ABRYSVO powder+solvent for injection medication leaflet

Abrysvo powder and solvent for solution for injection

Abrysvo powder and solvent for solution for injection in multidose container

Respiratory syncytial virus vaccine (bivalent, recombinant)

After reconstitution, one dose (0.5 mL) contains:

RSV subgroup A stabilised prefusion F antigen1,2 60 micrograms

RSV subgroup B stabilised prefusion F antigen1,2 60 micrograms(RSV antigens)1glycoprotein F stabilised in the prefusion conformation2produced in Chinese Hamster Ovary cells by recombinant DNA technology.

One dose contains 0.08 milligrams of polysorbate 80 (see section 4.4).

For the full list of excipients, see section 6.1.

Powder and solvent for solution for injection.

Powder and solvent for solution for injection in multidose container.

The powder is white.

The solvent is a clear, colourless liquid.

Abrysvo is indicated for:

* Active immunisation of pregnant individuals to protect infants from birth through 6 months ofage against lower respiratory tract disease caused by respiratory syncytial virus (RSV). Seesections 4.2 and 5.1.

* Active immunisation of individuals 18 years of age and older for the prevention of lowerrespiratory tract disease caused by RSV.

The use of this vaccine should be in accordance with official recommendations.

Pregnant individuals

A single dose of 0.5 mL should be administered between weeks 24 and 36 of gestation (see sections4.4 and 5.1).

A single dose of 0.5 mL should be administered.

The need for revaccination has not been established.

A single dose of 0.5 mL should be administered. The need for a second dose has not been established(see section 5.1).

The safety and efficacy of Abrysvo in children (from birth to less than 18 years of age) have not yetbeen established. Limited data are available in pregnant adolescents and their infants (see section 5.1).

Abrysvo is for intramuscular injection into the deltoid region of the upper arm.

The vaccine should not be mixed with any other vaccines or medicinal products.

For instructions on reconstitution and handling of the medicinal product before administration, seesection 6.6.

Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.

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

Appropriate medical treatment and supervision should always be readily available in case of ananaphylactic event following the administration of the vaccine.

Anxiety-related reactions, including vasovagal reactions (syncope), hyperventilation or stress-relatedreactions may occur in association with vaccination as a psychogenic response to the needle injection.

It is important that procedures are in place to avoid injury from fainting.

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

Abrysvo should be given with caution to individuals with thrombocytopenia or any coagulationdisorder since bleeding or bruising may occur following an intramuscular administration to theseindividuals.

Safety and immunogenicity have been assessed in immunocompromised individuals, including thosereceiving immunosuppressant therapy (see sections 4.8 and 5.1). The efficacy of Abrysvo may belower in immunosuppressed individuals.

Individuals less than 24 weeks of gestation

Abrysvo has not been studied in pregnant individuals less than 24 weeks of gestation. Since protectionof the infant against RSV depends on transfer of maternal antibodies across the placenta, Abrysvoshould be administered between weeks 24 and 36 of gestation (see sections 4.2 and 5.1).

As with any vaccine, a protective immune response may not be elicited after vaccination.

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

This medicinal product contains polysorbate 80. Polysorbates may cause allergic reactions.

Abrysvo can be administered concomitantly with:

* seasonal influenza vaccines, either standard dose adjuvanted or high dose unadjuvanted

* COVID-19 mRNA vaccines, with or without high dose unadjuvanted influenza vaccineadministered concomitantly.

A minimum interval of two weeks is recommended between administration of Abrysvo andadministration of a tetanus, diphtheria and acellular pertussis vaccine (Tdap). There were no safetyconcerns when Abrysvo was co-administered with Tdap in healthy non-pregnant women. Immuneresponses to RSV A, RSV B, diphtheria and tetanus on co-administration were non-inferior to thoseafter separate administration. However, the immune responses to the pertussis components were loweron co-administration compared to separate administration and did not meet the criteria for non-inferiority. The clinical relevance of this finding is unknown.

Data on pregnant women (more than 4 000 exposed outcomes) indicate no malformative norfeto/neonatal toxicity.

Results from animal studies with Abrysvo do not indicate direct or indirect harmful effects withrespect to reproductive toxicity (see section 5.3).

In a phase 3 study (Study 1), maternal adverse events reported within 1 month after vaccination weresimilar in the Abrysvo group (14%) and the placebo group (13%).

No safety signals were detected in infants up to 24 months of age. The incidences of adverse eventsreported within 1 month after birth in infants were similar in the Abrysvo group (38%) and the placebogroup (35%). Major birth outcomes assessed in the Abrysvo group compared to placebo includedpremature birth (207 (6%) and 172 (5%), respectively), low birth weight (186 (5%) and 158 (4%),respectively) and congenital anomalies (205 (6%) and 245 (7%), respectively).

It is unknown whether Abrysvo is excreted in human milk. No adverse effects of Abrysvo have beenshown in breastfed newborns of vaccinated mothers.

No human data on the effect of Abrysvo on fertility are available.

Animal studies do not indicate direct or indirect harmful effects with respect to female fertility (seesection 5.3).

Abrysvo has no or negligible influence on the ability to drive and use machines.

Pregnant individuals

In pregnant women at 24-36 weeks of gestation the most frequently reported adverse reactions werevaccination site pain (41%), headache (31%) and myalgia (27%). The majority of local and systemicreactions in maternal participants were mild to moderate in severity and resolved within 2-3 days ofonset.

In individuals 18 years of age and older the most frequently reported adverse reactions were fatigue(23%), headache (20%), vaccination site pain (19%) and myalgia (16%). The majority of reactionswere mild to moderate in severity and resolved within 1-2 days of onset.

The safety of administering a single dose of Abrysvo to pregnant women at 24-36 weeks of gestation(n=3 698) and to individuals 18 years of age and older (n=20 275) was evaluated in clinical trials.

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).

Adverse reactions reported are listed per system organ class, in decreasing order of seriousness.

Table 1 Adverse reactions following administration of Abrysvo

System organ class Adverse reactions Adverse reactionspregnant individuals individuals≤49 years ≥18 years

Lymphadenopathy Rare Rare

Anaphylaxis Very rare

Hypersensitivity reactions Rare Rare(includes rash, urticaria)

Headache Very common Very common

Guillain-Barré syndrome Very rare

Myalgia Very common Very common

Arthralgia Common

Fatigue Very common

Vaccination site pain Very common Very common

Vaccination site redness Common Common

Vaccination site swelling Common Common

Pyrexia Uncommon

Vaccination site pruritus Rare

Vaccination site bruising Rare

Vaccination site haematoma Rare

Immunocompromised individuals 18 years of age and older

Reactogenicity was consistent with the known profile of Abrysvo. There were no unexpected safetyfindings.

Reporting suspected adverse reactions after authorisation of the medicinal product is important. Itallows continued monitoring of the benefit/risk balance of the medicinal product. Healthcareprofessionals are asked to report any suspected adverse reactions via the national reporting systemlisted in Appendix V.

There is no specific treatment for an overdose with Abrysvo. In the event of an overdose, theindividual should be monitored and provided with symptomatic treatment as appropriate.

Pharmacotherapeutic group: Vaccines, other viral vaccines; ATC code: J07BX05

Abrysvo contains two recombinant stabilised RSV prefusion F antigens representing subgroups

RSV-A and RSV-B. Prefusion F is the primary target of neutralising antibodies that block RSVinfection. Following intramuscular administration, the prefusion F antigens elicit an immune response,which protects against RSV-associated lower respiratory tract disease (LRTD).

In infants born to mothers who were vaccinated with Abrysvo between weeks 24 and 36 of gestation,protection against RSV-associated LRTD is due to transplacental transfer of RSV neutralisingantibodies. Adults 18 years of age and older are protected by active immunisation.

Infants from birth through 6 months of age by active immunisation of pregnant individuals

Study 1 was a phase 3, multicentre, randomised (1:1), double-blind, placebo-controlled study to assessthe efficacy of a single dose of Abrysvo in the prevention of RSV-associated LRTD in infants born topregnant individuals vaccinated between weeks 24 and 36 of gestation. The need for revaccinationwith subsequent pregnancies has not been established.

RSV-associated LRTD was defined as a medically attended visit in individuals with a reversetranscription-polymerase chain reaction (RT-PCR) confirmation of RSV and with one or more of thefollowing respiratory symptoms: fast breathing, low oxygen saturation (SpO2 <95%) and chest wallindrawing. Severe RSV-associated LRTD was defined as RSV-associated LRTD that additionally metat least one of the following criteria: very fast breathing, low oxygen saturation (SpO2 <93%), high-flow oxygen supplementation via nasal cannula or mechanical ventilation, ICU admission for >4 hoursand/or failure to respond/unconscious.

In this study, 3 711 pregnant individuals with uncomplicated, singleton pregnancies were randomisedto the Abrysvo group and 3 709 to placebo.

Vaccine efficacy (VE) was defined as the relative risk reduction of the endpoint in the Abrysvo groupcompared to the placebo group for infants born to pregnant individuals who received the assignedintervention. At the primary analysis, there were two primary efficacy endpoints, assessed in parallel,severe RSV-positive medically attended LRTD and RSV-positive medically attended LRTD,occurring within 90, 120, 150 or 180 days after birth.

Of the pregnant women who received Abrysvo, 65% were White, 20% were Black or African

American and 29% were Hispanic/Latino. The median age was 29 years (range 16-45 years); 0.2% ofparticipants were under 18 years of age and 4.3% were under 20 years of age. The median gestationalage at vaccination was 31 weeks and 2 days (range 24 weeks and 0 days to 36 weeks and 4 days). Themedian infant gestational age at birth was 39 weeks and 1 day (range 27 weeks and 3 days to 43 weeksand 6 days).

Vaccine efficacy is presented in Tables 2 and 3.

Table 2 Vaccine efficacy of Abrysvo against severe medically attended LRTD caused by RSV ininfants from birth through 6 months of age by active immunisation of pregnantindividuals - Study 1

Time period Abrysvo Placebo VE %

Number of cases Number of cases (CI)a

N=3 495 N=3 48090 days 6 33 81.8 (40.6, 96.3)120 days 12 46 73.9 (45.6, 88.8)150 days 16 55 70.9 (44.5, 85.9)180 days 19 62 69.4 (44.3, 84.1)

CI = confidence interval; VE = vaccine efficacya 99.5% CI at 90 days; 97.58% CI at later intervals

Table 3 Vaccine efficacy of Abrysvo against medically attended LRTD caused by RSV ininfants from birth through 6 months of age by active immunisation of pregnantindividuals - Study 1

Time period Abrysvo Placebo VE %

Number of cases Number of cases (CI)a

N=3 495 N=3 48090 days 24 56 57.1 (14.7, 79.8)120 days 35 81 56.8 (31.2, 73.5)150 days 47 99 52.5 (28.7, 68.9)180 days 57 117 51.3 (29.4, 66.8)

CI = confidence interval; VE = vaccine efficacya 99.5% CI at 90 days; 97.58% CI at later intervals

A post-hoc analysis of VE by maternal gestational age was conducted. For severe medically attended

LRTD occurring within 180 days, VE was 57.2% (95% CI 10.4, 80.9) for women vaccinated early inpregnancy (24 to <30 weeks) and 78.1% (95% CI 52.1, 91.2) for women vaccinated later in thepregnancy eligible window (30 to 36 weeks). For medically attended LRTD occurring within 180days, VE was 30.9% (95% CI -14.4, 58.9) for women vaccinated early in pregnancy (24 to <30 weeks)and 62.4% (95% CI 41.6, 76.4) for women vaccinated later in the pregnancy eligible window (30 to 36weeks).

Individuals 60 years of age and older

Study 2 was a phase 3, multicentre, randomised, double-blind, placebo-controlled study to assess theefficacy of Abrysvo in the prevention of RSV-associated LRTD in individuals 60 years of age andolder.

RSV-associated LRTD was defined as RT-PCR confirmed RSV disease with two or more or three ormore of the following respiratory symptoms within 7 days of symptom onset and lasting more than 1day during the same illness: new or increased cough, wheezing, sputum production, shortness ofbreath or tachypnoea (≥25 breaths/min or 15% increase from resting baseline).

Participants were randomised (1:1) to receive Abrysvo (n=18 487) or placebo (n=18 479). Enrollmentwas stratified by age 60-69 years (63%), 70-79 years (32%) and ≥80 years (5%). Subjects with stablechronic underlying conditions were eligible for this study and 52% of participants had at least 1prespecified condition; 16% of participants were enrolled with stable chronic cardiopulmonaryconditions such as asthma (9%), chronic obstructive pulmonary disease (7%) or congestive heartfailure (2%). Immunocompromised individuals were ineligible.

The primary objective was assessment of vaccine efficacy (VE), defined as the relative risk reductionof first episode of RSV-associated LRTD in the Abrysvo group compared to the placebo group in thefirst RSV season.

Of the participants who received Abrysvo, 51% were male and 80% were White, 12% were Black or

African American and 42% were Hispanic/Latino. The median age of participants was 67 years (range59-95 years).

At the end of the first RSV season the analysis demonstrated statistically significant efficacy for

Abrysvo for reduction of RSV-associated LRTD with ≥2 symptoms and with ≥3 symptoms.

Vaccine efficacy information at the end of the first RSV season (median follow-up time 7.4 months) ispresented in Table 4.

Table 4 Vaccine efficacy of Abrysvo against RSV disease - active immunisation ofindividuals 60 years of age and older - Study 2

Efficacy Abrysvo Placebo VE (%)endpoint (95% CI)

N n N n

First episode Overall 18 058 15 18 076 43 65.1 (35.9, 82.0)of RSV- Age 60-69 years 11 305 10 11 351 25 60.0 (13.8, 82.9)associated Age 70-79 years 5 750 4 5 742 12 66.7 (-10.0, 92.2)

LRTD with With ≥1 significant 9 377 8 9 432 22 63.6 (15.2, 86.0)≥2 symptomsa underlying condition

First episode Overall 18 058 2 18 076 18 88.9 (53.6, 98.7)of RSV- Age 60-69 years 11 305 2 11 351 11 81.8 (16.7, 98.0)associated Age 70-79 years 5 750 0 5 742 4 100 (-51.5, 100.0)

LRTD with With ≥1 significant 9 377 2 9 432 11 81.8 (16.7, 98.0)≥3 symptomsb underlying condition

CI - confidence interval; RSV - respiratory syncytial virus; VE - vaccine efficacy

N = number of participants; n = number of casesa In an exploratory analysis in RSV subgroup A (Abrysvo n=3, placebo n=16) VE was 81.3% (CI 34.5, 96.5);and in RSV subgroup B (Abrysvo n=12, placebo n=26) VE was 53.8% (CI 5.2, 78.8).

b In an exploratory analysis in RSV subgroup A (Abrysvo n=1, placebo n=5) VE was 80.0% (CI -78.7, 99.6);and in RSV subgroup B (Abrysvo n=1, placebo n=12) VE was 91.7% (CI 43.7, 99.8).

Vaccine efficacy in the subgroup of participants 80 years of age and older (995 and 981 participants inthe Abrysvo and placebo groups, respectively) cannot be concluded due to the low number of totalcases accrued (7 cases of RSV-associated LRTD with ≥2 symptoms and 3 cases of RSV-associated

LRTD with ≥3 symptoms).

Efficacy against RSV-associated lower respiratory tract disease over 2 RSV seasons in individuals60 years of age and older

Across 2 RSV seasons with median follow-up time of 16.4 months, VE against RSV-associated LRTDwith ≥2 symptoms was 58.8% (95% CI 43.0, 70.6; 54 cases in the Abrysvo group and 131 cases in theplacebo group) and with ≥3 symptoms was 81.5% (95% CI 63.3, 91.6; 10 cases in the Abrysvo groupand 54 cases in the placebo group). VE against RSV-associated LRTD caused by RSV-A and RSV-Bwas 66.3% (95% CI 47.2, 79.0) and 50.0% (95% CI 18.5, 70.0) for cases with ≥2 LRTD symptomsrespectively, and 80.6% (95% CI 52.9, 93.4) and 86.4% (95% CI 54.6, 97.4) for cases with ≥3 LRTDsymptoms, respectively.

Across 2 RSV seasons, subgroup analyses of VE by age and significant underlying conditions wereconsistent with VE at the end of the first RSV season and support consistent VE across different ageand risk groups.

Immunogenicity in individuals 18 through 59 years of age

Study 3 was a Phase 3, multicentre, randomised, double-blind, placebo-controlled study to assess thesafety and immunogenicity of Abrysvo in individuals 18 through 59 years of age considered to be athigh risk of developing severe LRTD caused by RSV. Study 3 enrolled individuals who had chronicpulmonary (including asthma), cardiovascular (excluding isolated hypertension), renal, hepatic,neurologic, haematologic or metabolic disorders (including diabetes mellitus andhyper/hypothyroidism). Participants were randomised (2:1) to receive a single dose of Abrysvo(n=437) or placebo (n=217).

Demographic characteristics in study 3 were generally similar with regard to age, race and ethnicityamong participants who received Abrysvo and those who received placebo. Fifty-three percent (53%)were 18 to 49 years and 47% were 50 to 59 years. The vaccine and placebo groups were similar withregards to having at least one prespecified medical condition, which included 53% with ≥1 chronicpulmonary condition, 8% with ≥1 cardiovascular condition, 42% with diabetes and 31% ≥1 otherdisease (liver, renal, neurologic, haematologic or other metabolic disease).

Vaccine efficacy in individuals 18 through 59 years of age is inferred by immunobridging to study 2where vaccine efficacy was demonstrated in individuals 60 years of age and older. The non-inferioritycriteria were met for high risk individuals 18 through 59 years of age compared to a randomly selectedimmunogenicity subset (external control group) of individuals ≥60 years of age from study 2 for theratio of RSV neutralising geometric mean titres (GMTs) by the lower bounds of the 2-sided 95% CIs>0.667 (1.5-fold non-inferiority margin), and for the difference in seroresponse rates by the lowerbounds of the 2-sided 95% CIs > -10% for both RSV A and RSV B.

Table 5 Comparison of model adjusted RSV neutralising titre GMTs at 1 month aftervaccination with Abrysvo, 18 through 59 years at high risk (Study 3) versus 60 yearsand older (Study 2)

Study 3 18-59 years of age Study 2 ≥60 years ANCOVAat high risk comparison

RSV n Adjusted GMT n Adjusted GMT Adjusted GMRsubgroups (95% CI) (95% CI) (95% CI)

A 435 41 097 408 26 225 1.57 (1.396, 1.759)(37 986, 44 463) (24 143, 28 486)

B 437 37 416 408 24 680 1.52 (1.333, 1.725)(34 278, 40 842) (22 504, 27 065)

CI - confidence interval; GMR - geometric mean ratio; GMT - geometric mean titre

Table 6 Comparison of RSV neutralising titre seroresponse rates 1 month after vaccinationwith Abrysvo, 18 through 59 years at high risk (Study 3) versus 60 years and older(Study 2)

Study 3 18-59 years of age at Study 2 ≥60 years Comparisonhigh risk

RSV n/N (%) 95% CI n/N (%) 95% CI Differencesubgroups (95% CI)

A 405/435 (93) 90.3, 95.3 359/408 (88) 84.4, 91.0 5.1 (1.2, 9.2)

B 408/437 (93) 90.6, 95.5 347/408 (85) 81.2, 88.4 8.3 (4.2, 12.6)

CI - confidence interval

Immunogenicity in immunocompromised individuals 18 years of age and older

Study 4 (C3671023 Substudy B) was a Phase 3, single-arm, open-label, multicentre study to assess thesafety and immunogenicity of Abrysvo in immunocompromised individuals ≥18 years of age.

Participants had history of a solid organ transplant (kidney, liver, lung or heart) at least 3 months priorto enrollment; end stage renal disease and on haemodialysis; autoimmune inflammatory disorders withactive immunomodulator therapy; or advanced non-small cell lung cancer and receiving activeimmunomodulator therapy. Participants received 2 doses of Abrysvo with an interval of 1 month.

A single dose of Abrysvo was sufficient to elicit robust neutralising responses approximately 8- or 9-fold above baseline against RSV A and RSV B in participants ≥18 years of age withimmunocompromising conditions (n=188). Responses did not further increase with a second dose of

Abrysvo 1 month after the first dose.

The European Medicines Agency has deferred the obligation to submit the results of studies with

Abrysvo in children from 2 to less than 18 years of age in prevention of lower respiratory tract diseasecaused by RSV (see section 4.2 for information on paediatric use).

Not applicable.

Non-clinical data reveal no special hazard for humans based on conventional studies of repeated dosetoxicity and toxicity to reproduction and development.

Abrysvo powder and solvent for solution for injection

Trometamol

Trometamol hydrochloride

Sucrose

Mannitol (E421)

Polysorbate 80 (E433)

Sodium chloride

Hydrochloric acid (for pH adjustment)

Water for injections

Abrysvo powder and solvent for solution for injection in multidose container

Trometamol

Trometamol hydrochloride

Sucrose

Mannitol (E421)

Polysorbate 80 (E433)

Sodium chloride

Hydrochloric acid (for pH adjustment)

Water for injections2-phenoxyethanol

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

Abrysvo powder and solvent for solution for injection4 years

Abrysvo powder and solvent for solution for injection in multidose container18 months

The unopened vial of antigens is stable for 5 days when stored at temperatures from 8 °C to 30 °C. Atthe end of this period Abrysvo should be used or discarded. This information is used to guidehealthcare professionals in case of temporary temperature excursions only.

Abrysvo powder and solvent for solution for injection

Single dose vials

Abrysvo should be administered immediately after reconstitution or within 4 hours if stored between15 °C and 30 °C. Do not freeze.

Chemical and physical in-use stability has been demonstrated for 4 hours between 15 °C and 30 °C.

From a microbiological point of view, the product should be used immediately. If not usedimmediately, in-use storage times and conditions prior to use are the responsibility of the user.

Abrysvo powder and solvent for solution for injection in multidose container

Multidose vials

After reconstitution, store in a refrigerator (2 °C to 8 °C). Abrysvo should be administered within8 hours with no more than 4 hours stored at room temperature (up to 30 °C). Do not freeze.

Store in a refrigerator (2 ºC - 8 ºC).

Do not freeze. Discard if the carton has been frozen.

For storage conditions after reconstitution of the medicinal product, see section 6.3.

Abrysvo powder and solvent for solution for injection

Powder for 1 dose in a vial (type 1 glass or equivalent) with a stopper (synthetic bromobutyl rubber orsynthetic chlorobutyl rubber) and a flip off cap.

Solvent for 1 dose in a pre-filled syringe (type 1 glass) with a stopper (synthetic chlorobutyl rubber)and a tip cap (synthetic isoprene/bromobutyl blend rubber).

Vial adaptor.

Pack containing 1 vial of powder (antigens), 1 pre-filled syringe of solvent, 1 vial adaptor with1 needle or without needles (1 dose pack).

Pack containing 5 vials of powder (antigens), 5 pre-filled syringes of solvent, 5 vial adaptors with5 needles or without needles (5 dose pack).

Pack containing 10 vials of powder (antigens), 10 pre-filled syringes of solvent, 10 vial adaptors with10 needles or without needles (10 dose pack).

Single dose vials

Powder for 1 dose in a vial (type 1 glass or equivalent) with a stopper (synthetic bromobutyl rubber orsynthetic chlorobutyl rubber) and a flip off cap.

Solvent for 1 dose in a vial (type 1 glass or equivalent) with a stopper (synthetic bromobutyl rubber)and a flip off cap.

Pack containing 5 vials of powder (antigens) and 5 vials of solvent (5 dose pack).

Pack containing 10 vials of powder (antigens) and 10 vials of solvent (10 dose pack).

Abrysvo powder and solvent for solution for injection in multidose container

Multidose vials

Powder for 3 doses in a vial (type 1 glass or equivalent) with a stopper (synthetic bromobutyl rubber)and a flip off cap.

Solvent for 3 doses in a vial (type 1 glass or equivalent) with a stopper (synthetic bromobutyl rubber)and a flip off cap.

Pack containing 10 multidose vials of powder (antigens) and 10 multidose vials of solvent (30 dosepack).

Not all pack sizes may be marketed.

Abrysvo powder and solvent for solution for injection

Abrysvo must be reconstituted prior to administration by adding the entire contents of the pre-filledsyringe of solvent to the vial containing the powder using the vial adaptor.

The vaccine must be reconstituted only with the solvent provided.

Preparation for administration

Pre-filled syringe containing solvent for Abrysvo Vial containing antigensfor Abrysvo (powder) Vial adaptor

Syringe cap Luer lock adaptor Vial stopper (with flip off cap removed)

Step 1. Attach vial adaptor

* Peel off the top cover from the vial adaptor packaging and remove the flip off capfrom the vial.

* While keeping the vial adaptor in its packaging, centre over the vial’s stopper andconnect with a straight downward push. Do not push the vial adaptor in at an angleas it may result in leaking. Remove the packaging.

Step 2. Reconstitute the powder component (antigens) to form Abrysvo

* For all syringe assembly steps, hold the syringe only by the Luer lock adaptor. Thiswill prevent the Luer lock adaptor from detaching during use.

* Twist to remove the syringe cap, then twist to connect the syringe to the vialadaptor. Stop turning when you feel resistance.

* Inject the entire contents of the syringe into the vial. Hold the plunger rod downand gently swirl the vial until the powder is completely dissolved. Do not shake.

Step 3. Withdraw reconstituted vaccine

* Invert the vial completely and slowly withdraw the entire contents into the syringeto ensure a 0.5 mL dose of Abrysvo.

* Twist to disconnect the syringe from the vial adaptor.

* Attach a sterile needle suitable for intramuscular injection.

The prepared vaccine is a clear and colourless solution. Visually inspect the vaccine for largeparticulate matter and discolouration prior to administration. Do not use if large particulate matter ordiscolouration is found.

Single dose vials

The vial containing antigens for Abrysvo (powder) must be reconstituted only with the vial of solventprovided to form Abrysvo.

Preparation for administration1. Using a sterile needle and sterile syringe, withdraw the entire contents of the vial containing thesolvent and inject the entire contents of the syringe into the vial containing the powder.2. Gently swirl the vial in a circular motion until the powder is completely dissolved. Do not shake.3. Withdraw 0.5 mL from the vial containing the reconstituted vaccine.

Abrysvo powder and solvent for solution for injection in multidose container

Multidose vials

The multidose vial containing antigens for Abrysvo (powder) must be reconstituted only with themultidose vial of solvent provided to form Abrysvo. Abrysvo is administered as a single dose of0.5 mL. The maximum number of doses per multidose vial is 3.

Preparation for administration1. Using a sterile needle and sterile syringe, withdraw the entire contents of the vial containing thesolvent and inject the entire contents of the syringe into the vial containing the powder.2. Gently swirl the vial in a circular motion until the powder is completely dissolved. Do not shake.

Withdraw 0.5 mL (1 dose) from the vial containing the reconstituted vaccine.3. Repeat step 2 using a new sterile needle and sterile syringe to withdraw additional 0.5 mL dosesfrom the vial containing the reconstituted vaccine. The maximum number of doses per multidosevial is 3. After preparing 3 doses, dispose of any unused vaccine.

The prepared vaccine is a clear and colourless solution. Visually inspect the vaccine for largeparticulate matter and discolouration prior to administration. Do not use if large particulate matter ordiscolouration is found.

Any unused medicinal product or waste material should be disposed of in accordance with localrequirements.

Pfizer Europe MA EEIG

Boulevard de la Plaine 171050 Bruxelles

Belgium

EU/1/23/1752/001 - 1 vial (antigens), 1 vial adaptor, 1 pre-filled syringe (solvent), 1 needle

EU/1/23/1752/002 - 1 vial (antigens), 1 vial adaptor, 1 pre-filled syringe (solvent)

EU/1/23/1752/003 - 5 vials (antigens), 5 vial adaptors, 5 pre-filled syringes (solvent), 5 needles

EU/1/23/1752/004 - 5 vials (antigens), 5 vial adaptors, 5 pre-filled syringes (solvent)

EU/1/23/1752/005 - 10 vials (antigens), 10 vial adaptors, 10 pre-filled syringes (solvent), 10 needles

EU/1/23/1752/006 - 10 vials (antigens), 10 vial adaptors, 10 pre-filled syringes (solvent)

EU/1/23/1752/007 - 5 vials (antigens), 5 vials (solvent)

EU/1/23/1752/008 - 10 vials (antigens), 10 vials (solvent)

EU/1/23/1752/009 - 10 multidose vials (antigens), 10 multidose vials (solvent)

Date of first authorisation: 23 August 2023

Detailed information on this medicinal product is available on the website of the European Medicines

Agency https://www.ema.europa.eu.