Varivax Adverse Reactions

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 as follows.
In clinical trials, VARIVAX was administered subcutaneously 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.
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 2: See Table 2.

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In addition, adverse events occurring at a rate of ≥1% are listed in decreasing order of frequency: upper respiratory illness, cough, irritability, fatigue, disturbed sleep, diarrhea, loss of appetite, vomiting, otitis, headache, malaise, abdominal pain, other rash, nausea, chills, lymphadenopathy, myalgia, lower respiratory illness, allergic reactions (including allergic rash, hives), stiff neck, arthralgia, 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.
Clinical safety of refrigerator-stable VARIVAX (n=635) was compared with that of the licensed frozen formulation of VARIVAX (n=323) for 42 days postvaccination in U.S. children 12 to 23 months of age. The safety profiles were comparable for the two different formulations. Pain/tenderness/soreness (24.8 to 28.9%) and erythema (18.4 to 21.0%) were the most commonly reported local reactions. The most common systemic adverse events (reported by ≥10% of subjects in one or more treatment groups, irrespective of causal relationship to vaccination) were: fever ≥102.0°F, oral equivalent (27.0 to 29.2%), upper respiratory infection (26.9 to 29.7%), otitis media (12.0 to 14.1%), cough (11.0 to 15.1%), rhinorrhea (8.7 to 10.6%), and irritability (6.5 to 11.9%). Six subjects reported serious adverse events.
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 3. (See Table 3.)

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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, lymphadenopathy, chills, abdominal pain, loss of appetite, arthralgia, otitis, itching, vomiting, other rashes, lower respiratory illness, allergic reactions (including allergic rash, hives).
In a randomized open-label clinical trial (NCT00432523), conducted in France and Germany, 752 children 12 months through 18 months of age received M-M-R II concomitantly administered with VARIVAX at a separate site, by either the intramuscular (n=374) or subcutaneous (n=378) route. In the overall population, 55.3% were male and the median age was 13.2 months. Local and systemic solicited adverse reactions were recorded by parents or guardians using standardized diary cards. Local solicited reactions were recorded for 4 days after vaccination, and systemic solicited adverse reactions were recorded for 42 days after vaccination. In the event that a participant experienced a rash or a mumps-like illness, parents and/or guardians were instructed to contact the investigator for an examination as soon as possible and no later than 72 hours following onset of symptoms. The nature of any rash was characterized by principal investigator either as measles-like, rubella-like, varicella-like or "other". Study investigators reviewed the diary card with the participant or participant's legal guardian 42 days after vaccination to ensure consistency with protocol definitions. Table 4 as follows presents the frequency of solicited adverse reactions based on the final assessment by the study investigators. (See Table 4.)

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Unsolicited adverse events that occurred within 42 days following vaccination were recorded using diary cards supplemented by medical review. Data on unsolicited adverse events were transcribed into the study database during an on-site visit at day 42. The rates and types of reported adverse events (AEs) across groups were similar and included common clinical events that are often reported in the evaluated populations. Serious adverse events occurred at rates of 0.3% and 1% in the intramuscular and subcutaneous groups, respectively. One moderate intensity case of otitis media occurred in a participant in the subcutaneous group was considered related to the vaccination.
Herpes Zoster: Overall, 9454 healthy children (12 months to 12 years of age) and 1648 adolescents and adults (13 years of age and older) have been vaccinated with VARIVAX in clinical trials. Eight cases of herpes zoster have been reported in children during 42,556 person-years of follow-up in clinical trials, resulting in a calculated incidence of at least 18.8 cases per 100,000 person-years. The completeness of this reporting has not been determined. One case of herpes zoster has been reported in the adolescent and adult age group during 5410 person-years of follow-up in clinical trials, resulting in a calculated incidence of 18.5 cases per 100,000 person-years. All 9 cases were mild and without sequelae. Two cultures (one child and one adult) obtained from vesicles were positive for wild-type VZV as confirmed by restriction endonuclease analysis. The long-term effect of VARIVAX on the incidence of herpes zoster, particularly in those vaccinees exposed to wild-type varicella, is unknown at present.
In children, the reported rate of herpes zoster in vaccine recipients appears not to exceed that previously determined in a population-based study of healthy children who had experienced wild-type varicella. The incidence of herpes zoster in adults who have had wild-type varicella infection is higher than that in children.
Post-Marketing Experience: The following adverse events have been identified during post approval use of VARIVAX. Because the events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to vaccine exposure.
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; syncope.
Cases of encephalitis or meningitis caused by vaccine strain varicella virus have been reported in immunocompromised and immunocompetent individuals previously vaccinated with VARIVAX months to years after vaccination. Reported cases were commonly associated with preceding or concurrent herpes zoster rash.
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; wild-type or vaccine strain herpes zoster.
Herpes Zoster: The vaccine virus (Oka/Merck strain) contained in VARIVAX may establish latency of varicella zoster virus in immunocompetent individuals, with the potential for later development of herpes zoster.