QDENGA Powder and solvent for solution for injection Ref.[50598] Active ingredients: Dengue vaccine

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.

General recommendations

Anaphylaxis

As with all injectable vaccines, appropriate medical treatment and supervision must always be readily available in the event of a rare anaphylactic reaction following administration of the vaccine.

Review of medical history

Vaccination should be preceded by a review of the individual’s medical history (especially with regard to previous vaccination and possible hypersensitivity reactions which occurred after vaccination).

Concurrent illness

Vaccination with Qdenga should be postponed in subjects suffering from an acute severe febrile illness. The presence of a minor infection, such as a cold, should not result in a deferral of vaccination.

Limitations of vaccine effectiveness

A protective immune response with Qdenga may not be elicited in all vaccinees against all serotypes of dengue virus and may decline over time (see section 5.1). It is currently unknown whether a lack of protection could result in an increased severity of dengue. It is recommended to continue personal protection measures against mosquito bites after vaccination. Individuals should seek medical care if they develop dengue symptoms or dengue warning signs.

There are no data on the use of Qdenga in subjects above 60 years of age and limited data in patients with chronic medical conditions.

Anxiety-related reactions

Anxiety-related reactions, including vasovagal reactions (syncope), hyperventilation or stress‐related reactions may occur in association with vaccination as a psychogenic response to the needle injection. It is important that precautions are in place to avoid injury from fainting.

Women of childbearing potential

As with other live attenuated vaccines, women of childbearing potential should avoid pregnancy for at least one month following vaccination (see sections 4.6 and 4.3).

Other

Qdenga must not be administered by intravascular, intradermal or intramuscular injection.

Excipients

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

Qdenga contains less than 1 mmol potassium (39 mg) per dose, that is to say essentially ‘potassiumfree’.

For patients receiving treatment with immunoglobulins or blood products containing immunoglobulins, such as blood or plasma, it is recommended to wait for at least 6 weeks, and preferably for 3 months, following the end of treatment before administering Qdenga, in order to avoid neutralisation of the attenuated viruses contained in the vaccine.

Qdenga should not be administered to subjects receiving immunosuppressive therapies such as chemotherapy or high doses of systemic corticosteroids within 4 weeks prior to vaccination (see section 4.3).

Use with other vaccines

If Qdenga is to be given at the same time as another injectable vaccine, the vaccines should always be administered at different injection sites.

Qdenga may be administered concomitantly with an hepatitis A vaccine. Coadministration has been studied in adults.

Qdenga may be administered concomitantly with a yellow fever vaccine. In a clinical study involving approximately 300 adult subjects who received Qdenga concomitantly with yellow fever 17D vaccine, there was no effect on yellow fever seroprotection rate. Dengue antibody responses were decreased following concomitant administration of Qdenga and yellow fever 17D vaccine. The clinical significance of this finding is unknown.

Women of childbearing potential

Women of childbearing potential should avoid pregnancy for at least one month following vaccination. Women who intend to become pregnant should be advised to delay vaccination (see sections 4.4 and 4.3).

Pregnancy

Animal studies are insufficient with respect to reproductive toxicity (see section 5.3).

There is limited amount of data from the use of Qdenga in pregnant women. These data are not sufficient to conclude on the absence of potential effects of Qdenga on pregnancy, embryo-foetal development, parturition and post-natal development.

Qdenga is a live attenuated vaccine, therefore Qdenga is contraindicated during pregnancy (see section 4.3).

Breast-feeding

It is unknown whether Qdenga is excreted in human milk. A risk to the newborns/infants cannot be excluded.

Qdenga is contraindicated during breast-feeding (see section 4.3).

Fertility

Animal studies are insufficient with respect to reproductive toxicity (see section 5.3).

No specific studies have been performed on fertility in humans.

Qdenga has minor influence on the ability to drive and use machines.

Summary of the safety profile

In clinical studies, the most frequently reported reactions in subjects 4 to 60 years of age were injection site pain (50%), headache (35%), myalgia (31%), injection site erythema (27%), malaise (24%), asthenia (20%) and fever (11%).

These adverse reactions usually occurred within 2 days after the injection, were mild to moderate in severity, had a short duration (1 to 3 days) and were less frequent after the second injection of Qdenga than after the first injection.

Vaccine viremia

In clinical study DEN-205, transient vaccine viremia was observed after vaccination with Qdenga in 49% of study participants who had not been infected with dengue before and in 16% of study participants who had been infected with dengue before. Vaccine viremia usually started in the second week after the first injection and had a mean duration of 4 days. Vaccine viremia was associated with transient, mild to moderate symptoms, such as headache, arthralgia, myalgia and rash in some subjects. Vaccine viraemia was rarely detected after the second dose.

Tabulated list of adverse reactions

Adverse reactions associated with Qdenga obtained from clinical studies are tabulated below (Table 1).

The safety profile presented below is based on a pooled analysis including 14,627 study participants aged 4 to 60 years (13,839 children and 788 adults) who have been vaccinated with Qdenga. This included a reactogenicity subset of 3,830 participants (3,042 children and 788 adults).

Adverse reactions are listed according to the following frequency categories: 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, Very rare: <1/10,000.

Table 1. Adverse reactions from Clinical Studies (Age 4 to 60 years):

^a Includes upper respiratory tract infection and viral upper respiratory tract infection.
^b Includes pharyngotonsillitis and tonsillitis.
^c Collected in children below 6 years of age in clinical studies.
^d Includes rash, viral rash, rash maculopapular, rash pruritic.
^e Reported in adults in clinical studies.

Paediatric population

Paediatric data in subjects 4 to 17 years of age

Pooled safety data from clinical trials are available for 13839 children (9210 aged 4 to 11 years and 4629 aged 12 to 17 years). This includes reactogenicity data collected in 3042 children (1865 aged 4 to 11 years and 1177 aged 12 to 17 years).

Frequency, type and severity of adverse reactions in children were largely consistent with those in adults. Adverse reactions reported more commonly in children than in adults were fever (11% versus 3%), upper respiratory tract infection (11% versus 3%), nasopharyngitis (6% versus 0.6%), pharyngotonsillitis (2% versus 0.3%), and influenza like illness (1% versus 0.1%). Adverse reactions reported less commonly in children than adults were injection site erythema (2% versus 27%), nausea (0.03% versus 0.8%) and arthralgia (0.03% versus 1%).

The following reactions were collected in 357 children below 6 years of age vaccinated with Qdenga: decreased appetite (17%), somnolence (13%) and irritability (12%).

Paediatric data in subjects below 4 years of age, i.e. outside the age indication

Reactogenicity in subjects below 4 years of age was assessed in 78 subjects who received at least one dose of Qdenga of which 13 subjects received the indicated 2-dose regimen. Reactions reported with very common frequency were irritability (25%), fever (17%), injection site pain (17%) and loss of appetite (15%). Somnolence (8%) and injection site erythema (3%) were reported with common frequency. Injection site swelling was not observed in subjects below 4 years of age.

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 medicinal product must not be mixed with other vaccine or medicinal products except for the solvent provided.