Kinpeygo · 4.8 Undesirable effects · 1

HOS-288427 · has-adverse-reaction-information · PDF-Seite 6

Summary of the safety profile In the Kinpeygo phase 3 clinical study the most commonly reported adverse drug reactions were acne reported in approximately 10% of patients, peripheral oedema, face oedema, weight increased and white blood cell count increased, each occurring in approximately 5% of patients; these were mainly of mild or moderate severity and reversible, reflecting the low systemic exposure to budesonide after oral administration. 6 Data for re-treatment of patients who were re-treated as part of an open-label extension study to the previous phase 3 study suggested a safety profile for re-treatment consistent with that observed in the phase 3 clinical study. Tabulated list of adverse reactions 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 Reaction classification Blood and lymphatic system Common White blood cell count increased disorders 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 spasms tissue disorders General disorders and administration Common Oedema peripheral site conditions Common Face oedema Common

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HOS-288423 · has-contraindication-information · PDF-Seite 3

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).

HOS-288422 · has-indication-information · PDF-Seite 2

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

HOS-288425 · has-interaction-information · PDF-Seite 5

Medicinal products/substances inhibiting CYP3A4 Budesonide is metabolised via CYP3A4. Potent inhibitors of CYP3A4 can increase plasma levels of budesonide. Co-administration of the potent CYP3A4 inhibitor ketoconazole or intake of grapefruit juice resulted in a 6.5-fold and 2-fold increase, respectively in the bioavailability of budesonide, compared to budesonide 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 may increase 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 systemic exposure. Medicinal products/substances metabolised by CYP3A4 Given its low affinity for CYP3A4 and P-gp, as well as the formulation, pharmacokinetic (PK) characteristics and low systemic exposure, Kinpeygo is unlikely to affect the systemic exposure of other medicinal products. Oral contraceptives Oral contraceptives containing ethinyl estradiol, which are also metabolised by CYP3A4, do not affect the pharmacokinetics of budesonide. Proton pump inhibitors 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 with the PPI omeprazole 40 mg once daily, intragastric and intraduodenal pH did not exceed that required for disintegration 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 serum potassium, such as cardiac glucosides, or when co-administered with diuretics that lower serum potassium. 5

HOS-288426 · has-pregnancy-information · PDF-Seite 6

Pregnancy 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 in humans. Although data on the use of inhaled budesonide in a large number of exposed pregnancies indicate no adverse effect, the maximal concentration of budesonide in plasma is expected to be higher in association with treatment with Kinpeygo compared to inhaled budesonide. In pregnant animals budesonide, 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 woman requires treatment with budesonide. The expected benefits for the pregnant woman have to be weighed against the potential risk for the fetus. Budesonide was found to cross the placental barrier. The relevance of this observation to humans has not been established. Hypoadrenalism may occur in neonates exposed to glucocorticosteroids in utero; carefully observe neonates for signs and symptoms of hypoadrenalism. Breast-feeding Budesonide is excreted in breast milk. Lactation studies have not been conducted with oral budesonide, including Kinpeygo, and no information is available on the effects of the medicinal product on the breast-fed infant or the effects of the medicinal product on 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 for the child and the benefit of therapy for the woman. Fertility There are no data on the effect of budesonide on human fertility. There were no effects on fertility in rats after treatment with budesonide.

HOS-288424 · has-warning-information · PDF-Seite 3

Hypercorticism and adrenal axis suppression When glucocorticosteroids are used chronically, systemic effects such as hypercorticism and adrenal suppression 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 given below, should be followed. Hepatic impairment Patients with moderate or severe hepatic impairment (Child-Pugh Class B or C respectively) could be at an increased risk of hypercorticism and adrenal axis suppression due to an increased systemic exposure of oral budesonide. Patients with moderate hepatic impairment (Child-Pugh Class B) should be monitored for increased 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 to glucocorticosteroids with lower systemic availability, such as budesonide, should be monitored since symptoms attributed to withdrawal of steroid therapy, including those of acute adrenal axis suppression or benign intracranial hypertension, may develop. Adrenocortical function monitoring may be required in these patients and the dose of glucocorticosteroid treatment with high systemic effects should be reduced cautiously. 3 Replacement of systemic glucocorticosteroids with budesonide may unmask allergies (e.g., rhinitis and eczema), which were previously controlled by the systemic medicinal product. Infections Patients who are on medicinal products that suppress the immune system are more susceptible to infection than healthy individuals. Chickenpox and measles, for example, can have a more serious or even fatal course in susceptible patients or patients on immunosuppressant doses of glucocorticosteroids. In patients who have not had these diseases, particular care should be taken to avoid exposure. How the dose, route, and duration of glucocorticosteroid administration affect the risk of developing a disseminated infection is not known. The contribution of the underlying disease and/or prior glucocorticosteroid treatment to the risk is also not known. If exposed to chickenpox, therapy with

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