Varicella Virus Vaccine Live (Monograph)

Brand name: Varivax
Drug class: Vaccines
ATC class: J07BK01
VA class: IM100

Varicella Virus Vaccine Live is also contained as an ingredient in the following combinations:
Measles, Mumps, Rubella and Varicella Virus Vaccine Live

Medically reviewed by Drugs.com on Apr 21, 2023. Written by ASHP.

Introduction

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

Uses for Varicella Virus Vaccine Live

Prevention of Varicella (Chickenpox) Infection

Prevention of varicella (chickenpox) in adults, adolescents, and children ≥12 months of age.

Varicella is caused by primary infection with varicella zoster virus (VZV). 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. 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). In the past, there were an average of 4 million cases of varicella and 100–150 varicella-associated deaths each year in the US. 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. The number of hospitalizations and deaths from varicella decreased >90% in the US since 1996.

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. (See Contraindications under Cautions.)

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. (See Contraindications under Cautions.)

For internationally adopted children whose immune status is uncertain, vaccinations can be repeated or serologic tests performed to confirm immunity. 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. (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.

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. ACIP, AAP, and AAFP state that use of a combination vaccine generally is preferred over separate injections of the equivalent component vaccines. However, although use of MMRV (ProQuad) reduces the number of required injections when both vaccines are indicated during a single health-care visit, 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. (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. Individuals without such evidence should be considered susceptible to varicella.

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. 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. This protects the worker following varicella exposure in the workplace and also may help reduce nosocomial transmission of VZV.

Travelers should be vaccinated against varicella. Varicella occurs worldwide. 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.

Certain immunocompromised individuals at risk of severe complications from varicella may benefit from vaccination against the disease. However, varicella vaccine generally is contraindicated in adults, adolescents, and children who are immunocompromised^{† [off-label]}. (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^{† [off-label]}, especially those who are asymptomatic or only mildly symptomatic. 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% and may be considered in HIV-infected adults, adolescents, and children >8 years of age with CD4⁺ T-cell counts ≥200/mm³. Other HIV-infected adults, adolescents, or children who are more severely immunocompromised should not receive varicella vaccine. (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)^{† [off-label]} in remission, this protocol has been terminated. 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. (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.

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

May prevent varicella or modify severity of the disease if given within 3 days, and possibly up to 5 days, after exposure.

If the exposure does not cause infection, postexposure vaccination should provide protection against subsequent exposure. 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.

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).

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

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. 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). If VZIG is not available for postexposure prophylaxis, immune globulin IV (IGIV) can be used.

Related/similar drugs

varicella virus vaccine, Varivax, ProQuad

Varicella Virus Vaccine Live Dosage and Administration

Administration

Sub-Q Administration

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

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

Do not administer monovalent or fixed-combination vaccine IM^{† [off-label]}. Inadvertent IM administration does not necessitate revaccination.

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

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

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

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

Do not administer concomitantly with VZIG. (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). (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. Separate injection sites by at least 1 inch (if anatomically feasible) to allow appropriate attribution of any local adverse effects that may occur. 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.

Reconstitution

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

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

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

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

Dosage

Pediatric Patients

Prevention of Varicella (Chickenpox)

Children 12 Months Through 12 Years of Age (Varivax)

Sub-Q

Each dose is 0.5 mL.

Primary immunization consists of 2 doses given at least 3 months apart.

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). 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. If second dose was inadvertently administered early (but at least 28 days after initial dose), it does not need to be repeated.

For catch-up vaccination in those not previously vaccinated, give 2 doses at least 3 months apart. 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.

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

Sub-Q

Each dose is 0.5 mL.

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.

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. (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.

Adolescents 13–16 Years of Age (Varivax)

Sub-Q

Each dose is 0.5 mL.

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

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.

HIV-infected Children† [off-label] 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. Give first dose as soon as possible after the first birthday.

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.

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.

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).

Adults

Prevention of Varicella (Chickenpox) Infection

Adults (Varivax)

Sub-Q

Each dose is 0.5 mL.

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

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

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.

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.

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).

Special Populations

Hepatic Impairment

No specific dosage recommendations.

Renal Impairment

No specific dosage recommendations.

Geriatric Patients

No specific dosage recommendations.

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. (See Gelatin Allergy under Cautions.)

• History of anaphylactic reaction to neomycin. (See Neomycin Allergy under Cautions.)

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

• Immunosuppressive therapy (e.g., corticosteroids, antineoplastic agents, radiation). (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. (See Individuals with Altered Immunocompetence under Cautions.)

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

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

• Pregnancy. (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.

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. 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.

Safety and efficacy not established in HIV-infected children, adolescents, or adults. 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. (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. Do not use MMRV (ProQuad) in HIV-infected individuals.

Safety and efficacy not established in children with leukemia^†. 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. 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.

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. Vaccination of household contacts decreases the likelihood that wild-type varicella will be introduced into the household. However, if vaccinee develops a varicelliform rash, they should avoid contact with immunocompromised household members. (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. (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. (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.

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. Serologic testing for antibody to MMR should be considered to determine whether additional doses should be given.

Risk of Transmissible Agents in Preparations Containing Albumin

MMRV (ProQuad) contains albumin human.

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).

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylaxis, rash, urticaria, hypersensitivity vasculitis, erythema multiforme, and Stevens-Johnson syndrome reported rarely.

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

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

Gelatin Allergy

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

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. Consider possibility of such reactions.

Although skin testing for gelatin sensitivity before administering a gelatin-containing vaccine can be considered, there are no specific protocols for this purpose. 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.

Neomycin Allergy

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

Neomycin allergy usually results in delayed-type (cell-mediated) hypersensitivity reactions manifested as contact dermatitis. 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.

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.

Allergy to Egg-related Antigens

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

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.

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. Use extreme caution and have adequate treatment readily available in case a reaction occurs.

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.

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. There is no evidence that individuals with allergies to chickens or feathers are at increased risk of allergic reactions to such vaccines.

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. 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.

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.

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

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.

Herpes zoster has been reported rarely in immunocompromised children and healthy children, adolescents, and adults who received primary immunization with varicella vaccine. Most cases occurred 3–5 years after vaccination and were mild without sequelae.

Herpes zoster in vaccinated individuals may be caused by vaccine virus or by wild-type virus. No evidence to date that latent vaccine virus infections are any more likely to reactivate than latent infections caused by wild-type virus.

Waning cell-mediated immunity to VZV may predispose to reactivation of the virus. 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. 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.

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.

Transmission of Vaccine Virus

Varivax and MMRV (ProQuad) contain live, attenuated virus. Transmission of vaccine virus may occur rarely between vaccinees and susceptible contacts.

Vaccine virus has been isolated from vesicular fluid obtained from vaccinated individuals who developed a varicelliform rash following primary immunization with varicella vaccine.

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. Transmission of vaccine virus from vaccinees without a varicella-like rash has been reported, but not confirmed.

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

Vaccine recipients should avoid close contact with susceptible, high-risk individuals for up to 6 weeks following vaccination, whenever possible. 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. 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.

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

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.

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. (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. 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]). 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⁾.

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; 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.

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. The ACIP states that a personal or family (i.e., sibling, parent) history of seizures is a precaution for use of MMRV (ProQuad). 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. 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.

Data not available regarding safety and efficacy of MMRV (ProQuad) in HIV-infected individuals; do not use the fixed-combination vaccine in HIV-infected individuals. 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).

Limitations of Vaccine Effectiveness

Varivax: May not protect all individuals from varicella.

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

Varivax: Not known whether administration of the vaccine immediately after exposure to natural varicella virus will prevent illness. (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.

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.

Although immunity wanes over time, protection against varicella may persist for at least 5–10 years after a single vaccine dose.

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

Pre- and Postvaccination Serologic Testing

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

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. 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. 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; 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.

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.

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 and because commercially available assays lack sensitivity to detect vaccine-induced immunity and may give false-negative results.

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

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. 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.

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.

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.

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.

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.

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

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).

Tuberculosis

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

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. However, tuberculin skin testing is not a prerequisite for vaccine administration.

Improper Storage and Handling

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

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

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

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

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

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

Specific Populations

Pregnancy

Category C.

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

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. 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. 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.

Pregnancy registry at 800-986-8999. Clinicians or vaccinees should report any exposure to varicella vaccine that occurs during pregnancy or any time during the 3 months prior to pregnancy.

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. Vaccination of susceptible household members will likely protect the susceptible pregnant woman from exposure to wild-type VZV.

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. (See Transmission of Vaccine Virus under Cautions.)

Lactation

Use with caution in nursing women.

Not known whether attenuated varicella virus contained in varicella vaccine is distributed into milk following sub-Q administration. 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.

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

Pediatric Use

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

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

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

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. Other reported clinical experience has not identified differences in responses between geriatric and younger individuals.

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

Common Adverse Effects

Varivax: Injection site reactions (pain, soreness, swelling, erythema), fever (≥38.3°C), generalized varicella-like maculopapular or papulovesicular rash.

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

Drug Interactions

Live Vaccines

Varicella vaccine is a live, attenuated virus vaccine. 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. 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. (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. (See Specific Drugs and Laboratory Tests under Interactions.)

Specific Drugs and Laboratory Tests

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. Must be shipped in insulated containers with dry ice and delivered within 2 days.

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.

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. A temperature recording device should be included in the transport container to ensure that the temperature is no warmer than 2–8°C.

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

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

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.

Do not freeze reconstituted Varivax or MMRV (ProQuad).

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

Actions

• Varicella vaccine available for use in the US is a lyophilized preparation of live, attenuated VZV of the Oka/Merck strain. 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.

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

• Varicella vaccine induces active immunity to VZV.

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

• Varicella is highly contagious; the secondary infection rate is 80–90% in healthy, susceptible individuals exposed through household contact. 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.

• Following exposure to the disease or virus, the incubation period in otherwise healthy individuals averages about 14–16 days (range: 9–21 days). In utero infections can occur; fetal infections occurring during the first and second trimesters may result in congenital varicella disease. 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.

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

• The vaccine virus differs slightly from wild-type VZV circulating in the US; immune responses elicited by the vaccine are not identical to those elicited by the wild-type virus.

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

• 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. In those ≥13 years of age, seroconversion rate is 75–94% after a single dose and 99% after a second dose.

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

• 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.

• 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.

• 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. (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 [Web]).

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

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

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

• 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).

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

• 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).

• 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. Clinicians or individuals can report any adverse reactions that occurs following vaccination to Vaccine Adverse Event Reporting System (VAERS) at 800-822-7967 or [Web].

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

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed. Advise women to avoid pregnancy for 1–3 months following a dose of Varivax and MMRV (ProQuad). Report any exposure to varicella vaccine that occurs during pregnancy to the pregnancy registry at 800-986-8999.

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

Preparations

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

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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Frequently asked questions

• Why did I get chickenpox even though I've been vaccinated?

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