4.1. Therapeutic indications

Kerendia is indicated for the treatment of chronic kidney disease (stage 3 and 4 with albuminuria) associated with type 2 diabetes in adults.

Kerendia is indicated for the treatment of symptomatic chronic heart failure with left ventricular ejection fraction (LVEF) ≥ 40% in adults.

4.2. Posology and method of administration

Posology

Chronic kidney disease associated with type 2 diabetes (T2D)

The recommended target dose is 20 mg finerenone once daily.

The maximum recommended dose is 20 mg finerenone once daily.

Initiation of treatment

Serum potassium and estimated glomerular filtration rate (eGFR) have to be measured to determine if finerenone treatment can be initiated (see also section 4.4) and to determine the starting dose.

For monitoring of serum potassium, see below 'Continuation of treatment.'

If serum potassium ≤ 4.8 mmol/L, finerenone treatment can be initiated.

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 (see section 4.4).

If serum potassium > 5.0 mmol/L, finerenone treatment should not be initiated (see section 4.4).

The recommended starting dose of finerenone is based on eGFR and is presented in table 1.

Table 1: Initiation of finerenone treatment and recommended dose

eGFR (mL/min/1.73 m2)

Starting dose (once daily)

≥ 25 to < 60

10 mg

< 25

Not recommended

Continuation of treatment

Serum potassium and eGFR have to be remeasured 4 weeks after initiation or re-start of finerenone treatment or increase in dose (see table 2 to determine continuation of finerenone treatment and dose adjustment).

Thereafter, serum potassium has to be remeasured periodically and as needed based on patient characteristics and serum potassium levels.

See sections 4.4 and 4.5 for more information.

Table 2: Continuation of finerenone treatment and dose adjustment

Current finerenone dose (once daily)

10 mg

20 mg

Current serum potassium (mmol/L)

≤ 4.8

Increase to 20 mg finerenone once daily*

Maintain 20 mg once daily

> 4.8 to 5.5

Maintain 10 mg once daily

Maintain 20 mg once daily

> 5.5

Withhold finerenone.

Consider re-starting at 10 mg once daily when serum potassium ≤ 5.0 mmol/L.

Withhold finerenone.

Re-start at 10 mg once daily when serum potassium ≤ 5.0 mmol/L.

* maintain 10 mg once daily, if eGFR has decreased > 30% compared to the previous measurement

Heart failure with LVEF ≥ 40%

The recommended target dose depends on renal function (eGFR) at initiation of finerenone treatment (see table 4):

- 40 mg once daily if eGFR ≥ 60 mL/min/1.73 m2

- 20 mg once daily if eGFR ≥ 25 to < 60 mL/min/1.73 m2

The maximum recommended dose is 40 mg finerenone once daily.

Initiation of treatment

If serum potassium ≤ 5.0 mmol/L, finerenone treatment can be initiated.

Serum potassium and estimated glomerular filtration rate (eGFR) have to be measured to determine if finerenone treatment can be initiated (see also section 4.4) and to determine the starting dose.

For monitoring of serum potassium, see below 'Continuation of treatment.'

The recommended starting dose of finerenone is based on eGFR and is presented in table 3.

Table 3: Initiation of finerenone treatment and recommended dose

eGFR (mL/min/1.73 m2)

Starting dose (once daily)

≥ 60

20 mg

≥ 25 to < 60

10 mg

< 25

Not recommended

Continuation of treatment

Serum potassium and eGFR have to be remeasured 4 weeks after initiation or re-start of finerenone treatment or change in dose (see table 4 to determine continuation of finerenone treatment and dose adjustment).

Thereafter, serum potassium and eGFR have to be remeasured periodically and as needed based on patient characteristics.

See sections 4.4 and 4.5 for more information.

Table 4: Continuation of finerenone treatment and dose adjustment

Current finerenone dose (once daily)

10 mg

20 mg

40 mg

Current serum potassium (mmol/L)

< 5.0

Increase to 20 mg finerenone once daily if eGFR has not decreased >30% compared to the previous measurement

Increase to 40 mg once daily if eGFR has not decreased >30% compared to the previous measurement

Maintain 20 mg once daily if eGFR < 60 mL/min/1.73 m2 at initiation

Maintain 40 mg once daily

Decrease to 20 mg once daily if eGFR has decreased > 30% compared to the previous measurement

5.0 to < 5.5

Maintain 10 mg once daily

Maintain 20 mg once daily

Maintain 40 mg once daily

Decrease to 20 mg once daily if eGFR has decreased > 30% compared to the previous measurement

5.5 to < 6.0

Withhold finerenone

Re-start at 10 mg once daily when serum potassium < 5.5 mmol/L.

Decrease to 10 mg once daily

Decrease to 20 mg once daily

≥ 6.0

Withhold finerenone.

Re-start at 10 mg once daily when serum potassium < 5.5 mmol/L or if repeatedly ≥ 5.5 mmol/L, wait to re-start until < 5.0 mmol/L.

If eGFR decreases by ≥ 40% compared to the previous measurement, consider reducing the dose or withholding finerenone. Once eGFR levels have stabilised, according to the individual patient´s characteristics, consider increasing the dose or restarting treatment.

Missed dose

A missed dose should be taken as soon as the patient notices, but only on the same day.

The patient should not take 2 doses to make up for a missed dose.

Special populations

Elderly (≥ 65 years)

No dose adjustment is necessary in elderly patients (see section 5.2) but regular monitoring of renal function is recommended (see section 4.4).

Renal impairment

Initiation of treatment

In patients with eGFR < 25 mL/min/1.73 m2, finerenone treatment should not be initiated due to limited clinical data (see sections 4.4 and 5.2).

Continuation of treatment

In patients with eGFR ≥ 15 mL/min/1.73 m2, finerenone treatment can be continued with dose adjustment based on serum potassium. eGFR should be measured 4 weeks after initiation to determine whether the starting dose can be increased (see 'Posology, Continuation of treatment' and tables 2 and 4).

Due to limited clinical data, finerenone treatment should be discontinued in patients who have progressed to end-stage renal disease (eGFR < 15 mL/min/1.73 m2) (see section 4.4).

Hepatic impairment

Patients with

- severe hepatic impairment:

Finerenone should not be initiated (see sections 4.4 and 5.2). No data are available.

- moderate hepatic impairment:

No initial dose adjustment is required. Consider additional serum potassium monitoring and adapt monitoring according to patient characteristics (see sections 4.4 and 5.2).

- mild hepatic impairment:

No initial dose adjustment is required.

Concomitant use of other medicinal products

In patients taking finerenone concomitantly with moderate or weak CYP3A4 inhibitors, potassium supplements, trimethoprim, or trimethoprim/sulfamethoxazole, additional serum potassium monitoring and adaptation of monitoring according to patient characteristics should be considered (see section 4.4). Finerenone treatment decisions should be made as directed in tables 2 and 4 (see 'Posology, Continuation of treatment').

Temporary discontinuation of finerenone may be necessary, when patients have to take trimethoprim, or trimethoprim/sulfamethoxazole. See sections 4.4 and 4.5 for more information.

Body weight

No dose adjustment is necessary based on body weight (see section 5.2).

Paediatric population

The safety and efficacy of finerenone in children and adolescents aged under 18 years have not yet been established. No data are available.

Method of administration

Oral use

Tablets may be taken with a glass of water and with or without food (see section 5.2).

Tablets should not be taken with grapefruit or grapefruit juice (see section 4.5).

Crushing of tablets

For patients who are unable to swallow whole tablets, Kerendia tablets may be crushed and mixed with water or soft foods, such as apple sauce, directly before oral use (see section 5.2).

4.3. Contraindications

- 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

4.4. Special warnings and precautions for use

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, re-start 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.

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 trimethoprim/sulfamethoxazole. Temporary discontinuation of finerenone may be necessary.

Worsening of renal function in patients with heart failure with LVEF ≥ 40%

An increased incidence of worsening of renal function has been reported in patients with heart failure with LVEF ≥ 40% treated with finerenone (see section 4.8). Monitoring of renal function is recommended periodically during treatment and as needed based on patient characteristics. Elderly patients and patients with impaired renal function (eGFR < 60 mL/min/1.73 m2) are at higher risk for worsening of renal function and should be monitored more frequently (see section 4.2).

Renal impairment

The risk of hyperkalaemia increases with decreasing renal function. Ongoing monitoring of renal function should be performed as needed according to standard practice (see section 4.2).

Initiation of treatment

Finerenone treatment should not be initiated in patients with eGFR < 25 mL/min/1.73 m2 as clinical data are limited (see sections 4.2 and 5.2).

Continuation of treatment

Due to limited clinical data, finerenone treatment should be discontinued in patients who have progressed to end‑stage renal disease (eGFR < 15 mL/min/1.73 m2).

Hepatic impairment

Finerenone treatment should not be initiated in patients with severe hepatic impairment (see section 4.2). These patients have not been studied (see section 5.2) but a significant increase in finerenone exposure is expected.

The use of finerenone in patients with moderate hepatic impairment may require additional monitoring due to an increase in finerenone exposure. Additional serum potassium monitoring and adaptation of monitoring have to be considered according to patient characteristics (see sections 4.2 and 5.2).

Patients with New York Heart Association (NYHA) class IV

Experience with finerenone in heart failure patients classified as NYHA class IV is limited (see section 5.1).

Elderly

Elderly are more likely to have impaired renal function and to be treated with medicinal products which may cause changes in renal function. Therefore, regular monitoring of renal function is recommended.

Concomitant use of substances that affect finerenone exposure

Moderate and weak CYP3A4 inhibitors

Serum potassium should be monitored during concomitant use of finerenone with moderate or weak CYP3A4 inhibitors (see sections 4.2 and 4.5).

Strong and moderate CYP3A4 inducers

Finerenone should not be used concomitantly with strong or moderate CYP3A4 inducers (see section 4.5).

Grapefruit

Grapefruit or grapefruit juice should not be consumed during finerenone treatment (see sections 4.2 and 4.5).

Embryo-foetal toxicity

Finerenone should not be used during pregnancy unless there has been careful consideration of the benefit for the mother and the risk to the foetus. If a woman becomes pregnant while taking finerenone, she should be informed of potential risks to the foetus.

Women of childbearing potential should be advised to use effective contraception during treatment with finerenone.

Women should be advised not to breast-feed during treatment with finerenone.

See sections 4.6 and 5.3 for more information.

Information about excipients

Kerendia contains lactose

Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose‑galactose malabsorption should not take this medicinal product.

Kerendia contains sodium

This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially 'sodium‑free'.

4.5. Interaction with other medicinal products and other forms of interaction

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).

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 initiation or changes to dosing of finerenone or the CYP3A4 inhibitor (see sections 4.2 and 4.4).

Certain medicinal products that increase serum potassium (see section 4.4)

Concomitant use of Kerendia with potassium supplements and trimethoprim, or trimethoprim/sulfamethoxazole is anticipated to increase the risk of hyperkalaemia. Monitoring of serum potassium is required.

Temporary discontinuation of Kerendia during trimethoprim, or trimethoprim/sulfamethoxazole treatment may be necessary.

Antihypertensive medicinal products

The risk for hypotension increases with concomitant use of multiple other antihypertensive medicinal products. In these patients, blood pressure monitoring is recommended.

Effect of 40 mg finerenone on CYP3A4 and CYP2C8 substrates

At 40 mg once daily, finerenone is a weak inhibitor of the CYP3A4 enzyme in vivo. Co‑administration of multiple doses of 40 mg finerenone with the CYP3A4 probe substrate midazolam resulted in a 1.31‑fold increase in mean midazolam AUC with no effect on Cₘₐₓ. The potentially increased exposure of sensitive CYP3A4 substrates with a narrow therapeutic window needs to be considered when used concomitantly with finerenone 40 mg once daily. A multiple‑dose regimen of 20 mg finerenone given once daily for 10 days had no relevant effect on the AUC of the CYP3A4 probe substrate midazolam. Therefore, a clinically relevant inhibition or induction of CYP3A4 by finerenone can be excluded at this dose level.

At 40 mg once daily, finerenone is a weak inhibitor of the CYP2C8 enzyme in vivo. Co‑administration of multiple doses of 40 mg finerenone with the CYP2C8 probe substrate repaglinide resulted in a 1.59‑fold increase in mean repaglinide AUC and a 1.30‑fold increase in Cₘₐₓ. The potentially increased exposure of CYP2C8 substrates with a narrow therapeutic window needs to be considered when used concomitantly with finerenone 40 mg once daily.

A single dose of 20 mg finerenone had no clinically relevant effect on AUC and Cₘₐₓ of the CYP2C8 probe substrate repaglinide. Thus, finerenone does not inhibit CYP2C8 at this dose level.

4.6. Fertility, pregnancy and lactation

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).

4.7. Effects on ability to drive and use machines

Kerendia has no influence on the ability to drive and use machines.

4.8. Undesirable effects

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.

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%

Metabolism and nutrition disorders

Very common

Hyperkalaemia

-

Common

Hyponatraemia

Hyperuricaemia

Hyperkalaemia

Hyponatraemia

Hyperuricaemia

Vascular disorders

Common

Hypotension

Hypotension

Gastrointestinal disorders

Common

-

Diarrhoea

Constipation

Skin and subcutaneous tissue disorders

Common

Pruritus

-

Renal and urinary disorders

Common

-

Renal impairment

Acute kidney injury

Investigations

Common

Blood creatinine increased/ Glomerular filtration rate decreased

Blood creatinine increased/ Glomerular filtration rate decreased

Uncommon

Haemoglobin decreased

-

Description of selected adverse reactions

Hyperkalaemia

An increase from baseline in mean serum potassium in the first month of treatment of up to 0.2 mmol/L was observed in the finerenone group compared to placebo, which remained stable thereafter.

In the pooled data of FIDELIO‑DKD and FIGARO-DKD studies, hyperkalaemia events were reported in 14.0% of finerenone‑treated patients compared with 6.9% of placebo-treated patients. Serious events of hyperkalaemia were reported more frequently for finerenone (1.1%) than for placebo (0.2%). Serum potassium concentrations > 5.5 mmol/L and > 6.0 mmol/L were reported in 16.8% and 3.3% of finerenone-treated patients and in 7.4% and 1.3% of placebo-treated patients, respectively.

Hyperkalaemia leading to permanent discontinuation in patients who received finerenone was 1.7% versus 0.6% in the placebo group. Hospitalisation due to hyperkalaemia in the finerenone group was 0.9% versus 0.2% in the placebo group.

In the FINEARTS‑HF study, hyperkalaemia events were reported in 9.7% of finerenone‑treated patients compared with 4.2% of placebo-treated patients. Hyperkalaemia leading to permanent discontinuation in patients who received finerenone was 0.4% versus 0.2% in the placebo group. Hospitalisation due to hyperkalaemia in the finerenone group was 0.5% versus 0.2% in the placebo group.

In all studies, the majority of hyperkalaemia events were mild to moderate and resolved in patients treated with finerenone.

For specific recommendations, see sections 4.2 and 4.4.

Worsening of renal function

In the pooled data of FIDELIO-DKD and FIGARO-DKD studies, GFR decreased events were reported in 5.4% of finerenone-treated patients compared with 4.2% of placebo-treated patients. GFR decreased events leading to permanent discontinuation were the same in patients receiving finerenone or placebo (0.2%). Hospitalisation due to decreased GFR was the same in patients receiving finerenone or placebo (< 0.1%).

Blood creatinine increased events were reported in 2.6% of finerenone-treated patients compared with 2.3% of placebo-treated patients.

The majority of GFR decreased/blood creatinine increased events were mild or moderate and resolved in patients treated with finerenone. Patients on finerenone experienced an initial decrease in eGFR (mean 2 mL/min/1.73 m2) that attenuated over time compared to placebo. This decrease appeared to be reversible during continuous treatment.

In the FINEARTS-HF study, events related to worsening of renal function were reported more frequently in patients treated with finerenone (17.7%) compared to those receiving placebo (10.9%). The reported events included renal impairment (6.6% vs. 3.9%), GFR decreased (5.2% vs. 3.6%), acute kidney injury (3.7% vs. 2.1%), renal failure (2.6% vs. 1.6%), and blood creatinine increased (1.2% vs. 0.8%).

Overall, most of the reported events related to worsening of renal function were mild to moderate and resolved in patients treated with finerenone. In some cases where finerenone was permanently discontinued, eGFR did not return to baseline levels. Events related to worsening of renal function that led to permanent discontinuation were identical in both the finerenone and placebo groups (0.3%). Events related to worsening of renal function leading to hospitalisation were reported more frequently in patients treated with finerenone compared to the placebo group (2.0% vs. 1.3%), with acute kidney injury being the most frequently reported event leading to hospitalisation (1.6% in finerenone vs. 0.8% in placebo).

Patients on finerenone experienced an initial decrease in GFR that appeared to be reversible during continuous treatment. The mean difference in GFR between finerenone and placebo was approximately 3-4 mL/min/1.73 m2 from month 1 to month 6. After month 6, the decline in GFR was slightly larger in the placebo group, with a mean difference between finerenone and placebo of approximately 2-3 mL/min/1.73 m2.

Hypotension

Finerenone treatment led to a mean systolic blood pressure decrease by 2‑4 mm Hg and a mean diastolic blood pressure decrease by 1‑2 mm Hg at month 1, remaining stable thereafter.

In the pooled data of FIDELIO-DKD and FIGARO-DKD studies, hypotension events were reported in 4.7% of finerenone-treated patients compared with 3.0% of placebo-treated patients. In 3 patients (< 0.1%), finerenone treatment was permanently discontinued due to hypotension. Hospitalisation due to hypotension was the same in patients receiving finerenone or placebo (0.1%).

In the FINEARTS‑HF study, hypotension events were reported in 7.6% of finerenone-treated patients compared with 4.7% of placebo-treated patients. In 3 patients (0.1%), finerenone treatment was permanently discontinued due to hypotension. Hospitalisation due to hypotension was 0.4% in the finerenone group versus 0.3% in the placebo group.

In all studies, the majority of hypotension events were mild or moderate and resolved in patients treated with finerenone.

Hyperuricaemia

In the pooled data of FIDELIO‑DKD and FIGARO‑DKD studies, hyperuricaemia events were reported in 5.1% of finerenone‑treated patients compared with 3.9% of placebo‑treated patients. An increase from baseline in mean serum uric acid of 0.3 mg/dL was seen in the finerenone group compared to placebo up to month 16, which attenuated over time. Gout reporting was comparable in finerenone‑treated patients (3.1%) and in placebo‑treated patients (3.0%).

In the FINEARTS‑HF study, hyperuricaemia reporting was comparable in finerenone‑treated patients (2.7%) and in placebo‑treated patients (2.4%). Gout reporting was comparable in finerenone‑treated patients (2.4%) and in placebo‑treated patients (2.8%).

In all studies, hyperuricaemia events were non-serious and did not result in permanent discontinuation in patients who received finerenone.

Gastrointestinal disorders

In the FINEARTS-HF study, diarrhoea (5.7% vs. 4.4%) and constipation (3.8% vs. 2.7%) were reported more frequently for finerenone compared with placebo.

Haemoglobin decreased

In the pooled data of FIDELIO‑DKD and FIGARO-DKD studies, finerenone was associated with a placebo-corrected absolute decrease in mean haemoglobin of 0.15 g/dL and mean haematocrit of 0.5% after 4 months of treatment. Anaemia reporting was comparable in finerenone‑treated patients (6.5%) and placebo‑treated patients (6.1%). The frequency of serious events of anaemia was low in both the finerenone‑treated and placebo‑treated patients (0.5%). Changes in haemoglobin and haematocrit were transient and reached comparable levels to those observed in the placebo-treated group after about 24-32 months.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9. Overdose

The most likely manifestation of overdose is anticipated to be hyperkalaemia. If hyperkalaemia develops, standard treatment should be initiated.

Finerenone is unlikely to be efficiently removed by haemodialysis given its fraction bound to plasma proteins of about 90%.