VARIVAX: Package Insert and Label Information

VARIVAX- varicella-zoster virus strain oka/merck live antigen injection, powder, lyophilized, for suspension
Merck Sharp & Dohme Corp.

1 INDICATIONS AND USAGE

VARIVAX® is a vaccine indicated for active immunization for the prevention of varicella in individuals 12 months of age and older.

2 DOSAGE AND ADMINISTRATION

Subcutaneous administration only

2.1 Recommended Dose and Schedule

VARIVAX is administered as an approximately 0.5-mL dose by subcutaneous injection into the outer aspect of the upper arm (deltoid region) or the anterolateral thigh.

Do not administer this product intravascularly or intramuscularly.

Children (12 months to 12 years of age)

If a second dose is administered, there should be a minimum interval of 3 months between doses [see Clinical Studies (14.1)].

Adolescents (≥13 years of age) and Adults

Two doses of vaccine, to be administered with a minimum interval of 4 weeks between doses [see Clinical Studies (14.1)].

2.2 Reconstitution Instructions

When reconstituting the vaccine, use only the sterile diluent supplied with VARIVAX. The sterile diluent does not contain preservatives or other anti-viral substances which might inactivate the vaccine virus.

Use a sterile syringe free of preservatives, antiseptics, and detergents for each reconstitution and injection of VARIVAX because these substances may inactivate the vaccine virus.

To reconstitute the vaccine, first withdraw the total volume of provided sterile diluent into a syringe. Inject all of the withdrawn diluent into the vial of lyophilized vaccine and gently agitate to mix thoroughly. Withdraw the entire contents into the syringe, inject the total volume (approximately 0.5 mL) of reconstituted vaccine subcutaneously, and discard vial. VARIVAX, when reconstituted, is a clear, colorless to pale yellow liquid.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use the product if particulates are present or if it appears discolored.

To minimize loss of potency, administer VARIVAX immediately after reconstitution. Discard if reconstituted vaccine is not used within 30 minutes.

Do not freeze reconstituted vaccine.

Do not combine VARIVAX with any other vaccine through reconstitution or mixing.

3 DOSAGE FORMS AND STRENGTHS

VARIVAX is a suspension for injection supplied as a single-dose vial of lyophilized vaccine to be reconstituted using the accompanying sterile diluent [see Dosage and Administration (2.2) and How Supplied/Storage and Handling (16)]. A single dose after reconstitution is approximately 0.5 mL.

4 CONTRAINDICATIONS

4.1 Severe Allergic Reaction

Do not administer VARIVAX to individuals with a history of anaphylactic or severe allergic reaction to any component of the vaccine (including neomycin and gelatin) or to a previous dose of a varicella-containing vaccine.

4.2 Immunosuppression

Do not administer VARIVAX to immunosuppressed or immunodeficient individuals, including those with a history of primary or acquired immunodeficiency states, leukemia, lymphoma or other malignant neoplasms affecting the bone marrow or lymphatic system, AIDS, or other clinical manifestations of infection with human immunodeficiency virus (HIV).

Do not administer VARIVAX to individuals receiving immunosuppressive therapy, including individuals receiving immunosuppressive doses of corticosteroids.

VARIVAX is a live, attenuated varicella-zoster vaccine (VZV) and may cause an extensive vaccine-associated rash or disseminated disease in individuals who are immunosuppressed or immunodeficient.

4.3 Concurrent Illness

Do not administer VARIVAX to individuals with any febrile illness. Do not administer VARIVAX to individuals with active, untreated tuberculosis.

4.4 Pregnancy

Do not administer VARIVAX to individuals who are pregnant because the effects of the vaccine on fetal development are unknown. Wild-type varicella (natural infection) is known to sometimes cause fetal harm. If vaccination of postpubertal females is undertaken, pregnancy should be avoided for three months following vaccination [see Use in Specific Populations (8.1) and Patient Counseling Information (17)].

5 WARNINGS AND PRECAUTIONS

5.1 Management of Allergic Reactions

Adequate treatment provisions, including epinephrine injection (1:1000), should be available for immediate use should anaphylaxis occur.

5.2 Family History of Immunodeficiency

Vaccination should be deferred in patients with a family history of congenital or hereditary immunodeficiency until the patient’s immune status has been evaluated and the patient has been found to be immunocompetent.

5.3 Use in HIV-Infected Individuals

The Advisory Committee for Immunization Practices (ACIP) has recommendations on the use of varicella vaccine in HIV-infected individuals.

5.4 Risk of Vaccine Virus Transmission

Post-marketing experience suggests that transmission of vaccine virus may occur rarely between healthy vaccinees who develop a varicella-like rash and healthy susceptible contacts. Transmission of vaccine virus from a mother who did not develop a varicella-like rash to her newborn infant has been reported.

Due to the concern for transmission of vaccine virus, vaccine recipients should attempt to avoid whenever possible close association with susceptible high-risk individuals for up to six weeks following vaccination with VARIVAX. Susceptible high-risk individuals include:

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

5.5 Immune Globulins and Transfusions

Immunoglobulins should not be given concomitantly with VARIVAX. Vaccination should be deferred for at least 5 months following blood or plasma transfusions, or administration of immune globulin(s) {1}.

Following administration of VARIVAX, immune globulin(s) should not be given for 2 months thereafter unless its use outweighs the benefits of vaccination {1}. [See Drug Interactions (7.2).]

5.6 Salicylate Therapy

Avoid use of salicylates (aspirin) or salicylate-containing products in children and adolescents 12 months through 17 years of age for six weeks following vaccination with VARIVAX because of the association of Reye syndrome with aspirin therapy and wild-type varicella infection. [See Drug Interactions (7.1).]

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a vaccine cannot be directly compared to rates in the clinical trials of another vaccine and may not reflect the rates observed in clinical practice. Vaccine-related adverse reactions reported during clinical trials were assessed by the study investigators to be possibly, probably, or definitely vaccine-related and are summarized below.

In clinical trials {2-9}, VARIVAX was administered to over 11,000 healthy children, adolescents, and adults.

In a double- blind, placebo- controlled study among 914 healthy children and adolescents who were serologically confirmed to be susceptible to varicella, the only adverse reactions that occurred at a significantly (p<0.05) greater rate in vaccine recipients than in placebo recipients were pain and redness at the injection site {2}.

Children 1 to 12 Years of Age

One-Dose Regimen in Children

In clinical trials involving healthy children monitored for up to 42 days after a single dose of VARIVAX, the frequency of fever, injection- site complaints, or rashes were reported as shown in Table 1:

Table 1: Fever, Local Reactions, and Rashes (%) in Children 1 to 12 Years of Age 0 to 42 Days After Receipt of a Single Dose of VARIVAX
Reaction N % Experiencing Reaction Peak Occurrence During Postvaccination Days
Fever ≥102.0°F (38.9°C) Oral 8827 14.7% 0 to 42
Injection-site complaints 8916 19.3% 0 to 2
(pain/soreness, swelling and/or erythema, rash, pruritus, hematoma, induration, stiffness)
Varicella-like rash (injection site) 8916 3.4% 8 to 19
Median number of lesions 2
Varicella-like rash (generalized) 8916 3.8% 5 to 26
Median number of lesions 5

In addition, adverse events occurring at a rate of ≥1% are listed in decreasing order of frequency: upper respiratory illness, cough, irritability/nervousness, fatigue, disturbed sleep, diarrhea, loss of appetite, vomiting, otitis, diaper rash/contact rash, headache, teething, malaise, abdominal pain, other rash, nausea, eye complaints, chills, lymphadenopathy, myalgia, lower respiratory illness, allergic reactions (including allergic rash, hives), stiff neck, heat rash/prickly heat, arthralgia, eczema/dry skin/dermatitis, constipation, itching.

Pneumonitis has been reported rarely (<1%) in children vaccinated with VARIVAX.

Febrile seizures have occurred at a rate of <0.1% in children vaccinated with VARIVAX.

Two-Dose Regimen in Children

Nine hundred eighty-one (981) subjects in a clinical trial received 2 doses of VARIVAX 3 months apart and were actively followed for 42 days after each dose. The 2-dose regimen of varicella vaccine had a safety profile comparable to that of the 1-dose regimen. The overall incidence of injection-site clinical complaints (primarily erythema and swelling) observed in the first 4 days following vaccination was 25.4% Postdose 2 and 21.7% Postdose 1, whereas the overall incidence of systemic clinical complaints in the 42-day follow-up period was lower Postdose 2 (66.3%) than Postdose 1 (85.8%).

Adolescents (13 Years of Age and Older) and Adults

In clinical trials involving healthy adolescents and adults, the majority of whom received two doses of VARIVAX and were monitored for up to 42 days after any dose, the frequencies of fever, injection-site complaints, or rashes are shown in Table 2.

Table 2: Fever, Local Reactions, and Rashes (%) in Adolescents and Adults 0 to 42 Days After Receipt of VARIVAX
Reaction N % PostDose 1 Peak Occurrence inPostvaccination Days N % PostDose 2 Peak Occurrence inPostvaccination Days
Fever ≥100.0°F (37.8°C) Oral 1584 10.2% 14 to 27 956 9.5% 0 to 42
Injection-site complaints 1606 24.4% 0 to 2 955 32.5% 0 to 2
(soreness, erythema, swelling, rash, pruritus, pyrexia, hematoma, induration, numbness)
Varicella-like rash (injection site) 1606 3% 6 to 20 955 1% 0 to 6
Median number of lesions 2 2
Varicella-like rash (generalized) 1606 5.5% 7 to 21 955 0.9% 0 to 23
Median number of lesions 5 5.5

In addition, adverse events reported at a rate of ≥1% are listed in decreasing order of frequency: upper respiratory illness, headache, fatigue, cough, myalgia, disturbed sleep, nausea, malaise, diarrhea, stiff neck, irritability/nervousness, lymphadenopathy, chills, eye complaints, abdominal pain, loss of appetite, arthralgia, otitis, itching, vomiting, other rashes, constipation, lower respiratory illness, allergic reactions (including allergic rash, hives), contact rash, cold/canker sore.

6.2 Post-Marketing Experience

Broad use of VARIVAX could reveal adverse events not observed in clinical trials.

The following additional adverse events, regardless of causality, have been reported during post-marketing use of VARIVAX:

Body as a Whole

Anaphylaxis (including anaphylactic shock) and related phenomena such as angioneurotic edema, facial edema, and peripheral edema.

Eye Disorders

Necrotizing retinitis (in immunocompromised individuals).

Hemic and Lymphatic System

Aplastic anemia; thrombocytopenia (including idiopathic thrombocytopenic purpura (ITP)).

Infections and Infestations

Varicella (vaccine strain).

Nervous/Psychiatric

Encephalitis; cerebrovascular accident; transverse myelitis; Guillain-Barré syndrome; Bell’s palsy; ataxia; non-febrile seizures; aseptic meningitis; meningitis; dizziness; paresthesia.

Cases of encephalitis or meningitis caused by vaccine strain varicella virus have been reported in immunocompetent individuals previously vaccinated with VARIVAX months to years after vaccination. Reported cases were commonly associated with preceding or concurrent herpes zoster rash. [See Clinical Pharmacology (12.2)].

Respiratory

Pharyngitis; pneumonia/pneumonitis.

Skin

Stevens-Johnson syndrome; erythema multiforme; Henoch-Schönlein purpura; secondary bacterial infections of skin and soft tissue, including impetigo and cellulitis; herpes zoster.

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