VYEPTI 100mg 100mg / ml concentrate for solution for infusion medication leaflet

VYEPTI 100 mg concentrate for solution for infusion.

VYEPTI 300 mg concentrate for solution for infusion.

VYEPTI 100 mg concentrate for solution for infusion

Each vial of concentrate contains 100 mg eptinezumab per mL.

VYEPTI 300 mg concentrate for solution for infusion

Each vial of concentrate contains 300 mg eptinezumab per 3 mL.

Eptinezumab is a humanized monoclonal antibody produced in Pichia pastoris yeast cells.

This medicinal product contains 40.5 mg of sorbitol in each mL and 0.15 mg of polysorbate 80 in eachmL.

For the full list of excipients, see section 6.1.

Concentrate for solution for infusion (sterile concentrate).

The concentrate for solution for infusion is clear to slightly opalescent, colourless to brownish-yellowwith a pH of 5.5-6.1 and osmolality of 290-350 mOsm/kg.

VYEPTI is indicated for the prophylaxis of migraine in adults who have at least 4 migraine days permonth.

The treatment should be initiated by a healthcare professional experienced in the diagnosis andtreatment of migraine. The infusion of VYEPTI should be initiated and supervised by a healthcareprofessional.

The recommended dose is 100 mg administered by intravenous infusion every 12 weeks. Somepatients may benefit from a dosage of 300 mg administered by intravenous infusion every 12 weeks(see section 5.1).

The need for dose escalation should be assessed within 12 weeks after initiation of the treatment.

When switching dosage, the first dose of the new regimen should be given on the next scheduleddosing date.

Overall benefit and continuation of treatment should be assessed 6 months after initiation of thetreatment. Any further decision to continue the treatment should be made on an individual patientbasis.

Elderly (aged 65 years and over)

There is limited data available for the use of VYEPTI in patients ≥65 years of age. No dose adjustmentis required in the elderly patients as the pharmacokinetics of eptinezumab were not affected by age.

Renal impairment/hepatic impairment

No dose adjustment is required in patients with renal impairment or hepatic impairment (see section5.2).

The safety and efficacy of VYEPTI in children aged 6 to 18 years has not yet been established.

Currently no data are available.

There is no relevant use of VYEPTI in children below the age of 6 years for the prophylaxis ofmigraine.

VYEPTI is for intravenous use only after dilution.

For instructions on dilution of the medicinal product prior to administration, see section 6.6.

Following dilution, infuse VYEPTI over approximately 30 minutes.

The treating healthcare professional should observe or monitor patients during and after the infusion inaccordance with normal clinical practice.

Do not administer VYEPTI as a bolus injection.

Hypersensitivity to the active substance 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 medicinal product should be clearly recorded.

Patients with cardiovascular, neurological or psychiatric diseases

Patients with a history of cardiovascular disease (e.g. hypertension, ischemic heart disease) wereexcluded from clinical studies (see section 5.1). No safety data are available in these patients. Limitedsafety data are available in patients with cardiovascular risk factors such as diabetes, circulatorydiseases and hyperlipidaemia.

Patients with a history of neurological diseases or patients with psychiatric conditions that wereuncontrolled and/or untreated were excluded from the clinical studies. Limited safety data areavailable in these patients.

Serious hypersensitivity

Serious hypersensitivity reactions, including anaphylactic reactions, have been reported and maydevelop within minutes of the infusion. Most hypersensitivity reactions occurred during infusion andwere not serious (see section 4.8). If a serious hypersensitivity reaction occurs, administration of

VYEPTI should be discontinued immediately and appropriate therapy initiated. If the hypersensitivityreaction is not serious, continuation of further treatment with VYEPTI is up to the discretion of thetreating physician, taking into account the benefit-risk for the individual patient.

VYEPTI contains sorbitol (E420). Patients with hereditary fructose intolerance (HFI) must not begiven this medicinal product unless strictly necessary.

A detailed history with regard to HFI symptoms has to be taken of each patient prior to being giventhis medicinal product.

Eptinezumab is not metabolized by cytochrome P450 enzymes. Therefore, interactions byeptinezumab with concomitant medications that are substrates, inducers, or inhibitors of cytochrome

P450 enzymes are considered unlikely.

There is limited data from the use of eptinezumab in pregnant women. Animal studies witheptinezumab do not indicate direct or indirect harmful effects with respect to reproductive toxicity (seesection 5.3). Human IgG is known to cross the placental barrier; therefore, eptinezumab may betransmitted from the mother to the developing fetus.

As a precautionary measure, it is preferable to avoid the use of VYEPTI during pregnancy.

There are no data on the presence of eptinezumab in human milk, the effects on the breastfed infant, orthe effects on milk production. Human IgG is known to be excreted in breast milk during the first fewdays after birth, which is decreasing to low concentrations soon afterward; consequently, a risk to thebreastfed infant cannot be excluded during this short period. Afterwards, use of eptinezumab could beconsidered during breast-feeding only if clinically needed.

The effect of eptinezumab on human fertility has not been evaluated. Animal studies witheptinezumab showed no impact on female and male fertility (see section 5.3).

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

Over 2 000 patients have been treated with VYEPTI in clinical studies. Of these, approximately 1 000patients were exposed for 48 weeks (four doses).

The most common adverse reactions were nasopharyngitis and hypersensitivity. Most hypersensitivityreactions occurred during infusion and were not serious. Infusion site related adverse events occurredinfrequently and in similar proportions of VYEPTI and placebo patients (< 2%) with no apparentrelationship to VYEPTI dose. The most frequently occurring infusion-site related adverse event wasinfusion site extravasation, which occurred in < 1% of VYEPTI and placebo patients.

Adverse reactions from clinical trials and post-marketing experience (table 1) are classified by

MedDRA system organ classification and frequency. Frequencies have been evaluated according tothe following convention: 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).

Table 1: List of Adverse Reactions

System organ class Adverse reaction Frequency categorypreferred term

Infections and infestations Nasopharyngitis Common

Immune system disorders Hypersensitivity reactions Common

Anaphylactic reaction1 Uncommon

General disorders and Infusion-related reaction Commonadministration siteconditions Fatigue Common1 Not reported in PROMISE 1 and PROMISE 2, but reported in other studies and in the post-marketing setting.

Nasopharyngitis

Approximately 8% of patients on 300 mg, 6% of patients on 100 mg and 6% of patients on placebo in

PROMISE 1 and PROMISE 2 experienced nasopharyngitis. Nasopharyngitis was most frequent afterthe first dose of VYEPTI at any dose. The incidence decreased notably with subsequent doses andremained fairly steady thereafter.

Hypersensitivity and infusion-related reactions

Serious hypersensitivity reactions, including anaphylactic reactions, have been reported and maydevelop within minutes of the infusion (see section 4.4). The reported anaphylactic reactions haveincluded symptoms of hypotension and respiratory difficulties, and have led to discontinuation of

VYEPTI. Other hypersensitivity reactions, including angioedema, urticaria, flushing, rash andpruritus, were reported in approximately 4% of patients on 300 mg, 3% of patients on 100 mg and 1%of patients on placebo in PROMISE 1 and PROMISE 2.

Other symptoms reported in association with eptinezumab infusion include respiratory symptoms(nasal congestion, rhinorrhea, throat irritation, cough, sneezing, dyspnea) and fatigue (see below).

Most of these events were non-serious and transient in nature.

Approximately 3% of patients on eptinezumab and 2% of patients on placebo in the placebo-controlled clinical trials experienced fatigue. Fatigue was most frequent on the day of the firstinfusion. Following the first week and with subsequent infusions, fatigue was reported in lowerincidences and the incidences were comparable to placebo.

In the clinical studies, PROMISE 1 (up to 56 weeks) and PROMISE 2 (up to 32 weeks), the incidenceof anti-eptinezumab antibodies across both studies was 18% (105/579) and 20% (115/574) in patientsreceiving 100 mg and 300 mg every 12 weeks, respectively. In both studies, the incidence of anti-eptinezumab antibodies peaked at week 24 and thereafter showed a steady decline even aftersubsequent dosing every 12 weeks. The incidence of neutralizing antibodies across both studies was8.3% (48/579) and 6.1% (35/574) for the 100 mg and 300 mg treatment groups, respectively.

In an open-label study, PREVAIL (up to 96 weeks of treatment with 300 mg VYEPTI every12 weeks), 18% (23/128) of patients developed anti-eptinezumab antibodies with an overall incidenceof neutralizing antibodies of 7% (9/128). 5.3% patients were ADA positive at week 48, 4% were ADApositive at week 72, and all patients, except one patient lost to follow up, were ADA negative atweek 104 (the last assessment in the study).

In the clinical studies, eptinezumab trough plasma concentrations appeared lower in patients whodeveloped anti-eptinezumab antibodies. There was no evidence of impact of anti-eptinezumabantibody development on efficacy or safety in the clinical studies.

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.

Doses up to 1 000 mg have been administered intravenously to humans without tolerability issues orclinically significant adverse reactions.

In the event of an overdose, the patient should be treated symptomatically, and supportive measuresinstituted as required.

Pharmacotherapeutic group: analgesics, calcitonin gene-related peptide (CGRP) antagonists, ATCcode: N02CD05.

Eptinezumab is a recombinant humanized immunoglobulin G1 (IgG1) antibody that binds to α- and β-forms of human calcitonin gene-related peptide (CGRP) ligand with low picomolar affinity (4 and3 pM Kd, respectively). Eptinezumab prevents the activation of the CGRP receptors and hence thedownstream cascade of physiological events linked to initiation of migraine attacks.

Eptinezumab inhibits α and β- CGRP-mediated neurogenic inflammation and vasodilation.

Eptinezumab is highly selective (>100 000-fold vs related neuropeptides amylin, calcitonin,adrenomedullin and intermedin).

VYEPTI (eptinezumab) was evaluated for the preventive treatment of migraine in two pivotalplacebo-controlled studies: PROMISE 1 was conducted in patients with episodic migraine (n=888)and PROMISE 2 in patients with chronic migraine (n=1072). Enrolled patients had a history ofmigraine (with or without aura) of at least 12 months, according to the International Classification of

Headache Disorders (ICHD-II or III) diagnostic criteria.

PROMISE 1: episodic migraine

PROMISE 1 was a parallel group, double-blind, placebo-controlled study to evaluate the efficacy andsafety of VYEPTI for the preventive treatment of episodic migraine in adults. 665 patients wererandomized to receive placebo (N=222), 100 mg eptinezumab (N=221), or 300 mg eptinezumab(N=222) every 12 weeks for 48 weeks (4 infusions). Episodic migraine was defined as ≥4 and≤14 headache days of which at least 4 had to be migraine days in each 28-day period in the 3 monthsprior to screening and confirmed during baseline period. Patients were allowed concurrent acutemigraine or headache medications, including migraine-specific medications (i.e., triptans, ergotaminederivatives), during the study. Regular use (greater than 7 days per month) of other treatments for theprevention of migraine was not allowed.

The primary efficacy endpoint was the change from baseline in mean monthly migraine days (MMD)over weeks 1-12. The key secondary endpoints included ≥50% and ≥75% migraine responder ratesdefined as the proportion of patients achieving at least the specified percent reduction in migraine daysover weeks 1-12, ≥75% migraine responder rate over weeks 1-4, and the percentage of patients with amigraine on the day after the first dosing (day 1).

Patients had a mean age of 40 years (range: 18 to 71 years), 84% were women, and 84% were white.

At baseline the mean number of migraine days per month at baseline was 8.6 and the rate of patientswith a migraine on a given day was 31%; both were similar across treatment groups.

Reduction in mean monthly migraine days from placebo for both doses was observed from the firstday after administration.

Figure 1 Mean changes from baseline of monthly migraine days in PROMISE 1

LS = least square; VYEPTI = eptinezumab

At each timepoint, an ANCOVA including treatment and prophylactic medication use as factors and baselinemigraine days as a continuous covariate was used to estimate the mean change from baseline.

Table 2: Primary and key secondary efficacy endpoint results in PROMISE 1 (episodicmigraine)

VYEPTI VYEPTI100 mg 300 mg Placebo

N=221 N=222 N=222

Monthly migraine days (MMD) - Weeks 1-12

Baseline 8.7 8.6 8.4

Mean change -3.9 -4.3 -3.2

Difference from placebo -0.7 -1.1

CI95% (-1.3, -0.1) (-1.7, -0.5)p-value vs placebo 0.0182 0.0001≥75% MMD responders - Weeks 1-4

Responders 30.8% 31.5% 20.3%

Difference from placebo 10.5% 11.3%p-value vs placebo 0.0112 0.0066≥75% MMD responders - Weeks 1-12

Responders 22.2% 29.7% 16.2%

Difference from placebo 6.0% 13.5%p-value vs placebo 0.1126 0.0007≥50% MMD responders - Weeks 1-12

Responders 49.8% 56.3% 37.4%

Difference from placebo 12.4% 18.9%p-value vs placebo 0.0085 0.0001

PROMISE 2: chronic migraine

PROMISE 2 was a parallel group, double-blind, placebo-controlled global study to evaluate theefficacy and safety of VYEPTI for the preventive treatment of chronic migraine in adults. A total of1,072 patients were randomized and received placebo (N=366), 100 mg eptinezumab (N=356), or300 mg eptinezumab (N=350) every 12 weeks for 24 weeks (2 infusions). Chronic migraine wasdefined as ≥ 15 to ≤26 headache days, of which ≥8 were assessed as migraine days in the 3 monthsprior to screening and confirmed during the 28-day screening period. During the study, patients wereallowed acute or preventive medication for migraine or headache on an established stable regimen(except for onabotulinumtoxinA).

A total of 431 patients (40%) with a dual diagnosis of chronic migraine and medication overuseheadache (associated with the overuse of triptans, ergotamine, or combination analgesics>10 days/month, or acetaminophen, acetylsalicylic acid, or non-steroidal anti-inflammatory drugs≥15 days/month) confirmed during screening period were included in the study population.

The primary efficacy endpoint was the change from baseline in mean MMD over weeks 1-12. The keysecondary endpoints included ≥50% and ≥75% migraine responder rates defined as the proportion ofpatients achieving the specified percent reduction in migraine days over weeks 1-12, ≥75% migraineresponder rate over weeks 1-4, the percentage of patients with a migraine on the day after dosing, thereduction in migraine prevalence from baseline to week 4, the change from baseline in the total scoreon the Headache Impact Test (HIT-6) at week 12 (300 mg dose only), and the change from baseline inacute monthly migraine medication days, mean over weeks 1-12 (300 mg dose only).

Patients had a mean age of 41 years (range: 18 to 65 years), 88% were women, and 91% were white.

Forty-one percent of patients were taking concomitant preventive medication for migraine. At baselinethe mean number of migraine days per month at baseline was 16.1 and the rate of patients with amigraine on a given day was 57.6%; both were similar across treatment groups.

Reduction in mean monthly migraine days from placebo for both doses was observed from the firstday after administration.

Figure 2: Mean changes from baseline of monthly migraine days in PROMISE 2

LS = least square; VYEPTI = eptinezumab

At each timepoint, an ANCOVA including treatment as a factor and baseline migraine days as a continuouscovariate was used to estimate the mean change from baseline.

Table 3: Primary and key secondary efficacy endpoint results in PROMISE 2 (chronicmigraine)

VYEPTI VYEPTI

Placebo100 mg 300 mg N=366

N=356 N=350

Monthly migraine days (MMD) - Weeks 1-12

Baseline 16.1 16.1 16.2

Mean change -7.7 -8.2 -5.6

Difference from placebo -2.0 -2.6

CI95% (-2.9, -1.2) (-3.5, -1.7)p-value vs placebo < 0.0001 < 0.0001≥75% MMD responders - Weeks 1-4

Responders 30.9% 36.9% 15.6%

Difference from placebo 15.3% 21.3%p-value vs placebo < 0.0001 < 0.0001≥75% MMD responders - Weeks 1-12

Responders 26.7% 33.1% 15.0%

Difference from placebo 11.7% 18.1%p-value vs placebo 0.0001 < 0.0001≥50% MMD responders - Weeks 1-12

Responders 57.6% 61.4% 39.3%

Difference from placebo 18.2% 22.1%p-value vs placebo < 0.0001 < 0.0001

HIT-6 score - Week 12a

Baseline 65.0 65.1 64.8

Mean change -6.2 -7.3 -4.5

Difference from placebo -1.7 -2.9

CI95% (-2.8, -0.7) (-3.9, -1.8)p-value vs placebo 0.0010 < 0.0001

Days per month with acute medication use - Weeks 1-12a,b

Baseline 6.6 6.7 6.2

Mean change -3.3 -3.5 -1.9

Difference from placebo -1.2 -1.4

CI95% (-1.7, -0.7) (-1.9, -0.9)p-value vs placebo < 0.0001 < 0.0001a The endpoint for the 100 mg dose was not a pre-specified key secondary endpoint.b A baseline was the average over the 28-day screening period prior to receiving treatment

Patients diagnosed with medication overuse headache

In the 431 (40%) patients diagnosed with medication-overuse headache (MOH) in PROMISE-2, themean change from baseline in MMD (weeks 1-12) was for VYEPTI 100 mg -8.4 days, VYEPTI300 mg -8.6 days, and placebo -5.4 days (mean difference to placebo of -3.0 days and -3.2 days for100 mg and 300 mg, respectively).

DELIVER: Prior migraine preventive treatment failures

VYEPTI has been evaluated in an efficacy and safety study (DELIVER) in patients with episodic(n=484) and chronic (n=405) migraine and documented failure of two to four classes of prior migrainepreventive treatment, which included a 24-week double-blind, placebo-controlled treatment period anda 48-week long term extension period.

The study showed that VYEPTI treatment led to a mean reduction in monthly migraine days (MMD)over Week 1-12: -4.8 in VYEPTI 100 mg group and -5.3 in the VYEPTI 300 mg group, compared to -2.1 in the placebo group, corresponding to a difference from placebo of -2.7 days (95% CI: -3.4 to -2.0) and -3.2 days (95% CI: -3.9 to -2.5), respectively.

The study also showed that ≥50% reduction in MMD over Week 1-12 was achieved for 42% in the

VYEPTI 100 mg group and for 50% in the VYEPTI 300 mg group, compared to 13% in the placebogroup. The ≥75% reduction in MMD over Week 1-12 was achieved in 16% in the VYEPTI 100 mggroup and 19% in the VYEPTI 300 mg group, compared to 2% of subjects in the placebo group.

The demonstrated efficacy in the placebo-controlled treatment period was sustained for up to 72 weeksof VYEPTI treatment in the extension period.

The safety data was consistent with the safety profile of VYEPTI as described in section 4.8.

RELIEF: Initiation of preventive treatment during a migraine attack

VYEPTI has been evaluated in an efficacy and safety study (RELIEF) in patients with 4 to 15migraine days per month (n=480). The patients received VYEPTI or placebo within 1-6 hours after theonset of a moderate to severe migraine attack.

The study supports that treatment with VYEPTI when initiated during a moderate to severe migraineattack, demonstrates statistically significantly shortened time to headache pain freedom (p<0.001;median time 4 hours vs 9 hours) and symptom resolution for the most bothersome symptom (p<0.001;median time 2 hours vs 3 hours) compared to placebo in patients eligible for migraine-preventivetreatment. More migraine patients treated with VYEPTI also experienced headache pain freedom(24% vs 12%) and absence of most bothersome symptoms (56% vs 36%) at 2 hours compared toplacebo (p<0.001), and within the first 24 hours after infusion, fewer patients required acute rescuemedication after VYEPTI treatment vs placebo (p<0.001).

The safety data was consistent with the safety profile of VYEPTI as described in section 4.8.

PREVAIL: long-term study

VYEPTI 300 mg was administered every 12 weeks by IV infusion for up to 96 weeks in 128 patientswith chronic migraine. The primary objective was to evaluate the long-term safety following repeateddoses of VYEPTI. Secondary objectives included characterization of the PK and immunogenicityprofiles for VYEPTI (section 4.8) and evaluation of the therapeutic effect of VYEPTI on severalpatient reported outcomes relating to migraine and quality of life including the Headache Impact Test(HIT-6). Patients had a mean age of 41.5 years (range: 18 to 65 years), 85% were women, 95% werewhite, and 36% took concomitant preventive medication for migraine. The mean number of migrainedays per 28-day period in the 3 months preceding screening was 14.1 days. In total, 100 patients(78.1%) completed the study (week 104). Patients were severely impacted at baseline with a meantotal HIT-6 of 65. The mean change from baseline through week 104 was -9.7 (p<0.0001). The safetyprofile was consistent with the safety profiles observed in the randomized, placebo-controlled studies,and a sustained effect on patient-relevant outcomes was observed for up to 96 weeks.

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

VYEPTI in one or more subset of the paediatric population in the preventive treatment of migraine(see section 4.2 for information on paediatric use)

As VYEPTI is administered intravenously, it is 100% bioavailable. Eptinezumab exhibits linearpharmacokinetics and exposure increases proportionally with doses from 10 to 1 000 mg. Steady-stateis attained after the first-dose during a once every 12 weeks dosing schedule. Median time tomaximum concentration (Cmax) is 30 minutes (end-of-infusion), and the average terminal eliminationhalf-life is 27 days. The mean accumulation ratios based on Cmax and AUC0-tau are 1.08 and 1.15,respectively.

VYEPTI is administered by intravenous infusion which bypasses extravascular absorption and is100% bioavailable. Median time to peak concentration was attained at the end of infusion(30 minutes).

The central volume of distribution (Vc) for eptinezumab was approximately 3.7 litres.

Eptinezumab is expected to be degraded by proteolytic enzymes into small peptides and amino acids.

Eptinezumab apparent clearance was 0.15 L/day, and the terminal elimination half-life wasapproximately 27 days.

A population pharmacokinetic analysis including 2 123 subjects explored the effect of age, gender,ethnicity and body weight on the pharmacokinetics of eptinezumab. Relative to a 70 kg subject, steadystate exposure of eptinezumab in a 190 kg subject was up to 52% lower, whereas is would be up to50% higher in a 39 kg subject. However, from the exposure-response evaluation, there was no effectof body weight on the clinical efficacy. No dose adjustment is required based on body weight. Thepharmacokinetics of eptinezumab were not affected by age (18-71), gender or race based onpopulation pharmacokinetics. Therefore, no dose adjustment is needed.

Renal or hepatic Impairment

No dedicated hepatic or renal impairment studies were conducted to assess the effects of hepatic andrenal impairment upon the pharmacokinetics of eptinezumab. Population pharmacokinetic analysis ofintegrated data from the VYEPTI clinical studies did not reveal any differences in patients with renalor hepatic impairment that would require dose adjustment. No data for patients with severe renalimpairment are available.

Non-clinical data reveal no special hazard for humans based on conventional studies of safetypharmacology, repeated-dose toxicity, juvenile toxicity, or toxicity to reproduction and development.

Genotoxicity and Carcinogenesis

As eptinezumab is unlikely to interact directly with DNA or other chromosomal material, evaluationsfor potential genotoxicity were considered unnecessary and not performed.

As no carcinogenicity risk has been identified by extensive evaluation of the literature related toinhibition of CGRP and as no eptinezumab-related proliferative findings were observed in long termstudies in monkeys, carcinogenicity testing was considered unnecessary and not performed.

Sorbitol (E420)

L-histidine

L-histidine hydrochloride monohydrate

Polysorbate 80

Water for injections

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinalproducts, except those mentioned in section 6.6.

3 years.

Following dilution, the VYEPTI solution for infusion (VYEPTI and 0.9% sodium chloride forinjection) must be infused within 8 hours (see section 6.6).

Store in a refrigerator (2°C - 8°C).

Do not freeze or shake.

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

If removed from the refrigerator, VYEPTI must be used within 7 days when stored in original cartonat room temperature (up to 25°C), or discarded. If it is stored at a higher temperature or for a longerperiod it must be discarded.

Following dilution, the VYEPTI solution for infusion (VYEPTI and 0.9% sodium chloride forinjection) may be stored at room temperature (below 25°C) or refrigerated at 2°C - 8°C. Followingdilution, VYEPTI solution for infusion must be infused within 8 hours.

4 mL type I glass vial with chlorobutyl rubber stopper. The vial stopper is made without natural rubberlatex.

VYEPTI 100 mg concentrate for solution for infusion

VYEPTI is available in pack sizes of 1 and 3 vial(s) for single-use.

VYEPTI 300 mg concentrate for solution for infusion

VYEPTI is available in pack size of 1 vial for single-use.

Not all pack sizes may be marketed.

The medicinal product requires dilution prior to administration. The dilution should be prepared by ahealthcare professional using aseptic technique to ensure the sterility of the prepared solution forinfusion.

The medicinal product contains no preservative and is intended for single use only and any unusedmedicinal product should be disposed.

Prior to dilution, the medicinal product (concentrate in the vials) should be inspected visually; do notuse if the concentrate contains visible particulate matter or is cloudy or discoloured (other than clear toslightly opalescent, colourless to brownish-yellow).

For both the 100 mg and the 300 mg dose, a 100 mL bag of sodium chloride 9 mg/mL (0.9%) solutionfor injection should be used to prepare the VYEPTI solution for infusion as described below. No otherintravenous diluents or volume may be used to prepare the VYEPTI solution for infusion.

Gently invert the VYEPTI solution for infusion to mix completely. Do not shake.

Following dilution, VYEPTI solution for infusion must be infused within 8 hours. During this time,

VYEPTI solution for infusion may be stored at room temperature (below 25°C) or refrigerated at2°C - 8°C. If stored at 2°C - 8°C, allow the VYEPTI solution for infusion to warm to roomtemperature prior to infusion. DO NOT FREEZE.

VYEPTI 100 mg dose

To prepare the VYEPTI solution for infusion, withdraw 1.0 mL of VYEPTI from one single-use 100mg vial using a sterile needle and syringe. Inject the 1.0 mL (100 mg) content into a 100 mL bag of0.9% sodium chloride for injection

VYEPTI 300 mg dose

To prepare the VYEPTI solution for infusion, withdraw 1.0 mL of VYEPTI from 3 single-use 100 mgvials or 3.0 mL of VYEPTI from one single-use 300 mg vial using a sterile needle and syringe. Injectthe resulting 3.0 mL (300 mg) content into a 100 mL bag of 0.9% sodium chloride for injection.

Infusion administration instructions

Parenteral medicinal products should be inspected visually for particulate matter and discolorationprior to administration. Do not use if the liquid contains visible particulate matter or is cloudy ordiscoloured.

Infuse VYEPTI 100 mg dose or VYEPTI 300 mg dose as prescribed, following dilution of the vialcontent in a 100 mL bag of 0.9% sodium chloride for injection, over approximately 30 minutes. Usean intravenous infusion set with a 0.2 or 0.22 μm in-line or add-on filter. After the infusion iscomplete, flush the line with 20 mL of 0.9% sodium chloride for injection.

Do not administer VYEPTI as a bolus injection.

No other medications should be administered through the infusion set or mixed with VYEPTI.

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

H. Lundbeck A/S

Ottiliavej 92500 Valby

Denmark

EU/1/21/1599/001

EU/1/21/1599/002

EU/1/21/1599/003

Date of first authorisation: 24. January 2022

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

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