IMVANEX Suspension for injection Ref.[28029] Active ingredients: Smallpox, live attenuated

Traceability

In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

As with all injectable vaccines, appropriate medical treatment and supervision should always be readily available in case of rare anaphylactic reactions following the administration of the vaccine.

Immunisation should be postponed in individuals suffering from an acute severe febrile illness or acute infection. The presence of a minor infection and/or low-grade fever should not result in the deferral of vaccination.

IMVANEX should not be administered by intravascular injection.

The protective efficacy of IMVANEX against smallpox has not been studied. See section 5.1.

A protective immune response may not be elicited in all vaccinees.

There are inadequate data to determine the appropriate timing of booster doses.

Prior vaccination with IMVANEX may modify the cutaneous response (‘take’) to subsequently administered replication-competent smallpox vaccine resulting in a reduced or absent take. See section 5.1.

Individuals with atopic dermatitis developed more local and general symptoms after vaccination (see section 4.8)

Data have been generated in HIV infected individuals with CD4 counts ≥100 cells/µl and ≤750 cells/µl. Lower immune response data have been observed in HIV infected individuals compared to healthy individuals (see section 5.1). There are no data on the immune response to IMVANEX in other immunosuppressed individuals.

Two doses of IMVANEX given at a 7-day interval showed lower immune responses and slightly more local reactogenicity than two doses given at a 28-day interval. Therefore, dose intervals of less than 4 weeks should be avoided.

Sodium content

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium-free’.

No interaction studies with other vaccines or medicinal products have been performed. Therefore, concomitant administration of IMVANEX with other vaccines should be avoided.

The concomitant administration of the vaccine with any immunoglobulin including Vaccinia Immune Globulin (VIG) has not been studied and should be avoided.

Pregnancy

There are limited data (less than 300 pregnancy outcomes) from the use of IMVANEX in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). As a precautionary measure the use of IMVANEX should be avoided during pregnancy unless it is considered that the possible benefit in terms of preventing smallpox would outweigh the potential risk.

Breast-feeding

It is not known whether IMVANEX is excreted in human milk. IMVANEX should be avoided during breastfeeding unless it is considered that the possible benefit in terms of preventing smallpox would outweigh the potential risk.

Fertility

Animal studies did not reveal any evidence of impaired female and male fertility.

Some of the undesirable effects mentioned in section 4.8 may affect the ability to drive or use machines (e.g. dizziness).

Summary of the safety profile

The safety of IMVANEX has been assessed in 20 clinical trials in which 5,261 Vaccinia-naïve individuals received two doses of no less than 5 × 10⁷ Inf.U four weeks apart while 534 Vaccinia- and IMVANEX-experienced individuals received a single booster dose.

The most common adverse reactions observed in clinical trials were injection site reactions and common systemic reactions typical for vaccines which were mild to moderate in intensity and resolved without intervention within seven days following vaccination.

Adverse reaction rates reported after either vaccination dose (1st, 2nd or booster) were similar.

Tabulated summary of adverse reactions

Adverse reactions from all clinical trials are listed according to the following frequency: Very common (≥1/10), Common (≥1/100 to <1/10), Uncommon (≥1/1,000 to <1/100), Rare (≥1/10,000 to <1/1,000).

Table 1. Adverse Reactions Reported in Completed Clinical Trials with IMVANEX (N=7,082 subjects):

Individuals with atopic dermatitis (AD)

In a non-placebo controlled clinical trial that compared the safety of IMVANEX in individuals with AD to healthy individuals, individuals with AD reported erythema (61.2%) and swelling (52.2%) at the injection site with a higher frequency than healthy individuals (49.3% and 40.8%, respectively). The following general symptoms were reported more frequently in individuals with AD compared to healthy individuals: headache (33.1% vs. 24.8%), myalgia (31.8% vs. 22.3%), chills (10.7% vs. 3.8%), nausea (11.9% vs. 6.8%), and fatigue (21.4% vs. 14.4%).

7% of the individuals with AD in clinical trials with IMVANEX experienced a flare-up or worsening of their skin condition during the course of the trial.

Rash

IMVANEX may trigger local rashes or more widespread eruptions. Events of rash after vaccination (related cases observed in 0.4% of subjects) with IMVANEX tend to occur within the first days after vaccination, are mild to moderate in intensity and usually resolve without sequelae.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

In the absence of compatibility studies, this vaccine must not be mixed with other medicinal products.