Finerenone

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

Initiation of treatment: In patients with eGFR <25 mL/min/1.73 m², finerenone treatment should not be initiated due to limited clinical data.

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 to the recommended daily dose of 20 mg.

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).

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.

Serum potassium should be monitored during concomitant use of finerenone with moderate or weak CYP3A4 inhibitors.

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 C_max. 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 C_max, 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.

Weak CYP3A4 inhibitors

The PBPK simulations suggest that fluvoxamine (100 mg twice daily), increases finerenone AUC (1.6-fold) and C_max (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.

Finerenone 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.

In patients with moderate hepatic impairment, no initial dose adjustment is required. Consider additional serum potassium monitoring and adapt monitoring according to patient characteristics.

In patients with severe hepatic impairment, finerenone should not be initiated. These patients have not been studied but a significant increase in finerenone exposure is expected.

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

The risk of hyperkalaemia also may increase with the intake of concomitant medications that may increase serum potassium.

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.
• trimethoprim, or trimethoprim/sulfamethoxazole. Temporary discontinuation of finerenone may be necessary.

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.

There are no data from the use of finerenone in pregnant women.

Studies in animals have shown reproductive toxicity.

Finerenone 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.

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.

A risk to the newborns/infants cannot be excluded.

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from finerenone therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Contraception in females

Women of childbearing potential should use effective contraception during finerenone treatment.

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.

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

Summary of the safety profile

The most frequently reported adverse reaction under treatment with finerenone was hyperkalaemia (14.0%). See 'Description of selected adverse reactions and Hyperkalaemia' below.

Tabulated list of adverse reactions

The safety of finerenone in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) was evaluated in 2 pivotal phase III studies, FIDELIO-DKD (diabetic kidney disease) and FIGARO-DKD. In the FIDELIO-DKD study 2,827 patients received finerenone (10 or 20 mg once daily) with a mean duration of treatment of 2.2 years. In the FIGARO-DKD study, 3,683 patients received finerenone (10 or 20 mg once daily) with a mean duration of treatment of 2.9 years.

The adverse reactions observed are listed in the table below. They are classified according to MedDRA's system organ class database 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).

Adverse reactions:

Description of selected adverse reactions

Hyperkalaemia

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. An increase from baseline in mean serum potassium in the first month of treatment of 0.17 mmol/L was observed in the finerenone group compared to placebo, which remained stable thereafter. The majority of hyperkalaemia events were mild to moderate and resolved in patients treated with finerenone. 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 1.2% 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.

Hypotension

In the pooled data of FIDELIO-DKD and FIGARO-DKD studies, hypotension events were reported in 4.6% 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%).

The majority of hypotension events were mild or moderate and resolved in patients treated with finerenone. The mean systolic blood pressure decreased by 2-4 mm Hg and the mean diastolic blood pressure decreased by 1-2 mm Hg at month 1, remaining stable thereafter.

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. All events were non-serious and did not result in permanent discontinuation in patients who received finerenone. 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. No difference between the finerenone group and the placebo group was observed for reported events of gout (3.0%).

Glomerular filtration rate (GFR) decreased

In the pooled data of FIDELIO-DKD and FIGARO-DKD studies, GFR decreased events were reported in 5.3% 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%). The majority of GFR decreased 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.

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.