Qdenga · 4.6 Fertility, pregnancy and lactation · 1

HOS-099251 · has-adverse-reaction-information · PDF-Seite 6

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 viraemia In clinical study DEN-205, transient vaccine viraemia 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 viraemia usually started in the second week after the first injection and had a mean duration of 4 days. Vaccine viraemia was associated with transient, mild to moderate symptoms, such as headache, arthralgia, myalgia and rash in some subjects that may also occur with dengue. Vaccine viraemia was rarely detected after the second dose. Dengue diagnostic tests may be positive during vaccine viraemia and cannot be used to distinguish vaccine viraemia from wild type dengue infection. Tabulated list of adverse reactions Adverse reactions associated with Qdenga obtained from clinical studies and post-authorisation experience are tabulated below (Table 1). The safety profile presented below is based on data generated in placebo-controlled clinical studies and post-authorisation experience. Pooled analysis of clinical studies included data from 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 Not known: cannot be estimated from the available data Table 1: Adverse reactions from clinical studies (age 4 to 60 years) and post-authorisation experience (age 4 years and older) MedDRA System Organ Frequency Adverse Reactions Class Infections and infestations Very common Upper respiratory tract infectiona Common Nasopharyngitis

Auszug; vollständigen Abschnitt im Original lesen.

HOS-099247 · has-contraindication-information · PDF-Seite 3

• Hypersensitivity to the active substances or to any of the excipients listed in section 6.1 or hypersensitivity to a previous dose of Qdenga. • Individuals with congenital or acquired immune deficiency, including those receiving immunosuppressive therapies such as high doses of systemic corticosteroids (e.g. 20 mg/day or 2 mg/kg body weight/day of prednisone for 2 weeks or more) within 4 weeks prior to vaccination, or any other medicinal product with known immunosuppressive properties including chemotherapy. The time to avoid vaccination after immunosuppressive treatment should be considered on an individual basis. • Individuals with symptomatic HIV infection or with asymptomatic HIV infection when accompanied by evidence of impaired immune function. • Pregnant women (see section 4.6). • Breast-feeding women (see section 4.6). 3

HOS-099246 · has-indication-information · PDF-Seite 2

Qdenga is indicated for the prevention of dengue disease in individuals from 4 years of age. The use of Qdenga should be in accordance with official recommendations. 2

HOS-099249 · has-interaction-information · PDF-Seite 4

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 4 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 high doses of systemic corticosteroids within 4 weeks prior to vaccination, or any other medicinal product with known immunosuppressive properties including chemotherapy (see section 4.3). The time to avoid vaccination after immunosuppressive treatment should be considered on an individual basis. 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 a 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. Qdenga may be administered concomitantly with a human papillomavirus (HPV) vaccine (see section 5.1).

HOS-099250 · has-pregnancy-information · PDF-Seite 5

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. 5

HOS-099248 · has-warning-information · PDF-Seite 4

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 Anaphylaxis has been reported in individuals who have received Qdenga. The majority of cases occurred within 30 minutes following vaccination. 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 ‘potassium- free’.