PROQUAD

General Administration Information
For storage information, see the specific product information within the How Supplied section.
-Inform the patient, parent, guardian, or responsible adult of the benefits and risks of the vaccine. Provide the Vaccine Information Statements from the manufacturer to the recipient or guardian before each immunization. The action is required by the National Childhood Vaccine Injury Act of 1986.
-Record the manufacturer, lot number, administration date, and the name and address of the person administering the vaccine in the patient's permanent record. These actions are required by the National Childhood Vaccine Injury Act of 1986.

Route-Specific Administration

Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. When reconstituted, ProQuad is a clear, pale yellow or light pink liquid. Discard if it appears otherwise.
-Due to the potential for errors, establish a process to keep vaccines and their corresponding prefilled diluent syringe together if storage requirements do not differ. Prepare only 1 vaccine at a time and relabel the diluent syringe with the vaccine name after reconstitution.
Intramuscular Administration
-Use only the sterile vaccine diluent supplied with this vaccine, which may be in the form of a vial or a prefilled syringe. This diluent is free from preservatives or other agents that might inactivate the vaccine. Aseptic technique must be observed because the products do not contain preservatives.
-If using the supplied vial of diluent, withdraw the entire volume of the supplied diluent from the diluent vial and inject into the vial containing the lyophilized vaccine. If using the supplied prefilled syringe, attach a needle to the prefilled syringe and inject the entire volume of diluent from the syringe slowly into the vaccine vial. Gently agitate to mix thoroughly.
-Storage of reconstituted vaccine: May be stored at room temperature, protected from light, for up to 30 minutes. Discard if not used within 30 minutes.

Intramuscular Injection
-Withdraw the entire volume of the reconstituted vaccine and inject intramuscularly.

Subcutaneous Administration
-Use only the sterile vaccine diluent supplied with this vaccine, which may be in the form of a vial or a prefilled syringe. This diluent is free from preservatives or other agents that might inactivate the vaccine. Aseptic technique must be observed because the products do not contain preservatives.
-If using the supplied vial of diluent, withdraw the entire volume of the supplied diluent from the diluent vial and inject into the vial containing the lyophilized vaccine. If using the supplied prefilled syringe, attach a needle to the prefilled syringe and inject the entire volume of diluent from the syringe slowly into the vaccine vial. Gently agitate to mix thoroughly.
-Storage of reconstituted vaccine: May be stored at room temperature, protected from light, for up to 30 minutes. Discard if not used within 30 minutes.

Subcutaneous Injection
-Withdraw the entire volume of the reconstituted vaccine and inject subcutaneously.

Report all adverse reactions to the Vaccine Adverse Event Reporting System (VAERS), as well as the manufacturer. The toll-free number for VAERS is 1-800-822-7967. Educate the responsible adult(s) to promptly report any adverse reaction after vaccine administration to a health care provider.

Reye's syndrome has been associated with natural varicella illness. Children and adolescents affected had usually received salicylates. Patients in clinical studies of varicella virus vaccine live were advised not to use salicylates for 6 weeks after vaccination. There were no reports of Reye's syndrome during clinical trials.

A clinical trial designed to compare the safety of the refrigerator-stable formulation of ProQuad (Measles virus; Mumps virus; Rubella virus; Varicella virus vaccine, live) to the frozen formulation found no significant difference.

In a clinical trial of 6,038 children 12 to 23 months of age, fever (21.5% vs. 14.9%) and measles-like rash (3% vs. 2.1%) were two systemic adverse reactions that were more common after measles virus; mumps virus; rubella virus; varicella virus (MMRV) vaccine administration compared to after the concomitant administration of mumps virus; rubella virus; varicella virus (MMR) and varicella vaccine at separate injection sites. The events usually occurred 5 to 12 days after vaccination and were of short duration. A rash (unspecified) at the injection site was also more common among recipients of MMRV vaccine. Overall, the reported incidence of rash (various types) after MMRV administration is approximately 0.6% to 6%, and there appears to be a higher risk of rash with the first dose. The Advisory Committee on Immunization Practices (ACIP) recommends administration of the MMR vaccine and varicella virus vaccine as separate vaccines for the first dose in children 12 to 47 months of age unless the parent or caregiver expresses a preference for the combination MMRV vaccine. When the MMRV combination vaccine is administered as the first dose to children younger than 48 months, the risk of fever and febrile seizures is higher compared to administration of MMR and varicella vaccines at different injection sites. In a postmarketing observational study in 31,298 children who received their first dose of vaccine, febrile seizures were noted 5 to 12 days after vaccination in 0.7 per 1,000 recipients of MMRV vaccine. In an age- and gender-matched historical cohort of children who received concurrent MMR and varicella vaccine, the incidence was 0.32 per 1,000 recipients. In the 0 to 30 day time period after vaccination, the incidence of febrile seizures with MMRV vaccine (1.41 per 1,000) was not statistically greater than that observed in children receiving MMR and varicella vaccine concomitantly (1.28 per 1,000). An increased risk of febrile seizures with MMRV vaccine in the early period after vaccination was also noted in preliminary results from a CDC observational study. A febrile seizure 7 to 10 days after vaccination with MMRV vaccine was noted in 9 per 10,000 vaccinations, whereas the incidence was 4 per 10,000 vaccinations among recipients of concurrent MMR and varicella vaccine.

Among 4,497 children 12 to 23 months old who received the frozen formulation of ProQuad (Measles virus; Mumps virus; Rubella virus; Varicella virus vaccine, live), most adverse events occurred in a similar or lower percentage of children as compared with 2,038 children who received MMR and Varivax concomitantly at separate injection sites. A rash at the injection site was more common among recipients of ProQuad (2.3% vs. 1.5%). An injection site reaction with symptoms such as pain/soreness/tenderness (22 to 30.4%), erythema (14.4 to 18%), swelling (8.4 to 9.2%), and ecchymosis (1.5%) was the most common adverse event noted in trials. Extravasation has also been reported during post-marketing use of the drug.

Irritability was the most common neurologic adverse events in measles; mumps; rubella; varicella virus (MMRV) vaccine in clinical trials occurring in 4.9% to 6.7% of young children 12 to 23 months of age (first dose) and 1% to 2.4% of children 15 to 31 months or 4 to 6 years of age (second dose). Headache was reported by 0.8% of 4 to 6 year olds. Other nervous system adverse reactions reported with the post-marketing use of MMRV vaccine include agitation, apathy, nervousness or anxiety, ataxia, Bell's palsy, cerebrovascular accident (stroke), afebrile and febrile seizures, dizziness, abnormal dreams, Guillain-Barre syndrome, hypersomnia, ocular palsies, paresthesias, polyneuritis, polyneuropathy, syncope, transverse myelitis, and tremor. Cases of aseptic meningitis have been reported to VAERS after measles, mumps, and rubella vaccination. 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.

Induction of a subclinical infection with attenuated virus particles is expected after vaccine receipt. The vaccine virus in measles virus; mumps virus; rubella virus; varicella virus (MMRV) may establish latency of varicella-zoster virus in immunocompetent patients, with the potential for later development of herpes zoster. Varicella and herpes zoster infections with the vaccine strain have been noted in vaccine recipients during postmarketing experience. Postmarketing experience suggests that transmission of varicella infection, including disseminated disease, may occur rarely between healthy vaccinees who may or may not develop a varicella-like rash and in both healthy and high-risk contacts. In addition to varicella infection, the albumin contained in the vaccine is derived from human blood and, thus, could be a source of viral transmission. For example, theoretically, Creutzfeld-Jakob disease (CJD) could be transmitted. No cases of CJD or viral disease transmission associated with albumin use have been identified. Cough, upper respiratory infection, rhinorrhea, and naso-pharyngitis were reported in less than 2% of patients who received the MMRV live vaccine in a clinical trial (n = 1,519 children 12 to 23 months old). Infection and symptoms of an infection reported during postmarketing use of the drug include atypical measles, bronchitis, candidiasis, epididymitis, herpes simplex, influenza, orchitis, parotitis, pneumonia, pneumonitis, pulmonary congestion, rhinitis, sinusitis, sneezing, throat irritation, and skin infections such as cellulitis and impetigo. Due to the voluntary nature of postmarketing reports, neither a frequency nor a definitive causal relationship can be established.

Encephalitis, measles inclusion body encephalitis, encephalopathy, acute disseminated encephalomyelitis (ADEM), aseptic meningitis, and meningitis have been reported during the postmarketing surveillance period for measles virus; mumps virus; rubella virus; varicella virus (MMRV) vaccine. Although not reported with MMRV vaccination, cases of encephalitis or meningitis caused by vaccine strain varicella virus have been reported in immunocompetent individuals months to years after vaccination with varicella virus vaccine. Reported cases were commonly associated with preceding or concurrent herpes zoster rash. Subacute sclerosing panencephalitis (SSPE) has also been reported in the postmarketing surveillance period. Measles inclusion body encephalitis, pneumonitis, and death as a direct consequence of disseminated measles vaccine virus infection have been reported in immunocompromised patients inadvertently vaccinated with measles-containing vaccine.

Eczema was reported by 1% of 1,006 children vaccinated with measles virus; mumps virus; rubella virus; varicella virus vaccine (MMRV) in one clinical trial. In addition, the following hypersensitivity and dermatologic adverse reactions have been reported with the post-marketing use of MMRV: anaphylactoid reactions, bronchospasm, wheezing, angioedema, angioneurotic edema, facial edema, peripheral edema, pruritus, erythema multiforme, Henoch-Schonlein purpura, panniculitis, photosensitivity (sunburn), purpura, acute hemorrhagic edema of infancy, and Stevens-Johnson syndrome.

Chronic joint symptoms are associated with the rubella vaccine; arthralgia and transient arthritis occur more frequently among adult females than among pre-pubertal children. Joint reactions are reported to occur in 0% to 3% of children following vaccination with rubella vaccine. Chronic joint symptoms have been reported with rubella-containing vaccines. Arthritis, arthralgia (usually transient and rarely chronic), myalgia, musculoskeletal pain, swelling, and hip, leg, or neck pain have been reported with the postmarketing surveillance of measles virus; mumps virus; rubella virus; varicella virus vaccine, live.

Cases of transient thrombocytopenia have been reported within 4 to 6 weeks after vaccination with measles, mumps, and rubella vaccine. Thrombocytopenia, aplastic anemia, epistaxis, lymphadenitis, and regional lymphadenopathy have been reported with the postmarketing use of measles virus; mumps virus; rubella virus; varicella virus vaccine.

Vomiting and diarrhea were reported in less than 2% of patients who received the measles virus; mumps virus; rubella virus; varicella virus (MMRV) live vaccine in a clinical trial (n = 1,519 children 12 to 23 months old). Abdominal pain, flatulence, hematochezia, and oral ulceration were reported during post-marketing use of the MMRV live vaccine.

Cases of otalgia, hearing loss, ocular irritation, eyelid edema (blepharedema), retinitis, necrotizing retinitis (in immunocompromised individuals), optic neuritis, and retrobulbar neuritis have been reported during postmarketing use of the measles virus; mumps virus; rubella virus; varicella virus (MMRV) vaccine. Due to the voluntary nature of postmarketing reports, neither a frequency nor a definitive cause relationship can be established.

Prior to administration, inform the parent, guardian, or responsible adult of the benefits and risks of the vaccine, and provide the Vaccine Information Statement, accessible at the Centers for Disease Control and Prevention (CDC) website. These actions are required by the National Childhood Vaccine Injury Act of 1986. If a dose of measles virus; mumps virus; rubella virus; varicella virus vaccine has been previously given, question the parent or guardian about previous adverse reactions that may preclude further administration. Report all adverse reactions to the Vaccine Adverse Event Reporting System (VAERS), as well as the manufacturer. The toll-free number for VAERS is 1-800-822-7967. Educate the responsible adult(s) to promptly report any adverse reaction after vaccine administration to a health care provider.

If patients have received blood or plasma transfusion or administration of immune globulins (IG), then defer MMRV vaccination for at least 3 months. If Varicella Zoster Immune Globulin (VZIG) was administered, delay the administration of MMRV for 5 months. After administration of MMRV, any IG including VZIG should not be given for at least 1 month unless its use outweighs the benefits of vaccination. Immune globulins contain antibodies that may interfere with vaccine virus replication and decrease the expected immune response.

Measles virus; mumps virus; rubella virus; varicella virus (MMRV) vaccine, live is preservative-free, but it does contain trace amounts of neomycin from the manufacturing process and is contraindicated in patients with a history of immediate-type neomycin hypersensitivity (e.g., anaphylactoid reactions). Contact dermatitis from neomycin exposure is not a contraindication for vaccine receipt. If vaccine receipt is necessary for a patient with a history of anaphylactic reactions to neomycin, consult an allergist or immunologist and be prepared to treat an anaphylactoid reaction. MMRV contains gelatin as a stabilizer; MMRV is contraindicated in patients with gelatin hypersensitivity. Measles and mumps viruses are cultured from chick embryos. In persons with egg hypersensitivity, the risk for serious allergic reactions following administration of measles- or mumps-containing vaccines is extremely low, but patients with a history of anaphylactic, anaphylactoid, or other immediate reactions subsequent to egg ingestion may be at an enhanced risk of an immediate-type hypersensitivity reaction. In a study of 54 children with documented egg allergy, a single 0.5 mL subcutaneous dose of the MMR vaccine was administered safely, despite the confirmation of egg allergy with a food challenge. Thus, according to the CDC, skin testing is not required before administering MMR to persons allergic to eggs. Data indicate that most anaphylactic reactions to measles- and mumps-containing vaccines are not associated with hypersensitivity to egg antigens but to other components of the vaccines. Carefully evaluate the potential risk to benefit ratio and have adequate treatment for anaphylaxis readily available if the decision is made to administer the vaccine. The health care professional should have immediate availability of epinephrine 1 mg/mL injection and other agents used in the treatment of severe anaphylaxis in the event of a serious allergic reaction to the vaccine.

Measles virus; mumps virus; rubella virus; varicella virus vaccine (MMRV), live is contraindicated in patients with an active febrile illness with fever > 101.3 degrees F. MMRV vaccine also is contraindicated in patients with active, untreated tuberculosis. The effect of measles virus vaccines on children with untreated tuberculosis is unknown. The decision to administer or to delay vaccination because of current or recent febrile illness depends on the severity of symptoms and on the etiology of the disease. The Advisory Committee on Immunization Practices recommends that vaccinations be delayed during the course of a moderate or severe acute febrile illness and administered after the acute phase of illness has resolved. All vaccines can be given to persons with minor illnesses such as diarrhea, mild upper-respiratory infection with or without low-grade fever, or other low-grade febrile illness.

Recommendations and precautions for patients with immunosuppression are complex, but the measles virus; mumps virus; rubella virus; varicella virus (MMRV) live vaccine is contraindicated in any person with a primary immunodeficiency state (i.e., severe combined immunodeficiency (SCID), IgA deficiency, hypogammaglobulinemia, agammaglobulinemia, or dysgammaglobulinemia) or an acquired immunodeficiency state. Measles inclusion body encephalitis, pneumonitis, and death as a direct consequence of disseminated measles vaccine virus infection have been reported in immunocompromised patients inadvertently vaccinated with measles-containing vaccine; additionally, disseminated mumps, rubella, and varicella virus infection has occurred in immunosuppressed patients who were inadvertently given a MMRV vaccine. In addition, although there is no confirmed evidence to indicate the rubella virus can be transmitted to susceptible persons in contact with the vaccinated patient, there is a theoretical risk. Excretion of small amounts of the live, attenuated rubella virus from the nose or throat has occurred in the majority of susceptive individuals 7 to 28 days after vaccination. A family history of congenital or hereditary immunodeficiency is also a contraindication for MMRV vaccine unless the immune competence of the potential vaccine recipient is demonstrated. Vaccine recipients should avoid close association with susceptible high-risk individuals for 6 weeks. High-risk individuals include immunocompromised individuals, pregnant women without a documented history of chickenpox or laboratory evidence of prior infection, newborn infants of mothers without documented history of chickenpox or laboratory evidence of prior infection, and all newborn infants born younger than 28 weeks gestation regardless of maternal varicella immunity. In circumstances where contact with high-risk individuals is unavoidable, weigh the potential risk of transmission of vaccine virus against the risk of acquiring and transmitting natural varicella virus. The vaccine should also not be administered to those with cellular immune deficiency or those patients on immunosuppressive therapy such as high-dose corticosteroid therapy. Vaccination with MMRV vaccine can result in a more extensive vaccine-associated rash or disseminated disease in these patients. However, corticosteroid therapy usually is not a contraindication to administering live-virus vaccines when administration is short-term (less than 2 weeks); a low-to-moderate dose (less than 2 mg/kg of body weight or 20 mg/day of prednisone or equivalent for persons who weigh more than 10 kg when administered for less than 2 weeks); long-term, alternate-day treatment with short-acting preparations; maintenance physiologic doses (replacement therapy); or when administered topically (skin, eyes), inhaled, or by local injection. Healthcare providers should wait at least 1 month after discontinuation of high-dose corticosteroid therapy given for more than 2 weeks before administering MMRV vaccine. The vaccine is also contraindicated in patients with blood dyscrasias or any neoplastic disease that causes bone marrow suppression or affects the lymphatic system such as leukemia or lymphoma, including patients currently receiving chemotherapy or radiation therapy. Patients with leukemia, lymphoma, or other malignancies whose disease is in remission and whose chemotherapy or radiation therapy has been terminated for at least 3 months can receive live-virus vaccines.

Educate individuals of reproductive capacity on the importance of prevention of pregnancy for 4 weeks after vaccination. Reports have indicated that contracting wild-type measles during pregnancy may increase fetal risk, including spontaneous abortion, stillbirth, congenital defects, and prematurity. Mumps vaccine virus has been shown to infect the placenta and fetus, although there is no evidence that it causes congenital malformations in humans. Wild-type varicella can sometimes cause congenital varicella infection. In a 10-year survey involving over 700 pregnant women (of whom 189 received the Wistar RA 27/3 strain), administration of rubella vaccine within 3 months before or after conception did not result in abnormalities compatible with congenital rubella syndrome. Evaluate pregnant individuals for evidence of immunity to rubella and varicella. Vaccinate patients without evidence of immunity to rubella and varicella immediately after delivery and administer a second dose of varicella vaccine 4 to 8 weeks later.

The administration of measles virus; mumps virus; rubella virus; varicella virus (MMRV) vaccine to children 12-23 months of age who have not been previously vaccinated against measles, mumps, rubella, or varicella, nor had a history of the wild-type infections is associated with higher rates of fever and febrile seizures 5-12 days after vaccination compared to children vaccinated with MMR and varicella vaccine separately. The ACIP recommends administering the first dose of MMR and varicella as the individual MMR and varicella vaccines in children < 48 months of age unless the parents or caregivers object. The combined MMRV vaccine is recommended for first-time vaccination in children >= 48 months of age or for second-dose vaccination in children of any age. MMRV is FDA-approved for use in children aged 1 to 12 years. Safety and efficacy have not been established in neonates, infants, or adolescents.

Children with a personal or family history of a seizure disorder or a personal history of cerebral injury may be at an increased risk of developing febrile seizures after measles virus; mumps virus; rubella virus; varicella virus (MMRV) vaccine administration. Therefore, the Advisory Committee on Immunization Practices recommends that children with a personal or family history of seizures of any etiology be vaccinated with the MMR vaccine and varicella vaccine as the risks for using MMRV vaccine in these patients generally outweigh the benefits.

Patients with thrombocytopenia or patients who developed thrombocytopenia after a measles, mumps, and rubella-containing vaccine may not be appropriate candidates for the Measles virus; Mumps virus; Rubella virus; Varicella virus vaccine, live. Transient thrombocytopenia has been reported within 4 to 6 weeks after vaccination. Consider the potential risk and benefit of vaccination in patients with thrombocytopenia or in those who experienced thrombocytopenia after vaccination with a previous dose of a measles, mumps, and rubella-containing vaccine.

Measles virus; mumps virus; rubella virus; varicella virus vaccine, live contains albumin, a derivative of human blood. As with other products derived from or purified with human blood components, the remote possibility of contamination with Creutzfeldt-Jakob disease (CJD) and other viral infection exists in patients receiving the vaccine. Screening plasma donors for prior exposure to certain viruses, testing for the presence of viruses, and inactivating and/or reducing viruses has reduced the risk of transmission of infectious agents. Although there is a theoretical risk for transmission of CJD or viral disease, no cases have been identified that were associated with the use of albumin.

Patients with human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS) should not receive the MMRV vaccine. HIV-infected pediatric patients who have met criteria for vaccination (age specific CD4 percentages 15% or more) should receive the single antigen varicella vaccine along with the MMR vaccine, and not the combination MMRV vaccine.

The measles, mumps, rubella, and varicella (MMRV) vaccine may result in temporary suppression of tuberculin reactivity causing a laboratory test interference with a tuberculin skin test. Therefore, administer a tuberculin skin test either before, simultaneously with, or at least 4 to 6 weeks after MMRV vaccination to avoid false-negative results. Additionally, syndromic polymerase chain reaction (PCR) panels may incorrectly identify a measles infection if a patient recently received an MMR vaccine. Approximately 5% of patients experience a rash after the MMR vaccine; approximately 1% of syndromic panels report a positive measles result after MMR vaccination. Patients identified with a positive result were pediatric patients without known measles risk who, in most cases, received the vaccine less than 3 weeks beforehand. Inclusion of measles virus in syndromic PCR panels can result in incidental detection of measles vaccines. Health care providers should assess clinical features and vaccine history after a positive test.

Description: Measles virus; mumps virus; rubella virus; varicella virus (MMRV) vaccine, live is a combination subcutaneous injection consisting of 4 live, attenuated virus vaccinations intended to confer immunity against measles (rubeola), mumps, varicella (chickenpox), and rubella (German measles) viruses. The measles component consists of the Ender's line measles virus obtained from the attenuated Edmonston strain cultured from chick embryos. The mumps component consists of the Jeryl Lynn strain cultured from chick embryos. The rubella component consists of the Wistar Institute RA 27/3 strain of rubella virus propagated in human diploid [WI-38] cells, and the varicella component consists of the Oka/Merck strain of varicella-zoster virus propagated in MRC-5 cells. The antibody responses to each of the antigens in MMRV vaccine were similar compared with the responses after a single dose of the measles virus, mumps virus, rubella virus (MMR) vaccine and varicella virus vaccine given at separate injection sites. The Advisory Committee on Immunization Practices (ACIP) recommends administration of MMR vaccine and varicella virus vaccine as separate vaccines for the first dose for children 12 to 47 months of age, unless the child's parent or caregiver objects to 2 injections. The combination MMRV vaccine is recommended for the second dose at any age and the first dose for children 48 months or older. MMRV vaccine is associated with a higher risk for fever and febrile seizures in children 48 months or younger. The Centers for Disease Control and Prevention (CDC) issued a Health Alert Network (HAN) Health Advisory to increase awareness of an increase in measles cases globally and in the United States. From January 1 to March 14, 2024, the CDC was notified of 58 confirmed cases in the United States. Fifty-four (93%) of cases were linked to international travel. Most cases reported in 2024 have been among children aged 12 months and older who have not received measles-mumps-rubella (MMR) vaccine. All U.S. residents traveling internationally should be current on their MMR vaccinations. MMRV was FDA-approved in September 2005. MMRV is approved in children 1 to 12 years of age; all children should receive 2 doses of vaccines against these viruses, either as the combination MMRV or as separate injections of MMR vaccine and varicella virus vaccine. For routine immunization, ideally, children should receive separate injections of MMR and varicella vaccines at 12 to 15 months of age, and then a dose of the combination MMRV vaccine at 4 to 6 years of age.

General Dosing Information
-The Centers for Disease Control and Prevention (CDC) issued a Health Alert Network (HAN) Health Advisory to alert clinicians and public health officials of an increase in measles cases globally and in the United States. All U.S. residents traveling internationally should be current on their MMR vaccinations.
-The Advisory Committee on Immunization Practices (ACIP) recommends administration of measles virus, mumps virus, rubella virus (MMR) vaccine and varicella virus vaccine as separate vaccines for the first dose in children 12 to 47 months of age unless the parent or caregiver expresses a preference for the combination MMRV vaccine. When the MMRV combination vaccine is administered as the first dose to children younger than 48 months, the risk of fever and febrile seizures is higher compared to administration of MMR and varicella vaccines at different injection sites.
-The combination MMRV vaccine is generally preferred for the second dose in patients of any age (15 months through 12 years) and for the first dose in children 48 months and older; however, considerations for using the 2 separate vaccines include provider assessment, patient/parent preference, and potential adverse reactions.

For measles prophylaxis, mumps prophylaxis, rubella prophylaxis, and varicella (chickenpox) infection prophylaxis:
Intramuscular or Subcutaneous dosage:
Children: 0.5 mL IM or subcutaneously for 2 doses. For routine immunization, the recommended schedule is administration of the first MMR dose at age 12 to 15 months and the second dose at age 4 to 6 years. The maximum age for MMRV use is 12 years. MMR and varicella can be administered as separate vaccines or as the combined product (MMRV); risk of febrile seizures is higher if MMRV is administered as the first dose to children younger than 48 months. For catch-up immunization, the 2 doses should be administered at least 1 to 3 months apart depending on which products are administered. If both doses are going to be administered as the MMRV combination vaccine, then 3 months should elapse between doses. If 1 of the doses is administered as the separate components (MMR and varicella vaccines), at least 1 month should elapse between administration of the MMR and the MMRV combination vaccine. At least 3 months should elapse between administration of the varicella vaccine and MMRV. A third MMR or MMRV dose is recommended in patients who were previously vaccinated with 2 doses of a mumps virus-containing vaccine and are identified by public health authorities as being at increased risk for acquiring mumps because of an outbreak.

Maximum Dosage Limits:
-Neonates
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Children
0.5 mL/dose IM or subcutaneous.
-Adolescents
Safety and efficacy have not been established.

Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed. However, consult current immunization schedules for recommended vaccines for use in young dialysis patients; the ACIP states that all routine vaccinations are likely effective in patients with chronic renal disease.

*non-FDA-approved indication

Monograph content under development

Mechanism of Action: Active immunization with the vaccine stimulates the immune system to produce disease-specific antibodies by inducing a subclinical infection with attenuated virus particles. The measles, mumps, and rubella infection is noncommunicable, but varicella could be transmitted from vaccinated patients to susceptible individuals during the first 6 weeks after vaccination. Vaccination with measles virus; mumps virus; rubella virus; varicella virus (MMRV) vaccine, live produces a detectable IgG antibody humoral immune response in a high proportion of individuals. Vaccine-induced antibodies are capable of virus neutralization by opsonization, complement activation, and induction of cell-mediated immunity. Among a subset of 2107 children enrolled in clinical trials evaluated one year after vaccination with MMRV vaccine, antibody was detected in 98.9% for measles, 96.7% for mumps, 99.6% for rubella, and 97.5% for varicella. Data from MMR II vaccine indicate antibodies to measles, mumps, and rubella viruses are detectable 11-13 years after primary vaccination. Among individuals tested who received one dose of varicella vaccine, varicella antibodies are present for up to 10 years.

Pharmacokinetics: The measles virus; mumps virus; rubella virus; varicella virus vaccine, live vaccine is administered intramuscularly or subcutaneously. The distrubution, metabolism, and excretion of the vaccine have not been well defined.


-Route-Specific Pharmacokinetics
Subcutaneous Route
The refrigerator-stable formulation of ProQuad (n = 1,006) was compared to the frozen formulation of ProQuad (n = 513) in pediatric patients age 12 to 23 months. Both vaccines were administered subcutaneously. A statistical analysis of non-inferiority in antibody response rates and geometric mean titers (GMTs) to measles, mumps, rubella, and varicella at 6 weeks postvaccination showed the immunogenicity of the refrigerator-stable formulation and the frozen formulation of ProQuad were similar. The estimated antibody response rate to measles in the refrigerator-stable formulation was 99.1% and the frozen formulation was 98.5%. The estimated antibody response rate to mumps in the refrigerator-stable formulation was 97.7% and the frozen formulation was 98.0%. The estimated antibody response rate to rubella in the refrigerator formulation was 99.6% and the frozen formulation was 99.6%. The estimated antibody response rate to varacella in the refrigerator formulation was 90.1% and for the frozen formulation was 88.8%.


-Special Populations
Pediatrics
Children 12 to 23 months
Similar antibody responses to each of the antigens are obtained after a single dose of measles virus; mumps virus; rubella virus; varicella virus (MMRV) vaccine as compared with a single dose of the measles, mumps, and rubella vaccine and of varicella virus vaccine. After a single MMRV dose, 97% of initially seronegative children 12 to 23 months had measles antibodies, 95% had mumps antibodies, 98% had rubella antibodies, and 91% had varicella antibodies.

Children 15 to 31 months
After a second dose of MMRV in children 15 to 31 months, 99% of children had measles antibodies, 99% had mumps antibodies, 98% had rubella antibodies, and 99% had varicella antibodies. Of children who received the measles, mumps, and rubella vaccine and the varicella vaccine at least 1 month before MMRV receipt, 99% had seropositivity for each of the 4 antigens.