Varivax

— THERAPEUTIC CATEGORIES —
  • Vaccines
PAGE CONTENTS
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  • Generic Name & Formulations
  • Indications
  • Dosage and Administration
  • Contraindications
  • Boxed Warnings
  • Warnings/Precautions
  • Pharmacokinetics
  • Interactions
  • Adverse Reactions
  • Clinical Trials
  • Note
  • Patient Counseling

    • Varivax Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Varicella virus vaccine live, attenuated (Oka/Merck) (human and guinea pig cell cultures) with 1350 plaque-forming units (PFU) minimum per 0.5mL after reconstitution; for SC or IM inj; lyophilized; preservative-free.

    Pharmacological Class

    VAR.

    How Supplied

    Single-dose vials—10 (w. diluent)

    Storage

    • During shipment, store at a temperature between −58°F and +5°F (−50°C and −15°C). Use of dry ice may subject Varivax to temperatures colder than −58°F (−50°C).

    • Before reconstitution, store the lyophilized vaccine in a freezer at a temperature between −58°F and +5°F (−50°C and −15°C). 

    • May store Varivax at refrigerator temperature  (36°F to 46°F, 2°C to 8°C) for up to 72 continuous hours prior to reconstitution. If Varivax is stored at 2°C to 8°C and not used within 72 hours, discard vial.

    • Discard if reconstituted vaccine is not used within 30 minutes.

    • Store the vial of diluent at room temperature (68°F to 77°F, 20°C to 25°C), or in the refrigerator.

    Manufacturer

    Merck & Co., Inc.

    Generic Availability

    NO

    Mechanism of Action

    Varivax induces both cell-mediated and humoral immune responses to varicella-zoster virus. The relative contributions of humoral immunity and cell-mediated immunity to protection from varicella are unknown.

    Varivax Indications

    Indications

    Varicella (chickenpox) vaccination.

    Varivax Dosage and Administration

    Adult

    Give by SC or IM inj. ≥13yrs: 1 dose of 0.5mL at elected date and a 2nd dose of 0.5mL at least 4 weeks later.

    Children

    <12mos: not established. Give by SC or IM inj. 12mos–12yrs: administer 1st dose of 0.5mL at 12 to 15 months of age but may give anytime through 12yrs of age, then give 2nd dose at 4–6yrs of age.

    Varivax Contraindications

    Contraindications

    Hypersensitivity to gelatin or neomycin. Immunodeficient or immunosuppressed. Active febrile illness with fever >101.3⁰F (>38.5⁰C). Active untreated tuberculosis. During pregnancy or individuals who are planning on becoming pregnant in the next 3 months. 

    Varivax Boxed Warnings

    Not Applicable

    Varivax Warnings/Precautions

    Warnings/Precautions

    Have epinephrine inj (1:1000) available. Defer vaccination if family history of congenital or hereditary immunodeficiency until immunocompetent. Avoid contact with susceptible high-risk individuals for up to 6 weeks after vaccination. HIV-infected: refer to ACIP recommendations. Nursing mothers.

    Warnings/Precautions

    Family History of Immunodeficiency

    • Defer vaccination if family history of congenital or hereditary immunodeficiency until immunocompetent. 

    Use in HIV-Infected Individuals

    • Refer to ACIP recommendations on the use of varicella vaccine in HIV-infected individuals.

    Risk of Vaccine Virus Transmission

    • Avoid contact with susceptible high-risk individuals for up to 6 weeks after vaccination. Susceptible high-risk individuals include:

      • Immunocompromised individuals;

      • Pregnant women without documented history of varicella or laboratory evidence of prior infection;

      • Newborn infants of mothers without documented history of varicella or laboratory evidence of prior infection and all newborn infants born at <28 weeks gestation regardless of maternal varicella immunity.

    Immune Globulins and Transfusions

    • Do not give Varivax concomitantly with immune globulins and other blood products.

    • The ACIP has specific recommendations for intervals between administration of antibody-containing products and live virus vaccines.

    Salicylate Therapy

    • Avoid salicylates in patients (12 months through 17 years of age) for 6 weeks after vaccination because of the association of Reye syndrome with salicylate therapy and wild-type varicella infection. 

    Pregnancy Considerations

    Risk Summary

    • See Contraindications.

    • Contraindicated for use in pregnant women.

     

    Nursing Mother Considerations

    Risk Summary

    • It is not known whether varicella vaccine virus is excreted in human milk.

    • Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for Varivax, and any potential adverse effects on the breastfed child from Varivax or from the underlying maternal condition.

     

    Pediatric Considerations

    • No clinical data are available on safety or efficacy of Varivax in children less than 12 months of age.

    Varivax Pharmacokinetics

    See Literature

    Varivax Interactions

    Interactions

    Avoid salicylates in patients (12 months through 17 years of age) for 6 weeks after vaccination. Concomitant administration with immune globulins and other blood products may interfere with the expected immune response; refer to ACIP recommendations. May interfere with tuberculin skin test. Separate by at least 1 month between a dose of a live attenuated measles virus-containing vaccine and Varivax. In children through 12yrs, separate by at least 3 months between 2 doses of a live attenuated varicella virus-containing vaccine and Varivax.

    Varivax Adverse Reactions

    Adverse Reactions

    Fever, inj site reactions, rash; others.

    Varivax Clinical Trials

    Clinical Trials

    Clinical Efficacy

    One-Dose Regimen in Children

    • In a placebo-controlled trial, the protective efficacy of a single dose of Varivax was 96 to 100% against varicella over a 2-year period. The study included healthy individuals 1 to 14 years of age (n=491 vaccine; n=465 placebo). 

      • In the 1st varicella season, the protective efficacy of Varivax was 100%, while 8.5% of placebo recipients contracted varicella.

      • In the 2nd varicella season, the protective efficacy of Varivax was 96%.

    • In early clinical trials, a total of 4240 children 1 to 12 years of age received 1000 to 1625 PFU of attenuated virus per dose of Varivax and have been followed for up to nine years post single-dose vaccination.

      • There were 0.3% to 3.8% of vaccines per year who reported varicella (called breakthrough cases). This represents an approximate 83% (95% CI, 82–84) decrease from the age-adjusted expected incidence rates.

      • In one study, a total of 47% (27/58) of breakthrough cases had <50 lesions compared with 8% (7/92) in unvaccinated individuals, and 7% (4/58) of breakthrough cases had >300 lesions compared with 50% (46/92) in unvaccinated individuals.

    • Among a subset of vaccines who were followed in these early clinical trials for up to 9 years postvaccination, 179 individuals had household exposure to varicella.

      • 84% of exposed children did not report breakthrough varicella, while 16% reported a mild form of varicella.

      • This represents an 81% reduction in the expected number of varicella cases utilizing the historical attack rate of 87% after household exposure.

    • In later clinical trials, a total of 1114 children 1 to 12 years of age received 2900 to 9000 PFU of attenuated virus per dose of Varivax and have been actively followed for up to 10 years post single-dose vaccination.

      • It was observed that 0.2% to 2.3% of vaccinees per year reported breakthrough varicella for up to 10 years post single-dose vaccination. 

      • This represents an estimated efficacy of 94% (95% CI, 93%-96%), compared with the age-adjusted expected incidence rates in susceptible subjects over the same period.

    • Among a subset of vaccinees who were actively followed in these later trials for up to 10 years postvaccination, 95 individuals were exposed to an unvaccinated individual with wild-type varicella in a household setting. There were no reports of breakthrough varicella in 92% (87/95) of exposed children, while 8% (8/95) reported a mild form of varicella (maximum total number of lesions <50; observed range, 10 to 34). This represents an estimated efficacy of 90% (95% CI, 82%, 96%) based on the historical attack rate of 87% following household exposure to varicella in unvaccinated individuals in the calculation of efficacy.

    Two-Dose Regimen in Children

    • In a clinical trial, a total of 2216 children 12 months to 12 years of age with a negative history of varicella were randomized to receive either 1 dose of Varivax (n=1114) or 2 doses of Varivax (n=1102) given 3 months apart.

    • The estimated vaccine efficacy for the 10-year observation period was 94% for 1 dose and 98% for 2 doses (P <.001).

    • This translates to a 3.4-fold lower risk of developing varicella >42 days postvaccination during the 10-year observation period in children who received 2 doses than in those who received 1 dose (2.2% vs. 7.5%, respectively). 

    Two-Dose Regimen in Adolescents and Adults

    • In early clinical trials, a total of 796 adolescents and adults received 905 to 1230 PFU of attenuated virus per dose of Varivax and have been followed for up to 6 years following 2-dose vaccination. A total of 50 clinical varicella cases were reported >42 days following 2-dose vaccination. There were no reports of breakthrough varicella in 83% (63/76) of exposed vaccinees, while 17% (13/76) reported a mild form of varicella.

    • In later clinical trials, a total of 220 adolescents and adults received 3315 to 9000 PFU of attenuated virus per dose of Varivax and have been actively followed for up to six years following 2-dose vaccination. A total of 3 clinical varicella cases were reported >42 days following 2-dose vaccination. There were no reports of breakthrough varicella among the exposed vaccinees. There are insufficient data to assess the rate of protective efficacy of Varivax against the serious complications of varicella in adults (e.g., encephalitis, hepatitis, pneumonitis) and during pregnancy (congenital varicella syndrome).

     

    Immunogenicity

    One-Dose Regimen in Children

    • In prelicensure efficacy studies, seroconversion was observed in 97% of vaccinees at approximately 4 to 6 weeks postvaccination in 6889 susceptible children 12 months to 12 years of age.

    • In an open label clinical trial (NCT00432523) 752 children 12 through 18 months of age received Varivax either intramuscularly (n=374) or subcutaneously (n=378), concomitantly with M-M-R II. The proportions of children achieving antibody titers above the seroresponse thresholds for varicella virus were 88.4% (95% CI: 84.5, 91.6) of children in the intramuscular group and 85.5% (95% CI: 81.3, 89.0) of children in the subcutaneous.

    Two-Dose Regimen in Children

    • In a multicenter study, 2216 healthy children 12 months to 12 years of age received either 1 dose or 2 doses of Varivax administered subcutaneously 3 months apart. VZV antibody levels after 2 doses given 3 to 6 years apart are comparable to those obtained when the 2 doses are given 3 months apart.

    Two-Dose Regimen in Adolescents and Adults

    • In a multicenter study involving susceptible adolescents and adults 13 years of age and older, 2 doses of Varivax administered subcutaneously 4 to 8 weeks apart induced a seroconversion rate of approximately 75% in 539 individuals 4 weeks after the first dose and of 99% in 479 individuals 4 weeks after the second dose. 

    • In another multicenter study involving adolescents and adults, 2 doses of Varivax administered subcutaneously 8 weeks apart induced a seroconversion rate of 94% in 142 individuals 6 weeks after the first dose and 99% in 122 individuals 6 weeks after the second dose.

     

    Persistence of Immune Response

    One-Dose Regimen in Children

    • In clinical studies involving healthy children who received 1 dose of Varivax subcutaneously, detectable VZV antibodies were present in 99.0% (3886/3926) at 1 year, 99.3% (1555/1566) at 2 years, 98.6% (1106/1122) at 3 years, 99.4% (1168/1175) at 4 years, 99.2% (737/743) at 5 years, 100% (142/142) at 6 years, 97.4% (38/39) at 7 years, 100% (34/34) at 8 years, and 100% (16/16) at 10 years postvaccination. 

    Two-Dose Regimen in Children

    • In recipients of 1 dose of Varivax administered subcutaneously over 9 years of follow-up, the GMTs and the percent of subjects with VZV antibody titers 5 gpELISA units/mL generally increased. 

    • The GMTs and percent of subjects with VZV antibody titers 5 gpELISA units/mL in the 2-dose recipients were higher than those in the 1-dose recipients for the first year of follow-up and generally comparable thereafter. 

    • The cumulative rate of VZV antibody persistence with both regimens remained very high at year 9 (99.0% for the 1-dose group and 98.8% for the 2-dose group).

    Two-Dose Regimen in Adolescents and Adults

    • In clinical studies involving healthy adolescents and adults who received 2 doses of Varivax subcutaneously, detectable VZV antibodies were present in 97.9% (568/580) at 1 year, 97.1% (34/35) at 2 years, 100% (144/144) at 3 years, 97.0% (98/101) at 4 years, 97.4% (76/78) at 5 years, and 100% (34/34) at 6 years postvaccination.

     

    Studies with Other Vaccines

    Concomitant Administration with M-M-R II

    • Seroconversion rates and antibody levels to measles, mumps, rubella, and varicella were comparable between the two groups at approximately six weeks postvaccination.

    Concomitant Administration with Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed (DTaP) and Oral Poliovirus Vaccine (OPV) 

    • At six weeks postvaccination, seroconversion rates for measles, mumps, rubella, and VZV and the percentage of vaccinees whose titers were boosted for diphtheria, tetanus, pertussis, and polio were comparable between the two groups. 

    • Anti-VZV levels were decreased when the investigational vaccine containing varicella was administered concomitantly with DTaP.

    Concomitant Administration with PedvaxHIB

    • At six weeks postvaccination, seroconversion rates for measles, mumps, rubella, and VZV, and GMTs for PedvaxHIB were comparable between the two groups. Anti-VZV levels were decreased when the investigational vaccine containing varicella was administered concomitantly with PedvaxHIB.

    Concomitant Administration with M-M-R II and Comvax

    • At 6 weeks postvaccination, the immune responses for the subjects who received the concomitant doses of Comvax, M-M-R II, and VARIVAX were similar to those of the subjects who received Comvax followed 6 weeks later by M-M-R II and Varivax with respect to all antigens administered.

    Varivax Note

    Not Applicable

    Varivax Patient Counseling

    Patient Counseling

    • Question the patient, parent, or guardian about reactions to previous vaccines. 

    • Provide a copy of the patient information (PPI) located at the end of this insert and discuss any questions or concerns. 

    • Inform patient, parent, or guardian that vaccination with Varivax may not result in protection of all healthy, susceptible children, adolescents, and adults. 

    • Inform female patients to avoid pregnancy for 3 months following vaccination. 

    • Inform patient, parent, or guardian of the benefits and risks of Varivax. 

    • Instruct patient, parent, or guardian to report any adverse reactions or any symptoms of concern to their healthcare professional.

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