Varicella Virus Vaccine Live

Class: Vaccines
ATC Class: J07BK01
VA Class: IM100
Brands: ProQuad, Varivax

Introduction

Live, attenuated virus vaccine.1 27 137 Varicella virus vaccine live contains varicella zoster virus (VZV) of the Oka/Merck strain1 27 and is used to stimulate active immunity to varicella (chickenpox).1 27 Commercially available in the US as a monovalent vaccine (Varivax) and a fixed-combination vaccine containing measles, mumps, rubella, and varicella antigens (MMRV; ProQuad).1 125 Other varicella vaccines may be available in other countries (e.g., Oka/Biken vaccine).8 11 15 27 45

Uses for Varicella Virus Vaccine Live

Prevention of Varicella (Chickenpox) Infection

Prevention of varicella (chickenpox) in adults, adolescents, and children ≥12 months of age.1 27 71 82 89 92 100 114 129 137

Varicella is caused by primary infection with varicella zoster virus (VZV).1 6 9 11 14 27 41 64 75 137 138 In otherwise healthy children, varicella usually is an acute, self-limited disease characterized by fever, malaise, and a generalized vesicular rash consisting of 200–500 lesions.1 6 9 11 14 27 41 64 75 137 138 In neonates, adolescents, adults, and immunocompromised individuals, it may be a more serious illness associated with a greater number of lesions and an increased risk of complications (e.g., pneumonia, encephalitis, glomerulonephritis, bacterial superinfection including necrotizing fasciitis).6 9 11 15 27 34 41 64 75 80 89 91 94 137 138 In the past, there were an average of 4 million cases of varicella and 100–150 varicella-associated deaths each year in the US.6 27 64 137 Since 1995, when varicella vaccine became commercially available, there have been substantial decreases in the incidence of varicella and varicella-associated hospitalizations in the US in all age groups, especially in children 1–9 years of age.112 138 The number of hospitalizations and deaths from varicella decreased >90% in the US since 1996.138

USPHS Advisory Committee on Immunization Practices (ACIP), AAP, and American Academy of Family Physicians (AAFP) recommend that all susceptible children 12 months through 12 years of age be vaccinated against varicella, unless the vaccine is contraindicated.27 71 100 137 (See Contraindications under Cautions.)

Slideshow: Prescription Drug Addiction - Are You at Risk?

ACIP, AAP, AAFP, American College of Obstetricians and Gynecologists (ACOG), and American College of Physicians (ACP) recommend that all susceptible adults and adolescents ≥13 years of age be vaccinated against varicella, unless contraindicated.27 71 89 100 114 129 (See Contraindications under Cautions.)

For internationally adopted children whose immune status is uncertain, vaccinations can be repeated or serologic tests performed to confirm immunity.26 Because varicella vaccine is not available in the majority of countries, especially developing countries, all internationally adopted children without reliable evidence of varicella immunity should be vaccinated according to the US recommended immunization schedule.26 112 (See Dosage and Administration.) Although serologic testing to verify immunization status in children >12 months of age is available, such testing prior to vaccination is not recommended in children <12 years of age coming from tropical countries, unless there is a history of the disease.112

The fixed-combination vaccine containing measles, mumps, and rubella virus vaccine live (MMR) and varicella virus vaccine live (MMRV; ProQuad) may be used instead of the monovalent varicella vaccine in children 12 months through 12 years of age when a dose of MMR and a dose of varicella vaccine is indicated in this age group.27 125 136 137 145 ACIP, AAP, and AAFP state that use of a combination vaccine generally is preferred over separate injections of the equivalent component vaccines.71 However, although use of MMRV (ProQuad) reduces the number of required injections when both vaccines are indicated during a single health-care visit,27 128 there is some evidence that the relative risk for febrile seizures in infants 12 through 23 months of age may be higher with MMRV (ProQuad) than when a dose of Varivax and a dose of MMR are given concomitantly.125 136 145 (See Use of Fixed Combinations under Cautions.)

ACIP states that evidence of varicella immunity includes documentation of age-appropriate vaccination against varicella, laboratory evidence of immunity or laboratory confirmation of prior varicella, birth in the US before 1980 (except pregnant women, immunocompromised individuals, health-care personnel), diagnosis or verification of history of varicella by health-care provider, or diagnosis or verification of history of herpes zoster (shingles, zoster) by health-care provider.27 Individuals without such evidence should be considered susceptible to varicella.27

Preexposure Vaccination Against Varicella Infection in High-risk Groups

Health-care personnel should ensure that they are immune to varicella, especially those who have close contact with individuals at high risk for serious complications from varicella.27 113 ACIP and the Hospital Infection Control Practices Advisory Committee of the US Public Health Service (HICPAC) recommend vaccination against varicella in all susceptible health-care personnel.27 113 This protects the worker following varicella exposure in the workplace and also may help reduce nosocomial transmission of VZV.11 27

Travelers should be vaccinated against varicella.27 112 Varicella occurs worldwide.112 138 Although vaccination against varicella is not a requirement for entry into any country (including the US), CDC states that individuals traveling or living abroad should ensure that they are immune.112

Certain immunocompromised individuals at risk of severe complications from varicella may benefit from vaccination against the disease.27 52 100 137 143 144 However, varicella vaccine generally is contraindicated in adults, adolescents, and children who are immunocompromised.1 54 70 100 137 (See Individuals with Altered Immunocompetence under Cautions.)

ACIP, AAP, CDC, National Institutes of Health (NIH), HIV Medicine Association of the Infectious Diseases Society of America (IDSA), Pediatric Infectious Diseases Society, and others recommend that vaccination against varicella be considered for certain HIV-infected individuals, especially those who are asymptomatic or only mildly symptomatic.27 100 137 143 144 These experts state that, after weighing risks and benefits, use of monovalent varicella vaccine should be considered in HIV-infected children 1–8 years of age with age-specific CD4+ T-cell percentages ≥15%27 137 144 and may be considered in HIV-infected adults, adolescents, and children >8 years of age with CD4+ T-cell counts ≥200/mm3.27 143 144 Other HIV-infected adults, adolescents, or children who are more severely immunocompromised should not receive varicella vaccine.1 27 143 144 (See Individuals with Altered Immunocompetence under Cautions.)

Although monovalent varicella vaccine was previously used under an investigational protocol in certain children and adolescents with acute lymphocytic (lymphoblastic) leukemia (ALL) in remission,27 52 100 this protocol has been terminated.100 The ACIP and AAP state that varicella vaccine should not be used routinely in susceptible children with leukemia and use of the vaccine in leukemic children in remission who do not have evidence of immunity to varicella should only be undertaken with expert guidance and only if antiviral therapy is available in case complications occur.27 100 137 (See Individuals with Altered Immunocompetence under Cautions.)

Postexposure Vaccination Against Varicella Infection and Outbreak Control

Postexposure vaccination in susceptible adults, adolescents, or children with recent exposure to varicella, unless contraindicated.27 100 138

Prevention and control of varicella outbreaks (e.g., in child-care facilities, schools, institutions).27 138 Varicella outbreaks can persist for up to 4–6 months.27 138

May prevent varicella or modify severity of the disease if given within 3 days, and possibly up to 5 days, after exposure.27 100 112 115 116 138

If the exposure does not cause infection, postexposure vaccination should provide protection against subsequent exposure.27 100 138 If the exposure results in infection, vaccination during the presymptomatic or prodromal stage of varicella does not appear to increase risk for vaccine-associated adverse effects or cause more severe natural disease.27 100 138

During varicella outbreaks, ACIP recommends a second dose of varicella vaccine for those who previously received only a single dose, provided the age-appropriate time interval has elapsed since the first dose (i.e., 3 months for children 12 months through 12 years of age, at least 4 weeks for adults and adolescents ≥13 years of age).27 138

In hospital settings, consider postexposure vaccination for unvaccinated health-care personnel who have no evidence of immunity at the time of varicella exposure.27 113 138 Preexposure vaccination is the preferred method for preventing varicella in health-care settings.27 138

When varicella vaccine cannot be used (e.g., pregnant women, neonates, immunocompromised individuals) and postexposure prophylaxis is considered necessary, passive immunization with varicella zoster immune globulin (VZIG) is recommended to prevent or reduce severity of varicella.15 27 100 138 143 144 The only VZIG preparation currently available for use in the US (VariZIG; Cangene) must be obtained through an investigational new drug (IND) expanded access protocol from the distributor (FFF Enterprises at 800-843-7477).134 135 If VZIG is not available for postexposure prophylaxis, immune globulin IV (IGIV) can be used.100

Varicella Virus Vaccine Live Dosage and Administration

Administration

Sub-Q Administration

Administer monovalent varicella vaccine (Varivax) by sub-Q injection.1

Administer fixed-combination vaccine containing MMR and varicella vaccine (MMRV; ProQuad) by sub-Q injection.125

Do not administer monovalent or fixed-combination vaccine IM.1 125 Inadvertent IM administration does not necessitate revaccination.26 30

Depending on patient age, administer sub-Q into the upper-outer triceps area or anterolateral thigh.1 26 125 For children ≥1 year of age, adolescents, and adults, the upper-outer triceps area usually is preferred.26

To ensure appropriate delivery, sub-Q injections should be made at a 45° angle using a 5/8-inch, 23- to 25-gauge needle.26

Prior to injection, ensure that needle is not in a blood vessel.1

Since syncope may occur following vaccination, observe vaccinees for approximately 15 minutes after the vaccine dose.26 If syncope occurs, observe patient until symptoms resolve.26 Syncope after vaccination occurs most frequently in adolescents and young adults.26

Do not administer concomitantly with VZIG.1 (See Specific Drugs and Laboratory Tests under Interactions.)

May be given simultaneously with other age-appropriate vaccines during the same health-care visit (using different syringes and different injection sites).26 71 100 129 137 (See Interactions.)

When multiple vaccines are administered during a single health-care visit, each vaccine should be given with a different syringe and at different injection sites.26 Separate injection sites by at least 1 inch (if anatomically feasible) to allow appropriate attribution of any local adverse effects that may occur.26 If multiple vaccines must be given into a single limb, the deltoid may be used in older children and adults, but the anterolateral thigh is preferred in infants and younger children.26

Reconstitution

Varicella vaccine (Varivax): Reconstitute lyophilized vaccine by adding 0.7 mL of diluent provided by the manufacturer and gently agitating vial.1 Use only the diluent supplied by the manufacturer.1

MMRV (ProQuad): Reconstitute lyophilized vaccine according to manufacturer’s directions using diluent provided by the manufacturer.125 Gently agitate vial.125 Use only the diluent supplied by the manufacturer.125

Use sterile syringes and needles free of preservatives, antiseptics, and detergents to avoid inactivating the live virus vaccine.1 125

To minimize loss of potency and ensure an adequate immunizing dose, administer immediately following reconstitution; discard reconstituted vaccine not used within 30 minutes.1 125

Dosage

Pediatric Patients

Prevention of Varicella (Chickenpox)
Children 12 Months Through 12 Years of Age (Varivax)
Sub-Q

Each dose is 0.5 mL.1

Primary immunization consists of 2 doses given at least 3 months apart.1 27 71 100 137

ACIP, AAP, and AAFP recommend that the initial dose be given at 12 through 15 months of age and the second dose at 4 through 6 years of age (i.e., before child begins kindergarten or first grade).27 71 100 137 Second dose may be administered prior to 4 years of age, provided at least 3 months have elapsed since initial dose and both doses are administered at ≥12 months of age.1 27 71 100 137 If second dose was inadvertently administered early (but at least 28 days after initial dose), it does not need to be repeated.27 71 100 137

For catch-up vaccination in those not previously vaccinated, give 2 doses at least 3 months apart.1 27 71 100 137 In those who previously received a single dose of vaccine containing varicella vaccine, give a second dose preferably at least 3 months after initial dose.1 27 71 100 137

Children 12 Months Through 12 Years of Age (MMRV; ProQuad)
Sub-Q

Each dose is 0.5 mL.125

May be used when simultaneous administration of the first or second dose of varicella vaccine and first or second dose of MMR is indicated or whenever any components of the fixed-combination vaccine are indicated and the other components are not contraindicated.27 71 125

When considering use in infants and children 12 through 47 months of age, ACIP states that providers should advise the parent or caregiver about the benefits and risks associated with MMRV (ProQuad) compared with the individual component vaccines.145 (See Use of Fixed Combinations under Cautions.)

At least 1 month should elapse between a dose of a measles-containing vaccine (e.g., MMR) and a dose of MMRV (ProQuad) and preferably at least 3 months should elapse between a dose of Varivax and a dose of MMRV (ProQuad); however, if a second dose of a varicella-containing vaccine was administered at least 28 days following the first dose, the second dose does not need to be repeated.71 125

Adolescents 13–16 Years of Age (Varivax)
Sub-Q

Each dose is 0.5 mL.1

Primary immunization consists of 2 doses given at least 4–8 weeks apart.1 27 71 89 100 137 The minimum interval between the first and second dose is 28 days.71 100 A longer interval between first and second doses does not necessitate a third dose, but may leave individual susceptible during the intervening months.27 100

For catch-up vaccination in those who previously received only a single dose, give second dose at least 4 weeks (28 days) after first dose.1 27 71 137

HIV-infected Children 12 Months Through 8 Years of Age with Age-specific CD4+ T-cell Percentages ≥15% (Varivax)
Sub-Q

2 doses given at least 3 months apart recommended by ACIP, AAP, CDC, NIH, HIV Medicine Association of IDSA, and Pediatric Infectious Diseases Society.27 144 Give first dose as soon as possible after the first birthday.144

HIV-infected Adolescents and Children >8 Years of Age with CD4+ T-cell Counts ≥200/mm3 (Varivax)
Sub-Q

2 doses given at least 3 months apart recommended by ACIP, AAP, CDC, NIH, HIV Medicine Association of IDSA, and Pediatric Infectious Diseases Society.27 137 143 144

Postexposure Vaccination Against Varicella Infection and Outbreak Control (Varivax)
Sub-Q

Children ≥12 months of age who are unvaccinated or incompletely vaccinated: Give a vaccine dose within 3–5 days after exposure and complete primary immunization.27

For outbreak control, give a second dose to those who previously received only a single dose, provided the appropriate interval has elapsed since first dose (i.e., at least 3 months in children 12 months through 12 years of age and at least 4 weeks in adolescents ≥13 years of age).27 138

Adults

Prevention of Varicella (Chickenpox) Infection
Adults (Varivax)
Sub-Q

Each dose is 0.5 mL.125

Primary immunization consists of 2 doses given 4–8 weeks apart.1 27 82 129 A longer interval between first and second doses does not necessitate a third dose, but may leave individual susceptible for the intervening months.27

For catch-up vaccination in those who previously received only a single dose, give second dose at least 4 weeks after first dose.1 27 129

HIV-infected Adults with CD4+ T-cell Counts ≥200/mm3 (Varivax)
Sub-Q

2 doses given at least 3 months apart recommended by ACIP, NIH, CDC, and HIV Medicine Association of IDSA.27 129 143 144

Postexposure Vaccination Against Varicella (Chickenpox) Infection and Outbreak Control (Varivax)
Sub-Q

Unvaccinated or incompletely vaccinated: Give a vaccine dose within 3–5 days after exposure and complete primary immunization.27

For outbreak control, give a second dose to those who previously received only a single dose, provided the appropriate interval has elapsed since first dose (i.e., at least 4 weeks in adults).27 138

Special Populations

Hepatic Impairment

No specific dosage recommendations.1

Renal Impairment

No specific dosage recommendations.1

Geriatric Patients

No specific dosage recommendations.1

Cautions for Varicella Virus Vaccine Live

Contraindications

  • Monovalent Varicella Vaccine (Varivax) or Fixed Combination of Varicella Vaccine and MMR (MMRV; ProQuad)
  • Hypersensitivity to the vaccine or any component in the formulation, including gelatin.1 27 100 125 (See Gelatin Allergy under Cautions.)

  • History of anaphylactic reaction to neomycin.1 26 100 125 (See Neomycin Allergy under Cautions.)

  • Blood dyscrasias, leukemia, lymphomas of any type, or any other malignant neoplasms affecting the bone marrow or lymphatic system.1 26 70 92 100 125 (See Individuals with Altered Immunocompetence under Cautions.)

  • Primary and acquired immunodeficiencies, including acquired immunodeficiency syndrome (AIDS) or other clinical manifestations of HIV infection, cellular immune deficiency, hypogammaglobulinemia, and dysgammaglobulinemia.1 26 54 70 92 100 125 (See Individuals with Altered Immunocompetence under Cautions.)

  • Immunosuppressive therapy (e.g., corticosteroids, antineoplastic agents, radiation).1 26 54 70 92 100 125 (See Specific Drugs and Laboratory Tests under Interactions.)

  • Family history of congenital or hereditary immunodeficiency, unless immune competence has been demonstrated in the potential vaccine recipient.1 125 (See Individuals with Altered Immunocompetence under Cautions.)

  • Active untreated tuberculosis.1 125 (See Tuberculosis under Cautions.)

  • Febrile respiratory illness or other active febrile infection.1 125 (See Concomitant Illness under Cautions.)

  • Pregnancy.1 125 (See Pregnancy under Cautions.)

Warnings/Precautions

Warnings

Individuals with Altered Immunocompetence

Because monovalent varicella vaccine (Varivax ) and MMRV (ProQuad) contain live, attenuated viruses, they generally are contraindicated in individuals with altered immunocompetence, including those with primary or acquired immunodeficiencies or those receiving immunosuppressive therapy.1 27 70 100 125 137 143 144

These vaccines usually contraindicated in those with primary immunodeficiencies (e.g., cellular immune deficiency, hypogammaglobulinemia, dysgammaglobulinemia) and in individuals with suppressed immune responses resulting from AIDS or other clinical manifestations of HIV infection, blood dyscrasias, leukemia, lymphomas of any type, or any other malignant neoplasms affecting the bone marrow or lymphatic systems.1 27 70 100 125 137 143 144 Also generally contraindicated in individuals with a family history of congenital or hereditary immunodeficiency in a first-degree relative (e.g., parents and siblings), unless the immune competence of the potential vaccine recipient has been clinically substantiated or verified by a laboratory.1 20 27 100 125 137

Safety and efficacy not established in HIV-infected children, adolescents, or adults.1 27 125 However, because HIV-infected adults, adolescents, and children are at increased risk for morbidity from varicella and herpes zoster, ACIP, AAP, CDC, NIH, HIV Medicine Association of IDSA, Pediatric Infectious Diseases Society, and others state that use of Varivax can be considered in selected HIV-infected individuals after weighing potential benefits and risks.27 100 137 143 144 (See Preexposure Vaccination Against Varicella Infection in High-risk Groups under Uses.) If Varivax is used in an HIV-infected individual, consider possibility that such individuals may be at increased risk for complications after vaccination with a live virus since they have impaired cellular immunity; encourage patient to consult clinicians if a postvaccination varicella-like rash develops.27 100 Do not use MMRV (ProQuad) in HIV-infected individuals.27 125 137 144

Safety and efficacy not established in children with leukemia.1 27 125 137 ACIP states that use of live virus vaccines can be considered in patients with leukemia or other malignancies if the disease is in remission and chemotherapy was terminated at least 3 months prior to vaccination.26 However, use of Varivax in susceptible leukemic children in remission should be undertaken only with expert guidance and only when antiviral agents are available to treat complications if they occur.27 100 137

The presence of an immunocompromised or HIV-infected individual in a household does not preclude administration of Varivax or MMRV (ProQuad) to other household members.27 100 137 Vaccination of household contacts decreases the likelihood that wild-type varicella will be introduced into the household.27 143 144 However, if vaccinee develops a varicelliform rash, they should avoid contact with immunocompromised household members.27 100 137 (See Transmission of Vaccine Virus under Cautions.)

Cerebral Injury or Seizures

MMRV (ProQuad): Use caution in individuals with a history of cerebral injury, individual or family history of seizures, or any other condition in which fever-induced stress should be avoided.125 (See Use of Fixed Combinations under Cautions.)

Interim results from an ongoing study indicate that the relative risk for febrile seizures 5–12 days after a dose of MMRV (ProQuad) in children 12–60 months of age (995 were 12–23 months of age) is 2.3 times higher than that reported with concurrent administration of a dose of Varivax and a dose of MMR given during a single health-care visit.136 (See Use of Fixed Combinations under Cautions.)

Thrombocytopenia

Thrombocytopenia has been reported after administration of varicella vaccine or MMR; thrombocytopenia has worsened in those with preexisting thrombocytopenia and may worsen with subsequent doses.27 125

Manufacturer of MMRV (ProQuad) states that potential benefits and risks should be evaluated before considering use of the vaccine in patients who develop thrombocytopenia or had worsening of thrombocytopenia with a previous dose.125 Serologic testing for antibody to MMR should be considered to determine whether additional doses should be given.125

Risk of Transmissible Agents in Preparations Containing Albumin

MMRV (ProQuad) contains albumin human.125

Since albumin is prepared from pooled human plasma, it is a potential vehicle for transmission of human viruses, including the causative agents of viral hepatitis and HIV infection, and theoretically may carry a risk of transmitting the causative agent of Creutzfeldt-Jakob disease (CJD) or variant CJD (vCJD).125 141

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylaxis,1 27 rash,1 urticaria,1 hypersensitivity vasculitis,105 erythema multiforme,1 27 and Stevens-Johnson syndrome1 reported rarely.

Prior to vaccine administration, question recipient and/or parent or guardian concerning reactions to previous doses of the vaccine or similar preparations.1 125

Epinephrine and other appropriate agents should be readily available in case anaphylaxis or similar reaction occurs.1 125

Gelatin Allergy

Varivax and MMRV (ProQuad) contain hydrolyzed gelatin as a stabilizer.1 125

Immediate reactions (i.e., wheezing and dyspnea with or without urticaria) and other reactions (i.e., erythema and swelling at injection site) have occurred and may be related to gelatin hypersensitivity.106 Consider possibility of such reactions.26 100 106 125

Although skin testing for gelatin sensitivity before administering a gelatin-containing vaccine can be considered, there are no specific protocols for this purpose.26 100 Because gelatin used in vaccines manufactured in the US usually is derived from porcine sources, and food gelatin may be derived solely from bovine sources, a negative food history does not exclude the possibility of a reaction to the gelatin contained in the vaccine.100

Neomycin Allergy

Varivax and MMRV (ProQuad) contain trace amounts of neomycin and are contraindicated in those with a history of anaphylactic reactions to neomycin.1 125

Neomycin allergy usually results in delayed-type (cell-mediated) hypersensitivity reactions manifested as contact dermatitis.26 27 100 125 ACIP and AAP state that vaccines containing trace amounts of neomycin should not be used in individuals with a history of anaphylactic reaction to neomycin, but use of such vaccines may be considered in those with a history of delayed-type neomycin hypersensitivity if benefits of vaccination outweigh risks.26 27 100

Manufacturer of MMRV (ProQuad) states that if use of this vaccine is considered medically necessary in an individual with a history of anaphylactic reactions to neomycin, an allergist or immunologist should be consulted and the vaccine should be given only in settings where anaphylactic reactions can be managed appropriately.125

Allergy to Egg-related Antigens

MMRV (ProQuad): MMR component of this fixed-combination vaccine is produced in chick embryo cell culture.125

Individuals with a history of anaphylactic or other immediate hypersensitivity reactions (e.g., hives, swelling of the mouth or throat, difficulty breathing, hypotension, shock) after egg ingestion may be at increased risk of immediate-type hypersensitivity reactions after receiving vaccines containing traces of chick embryo antigen.125

Consider potential benefits versus possible risks before administering MMRV (ProQuad) to an individual with a history of anaphylactic or other immediate hypersensitivity reaction to egg ingestion.125 Use extreme caution and have adequate treatment readily available in case a reaction occurs.125

Children with egg allergy, even those with severe hypersensitivity, are at low risk for anaphylactic reactions to MMRV (Proquad) and skin testing with dilute vaccine in such children is not predictive of reactions to the vaccine.100 125

Individuals who have egg allergies that are not anaphylactic in nature generally are not at increased risk of hypersensitivity reactions to vaccines produced in chick embryo cell cultures.26 125 There is no evidence that individuals with allergies to chickens or feathers are at increased risk of allergic reactions to such vaccines.26 125

General Precautions

Breakthrough Varicella Infections

Despite seroconversion following vaccination with varicella vaccine, breakthrough varicella infections may occur in some children or adults exposed to wild-type virus.1 13 16 17 18 20 24 27 42 44 47 48 52 53 55 75 77 122 123 137 These infections (i.e., wild-type VZV infection occurring >42 days after vaccination) generally are milder than those reported in unvaccinated individuals and are associated with a low rate of fever and rapid recovery.1 13 16 17 24 27 42 47 48 52 75 77 137

In vaccinated healthy children and adolescents 12 months to 17 years of age, breakthrough infections occur in about 19% within 10 years and generally involve <100 vesicles.1 13 16 17 27 47 48 75 77

In vaccinated healthy adults, breakthrough infections have occurred following household exposure in 4–27%.1 These infections generally involve <50 vesicles,1 11 27 137 but may be associated with ≥50–300 vesicles.1 11

Latent Infections and Herpes Zoster

Primary immunization with varicella vaccine does not necessarily ensure protection against subsequent latent infection with natural wild-type VZV or reactivation of latent infections.8 9 27 42 49 50 74 137

Herpes zoster has been reported rarely in immunocompromised children and healthy children, adolescents, and adults who received primary immunization with varicella vaccine.1 8 9 42 47 49 50 51 52 55 74 Most cases occurred 3–5 years after vaccination and were mild without sequelae.1 9 50 74

Herpes zoster in vaccinated individuals may be caused by vaccine virus or by wild-type virus.1 8 9 27 49 74 137 No evidence to date that latent vaccine virus infections are any more likely to reactivate than latent infections caused by wild-type virus.8 55

Waning cell-mediated immunity to VZV may predispose to reactivation of the virus.6 9 74 137 The long-term effect of primary immunization with varicella vaccine on the incidence of subsequent herpes zoster, particularly in vaccinees exposed to natural varicella, is unknown.1 9 21 24 32 37 38 39 78 The reported rate of herpes zoster in vaccine recipients appears to be considerably lower than that reported in population-based studies in healthy children who have had natural varicella.1 8 11 27 42 74 137

In children with ALL, herpes zoster appears to occur less frequently in those who have received varicella vaccine than in those who have had natural varicella infection.11 49 55 78

Transmission of Vaccine Virus

Varivax and MMRV (ProQuad) contain live, attenuated virus.1 8 11 27 45 54 125 Transmission of vaccine virus may occur rarely between vaccinees and susceptible contacts.1 125

Vaccine virus has been isolated from vesicular fluid obtained from vaccinated individuals who developed a varicelliform rash following primary immunization with varicella vaccine.1 8 9 10 11 14 20 42 45 54 79

Risk for transmission of vaccine virus to susceptible close contacts is greatest if vaccine recipient develops a varicelliform rash following vaccination and/or the vaccine recipient is immunocompromised.10 27 40 Transmission of vaccine virus from vaccinees without a varicella-like rash has been reported,1 but not confirmed.1

Vaccine-related contact infections reported to date generally have been mild or subclinical, indicating the vaccine virus remains attenuated when transmitted.8 10 54

Vaccine recipients should avoid close contact with susceptible, high-risk individuals for up to 6 weeks following vaccination, whenever possible.1 125 High-risk individuals include immunocompromised individuals, pregnant women without a documented history of varicella or laboratory evidence of prior infection, and neonates of such susceptible pregnant women.1 93 125 If contact with high-risk individuals is unavoidable, the potential risk of transmission of vaccine virus should be weighed against the risk of acquiring and transmitting natural varicella virus.1 125

Ensure that vaccinees who develop a rash avoid contact with susceptible, immunocompromised individuals until the rash resolves.10 27 54 If contact inadvertently occurs, postexposure prophylaxis with VZIG is unnecessary since transmission is rare and contact infections generally are mild.27 94

Use of Fixed Combinations

Whenever fixed-combination vaccine containing measles, mumps, rubella, and varicella antigens (MMRV; ProQuad) is used, consider contraindications and cautions related to each antigen.125

There is some evidence that the relative risk for febrile seizures in children 12–60 months of age after a dose of MMRV (ProQuad) is higher than that reported when a dose of Varivax and a dose of MMR are given during a single health-care visit.136 (See Cerebral Injury or Seizures under Cautions.)

When the first dose of MMR and first dose of Varivax are indicated in infants and children 12 through 47 months of age, ACIP states that providers considering use of ProQuad should advise the parent or caregiver about the benefits and risks associated with MMRV (ProQuad) compared with the individual component vaccines.145 Although MMRV (ProQuad) results in 1 less injection, it is associated with a higher risk for fever and febrile seizures on days 5 through 12 after the first dose in children 12 through 23 months of age (i.e., about 1 extra febrile seizure for every 2300–2600 doses of MMRV [ProQuad]).145 ACIP states that if providers face any barriers to clearly communicating these benefits and risks (e.g., language barrier), then MMR and varicella virus vaccine live should be administered instead of MMRV (ProQuad).145

When the first dose of MMR and first dose of Varivax are indicated in children ≥48 months of age and when second doses are indicated in those 15 months through 12 years of age, ACIP states that use of MMRV (ProQuad) generally is preferred over separate injections of the component vaccines;145 considerations should include provider assessment (e.g., number of injections, vaccine availability, likelihood of improved coverage, likelihood of patient return, storage and cost considerations), patient preference, and potential for adverse effects.145

The manufacturer recommends that MMRV (ProQuad) be used with caution in individuals with a history of cerebral injury, personal or family history of seizures, or any other condition in which fever-induced stress should be avoided.125 The ACIP states that a personal or family (i.e., sibling, parent) history of seizures is a precaution for use of MMRV (ProQuad).145 Studies suggest that children with a personal or family history of febrile seizures or family history of epilepsy are at increased risk for febrile seizures compared with children who do not have such histories.145 ACIP states that children with a personal or family history of seizures generally should receive a dose of MMR and a dose of varicella virus vaccine live because the risks of using MMRV (ProQuad) in these children generally outweigh the benefits.145

Data not available regarding safety and efficacy of MMRV (ProQuad) in HIV-infected individuals;27 do not use the fixed-combination vaccine in HIV-infected individuals.27 144 If vaccination against varicella is indicated in an HIV-infected individual, (see Preexposure Vaccination Against Varicella Infection in High-risk Groups under Uses) use monovalent vaccine (Varivax).27 137

Limitations of Vaccine Effectiveness

Varivax: May not protect all individuals from varicella.1 27

MMRV (ProQuad): May not protect all individuals from measles, mumps, rubella, and varicella.125

Varivax: Not known whether administration of the vaccine immediately after exposure to natural varicella virus will prevent illness.1 27 (See Postexposure Vaccination Against Varicella Infection and Outbreak Control under Uses.)

MMRV (ProQuad): Safety and efficacy for postexposure prophylaxis after exposure to measles, mumps, rubella, or varicella not established.125

Duration of Immunity

Duration of protection following primary immunization with 2 doses of varicella vaccine and need for revaccination or additional (booster) doses after primary immunization not fully determined to date.1 27 77 100

Although immunity wanes over time,122 123 protection against varicella may persist for at least 5–10 years after a single vaccine dose.1 4 19 65 27 66 100

Subsequent exposure to natural wild-type varicella infection appears to boost anti-VZV antibody levels in vaccinated individuals.1 24 27 77 This boosting theoretically could contribute to long-term protection against the disease.1 24 The duration of protection against varicella in vaccinated individuals in the absence of such wild-type boosting is unknown.1 24 35 77

Pre- and Postvaccination Serologic Testing

Prevaccination serologic testing is not required before vaccination since the vaccine is well tolerated by immune individuals100 and a prior history of chickenpox is not a contraindication to varicella vaccine.138

The ACIP states that individuals have evidence of immunity to varicella if there is written documentation of age-appropriate vaccination (one vaccine dose in preschool children 12 months of age or older or 2 doses in school-aged children, adolescents, and adults), they were born in the US before 1980 (US birth before 1980 should not be considered evidence of immunity for health-care providers and pregnant women), they have a history of herpes zoster based on a diagnosis by a health-care provider, or there is laboratory evidence of immunity or laboratory confirmation of varicella infection.27 129 In addition, the ACIP states that individuals with a history of typical varicella disease based on a diagnosis or verification of such history by any health-care provider (e.g., school or occupational clinic nurse, nurse practitioner, physician assistant, clinician) can be considered to have evidence of immunity to varicella.27 129 For those reporting a history of or presenting with atypical and/or mild varicella, health-care providers should seek either an epidemiologic link to a typical varicella case (e.g., case occurred in the context of an outbreak or patient had household exposure to varicella in the previous 3 weeks) or evidence of laboratory confirmation performed at the time of acute disease;27 129 when such documentation is lacking, individuals should not be considered as having a valid history of varicella since other diseases may mimic mild, atypical varicella.27

Prevaccination serologic testing is not warranted in children 12 months through 12 years of age without a history of chickenpox since the majority of these children are susceptible.138

Routine postvaccination serologic testing to confirm seroconversion following administration of varicella vaccine in otherwise healthy children, adolescents, or adults is not routinely recommended because of the high rate of seroconversion in these individuals 94 100 and because commercially available assays lack sensitivity to detect vaccine-induced immunity and may give false-negative results.27 137 138

In health-care institutions, prevaccination serologic screening of personnel who have a negative or uncertain history of varicella may be cost-effective.27 113 ACIP and HICPAC state that routine postvaccination testing of health-care personnel probably is not recommended.27 113

Ideally, individuals ≥12 months of age who are scheduled to undergo solid organ transplantation should be tested for serologic evidence of varicella immunity and, if susceptible, should receive varicella vaccine at least 1 month prior to the procedure.100 104 At ≥1 year after transplantation, AAP recommends that serum antibody concentrations be measured in all solid organ transplant recipients and appropriate vaccines administered if indicated.100

When postvaccination serologic testing is used to measure seroconversion (e.g., in individuals with altered immunocompetence, pregnant women, health-care personnel), such testing usually has been performed 6 weeks following vaccination.27

Levels of anti-VZV antibodies that protect against varicella infection have not been identified and seroconversion following administration of varicella vaccine generally is defined as acquisition of any detectable level of anti-VZV antibodies.1 27 52

Although varicella is unlikely to develop in individuals who have detectable anti-VZV antibodies, breakthrough varicella infections can occur despite seroconversion and presence of such antibodies.5 27 42 73 75 77 81

Concomitant Illness

A decision to administer or delay vaccination in an individual with a current or recent febrile illness depends on the severity of symptoms and etiology of the illness.26 27

Manufacturers state Varivax and MMRV (ProQuad) are contraindicated in individuals with any febrile respiratory illness or other active febrile infections. 1 125

ACIP states that minor acute illness, such as mild diarrhea or mild upper respiratory tract infection (with or without fever), generally does not preclude vaccination, but defer vaccination in individuals with moderate or severe acute illness (with or without fever).26 27

Tuberculosis

Manufacturers state Varivax and MMRV (ProQuad) are contraindicated in individuals with active untreated tuberculosis.1 125

ACIP states that, although no data exist regarding whether tuberculosis is exacerbated by natural varicella or varicella vaccine, vaccination is not recommended for those with untreated, active tuberculosis.27 However, tuberculin skin testing is not a prerequisite for vaccine administration.27 100

Improper Storage and Handling

Improper storage or handling of vaccines may result in loss of vaccine potency26 139 and reduced immune response in vaccinees.26

Do not administer Varivax or ProQuad vaccine that has been mishandled or has not been stored at the recommended temperature.1 26 125 139 (See Storage under Stability.)

Protect lyophilized vaccine from light at all times;1 125 139 exposure to light may inactivate the vaccine virus.125 139

Avoid freezing or exposing the diluent supplied by the manufacturer to freezing temperatures;1 125 139 diluent may be refrigerated or stored at room temperature.1 125 139 (See Storage under Stability.)

Inspect all vaccines upon delivery and monitor during storage to ensure that the appropriate temperature is maintained.26 If there are concerns about mishandling, contact the manufacturer or state or local health departments for guidance on whether the vaccine is usable.26 139

Discard any reconstituted vaccine not used within 30 minutes; do not freeze.1 125 139 (See Storage under Stability.)

Specific Populations

Pregnancy

Category C.1 125

Contraindicated during pregnancy.1 26 27 100 125 129 In addition, manufacturer of Varivax and MMRV (ProQuad) states pregnancy should be avoided for 3 months after vaccination.1 125 ACIP, AAP, and others state avoid pregnancy for 1 month following vaccination.26 27 100 129 137 140

Natural varicella infection during pregnancy, especially during the first 2 trimesters, has been associated with congenital varicella syndrome which may result in spontaneous abortion, fetal death, or congenital abnormalities.1 15 25 27 31 93 138 In addition, neonates whose mothers had signs and symptoms of varicella at the time of delivery (from 5 days before to 2 days after delivery) are at risk of severe, potentially fatal varicella.27 100 138 Assess all pregnant women for evidence of varicella immunity; if there is no evidence of immunity, initiate varicella vaccination immediately after pregnancy is completed or terminated.26 27 129 137

Pregnancy registry at 800-986-8999.1 27 72 125 Clinicians or vaccinees should report any exposure to varicella vaccine that occurs during pregnancy or any time during the 3 months prior to pregnancy.1 27 72 125

ACIP and AAP state that the presence of a pregnant woman in a household does not contraindicate use of varicella vaccine in other household members.26 27 100 137 Vaccination of susceptible household members will likely protect the susceptible pregnant woman from exposure to wild-type VZV.100

If varicella vaccine is administered to a household member and the recipient develops a varicelliform rash, contact with the susceptible pregnant woman should be avoided if possible.27 95 103 (See Transmission of Vaccine Virus under Cautions.)

Lactation

Use with caution in nursing women.1

Not known whether attenuated varicella virus contained in varicella vaccine is distributed into milk following sub-Q administration.1 Although organisms contained in live vaccines multiply in the body and some may be distributed into milk following immunization of the mother (e.g., rubella vaccine), there is no evidence that this occurs with varicella vaccine and no evidence that it would adversely affect a nursing infant.26 27 100

ACIP and AAP state that monovalent varicella vaccine may be used in susceptible nursing women,26 27 100 137 especially if the risk for exposure to natural infection is high.100

Pediatric Use

Varivax: Safety and efficacy not established in children <12 months of age.1 27

MMRV (ProQuad): Safety and efficacy not established in children <12 months of age.125 Should not be used in children or adolescents ≥13 years of age.125

Transplacental antibodies to VZV reportedly persist for up to 6–8 months after delivery44 and should not interfere with the immunologic response if vaccines containing varicella antigen are administered to children at ≥12 months of age.44 100

Geriatric Use

Varivax: Clinical studies did not include sufficient numbers of seronegative adults ≥65 years of age to determine whether geriatric adults respond differently than younger individuals.1 Other reported clinical experience has not identified differences in responses between geriatric and younger individuals.1

MMRV (ProQuad): Not indicated for use in adults, including geriatric adults.125

Common Adverse Effects

Varivax: Injection site reactions (pain, soreness, swelling, erythema),1 9 11 27 30 42 43 44 45 47 80 fever (≥38.3°C),1 3 27 30 42 generalized varicella-like maculopapular or papulovesicular rash.1 3 14 27 30 42 43 44 45 47 75 80

MMRV (ProQuad): Adverse effects similar to those reported when varicella vaccine and MMR are administered simultaneously at separate sites,125 but higher incidence of fever (≥38.9°),125 febrile seizures,136 measles-like rash.125

Interactions for Varicella Virus Vaccine Live

Live Vaccines

Varicella vaccine is a live, attenuated virus vaccine.1 26 27 137 Some oral live vaccines (e.g., rotavirus vaccine live oral, typhoid vaccine live oral, poliovirus vaccine live oral [OPV; no longer commercially available in the US]) can be administered simultaneously with or at any interval before or after varicella vaccine.26 100 However, because of theoretical concerns that the immune response to intranasal live vaccines or other parenteral live virus vaccines might be impaired if given within 28–30 days of another live virus vaccine, if varicella vaccine and these live vaccines are not administered on the same day, they should be administered at least 4 weeks (i.e., 28 days) apart to minimize the potential for interference.26 100 (See Specific Drugs and Laboratory Tests under Interactions.)

Inactivated Vaccines and Toxoids

Varicella vaccine may be administered simultaneously with (using different syringes and different injection sites) or at any interval before or after inactivated vaccines, recombinant vaccines, polysaccharide vaccines, or toxoids.26 27 100 121 137 (See Specific Drugs and Laboratory Tests under Interactions.)

Specific Drugs and Laboratory Tests

Drug or Test

Interaction

Comments

Antiviral agents active against Herpesviruses (e.g., acyclovir, famciclovir, valacyclovir)

May reduce efficacy of varicella vaccine26

Discontinue antiviral agent active against Herpesviruses at least 24 hours before administration of varicella vaccine, if possible26

Blood products (e.g., whole blood, packed RBCs, plasma)

Although specific studies not available, antibodies contained in blood products may interfere with the immune response to varicella vaccine1 26 27 125

Do not administer varicella vaccine simultaneously with or for specified intervals before or after administration of blood products1 26 27 125

Defer varicella vaccine for ≥3 months following administration of RBCs (with adenine-saline added); for ≥6 months following administration of packed RBCs or whole blood; or for ≥7 months following administration of plasma or platelet products;26 however, because of the importance of postpartum vaccination in women without evidence of varicella immunity, vaccination of such women should not be delayed because they received a blood product26

After administering varicella vaccine, avoid blood products for 2 weeks; if use of a blood product is considered necessary during this period, give a repeat vaccine dose after the recommended interval unless serologic testing is feasible and indicates a response to the vaccine was attained27

Diphtheria and tetanus toxoids and acellular pertussis vaccines adsorbed (DTaP)

Varivax: May be administered concurrently (using different syringes and different injection sites) or at any interval before or after DTaP26 27 100 137

MMRV (ProQuad): Manufacturer states data insufficient to date to recommend concurrent administration with DTaP125

Haemophilus b (Hib) vaccine

Although specific studies not available, Hib vaccines are inactivated vaccines and interactions are not expected27 100

MMRV (ProQuad): Has been administered concomitantly with Hib vaccine and HepB vaccine at separate injection sites and seroconversion rates and antibody titers for the measles, mumps, rubella, varicella, Hib, and hepatitis B antigens were comparable with results obtained when the vaccines were administered 6 weeks apart125

Varivax or MMRV (ProQuad): May be administered concurrently with (using different syringes and different injection sites) or at any interval before or after Hib vaccine27 100 121 125

Hepatitis B (HepB) vaccine

Although specific studies not available, HepB vaccine is an inactivated vaccine and interactions are not expected27 100

MMRV (ProQuad): Has been administered concomitantly with HepB and Hib vaccines at separate injection sites and seroconversion rates and antibody titers for measles, mumps, rubella, varicella, anti-PRP, and hepatitis B were comparable with results obtained when the vaccines were administered 6 weeks apart125

Varivax or MMRV (ProQuad): May be administered concurrently with or at any interval before or after HepB vaccine27 100 121 125

Immune globulin (immune globulin IM [IGIM], immune globulin IV [IGIV]) or specific immune globulin (hepatitis B immune globulin [HBIG], rabies immune globulin [RIG], tetanus immune globulin [TIG], varicella zoster immune globulin [VZIG])

Although specific studies not available, antibodies contained in immune globulin preparations may interfere with the immune response to varicella vaccine1 26 27 125

Varivax or MMRV (ProQuad) should not be administered simultaneously with or for specified intervals before or after administration of immune globulin preparations1 26 27 125

Defer administration of varicella vaccine for ≥3 months following administration of tetanus immune globulin (TIG), hepatitis B immune globulin (HBIG), immune globulin IM (IGIM) used for postexposure prophylaxis of hepatitis A virus (HAV);26 for ≥4 months following administration of rabies immune globulin (RIG);26 for ≥5 months following administration of IGIM used for measles prophylaxis in immunocompetent individuals;26 for ≥6 months following administration of cytomegalovirus immune globulin IV (CMV-IGIV) or IGIM for measles prophylaxis in immunocompromised individuals;26 for ≥5–8 months following administration of VZIG or IGIV for postexposure prophylaxis of severe varicella;26 27 126 for≥8 months following administration of immune globulin IV (IGIV) for replacement therapy of immunodeficiencies; for ≥8–10 months following administration of IGIV for treatment of idiopathic thrombocytopenic purpura (ITP);26 or for ≥11 months following administration of IGIV for Kawasaki syndrome26

If varicella vaccine is administered simultaneously with an immune globulin preparation or was administered at less than the recommended interval, consider that vaccine-induced immunity may be compromised; give an additional vaccine dose after the specified interval unless serologic testing is feasible and indicates a response to the vaccine was attained26

After administering varicella vaccine, avoid immune globulin preparations for 2 weeks; if use of an immune globulin is considered necessary during this period, give a repeat vaccine dose after the recommended interval unless serologic testing is feasible and indicates a response to the vaccine was attained26 27

Immunosuppressive agents (e.g., alkylating agents, antimetabolites, corticosteroids, radiation)

Use of varicella vaccine in individuals receiving immunosuppressive therapy may result in more extensive vaccine-associated rash or disseminated disease1 27 125

Corticosteroid therapy (prednisone or equivalent) in a dosage ≥2 mg/kg daily or ≥20 mg daily given for ≥2 weeks is considered immunosuppressive26 137

Short-term (<2 weeks), low- to moderate-dose systemic corticosteroid therapy; long-term, alternate-day systemic corticosteroid therapy using low to moderate doses of short-acting drugs; topical corticosteroid therapy (e.g., nasal, cutaneous, ophthalmic); or intra-articular, bursal, or tendon injections with corticosteroids should not be immunosuppressive in usual dosages26 63 70

Defer varicella vaccine until immunosuppressive therapy is discontinued1 27 125 137

Optimum interval between discontinuance of immunosuppressive therapy and subsequent administration of a live viral vaccine not determined;26 137 live viral vaccines generally should not be administered for at least 3 months after immunosuppressive therapy is discontinued26 63 70 137

In patients who received corticosteroid therapy that is considered immunosuppressive,26 63 70 delay administration of varicella vaccine for at least 1 month after the corticosteroid is discontinued26 27 137

MMRV (ProQuad): Manufacturer states this vaccine may be used in individuals receiving topical corticosteroids or low-dose corticosteroids for asthma prophylaxis or replacement therapy (e.g., for Addison’s disease)125

Influenza vaccine

Intranasal live influenza vaccine: Studies using seasonal intranasal live influenza vaccine indicate simultaneous administration with varicella vaccine in children 12–15 months of age did not interfere with the immune response to either vaccine and did not increase the frequency of adverse effects;142 safety and immunogenicity of concomitant administration not evaluated in infants >15 months of age142

Parenteral inactivated influenza vaccine: Interactions with live vaccines such as varicella vaccine unlikely26

Intranasal live influenza vaccine: If not given simultaneously, give at least 4 weeks apart, if possible26

Parenteral inactivated influenza vaccine: May be administered simultaneously with (using different syringes and different injection sites) or at any interval before or after varicella vaccine26

Measles, mumps, and rubella vaccine (MMR)

Simultaneous administration of monovalent varicella vaccine and MMR does not interfere with the immune response to either vaccine;1 26 76 varicella vaccine may be less effective if given <30 days after MMR26 121

The fixed-combination vaccine containing varicella vaccine and MMR (MMRV; ProQuad) results in antibody responses similar to those obtained after simultaneous administration of a single dose of MMR and a single dose of Varivax90

Monovalent varicella vaccine and MMR may be given simultaneously (using different syringes and different injection sites);1 5 7 26 27 87 100 if not administered simultaneously, give at least 1 month apart26 27 100

Alternatively, may be given simultaneously as the fixed-combination vaccine containing varicella vaccine and MMR (MMRV; ProQuad)90

Pneumococcal vaccine

Although specific studies not available, pneumococcal vaccines are inactivated vaccines and interactions with varicella vaccine are not expected26 119 120

Manufacturer states data not available to date regarding concurrent administration of MMRV (ProQuad) and PCV7 (Prevnar)125

Pneumococcal vaccine may be administered concurrently with (using different syringes and different injection sites) or at any interval before or after varicella vaccine26 27 100 121

Poliovirus vaccine inactivated (IPV)

Although specific studies not available, IPV is an inactivated vaccine and interactions with varicella vaccine are not expected26

Manufacturer states data not available to date regarding concurrent administration of MMRV (ProQuad) and IPV125

Varicella vaccine may be administered concurrently with (using different syringes and different injection sites) or any time before or after IPV26 27 100 121

Rho(D) immune globulin

Specific studies not available evaluating whether passively acquired antibodies from Rho(D) immune globulin interfere with the immune response to varicella vaccine26

Because of the importance of postpartum varicella vaccination in women who do not have evidence of varicella immunity, vaccination of such women should not be delayed because they received Rho(D) immune globulin26

Rotavirus vaccine

No evidence to date that parenterally administered live vaccines such as varicella vaccine interfere with the immune response to oral rotavirus vaccine26

May be administered concomitantly with or at any interval before or after varicella vaccine26

Salicylates

Reye’s syndrome has been reported in children and adolescents who received salicylates during natural varicella infection;1 100 125 an association between Reye’s syndrome, administration of varicella vaccine, and use of salicylates has not been established1 27 42 100

Because Reye’s syndrome has been reported in children and adolescents who received salicylates during natural varicella infection, manufacturer of Varivax and MMRV (ProQuad) recommends that salicylates be avoided for 6 weeks following vaccination1 125

ACIP states that children with rheumatoid arthritis or other conditions requiring therapeutic salicylate therapy probably should receive the vaccine in conjunction with subsequent close monitoring since risk for serious salicylate-associated complications is likely to be greater in children who develop natural varicella than in those who receive varicella vaccine27

In children receiving long-term salicylate therapy, AAP suggests that the theoretical risks associated with varicella vaccine be weighed against the known risks of the wild-type virus100

Tuberculin

Effect of varicella vaccine, if any, on tuberculin testing has not been determined;26 100 another live virus vaccine (measles vaccine) has been reported to temporarily suppress tuberculin skin sensitivity26 100 125

Tuberculin tests (if required) should be administered before, simultaneously with, or 4–6 weeks after administration of Varivax or MMRV (ProQuad)26 125

ACIP states that vaccination with varicella vaccine should not be delayed based only on a theoretical concern about a possible interaction with tuberculin skin testing26

Typhoid vaccine

Oral live typhoid vaccine (Vivotif): Specific data not available regarding immunogenicity when administered concurrently with or within 30 days of varicella vaccine26

Parenteral inactivated typhoid vaccine (Typhim Vi): Since this typhoid vaccine is an inactivated vaccine, interactions with live vaccines such as varicella vaccine are unlikely26

Oral live typhoid vaccine (Vivotif): May be administered simultaneously with or at any interval before or after varicella vaccine26

Parenteral inactivated typhoid vaccine (Typhim Vi): May be administered simultaneously with (using different syringes and injection sites) or at any interval before or after varicella vaccine26

Yellow fever vaccine

Data regarding nonsimultaneous administration not available26

Yellow fever vaccine and varicella vaccine may be given simultaneously (using different syringes and different injection sites)26

If not given simultaneously, give at least 4 weeks apart, if possible26

Stability

Storage

Parenteral

For Injection, for Sub-Q Use

To maintain potency, lyophilized varicella vaccines (Varivax, MMRV [ProQuad]) must be kept frozen at -15°C or colder and protected from light during shipment and storage.1 27 125 139 Must be shipped in insulated containers with dry ice and delivered within 2 days.139

After delivery, keep lyophilized vaccine frozen at -15°C or colder and protect from light; any freezer (e.g., chest, frost-free) that reliably maintains an average temperature of -15°C or colder and has a separate sealed freezer door is acceptable.1 27 125 139

When optimal handling conditions are not feasible (e.g., during transportation to off-site clinics, unavailability of dry ice), potency can be maintained if vials of lyophilized vaccine are stored for ≤72 hours at 2–8°C.1 27 125 139 A temperature recording device should be included in the transport container to ensure that the temperature is no warmer than 2–8°C.27

Discard any vials of lyophilized vaccine that have been stored at 2–8°C for >72 hours.1 27 125 139 Contact manufacturer at 800-637-2590 for information regarding vaccine stability under conditions other than those recommended.1 125 139

Store diluent provided by the manufacturer separately, either at room temperature (20–25°C) or in a refrigerator (2–8°C);1 125 139 do not freeze.139

To minimize loss of potency and ensure an adequate immunizing dose, use Varivax or MMRV (ProQuad) immediately after reconstitution; discard any reconstituted vaccine not used within 30 minutes.1 125

Do not freeze reconstituted Varivax or MMRV (ProQuad).1 125

Varivax and MMRV (ProQuad) do not contain thimerosal or any other preservatives.1 125

Actions

  • Varicella vaccine available for use in the US is a lyophilized preparation of live, attenuated VZV of the Oka/Merck strain.1 27 42 It is similar, but not identical, to varicella vaccines available in Japan and other countries that contain Oka/Biken or Oka/RIT strains of VZV.8 11 15 42 45

  • Commercially available in the US as a monovalent vaccine (Varivax)) and a fixed-combination vaccine containing measles, mumps, rubella, and varicella antigens (MMRV; ProQuad).125 The varicella antigen contained in these vaccines is identical, but MMRV has a higher titer of the antigen than the monovalent vaccine.27

  • Varicella vaccine induces active immunity to VZV.1 4 8 9 65 67

  • VZV causes varicella (chickenpox) and herpes zoster (shingles, zoster).8 138 During varicella (the primary infection), VZV invades sensory neurons and becomes latent in sensory nerve ganglia, establishing a source of potential secondary infection.6 8 27 33 41 138 In some individuals (especially older adults and immunocompromised individuals), reactivation of VZV results in herpes zoster.6 8 27 33 41 138

  • Varicella is highly contagious; the secondary infection rate is 80–90% in healthy, susceptible individuals exposed through household contact.6 8 27 The disease is transmitted person-to-person through airborne respiratory droplet infection or direct contact, droplet, or aerosol from vesicular fluid of skin vesicles, which contain high titers of VZV.6 8 27 41

  • Following exposure to the disease or virus, the incubation period in otherwise healthy individuals averages about 14–16 days (range: 9–21 days).6 27 100 138 In utero infections can occur; fetal infections occurring during the first and second trimesters may result in congenital varicella disease.100 138 Infants born to mothers with active varicella at the time of delivery may develop the disease within the first 2 weeks of life; the usual interval from onset of rash in the mother to disease onset in the neonate is 9–15 days.100

  • Natural varicella infection elicits development of specific antibodies and cell-mediated immunity and generally confers lifelong protection against subsequent varicella infection.6 27 41

  • The vaccine virus differs slightly from wild-type VZV circulating in the US;5 8 9 33 35 immune responses elicited by the vaccine are not identical to those elicited by the wild-type virus.8 65 67 94

  • Efficacy of varicella vaccine in preventing varicella infection varies depending on age and immunocompetence of the vaccinee.11 54 65 In some individuals, especially healthy adults and immunocompromised children, the vaccine provides partial immunity and modification of subsequent varicella infection rather than complete protection.5 8 11 13 24 41 65

  • In healthy children 12 months through 12 years of age, the seroconversion rate is 98% after a single dose of varicella vaccine and 100% after a second vaccine dose given 3 months after first dose.101 In those ≥13 years of age, seroconversion rate is 75–94% after a single dose and 99% after a second dose.1

  • Varicella vaccine is less immunogenic in healthy adolescents and adults than in healthy children.1 5 8 9 11 65 80 Many healthy adults who do not seroconvert after a single dose of varicella vaccine do so after a second dose.9 11 27 There is no evidence that the second dose affects the duration of protection against varicella.8 9

  • Clinical studies in healthy children 12–23 months of age indicate that those who received a single dose of MMRV (ProQuad) developed antibody levels against measles, mumps, rubella, and varicella that were similar to levels attained in children who received a single dose of MMR and a single dose of varicella vaccine concomitantly at separate sites.128

  • Levels of anti-VZV antibodies that protect against varicella infection have not been defined and any detectable level of anti-VZV antibodies after vaccination generally has been used to indicate seroconversion.1 27 52

  • Seroconversion does not result in complete protection in all individuals, and breakthrough varicella infections may occur in some children or adults who seroconverted following vaccination and are subsequently exposed to wild-type virus.1 4 5 8 27 42 65 75 80 (See Breakthrough Varicella Infections under Cautions.)

Advice to Patients

  • Prior to administration of each vaccine dose, provide a copy of the appropriate CDC Vaccine Information Statement (VIS) to the patient or patient’s legal representative as required by the National Childhood Vaccine Injury Act (VISs are available at ).1 125 140

  • Advise patient and/or patient’s parent or guardian of the risks and benefits of vaccination with varicella vaccine.1 125

  • Importance of receiving the complete immunization series (2 doses) to ensure highest level of protection against varicella.1

  • Advise patient that Varivax and MMRV (ProQuad) may not provide protection in all vaccinees.1 125

  • Advise patient they should not receive Varivax and MMRV (ProQuad) if they have had a life-threatening allergic reaction to a previous dose or are allergic to ingredients of the vaccine (e.g., gelatin, neomycin).1 125 140

  • Advise patient of the theoretical risk of transmitting the vaccine virus to varicella-susceptible individuals, including pregnant women who have not had chickenpox.1

  • Advise patient they should not receive varicella vaccine if they have a disease that weakens the immune system (e.g., cancer, HIV/AIDS) or are receiving treatment that may weaken the immune system (e.g., cancer treatment with radiation or drugs, corticosteroids).1 140

  • Importance of contacting clinician if a hypersensitivity reaction (difficulty breathing, hoarseness, wheezing, hives, paleness, weakness, fast heart beat, dizziness) or other moderate or severe reaction (high fever, behavior changes) occurs following a dose of varicella vaccine.1 140 Clinicians or individuals can report any adverse reactions that occurs following vaccination to Vaccine Adverse Event Reporting System (VAERS) at 800-822-7967 or .1 125 137 140

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1 125 Importance of avoiding salicylates for 6 weeks after vaccination.125

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 125 140 Advise women to avoid pregnancy for 1–3 months following a dose of Varivax and MMRV (ProQuad).1 27 125 140 Report any exposure to varicella vaccine that occurs during pregnancy to the pregnancy registry at 800-986-8999.1 27 72 125

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Varicella Virus Vaccine Live

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, for subcutaneous use

1350 plaque-forming units (PFU) per 0.5 mL

Varivax

Merck

Measles, Mumps, Rubella and Varicella Virus Vaccine Live (MMRV)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, for subcutaneous use

Measles Virus Vaccine Live (More Attenuated Enders’ Line) ≥3 log 10 tissue culture infective dose 50% (TCID50), Mumps Virus Vaccine Live (Jeryl Lynn [B level] Strain) ≥4.3 log 10 TCID50, Rubella Virus Vaccine Live (Wistar RA 27/3 Strain) ≥3 log 10 TCID50, and Varicella Virus Vaccine Live (Oka/Merck Strain) ≥3.99 log 10 plaque-forming units (PFU) per 0.5 mL

ProQuad

Merck

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions May 1, 2010. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Merck & Co. Varivax (varicella virus vaccine live) prescribing information. Whitehouse Station, NJ; 2009 Jun.

3. Weibel RE, Kuter BJ, Neff BJ et al. Live Oka/Merck varicella vaccine in healthy children: further clinical and laboratory assessment. JAMA. 1995; 254:2435-9.

4. Asano Y, Nagai T, Miyata T et al. Long-term protective immunity of recipients of the OKA strain of live varicella vaccine. Pediatrics. 1985; 75:667-71. [IDIS 198189] [PubMed 2984636]

5. Gershon AA. Live attenuated varicella vaccine. J Pediatr. 1987; 110:154-7. [IDIS 225711] [PubMed 3025393]

6. Straus SE, Ostrove JM, Inchauspé G et al. Varicella-zoster virus infections: biology, natural history, treatment, and prevention. Ann Intern Med. 1988; 108:221-37. [IDIS 238469] [PubMed 2829675]

7. Englund JA, Suarez CS, Kelly J et al. Placebo-controlled trial of varicella vaccine given with or after measles-mumps-rubella vaccine. J Pediatr. 1989; 114:37-44. [IDIS 250887] [PubMed 2535873]

8. Gershon AA. Viral vaccines of the future. Pediatr Clin North Am. 1990; 37:689-707. [PubMed 2161508]

9. Feldman S, Moffitt JE. Varicella vaccine. Pediatr Ann. 1990; 19:721-6. [PubMed 2177874]

10. Tsolia M, Gershon AA, Steinberg SP et al. Live attenuated varicella vaccine: evidence that the virus is attenuated and the importance of skin lesions in transmission of varicella-zoster virus. J Pediatr. 1990; 116:184-9. [IDIS 266701] [PubMed 2153790]

11. Hardy IRB, Gershon AA. Prospects for use of a varicella vaccine in adults. Infect Dis Clin North Am. 1990; 4:159-73. [PubMed 2155261]

12. Brunell PA. Chickenpox—examining our options. N Engl J Med. 1991; 325:1577-9. [IDIS 289184] [PubMed 1658651]

13. White CJ, Kuter BJ, Ngai A et al. Modified cases of chickenpox after varicella vaccination: correlation of protection with antibody response. Pediatr Infect Dis J. 1992; 11:19-23. [PubMed 1312704]

14. Gershon AA, LaRussa P, Hardy I et al. Varicella vaccine: the American experience. J Infect Dis. 1992; 166(Suppl 1):S63-8. [IDIS 299528] [PubMed 1320652]

15. Clements DA, Katz SL. Varicella in a susceptible pregnant woman. Curr Clin Top Infect Dis. 1993; 13:123-30. [PubMed 8397905]

16. Watson BM, Piercy SA, Plotkin SA et al. Modified chickenpox in children immunized with the Oka/Merck varicella vaccine. Pediatrics. 1993; 91:17-22. [IDIS 307733] [PubMed 8416499]

17. Bernstein HH, Rothstein EP, Watson BM et al. Clinical survey of natural varicella compared with breakthrough varicella after immunization with live attenuated Oka/Merck varicella vaccine. Pediatrics. 1993; 92:833-7. [IDIS 323434] [PubMed 8233746]

18. Asano Y, Suga S, Yoshikawa T et al. Experience and reason: twenty-year follow-up of protective immunity of the Oka strain live varicella vaccine. Pediatrics. 1994; 94:524-6. [IDIS 336760] [PubMed 7936864]

19. Watson B, Gupta R, Randall T et al. Persistence of cell-mediated and humoral immune response in healthy children immunized with live attenuated varicella vaccine. J Infect Dis. 1994; 169:197-9. [IDIS 324769] [PubMed 8277182]

20. Hughes P, LaRussa P, Pearce JM et al. Transmission of varicella-zoster virus from a vaccinee with leukemia, demonstrated by polymerase chain reaction. J Pediatr. 1994; 124:932-5. [IDIS 331651] [PubMed 8201480]

21. Huse DM, Meissner HC, Lacey MJ et al. Childhood vaccination against chickenpox: an analysis of benefits and costs. J Pediatr. 1994; 124:869-74. [IDIS 331645] [PubMed 8201469]

22. Lieu TA, Cochi SL, Black SB et al. Cost-effectiveness of a routine varicella vaccination program for US children. JAMA. 1994; 271:375-81. [IDIS 325018] [PubMed 8283587]

23. Lieu TA, Black SB, Rieser N et al. The cost of childhood chickenpox: parents’ perspective. Pediatr Infect Dis J. 1994; 13:173-7. [IDIS 327036] [PubMed 8177622]

24. Halloran ME, Cochi SL, Lieu TA et al. Theoretical epidemiologic and morbidity effects of routine varicella immunization of preschool children in the United States. Am J Epidemiol. 1994; 140:81-104. [PubMed 8023813]

25. Brunell PA. Varicella in pregnancy, the fetus, and the newborn: problems in management. J Infect Dis. 1992; 166(Suppl 1):S42-7. [IDIS 299526] [PubMed 1624811]

26. Centers for Disease Control and Prevention. General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2006; 55(RR-15):1-47.

27. Centers for Disease Control and Prevention. Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2007; 56(RR-4):1-40.

28. Arbeter AM, Baker L, Starr SE et al. Combination measles, mumps, rubella, and varicella vaccine. Pediatrics. 1986; 76(Suppl):742-7.

29. Brunell PA, Novelli VM, Lipton SV et al. Combined vaccine against measles, mumps, rubella, and varicella. Pediatrics. 1988; 81:779-84. [IDIS 242276] [PubMed 2835743]

30. Dennehy PH, Reisinger KS, Blatter MM et al. Immunogenicity of subcutaneous versus intramuscular Oka/Merck varicella vaccination in healthy children. Pediatrics. 1991; 88:604-7. [IDIS 287790] [PubMed 1881743]

31. Enders G, Miller E, Cradock-Watson J et al. Consequences of varicella and herpes zoster in pregnancy: prospective study of 1739 cases. Lancet. 1994; 343:1548-51. [PubMed 7802767]

32. Finger R, Hughes JP, Meade BJ et al. Age-specific incidence of chickenpox. Public Health Rep. 1994; 109:750-5. [PubMed 7800783]

33. Weller TH. Varicella and herpes zoster: changing concepts of the natural history, control, and importance of a not-so-benign virus (first of two parts). N Engl J Med. 1983; 309:1362-8. [PubMed 6314138]

34. Weller TH. Varicella and herpes zoster: changing concepts of the natural history, control, and importance of a not-so-benign virus (second of two parts). N Engl J Med. 1983; 309:1434-40. [PubMed 6195526]

35. Takahashi M. Clinical overview of varicella vaccine: development and early studies. Pediatrics. 1986; 78(Suppl):736-41. [IDIS 222691] [PubMed 3020493]

36. Watson BA, Starr SE. Varicella vaccine for healthy children. Lancet. 1994; 343:928-9. [IDIS 328240] [PubMed 7909003]

37. Simini B. Varicella-zoster vaccination for health care workers. Lancet. 1994; 343:1363. [IDIS 330054] [PubMed 7910352]

38. Lavin A. Varicella-zoster vaccination for health care workers. Lancet. 1994; 343:1363. [IDIS 330055] [PubMed 7910351]

39. Mangano MF. Varicella vaccine reflux. Pediatrics. 1992; 89:353-4. [IDIS 291354] [PubMed 1310355]

40. White CJ. Varicella vaccine reflux. Pediatrics. 1992; 89:354. [IDIS 291355] [PubMed 1734415]

41. Gershon AA. Varicella vaccine: still at the crossroads. Pediatrics. 1992; 90:144-8. [IDIS 300070] [PubMed 1318541]

42. White CJ, Kuter BJ, Hildebrand CS et al. Varicella vaccine (Varivax) in healthy children and adolescents: results from clinical trials, 1987 to 1989. Pediatrics. 1991; 87:604-10. [IDIS 282646] [PubMed 1850506]

43. Weibel RE, Neff BJ, Kuter BJ et al. Live attenuated varicella virus vaccine: efficacy trial in healthy children. N Engl J Med. 1984; 310:1409-15. [IDIS 185436] [PubMed 6325909]

44. Johnson CE, Shurin PA, Fattlar D et al. Live attenuated varicella vaccine in healthy 12- to 24-month-old children. Pediatrics. 1988; 81:512-8. [IDIS 241316] [PubMed 2832819]

45. Arbeter AM, Starr SE, Plotkin SA. Varicella vaccine studies in healthy children and adults. Pediatrics. 1986; 78(Suppl):748-56. [IDIS 222693] [PubMed 3020494]

46. Arbeter AM, Starr SE, Weibel RE et al. Live attenuated varicella vaccine: immunization of healthy children with the OKA strain. J Pediatr. 1982; 100:886-93. [IDIS 157200] [PubMed 6283051]

47. Gershon AA, Steinberg SP, LaRussa P et al Immunization of healthy adults with live attenuated varicella vaccine. J Infect Dis. 1988; 158:132-7.

48. Gershon AA, Steinberg SP, National Institute of Allergy and Infectious Diseases Varicella Vaccine Collaborative Study Group. Live attenuated varicella vaccine: protection in healthy adults compared with leukemic children. J Infect Dis. 1990; 161:661-6. [IDIS 300935] [PubMed 2156941]

49. Hardy I, Gershon AA, Steinberg SP et al. The incidence of zoster after immunization with live attenuated varicella vaccine: a study in children with leukemia. N Engl J Med. 1991; 325:1545-50. [IDIS 289182] [PubMed 1658650]

50. Plotkin SA, Starr SE, Connor K et al. Zoster in normal children after varicella vaccine. J Infect Dis. 1989; 159:1000-1. [IDIS 254202] [PubMed 2540244]

51. Hammerschlag MR, Gershon AA, Steinberg SP et al. Herpes zoster in an adult recipient of live attenuated varicella vaccine. J Infect Dis. 1989; 160:535-7. [IDIS 305057] [PubMed 2547882]

52. Arbeter AM, Granowetter L, Starr SE et al Immunization of children with acute lymphoblastic leukemia with live attenuated varicella vaccine without complete suspension of chemotherapy. Pediatrics. 1990; 85:338-44.

53. Gershon AA, Steinberg SP, Varicella Vaccine Collaborative Study Group of the National Institute of Allergy and Infectious Diseases. Persistence of immunity to varicella in children with leukemia immunized with live attenuated varicella vaccine. N Engl J Med. 1989; 320:892-7. [IDIS 252965] [PubMed 2538749]

54. Brunell PA, Geiser CF, Novelli V et al. Varicella-like illness caused by live varicella vaccine in children with acute lymphocytic leukemia. Pediatrics. 1987; 79:922-7. [IDIS 230836] [PubMed 3035478]

55. Gershon AA, Steinberg SP, Gelb L et al. Live attenuated varicella vaccine use in immunocompromised children and adults. Pediatrics. 1986; 78(Suppl):757-62. [IDIS 222694] [PubMed 3020495]

56. Watson B, Piercy S, Soppas D et al. The effect of decreasing amounts of live virus, while antigen content remains constant, on immunogenicity of Oka/Merck varicella vaccine. J Infect Dis. 1993; 168:1356-60. [IDIS 322488] [PubMed 8245520]

57. Bader M. Varicella vaccine. JAMA. 1994; 271:1744-5. [IDIS 330657] [PubMed 8196114]

58. Brunell PA, Shehab Z, Geiser C et al. Administration of live varicella vaccine to children with leukaemia. Lancet. 1982; 2:1069-73. [IDIS 160937] [PubMed 6127546]

59. Gray GC, Palinkas LA, Kelley PW. Increasing incidence of varicella hospitalizations in United States army and navy personnel: are today’s teenagers more susceptible? Should recruits be vaccinated? Pediatrics. 1990; 86:867-73.

60. Longfield JN, Winn RE, Gibson RL et al. Varicella outbreaks in army recruits from Puerto Rico: varicella susceptibility in a population from the tropics. Arch Intern Med. 1990; 150:970-3. [PubMed 2158774]

61. Smukler M. Routine childhood varicella vaccination. JAMA. 1994; 271:1906. [PubMed 8201730]

62. Lieu TA, Black SB, Shinefield HR et al. Routine childhood varicella vaccination. JAMA. 1994; 271:1906.

63. Anon. Merck Varivax vaccine approved March 17 with postmarketing studies requirement; 25,000-children phase IV study will be conducted through Kaiser. F-D-C Rep. March 20, 1995:6-7.

64. Preblud SR. Varicella: complications and costs. Pediatrics. 1986; 78(Suppl):728-35. [PubMed 3093966]

65. Gershon AA. Human immune responses to live attenuated varicella vaccine. Rev Infect Dis. 1991; 13(Suppl 11):S957-9. [IDIS 295862] [PubMed 1664134]

66. Asano Y, Albrecht P, Vujcic LK et al. Five-year follow-up study of recipients of live varicella vaccine using enhanced neutralization and fluorescent antibody membrane antigen assays. Pediatrics. 1983; 72:291-4. [IDIS 175722] [PubMed 6310478]

67. Ndumbe PM, Cradock-Watson J, Levinsky RJ. Natural and artificial immunity to varicella zoster virus. J Med Virol. 1988; 25:171-8. [PubMed 2839610]

68. Bergen RE, Diaz PS, Arvin AM. The immunogenicity of the Oka/Merck varicella vaccine in relation to infectious varicella-zoster virus and relative viral antigen content. J Infect Dis. 1990; 162:1049-54. [IDIS 274442] [PubMed 2172393]

69. Diaz PS, Smith S, Hunter E et al. Immunity to whole varicella-zoster virus antigen and glycoproteins I and p170: relation to the immunizing regimen of live attenuated varicella vaccine. J Infect Dis. 1988; 158:1245-52. [IDIS 311669] [PubMed 2848901]

70. Centers for Disease Control and Prevention. Recommendations of the Advisory Committee on Immunization Practices (ACIP): use of vaccines and immune globulins in persons with altered immunocompetence. MMWR Recomm Rep. 1993; 42(RR-4):1-18.

71. Centers for Disease Control and Prevention Advisory Committee on Immunization Practices, American Academy of Pediatrics, and American Academy of Family Physicians. Recommended immunization schedules for persons 0–18 years–United States, 2010; 59.

72. Anon. Establishment of Varivax pregnancy registry. MMWR Morb Mortal Wkly Rep. 1996; 45:239. [PubMed 8606684]

73. Grossman M. Varicella vaccine and health care workers. Pediatr Infect Dis J. 1996; 15:395-6. [PubMed 8724059]

74. Matsubara K, Nigami H, Harigaya H et al. Herpes zoster in a normal child after varicella vaccination. Acta Paediatricia Japonic. 1995; 37:648-50.

75. Clements DA, Armstrong CB, Ursano AM et al. Over five-year follow-up of Oka/Merck varicella vaccine recipients in 465 infants and adolescents. Pediatr Infect Dis J. 1995; 14:874-9. [IDIS 355045] [PubMed 8584315]

76. Watson BM, Laufer DS, Kuter BJ et al. Safety and immunogenicity of a combined live attenuated measles, mumps, rubella, and varicella vaccine (MMRIIV) in healthy children. J Infect Dis. 1996; 173:731-4. [IDIS 364240] [PubMed 8627041]

77. Krause PR, Klinman DM. Efficacy, immunogenicity, safety, and use of live attenuated chickenpox vaccine. J Pediatr. 1995; 127:518-25. [IDIS 355793] [PubMed 7562270]

78. Brunell PA, Taylor-Wiedeman J, Geiser CF et al. Risk of herpes zoster in children with leukemia: varicella vaccine compared with history of chickenpox. Pediatrics. 1986; 77:53-6. [IDIS 210737] [PubMed 3455669]

79. Diaz PS, Au D, Smith S et al. Lack of transmission of the live attenuated varicella vaccine virus to immunocompromised children after immunization of their siblings. Pediatrics. 1991; 87:166-70. [IDIS 277346] [PubMed 1846236]

80. Kuter BJ, Ngai A, Patterson CM et al. Safety, tolerability, and immunogenicity of two regimens of Oka/Merck varicella vaccine (Varivax) in healthy adolescents and adults. Vaccine. 1995; 13:967-72. [PubMed 8525689]

81. Oshiro AC, Begue RE, Steele RW. Varicella disease and transmission in pediatric house officers. Pediatr Infect Dis J. 1996; 15:461-2. [PubMed 8724072]

82. Gardner P, Eickhoff T, Poland GA et al. Adult immunizations. Ann Intern Med. 1996; 12:35-40.

83. Levin MJ, Murray M, Zerbe GO et al. Immune responses of elderly persons 4 years after receiving a live attenuated varicella vaccine. J Infect Dis. 1994; 170:522-6. [IDIS 335938] [PubMed 8077709]

84. Levin MJ, Murray M, Rotbart HA et al. Immune response of elderly individuals to a live attenuated varicella vaccine. J Infect Dis. 1992; 166:253-9. [IDIS 299305] [PubMed 1321859]

85. Ellis RW. Varicella vaccine. Vaccine. 1995; 13:1387-8. [PubMed 8578813]

86. Gershon AA. Varicella vaccine: its past, present and future. Pediatr Infect Dis J. 1995; 14:742-4. [IDIS 354052] [PubMed 8559621]

87. Anon. Varicella vaccine. Med Lett Drugs Ther. 1995; 37:55-7. [PubMed 7783692]

88. DiNicola AF. Varicella vaccine guidelines Pediatrics. 1995; 96:375. Letter.

89. American Academy of Pediatrics Committee on Infectious Diseases. Immunization of adolescents: recommendations of the Advisory Committee on Immunization Practices, the American Academy of Pediatrics, the American Academy of Family Physicians, and the American Medical Association. Pediatrics. 1997; 99:479-88. [IDIS 380570] [PubMed 9041309]

90. White CJ, Stinson D, Staehle B et al. Measles, mumps, rubella, and varicella combination vaccine: safety and immunogenicity alone and in combination with other vaccines given to children. Clin Infect Dis. 1997; 24:925-31. [IDIS 386051] [PubMed 9142794]

91. American Academy of Family Physicians. Summary of policy recommendations for periodic health examination November 1996. Kansas City, MO: American Academy of Family Physicians. August 1996. (AAFP Order No. 962, Reprint No. 510)

92. Anon. Varicella-related deaths among adults—United States, 1997. MMWR Morb Mortal Wkly Rep. 1997; 46:409-12. [PubMed 9162840]

93. Seidman DS, Stevenson DK, Arvin AM. Varicella vaccine in pregnancy: routine screening and vaccination should be considered. BMJ. 1996; 313:701-2. [IDIS 372596] [PubMed 8819427]

94. Reviewers’ comments (personal observations).

95. Kohl S. Varicella vaccine and susceptible pregnant mothers. Pediatrics. 1996; 97:441. [IDIS 361348] [PubMed 8604291]

96. Plotkin SA. Varicella vaccine. Pediatrics. 1996; 97:251-3. [IDIS 360406] [PubMed 8584387]

97. Stein ND. Recommendations for varicella vaccine. Pediatrics. 1996; 97:545.

99. Walter EB, Simmons SS, Bland CL et al. Modified varicella-like syndrome in children previously vaccinated with live attenuated measles, mumps, rubella and varicella vaccine. Pediatr Infect Dis J. 1997; 16:626-7. [IDIS 388812] [PubMed 9194116]

100. American Academy of Pediatrics. 2009 Red Book: Report of the Committee on Infectious Diseases. 28th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2009.

101. Ngai AL, Staehle BO, Kuter BJ et al. Safety and immunogenicity of one vs two injections of Oka/Merck varicella vaccine in healthy children. Pediatr Infect Dis J. 1996; 15:49-54. [IDIS 359423] [PubMed 8684876]

102. American Academy of Pediatrics Committee on Infectious Diseases, Committee on Fetus and Newborn. Respiratory syncytial virus immune globulin intravenous: indications for use. Pediatrics. 1997; 99:645-50. [IDIS 383952] [PubMed 9093323]

103. Kan BD, Ault MJ, Greenspoon JS. Varicella vaccine and susceptible pregnant mothers. Pediatrics. 1996; 97:441. [IDIS 361348] [PubMed 8604291]

104. Giacchino R, Marcellini M, Timitilli A et al. Varicella vaccine in children requiring renal or hepatic transplantation. Transplantation. 1995; 60:1055-6. [IDIS 359129] [PubMed 7491684]

105. Gerecitano J, Friedman-Kien A, Chazen GD. Allergic reaction to varicella vaccine. Ann Intern Med. 1997; 126:833-4. [IDIS 385623] [PubMed 9148672]

106. Kumagai T, Yamanaka T, Wataya Y et al. Gelatin-specific humoral and cellular immune responses in children with immediate- and nonimmediate-type reactions to live measles, mumps, rubella, and varicella vaccines. J Allergy Clin Immunol. 1997; 100:130-4. [IDIS 391338] [PubMed 9257797]

107. Reuman PD, Sawyer MH, Kuter BJ et al. Safety and immunogenicity of concurrent administration of measles-mumps-rubella-varicella vaccine and PedvaxHIB vaccines in healthy children twelve to eighteen months old. Pediatr Infect Dis J. 1997; 16:662-7. [IDIS 390072] [PubMed 9239770]

108. Salzman B, Sharrar RG, Steinberg S et al. Transmission of varicella-vaccine virus from a healthy 12-month-old child to his pregnant mother. J Pediatr. 1997; 131:151-4. [IDIS 391109] [PubMed 9255208]

109. Vaccine Adverse Event Reporting System (VAERS). Table of reportable events following vaccination. Rockville, MD; 1997 March 24.

110. Public Health Service. National Childhood Vaccine Injury Program: revisions and additions to the vaccine injury table: II. Final rule. Fed Regist. 1997; 62:7685-90.

112. Centers for Disease Control and Prevention. Health information for international travel, 2010. Atlanta, GA: US Department of Health and Human Services. Updates available from CDC website.

113. Centers for Disease Control and Prevention. Immunization of health-care workers: recommendations of the Advisory Committee on Immunization Practices (ACIP) and the Hospital Infection Control Practices Advisory Committee (HICPAC). MMWR Recomm Rep. 1997; 46(RR-18):1-42.

114. Gershon AA, Gardner P, Peter G et al. Guidelines from the Infectious Diseases Society of America: quality standards for immunization. Clin Infect Dis. 1997; 25:782-6. [IDIS 395784] [PubMed 9356789]

115. Izurieta HS, Strebel PM, Blake PA. Postlicensure effectiveness of varicella vaccine during an outbreak in a child care center. JAMA. 1997; 278:1495-9. [IDIS 394447] [PubMed 9363968]

116. Salzman MB, Garcia C. Postexposure varicella vaccination in siblings of children with active varicella. Pediatr Infect Dis J. 1998; 17:256-7. [IDIS 402992] [PubMed 9535260]

117. Anon. Varicella-related deaths among children—United States, 1997. MMWR Morb Mortal Wkly Rep. 1998; 47:365-8. [PubMed 9603627]

118. American Academy of Pediatrics Committee on Infectious Diseases. Varicella vaccine update. Pediatrics. 2000; 105:136-41. [IDIS 441643] [PubMed 10617719]

119. Centers for Disease Control and Prevention. Preventing pneumococcal disease among infants and young children: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2000; 49(RR-9):1-35.

120. American Academy of Pediatrics Committee on Infectious Diseases. Policy statement: recommendations for the prevention of pneumococcal infections, including the use of pneumococcal conjugate vaccine (Prevnar), pneumococcal polysaccharide vaccine, and antibiotic prophylaxis. Pediatrics. 2000; 106:362-6. [IDIS 451984] [PubMed 10920169]

121. Centers for Disease Control and Prevention. Simultaneous administration of varicella vaccine and other recommended childhood vaccines—United States, 1995-1999. MMWR Morb Mortal Wkly Rep. 2001; 50:1058-61. [IDIS 473729] [PubMed 11808928]

122. Galil K, Lee B, Strine T. Outbreak of varicella at a day-care center despite vaccination. N Engl J Med. 2002; 347:1909-15. [IDIS 490250] [PubMed 12477940]

123. Gershon AA. Varicella vaccine—are two doses better than one? N Engl J Med. 2002; 347: 1962-63. Editorial.

125. Merck & Co. ProQuad (measles, mumps, rubella and varicella virus vaccine live) prescribing information. Whitehouse Station, NJ; 2008 Feb.

126. Centers for Disease Control and Prevention. Provisional ACIP recommendations for postexposure prophylaxis of severe varicella during a varicella zoster immune globulin shortage. From CDC website. Accessed 2005 Dec 14.

127. Centers for Disease Control and Prevention. Prevention of varicella - provisional updated ACIP recommendations for varicella vaccine use. From CDC website. Accessed 2005 Dec 14.

128. Centers for Disease Control and Prevention. Licensure of a combined live attenuated measles, mumps, rubella, and varicella vaccine. MMWR Morb Mortal Wkly Rep. 2005; 54:1212-4.

129. Centers for Disease Control and Prevention. Recommended adult immunization schedule—United States, 2010. MMWR Morb Mortal Wkly Rep. 2010; 59

131. Centers for Disease Control and Prevention. Prevention of herpes zoster. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2008; 57(RR-5):1-30.

132. Centers for Disease Control and Prevention. CDC’s advisory committee recommends “shingles” vaccination. 2006 Oct 26. Press release. From CDC website.

133. Merck & Co. Zostavax (zoster vaccine live suspension for subcutaneous injection) prescribing information. Whitehouse Station, NJ; 2009 Jul.

134. FFF Enterprises. VariZIG IND protocol. From website.

135. Centers for Disease Control and Prevention. A new product (variZIG™) for postexposure prophylaxis of varicella available under an investigational new drug application expanded access protocol. MMWR Morb Mortal Wkly Rep. 2006; 55:209-10. [PubMed 16511443]

136. Centers for Disease Control and Prevention. Update: recommendations from the Advisory Committee on Immunization Practices (ACIP) regarding administration of combination MMRV vaccine. MMWR Morb Mortal Wkly Rep. 2008; 57:258-60. [PubMed 18340332]

137. Committee on Infectious Diseases, American Academy of Pediatrics. Prevention of varicella: recommendations for the use of varicella vaccine in children, including a recommendation for a routine 2-dose varicella immunization schedule. Pediatrics. 2007; 120:221-31. [PubMed 17606582]

138. Centers for Disease Control and Prevention. Epidemiology and prevention of vaccine-preventable diseases. 11th ed. Washington DC: Public Health Foundation; 2009.

139. Centers for Disease Control and Prevention. Vaccine management: recommendations for storage and handling of selected biologicals. 2007 Nov. From CDC website. Accessed 2007 Dec 12.

140. Centers for Disease Control and Prevention. Chickenpox vaccine information statement. 2008 Mar 13. From CDC website.

141. Department of Health and Human Services, Food and Drug Administration, Center for Biologics Evaluation and Research (CBER). Guidance for industry. Revised preventive measures to reduce the possible risk of transmission of Creutzfeldt-Jacob disease (CJD) and variant Creutzfeldt-Jacob disease (vCJD) by blood and blood products. January 2002. From FDA website. Accessed 2008 Feb 20.

142. MedImmune LLC. FluMist (influenza virus vaccine live, intranasal) prescribing information. Gaithersburg, MD; 2009 Jun.

143. Kaplan JE, Benson C, Holmes KH et al. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR Recomm Rep. 2009; 58:1-207; quiz CE1-4.

144. Mofenson LM, Brady MT, Danner SP et al. Guidelines for the Prevention and Treatment of Opportunistic Infections among HIV-exposed and HIV-infected children: recommendations from CDC, the National Institutes of Health, the HIV Medicine Association of the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the American Academy of Pediatrics. MMWR Recomm Rep. 2009; 58:1-166. [PubMed 19730409]

145. Centers for Disease Control and Prevention. ACIP provisional recommendations for use of measles, mumps, rubella, and varicella (MMRV) vaccine. October 20, 2009. From CDC website. Accessed 2009 Oct 29.

Hide
(web2)