DRUG INTERACTIONS-(summary)

­ • Strong CYP3A4 Inhibitors: Use is contraindicated. 

• Grapefruit or Grapefruit Juice: Avoid concomitant use. 

 • Moderate or weak CYP3A4 Inhibitors: Monitor serum potassium during drug initiation or dosage adjustment of either Kerendia or the moderate or weak CYP3A4 inhibitor, and adjust Kerendia dosage as appropriate 

• Strong or moderate CYP3A4 Inducers: Avoid concomitant use.

BRIEF SUMMARY

FINERENONE- (July 2021)

Indn-   To reduce the risk of kidney and heart  complications in chronic kidney disease                 associated with type 2 diabetes   

Comp-   Tablets: 10 mg and 20 mg . The recommended starting dosage is 10 mg or 20 mg orally once daily based on estimated glomerular filtration rate (eGFR) and serum potassium thresholds.

ADR-  Adverse reactions occurring  on Kerendia and more frequently than placebo are hyperkalemia, hypotension, and hyponatremia.

CI-   Concomitant use with strong CYP3A4 inhibitors. 

• Patients with adrenal insufficiency. Patients with decreased kidney function and higher baseline potassium levels are at increased risk. Monitor serum potassium levels and adjust dose as needed

Pat Inform-

 Avoid concomitant intake of grapefruit or grapefruit juice as it is expected

Advise women that breastfeeding is not recommended at the time of treatment with  for 1 day after treatment

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U.S. FDA APPROVED DRUGS SURING 2021                                          

Serial No 29

Name of the Drug-    KERENDIA

Active Ingredient -   Finerenone

Pharmacological Classification- To reduce the risk of kidney and heart                                                                             complications in chronic kidney disease                                                                          associated with type 2 diabetes                                 

 Date of Approval-          7/9/2021                                                                                

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use                         KERENDIA safely and effectively.                                                                                   See full prescribing information for KERENDIA. KERENDIA (finerenone) tablets, for oral use

Initial U.S. Approval: 2021

 INDICATIONS AND USAGE

 Kerendia is a non-steroidal mineralocorticoid receptor antagonist (MRA) indicated to reduce the risk of sustained eGFR decline, end stage kidney disease, cardiovascular death, non-fatal myocardial infarction, and hospitalization for heart failure in adult patients with chronic kidney disease (CKD) associated with type 2 diabetes (T2D).

ADVERSE REACTIONS 

Adverse reactions occurring in = 1% of patients on Kerendia and more frequently than placebo are hyperkalemia, hypotension, and hyponatremia.

CONTRAINDICATIONS

­ • Concomitant use with strong CYP3A4 inhibitors. 

• Patients with adrenal insufficiency. Patients with decreased kidney function and higher baseline potassium levels are at increased risk. Monitor serum potassium levels and adjust dose as needed.

 INDICATIONS AND USAGE

 Kerendia is a non-steroidal mineralocorticoid receptor antagonist (MRA) indicated to reduce the risk of sustained eGFR decline, end stage kidney disease, cardiovascular death, non-fatal myocardial infarction, and hospitalization for heart failure in adult patients with chronic kidney disease (CKD) associated with type 2 diabetes (T2D).

DOSAGE AND ADMINISTRATION

­ • The recommended starting dosage is 10 mg or 20 mg orally once daily based on estimated glomerular filtration rate (eGFR) and serum potassium thresholds.

Based on eGFR and serum potassium thresholds. 

• Tablets may be taken with or without food

 DOSAGE FORMS AND STRENGTHS

 Tablets: 10 mg and 20 mg 

 PATIENT COUNSELING INFORMATION

Advise patients of the need for periodic monitoring of serum potassium levels. 

 Advise patients receiving Kerendia to consult with their physician before using potassium supplem

Advise patients to avoid strong or moderate CYP3A4 inducers and to find alternative medicinal products with no or weak potential to induce CYP3A4 [see Drug Interactions

 Avoid concomitant intake of grapefruit or grapefruit juice as it is expected

Advise women that breastfeeding is not recommended at the time of treatment with KERENDIA and for 1 day after treatment

Manufactured for: Bayer HealthCare Pharmaceuticals Inc. Whippany, NJ 07981 Manufactured in Germany

 CLINICAL PHARMACOLOGY

1. Mechanism of Action-

Finerenone is a nonsteroidal, selective antagonist of the mineralocorticoid receptor (MR), which is activated by aldosterone and cortisol and regulates gene transcription. Finerenone blocks MR mediated sodium reabsorption and MR overactivation in both epithelial (e.g., kidney) and nonepithelial (e.g., heart, and blood vessels) tissues. MR overactivation is thought to contribute to fibrosis and inflammation.

Finerenone has a high potency and selectivity for the MR and has no relevant affinity for androgen, progesterone, estrogen, and glucocorticoid receptors.

2. Pharmacodynamics-                                                                                                    In FIDELIO-DKD, a randomized, double-blind, placebo-controlled, multicenter study in adult patients with chronic kidney disease associated with type 2 diabetes, the placebo-corrected relative reduction in urinary albumin-to-creatinine ratio (UACR) in patients randomized to finerenone was 31% at Month 4 (95% CI 29-34%) and remained stable for the duration of the trial. In patients treated with Kerendia, the mean systolic blood pressure decreased by 3 mmHg and the mean diastolic blood pressure decreased by 1-2 mmHg at month 1, remaining stable thereafter.

Cardiac Electrophysiology- At a dose 4 times the maximum approved recommended dose, finerenone does not prolong the QT interval to any clinically relevant extent.

3. Pharmacokinetics Finerenone exposure increased proportionally over a dose range of 1.25 to 80 mg (0.06 to 4 times the maximum approved recommended dosage). Steady state of finerenone was achieved after 2 days of dosing.

The estimated steady-state geometric mean Cmax,md was 160 µg/L and steady-state geometric mean AUCt,md was 686 µg.h/L following administration of finerenone 20 mg to patients.

Absorption- Finerenone is completely absorbed after oral administration but undergoes metabolism resulting in absolute bioavailability of 44%. Finerenone Cmax was achieved between 0.5 and 1.25 hours after dosing.

Effect of Food- There was no clinically significant effect on finerenone AUC following administration with high fat, high calorie food.

Distribution- The volume of distribution at steady-state (Vss) of finerenone is 52.6 L. Plasma protein binding of finerenone is 92%, primarily to serum albumin, in vitro. Elimination The terminal half-life of finerenone is about 2 to 3 hours, and the systemic blood clearance is about 25 L/h.

Metabolism- Finerenone is primarily metabolized by CYP3A4 (90%) and to a lesser extent by CYP2C8 (10%) to inactive metabolites.

Excretion- About 80% of the administered dose is excreted in urine (<1% as unchanged) and approximately 20% in feces (< 0.2% as unchanged).

 USE IN SPECIFIC POPULATIONS

1. Pregnancy Risk Summary

There are no available data on Kerendia use in pregnancy to evaluate for a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Animal studies have shown developmental toxicity at exposures about 4 times those expected in humans.

The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

2. Lactation Risk Summary -                                                                                     There are no data on the presence of finerenone or its metabolite in human milk, the effects on the breastfed infant or the effects of the drug on milk production.

In a pre- and postnatal developmental toxicity study in rats, increased pup mortality and lower pup weight were observed at about 4 times the AUCunbound expected in humans. These findings suggest that finerenone is present in rat milk

 When a drug is present in animal milk, it is likely that the drug will be present in human milk.

Because of the potential risk to breastfed infants from exposure to KERENDA, avoid breastfeeding during treatment and for 1 day after treatment.

3. Pediatric Use The safety and efficacy of Kerendia have not been established in patients below 18 years of age.

4. Geriatric Use Of the 2827 patients who received Kerendia in the FIDELIO-DKD study, 58% of patients were 65 years and older, and 15% were 75 years and older. No overall differences in safety or efficacy were observed between these patients and younger patients. No dose adjustment is required.

5. Hepatic Impairment Avoid use of Kerendia in patients with severe hepatic impairment (Child Pugh C). No dosage adjustment is recommended in patients with mild or moderate hepatic impairment (Child Pugh A or B). Consider additional serum potassium monitoring in patients with moderate hepatic impairment (Child Pugh B)

OVERDOSAGE

In the event of suspected overdose, immediately interrupt Kerendia treatment. The most likely manifestation of overdose is hyperkalemia. If hyperkalemia develops, standard treatment should be initiated. Finerenone is unlikely to be efficiently removed by hemodialysis given its fraction bound to plasma proteins of about 90%.