RYSTIGGO 140mg / ml injectible solution medication leaflet

Rystiggo 140 mg/ml solution for injection

Each ml of solution for injection contains 140 mg of rozanolixizumab.

One vial of 2 ml contains 280 mg of rozanolixizumab.

One vial of 3 ml contains 420 mg of rozanolixizumab.

One vial of 4 ml contains 560 mg of rozanolixizumab.

One vial of 6 ml contains 840 mg of rozanolixizumab.

Rozanolixizumab is a recombinant, humanised anti-neonatal Fc receptor (FcRn) immunoglobulin G4P (IgG4P) monoclonal antibody produced in Chinese Hamster Ovary (CHO) by recombinant DNAtechnology.

Each ml of solution for injection contains 29 mg proline, see section 4.4.

Each ml of solution for injection contains 0.3 mg polysorbate 80, see section 4.4.

For the full list of excipients, see section 6.1.

Solution for injection (injection)

Colourless to pale brownish-yellow, clear to slightly opalescent solution, pH 5.6.

Rystiggo has an osmolality of 309-371 mOsmol/kg.

Rystiggo is indicated as an add-on to standard therapy for the treatment of generalised myastheniagravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) or anti-muscle-specifictyrosine kinase (MuSK) antibody positive.

Treatment should be initiated and supervised by specialist healthcare professionals experienced in themanagement of patients with neuromuscular or neuro-inflammatory disorders.

A treatment cycle consists of 1 dose per week for 6 weeks.

The following table indicates the recommended total weekly dose of rozanolixizumab according to thepatient’s body weight. One or more vials might be needed to meet the appropriate volume to beadministered, depending on vial size availability.

Body weight ≥ 35 to <50 kg ≥ 50 to < 70 kg ≥ 70 to < 100 kg ≥ 100 kg

Weekly dose (mg) 280 mg 420 mg 560 mg 840 mg

Weekly dose (ml) 2 ml* 3 ml* 4 ml* 6 ml*

* One ml of solution for injection contains 140 mg of rozanolixizumab. Each vial contains excess volume for priming of theinfusion line, see “Instructions For Use in the Package leaflet”.

Subsequent treatment cycles should be administered according to clinical evaluation. The frequency oftreatment cycles may vary by patient. In the clinical development program, most patients hadtreatment-free intervals of 4-13 weeks between cycles. From cycle to cycle approximately 10 % ofpatients had a treatment-free interval of less than 4 weeks.

If a scheduled infusion is missed, rozanolixizumab may be administered up to 4 days after thescheduled time point. Thereafter, the original dosing schedule should be resumed until the treatmentcycle is completed.

No dose adjustment is required (see section 5.2).

Limited safety and efficacy data is available in patients with mild to moderate renal impairment(eGFR > 45 ml/min/1.73 m2). No data is available in patients with severe renal impairment. No doseadjustment is considered necessary as the pharmacokinetics of rozanolixizumab are unlikely to beaffected by renal impairment (see section 5.2).

No data is available in patients with hepatic impairment. No dose adjustment is considered necessaryas the pharmacokinetics of rozanolixizumab are unlikely to be affected by hepatic impairment (seesection 5.2).

The safety and efficacy of rozanolixizumab in children and adolescents below the age of 18 years havenot been established. No data are available.

For subcutaneous use.

It is recommended that rozanolixizumab is administered subcutaneously preferably into the lower rightor lower left part of the abdomen, below the belly button. Infusions should not be given into areaswhere the skin is tender, erythematous, or indurated.

During administration of the first treatment cycle and administration of the first dose of the secondtreatment cycle of rozanolixizumab, appropriate treatment for injection and hypersensitivity-relatedreactions should be readily available (see section 4.4).

For instructions on material specificities for administration, see below and section 6.6.

Before administering rozanolixizumab, the instructions for use must be read carefully, see section 6.6.

Rystiggo can be administered using:

* An infusion pump (also known as syringe pump), or

* By manual push with a syringe

Rystiggo can be self-administered or administered by a caregiver, following the Instructions for Useafter proper training by a healthcare professional on how to administer subcutaneous infusions.

Infusion with a pump

Infusion pumps, syringes and infusion sets appropriate for subcutaneous administration of medicinalproducts should be used (see section 6.6).

If not using a programmable pump, the volume in the syringe should be adjusted to the prescribeddose prior to administration.

Rozanolixizumab administration using an infusion pump should be performed at a constant flow rateup to 20 ml/hr.

Infusion by manual push with a syringe

Syringes and infusion sets appropriate for subcutaneous administration of medicinal products shouldbe used.

The volume in the syringe should be adjusted to the prescribed dose prior to administration.

Rozanolixizumab administration using a syringe should be performed at a flow rate that is comfortablefor the patient. In clinical trials, infusion times by manual push ranged from 1 to 30 minutes with amedian infusion time of 5 minutes per patient. This range of infusion times may serve as a guide whentraining the patient or caregiver.

Hypersensitivity to the active substance(s) 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.

Myasthenic crisis

Treatment with rozanolixizumab in patients with impending or manifest myasthenic crisis has notbeen studied. The sequence of therapy initiation between established therapies for MG crisis androzanolixizumab, and their potential interactions, should be considered (see section 4.5).

Aseptic meningitis (drug induced aseptic meningitis) has been reported following rozanolixizumabtreatment. If symptoms consistent with aseptic meningitis (headache, pyrexia, neck stiffness, nausea,vomiting) occur, diagnostic workup and treatment should be initiated as per standard of care.

As rozanolixizumab causes transient reduction in IgG levels the risk of infections may increase (seesection 5.1). Upper respiratory tract infections and herpes simplex infections have been observed witha higher dose of rozanolixizumab. Overall, in phase 3 studies in gMG, infections were reported in45.2 % of all rozanolixizumab treated patients. No increase in the incidence of infections wasobserved from cycle to cycle. Serious infections were reported in 4.3 % of patients.

Treatment with rozanolixizumab should not be initiated in patients with a clinically important activeinfection until the infection resolves or is adequately treated. During treatment with rozanolixizumab,clinical signs and symptoms of infections should be monitored. If a clinically important activeinfection occurs, withholding rozanolixizumab until the infection has resolved should be considered.

Infusion reactions such as rash or angioedema may occur (see section 4.8). In the clinical trial, thesewere mild to moderate. Patients should be monitored during treatment with rozanolixizumab and for15 minutes after the administration is complete for clinical signs and symptoms of hypersensitivityreactions. If a hypersensitivity reaction occurs during administration (see section 4.8),rozanolixizumab infusion should be discontinued and appropriate measures should be initiated ifneeded. Once resolved, administration may be resumed.

Immunisation with vaccines during rozanolixizumab therapy has not been studied. The safety ofimmunisation with live or live-attenuated vaccines and the response to immunisation with vaccines areunknown. All vaccines should be administered according to immunisation guidelines and at least4 weeks before initiation of treatment. For patients that are on treatment, vaccination with live orlive-attenuated vaccines is not recommended. For all other vaccines, they should take place at least2 weeks after the last infusion of a treatment cycle and 4 weeks before initiating the next cycle.

In the pooled cyclic treatment data from the phase 3 program, after 1 treatment cycle of6 rozanolixizumab weekly doses, 27.1 % (42/155) of patients developed antidrug antibodies and10.3 % (16/155) had antibodies that were classified as neutralising. Upon reinitiating therapy, theproportion of patients who developed antidrug antibodies and neutralising antibodies increased to65 % (13/20) and 50 % (10/20) respectively, after 5 treatment cycles. Development of neutralisingantibodies was associated with a 24 % decrease in overall plasma exposure of rozanolixizumab. Therewas no apparent impact of immunogenicity on efficacy and safety (see sections 5.1 and 5.2).

This medicinal product contains 29 mg of proline in each ml.

The use in patients suffering from hyperprolinaemia should be restricted to cases where no alternativetreatment is available.

This medicinal product contains 0.3 mg of polysorbate 80 in each ml.

Polysorbates may cause allergic reactions.

No interaction studies have been performed.

As rozanolixizumab interferes with the FcRn recycling mechanism of immunoglobulin G (IgG),the serum concentrations of IgG-based medicinal products (e.g. monoclonal antibodies andintravenous immunoglobulin [IVIg]) and Fc-peptide fusion proteins are expected to be decreased ifadministered concomitantly or within 2 weeks after administration of rozanolixizumab. It isrecommended to initiate these treatments 2 weeks after administration of rozanolixizumab and tomonitor for attenuated efficacy of these medicinal products when administered concomitantly.

Treatment with IV or SC immunoglobulins, PLEX/plasmapheresis and immunoadsorption may reducecirculating levels of rozanolixizumab.

Vaccination during treatment with rozanolixizumab has not been studied and the response to anyvaccine is unknown. Because rozanolixizumab causes a reduction in IgG levels, vaccination withlive-attenuated or live vaccines is not recommended during treatment with rozanolixizumab (seesections 4.4 and 5.3).

There are limited amount of data from the use of rozanolixizumab in pregnant women. In animalstudies, offspring from treated dams had very low levels of IgG at birth, as expected by thepharmacological mode of action of rozanolixizumab (see section 5.3). However, animal studies do notindicate direct or indirect harmful effects with respect to pregnancy, embryonic/foetal development,parturition or postnatal development. Treatment of pregnant women with rozanolixizumab should onlybe considered if the clinical benefit outweighs the risks.

As rozanolixizumab is expected to reduce maternal antibody levels, and is also expected to inhibit thetransfer of maternal antibodies to the foetus, reduction in passive protection to the newborn isanticipated. Therefore, risks and benefits of administering live/live attenuated vaccines to infantsexposed to rozanolixizumab in utero should be considered (see section 4.4, subsection “Vaccination”).

It is unknown whether rozanolixizumab is excreted in human milk. Maternal IgG is known to beexcreted in breast milk during the first days after birth, which is decreasing to low concentrations soonafterwards; consequently, a risk to breast-fed infants cannot be excluded during this short period.

Afterwards, use of rozanolixizumab could be considered during breast-feeding only if the clinicalbenefit outweighs the risks.

The effect of rozanolixizumab on human fertility is not known. Animal studies do not indicate harmfuleffects with respect to fertility (see section 5.3).

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

The most commonly reported adverse reactions were headache (48.4 %), diarrhoea (25.0 %) andpyrexia (12.5 %).

Adverse reactions from clinical studies in gMG are listed in Table 1 below, classified by MedDRA

System Organ Class (SOC). Within each SOC, the adverse reactions are ranked by frequency, with themost frequent reactions first.

Frequency categories are 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 the available data).

Table 1: List of adverse reactions

MedDRA system organ class Adverse reactions Frequency category

Infections and infestations Upper respiratory tract Commoninfections1

Nervous system disorders Headache2 Very common

Aseptic meningitis* Not known

Gastrointestinal disorders Diarrhoea Very common

Skin and subcutaneous tissue Rash3 Commondisorders Angioedema4 Common

Musculoskeletal and Arthralgia Commonconnective tissue disorders

General disorders and Pyrexia Very commonadministration site conditions Injection site reactions5 Common1 Includes cases of nasopharyngitis2 Includes headache and migraine3 Includes rash, rash papular and rash erythematous4 Includes swollen tongue5 Includes injection site rash, reaction, erythema, inflammation, discomfort, and infusion site erythema, pain

*From spontaneous post-marketing reporting

In MG0003, headache was the most common reaction reported in 31 (48.4 %) and 13 (19.4 %) of thepatients treated with rozanolixizumab and placebo, respectively. Headache occurred most frequentlyafter the first infusion of rozanolixizumab and within 1 to 4 days after infusion. Except for 1 (1.6 %)severe headache, all headaches were either mild (28.1 % [n=18]) or moderate (18.8 % [n=12]) andthere was no increase in incidences of headache with repeated cyclic treatment.

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 are no data on symptoms associated with an overdose. Single subcutaneous dose of up to20 mg/kg (2 162 mg) and weekly subcutaneous doses of ≈10 mg/kg (1 120 mg) for up to 52 weekshave been administered per protocol in clinical studies without dose limiting toxicity.

In case of overdose, it is recommended that patients are monitored closely for any adverse reactions,and appropriate supportive measures should be instituted immediately.

Pharmacotherapeutic group: Immunosuppressants, monoclonal antibodies, ATC code: L04AG16

Rozanolixizumab is a humanised IgG4 monoclonal antibody that decreases serum IgG concentrationby inhibiting the binding of IgG to FcRn, a receptor that under physiological conditions protects IgGfrom intracellular degradation and recycles IgG back to the cell surface.

By the same mechanism, rozanolixizumab decreases the concentration of pathogenic IgGautoantibodies associated with gMG. Clinical data with rozanolixizumab have not identified anyclinically relevant impact on levels of albumin, which binds at a different site on FcRn.

In a double-blind placebo-controlled study in gMG patients, weekly subcutaneous administration ofrozanolixizumab at the recommended dose (see section 4.2) resulted in a rapid and sustained reductionin total IgG serum concentrations, with significant lowering of IgG of 45 % compared to baselinewithin 1 week, and a maximum decrease of 73 % at about 3 weeks. After stopping administration, IgGconcentrations recovered towards baseline levels within approximately 8 weeks. Similar changes wereobserved during the subsequent cycles of the study.

The reduction in total IgG by rozanolixizumab in neutralising antibody-positive patients was notdifferent from patients who were antidrug antibody-negative (see section 4.4).

The safety and efficacy of rozanolixizumab was evaluated in patients with gMG in the pivotal phase 3study MG0003. Long-term safety, tolerability and efficacy of rozanolixizumab were evaluated in 2phase 3 open-label extension (OLE) studies, with 1 OLE (MG0007) administering rozanolixizumab as6-week treatment cycles based on clinical needs.

Study MG0003

The study MG0003 evaluated 200 patients for up to 18 weeks where patients were randomised toreceive weight-tiered doses of rozanolixizumab equivalent to approximately (≈) 7 mg/kg(corresponding to the recommended dose; see section 4.2) or a higher dose, or placebo. Treatmentconsisted of 1 dose per week for a period of 6 weeks followed by an 8-week observation period.

In this study, patients had to meet the following main criteria at screening:

* at least 18 years of age, had a bodyweight of at least 35 kg

* diagnosis of gMG and had autoantibodies against AChR or MuSK

* a Myasthenia Gravis Foundation of America (MGFA) Class II to IVa,

* an MG-Activities of Daily Living (MG-ADL, a patient reported outcome [PRO] measure)score of at least 3 (with ≥ 3 points from non-ocular symptoms)

* a Quantitative Myasthenia Gravis (QMG) score of at least 11

* if on gMG therapy, to be kept stable prior to baseline and for the duration of the study (exceptfor cholinesterase inhibitors)

* considered for additional treatment such as IVIg and/or PLEX

Patients were not permitted in the study if they had:

* a serum total IgG level ≤ 5.5 g/l or an absolute neutrophil count < 1 500 cells/mm3

* clinically relevant active infection or serious infections, mycobacterial infections, hepatitis B,hepatitis C, HIV infections

* been treated with PLEX, IVIg 1 month and monoclonal antibodies 3 to 6 months prior tostarting treatment

The primary endpoint was the change from baseline to day 43 in the MG-ADL score. Secondaryefficacy endpoints included a change from baseline to day 43 in MG-C (Myasthenia Gravis

Composite) score and QMG score. Response in this study was defined as an at least 2.0-pointsimprovement in MG-ADL at day 43 compared to the treatment cycle baseline.

In general, patient demographics and baseline disease characteristics were balanced across treatmentgroups. The majority of patients were female (60.5 %), below 65 years of age (75.5 %), were ofpredominantly White (68.0 %) or Asian (10.5 %) race, and presented with MGFA class II or III gMG(96.0 %). The median age at MG diagnosis was 44.0 years, and the median time since diagnosis was5.8 years. There was a lower proportion of male patients in the placebo group (29.9 %) than in therozanolixizumab ≈7 mg/kg dose group (40.9 %). The autoantibody distribution among MG0003patients were 10.5 % anti-MuSK positive, 89.5 % anti-AChR positive. Overall, 95.5 % of patientsreceived at least one MG baseline medication that continued during the study, including 85.5 %receiving acetylcholinesterase inhibitors, as well as 64.0 % receiving corticosteroids, 50.0 % receivingimmunosuppressants, and 35.5 % receiving corticosteroids and immunosuppressants at stable doses.

In the rozanolixizumab and placebo groups, the median MG-ADL total score was 8.0, and the median

QMG total score was 15.0.

Results for the primary and secondary efficacy endpoints are provided in Table 2 below. In total,71.9 % and 31.3 % of patients in the rozanolixizumab and placebo groups, respectively, met MG-ADLresponder criteria.

Table 2: Efficacy outcomes change from baseline to day 43

Placebo Rozanolixizumab(N=67) ≈7 mg/kg(N=66)

MG-ADL

Baseline mean 8.4 8.4

Change from baseline -0.784 (0.488) -3.370 (0.486)

LS mean (SE)

Difference vs placebo -2.58695 % CI for difference -4.091, -1.249

P-value for difference < 0.001

MG-C

Baseline mean 15.6 15.9

Change from baseline -2.029 (0.917) -5.930 (0.916)

LS mean (SE)

Difference vs placebo -3.90195 % CI for difference -6.634, -1.245

P-value for difference < 0.001

QMG

Baseline mean 15.8 15.4

Change from baseline -1.915 (0.682) -5.398 (0.679)

LS mean (SE)

Difference vs placebo -3.48395 % CI for difference -5.614, -1.584

P-value for difference < 0.001≈=approximate dose; CI= confidence interval; N=total number of patients in treatment group;

LS=least square; SE=standard error; MG-ADL=MG-Activities of Daily Living;

MG-C=Myasthenia Gravis Composite score; QMG= Quantitative Myasthenia Gravis;

MG=myasthenia gravis.

For the MuSK+ patients who received rozanolixizumab ≈7 mg/kg and had data available at day 43(n=5), the results were consistent with the overall group.

No rozanolixizumab-treated patients and 3 placebo-treated patients received rescue therapy during thetreatment period. During the course of the observation period, amongst the patients treated with≈7 mg/kg, one patient received rescue therapy and 19 patients rolled over early to an open labelextension study to receive treatment with rozanolixizumab.

In the OLE study MG0007, consistent clinical improvement has been observed followingadministration of subsequent cycles of rozanolixizumab.

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

Rystiggo in one or more subsets of the paediatric population in the treatment of myasthenia gravis (seesection 4.2 for information on paediatric use).

Following subcutaneous administration of rozanolixizumab, peak plasma levels are achieved afterapproximately 2 days. The absolute bioavailability of rozanolixizumab after subcutaneousadministration was about 70 % as estimated by population pharmacokinetic analysis.

The apparent volume of distribution of rozanolixizumab is approximately 7 l estimated by populationpharmacokinetic analysis.

Rozanolixizumab is expected to be degraded into small peptides and amino acids via catabolicpathways in a manner similar to endogenous IgG.

The apparent linear clearance for the free active substance is approximately 0.9 l/day. The half-life ofrozanolixizumab is concentration-dependent and cannot be calculated. Rozanolixizumab plasmaconcentrations are undetectable within one week after dosing.

Rozanolixizumab exhibited nonlinear pharmacokinetics typical for a monoclonal antibody thatundergoes target-mediated drug disposition. At steady-state, maximum plasma concentrations andarea under the concentration time curve (AUC) were predicted to be 3-fold and 4-fold higher atweight-tiered doses of ≈10 mg/kg as compared to ≈7 mg/kg, respectively.

Age, sex, or race

A population pharmacokinetic analysis did not reveal a clinically significant impact of age, sex or raceon the pharmacokinetics of rozanolixizumab.

No dedicated studies have been conducted in patients with renal or hepatic impairment. However,renal or hepatic impairment is not expected to affect the pharmacokinetics of rozanolixizumab. Basedon a population pharmacokinetic analysis, renal function (estimated glomerular filtration rate [eGFR]38-161 ml/min/1.73 m2) or hepatic biochemical and function tests (alanine transaminase [ALT],aspartate transaminase [AST], alkaline phosphatase and bilirubin) had no clinically significant effecton rozanolixizumab apparent linear clearance.

Development of neutralising antibodies was associated with a 24 % decrease in overall plasmaexposure of rozanolixizumab. There was no apparent impact of immunogenicity on efficacy and safety(see section 4.4).

Non-clinical data reveal no special hazard for humans based on conventional studies of repeated dosetoxicity (including safety pharmacology and fertility endpoints) and toxicity to reproduction anddevelopment. Administration to cynomolgus and rhesus monkeys resulted in the expected reduction in

IgG. Vaccination during the treatment phase elicited normal IgM levels and a low IgG response due toaccelerated IgG degradation. However, boost vaccination after rozanolixizumab clearance resulted innormal IgM and IgG response.

The mutagenic potential of rozanolixizumab has not been evaluated; however, monoclonal antibodiesare not expected to alter DNA or chromosomes.

Carcinogenicity studies have not been conducted with rozanolixizumab.

No treatment-related changes were noted in the male and female reproductive organs or male andfemale fertility parameters of sexually mature animals in 26-week repeated dose toxicity study.

Rozanolixizumab had no effects on embryo-foetal and postnatal development. Offspring from treateddams had very low levels of IgG at birth, as expected from the pharmacology. IgG level recovered tocontrol values or greater within 60 days. There was no impact on immune cell number, lymphoidorgan architecture and immune function of the pups of treated mothers as assessed by a T-cell

Dependent Antibody Response (TDAR) assay.

Histidine

Histidine hydrochloride monohydrate

Proline

Polysorbate 80

Water for injections

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

3 years

The chemical and physical in-use stability has been demonstrated for 19 hours at 25 °C. From amicrobiological point of view, unless the method of preparation precludes the risks of microbialcontamination, the product should be used immediately. If not used immediately, in-use storage timesand conditions are the responsibility of the user.

Store in a refrigerator (2 °C - 8 °C).

Do not freeze.

Keep the vial in the outer carton in order to protect from light.

Vial (Type I glass) with a stopper (rubber) sealed with a crimp seal and flip off cap. Pack size of 1vial.

Each single use vial contains 2 ml, 3 ml, 4 ml or 6 ml of solution for injection.

Not all vials may be marketed.

Material specificities

The rozanolixizumab solution for injection can be administered using polypropylene syringes as wellas infusion sets containing polyethylene (PE), polypropylene (PP), low density polyethylene (LDPE),polyester, polyvinyl chloride (PVC without DEHP), polycarbonate (PC), fluorinated ethylenepolypropylene (FEP), urethane/acrylate, polyurethane, meta-acrylonitrile butadiene styrene (MABS),silicone or cyclohexanone. Do not use administration devices labelled as containing di(2-ethylhexyl)phthalate (DEHP).

Each vial is for single use only. Any unused medicinal product or waste material should be disposedof in accordance with local requirements.

Before administering Rystiggo, the instructions for use must be read carefully (for further detailsplease refer to the instructions for use included in the patient information leaflet):

Common instructions for infusion with a pump and manual push

* Allow vials to reach room temperature. This may take a minimum of 30 minutes up to120 minutes. Do not use heating devices.

* Check each vial before using:

- Expiration date: do not use beyond expiration date.

- Colour: the solution should be colourless to pale brownish-yellow, clear to slightlyopalescent. Do not use the vial if the liquid looks cloudy, contains foreign particles, or haschanged colour.

- Cap: do not use if protective cap of the vial is missing or defective.

* Collect all items for the infusion. In addition to the vial unit(s), collect the following, whichare not supplied: syringe (5-10 ml, depending on the prescribed dose), syringe needle (s),transfer needle or vented vial adaptor, alcohol wipe, infusion set, bowl or paper towel, tape ortransparent dressing, infusion pump (if applicable) and sharps container.

* In order to avoid potential interruptions in delivery of Rystiggo, the following criteria shouldbe respected:

o Administration tubing length of 61 cm or shorter is recommended.

An infusion set with a needle of 26 gauge or with a larger diameter should be used.

* Use aseptic technique when preparing and administering this product.

* Use transfer needles with a needle of 18 gauge or with a larger diameter to fill the syringe.

* Extract the entire content of the vial into the syringe. A small amount will remain in the vialand should be discarded.

* For multiple vials, use a fresh needle and repeat previous steps.

* Remove the needle from the syringe and attach the infusion set to the syringe.

* Each vial contains excess volume (to allow priming of the infusion line); therefore, pre-set thepump to deliver the prescribed volume or adjust the volume to be administered by expellingany excess volume.

* Administer immediately after priming the infusion set

* Choose an infusion area: lower right or lower left part of the abdomen, below the belly button.

Never infuse into areas where the skin is tender, bruised, red or hard. Avoid infusing into scarsor stretch marks.

* Clean the infusion site using alcohol wipe. Allow to dry.

* Insert the infusion set needle into the subcutaneous tissue.

* If necessary, use tape or transparent dressing to hold the needle in place.

* When the infusion is complete, do not flush the infusion line as the volume of infusion hasbeen adjusted taking into account the losses in the line.

When Rystiggo is administered through an infusion pump

* Syringe pump occlusion alarm limits must be set to the maximum setting, if applicable.

* Follow the instructions provided with the infusion pump to prepare the pump and primethe infusion line.

UCB Pharma S.A.

Allée de la Recherche 60

B-1070 Bruxelles

Belgium

EU/1/23/1780/001

EU/1/23/1780/002

EU/1/23/1780/003

EU/1/23/1780/004

Date of first authorisation: 05 January 2024

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

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