reduced levels of consciousness, convulsions or ataxia with fever and headaches.4.4, 4.8
  • Complications of varicella from vaccine strain, including herpes zoster and disseminated disease such as aseptic meningitis and encephalitis, have been reported in both immunocompromised and immunocompetent individuals, with a few fatal cases of encephalitis especially in immunocompromised peoples.4.8
  • Aseptic meningitis has been reported after MMR vaccination, and although a causal relationship has been shown for other strains of mumps vaccine, 'there is no evidence to link Jeryl Lynn mumps vaccine to aseptic meningitis's.4.8
  • On subacute sclerosing panencephalitis: 'There is no evidence that measles vaccine can cause subacute sclerosing panencephalitis.' There have been reports of SSPE in children with no history of wild-type measles who received measles vaccine, some of which may have resulted from unrecognised measles in the first year of life or possibly from vaccination. A CDC retrospective case-controlled study showed the overall effect of measles vaccine has been to protect against SSPE by preventing measles with its inherent risks.4.8
  • Not-known-frequency post-marketing reactions include aseptic meningitis, encephalitis, herpes zoster, measles, orchitis, parotitis, epididymitis, thrombocytopenia, anaphylactic and anaphylactoid reactions, angioedema, measles inclusion body encephalitis, subacute sclerosing panencephalitis, Guillain-Barre syndrome, encephalopathy, transverse myelitis, Bell's palsy, cerebrovascular accident, optic neuritis, retinitis, retrobulbar neuritis, neurosensory deafness, pneumonitis, pneumonia, Stevens-Johnson syndrome, Henoch-Schonlein purpura, skin granuloma associated with vaccine-derived rubella virus, and arthritiss.4.8
  • Necrotizing retinitis has been reported post-marketing in immunocompromised individualss.4.8
  • Joint reactions vary with age and sex and are features of wild-type rubella infection: after vaccination in children they are generally uncommon (0 to 3 per cent) and brief, whereas in women rates are higher (12 to 20 per cent) and reactions tend to be more marked and longer, with symptoms persisting for months or rarely yearss.4.8
  • The long-term effect of varicella vaccination on the incidence of herpes zoster is unknown, and there are no long-term data currently available with ProQuads.4.8
  • Pregnancy: in a review of more than 3,500 susceptible women unknowingly in early pregnancy when vaccinated with a rubella-containing vaccine, no cases of congenital rubella syndrome were reported, but post-marketing surveillance has identified congenital rubella syndrome associated with a rubella vaccine strain after inadvertent vaccination in pregnancy. Foetal damage has not been documented when measles, mumps or varicella vaccines have been given to pregnant womens.4.6
  • Breastfeeding: breastfeeding women vaccinated with live attenuated rubella vaccine may secrete the virus in breast milk and transmit it to breastfed infants, with none developing symptomatic disease in those with serological evidence of infection. There is no evidence that varicella vaccine virus is excreted in breast milk, and it is not known whether measles or mumps vaccine virus is secreted in human milk, so caution is adviseds.4.6
  • Immunoglobulin or varicella-zoster immune globulin must not be given at the same time as ProQuad, and vaccination should be deferred for at least 3 months after blood or plasma transfusions or immune globulins, with the interval varying by product - for example 5 months for varicella-zoster immune globulins.4.5
  • Giving varicella zoster antibody-containing blood products within 1 month after a dose may reduce the immune response and hence protective efficacy, so should be avoided unless essentials.4.5
  • A tuberculin test should be done any time before, at the same time as, or at least 4 to 6 weeks after immunisation, because live MMR vaccines may temporarily depress tuberculin skin sensitivitys.4.5
  • There are insufficient data to support use with any other vacciness.4.5
  • Fertility: animal reproduction studies have not been conducted with ProQuad, and it has not been evaluated for potential to impair fertilitys.4.6
  • Overdose with a higher than recommended dose has been reported rarely, with an adverse reaction profile comparable to the recommended doses.4.9

Evidence and claims

  • 'Formal studies to evaluate the efficacy of ProQuad have not been performed.' Efficacy is taken from studies of the separate MMR and varicella vaccines made by the same companys.5.1
  • Seroconversion in response to MMR vaccination 'paralleled protection from these diseases', and ProQuad elicits antibody response rates similar to the separate MMR vaccines.5.1
  • More than 518 million doses of the company's MMR vaccine were distributed worldwide between 1978 and 2007, and widespread use of a two-dose schedule in the US, Finland and Sweden led to more than a 99 per cent reduction in the incidence of each of the three targeted diseasess.5.1
  • In combined trials of a single dose of the separate varicella vaccine in healthy children, protective efficacy against all severities of varicella ranged from 81 to 100 per cent; a large case-control study estimated 85 per cent effectiveness against all forms and 97 per cent against moderately severe and severe diseases.5.1
  • In a study comparing one dose (N=1,114) with two doses (N=1,102) of the separate varicella vaccine, efficacy over a 10-year period was 94 per cent for one dose and 98 per cent for two, and the cumulative rate of varicella was 7.5 per cent after one dose and 2.2 per cent after twos.5.1
  • Only the antibody threshold of 5 gpELISA units/ml - measured in an assay that is not commercially available - has been shown to correlate highly with long-term protection, and after a single dose of ProQuad the response rate by that measure was 90.9 per cent, against a varicella seroconversion rate of 97.9 to 99.8 per cent which 'has not been shown to correlate well with protection's.5.1
  • Vaccine response rates after a single dose were 97.7 per cent for measles, 96.3 to 98.8 per cent for mumps and 98.8 per cent for rubella, in clinical trials involving 6,987 subjectss.5.1
  • The safety profile is based on 5 clinical trials in which ProQuad was given without concomitant vaccines to 6,038 children aged 12 to 23 months, monitored for six weekss.4.8
  • Fever above 39.4C after ProQuad given alone ranged from 10.1 to 39.4 per cent across 7 clinical trials; given with the pneumococcal and/or hepatitis A vaccine it ranged from 15.2 to 27.2 per cents.4.8
  • With Infanrix Hexa, fever of 38.0C or above occurred in 69.3 per cent when given together, 61.1 per cent with ProQuad alone and 57.3 per cent with Infanrix Hexa alone; fever above 39.4C in 22.6, 20.5 and 15.9 per cent respectivelys.4.8
  • After a second dose, overall reaction rates were generally similar to or lower than after the first dose, and fever was lower after the second dose in all eight studiess.4.8
  • No specific studies have been conducted in individuals from 2 years of age who had not previously received measles, mumps, rubella and varicella vacciness.4.8
  • In clinical studies 2 cases of herpes zoster were reported in 2,108 healthy subjects aged 12 to 23 months followed for 1 year after one dose, both unremarkable with no sequelaes.4.8
  • Preclinical: 'Traditional non-clinical studies were not performed, but there are no non-clinical concerns considered relevant to clinical safety's.5.3

Document and licensing

  • Marketing authorisation holder: Merck Sharp & Dohme (UK) Limited, Londons.7
  • First authorised 1 January 2021s.9
  • Text last revised 17 December 2025; the document carries a 2025 copyright notice for Merck & Co., Rahway, New Jerseys.10
  • The label states that no formal efficacy studies of the combination were performed, and that no traditional preclinical studies were carried outs.5.1, 5.3
  • Suspected reactions are reported through the MHRA Yellow Card schemes.4.8

Every line above is a summary of a statement in the manufacturer's own label, with the section number it comes from. Nothing has been added from any other source. The full list of flagged sentences is below, as it came out of the document.

Listed ingredients

Section 2 - qualitative and quantitative composition source ↗

After reconstitution, one dose (0.5 mL) contains:
 Measles virus^1 Enders' Edmonston strain (live, attenuated) ........ not less than 3.00 log10 TCID50*
 Mumps virus^1 Jeryl Lynn™ (Level B) strain (live, attenuated) ... not less than 4.30 log10 TCID50*
 Rubella virus^2 Wistar RA 27/3 strain (live, attenuated) ............... not less than 3.00 log10 TCID50*
 Varicella virus^3 Oka/Merck strain (live, attenuated) .................... not less than 3.99 log10 PFU**
 *50% tissue culture infectious dose
 **plaque-forming units
 (^1) Produced in chick embryo cells.
 (^2) Produced in human diploid lung (WI-38) fibroblasts.
 (^3) Produced in human diploid (MRC-5) cells.
 The vaccine may contain traces of recombinant human albumin (rHA).
 This vaccine contains a trace amount of neomycin. See section 4.3.
 Excipient(s) with known effect 
 The vaccine contains 16 milligrams of sorbitol per dose. See section 4.4. 
 For the full list of excipients, see section 6.1.

What these are, in plain English

  • attenuated - Weakened on purpose so the organism cannot cause the disease in a healthy person.
  • recombinant - Made by genetic engineering: the gene for one piece of the germ is put into a laboratory cell or bacterium, which then makes that piece.
  • neomycin - An antibiotic used during manufacture to stop bacteria growing. Traces may remain, which is why a neomycin allergy is a contraindication.
  • sorbitol - A sugar alcohol used as a stabiliser and to give the liquid bulk. Also found in sugar-free food.

Other ingredients (excipients)

Section 6.1 source ↗

  • Powder
  • SucroseSugar. Used as a stabiliser so the vaccine keeps its potency in storage.
  • Hydrolysed gelatinA protein made by boiling animal collagen. Porcine gelatin comes from pig skin or bone; hydrolysed gelatin is broken into smaller pieces. Used as a stabiliser, and it is the reason some people with a gelatin allergy cannot have this vaccine.
  • Sodium chlorideSalt. Used to keep the liquid at the same saltiness as the body.
  • Sorbitol (E 420)A sugar alcohol used as a stabiliser and to give the liquid bulk. Also found in sugar-free food.
  • Monosodium glutamateThe flavour enhancer known as MSG, a salt of the amino acid glutamate. Here it acts as a stabiliser, not a flavour.
  • Sodium phosphateA phosphate buffer, used to hold the liquid at a steady acidity.
  • Sodium bicarbonateBicarbonate of soda, used to hold the acidity steady.
  • Potassium phosphateA phosphate buffer, used to hold the liquid at a steady acidity.
  • Potassium chlorideA mineral salt, similar to salt, used to balance the liquid.
  • Medium 199 with Hanks' SaltsA standard laboratory nutrient mixture (salts, vitamins, amino acids, sugars) that cells are grown in. Its residues are diluted out almost entirely.
  • Minimum Essential Medium, Eagle (MEM)A standard laboratory nutrient mixture that cells are grown in.
  • NeomycinAn antibiotic used during manufacture to stop bacteria growing. Traces may remain, which is why a neomycin allergy is a contraindication.
  • Phenol redA preservative that stops bacteria growing. Also used in some antiseptics. It is toxic in large amounts, which is why only trace quantities are used.
  • Hydrochloric acid (to adjust pH)A strong acid used in tiny amounts to adjust the acidity of the liquid.
  • Sodium hydroxide (to adjust pH)An alkali used in tiny amounts to adjust the acidity of the liquid.
  • UreaA waste product the body makes anyway, used here in a small amount as a stabiliser.
  • Solvent
  • Water for injections.Purified water to the standard used for injected medicines. It is the liquid the other ingredients are dissolved in.
Audit trail: every flagged sentence in the document (83)

These are the sentences the mechanical filter pulled out, in the document's own words, grouped by section. They are what the briefing above was built from, kept here so you can check nothing was left out. Some are fragments and some are technical, which is why the briefing exists.

4.2 Posology and method of administration

  1. At least one month must elapse between the first and second dose of any live viral attenuated vaccine.

    Section 4.2 Posology and method of administration source ↗

    In plain English

    • attenuated - Weakened on purpose so the virus or bacterium can no longer cause the disease in a healthy person.

    Genetic engineering, vectors and GMOs matched: attenuated

  2. ProQuad is not indicated in this subset of the paediatric population.

    Section 4.2 Posology and method of administration source ↗

    Not recommended, contraindicated or restricted matched: is not indicated

  3. The safety and efficacy of ProQuad in children under 9 months of age have not been established.

    Section 4.2 Posology and method of administration source ↗

    In plain English

    • not been established - There is not yet enough evidence to state a conclusion.
    • efficacy - How well it works in the controlled conditions of a trial.

    Efficacy, effectiveness and endpointsNo data / not studied matched: efficacy, have not been established

4.3 Contraindications

  1. Hypersensitivity to any varicella vaccine or measles, mumps, or rubella vaccine or to any of the excipients listed in section 6.1, including neomycin (see sections 2 and 4.4).

    Section 4.3 Contraindications source ↗

    In plain English

    • hypersensitivity - An allergic-type reaction, from a mild rash up to a severe reaction.

    Trace residues and process chemicals matched: neomycin

  2. Blood dyscrasias, leukaemia, lymphomas of any type, or other malignant neoplasms affecting the haematopoietic and lymphatic system.

    Section 4.3 Contraindications source ↗

    Animal, human or cell-line derived material matched: blood

  3. ProQuad is not contraindicated in individuals who are receiving topical or low-dose parenteral corticosteroids (e.g., for asthma prophylaxis or replacement therapy).

    Section 4.3 Contraindications source ↗

    In plain English

    • contraindicated - A situation where the medicine should not be given at all.

    Not recommended, contraindicated or restricted matched: contraindicated

  4. In severely immunocompromised individuals inadvertently vaccinated with measles-containing vaccine, measles inclusion body encephalitis, pneumonitis, and fatal outcome as a direct consequence of disseminated measles vaccine virus infection have been reported.

    Section 4.3 Contraindications source ↗

    In plain English

    • immunocompromised - Having a weakened immune system, from illness or from medicines such as chemotherapy.
    • encephalitis - Inflammation of the brain.

    Immune system, shedding and transmissionRare or very rare serious events matched: fatal, immunocompromised

  5. Children under treatment for tuberculosis have not experienced exacerbation of the disease when immunized with live measles virus vaccine.

    Section 4.3 Contraindications source ↗

    Genetic engineering, vectors and GMOs matched: live

  6. No studies have been reported to date on the effect of measles virus vaccines on children with untreated tuberculosis.

    Section 4.3 Contraindications source ↗

    In plain English

    • no studies - No research has been done on this point.

    No data / not studied matched: no studies

  7. Furthermore, pregnancy should be avoided for 1 month following vaccination (see section 4.6).

    Section 4.3 Contraindications source ↗

    Not recommended, contraindicated or restricted matched: should be avoided

4.4 Special warnings and precautions for use

  1. Additionally, live measles vaccine and live mumps vaccine are produced in chick embryo cell culture.

    Section 4.4 Special warnings and precautions for use source ↗

    Genetic engineering, vectors and GMOs matched: live

  2. Persons 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.

    Section 4.4 Special warnings and precautions for use source ↗

    In plain English

    • hypersensitivity - An allergic-type reaction, from a mild rash up to a severe reaction.

    Animal, human or cell-line derived material matched: egg

  3. Vaccine recipients should avoid use of salicylates for 6 weeks after vaccination with ProQuad as Reye syndrome has been reported following the use of salicylates during wild-type varicella infection.

    Section 4.4 Special warnings and precautions for use source ↗

    In plain English

    • reye - Reye's syndrome: a rare and serious illness affecting the brain and liver that can follow a viral infection in children given aspirin-type medicines.

    Immune system, shedding and transmissionRare or very rare serious events matched: reye

  4. Excretion of small amounts of the live attenuated rubella virus from the nose or throat has occurred in the majority of susceptible individuals 7 to 28 days after vaccination.

    Section 4.4 Special warnings and precautions for use source ↗

    In plain English

    • live attenuated - A vaccine containing a weakened but still living organism. It can still replicate in the body and, with a nasal flu vaccine, be passed on.

    Genetic engineering, vectors and GMOs matched: attenuated

  5. Consequently, transmission through close personal contact, while accepted as a theoretical possibility, is not regarded as a significant risk; however, transmission of the rubella vaccine virus to infants via breast milk has been documented without any evidence of clinical disease (see section 4.6).

    Section 4.4 Special warnings and precautions for use source ↗

    In plain English

    • transmission - Passing something from one person to another.

    Immune system, shedding and transmission matched: transmission

  6. There are no reports of transmission of the more attenuated Enders' Edmonston strain of measles virus or the Jeryl Lynn™ strain of mumps virus from vaccine recipients to susceptible contacts.

    Section 4.4 Special warnings and precautions for use source ↗

    In plain English

    • transmission - Passing something from one person to another.
    • attenuated - Weakened on purpose so the virus or bacterium can no longer cause the disease in a healthy person.

    Genetic engineering, vectors and GMOsImmune system, shedding and transmission matched: attenuated, transmission

  7. Post-marketing experience suggests that transmission of varicella vaccine virus (Oka/Merck strain) resulting in varicella infection including disseminated disease may rarely occur between vaccine recipients (who develop or do not develop a varicella-like rash) and contacts susceptible to varicella including healthy as well as high-risk individuals (see section 4.8).

    Section 4.4 Special warnings and precautions for use source ↗

    In plain English

    • post-marketing - After the product went on the market and was given to the public, as opposed to during the original clinical trials.
    • transmission - Passing something from one person to another.

    Immune system, shedding and transmission matched: transmission

  8. In circumstances where contact with high-risk individuals susceptible to varicella is unavoidable, the potential risk of transmission of the varicella vaccine virus should be weighed against the risk of acquiring and transmitting wild-type varicella virus.

    Section 4.4 Special warnings and precautions for use source ↗

    In plain English

    • transmission - Passing something from one person to another.

    Immune system, shedding and transmission matched: transmission

  9. Post-marketing experience with live measles, mumps, and rubella vaccine indicates that individuals with current thrombocytopenia may develop more severe thrombocytopenia following vaccination.

    Section 4.4 Special warnings and precautions for use source ↗

    In plain English

    • thrombocytopenia - A low platelet count, which makes bruising and bleeding easier.
    • post-marketing - After the product went on the market and was given to the public, as opposed to during the original clinical trials.

    Genetic engineering, vectors and GMOs matched: live

  10. In addition, individuals who experienced thrombocytopenia following the first dose of a live measles, mumps, and rubella vaccine may develop thrombocytopenia with repeat doses.

    Section 4.4 Special warnings and precautions for use source ↗

    In plain English

    • thrombocytopenia - A low platelet count, which makes bruising and bleeding easier.

    Genetic engineering, vectors and GMOs matched: live

  11. In the 5- to 12-day timeframe after the administration of the first dose of quadrivalent measles, mumps, rubella and varicella vaccines in children, an increased risk of febrile seizure was observed compared to concomitant administration of measles, mumps, rubella and varicella vaccines (see sections 4.8 and 5.1).

    Section 4.4 Special warnings and precautions for use source ↗

    Rare or very rare serious events matched: seizure

  12. Immunocompromised patients who have no contraindication for this vaccination (see section 4.3) may not respond as well as immunocompetent patients; therefore, some of these patients may acquire measles, mumps, rubella, or varicella in case of contact, despite appropriate vaccine administration.

    Section 4.4 Special warnings and precautions for use source ↗

    In plain English

    • immunocompromised - Having a weakened immune system, from illness or from medicines such as chemotherapy.

    Immune system, shedding and transmission matched: immunocompromised

  13. However, post-exposure prophylaxis for varicella and measles has been demonstrated with Varicella Vaccine live (Oka/Merck) and the measles-containing vaccines manufactured by Merck Sharp & Dohme LLC, Rahway, NJ 07065, USA (herein after MSD), respectively.

    Section 4.4 Special warnings and precautions for use source ↗

    Genetic engineering, vectors and GMOs matched: live

  14. Encephalitis has been reported during post-marketing use of live attenuated measles, mumps, rubella and varicella vaccines.

    Section 4.4 Special warnings and precautions for use source ↗

    In plain English

    • live attenuated - A vaccine containing a weakened but still living organism. It can still replicate in the body and, with a nasal flu vaccine, be passed on.
    • post-marketing - After the product went on the market and was given to the public, as opposed to during the original clinical trials.
    • encephalitis - Inflammation of the brain.

    Genetic engineering, vectors and GMOs matched: attenuated

  15. In a few cases fatal outcomes have been observed, especially in patients who were immunocompromised (see section 4.3).

    Section 4.4 Special warnings and precautions for use source ↗

    In plain English

    • immunocompromised - Having a weakened immune system, from illness or from medicines such as chemotherapy.

    Immune system, shedding and transmissionRare or very rare serious events matched: fatal, immunocompromised

4.5 Interaction with other medicinal products and other forms of interaction

  1. At least 1 month should elapse between receipt of a live virus vaccine and ProQuad.

    Section 4.5 Interaction with other medicinal products and other forms of interaction source ↗

    Genetic engineering, vectors and GMOs matched: live

  2. Administration of immune globulins concomitantly with ProQuad may interfere with the expected immune response.

    Section 4.5 Interaction with other medicinal products and other forms of interaction source ↗

    Efficacy, effectiveness and endpoints matched: immune response

  3. Vaccination should be deferred for at least 3 months following blood or plasma transfusions, or administration of immune globulins (Ig).

    Section 4.5 Interaction with other medicinal products and other forms of interaction source ↗

    Animal, human or cell-line derived material matched: blood

  4. Administration of varicella zoster virus antibody-containing blood products, including VZIG or other immune globulin preparations, within 1 month following a dose of ProQuad may reduce the immune response to the vaccine and hence reduce its protective efficacy.

    Section 4.5 Interaction with other medicinal products and other forms of interaction source ↗

    In plain English

    • efficacy - How well it works in the controlled conditions of a trial.

    Animal, human or cell-line derived materialEfficacy, effectiveness and endpoints matched: blood, efficacy

  5. Therefore, administration of any of these products should be avoided within 1 month after a dose of ProQuad unless considered to be essential.

    Section 4.5 Interaction with other medicinal products and other forms of interaction source ↗

    Not recommended, contraindicated or restricted matched: should be avoided

  6. It has been reported that live attenuated measles, mumps and rubella virus vaccines given individually may result in a temporary depression of tuberculin skin sensitivity.

    Section 4.5 Interaction with other medicinal products and other forms of interaction source ↗

    In plain English

    • live attenuated - A vaccine containing a weakened but still living organism. It can still replicate in the body and, with a nasal flu vaccine, be passed on.

    Genetic engineering, vectors and GMOs matched: attenuated

  7. There are insufficient data to support the use of ProQuad with any other vaccines.

    Section 4.5 Interaction with other medicinal products and other forms of interaction source ↗

    In plain English

    • insufficient - Not enough to draw a conclusion from.

    Limited, insufficient or inconclusive matched: insufficient

4.6 Fertility, pregnancy and lactation

  1. Foetal damage has not been documented when measles, mumps or varicella vaccines have been given to pregnant women.

    Section 4.6 Fertility, pregnancy and lactation source ↗

    Animal, human or cell-line derived material matched: foetal

  2. Pregnancy should be avoided for 1 month following vaccination.

    Section 4.6 Fertility, pregnancy and lactation source ↗

    Not recommended, contraindicated or restricted matched: should be avoided

  3. Studies have shown that breast-feeding postpartum women vaccinated with live attenuated rubella vaccine may secrete the virus in breast milk and transmit it to breast-fed infants.

    Section 4.6 Fertility, pregnancy and lactation source ↗

    In plain English

    • live attenuated - A vaccine containing a weakened but still living organism. It can still replicate in the body and, with a nasal flu vaccine, be passed on.

    Genetic engineering, vectors and GMOsImmune system, shedding and transmission matched: attenuated, transmit

  4. It is not known whether measles or mumps vaccine virus is secreted in human milk.

    Section 4.6 Fertility, pregnancy and lactation source ↗

    In plain English

    • not known - The label's lowest band: the number of cases is too small, or the reporting too patchy, to work out how often it happens.

    No data / not studied matched: not known

  5. ProQuad has not been evaluated for potential to impair fertility.

    Section 4.6 Fertility, pregnancy and lactation source ↗

    In plain English

    • has not been evaluated - It has not been tested or measured in this group or situation.

    No data / not studied matched: has not been evaluated

4.8 Undesirable effects

  1. The only vaccine-related systemic adverse reactions reported at a significantly greater rate in individuals who received the earlier formulation of ProQuad compared to individuals who received the measles, mumps, and rubella vaccine manufactured by MSD and Varicella Vaccine live (Oka/Merck) were fever (≥39.4°C rectal equivalent or abnormal) and measles-like rash.

    Section 4.8 Undesirable effects source ↗

    Genetic engineering, vectors and GMOs matched: live

  2. The only vaccine related injection-site adverse reaction that was more frequent among recipients of ProQuad than among recipients of Varicella Vaccine live (Oka/Merck) and the measles, mumps, and rubella vaccine manufactured by MSD was rash at the injection site.

    Section 4.8 Undesirable effects source ↗

    Genetic engineering, vectors and GMOs matched: live

  3. Children who received ProQuad at 4 through 6 years of age after primary immunization with Varicella Vaccine live (Oka/Merck) and the measles, mumps, and rubella vaccine manufactured by MSD

    Section 4.8 Undesirable effects source ↗

    Genetic engineering, vectors and GMOs matched: live

  4. The rates and types of adverse reactions seen in the study group that received ProQuad were generally similar to those seen in the groups that received Varicella Vaccine live (Oka/Merck) and the measles, mumps, and rubella vaccine manufactured by MSD (see section 5.1 for study description).

    Section 4.8 Undesirable effects source ↗

    Genetic engineering, vectors and GMOs matched: live

  5. Additionally, other adverse events have been reported with post-marketing use of ProQuad and/or in clinical studies and post-marketing use of either the measles, mumps, and rubella vaccine manufactured by MSD, the monovalent component vaccines of the measles, mumps, and rubella vaccine manufactured by MSD, or Varicella Vaccine live (Oka/Merck).

    Section 4.8 Undesirable effects source ↗

    In plain English

    • post-marketing - After the product went on the market and was given to the public, as opposed to during the original clinical trials.

    Genetic engineering, vectors and GMOs matched: live

  6. The frequency of these adverse events is qualified as "not known" when it cannot be estimated based on the available data.

    Section 4.8 Undesirable effects source ↗

    In plain English

    • not known - The label's lowest band: the number of cases is too small, or the reporting too patchy, to work out how often it happens.

    No data / not studied matched: not known

  7. Not known (cannot be estimated from the available data)

    Section 4.8 Undesirable effects source ↗

    In plain English

    • not known - The label's lowest band: the number of cases is too small, or the reporting too patchy, to work out how often it happens.

    No data / not studied matched: not known

  8. Aseptic meningitis*, Encephalitis*, Epididymitis, Herpes zoster*, Infection, Measles, Orchitis, Parotitis

    Section 4.8 Undesirable effects source ↗

    In plain English

    • encephalitis - Inflammation of the brain.
    • meningitis - Inflammation of the lining around the brain and spinal cord.

    Rare or very rare serious events matched: meningitis

  9. Ataxia, Seizure, Headache, Hyperkinesia, Hypersomnia, Lethargy, Tremor

    Section 4.8 Undesirable effects source ↗

    Rare or very rare serious events matched: seizure

  10. Bell's palsy, Cerebrovascular accident, Dizziness, Encephalopathy*, Guillain-Barré syndrome, Measles inclusion body encephalitis (see section 4.3), Ocular palsies, Paraesthesia, Polyneuropathy, Subacute sclerosing panencephalitis*, Syncope, Transverse myelitis

    Section 4.8 Undesirable effects source ↗

    In plain English

    • encephalitis - Inflammation of the brain.

    Rare or very rare serious events matched: bell's palsy

  11. Arthritis, Arthralgia* , Musculoskeletal pain, Myalgia, Swelling

    Section 4.8 Undesirable effects source ↗

    In plain English

    • arthralgia - Joint pain.
    • myalgia - Muscle aches.

    Rare or very rare serious events matched: arthritis

  12. ^+ Varicella caused by vaccine strain was observed in post-marketing use with Varicella Vaccine live (Oka/Merck).

    Section 4.8 Undesirable effects source ↗

    In plain English

    • post-marketing - After the product went on the market and was given to the public, as opposed to during the original clinical trials.

    Genetic engineering, vectors and GMOs matched: live

  13. Cases of aseptic meningitis have been reported following measles, mumps, and rubella vaccination.

    Section 4.8 Undesirable effects source ↗

    In plain English

    • meningitis - Inflammation of the lining around the brain and spinal cord.

    Rare or very rare serious events matched: meningitis

  14. Although a causal relationship between other strains of mumps vaccine and aseptic meningitis has been shown, there is no evidence to link Jeryl Lynn™ mumps vaccine to aseptic meningitis.

    Section 4.8 Undesirable effects source ↗

    In plain English

    • meningitis - Inflammation of the lining around the brain and spinal cord.

    Rare or very rare serious events matched: meningitis

  15. Complications of varicella from vaccine strain including herpes zoster and disseminated disease such as aseptic meningitis and encephalitis have been reported in immunocompromised or immunocompetent individuals.

    Section 4.8 Undesirable effects source ↗

    In plain English

    • immunocompromised - Having a weakened immune system, from illness or from medicines such as chemotherapy.
    • encephalitis - Inflammation of the brain.
    • meningitis - Inflammation of the lining around the brain and spinal cord.

    Immune system, shedding and transmissionRare or very rare serious events matched: immunocompromised, meningitis

  16. A few cases of encephalitis with a fatal outcome have been observed following vaccination with live attenuated varicella vaccines, especially in immunocompromised people (see section 4.4).

    Section 4.8 Undesirable effects source ↗

    In plain English

    • immunocompromised - Having a weakened immune system, from illness or from medicines such as chemotherapy.
    • live attenuated - A vaccine containing a weakened but still living organism. It can still replicate in the body and, with a nasal flu vaccine, be passed on.
    • encephalitis - Inflammation of the brain.

    Genetic engineering, vectors and GMOsImmune system, shedding and transmissionRare or very rare serious events matched: attenuated, fatal, immunocompromised

  17. Consistent with clinical study data on the timing of fever and measles-like rash, a post-marketing observational study in children 12 to 60 months of age revealed an approximate two-fold increase (0.70 per 1 000 vs. 0.32 per 1 000 children) in the risk of febrile seizures in the 5- to 12-day timeframe after a first dose of ProQuad (N=31,298) compared with concomitant administration of the [...]

    Section 4.8 Undesirable effects source ↗

    In plain English

    • post-marketing - After the product went on the market and was given to the public, as opposed to during the original clinical trials.

    Genetic engineering, vectors and GMOsRare or very rare serious events matched: live, seizure

  18. In severely immunocompromised individuals inadvertently vaccinated with measles-containing vaccine, measles inclusion body encephalitis, pneumonitis, and fatal outcome as a direct consequence of disseminated measles vaccine virus infection have been reported (see section 4.3); disseminated mumps and rubella vaccine virus infection has also been reported.

    Section 4.8 Undesirable effects source ↗

    In plain English

    • immunocompromised - Having a weakened immune system, from illness or from medicines such as chemotherapy.
    • encephalitis - Inflammation of the brain.

    Immune system, shedding and transmissionRare or very rare serious events matched: fatal, immunocompromised

  19. Arthralgia and/or arthritis (usually transient and rarely chronic), and polyneuritis are features of infection with wild-type rubella and vary in frequency and severity with age and gender, being greatest in adult females and least in prepubertal children.

    Section 4.8 Undesirable effects source ↗

    In plain English

    • arthralgia - Joint pain.

    Rare or very rare serious events matched: arthritis

  20. In women, incidence rates for arthritis and arthralgia are generally higher than those seen in children (12 to 20%), and the reactions tend to be more marked and of longer duration.

    Section 4.8 Undesirable effects source ↗

    In plain English

    • arthralgia - Joint pain.

    Rare or very rare serious events matched: arthritis

  21. Chronic arthritis has been associated with wild-type rubella infection and has been related to persistent virus and/or viral antigen isolated from body tissues.

    Section 4.8 Undesirable effects source ↗

    In plain English

    • antigen - The part of a germ that the immune system recognises and remembers.

    Rare or very rare serious events matched: arthritis

  22. Active surveillance data in children vaccinated with Varicella Vaccine live (Oka/Merck) and followed for 14 years after vaccination showed no increase in the frequency of herpes zoster compared to children with prior wild-type varicella during the pre-vaccine era.

    Section 4.8 Undesirable effects source ↗

    Genetic engineering, vectors and GMOs matched: live

  23. However, the long-term effect of varicella vaccination on the incidence of herpes zoster is unknown at present.

    Section 4.8 Undesirable effects source ↗

    No data / not studied matched: is unknown

  24. Necrotizing retinitis has been reported post-marketing in immunocompromised individuals.

    Section 4.8 Undesirable effects source ↗

    In plain English

    • immunocompromised - Having a weakened immune system, from illness or from medicines such as chemotherapy.
    • post-marketing - After the product went on the market and was given to the public, as opposed to during the original clinical trials.

    Immune system, shedding and transmission matched: immunocompromised

5.1 Pharmacodynamic properties

  1. Formal studies to evaluate the efficacy of ProQuad have not been performed.

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • efficacy - How well it works in the controlled conditions of a trial.

    Efficacy, effectiveness and endpoints matched: efficacy

  2. However, the efficacy of Varicella Vaccine live (Oka/Merck) and the measles, mumps, and rubella vaccine manufactured by MSD has been demonstrated in numerous studies.

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • efficacy - How well it works in the controlled conditions of a trial.

    Efficacy, effectiveness and endpointsGenetic engineering, vectors and GMOs matched: efficacy, live

  3. Efficacy of the measles, mumps, and rubella components of ProQuad was previously established in a series of double-blind controlled field trials with the monovalent vaccines manufactured by MSD, which demonstrated a high degree of protective efficacy.

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • efficacy - How well it works in the controlled conditions of a trial.

    Efficacy, effectiveness and endpoints matched: efficacy

  4. In these studies seroconversion in response to vaccination against measles, mumps, and rubella paralleled protection from these diseases.

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • seroconversion - A rise in antibodies after vaccination, measured in the blood.

    Efficacy, effectiveness and endpoints matched: seroconversion

  5. In combined clinical trials of a single dose of Varicella Vaccine live (Oka/Merck) in healthy children, the protective efficacy of the vaccine against all severities of varicella disease ranged from 81% to 100%.

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • efficacy - How well it works in the controlled conditions of a trial.

    Efficacy, effectiveness and endpointsGenetic engineering, vectors and GMOs matched: efficacy, live

  6. In a study comparing 1 dose (N=1 114) to 2 doses (N=1 102) of Varicella Vaccine live (Oka/Merck), the estimated vaccine efficacy against all severities of varicella disease for the 10-year observation period was 94% for 1 dose and 98% for 2 doses (p<0.001).

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • efficacy - How well it works in the controlled conditions of a trial.

    Efficacy, effectiveness and endpointsGenetic engineering, vectors and GMOs matched: efficacy, live

  7. Clinical studies have shown that immunization with ProQuad elicits rates of antibody responses against varicella virus ≥5 gpELISA Units/mL similar to those observed after vaccination with Varicella Vaccine live (Oka/Merck).

    Section 5.1 Pharmacodynamic properties source ↗

    Genetic engineering, vectors and GMOs matched: live

  8. The immunogenicity of a single dose of an earlier formulation of ProQuad was comparable to the immunogenicity of a single dose of its individual component vaccines (Varicella Vaccine live (Oka/Merck) and the measles, mumps, and rubella vaccine manufactured by MSD), currently used in routine vaccination in some countries.

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • immunogenicity - How strongly the vaccine provokes an immune response. It is measured in the blood, not by how many people avoided the illness.

    Genetic engineering, vectors and GMOs matched: live

  9. While the seroconversion rate for varicella was uniformly high (97.9% to 99.8% across all studies), seroconversion has not been shown to correlate well with protection.

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • seroconversion - A rise in antibodies after vaccination, measured in the blood.

    Efficacy, effectiveness and endpoints matched: seroconversion

  10. These results were similar to the immune response rates induced by concomitant administration of a single dose of Varicella Vaccine live (Oka/Merck) and the measles, mumps, and rubella vaccine manufactured by MSD at separate injection sites.

    Section 5.1 Pharmacodynamic properties source ↗

    Efficacy, effectiveness and endpointsGenetic engineering, vectors and GMOs matched: immune response, live

  11. The post-dose 2 geometric mean titres (GMTs) against mumps, rubella, and varicella 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.

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • geometric mean - An average used for antibody levels, because those vary over a huge range.

    Efficacy, effectiveness and endpoints matched: geometric mean

  12. The geometric mean titres (GMTs) following the second dose of ProQuad increased approximately 2 fold each for measles, mumps, and rubella, and approximately 41 fold for varicella (for safety information, see section 4.8).

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • geometric mean - An average used for antibody levels, because those vary over a huge range.

    Efficacy, effectiveness and endpoints matched: geometric mean

  13. Children who received ProQuad at 4 through 6 years of age after primary vaccination with Varicella Vaccine live (Oka/Merck) and the measles, mumps, and rubella vaccine manufactured by MSD

    Section 5.1 Pharmacodynamic properties source ↗

    Genetic engineering, vectors and GMOs matched: live

  14. The immunogenicity and safety of ProQuad were evaluated in a clinical trial involving 799 subjects 4 through 6 years of age who had received Varicella Vaccine live (Oka/Merck) and the measles, mumps, and rubella vaccine manufactured by MSD at least 1 month prior to study entry.

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • immunogenicity - How strongly the vaccine provokes an immune response. It is measured in the blood, not by how many people avoided the illness.

    Genetic engineering, vectors and GMOs matched: live

  15. Following the dose of ProQuad, GMTs for measles, mumps, rubella, and varicella were similar to those following a second dose of Varicella Vaccine live (Oka/Merck) and the measles, mumps, and rubella vaccine manufactured by MSD administered concomitantly at separate injection sites.

    Section 5.1 Pharmacodynamic properties source ↗

    Genetic engineering, vectors and GMOs matched: live

  16. In clinical studies involving healthy subjects who received 1 dose of Varicella Vaccine live (Oka/Merck), detectable varicella antibodies were present in most individuals tested for up to 10 years postvaccination.

    Section 5.1 Pharmacodynamic properties source ↗

    Genetic engineering, vectors and GMOs matched: live

  17. Observational studies of long-term effectiveness of varicella vaccine

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • effectiveness - How well it works in ordinary use in the real world.

    Efficacy, effectiveness and endpoints matched: effectiveness

  18. Surveillance data from two U.S. observational effectiveness studies confirmed that widespread varicella vaccination reduces the risk of varicella by approximately 90% and that protection is maintained over at least 15 years both in vaccinated and unvaccinated individuals.

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • effectiveness - How well it works in ordinary use in the real world.

    Efficacy, effectiveness and endpoints matched: effectiveness

  19. Over the entire follow-up, the incidence of varicella was approximately 10-fold lower among vaccinees than among children of the same age in the pre-vaccine era (estimated vaccine effectiveness over the study period was between 73% and 90%).

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • effectiveness - How well it works in ordinary use in the real world.

    Efficacy, effectiveness and endpoints matched: effectiveness

  20. Safety was evaluated in an observational study that included 69 237 children vaccinated with ProQuad 12 months to 12 years old and 69 237 matched children in a historical comparison group who were vaccinated concomitantly with the measles, mumps, and rubella vaccine manufactured by MSD, and the Varicella Vaccine live (Oka/Merck).

    Section 5.1 Pharmacodynamic properties source ↗

    Genetic engineering, vectors and GMOs matched: live

  21. Other than the increase in febrile seizure after the first dose, no safety concerns after the first or second dose were identified.

    Section 5.1 Pharmacodynamic properties source ↗

    Rare or very rare serious events matched: seizure

6.6 Special precautions for disposal and other handling

  1. It is important to use a separate sterile syringe and needle for each individual to prevent transmission of infectious agents from one individual to another.

    Section 6.6 Special precautions for disposal and other handling source ↗

    In plain English

    • transmission - Passing something from one person to another.

    Immune system, shedding and transmission matched: transmission

Read the whole document at the source ↗