APEXXNAR Suspension for injection Ref.[49639] Active ingredients: Pneumococcus, purified polysaccharides antigen

Do not inject Apexxnar intravascularly.

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.

Hypersensitivity

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

Concurrent illness

Vaccination should be postponed in individuals suffering from acute severe febrile illness. However, the presence of a minor infection, such as a cold, should not result in the deferral of vaccination.

Thrombocytopenia and coagulation disorders

The vaccine must be administered with caution to individuals with thrombocytopenia or a bleeding disorder since bleeding may occur following an intramuscular administration.

The risk of bleeding in patients with coagulation disorders needs to be carefully evaluated before intramuscular administration of any vaccine, and subcutaneous administration should be considered if the potential benefit clearly outweighs the risks.

Protection against pneumococcal disease

Apexxnar will only protect against Streptococcus pneumoniae serotypes included in the vaccine, and will not protect against other microorganisms that cause invasive disease or pneumonia. As with any vaccine, Apexxnar may not protect all individuals receiving the vaccine from pneumococcal invasive disease or pneumonia. For the most recent epidemiological information in your country, you should consult with the relevant national organisation.

Immunocompromised individuals

Safety and immunogenicity data on Apexxnar are not available for individuals in immunocompromised groups. Vaccination should be considered on an individual basis.

Based on experience with pneumococcal vaccines, some individuals with altered immunocompetence may have reduced immune responses to Apexxnar.

Individuals with impaired immune response, whether due to the use of immunosuppressive therapy, a genetic defect, HIV infection, or other causes, may have reduced antibody response to active immunization. The clinical relevance of this is unknown.

Safety and immunogenicity data with Prevenar 13 (a pneumococcal conjugate vaccine consisting of 13 polysaccharide conjugates that are also in Apexxnar) are available for a limited number of individuals with HIV infection, or with a HSCT (see sections 4.8 and 5.1).

In adults across all studied age groups, formal non-inferiority criteria were met although numerically lower geometric mean titres were observed with Apexxnar for most of the serotypes compared to Prevenar 13 (see section 5.1), however the clinical relevance of this observation for immunocompromised individuals is unknown.

Excipient

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

No interaction studies have been performed.

Different injectable vaccines should always be given at different vaccination sites.

Do not mix Apexxnar with other vaccines/medicinal products in the same syringe.

Pregnancy

There are no data on the use of Apexxnar in pregnant women.

Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity.

Administration of Apexxnar in pregnancy should only be considered when the potential benefits outweigh any potential risks for the mother and foetus.

Breast-feeding

It is unknown whether Apexxnar is excreted in human milk.

Fertility

No human data on the effect of Apexxnar on fertility are available. Animal studies do not indicate direct or indirect harmful effects with respect to female fertility (see section 5.3).

Apexxnar has no or negligible influence on the ability to drive and use machines. However, some of the effects mentioned under section 4.8 may temporarily affect the ability to drive or use machines.

Summary of the safety profile

Participants 18 years of age and older

The safety of Apexxnar was evaluated in 4,552 participants 18 years of age and older in six clinical trials (two Phase 1, one Phase 2, and three Phase 3), and 2,496 participants in the control groups.

In the Phase 3 trials, 4,263 participants received Apexxnar. This, included 1,798 participants 18 through 49 years of age, 334 participants 50 through 59 years of age, and 2,131 participants 60 years of age and older (1,138 were 65 years of age and older). Of the participants who received Apexxnar in the Phase 3 trials, 3,639 were naïve to pneumococcal vaccines, 253 had previously received Pneumovax 23 (pneumococcal polysaccharide vaccine [23-valent]; PPSV23) (≥1 to ≤5 years prior to enrollment), 246 had previously received Prevenar 13 only (≥6 months prior to enrollment), and 125 had previously received Prevenar 13 followed by PPSV23 (the dose of PPSV23 ≥1-year prior to enrollment).

Participants in the Phase 3 trial B7471007 (Pivotal Study 1007) were evaluated for adverse events for 1 month after vaccination, and serious adverse events through 6 months after vaccination. This study included 447 participants 18 to 49 years of age, 445 participants 50 to 59 years of age, 1,985 participants 60 to 64 years of age, 624 participants 65 to 69 years of age, 319 participants 70 to 79 years of age, and 69 participants ≥80 years of age.

In participants 18 to 49 years of age in Studies 1007 and a Phase 3 trial B7471008 (Lot Consistency Study 1008), the most frequently reported adverse reactions were pain at injection site (79.2%), muscle pain (62.9%), fatigue (46.7%), headache (36.7%), and joint pain (16.2%). In participants 50 to 59 years of age in Study 1007, the most frequently reported adverse reactions were pain at injection site (72.5%), muscle pain (49.8%), fatigue (39.3%), headache (32.3%), and joint pain (15.4%). In participants ≥60 years of age in Study 1007, the most frequently reported adverse reactions were pain at injection site (55.4%), muscle pain (39.1%), fatigue (30.2%), headache (21.5%), and joint pain (12.6%). These were usually mild or moderate in intensity and resolved within a few days after vaccination.

Phase 3 Study B7471006 (Study 1006) evaluated Apexxnar in participants ≥65 years of age with varying prior pneumococcal status (prior PPSV23, prior Prevenar 13 or prior Prevenar 13 followed by PPSV23). In this study, the most frequently reported adverse reactions for participants were similar in frequency to those described for participants ≥60 years of age in Study 1007, with slightly higher injection site pain (61.2%) in participants with prior Prevenar 13, and joint pain (16.8%) in participants with prior Prevenar 13 followed by PPSV23.

Tabulated list of adverse reactions

Tabulated lists of adverse reactions from the Phase 3 clinical trials and postmarketing experience are presented below.

Adverse reactions from clinical trials

As Apexxnar contains the same 13 serotype-specific capsular polysaccharide conjugates and the same vaccine excipients as Prevenar 13, the adverse reactions already identified for Prevenar 13 have been adopted for Apexxnar. Table 1 presents adverse reactions reported in Phase 3 trials of Apexxnar, based on the highest frequency among adverse reactions, local reactions, or systemic events after vaccination in any Apexxnar group. In clinical trials, the safety profile of Apexxnar was similar to that of Prevenar 13. No new adverse reactions were identified as compared to Prevenar 13.

Adverse reactions are listed by system organ class in decreasing order of frequency and seriousness. The frequency is defined as follows: 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 available data).

Table 1. Adverse Drug Reactions From Apexxnar Clinical Trials:

^a Event reported in clinical trials with Prevenar 13 with very common frequency (≥1/10). Decreased appetite and limitation of arm movement were not reported in the adult Phase 3 trials of Apexxnar; therefore, the frequency is not known.

Adverse reactions from postmarketing experience

Table 2 includes adverse experiences that have been spontaneously reported during the postmarketing use of Prevenar 13, which may also occur with Apexxnar. The postmarketing safety experience with Prevenar 13 is relevant to Apexxnar, as Apexxnar contains all components (polysaccharide conjugates and excipients) of Prevenar 13. These events were reported voluntarily from a population of uncertain size. Therefore, it is not possible to reliably estimate their frequency or to establish, for all events, a causal relationship to vaccine exposure.

Table 2. Adverse Reactions From Prevenar 13 Postmarketing Experience:

Events reported spontaneously in Prevenar 13 postmarketing experience; therefore, the frequencies could not be estimated from the available data and are considered as not known.

Additional information in special populations in studies with Prevenar 13

Participants ≥18 years of age with HIV infection have similar frequencies of adverse reactions in Table 1, except for pyrexia (5% to 18%) and vomiting (8% to 12%) which were very common and nausea (<1% to 3%) which was common.

Participants ≥18 years of age with an HSCT have similar frequencies of adverse reactions in Table 1, except for pyrexia (4% to 15%), vomiting (6% to 21%), and diarrhoea (25% to 36%) which were very common.

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.