Xevudy

o l Concentrate for solution for infusion (sterile concentrate) o A clear, colourless or yellow to brown solution, free from visible particles, with a pH of approximately n 6 and an osmolality of approximately 290 mOsm/kg. t c

u

o Xevudy is indicated for the treatment of adults and adolescents (aged 12 years and over and weighing r at least 40 kg) with coronavirus disease 2019 (COVID-19) who do not require oxygen supplementation and who apre at increased risk of progressing to severe COVID-19 (see section 5.1).

l The use of Xevudy should take into account information on the activity of sotrovimab against viral a variants of concern (see sections 4.4 and 5.1). n

c Xevudy shouild be administered under conditions where management of severe hypersensitivity reactions,dsuch as anaphylaxis, is possible and patients can be monitored during and for at least one hour afeter administration (see section 4.4).

It iMs recommended that Xevudy is administered within 5 days of onset of symptoms of COVID-19 (see section 5.1).

Posology

Adults and adolescents (from 12 years and 40 kg body weight) The recommended dose is a single 500 mg intravenous infusion administered following dilution (see sections 4.4 and 6.6).

Special populations

Elderly No dose adjustment is required in elderly patients (see section 5.2).

Renal impairment d No dose adjustment is required in patients with renal impairment (see section 5.2). e Hepatic impairment s No dose adjustment is required in patients with hepatic impairment (see section 5.2). i r Paediatric population o The safety and efficacy of Xevudy in children under 12 years old or weighing less than 40 kg have not h yet been established. Currently available data are described in sections 4.8 and 5.2 but no t recommendation on posology can be made. u Method of administration a

For intravenous use. r e This medicinal product must be diluted prior to administration. g Once diluted, it is recommended that the solution is administenred over 15 minutes (when using a 50 mL infusion bag) or over 30 minutes (when using a 100 mL infusion bag) with a 0.2-μm in-line o filter. l

Xevudy must not be administered as an intravenousopush or bolus injection.

n For instructions on dilution of the medicinal product, see section 6.6.

t

c

Hypersensitivity to the active substanceuor to any of the excipients listed in section 6.1. d

o r Traceability p In order to improve the traceability of biological medicinal products, the name and the batch number l of the administered product should be clearly recorded. a Hypersensitivity rneactions including anaphylaxis i Hypersensitivicty reactions, including anaphylaxis, have been reported with administration of sotrovimab (isee section 4.8). If signs or symptoms of a clinically significant hypersensitivity reaction or anaphydlaxis occur, administration should be discontinued immediately and appropriate medications and/or supportive care should be given. e

InfMusion-related reactions

Infusion-related reactions (IRRs) have been observed with intravenous administration of monoclonal antibodies (see section 4.8). These reactions may be severe or life threatening. If an IRR occurs, the infusion may be interrupted, slowed or stopped.

Antiviral resistance

Decisions regarding the use of Xevudy should take into consideration what is known about the characteristics of the circulating SARS-CoV-2 viruses including regional or geographical differences and available information on sotrovimab susceptibility patterns (see section 5.1).

When molecular testing or sequencing data are available, they should be considered to rule out SARS CoV-2 variants that are shown to have reduced susceptibility to sotrovimab. d Polysorbate e s This medicinal product contains 4.8 mg of polysorbate 80 in each 500 mg dose. Polysorbates may i cause allergic reactions. r o

h t Pharmacokinetic interactions u No interaction studies have been performed. Sotrovimab is not renally excreted or metabolised by a cytochrome P450 (CYP) enzymes; therefore, interactions with medicinal products that are renally excreted or that are substrates, inducers, or inhibitors of CYP enzymesrare unlikely. e Pharmacodynamic interactions g In vitro pharmacodynamic studies showed no antagonism betnween sotrovimab and remdesivir or bamlanivimab. o l

o Pregnancy n There are no data from the use of sotrovimab in pregnant women. Animal studies have not been t evaluated with respect to reproductive toxicity (see section 5.3). In a cross-reactive binding assay c using a protein array enriched for human embryofoetal proteins, no off-target binding was detected. Since sotrovimab is a human immunogulobulin G (IgG), it has the potential for placental transfer from the mother to the developing foetus. The potential treatment benefit or risk of placental transfer of d sotrovimab to the developing foetus is not known. o Sotrovimab should be used durring pregnancy only if the expected benefit to the mother justifies the potential risk to the foetus. p

Breast-feeding l a It is not known whnether sotrovimab is excreted in human milk or absorbed systemically after ingestion. Administration of sotrovimab while breast-feeding can be considered when clinically i indicated. c i Fertility d e There are no data on the effects of sotrovimab on human male or female fertility. Effects on male and femMale fertility have not been evaluated in animal studies.

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

Summary of the safety profile

The safety of a 500 mg dose of sotrovimab administered intravenously was evaluated in non hospitalised patients with COVID-19 in a placebo-controlled randomised study (COMET-ICE, 1049 patients treated in a 1:1 ratio of sotrovimab:placebo), and in two non-placebo controlled randomised studies (COMET-PEAK, 193 patients and COMET-TAIL, 393 patients) (see section 5.1). The most common adverse reactions were hypersensitivity reactions (2%) and infusion-related reactions (1%). d The most serious adverse reaction was anaphylaxis (0.05%). e Tabulated list of adverse reactions s i The adverse reactions in Table 1 are listed by system organ class and frequency. Frequenrcies are defined as follows: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1o/1,000 to <1/100); rare (≥1/10,000 to <1/1,000), very rare (<1/10,000). h t Table 1: Tabulated list of adverse reactions

System organ class	Adverse reaction	Frequencuy
Immune system disorders	Hypersensitivity reactions a Anaphylaxis	Commoan Rare
Respiratory, thoracic and mediastinal disorders	Dyspnoea	Unrcommon e
Injury, poisoning and procedural complications	Infusion-related reactions g	Common

aSuch as rash and bronchospasm. Pruritus may also be seen ans a manifestation of hypersensitivity reactions. o l Description of selected adverse reactions o Infusion-related reactions n IRRs may be severe or life threatening (see section 4.4). Signs and symptoms of IRRs may include fever, difficulty breathing, reduced oxygen saturation, chills, nausea, arrhythmia (e.g. atrial t fibrillation), tachycardia, bradycardia, chest pain or discomfort, weakness, altered mental status, c headache, bronchospasm, hypotension, hypertension, angioedema, throat irritation, rash including u urticaria, pruritus, myalgia, dizziness, fatigue and diaphoresis. d Paediatric population o r Based on limited data (n=7) from adolescents (aged 12 to less than 18 years and weighing at least 40 kg), there were no new adveprse reactions identified beyond those observed in the adult population.

l Data (n=3) obtained in children (aged 6 to less than 12 years and weighing at least 15 kg), are too a limited to establish safety in this group. n Reporting of suspiected adverse reactions c Reporting suispected adverse reactions after authorisation of the medicinal product is important. It allows codntinued monitoring of the benefit/risk balance of the medicinal product. Healthcare professeionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V. M

There is no specific treatment for an overdose of sotrovimab. If overdose occurs, the patient should be treated supportively with appropriate monitoring as necessary.

A single 2000 mg dose of sotrovimab (4 times the recommended dose) administered by intravenous infusion over 60 minutes has been evaluated in a clinical trial (N=81) without evidence of dose limiting toxicity.

5.1 Farmakodynamika

d Pharmacotherapeutic group: Immune sera and immunoglobulins, antiviral monoclonal antibodies, ATC code: J06BD05 e s Mechanism of action i r Sotrovimab is a human IgG1 mAb that binds to a conserved epitope on the spike proteoin receptor binding domain of SARS-CoV-2. h t Antiviral activity u Sotrovimab neutralised wild-type SARS-CoV-2 virus in vitro with a half maaximal effective concentration (EC50) of 100.1 ng/mL. r Table 2: Sotrovimab neutralisation data for SARS-CoV-2 variaents

SARS-CoV-2 Variant		Fold Reduction in Susceptibility a g
Lineage	WHO Nomenclature	n Pseudotyped Virus o	Authentic Virus
B.1.1.7	Alpha	Nlo change	No change
B.1.351	Beta	No change o	No change
P.1	Gamma	No change n	No change
B.1.617.2	Delta	No change	No change
AY.1 and AY.2	Delta [+K417N]t	No change	Not tested
AY.4.2	Delta [+] c	No change	Not tested
B.1.427/B.1.429	Epsiloun	No change	Not tested
B.1.526	Iodta	No change	Not tested
B.1.617.1	oKappa	No change	No change
C.37	rLambda	No change	Not tested
B.1.621	p Mu	No change	Not tested
B.1.1.529/BA.1	l Omicron	No change	No change
BA.1.1 a	Omicron	No change	No change
BA.2 n	Omicron	16	15.7
i BA.2.12.1 c	Omicron	16.6	25.1
BA.2i.75	Omicron	8.3	15.6
BAd.2.75.2	Omicron	10	Not tested
eBA.2.86c	Omicron	100	Not determined
M BA.3	Omicron	7.3	Not tested
BA.4	Omicron	21.3	48.4
BA.4.6	Omicron	57.9	115
BA.5	Omicron	22.6	21.6
BF.7	Omicron	74.2	Not tested
BN.1c	Omicron	778	Not tested
BQ.1	Omicron	28.5	Not tested

BQ.1.1 Omicron
BR.2 Omicron
CH.1.1 Omicron
EG.5.1 Omicron
FL.1.5.1 Omicron
HK.3 Omicron
HV.1 Omicron
JN.1c Omicron
XBB.1 Omicron
XBB.1.5 Omicron
XBB.1.5.10 Omicron
XBB.1.16 Omicron
XBB.1.16.1 Omicron
XBB.1.16.6 Omicron
XBB.2.3 Omicron
XBF Omicron
XD Noneb

94 31.2 10.2 Not tested 12.4 57.3 Not tested 9.5

7.5 No change d 8.4 Not tested e 6.4 Not tested s 252 Not tested i r 6.5 Not tested o 11.3 33.3 h 7.6 Not tested t 6.9 10.6 u 7.3 Not tested a 6.2 Not tested r 5.7 No change e 9.4 Not tested g Not tested No change a Based on EC50 fold change compared to wild-type. No channge: ≤5-fold change in EC50 compared to wild-type. o b Variant has not been named by the WHO. l c The BA.2.86, BN.1 and JN.1 variants contain the K356T substitution. o Antiviral resistance n

Cell culture studies: No viral breakthrough was observed when virus was passaged for 10 passages t (34 days) in the presence of fixed concentration of antibody at the lowest concentration tested (~10x c

EC50). Forcing the emergence of resistance variants through an increasing concentration selection u

method identified E340A as a sotrovimab mAb resistance mutant (MARM). An E340A substitution emerged in cell culture selection of dresistant virus and had a >100-fold reduction in activity in a pseudotyped virus-like particle (VLP) assay. o r Table 3 shows the activity data for sotrovimab against epitope sequence polymorphisms evaluated in p pseudotyped VLP assessments in cell culture using the Wuhan-Hu-1 and Omicron BA.1, BA.2 and BA.5 spike proteins. l a Table 3 Sotrovimab pseudotyped VLP assessments in cell culture against epitope substitutions

	n i	Fold Reduction in Susceptibilitya
Reference c position i	Substitution	Wuhan-Hu 1	Omicron BA.1	Omicron BA.2	Omicron BA.5
337 d e M	P337A	No change	-	-	>133
	P337H	5.13	>631	>117	>120
	P337K	>304	-	-	-
	P337L	>192	-	-	-
	P337N	5.57	-	>143	>135
	P337Q	24.9	-	-	-
	P337R	>192	-	-	-
	P337S	No change	>609	>117	>152
	P337T	10.62	-	>117	>120
340	E340A	>100	-	-	-
	E340D	No change	>609	>117	>91.4
	E340G	18.21	-	>117	>91.4

E340I >190 - - - E340K >297 - - - E340L >1696 - - - E340N >1696 - - - E340Q >50 - - - E340R >1696 - - - d E340S 68 - - - e E340V >200 - - - 341 V341F No change 5.89 - 5.83s i 345 T345P 225 - - - r 356 K356A No change - >129 >60.3 o K356E No change - - >51.8 h K356M No change - >132 >86.1 K356N No change - >101 t >86.1 K356Q No change - 70.2 u >86.1 K356R No change - 22a >69 K356S No change - >143 >86.1 K356T 5.90 >631 r>117 >91.4 440 Nb/Kc440D No change - e 5.13 No change 441 L441N 72 - - - g L441R No change - No change 5.88 a n Based on EC50 fold change relative to each spike viral variant. No change: ≤5-fold change; –: depicts not tested. o b Wuhan-Hu-1 strain l c Omicron lineages o Clinical studies: SARS-CoV-2 viruses with basenline and treatment-emergent substitutions at amino acid positions associated with reduced susceptibility to sotrovimab in vitro were observed in patients enrolled in clinical studies who received a 50t0 mg intravenous infusion of sotrovimab (Table 4). In the COMET-ICE and COMET-TAIL studies,camong patients who were treated with a 500 mg intravenous infusion of sotrovimab and had a substitution detected at amino acid positions 337 and/or 340 at any u visit baseline or post-baseline, 1 of 32 and none of 33 patients, respectively, met the primary endpoint for progression to hospitalisation fodr >24 hours for acute management of any illness or death from any cause through Day 29. This singloe patient had E340K detected post-baseline and was infected with the Epsilon variant of SARS-CoV-2. r p l a n i c i d e

M

Table 4. Baseline and treatment-emergent substitutions detected in sotrovimab-treated patients at amino acid positions associated with reduced susceptibility to sotrovimab

Clinical Study	Baselinea		Treatment-Emergentb
	Substitutions	Frequency, % (n/N)	Substitutions	Frequency, d % (n/N) e
COMET-ICE	P337H, E340A	1.3 (4/307)	P337L/R, E340A/K/V	14.1 (24/17s0) i r
COMET-TAIL	P337S, E340STOP	0.6 (2/310)	P337L, E340A/K/V	19.5 o(31/159) h
COMET-PEAK	P337H	0.8 (1/130)	P337L, E340A/K/V u	t13.5 (15/111)
LUNARc	E340D/Q, K356T	4.6 (9/195)	P337A/H/L/R/S, a E340A/D/G/K/Q/V, K356M/R/T r	29.5 (46/156)

a n = number of sotrovimab-treated patients with a baseline substituetion detected at spike amino acid positions 337 or 340. Spike position 356 was also included for the LUNAR study which enrolled g patients with Omicron BA.2, BA.4 or BA.5 lineage SARS-CoV-2 variants; N = total number of sotrovimab-treated patients with baseline sequence results. n b n = number of sotrovimab-treated patients with treatment-emergent substitutions detected at spike o amino acid positions 337 or 340. Spike position 356 was also included for the LUNAR study which l enrolled patients with Omicron BA.2, BA.4 or BA.5 lineage variants; N = total number of sotrovimab treated patients with paired baseline and post-baselione sequence results. c A multicentre, single arm, prospective, genomic surveillance study that followed non-hospitalised n immunocompromised patients who received 500 mg intravenous infusion of sotrovimab.

t Immunogenicity c u Treatment-emergent anti-drug antibodies (ADAs) to a single 500 mg intravenous infusion of sotrovimab were detected in 9% (10d1/1101) of participants, in controlled clinical studies with follow up durations of 18-36 weeks. No participants with confirmed treatment-emergent ADAs had o neutralising antibodies against sotrovimab, and there was no evidence of an association of ADA with r any impact on the safety, efficacy, or pharmacokinetics after a single intravenous infusion. p Clinical efficacy l a Study 214367 (COMET-ICE) was a Phase II/III randomised, double-blind, placebo-controlled study which evaluated sontrovimab as treatment for COVID-19 in non-hospitalised, non-vaccinated adult patients who didinot require any form of oxygen supplementation at study entry. The study included c patients with symptoms for ≤ 5 days and laboratory confirmed SARS-CoV-2 infection and was i conducted when the wild-type Wuhan-Hu-1 virus was predominant, with the highest frequency of d variants being Alpha and Epsilon. Eligible patients had at least 1 of the following: diabetes, obesity (BMI>e30), chronic kidney disease, congestive heart failure, chronic obstructive pulmonary disease, or moderate to severe asthma, or were aged 55 years and older. M

Patients were randomised to a single 500 mg infusion of sotrovimab (N=528) or placebo (N=529) over 1 hour. In the Intent to Treat (ITT) population at Day 29, 46% were male and the median age was 53 years (range: 17-96), with 20% aged 65 years or older and 11% over 70 years. Treatment was given within 3 days of COVID-19 symptom onset in 59% and 41% were treated within 4-5 days. The four most common pre-defined risk factors or comorbidities were obesity (63%), 55 years of age or older (47%), diabetes requiring medicine (22%) and moderate to severe asthma (17%).

The adjusted relative risk reduction in hospitalisation or death by Day 29 in the ITT population was 79% (95% CI: 50%, 91%). The difference was driven by rates of hospitalisation, with no deaths in the sotrovimab arm and two deaths in the placebo arm up to Day 29. No patients in the sotrovimab arm, versus 14 in the placebo arm, required high flow oxygen or mechanical ventilation up to Day 29.

d Table 5: Results of primary and secondary endpoints in the ITT population (COMET-ICE)

	Sotrovimab (500 mg IV infusion) N=528	Placebo e s N=529 i
Primary endpoint r
Progression of COVID-19 as defined by hospitalisation for >24 hours for acute o management of any illness or death from any cause (day 29) h
Proportion (n, %) a	6 (1%)	30 (6%) t
Adjusted relative risk reduction (95% CI)	79% u (50%, 91%) a
p-value	<0.001
Secondary endpoint r
Progression to develop severe and/or critical respiratory COVID-19 (day 29) b e
Proportion (n, %)	7 (1%)	28 (5%)
Adjusted relative risk reduction (95% Cl)	7g4% (4n1%, 88%)
p-value	0.002 o
a No participants required intensive care unit (ICU) stay in the sotrovimab arm versus 9 l participants in the placebo arm. b Progression to develop severe and/or critical respoiratory COVID-19 defined as the requirement for supplemental oxygen (low flow nasal cannulae/face mask, high flow n oxygen, non-invasive ventilation, mechanical ventilation or extracorporeal membrane oxygenation [ECMO]). t

c Paediatric population u The European Medicines Agency hads deferred the obligation to submit the results of studies with Xevudy in one or more subsets of the paediatric population in the treatment of COVID-19 (see section o 4.2 for information on paediatric use). r

5.2 Farmakokinetyka

l Absorption a Based on populatinon pharmacokinetic analyses, following a 15 minute to 1 hour intravenous infusion of 500 mg, the geiometric mean Cmax was 170 µg/mL (N = 1188, CVb% 53.4), and the geometric mean Day 28 concenctration was 39.7 µg/mL (N = 1188, CVb% 37.6). i Distributidon e Based on population pharmacokinetic analysis, the geometric mean steady-state volume of distribution M was 7.9 L.

Biotransformation

Sotrovimab is degraded by proteolytic enzymes which are widely distributed in the body.

Elimination

Based on population pharmacokinetic analysis, the mean systemic clearance (CL) was 95 mL/day, with a median terminal half-life of approximately 61 days.

Special populations

Elderly patients d Based on population pharmacokinetic analyses, there was no difference in sotrovimab pharmacokinetics in elderly patients. e s Renal impairment i Sotrovimab is too large to be excreted renally, thus renal impairment is not expected to hrave any effect on elimination. Furthermore, based on population pharmacokinetic analyses there wasono difference in sotrovimab pharmacokinetics in patients with mild or moderate renal impairment. h t Hepatic impairment Sotrovimab is degraded by widely distributed proteolytic enzymes, not restricuted to hepatic tissue, therefore changes in hepatic function are not expected to have any effect on elimination. Furthermore, a based on population pharmacokinetic analyses there was no difference in sotrovimab pharmacokinetics in patients with mild to moderate elevations in alanirne aminotransferase (1.25 to < 5 x ULN). e g Paediatric population Limited data on the pharmacokinetics of sotrovimab in patiennts aged less than 18 years, has been obtained from the COMET-TAIL study (see section 4.8) and the COMET-PACE study. The COMET o PACE study is an open-label, non-conparator paediatric study, that was terminated prior to completion l of recruitment. The recommended dose for adolescents aged from 12 years and from 40 kg body weight was based on an allometric scaling approacho, which accounted for effect of body weight changes associated with age on clearance and volume of distribution. This approach is supported by a n population pharmacokinetic analysis, which shows comparable serum exposures of sotrovimab in adolescents as those observed in adults. Following intravenous infusion of 500 mg sotrovimab in 7 t adolescents, the geometric mean Cmax was 180 µg/mL (geometric CV% 25.6) and the geometric mean c Day 29 concentration was 47.4 µg/mL (geometric CV% 17.0). u

Data (n=3) in children (aged 6 to lesds than 12 years and weighing at least 15 kg), are too limited to establish pharmacokinetics of sotrovimab in this age group. o r Other special populations p Based on population pharmacokinetic analyses, the pharmacokinetics of sotrovimab following intravenous infusion were not affected by age, sex or BMI. No dose adjustment is warranted based on l these characteristics. Body weight was a significant covariate, but the magnitude of effect does not a warrant dose adjustment. n i

5.3 Przedkliniczne dane o bezpieczeństwie

c i Carcinogenesis/mutagenesis d e Genotoxicity and carcinogenicity studies have not been conducted with sotrovimab. M Reproductive toxicology

Nonclinical reproductive and developmental toxicity studies have not been conducted with sotrovimab.

Animal toxicology and pharmacology

No toxicity with sotrovimab was identified in a cynomolgus monkey 2-week repeat-dose IV infusion toxicology study with 105-day recovery period at doses up to 500 mg/kg, the no observed adverse effect level (NOAEL) and highest dose tested. The Cmax and total exposure AUC [sum of AUC0-168h after Dose 1 and AUC0-last after Dose 2 (Day 8)] values at the NOAEL of 500 mg/kg were 13500 µg/mL and 216000 day*µg/mL, respectively.

d

6. PHARMACEUTICAL PARTICULARS e

s

6.1 Substancje pomocnicze

i r Histidine o Histidine monohydrochloride h Sucrose t Polysorbate 80 (E 433) Methionine u Water for injections a

6.2 Niezgodności farmaceutyczne

e This medicinal product must not be mixed with other medicinal products except those mentioned in g section 6.6. n

6.3 Okres ważności

o l Unopened vial o 4 years. n Diluted solution for infusion t c The diluted solution is intended to be used immediately. If after dilution, immediate administration is not possible, the diluted solution may bue stored at room temperature (up to 25°C) for up to 6 hours or refrigerated (2°C to 8°C) for up to 24 hours from the time of dilution until the end of administration. d o

6.4 Specjalne środki ostrożności podczas przechowywania

r Store in a refrigerator (2°C pto 8°C). Do not freeze. Store in the original cartlon in order to protect from light. For storage conditionas after dilution of the medicinal product, see section 6.3. n

6.5 Rodzaj i zawartość opakowania

i c 10 mL TypeiI borosilicate clear glass single-use vial, with a grey chlorobutyl elastomer stopper laminateddwith fluoropolymer, sealed with an aluminium flip-off cap. e Pack size: 1 vial. M

6.6 Specjalne środki ostrożności dotyczące usuwania

Treatment should be prepared by a qualified healthcare professional using aseptic technique.

Preparation for dilution

1. Remove one vial of sotrovimab from the refrigerator (2°C to 8°C). Allow the vial to

equilibrate to ambient room temperature, protected from light, for approximately 15 minutes.

2. Visually inspect the vial to ensure it is free from particulate matter and that there is no visible

damage to the vial. If the vial is identified to be unusable, discard and restart the preparation with a new vial.

3. Gently swirl the vial several times before use without creating air bubbles. Do not shake or

vigorously agitate the vial.

d Dilution instructions e

1. Withdraw and discard 8 mL from an infusion bag containing 50 mL or 100 mL of sodium

s chloride 9 mg/mL (0.9%) solution for infusion or 5% glucose for infusion. i

2. Withdraw 8 mL from the vial of sotrovimab. r

3. Inject the 8 mL of sotrovimab into the infusion bag via the septum. o

4. Discard any unused portion left in the vial. The vial is single-use only and should only be used

h for one patient. t

5. Prior to the infusion, gently rock the infusion bag back and forth 3 to 5 times. Do not invert

the infusion bag. Avoid forming air bubbles. u a Disposal r Any unused medicinal product or waste material should be disposed of in accordance with local e requirements. g n

7. Podmiot odpowiedzialny

o l GlaxoSmithKline Trading Services Limited

12 Riverwalk

o Citywest Business Campus n Dublin 24 D24 YK11 t Ireland c u

8. Numer pozwolenia

d o EU/1/21/1562/001 r p

9. Data wydania lub przedłużenia pozwolenia

l Date of first authorisaation: 17 December 2021 n i

10. DATE cOF REVISION OF THE TEXT

i Detailed idnformation on this medicinal product is available on the website of the European Medicines Agency https://www.ema.europa.eu. e

M d e s i r o h t u a r e g ANNEX II n o A. MANUFACTURERS OF THE BIOLOGICAL ACTIVE l SUBSTANCE AND MANUFACTURER RESPONSIBLE FOR BATCH RELEASE o n B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE t c C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUuTHORISATION d D. CONDITIONS OR RESTRICTIONS WITH REGARD TO o THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCTr p l a n i c i d e

M

A. MANUFACTURERS OF THE BIOLOGICAL ACTIVE SUBSTANCE AND MANUFACTURER RESPONSIBLE FOR BATCH RELEASE

Name and address of the manufacturers of the biological active substance

WuXi Biologics Co., Ltd., d 108 Meiliang Road, Mashan, Binhu District, e WuXi, Jiangsu, 214092, s China i r Or o h Samsung Biologics Co., Ltd., t 300 Songdo bio-daero, Yeonsu-gu Incheon 21987, u Republic of Korea a

Name and address of the manufacturer responsible for batch release r e GlaxoSmithKline Manufacturing S.p.A. g Strada Provinciale Asolana, 90,

43056 San Polo di Torrile, Parma, n

Italy o l

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE o n Medicinal product subject to medical prescription.

t c C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION u d

• Periodic safety update reports (PSURs) o The requirements for submissiron of PSURs for this medicinal product are set out in the list of Union reference dates (EURpD list) provided for under Article 107c(7) of Directive 2001/83/EC and any subsequent updates published on the European medicines web-portal. l The marketing authoraisation holder (MAH) shall submit the first PSUR for this product within 6 months followinng authorisation. i c D. CONDiITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFdFECTIVE USE OF THE MEDICINAL PRODUCT e
• Risk management plan (RMP) M The marketing authorisation holder (MAH) shall perform the required pharmacovigilance activities and interventions detailed in the agreed RMP presented in Module 1.8.2 of the marketing authorisation and any agreed subsequent updates of the RMP.

An updated RMP should be submitted:

• At the request of the European Medicines Agency;

• Whenever the risk management system is modified, especially as the result of new information being received that may lead to a significant change to the benefit/risk profile or as the result of an important (pharmacovigilance or risk minimisation) milestone being reached.

d e s i r o h t u a r e g n o l o n t c u d o r p l a n i c i d e

M d e s i r o h t u a r e g ANNEX III n o LABELLING AND PACKAGE LEAFLET l o n t c u d o r p l a n i c i d e

M d e s i r o h t u a r e g A. LABELLING n o l o n t c u d o r p l a n i c i d e

M

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

VIAL CARTON

1. NAME OF THE MEDICINAL PRODUCT d e Xevudy 500 mg concentrate for solution for infusion sotrovimab s i r o 2. STATEMENT OF ACTIVE SUBSTANCE h Each vial contains 500 mg sotrovimab in 8 mL (62.5 mg/mL). t u a 3. LIST OF EXCIPIENTS r Also contains: histidine, histidine monohydrochloride, sucrose, polysorbate 80 (E 433), methionine, e water for injections. g n 4. PHARMACEUTICAL FORM AND CONTENTS o l Concentrate for solution for infusion o 1 vial. n t 5. METHOD AND ROUTE OF ADMINISTRATION c u For intravenous use after dilution Read the package leaflet before use.d o Press here to open r p

2. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT

l OF THE SIGHT AND REACH OF CHILDREN a n Keep out of the sight and reach of children. i c i 7. OTHER SPECIAL WARNING(S), IF NECESSARY d e

8. MEXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

Store in a refrigerator. Do not freeze.

Store in the original carton in order to protect from light.

10. Data zatwierdzenia lub aktualizacji tekstu

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE d e 11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDERs i r GlaxoSmithKline Trading Services Limited o

12 Riverwalk

Citywest Business Campus h Dublin 24 t D24 YK11 u Ireland a r 12. MARKETING AUTHORISATION NUMBER(S) e EU/1/21/1562/001 g n o 13. BATCH NUMBER l

Lot o n

14. GENERAL CLASSIFICATION FOR SUPPLY t c u 15. INSTRUCTIONS ON USE d o 16. INFORMATION IN BrRAILLE p Justification for not including Braille accepted. l a 17. UNIQUE IDENTIFIER – 2D BARCODE n i 2D barcode cacrrying the unique identifier included. i d 18. UNIQUE IDENTIFIER - HUMAN READABLE DATA e

PCM SN NN

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS

VIAL LABEL

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE OF ADMINISTRATION d e Xevudy 500 mg sterile concentrate sotrovimab s IV i r o 2. METHOD OF ADMINISTRATION h t IV use u a

2. EXPIRY DATE r e EXP g n 4. BATCH NUMBER o l Lot o n 5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT t c u 6. OTHER d o r p l a n i c i d e

M d e s i r o h t u a r e g B. PACKAGE LEAFLnET o l o n t c u d o r p l a n i c i d e

M

Package leaflet: Information for the patient

Xevudy 500 mg concentrate for solution for infusion sotrovimab

This medicine is subject to additional monitoring. This will allow quick identification of new d safety information. You can help by reporting any side effects, you may get. See the end of section 4 for how to report side effects. e s Read all of this leaflet carefully before you receive this medicine. i

• Keep this leaflet. You may need to read it again. r
• If you have any questions, ask your doctor or pharmacist. o
• If you get any side effects, talk to your doctor. This includes any possible side effects not listed h in this leaflet. See section 4. t u What is in this leaflet a

1. What Xevudy is and what it is used for

2. What you need to know before you are given Xevudy r

3. How Xevudy is given e

4. Possible side effects

g

5. How to store Xevudy

6. Contents of the pack and other information n

o l

1. What Xevudy is and what it is used for

o Xevudy contains the active substance sotrovimab. Sotrovimab is a monoclonal antibody, a type of n protein designed to recognise a specific target on the SARS-CoV-2 virus, the virus that causes COVID-19. t c Xevudy is used to treat COVID-19 in adults and adolescents (from 12 years and weighing at least u 40 kg). It targets the spike protein that the virus uses to attach to cells, blocking the virus from entering the cell and making new viruses. Bydpreventing the virus from multiplying in the body, Xevudy can help your body overcome the infection and prevent you from getting seriously ill. o r

2. What you need to knpow before you are given Xevudy

l You must not receive Xevudy a

• if you are allergic to sotrovimab or any of the other ingredients of this medicine (listed in section 6). n ➔ Checkiwith your doctor if you think this applies to you. c i Warnings and precautions d Allergeic reactions Xevudy can cause allergic reactions. M ➔ See ‘Allergic reactions’ in Section 4.

Infusion-related reactions Xevudy can cause infusion-related reactions. ➔ See ‘Infusion-related reactions’ in Section 4.

Children and adolescents Xevudy should not be given to children or adolescents younger than 12 years old or weighing less than 40 kg.

Other medicines and Xevudy Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

Pregnancy and breast-feeding d If you are pregnant, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before receiving Xevudy. Your doctor will advise you whether the benefits of treatmeent with Xevudy are greater than any likely risks for you and your baby. s i It is not known whether the ingredients of Xevudy can pass into breast milk. If you arer breast-feeding, you must check with your doctor before you receive Xevudy. o h Driving and using machines t Xevudy is not expected to have any effect on your ability to drive or use macuhines. a Xevudy contains polysorbate r This medicine contains 4.8 mg of polysorbate 80 in each 500 mg dose. Polysorbates may cause e allergic reactions. Tell your doctor if you have any known allergies. g n

3. How Xevudy is given

o l The recommended dose for adults and adolescents (aged 12 years and older and weighing at least 40 kg) is: o

• 500 mg (one vial) n

The medicine will be made up into a solution and given to you by a drip (infusion) into a vein by a t doctor or nurse. It takes up to 30 minutes to give you the full dose of medicine. You will be monitored c during and for at least 1 hour after your treatment is given. u The ‘Instructions for healthcare profdessionals’ below give details for your doctor, pharmacist or nurse on how the Xevudy infusion is made up and given. o r

4. Possible side effectsp

l Like all medicines, this medicine can cause side effects, although not everybody gets them. a Allergic reactionsn i Allergic reacticons to Xevudy are common, affecting up to 1 in 10 people. Rarely, theseiallergic reactions may be severe (anaphylaxis), affecting up to 1 in 1,000 people (rare). If you havde any of the following symptoms after receiving Xevudy you may be having an allergic reactioen and should get medical help immediately:

• skin rash, similar to nettle rash (hives) or redness M
• itching
• swelling, sometimes of the face or mouth (angioedema)
• becoming very wheezy, coughing or having difficulty in breathing
• suddenly feeling weak or light-headed (may lead to loss of consciousness or falls).

Infusion-related reactions

Allergic-like reactions when you receive an infusion are common, affecting up to 1 in 10 people. These usually develop within minutes or hours but may develop up to 24 hours after treatment or later. Possible symptoms are presented below. If you get any of the following symptoms after receiving Xevudy, you may be having an infusion-related reaction and should get medical help immediately:

• flushing
• chills d
• fever e
• difficulty in breathing s
• rapid heartbeat i
• drop in blood pressure r o Other side effects h Uncommon (may affect up to 1 in 100 people) t
• shortness of breath (dyspnoea). u a Reporting of side effects If you get any side effects, talk to your doctor or nurse. This includes arny possible side effects not listed in this leaflet. You can also report side effects directly via theenational reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this g medicine. n o

5. How to store Xevudy l

The healthcare professionals caring for you are respoonsible for storing this medicine and disposing of any unused product correctly. n

Keep this medicine out of the sight and reach of children. t c Do not use this medicine after the expiry date which is stated on the label and carton after EXP. The u expiry date refers to the last day of that month. d Do not freeze. o r Before diluting: p

• store in a refrigerator (2°C – 8°C).
• store in the original carton in order to protect from light. l a Once diluted, this nmedicine is intended to be used immediately. If after dilution, immediate administration isinot possible, the diluted solution may be stored at room temperature (up to 25°C) for up to 6 hours ocr refrigerated (2°C – 8°C) for up to 24 hours from the time of dilution until the end of administratioin. d e

6. Contents of the pack and other information

M What Xevudy contains

• The active substance is sotrovimab. Each vial contains 500 mg of sotrovimab in 8 mL concentrate.
• The other ingredients are histidine, histidine monohydrochloride, sucrose, polysorbate 80 (E 433) (see Section 2 “Xevudy contains polysorbate”), methionine and water for injections.

What Xevudy looks like and contents of the pack

Xevudy is a clear, colourless or yellow to brown liquid supplied in a single-use glass vial with a rubber stopper and flip-off aluminium over-seal. Each carton contains one vial.

Marketing Authorisation Holder GlaxoSmithKline Trading Services Limited

12 Riverwalk

d Citywest Business Campus Dublin 24 e D24 YK11 s Ireland i r Manufacturer o GlaxoSmithKline Manufacturing S.p.A. h Strada Provinciale Asolana, 90, t

43056 San Polo di Torrile, Parma

Italy u a For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder: r e

België/Belgique/Belgien GlaxoSmithKline Pharmaceuticals s.a./n.v. Tél/Tel: + 32 (0) 10 85 52 00	Lietuva GlaxoSmgithKline Trading Services Limited Tel: +n370 80000334 o l
България GlaxoSmithKline Trading Services Limited o Teл.: + 359 80018205 n t	Luxembourg/Luxemburg GlaxoSmithKline Pharmaceuticals s.a./n.v. Belgique/Belgien Tél/Tel: + 32 (0) 10 85 52 00
Česká republika c GlaxoSmithKline, s.r.o. Tel: + 420 222 001 111 u [email protected] d	Magyarország GlaxoSmithKline Trading Services Limited. Tel: + 36 80088309
Danmark o GlaxoSmithKline Pharma Ar/S Tlf.: + 45 36 35 91 00 p [email protected] l	Malta GlaxoSmithKline Trading Services Limited. Tel: + 356 80065004
Deutschland a GlaxoSmithKlinne GmbH & Co. KG Tel.: + 49 (0)8i9 36044 8701 [email protected]	Nederland GlaxoSmithKline BV Tel: + 31 (0)33 2081100
iEesti dGlaxoSmithKline Trading Services Limited.eTel: + 372 8002640M	Norge GlaxoSmithKline AS Tlf: + 47 22 70 20 00
Ελλάδα GlaxoSmithKline Μονοπρόσωπη A.E.B.E. Τηλ: + 30 210 68 82 100	Österreich GlaxoSmithKline Pharma GmbH Tel: + 43 (0)1 97075 0 [email protected]
España GlaxoSmithKline, S.A.	Polska GSK Services Sp. z o.o.
Tel: + 34 900 202 700 [email protected]	Tel.: + 48 (0)22 576 9000
France Laboratoire GlaxoSmithKline Tél: + 33 (0)1 39 17 84 44 [email protected]	Portugal GlaxoSmithKline – Produtos Farmacêuticos, Lda. Tel: + 351 21 412 95 00 [email protected] d e
Hrvatska GlaxoSmithKline Trading Services Limited Tel: +385 800787089 Ireland GlaxoSmithKline (Ireland) Limited Tel: + 353 (0)1 4955000	România s GlaxoSmithKline Trading ServicesiLimited Tel: + 40800672524 r o Slovenija h GlaxoSmithKline Trading Services Limited Tel: + 386 80688869 t u
Ísland Vistor ehf. Sími: + 354 535 7000	aSlovenská republikaGlaxoSmithKlirne Trading Services LimitedTel: + 421 800500589eg
Italia GlaxoSmithKline S.p.A. Tel: + 39 (0)45 7741111 o	Suomni/Finland GlaxoSmithKline Oy o Puh/Tel: + 358 (0)10 30 30 30 l
Κύπρος GlaxoSmithKline Trading Services Limited n Τηλ: + 357 80070017 t c	Sverige GlaxoSmithKline AB Tel: + 46 (0)8 638 93 00 [email protected]
Latvija u GlaxoSmithKline Trading Services Limited d Tel: + 371 80205045 o

r This leaflet was last revisepd in

Other sources of informlation a Detailed informatinon on this medicine is available on the European Medicines Agency website: https://www.ema.europa.eu. i c ----------------i------------------------------------------------------------------------------------------------------- d The following information is intended for healthcare professionals only. e Please refer to the Summary of Product Characteristics for further information. M Treatment should be prepared by a qualified healthcare professional using aseptic technique.

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.

Preparation for dilution

1. Remove one vial of sotrovimab from the refrigerator (2°C to 8°C). Allow the vial to equilibrate

to ambient room temperature, protected from light, for approximately 15 minutes.

2. Visually inspect the vial to ensure it is free from particulate matter and that there is no visible

damage to the vial. If the vial is identified to be unusable, discard and restart the preparation with a new vial.

3. Gently swirl the vial several times before use without creating air bubbles. Do not shake or

d vigorously agitate the vial. e Dilution instructions s

1. Withdraw and discard 8 mL from an infusion bag containing 50 mL or 100 mL of sodium

i chloride 9 mg/mL (0.9%) solution for infusion or 5% glucose for infusion. r

2. Withdraw 8 mL from the vial of sotrovimab. o

3. Inject the 8 mL of sotrovimab into the infusion bag via the septum.

h

4. Discard any unused portion left in the vial. The vial is single-use only and should only be used

t for one patient.

5. Prior to the infusion, gently rock the infusion bag back and forth 3 to 5utimes. Do not invert the

infusion bag. Avoid forming air bubbles. a The diluted solution of sotrovimab is intended to be used immediately. If after dilution, immediate administration is not possible, the diluted solution may be stored at roorm temperature (up to 25°C) for up to 6 hours or refrigerated (2°C to 8°C) up to 24 hours from the time of dilution until the end of e administration. g Administration instructions n

1. Attach an infusion set to the infusion bag using standard bore tubing. The intravenous dosing

o solution is recommended to be administered with a 0.2-μm in-line filter. l

2. Prime the infusion set.

3. Administer as an intravenous infusion over 15 minutes (when using a 50 mL infusion bag) or

o over 30 minutes (when using a 100 mL infusion bag) at room temperature. n Disposal t c Any unused medicinal product or waste material should be disposed of in accordance with local requirements. u d o r p l a n i c i d e

M