Updated adverse events (Syncope)

Removal of adverse events.

Deletion of presentation with attached needle.

Previous upload not displaying published PIL, had to upload again due to technical error on this website

section 1: product name amended to “VARIVAX powder and solvent for suspension for injection in a pre-filled syringe”

section 4.4: added headings on “Traceability”, “Sodium” and “Potassium”

Section 6.6: updated directions for vaccine preparation

Section 4.8: Addition of text: “Complications of varicella from vaccine strain, including herpes zoster and disseminated disease such as aseptic meningitis and encephalitis, have been reported in immunocompromised or immunocompetent individuals.”

SPC change details: New Marketing Authorisation Holder and MA Number following PA transfer to Merck Sharp & Dohme Ireland (Human Health) Limited

Reporting of suspected adverse reactions paragraph has been updated following comment from the IMB after publishing the SPC following the approval of the variation.

section 2: editorial change
section 4.5: editorial change
section 4.8: addition of the text "Necrotizing retinitis has been reported post-marketing in immunocompromised individuals."

and the description of reporting process for suspected adverse reactions in Ireland

section 6.2: replacement of "should" by "must".

The main changes to the SPC are as follows:

Section 4.3 Contraindications

The updated text (see below) clarifies the fact that that the contraindication applies to individuals with severe humoral or cellular immunodeficiency:

Severe humoral or cellular (primary or acquired) immunodeficiency, e.g. severe combined immunodeficiency, agammaglobulinemia and AIDS or symptomatic HIV infection or an age-specific CD4+ T-lymphocyte percentage in children below 12 months: CD4+ <25%; children between 12-35 months: CD4+ < 20%; children between 36-59 months: CD4+ < 15% (see section 4.4).

The contraindication below has been expanded to include the fact that pregnancy should be avoided for 1 month following vaccination:

Pregnancy. Furthermore, pregnancy should be avoided for 1 month following vaccination (see section 4.6).

Section 4.4 Special warnings and precautions for use

Information on the use of the product in children with HIV infection has now been moved to section 4.3 Contraindications (see above).

Section 4.4 has also been updated (see updated text below) to include patients with selected immune deficiencies and clarification added about immunocompromised patients receiving the vaccine .

Vaccination may be considered in patients with selected immune deficiencies where the benefits outweigh the risks (e.g., asymptomatic HIV subjects, IgG subclass deficiencies, congenital neutropenia, chronic granulomatous disease, and complement deficiency diseases).

Immunocompromised patients who have no contraindication for this vaccination (see section 4.3) may not respond as well as immunocompetent subjects; therefore, some of these patients may acquire varicella in case of contact, despite appropriate vaccine administration. These patients should be monitored carefully for signs of varicella.

The sub-heading, ‘Pregnancy and breastfeeding’ has been deleted and the information associated with the heading has now been moved to sections 4.3 Contraindications and 4.6 Fertility, pregnancy and lactation.

Section 4.6 Fertility, pregnancy and lactation

This section has been updated (see updated text below) to clarify that pregnant women should not be vaccinated with the product.

Pregnancy

Pregnant women should not be vaccinated with VARIVAX.

Studies have not been conducted with VARIVAX in pregnant women.

However, fetal damage has not been documented when varicella vaccines have been given to pregnant women.It is not known whether VARIVAX can cause foetal harm when administered to a pregnant woman or can affect reproduction capacity.

Pregnancy should be avoided for 1 month following vaccination. Women who intend to become pregnant should be advised to delay.

Date of revision in Section 10 has been changed to June 2013.

The long-term effect of varicella vaccine (live) (Oka/Merck strain) on the incidence of herpes zoster, particularly in those vaccinees exposed to wild-type varicella, is unknown at present.

Active surveillance data in children vaccinated with varicella vaccine (live) (Oka/Merck strain) and followed for 14 years after vaccination showed no increase in the frequency of herpes zoster compared to children with prior wild-type varicella during the pre-vaccine era. However, the long-term effect of varicella vaccine (live) (Oka/Merck strain) on the incidence of herpes zoster is unknown at present (see section 5.1).

Effectiveness of varicella vaccine (live) (Oka/Merck strain)

Observational studies of long-term effectiveness of VARIVAX

Surveillance data from two U.S. observational effectiveness studies confirmed that widespread varicella vaccination reduces the risk of varicella by approximately 90%. Furthermore, the reduced risk of varicella was maintained at the population level over at least 15 years both in vaccinated and unvaccinated individuals. The data also suggest that varicella vaccination may reduce the risk of herpes zoster in vaccinated individuals.

In the first study, a long-term prospective cohort study, approximately 7,600 children vaccinated in 1995 with varicella vaccine in their second year of life were actively followed for 14 years in order to estimate the occurrence of varicella and herpes zoster. By the end of the study in 2009, 38% of the study children were known to have received a second dose of varicella vaccine. Of note, in 2006, a second dose of varicella vaccine was recommended in the U.S. Over the entire follow-up, the incidence of varicella was approximately 10-fold lower among vaccinees than among children of the same age in the pre-vaccine era (estimated vaccine effectiveness over the study period was between 73% and 90%). Regarding herpes zoster, there were fewer herpes zoster cases among varicella vaccinees during the follow-up period than expected from rates in children of the same age with prior wild-type varicella during the pre-vaccine era (relative risk = 0.61, 95% CI 0.43 - 0.89). Breakthrough varicella and zoster cases were usually mild.

In a second long‑term surveillance study, five cross‑sectional surveys on varicella incidence, each from a random sample of approximately 8,000 children and adolescents 5 to 19 years of age, were conducted over 15 years, from 1995 (pre‑vaccine) through 2009. Results showed a gradual decline of varicella rates by an overall 90% to 95% (approximately 10‑ to 20‑fold) from 1995 to 2009 in all age groups, both in vaccinated and unvaccinated children and adolescents. In addition, a decrease by approximately 90% (approximately 10‑fold) in varicella hospitalization rates was observed in all age groups.

4.1 Therapeutic indications

addition of a new paragraph:

VARIVAX can be administered to infants from 9 months of age under special circumstances, such as to conform with national vaccination schedules or in outbreak situations (see sections 4.2, 4.5, and 5.1).

4.2 Posology and method of administration

addition of a new paragraph: in Posology

The use of VARIVAX should be based on official recommendations.

Individuals less than 9 months of age

VARIVAX should not be administered to individuals less than 9 months of age.

Individuals from 9 months of age

Individuals should receive two doses of VARIVAX to ensure optimal protection against varicella (see section 5.1).

Individuals from 9 to 12 months of age

In settings in which vaccination is initiated between 9 and 12 months of age, a second dose is needed and should be given after a minimum interval of 3 months (see section 5.1).

Individuals from 12 months to 12 years of age

 For individuals from 12 months to 12 years of age, at least one month must elapse between the first and second dose (see section 5.1).

Addition of a new parapgraph and table in section 5.1 Pharmacodynamic properties

As a reminder, the purpose of this variation is to update the Summary of Product Characteristics

(SmPC) of Varivax to refiect changes that have been made to the Company Core Datasheet (CCDS)

with respect to section 4.4 “Speciai warnings and precautions for use” and section 4.8 “Undesirabie

effects”, each under the subsection of “Transmission”. Additionaiiy, in section 4.8 “Undesirable

effects”, under the subsection of “Post-Marketing Surveiliance”, aplastic anemia has been added to

Change to section 2

Description of product updated

Change to section 3

Description of product updated

Change to section 4.1

Rewording of section,

Change to section 4.2

Introduction of 2 dose schedule, update to method of administration

Change to section 4.4

Reformatting of section.

Change to section 4.7

Reformatting of section

Change to section 4.8

Reformatting of section, addition of side effect observed following 2 dose regimen.

Change to section 5.1

Addition of data supporting 2 dose regimen. 

Change to section 6.2

Additional statement concerning reconstitution with other medicinal products.

Change to section 6.4

Reformatting of section

Change to section 6.6

Section 4.2

Addition of intramuscular route of administration.  

Section 4.8

Update of information, following the addition if intramuscular route of administration - safety profile is comparable between intramuscular and subcutaneous routes of administration.

Section 5.1

Addition of information - Immunogenicity profile similar for both intramuscular and subcutaneous routes of administration.

Section 7 - updated the address of the Marketing Authorisation Holder.

Section 10 - changed date of revision to March 2007