Firialta film-coated tablets 20 mg No. 28

Instructions for Firialta film-coated tablets 20 mg No. 28

Composition

active ingredient: finerenone;

1 film-coated tablet contains 10 mg of finerenone;

1 film-coated tablet contains 20 mg of finerenone;

excipients:

film-coated tablets, 10 mg: microcrystalline cellulose, croscarmellose sodium, hypromellose 5 cP (hydroxypropylmethylcellulose 2910), lactose monohydrate, magnesium stearate, sodium lauryl sulfate; film-coating: light pink lacquer or alternatively hypromellose 5 cP (hydroxypropylmethylcellulose 2910), titanium dioxide (E 171), talc, iron oxide red (E 172);

film-coated tablets, 20 mg: microcrystalline cellulose, croscarmellose sodium, hypromellose 5 cP (hydroxypropylmethylcellulose 2910), lactose monohydrate, magnesium stearate, sodium lauryl sulfate; film-coating: light yellow lacquer or alternatively hypromellose 5 cP (hydroxypropylmethylcellulose 2910), titanium dioxide (E 171), talc, iron oxide yellow (E 172).

Dosage form

Film-coated tablets.

Main physicochemical properties:

film-coated tablets, 10 mg: pink oval-oblong film-coated tablet, 10 mm long and 5 mm wide, marked on the top side of the tablet with “10” and on the bottom side of the tablet with “FI”;

Film-coated tablets, 20 mg: pale yellow, oval-oblong film-coated tablet, 10 mm long and 5 mm wide, marked on the top side of the tablet with “20” and on the bottom side of the tablet with “FI”.

Pharmacotherapeutic group

Drugs affecting the cardiovascular system. Diuretics. Aldosterone antagonists and other potassium-sparing drugs. Aldosterone antagonists. Finerenone.

ATX code C03D A05.

Pharmacological properties

Pharmacodynamics.

Mechanism of action

Finerenone is a nonsteroidal, selective antagonist of mineralocorticoid receptors (MRs), which are activated by aldosterone and cortisol and regulate gene transcription. Its binding to MRs results in the formation of a specific receptor-ligand complex that blocks the recruitment of transcriptional coactivators of genes involved in the expression of proinflammatory and profibrotic mediators.

Pharmacodynamic effects

In the randomized, double-blind, placebo-controlled, multicenter, phase III FIDELIO-DKD study in adult patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM), the relative reduction in placebo-adjusted urinary albumin-to-creatinine ratio (UCAR) in the finerenone treatment group was 31% at month 4.

In the ARTS-DN randomized, double-blind, placebo-controlled, multicenter, phase IIb study in adult patients with CKD and T2DM, the relative reduction in placebo-adjusted SACC at day 90 was 25% and 38% in the finerenone 10 mg and 20 mg once daily groups, respectively.

Cardiac electrophysiology

A dedicated QT study in 57 healthy subjects showed that finerenone had no effect on myocardial repolarization. There was no evidence of finerenone prolonging the QT/QTc interval after single doses of 20 mg (therapeutic) or 80 mg (supratherapeutic).

Clinical efficacy and safety

The FIDELIO-DKD study investigated the effects of finerenone versus placebo on renal and cardiovascular (CV) outcomes in adult patients with CKD and type 2 diabetes. Patients were enrolled if they had persistent albuminuria (>30 mg/g to 5000 mg/g), a GFR of 25 to 75 mL/min/1.73 m2, a serum potassium level ≤ 4.8 mmol/L at screening, and were required to receive standard of care, including the maximum tolerated labeled dose of an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB). Patients with diagnosed heart failure with reduced ejection fraction (New York Heart Association (NYHA) functional classes II–IV) were excluded from the study due to the class 1A recommendation for treatment with mineralocorticoid receptor antagonists.

The primary endpoint of the study was time to the first occurrence of a composite of the following events: first occurrence of renal failure (defined as chronic dialysis or kidney transplantation, or a persistent decrease in eGFR to < 15 mL/min/1.73 m2 for at least 4 weeks), a persistent decrease in eGFR of 40% or more from baseline for at least 4 weeks, or death due to renal failure. The key secondary endpoint was time to the first occurrence of a composite of the following events: death from CV disease, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for heart failure.

At the end of the study, vital status information was available for 99.7% of patients. The study population was 63% Caucasian, 25% Asian, and 5% Black. The mean age of patients at baseline was 66 years, and 70% were male. At baseline, the mean eGFR was 44.3 mL/min/1.73 m2, with 55% of patients having an eGFR < 45 mL/min/1.73 m2, median SAKS was 852 mg/g, and mean HbA1c was 7.7%, 46% had a history of atherosclerotic cardiovascular disease, 30% had ischemic heart disease, 8% had heart failure, and mean blood pressure was 138/76 mm Hg. The mean duration of T2DM at baseline was 16.6 years, and a history of diabetic retinopathy and diabetic neuropathy was present in 47% and 26% of patients, respectively, at baseline. At baseline, almost all patients were taking an ACE inhibitor (34%) or an ARB (66%), and 97% of patients were taking one or more antidiabetic medications (insulin [64%], biguanides [44%], glucagon-like peptide-1 receptor agonists [7%], sodium-dependent glucose cotransporter-2 inhibitor [5%]). Other medications most commonly used at baseline were statins (74%) and calcium channel blockers (63%).

A statistically significant difference in favor of finerenone was shown for the primary composite endpoint and the key secondary composite endpoint (see Figure 1/Table 1 below).

For the secondary endpoint of change in SAH from baseline to month 4, the finerenone group showed a relative reduction of 31.2% compared to placebo. The treatment effect on the primary and key secondary endpoints was generally similar across subgroups, including eGFR, SAH, systolic blood pressure, and HbA1c at baseline.

Table 1

Analysis of primary and secondary endpoints of time to event (and their individual components) in the phase III FIDELIO-DKD study

* Therapy with 10 or 20 mg once daily in addition to the maximum tolerated doses of ACE inhibitors or ARBs.

** p is not statistically significant after adjustment for multiplicity.

Fig. 1. Time to first occurrence of renal failure, sustained decline in eGFR ≥ 40% from baseline, or death due to renal failure in the FIDELIO-DKD study.

Pediatric patients

The European Medicines Agency has deferred the obligation to submit the results of studies with Firialta in one or more subsets of the paediatric population in the treatment of chronic kidney disease (for information on paediatric use, see “Dosage and administration”).

Pharmacokinetics.

Finerenone is almost completely absorbed after oral administration. Absorption is rapid, with peak plasma concentrations (Cₘₐₓ) occurring 0.5–1.25 hours after administration of the tablet in the fasting state. The absolute bioavailability of finerenone is 43.5% due to first-pass metabolism in the intestinal wall and liver. Finerenone is a substrate of the efflux transporter P-glycoprotein in vitro, which is, however, not considered relevant for its absorption in vivo due to the high permeability of finerenone.

Effect of food: Intake of a high-fat, high-calorie meal increased the AUC of finerenone by 21%, decreased Cₘₐₓ by 19%, and delayed the time to reach Cₘₐₓ by 2.5 hours. Since this is not considered clinically significant, finerenone can be taken without regard to food.

Distribution

The steady-state volume of distribution (Vₛₛ) of finerenone is 52.6 L. The binding of finerenone to human plasma proteins in vitro is 91.7%, with serum albumin being the major binding protein.

Biotransformation

Approximately 90% of the metabolism is mediated by CYP3A4 and 10% by CYP2C8. Four major metabolites have been identified in plasma. All metabolites are pharmacologically inactive.

Breeding

Finerenone is rapidly eliminated from plasma, with a half-life (t½) of approximately 2 to 3 hours. The systemic clearance of finerenone in the blood is approximately 25 l/h. Approximately 80% of the administered dose was excreted in the urine and approximately 20% in the feces. Elimination occurred almost exclusively as metabolites, while excretion of unchanged finerenone is a minor route (< 1% of the dose in the urine due to glomerular filtration, < 0.2% in the feces).

Linearity

The pharmacokinetics of finerenone are linear in the studied dose range of 1.25 to 80 mg.

Special patient groups

Elderly patients: Of the 2,827 patients treated with finerenone in the FIDELIO-DKD study, 58% were 65 years of age or older and 15% were 75 years of age or older. Overall, no differences in the safety or efficacy of finerenone were observed between these patients and younger patients.

In a phase I study (N = 48), elderly patients (≥ 65 years) had higher plasma concentrations of finerenone than younger patients (≤ 45 years), with mean AUC and Cmax values being 34% and 51% higher in elderly patients (see Dosage and Administration). Population pharmacokinetic analysis did not identify age as a covariate for finerenone AUC or Cmax.

Renal impairment: Mild renal impairment (creatinine clearance (CLcr) 60 to <90 mL/min) had no effect on the AUC and Cₘₐₓ of finerenone. Compared with patients with normal renal function (CLcr ≥90 mL/min), the effect of moderate (CLcr 30 to <60 mL/min) and severe (CLcr <30 mL/min) renal impairment on the AUC of finerenone was similar, with an increase of 34–36%. Moderate or severe renal impairment had no effect on Cₘₐₓ (see section 4.2).

Due to its high level of plasma protein binding, finerenone is not expected to be dialyzable.

Hepatic impairment: Finerenone exposure was not altered in patients with cirrhosis and mild hepatic impairment (see Dosage and Administration).

In cirrhotic patients with moderate hepatic impairment, compared to healthy controls, the total AUC of finerenone and the AUC of unbound finerenone increased by 38% and 55%, respectively, while no changes in Cmax were observed (see section 4.2).

There are no data in patients with severe hepatic impairment (see sections “Method of administration and dosage” and “Interaction with other medicinal products and other types of interactions”).

Body weight: A population pharmacokinetic analysis identified body weight as a covariate for Cₘₐₓ of finerenone. In a patient weighing 50 kg, Cₘₐₓ is estimated to be 43-51% higher compared to a patient weighing 100 kg. No dose adjustment based on body weight is warranted (see section 4.2).

Pharmacokinetic/pharmacodynamic relationships

The concentration-effect relationship for urinary albumin to creatinine ratio (UCRR) over time was characterized by a maximal effect model, indicating saturation at high exposure. The model predicted time to reach full (99%) drug effect at steady state on UCRR was 138 days. The pharmacokinetic (PK) half-life was 2–3 hours, and PK steady state was reached after 2 days, indicating an indirect and delayed effect on pharmacodynamic effects.

Clinical studies without significant drug interactions

Concomitant administration of gemfibrozil (600 mg twice daily), a strong CYP2C8 inhibitor, increased the mean AUC and Cₘₐₓ of finerenone by 1.1- and 1.2-fold, respectively. This is not considered clinically relevant.

Pre- and concomitant therapy with the proton pump inhibitor omeprazole (40 mg once daily) had no effect on the mean AUC and mean Cₘₐₓ of finerenone.

Co-administration of the antacid aluminum hydroxide and magnesium hydroxide (70 mV) had no effect on the mean AUC of finerenone and decreased the mean Cmax by 19%. This is not considered clinically significant.

A single dose of 20 mg finerenone also had no clinically significant effect on the AUC and Cₘₐₓ of repaglinide, a CYP2C8 substrate. Therefore, finerenone does not inhibit CYP2C8.

No pharmacokinetic interaction was demonstrated between finerenone and the CYP2C9 substrate warfarin and between finerenone and the P-gp substrate digoxin.

Preclinical safety data

Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, single dose toxicity, repeated dose toxicity, genotoxicity, phototoxicity, carcinogenic potential, and effects on male and female fertility.

Indication

The drug Firialta is indicated for the treatment of chronic kidney disease (stages 3 and 4 with albuminuria) associated with type 2 diabetes mellitus in adults.

Contraindication

Hypersensitivity to the active substance or to any of the excipients.

Concomitant use with strong CYP3A4 inhibitors (see section "Interaction with other medicinal products and other forms of interaction"), e.g. itraconazole, ketoconazole, ritonavir, nelfinavir, cobicistat, clarithromycin, telithromycin, nefazodone. Addison's disease.

Interaction with other medicinal products and other types of interactions

Interaction studies have only been conducted in adult patients.

Finerenone is eliminated almost exclusively by oxidative metabolism mediated by cytochrome P450 (CYP) (primarily CYP3A4 [90%] with a minor contribution from CYP2C8 [10%]).

Concomitant use is contraindicated

Strong CYP3A4 inhibitors

Concomitant use of Firialta with itraconazole, clarithromycin and other strong CYP3A4 inhibitors (e.g. ketoconazole, ritonavir, nelfinavir, cobicistat, telithromycin or nefazodone) is contraindicated (see section 4.3) as a marked increase in finerenone exposure is expected.

Concomitant use is not recommended.

Strong and moderate CYP3A4 inducers

Firialta 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 concentrations and lead to reduced therapeutic effect (see section 4.4).

Some medications that increase serum potassium levels

Firialta should not be used concomitantly with potassium-sparing diuretics (e.g. amiloride, triamterene) and other mineralocorticoid receptor antagonists (e.g. eplerenone, esaxerenone, spironolactone, canrenone). These medicinal products are expected to increase the risk of hyperkalaemia (see section 4.4).

Grapefruit

Grapefruit or grapefruit juice should not be consumed during treatment with finerenone, as this is expected to increase finerenone plasma concentrations due to inhibition of CYP3A4 (see sections 4.2 and 4.4).

Concomitant use with precautions

Moderate CYP3A4 inhibitors

In a clinical study, concomitant administration of erythromycin (500 mg three times daily) resulted in a 3.5-fold increase in finerenone AUC and a 1.9-fold increase in its Cₘₐₓ. In another clinical study, verapamil (controlled-release tablets 240 mg once daily) resulted in a 2.7- and 2.2-fold increase in finerenone AUC and Cₘₐₓ, respectively.

Serum potassium levels may increase, therefore it is recommended to monitor serum potassium levels, especially when starting or changing the dose of finerenone or a CYP3A4 inhibitor (see sections “Method of administration and dosage” and “Special warnings and precautions for use”).

Weak CYP3A4 inhibitors

Pharmacokinetic physiologically based modeling shows that fluvoxamine (100 mg twice daily) increases finerenone AUC (1.6-fold) and Cₘₐₓ (1.4-fold).

Serum potassium levels may increase, therefore it is recommended to monitor serum potassium levels, especially at the beginning of therapy or in case of a change in the dose of finerenone or a CYP3A4 inhibitor (see sections “Method of administration and dosage” and “Special warnings and precautions for use”).

Certain medicines that increase serum potassium levels (see section "Special warnings and precautions for use")

Concomitant use of Firialta with potassium supplements and trimethoprim or trimethoprim/sulfamethoxazole is expected to increase the risk of hyperkalemia. Serum potassium levels should be monitored.

It may be necessary to temporarily discontinue Firialta during treatment with trimethoprim or trimethoprim/sulfamethoxazole.

Antihypertensive drugs

The risk of hypotension is increased when several other antihypertensive drugs are used concomitantly. Blood pressure monitoring is recommended in such patients.

Application features

Hyperkalemia

Hyperkalemia has been observed in patients treated with finerenone (see section 4.8).

Risk factors include low eGFR, high serum potassium, and previous episodes of hyperkalemia. More frequent monitoring of these patients should be considered.

Initiation and continuation of therapy (see section “Method of administration and dosage”)

If serum potassium is > 5.0 mmol/L, finerenone therapy should not be initiated.

If serum potassium is > 4.8–5.0 mmol/L, initiation of finerenone therapy with additional serum potassium monitoring for the first 4 weeks may be considered depending on patient characteristics and serum potassium levels.

If serum potassium levels are > 5.5 mmol/L, finerenone treatment should be discontinued. Standard recommendations for the treatment of hyperkalemia should be followed.

Once serum potassium is ≤ 5.0 mmol/L, finerenone treatment can be resumed at a dosage of 10 mg once daily.

CONTROL

Serum potassium and eGFR should be re-measured in all patients 4 weeks after initiation, resumption of therapy, or dose increase of finerenone. Thereafter, serum potassium should be assessed periodically and as needed, depending on patient characteristics and serum potassium levels (see section 4.2).

Concomitant therapy

The risk of hyperkalemia may also be increased by concomitant use of medicinal products that may increase serum potassium levels (see section 4.5). See also Concomitant use of substances affecting finerenone exposure.

Finerenone should not be used concomitantly with:

• potassium-sparing diuretics (e.g. amiloride, triamterene) and
• other mineralocorticoid receptor antagonists ((AMRA), e.g. eplerenone, esaxerenone, spironolactone, canrenone).

Finerenone should be used with caution and serum potassium levels should be monitored when co-administered with:

• potassium preparations;
• trimethoprim or trimethoprim/sulfamethoxazole. Temporary discontinuation of finerenone may be required.

Kidney dysfunction

The risk of hyperkalemia increases with decreased renal function. If necessary, regular monitoring of renal function should be performed according to standard practice (see section "Method of administration and dosage").

Beginning of therapy

Finerenone therapy 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 therapy

Finerenone therapy should be discontinued in patients with advanced end-stage renal disease (eGFR < 15 mL/min/1.73 m2) as clinical data are limited.

Liver dysfunction

Finerenone therapy should not be initiated in patients with severe hepatic impairment (see section 4.2). Use in these patients has 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 increased exposure to finerenone. Additional monitoring of serum potassium levels and adaptation of monitoring to patient characteristics should be considered (see sections 4.2 and 5.2).

Heart failure

Patients with established heart failure with reduced ejection fraction (New York Heart Association (NYHA) functional classes II–IV) were excluded from the phase III clinical study (see Pharmacodynamics).

Concomitant use of substances that affect finerenone exposure

Moderate and weak CYP3A4 inhibitors

Serum potassium levels should be monitored when finerenone is used concomitantly with moderate or weak CYP3A4 inhibitors (see sections 4.2 and 4.4).

Strong and moderate CYP3A4 inducers

Finerenone should not be used concomitantly with strong or moderate CYP3A4 inducers (see section “Interaction with other medicinal products and other types of interactions”).

Grapefruit

Grapefruit or grapefruit juice should not be consumed during treatment with finerenone (see sections “Dosage and administration” and “Interaction with other medicinal products and other forms of interaction”).

Embryofetal toxicity

Finerenone should not be used during pregnancy unless the benefits to the mother and the risks to the fetus have been carefully weighed. If a woman becomes pregnant while using finerenone, she should be informed of the potential risks to the fetus.

Women of reproductive age should be advised to use effective contraception during treatment with finerenone.

Women should be advised to discontinue breastfeeding during treatment with finerenone.

For further information, see sections “Use during pregnancy or lactation” and “Preclinical safety data”.

Information on excipients

The drug Firialta contains lactose.

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

This medicine contains less than 1 mmol sodium (23 mg) per tablet, i.e. essentially 'sodium-free'.

Use during pregnancy or breastfeeding

Contraception in women

Women of reproductive age should use effective contraception during treatment with finerenone (see section "Special warnings and precautions for use").

Pregnancy

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

Animal studies have shown reproductive toxicity.

Firialta should not be used during pregnancy unless the clinical condition of the woman requires treatment with finerenone. If a woman becomes pregnant while taking finerenone, she should be informed of the potential risks to the fetus (see section "Special warnings and precautions for use").

Breast-feeding

It is not known whether finerenone or its metabolites are excreted in human milk.

Available pharmacokinetic/toxicological data have shown excretion of finerenone and its metabolites in milk in animals. Adverse effects were observed in rats exposed to the drug by this route. A risk to the newborn/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 (see section 4.4).

Fertility

There are no data on the effect of finerenone on human fertility.

Animal studies have shown reduced female fertility at exposures exceeding the maximum human exposure, which is of low clinical relevance.

Ability to influence reaction speed when driving vehicles or other mechanisms

The drug Firialtane affects the reaction speed when driving vehicles or other mechanisms.

Method of administration and doses

Dosage

The recommended dose is 20 mg of finerenone once daily.

The maximum recommended dose is 20 mg of finerenone once daily.

Beginning of therapy

Serum potassium and eGFR should be measured to determine whether treatment with finerenone can be initiated and to calculate the initial dose.

If serum potassium is ≤ 4.8 mmol/L, finerenone therapy can be initiated. For monitoring of serum potassium, see “Continuation of therapy” below.

If serum potassium is > 4.8-5.0 mmol/L, initiation of finerenone therapy with additional serum potassium monitoring for the first 4 weeks may be considered depending on patient characteristics and serum potassium levels (see section 4.4).

If the serum potassium level is > 5.0 mmol/L, then finerenone therapy should not be initiated (see section "Special warnings and precautions for use").

The recommended starting dose of finerenone is based on eGFR and is presented in Table 2.

Table 2

Initiation of finerenone therapy and recommended dose

Continuation of therapy

Serum potassium and eGFR should be re-measured 4 weeks after initiation or resumption of finerenone therapy or dose increase (see Table 3 for determination of continued finerenone therapy and dose adjustment).

Thereafter, serum potassium levels should be measured periodically and as needed, depending on patient characteristics and serum potassium levels.

For additional information, see sections “Special warnings and precautions for use” and “Interaction with other medicinal products and other types of interactions”.

Table 3

Continuation of finerenone therapy and dose adjustment

* Maintain 10 mg once daily if eGFR decreases > 30% from previous measurement

Missed dose

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

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

Special patient groups

Elderly patients

No dose adjustment is required for elderly patients (see Pharmacokinetics).

Kidney dysfunction

Starting treatment

Finerenone therapy should not be initiated in patients with eGFR < 25 ml/min/1.73 m2 due to limited clinical data (see sections 4.4 and 5.2).

In patients with eGFR ≥ 15 mL/min/1.73 m2, finerenone therapy may be continued with dose adjustments based on serum potassium levels. eGFR should be measured 4 weeks after initiation of therapy to determine whether the initial dose can be increased to the recommended daily dose of 20 mg (see Dosage, Continued Therapy and Table 3).

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

Liver dysfunction

Patients with

• severe liver failure:

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

• moderate hepatic insufficiency:

No adjustment of the initial dose is necessary. Additional monitoring of serum potassium should be considered and monitoring should be adapted to the patient's characteristics (see sections 4.4 and 5.2).

• mild liver failure:

no adjustment of the initial dose is required.

Concomitant therapy

For patients taking finerenone concomitantly with moderate or weak CYP3A4 inhibitors, potassium supplements, trimethoprim or trimethoprim/sulfamethoxazole, additional monitoring of serum potassium should be considered and monitoring should be adapted to the patient's characteristics (see section 4.4). The decision to continue finerenone therapy should be made according to the guidelines in Table 3 (Dosage, continuation of therapy).

Temporary discontinuation of finerenone may be necessary if patients are required to take trimethoprim or trimethoprim/sulfamethoxazole. For further information, see sections 4.4 and 4.5.

Body weight

No dose adjustment based on body weight is required (see Pharmacokinetics).

Method of application

Administer orally.

The tablets can be taken with a glass of water, regardless of food intake (see section "Pharmacokinetics").

The tablets should not be taken with grapefruit or grapefruit juice (see section “Interaction with other medicinal products and other types of interactions”).

Tablet crushing

For patients who are unable to swallow whole tablets, Firialta tablets may be crushed and mixed with water or soft food, such as applesauce, immediately prior to oral administration (see Pharmacokinetics).

Children.

The safety and efficacy of finerenone in children (under 18 years of age) have not yet been established. Data are not available.

Overdose

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

Finerenone is unlikely to be effectively removed by hemodialysis, as its plasma protein binding fraction is approximately 90%.

Side effects

Summary of safety profile

The most common adverse reaction observed with Firialta therapy was hyperkalemia (≥ 10%), see “Hyperkalemia” below and the “Special warnings and precautions for use” section.

The safety of Firialta in patients with chronic kidney disease and type 2 diabetes was evaluated in the pivotal phase III study FIDELIO-DKD (diabetic kidney disease). In this study, 2,827 patients received Firialta (10 or 20 mg once daily) and 2,831 received placebo. The median duration of treatment was 2.2 years.

The adverse reactions reported are listed in the table below.