KINPEYGO 4mg modified release capsules medication leaflet

Kinpeygo 4 mg modified-release hard capsules

Each modified-release hard capsule contains budesonide 4 mg.

Each capsule contains 230 mg of sucrose.

For the full list of excipients, see section 6.1.

Modified-release hard capsule.

19 mm white coated opaque capsules printed with “CAL10 4MG” in black ink.

Kinpeygo is indicated for the treatment of adults with primary immunoglobulin A nephropathy (IgAN) with aurine protein excretion ≥1.0 g/day (or urine protein-to-creatinine ratio ≥0.8 g/g).

The recommended dose is 16 mg once daily in the morning, at least one hour before a meal, for an initialduration of 9 months. When treatment is to be discontinued, the dose should be reduced to 8 mg once daily for2 weeks of therapy; the dose may be reduced to 4 mg once daily for an additional 2 weeks, at the discretion ofthe treating physician.

Re-treatment may be considered at the discretion of the treating physician. Safety and efficacy of treatmentwith subsequent courses of Kinpeygo have not been established.

If the patient forgets to take Kinpeygo, the patient should take Kinpeygo the next day, in the morning as usual.

The patient should not double the daily dose to make up for a missed dose.

Experience of the use of Kinpeygo in the elderly is limited. However, from the clinical data available, theefficacy and safety of Kinpeygo are expected to be similar to that of other age groups studied.

The safety and efficacy of Kinpeygo capsules in patients with hepatic impairment have not been studied.

Kinpeygo is contraindicated in patients with severe hepatic impairment (Child-Pugh Class C). See section pct. 4.3,4.4 and 5.2.

The pharmacokinetics of budesonide are not expected to be altered in patients with renal impairment.

The safety and efficacy of Kinpeygo capsules in children and adolescents below 18 years of age have not yetbeen established. No data are available.

Kinpeygo is for oral use. The modified-release hard capsules should be swallowed whole with water in themorning, at least 1 hour before a meal (see section 5.2). The capsules must not be opened, crushed or chewed,as it could affect the release profile.

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

Patients with severe hepatic impairment (Child-Pugh Class C).

Hypercorticism and adrenal axis suppression

When glucocorticosteroids are used chronically, systemic effects such as hypercorticism and adrenalsuppression may occur. Glucocorticosteroids can reduce the response of the hypothalamus-pituitary-adrenal(HPA) axis to stress. In situations where patients are subject to surgery or other stress situations,supplementation with a systemic glucocorticosteroid is recommended.

Since Kinpeygo contains a glucocorticosteroid, general warnings concerning glucocorticosteroids, as givenbelow, should be followed.

Patients with moderate or severe hepatic impairment (Child-Pugh Class B or C respectively) could be at anincreased risk of hypercorticism and adrenal axis suppression due to an increased systemic exposure of oralbudesonide. Patients with moderate hepatic impairment (Child-Pugh Class B) should be monitored forincreased signs and/or symptoms of hypercorticism.

Symptoms of steroid withdrawal in patients transferred from systemic corticosteroids

Patients who are transferred from glucocorticosteroid treatment with high systemic availability toglucocorticosteroids with lower systemic availability, such as budesonide, should be monitored sincesymptoms attributed to withdrawal of steroid therapy, including those of acute adrenal axis suppression orbenign intracranial hypertension, may develop. Adrenocortical function monitoring may be required in thesepatients and the dose of glucocorticosteroid treatment with high systemic effects should be reduced cautiously.

Replacement of systemic glucocorticosteroids with budesonide may unmask allergies (e.g., rhinitis andeczema), which were previously controlled by the systemic medicinal product.

Patients who are on medicinal products that suppress the immune system are more susceptible to infection thanhealthy individuals. Chickenpox and measles, for example, can have a more serious or even fatal course insusceptible patients or patients on immunosuppressant doses of glucocorticosteroids. In patients who have nothad these diseases, particular care should be taken to avoid exposure.

How the dose, route, and duration of glucocorticosteroid administration affect the risk of developing adisseminated infection is not known. The contribution of the underlying disease and/or priorglucocorticosteroid treatment to the risk is also not known. If exposed to chickenpox, therapy with varicellazoster immune globulin (VZIG) or pooled intravenous immunoglobulin (IVIG), as appropriate, may beindicated. If exposed to measles, prophylaxis with pooled intramuscular immunoglobulin (IG) may beindicated. (See Summaries of Product Characteristics for VZIG and IG.) If chickenpox develops, treatmentwith antiviral agents may be considered.

Glucocorticosteroids should be used with caution, if at all, in patients with active or quiescent tuberculosisinfection, untreated fungal, bacterial, systemic viral or parasitic infections, or ocular herpes simplex.

Caution with special diseases

Patients with infections, hypertension, diabetes mellitus, osteoporosis, peptic ulcer, glaucoma or cataracts, orwith a family history of diabetes or glaucoma, or with any other condition where use of glucocorticosteroidsmay be associated with an increased risk of adverse effects, should be monitored.

Visual disturbance

Visual disturbance may be reported with systemic and topical glucocorticosteroid use. If a patient presents withsymptoms such as blurred vision or other visual disturbances, the patient should be considered for referral to anophthalmologist for evaluation of possible causes which may include cataract, glaucoma or rare diseases suchas central serous chorioretinopathy (CSCR) which have been reported after use of systemic and topicalglucocorticosteroids.

Concomitant treatment with potent CYP3A4 inhibitors

Concomitant treatment with potent CYP3A4 inhibitors, including ketoconazole and cobicistat-containingproducts, is expected to increase the risk of systemic side effects attributable to budesonide. The combinationshould be avoided unless the benefit outweighs the increased risk of systemic glucocorticosteroid side effects.

If this is not possible, the period between treatments should be as long as possible and a reduction of thebudesonide dose to 8 mg budesonide daily could also be considered (see section 4.5).

After extensive intake of grapefruit juice (which inhibits CYP3A4 activity predominantly in the intestinalmucosa), the systemic exposure to budesonide after oral administration increased approximately two-fold. Aswith other medicinal products primarily metabolised through CYP3A4, regular ingestion of grapefruit or itsjuice should be avoided in connection with Kinpeygo administration (other juices such as orange juice or applejuice do not inhibit CYP3A4). See also section 4.5.

ACTH stimulation test

Because adrenal function may be suppressed, an ACTH stimulation test for diagnosing pituitary insufficiencymight show false results (low values).

Sucrose

Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrose-isomaltase insufficiency should not take this medicinal product.

Medicinal products/substances inhibiting CYP3A4

Budesonide is metabolised via CYP3A4. Potent inhibitors of CYP3A4 can increase plasma levels ofbudesonide. Co-administration of the potent CYP3A4 inhibitor ketoconazole or intake of grapefruit juiceresulted in a 6.5-fold and 2-fold increase, respectively in the bioavailability of budesonide, compared tobudesonide alone.

Thus, clinically relevant interactions with potent CYP3A inhibitors, such as ketoconazole, itraconazole,ritonavir, indinavir, saquinavir, erythromycin, cyclosporine, and grapefruit juice, are to be expected, and mayincrease systemic budesonide concentrations (see sections 4.4 and 5.2).

Medicinal products/substances inducing CYP3A4

Concomitant treatment with CYP3A4 inducers such as carbamazepine may reduce budesonide systemicexposure.

Medicinal products/substances metabolised by CYP3A4

Given its low affinity for CYP3A4 and P-gp, as well as the formulation, pharmacokinetic (PK) characteristicsand low systemic exposure, Kinpeygo is unlikely to affect the systemic exposure of other medicinal products.

Oral contraceptives containing ethinyl estradiol, which are also metabolised by CYP3A4, do not affect thepharmacokinetics of budesonide.

The pharmacokinetics of budesonide have not been evaluated in combination with proton pump inhibitors(PPIs). In a study assessing intragastric and intraduodenal pH in healthy volunteers after repeated dosing withthe PPI omeprazole 40 mg once daily, intragastric and intraduodenal pH did not exceed that required fordisintegration of Kinpeygo. Beyond the duodenum, PPIs such as omeprazole are unlikely to affect pH.

Other interactions to be considered

Budesonide treatment may reduce serum potassium, which should be considered when Kinpeygo is co-administered with a medicinal product where the pharmacological effects may be potentiated by low serumpotassium, such as cardiac glucosides, or when co-administered with diuretics that lower serum potassium.

Administration during pregnancy should be avoided unless there are compelling reasons for therapy with

Kinpeygo. There are only few data of pregnancy outcomes after oral administration of budesonide inhumans. Although data on the use of inhaled budesonide in a large number of exposed pregnanciesindicate no adverse effect, the maximal concentration of budesonide in plasma is expected to be higher inassociation with treatment with Kinpeygo compared to inhaled budesonide. In pregnant animalsbudesonide, like other glucocorticosteroids, has been shown to cause abnormalities of fetal development(see section 5.3). The relevance of this to man has not been established.

Therefore, Kinpeygo should not be used during pregnancy unless the clinical condition of the womanrequires treatment with budesonide. The expected benefits for the pregnant woman have to be weighedagainst the potential risk for the fetus.

Budesonide was found to cross the placental barrier. The relevance of this observation to humans has notbeen established.

Hypoadrenalism may occur in neonates exposed to glucocorticosteroids in utero; carefully observeneonates for signs and symptoms of hypoadrenalism.

Budesonide is excreted in breast milk.

Lactation studies have not been conducted with oral budesonide, including Kinpeygo, and no information isavailable on the effects of the medicinal product on the breast-fed infant or the effects of the medicinal producton milk production. A risk to the breast-fed infant cannot be excluded.

If Kinpeygo is used when a mother is breast-feeding, a decision must be made whether to discontinue breast-feeding or to discontinue/abstain from budesonide therapy taking into account the benefit of breast-feeding forthe child and the benefit of therapy for the woman.

There are no data on the effect of budesonide on human fertility. There were no effects on fertility in rats aftertreatment with budesonide.

No studies on the effects of Kinpeygo on the ability to drive and use machines have been performed. It isexpected that Kinpeygo has no or negligible influence on the ability to drive or use machinery.

In the Kinpeygo phase 3 clinical study the most commonly reported adverse drug reactions were acne reportedin approximately 10% of patients, peripheral oedema, face oedema, weight increased and white blood cellcount increased, each occurring in approximately 5% of patients; these were mainly of mild or moderateseverity and reversible, reflecting the low systemic exposure to budesonide after oral administration.

Adverse drug reactions reported in the pivotal phase 3 clinical study and from post-marketing data with

Kinpeygo are presented in Table 1.

Adverse reactions reported are listed according to the following frequency: 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: Adverse drug reactions by frequency and system organ class

MedDRA system organ Frequency Reactionclassification

Blood and lymphatic system Common White blood cell count increaseddisorders Common Neutrophil count increased

Endocrine disorders Common Cushingoid

Metabolism and nutrition disorders Very common Hypokalaemia

Common Diabetes mellitus*

Eye disorders Rare Vision blurred (see also section 4.4)

Vascular disorders Common Hypertension

Gastrointestinal disorders Common Dyspepsia

Skin and subcutaneous tissue Very common Skin reactions (acne, dermatitis)disorders

Musculoskeletal and connective Common Muscle spasmstissue disorders

General disorders and administration Common Oedema peripheralsite conditions Common Face oedema

Common Weight increased

* All patients with new onset of diabetes diagnosed during or following Kinpeygo treatment had levels of

FBG and HbA1c prior to the start of treatment that were indicative of pre-diabetes (HbA1c ≥ 5.7% or

FBG≥100 mg/dL).

Potential class effects

Adverse drug reactions typical of systemic glucocorticosteroids may occur (e.g., cushingoid features, increasedblood pressure, increased risk of infection, delayed wound healing, reduced glucose tolerance, sodium retentionwith oedema formation, muscle weakness, osteoporosis, glaucoma, mental disorders, peptic ulcer, increased riskof thrombosis). These adverse drug reactions are dependent on dose, treatment time, concomitant and previousglucocorticosteroid intake, and individual sensitivity. Not all of these adverse reactions were observed in theclinical study program of Kinpeygo.

No data available.

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allowscontinued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are askedto report any suspected adverse reactions via the national reporting system listed in Appendix V.

Reports of acute toxicity or death following overdose of glucocorticosteroids are rare. Acute overdose, even inexcessive doses, is not expected to lead to clinically significant consequences. In the event of acute overdose,no specific antidote is available. Treatment consists supportive and symptomatic therapy.

Pharmacotherapeutic group: Antidiarrheals, intestinal antiinflammatory/antiinfective agents, corticosteroidsacting locally, ATC code: A07EA06

The intended action of Kinpeygo is the suppression of mucosal B-cells, located in the Peyer’s patches in theileum where the majority of galactose-deficient IgA1 antibodies (Gd-IgA1) are produced. The inhibition oftheir proliferation and differentiation into plasma cells is expected to lower the occurrence of Gd-IgA1antibodies and hence the formation of immune complexes in the systemic circulation, therefore preventing thedownstream effects of glomerular mesangial deposition of immune complexes containing Gd-IgA1,manifesting as glomerulonephritis and loss of renal function.

Kinpeygo is an oral, modified-release hard capsule formulation of budesonide which combines a delayedcapsule disintegration with a prolonged release of the active substance budesonide in the ileum. By directingthe release of budesonide to the ileum, where Peyer’s patches reside in high density, a local pharmacologicaleffect is anticipated.

Primary IgA nephropathy

The efficacy of Kinpeygo has been evaluated in 2 randomised, double-blind, placebo-controlled studies ofpatients with primary IgAN, who were receiving optimised dose (maximum allowed dose or maximumtolerated dose) of Renin-Angiotensin System (RAS) inhibitor therapy as a standard of care (SOC). The effectof Kinpeygo on kidney function decline based on estimated glomerular filtration rate (eGFR) and proteinuriareduction based on urine protein creatinine ratio (UPCR) was assessed in a randomised, double-blind,multicentre phase 3 study in patients with biopsy proven IgAN. 364 patients in the Full Analysis Set wererandomised 1:1 to either Kinpeygo 16 mg once daily or placebo and treated for 9 months followed by a 2-weektaper phase of 8 mg and 15 months of observational follow-up.

The final analysis of the study demonstrated that over the 2-year period, a 9-month treatment course of

Kinpeygo (Nefecon) 16 mg/day reduced the loss of kidney function at 2 years in patients with primary IgAN ina statistically significant manner. The eGFR benefit accrued by the end of 9 months of treatment wasmaintained during 15 months of observational follow-up (Figure 1).

Figure 1: Mean absolute change in eGFR from baseline in Phase 3 NefIgArd Study

The treatment effect eGFR difference at 2 years was 6.00 mL/min/1.73 m2 using the MMRM analysis withoutexplicit missing data assumptions (MAR assumption) and was statistically significant. The change frombaseline in eGFR at 24 months was -7.50 mL/min/1.73 m2 in the Kinpeygo group compared to -13.50mL/min/1.73 m2 in the placebo group; there was a treatment benefit of 6.00 mL/min/1.73 m2 (95% CI: 2.76 to10.08) with Kinpeygo treatment compared to placebo (Table 2).

A supplementary analysis of 2-year eGFR total slope using a linear spline mixed effects analysis method toaccount for the acute (baseline to 3 months) and chronic (from 3 months onwards) phases estimated an overalltreatment benefit of 2.62 mL/min/1.73 m2 per year (95% CI 1.23 to 4.00) in favour of Kinpeygo (Table 2).

Table 2: Analysis of eGFR at 24 months in Phase 3 NefIgArd StudyeGFR (CKD-EPI) (mL/min/1.73 m2) a Kinpeygo Placebo16 mg(N=182) (N=182)

Mean change from baseline (mL/min/1.73 m2) at 24 months (15 months after Kinpeygo -7.50 -13.50treatment ended) b

Kinpeygo 16 mg versus Placebo: (95% CI)

Change from baseline in eGFR at 24 months (mL/min/1.73 m2) b 6.00 (2.76 to 10.08)2-year eGFR total slope (mL/min/1.73 m2 per year) c 2.62 (1.23 to 4.00)a Including all observed eGFR data recorded after use of prohibited medication.b Adjusted geometric least squares mean ratio of eGFR relative to baseline analysed using mixed model repeatedmeasures analysis. Mean changes derived directly from the analysis performed on a log scale.c Linear-spline mixed effects model in which eGFR was modelled simultaneously and separately over the acute(baseline to 3 months) and chronic (from 3 months onwards) phases and then combined to estimate the overall totalslope. Data not log-transformed and including all observed eGFR data regardless of the use of prohibited medicationsor starting dialysis or having a renal transplant.

CI: confidence interval; eGFR (CKD-EPI): estimated glomerular filtration rate based on Chronic Kidney Disease

Epidemiology Collaboration calculation

The 2-year eGFR treatment effect was consistent across all key subgroups, including key demographic (such asage, sex, race) and baseline disease (such as baseline proteinuria) characteristics.

The time to a confirmed 30% reduction in eGFR or end-stage renal disease (defined as renal-related death,renal transplantation, dialysis, or sustained eGFR <15 mL/min/1.73 m2) was delayed in patients who received

Kinpeygo compared with those who received placebo (HR 0.45; 95% CI 0.26 to 0.75). The proportion ofpatients with a confirmed event over the 2-year study period was 11.5% in the Kinpeygo group versus 21.4%of patients in the placebo group.

The final analysis of treatment effect on proteinuria at 2 years was consistent with that observed at the end ofthe 9 months course of Kinpeygo treatment. However, in the Kinpeygo treatment arm proteinuria increasedafter a peak reduction at 12 months (Table 3). The UPCR treatment effect at 9 months was highly consistentacross subgroups, including key demographic (such as age, sex, race) and baseline disease (such as baselineproteinuria) characteristics. A similarly consistent pattern in UPCR across subgroups was observed at 2 years.

Table 3: Proteinuria reduction at 9, 12, and 24 months and averaged over 12 to 24 months in

Phase 3 NefIgArd Study

Percentage reduction from baseline in UPCR g/g a, b Kinpeygo Placebo16 mg(N=182) (N=182)

At 9 months c 34% 5%

At 12 months (3 months after Kinpeygo treatment ended) 51% 3%

At 24 months (15 months after Kinpeygo treatment ended) 31% 1%

Kinpeygo 16 mg versus placebo: Average UPCR percentagereduction over 12 to 24 months compared to baseline d (95% CI) 41% (32% to 49%)a Excluding UPCR data recorded after use of prohibited medication.b Adjusted geometric least squares mean ratio of UPCR relative to baseline were based on a longitudinal repeatedmeasures model.c Percent reduction in UPCR was previously evaluated in the first 199 patients randomised (p=0.0003). The finalanalysis in all 364 patients confirmed a 30% reduction in UPCR at 9 months with Kinpeygo compared with placebo(95% CI 20% to 39%).

d Average UPCR percentage reduction during follow-up (over 12 to 24 months) based on longitudinal repeatedmeasures model.

CI: confidence interval; UPCR: urine protein creatinine ratio.

A supportive phase 2b study with a similar study design was conducted in a total of 153 randomised patientswho received Kinpeygo 16 mg, Kinpeygo 8 mg, or placebo, once daily for 9 months followed by a 2-weektaper phase and 3 months of observational follow-up, while continuing to receive RAS inhibitor therapy.

The primary objective was met at an interim analysis that compared Kinpeygo to placebo and showed astatistically significant reduction in UPCR at 9 months for the combined Kinpeygo 16 mg/day and 8 mg/daydose groups compared to placebo (p=0.0066).

Using the same statistical methodology as in the phase 3 study, a statistically significant 26% reduction in theprimary endpoint UPCR was shown at 9 months for the 16 mg dose of Kinpeygo versus placebo (p=0.0100)and a 29% reduction at 12 months (p=0.0027).

The difference in eGFR CKD-EPI (serum creatinine) for the 16 mg dose of Kinpeygo versus placebo was3.57 mL/min/1.73m2 at 9 months (p=0.0271), and 4.46 mL/min/1.73 m2 at 12 months (p=0.0256). Theimprovement in 1-year eGFR slope was estimated to be 5.69 mL/min/1.73 m2 per year with Kinpeygo 16 mgonce daily compared to placebo (p=0.0007).

Kinpeygo has not been studied in the paediatric population.

The Kinpeygo formulation is designed to deliver budesonide topically in the ileum. Oral absorption ofbudesonide seems to be complete and is rapid, whereas systemic bioavailability due to high first-passmetabolism is low (approximately 10%).

Following single oral administration of Kinpeygo 16 mg to healthy subjects, the geometric mean Cmax rangedbetween 3.2 and 4.4 ng/mL, and AUC(0-24) ranged between 24.1 and 24.8 ng/mL×h.

There was no clinically relevant food effect observed on the overall systemic exposure of budesonide wheneither a moderate or high fat meal was consumed 1 hour after dosing.

Budesonide is rapidly and extensively distributed into tissues and organs. Approximately 85 to 90% ofbudesonide binds to plasma proteins in blood over the concentration range of 1 to 100 nmol/L. The volume ofdistribution at steady state is 3 to 4 L/kg.

Budesonide is rapidly metabolised by the liver (and to lesser extent the gut), primarily by oxidative pathwaysvia CYP3A4 to two main metabolites, 16α-hydroxyprednisolone and 6β-hydroxybudesonide, which have lessthan 1% of the glucocorticosteroid receptor affinity and anti-inflammatory activity of budesonide.

The metabolism of budesonide is 2- to 5-fold faster than that of hydrocortisone and 8- to 15-fold faster thanthat of prednisolone.

Budesonide has a high clearance rate of approximately 72 to 80 L/h, which is close to the estimated liver bloodflow, and, accordingly, suggests that budesonide is a high hepatic clearance medicinal product.

T½ for budesonide after dosing with Kinpeygo ranged from 5 to 6.8 hours in healthy volunteer studies.

Budesonide is excreted in urine and feces in the form of metabolites. The major metabolites, including16α-hydroxyprednisolone and 6β-hydroxybudesonide, are mainly renally excreted, intact or in conjugatedforms. No unchanged budesonide was detected in urine.

Budesonide is predominantly metabolised by hepatic biotransformation.

In subjects with moderate hepatic impairment (Child-Pugh class B), systemic availability of orallyadministered budesonide was 3.5-fold higher (27%) compared with healthy volunteers (systemic availability7.4%); there was no clinically relevant increase in systemic availability in patients with mild hepaticimpairment (Child-Pugh class A).

Patients with severe hepatic impairment have not been studied.

Intact budesonide is not excreted renally. The main metabolites of budesonide, which have negligibleglucocorticosteroid activity, are largely (60%) excreted in urine.

Kinpeygo was not studied in the paediatric population.

The preclinical safety of budesonide has been documented in studies during the development of otherformulations of this compound. No preclinical studies have been conducted with the Kinpeygo formulationitself.

Results from acute, subacute and chronic toxicity studies show that the systemic effects of budesonide, e.g.decreased body-weight gain and atrophy of lymphoid tissues and adrenal cortex, are less severe or similar tothose observed after administration of other glucocorticosteroids.

Budesonide, evaluated in six different test systems, did not show any signs of mutagenic or clastogenic effects.

An increased incidence of brain gliomas in male rats in a carcinogenicity study could not be verified in a repeatstudy, in which the incidence of gliomas did not differ between any of the groups on active treatment(budesonide, prednisolone, triamcinolone acetonide) and the control group.

Liver changes (primary hepatocellular neoplasms) found in male rats in the original carcinogenicity study werenoted again in the repeat study with budesonide, as well as the reference glucocorticosteroids. These effects aremost probably related to a receptor effect and thus represent a class effect in this species.

Available clinical experience shows that there are no indications that budesonide or other glucocorticosteroidsinduce brain gliomas or primary hepatocellular neoplasms in humans.

Budesonide had no effect on fertility in rats. In pregnant animals, budesonide, like other glucocorticoids, hasbeen shown to caues foetal death and abnormalities of foetal development (smaller litter size, intrauterinegrowth retardation of foetuses and skeletal abnormalities). The clinical relevance of these findings to humanhas not been established (see section 4.6).

The toxicity of budesonide modified-release hard capsules, with focus on the gastro-intestinal tract, has beenstudied in cynomolgus monkeys at doses of up to 5 mg/kg (approximately 15 times the recommended dailydose of Kinpeygo in humans on a dose per body weight basis) after repeated oral administration for up to6 months. No effects were observed in the gastrointestinal tract, either from gross pathology orhistopathological examination.

Sugar spheres (sucrose and corn starch)

Hypromellose

Macrogol

Citric acid monohydrate

Ethylcellulose

Medium chain triglycerides

Oleic acid

Hypromellose

Macrogol

Titanium dioxide (E171)

Methacrylic acid - methyl methacrylate co-polymers

Talc

Dibutylsebacate

Shellac

Black iron oxide (E172)

Not applicable.

4 years

Do not store above 25°C .

White high density polyethylene (HDPE) bottle with a white polypropylene (PP) child-resistant closure with aninduction seal.

Pack sizes: 1 bottle containing 28 or 120 modified-release hard capsules and multipacks containing 360 (3packs of 120) modified-release hard capsules.

Not all pack sizes may be marketed.

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

STADA Arzneimittel AG

Stadastrasse 2-1861118 Bad Vilbel

Germany

EU/1/22/1657/001

EU/1/22/1657/002

EU/1/22/1657/003

Date of first authorisation: 15 July 2022

Date of latest renewal: 17 June 2024

Detailed information on this medicinal product is available on the website of the European Medicines Agencyhttp://www.ema.europa.eu.