Kerendia · 4.4 Special warnings and precautions for use · 1

HOS-099335 · has-adverse-reaction-information · PDF-Seite 11

Summary of the safety profile The most frequently reported adverse reaction under treatment with finerenone was hyperkalaemia (12.6%). See ‘Description of selected adverse reactions, Hyperkalaemia’ below and section 4.4. Tabulated list of adverse reactions The safety of finerenone in patients with chronic kidney disease (CKD) and T2D was evaluated in 2 pivotal phase III studies, FIDELIO-DKD (diabetic kidney disease) and FIGARO-DKD. In the FIDELIO-DKD study 2 818 patients received finerenone (10 mg or 20 mg once daily) with a mean duration of treatment of 2.2 years. In the FIGARO-DKD study, 3 671 patients received finerenone (10 mg or 20 mg once daily) with a mean duration of treatment of 2.9 years. The safety of finerenone in patients with heart failure (HF) with LVEF ≥ 40% was evaluated in the phase III study, FINEARTS-HF. In this study, 2 993 patients received finerenone (10 mg, 20 mg, or 40 mg once daily) with a mean duration of treatment of 2.1 years. 11 The adverse reactions observed are listed in table 5. They are classified according to MedDRA system organ class and frequency convention. Adverse reactions are grouped according to their frequencies in the order of decreasing seriousness. Frequencies 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 5: Adverse reactions System organ class Frequency CKD with T2D HF with LVEF ≥ 40% Very common Hyperkalaemia - Metabolism and Hyperkalaemia nutrition disorders Hyponatraemia Common Hyponatraemia Hyperuricaemia Hyperuricaemia Vascular disorders Common Hypotension Hypotension Gastrointestinal Diarrhoea Common - disorders Constipation Skin and subcutaneous tissue Common Pruri

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HOS-099331 · has-contraindication-information · PDF-Seite 7

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. - Concomitant treatment with strong inhibitors of CYP3A4 (see section 4.5), e.g., - itraconazole - ketoconazole - ritonavir - nelfinavir - cobicistat - clarithromycin - telithromycin - nefazodone - Addison's disease

HOS-099330 · has-indication-information · PDF-Seite 3

Kerendia is indicated for the treatment of chronic kidney disease (with albuminuria) associated with type 2 diabetes in adults. For study results with respect to renal and cardiovascular events, see section 5.1. Kerendia is indicated for the treatment of symptomatic chronic heart failure with left ventricular ejection fraction (LVEF) ≥ 40% in adults.

HOS-099333 · has-interaction-information · PDF-Seite 9

Interaction studies have only been performed in adults. Finerenone is cleared almost exclusively via cytochrome P450 (CYP)-mediated oxidative metabolism (mainly CYP3A4 [90%] with a small contribution of CYP2C8 [10%]). Concomitant use contraindicated Strong CYP3A4 inhibitors Concomitant use of Kerendia with itraconazole, clarithromycin and other strong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir, nelfinavir, cobicistat, telithromycin or nefazodone) is contraindicated (see section 4.3), since a marked increase in finerenone exposure is expected. Concomitant use not recommended Strong and moderate CYP3A4 inducers Kerendia should not be used concomitantly with rifampicin and other strong CYP3A4 inducers (e.g., carbamazepine, phenytoin, phenobarbital, St John’s Wort) or with efavirenz and other moderate CYP3A4 inducers. These CYP3A4 inducers are expected to markedly decrease finerenone plasma concentration and result in reduced therapeutic effect (see section 4.4). Certain medicinal products that increase serum potassium Kerendia should not be used concomitantly with potassium-sparing diuretics (e.g., amiloride, triamterene) and other MRAs (e.g., eplerenone, esaxerenone, spironolactone, canrenone). It is anticipated that these medicinal products increase the risk for hyperkalaemia (see section 4.4) Grapefruit Grapefruit or grapefruit juice should not be consumed during finerenone treatment, as it is expected to increase the plasma concentrations of finerenone through inhibition of CYP3A4 (see sections 4.2 and 4.4). 9 Concomitant use with precautions Moderate CYP3A4 inhibitors In a clinical study, concomitant use of erythromycin (500 mg three times a day) led to a 3.5-fold increase in finerenone AUC and 1.9-fold increase in its Cₘₐₓ. In another clinical study, verapamil (240 mg controlled-release tablet once daily) led to a 2.7- and 2.2-fold increase in finerenone AUC and Cₘₐₓ, respectively. Serum potassium may increase, and therefore, monitoring of serum potassium is recommended, especially during initiation or changes to dosing of finerenone or the CYP3A4 inhibitor (see sections 4.2 and 4.4). Weak CYP3A4 inhibitors The physiologically based pharmacokinetic (PBPK) simulations suggest that fluvoxamine (100 mg twice daily), increases finerenone AUC (1.6-fold) and Cₘₐₓ (1.4-fold). Serum potassium may increase, and therefore, monitoring of serum potassium is recommended, especially during initiatio

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HOS-099334 · has-pregnancy-information · PDF-Seite 11

Contraception in females Women of childbearing potential should use effective contraception during finerenone treatment (see section 4.4). Pregnancy There are no data from the use of finerenone in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). Kerendia should not be used during pregnancy unless the clinical condition of the woman requires treatment with finerenone. If the woman becomes pregnant while taking finerenone, she should be informed of potential risks to the foetus (see section 4.4). Breast-feeding It is unknown whether finerenone/metabolites are excreted in human milk. Available pharmacokinetic/toxicological data in animals have shown excretion of finerenone and its metabolites in milk. Rat pups exposed via this route showed adverse reactions (see section 5.3). A risk to the newborns/infants cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Kerendia therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman (see section 4.4). Fertility There are no data on the effect of finerenone on human fertility. Animal studies have shown impaired female fertility at exposures considered in excess to the maximum human exposure, indicating low clinical relevance (see section 5.3).

HOS-099332 · has-warning-information · PDF-Seite 7

Hyperkalaemia Hyperkalaemia has been observed in patients treated with finerenone (see section 4.8). Some patients are at a higher risk to develop hyperkalaemia. Risk factors include low eGFR, higher serum potassium and previous episodes of hyperkalaemia. In these patients more frequent monitoring has to be considered. If serum potassium > 5.0 mmol/L, finerenone treatment should not be initiated. Monitoring Serum potassium and eGFR have to be remeasured 4 weeks after initiation, restart or dose adjustment of finerenone. Thereafter, serum potassium has to be assessed periodically and as needed based on patient characteristics and serum potassium levels (see section 4.2). Chronic kidney disease associated with T2D Initiation and continuation of treatment (see section 4.2) If serum potassium > 4.8 to 5.0 mmol/L, initiation of finerenone treatment may be considered with additional serum potassium monitoring within the first 4 weeks based on patient characteristics and serum potassium levels. If serum potassium > 5.5 mmol/L, finerenone treatment has to be withheld. Local guidelines for the management of hyperkalaemia have to be followed. Once serum potassium ≤ 5.0 mmol/L, finerenone treatment can be restarted at 10 mg once daily. Heart failure with LVEF ≥ 40% Initiation and continuation of treatment (see section 4.2) If serum potassium  6.0 mmol/L, finerenone treatment has to be withheld. Local guidelines for the management of hyperkalaemia have to be followed. Once serum potassium ˂ 5.5 mmol/L, finerenone treatment can be restarted at 10 mg once daily. In case of repeated measurements of serum potassium  5.5 mmol/L, finerenone treatment can only be restarted, when serum potassium is ˂ 5.0 mmol/L. Concomitant use of other medicinal products The risk of hyperkalaemia also may increase with the intake of concomitant medicinal products that may increase serum potassium (see section 4.5). See also ‘Concomitant use of substances that affect finerenone exposure’. Finerenone should not be given concomitantly with - potassium-sparing diuretics (e.g., amiloride, triamterene) and - other mineralocorticoid receptor antagonists (MRAs), e.g., eplerenone, esaxerenone, spironolactone, canrenone. 7 Finerenone should be used with caution and serum potassium should be monitored when taken concomitantly with - potassium supplements or potassium-enriched salt substitutes. - trimethoprim, or trime

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