Source: European Medicines Agency (EU) Revision Year: 2022 Publisher: Bayer AG, 51368 Leverkusen, Germany
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. 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.
Serum potassium and eGFR have to be remeasured in all patients 4 weeks after initiation, re-start or increase in dose 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).
The risk of hyperkalaemia also may increase with the intake of concomitant medications 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:
Finerenone should be used with caution and serum potassium should be monitored when taken concomitantly with:
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).
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).
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).
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 diagnosed heart failure with reduced ejection fraction and New York Heart Association II-IV were excluded from the phase III clinical study (see section 5.1).
Serum potassium should be monitored during concomitant use of finerenone with moderate or weak CYP3A4 inhibitors (see sections 4.2 and 4.5).
Finerenone should not be used concomitantly with strong or moderate CYP3A4 inducers (see section 4.5).
Grapefruit or grapefruit juice should not be consumed during finerenone treatment (see sections 4.2 and 4.5).
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.
Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.
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 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.
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).
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 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).
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).
The 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).
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.
The risk for hypotension increases with concomitant use of multiple other antihypertensive medicinal products. In these patients, blood pressure monitoring is recommended.
Women of childbearing potential should use effective contraception during finerenone treatment (see section 4.4).
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).
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).
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).
Kerendia has no influence on the ability to drive and use machines.
The most frequently reported adverse reaction under treatment with finerenone was hyperkalaemia (18.3%). See ‘Description of adverse reactions, Hyperkalaemia’ below and section 4.4.
The safety of finerenone in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) was evaluated in the pivotal phase III study FIDELIO-DKD (diabetic kidney disease). In this study 2,827 patients received finerenone (10 or 20 mg once daily) with a mean duration of treatment of 2.2 years.
The adverse reactions observed are listed in table 3. 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).
Table 3. Adverse reactions:
| System Organ Class (MedDRA) | Very common | Common | Uncommon |
|---|---|---|---|
| Metabolism and nutrition disorders | Hyperkalaemia | Hyponatraemia | |
| Vascular disorders | Hypotension | ||
| Skin and subcutaneous tissue disorders | Pruritus | ||
| Investigations | Glomerular filtration rate decreased | Haemoglobin decreased |
In the FIDELIO-DKD study, hyperkalaemia events were reported in 18.3% of finerenone-treated patients compared with 9.0% of placebo-treated patients. In patients treated with finerenone, the majority of hyperkalaemia events were mild to moderate and resolved. Serious events of hyperkalaemia were reported more frequently for finerenone (1.6%) than for placebo (0.4%). Serum potassium concentrations >5.5 mmol/L and >6.0 mmol/L were reported in 21.7% and 4.5% of finerenone-treated patients and in 9.8% and 1.4% of placebo-treated patients, respectively.
Hyperkalaemia leading to permanent discontinuation in patients who received finerenone was 2.3% versus 0.9% in the placebo group. Hospitalisation due to hyperkalaemia in the finerenone group was 1.4% versus 0.3% in the placebo group.
An increase from baseline in mean serum potassium was observed in the first month of finerenone treatment compared to placebo and a maximum between-group difference of 0.23 mmol/L at month 4. The difference in serum potassium between finerenone and placebo remained stable thereafter.
For specific recommendations, refer to sections 4.2 and 4.4.
In the FIDELIO-DKD study, hypotension events were reported in 4.8% of finerenone-treated patients compared with 3.4% of placebo-treated patients. In patients treated with finerenone, the majority of hypotension events were mild or moderate and resolved. In one patient (<0.1%), finerenone treatment was permanently discontinued due to hypotension. Hospitalisation due to hypotension in the finerenone group was 0.2% versus 0.2% in the placebo group.
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.
In the FIDELIO-DKD study, GFR decreased events were reported in 6.3% of finerenone-treated patients compared with 4.7% of placebo-treated patients. In patients treated with finerenone, the majority of GFR rate decreased events were mild or moderate and resolved. GFR rate decreased events leading to permanent discontinuation in patients who received finerenone were 0.2% versus 0.3% in the placebo group. Hospitalisation due to decreased GFR filtration rate in the finerenone group was 0.1% versus 0.1% in the placebo group. 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.
After 4 months of treatment, finerenone was associated with a placebo-corrected absolute decrease in mean haemoglobin of 0.14 g/dL and mean haematocrit of 0.46%. Changes in haemoglobin and haematocrit were transient and reached comparable levels to those observed in the placebo-treated group after about 24 months. Anaemia was slightly increased in finerenone-treated patients (7.4%) compared with placebo-treated patients (6.7%). The frequency of serious events of anaemia was low and balanced (0.5% in finerenone-treated patients versus 0.7% in placebo-treated patients).
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 national reporting system listed in Appendix V.
Not applicable.
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