Lyvelsa 10 FC Tablet

Finerenone is a nonsteroidal, selective antagonist of the mineralocorticoid receptor (MR). Aldosterone and cortisol activate this receptor, and it regulates gene transcription. Finerenone blocks MR mediated sodium reabsorption and MR overactivation in epithelial tissues (e.g., kidney) and in nonepithelial tissues (e.g., heart and blood vessels). MR overactivation is thought to contribute to fibrosis and inflammation. The medicine has high potency and selectivity for the MR, and it has no relevant affinity for androgen, progesterone, estrogen and glucocorticoid receptors.

In patients treated with finerenone, the mean systolic blood pressure decreased by 3 mmHg and the mean diastolic blood pressure decreased by 1 to 2 mmHg at month 1, then stayed stable. At a dose 4 times the maximum approved recommended dose, finerenone does not prolong the QT interval to any clinically relevant extent.

It is completely absorbed after oral administration, but metabolism reduces the absolute bioavailability to 44%. Cmax was reached between 0.5 and 1.25 hours after dosing. Exposure rose in proportion to the dose across 1.25 to 80 mg (0.06 to 4 times the maximum approved recommended dosage). Steady state was reached after 2 days of dosing. After finerenone 20 mg was given to patients, the estimated steady-state geometric mean Cmax, md was 160 μg/L and the steady-state geometric mean AUCt,md was 686 μg.h/L.

Absorption: Finerenone is completely absorbed after oral administration, but it is metabolised on the way, which gives an absolute bioavailability of 44%. Cmax was reached between 0.5 and 1.25 hours after dosing.

Effect of Food: There was no clinically significant effect on finerenone AUC when it was taken with high fat, high calorie food.

Distribution: The volume of distribution at steady-state (Vss) is 52.6 L. In vitro, plasma protein binding is 92%, mainly to serum albumin.

Elimination: The terminal half-life is about 2 to 3 hours, and the systemic blood clearance is about 25 L/h.

Metabolism: Finerenone is mainly metabolised by CYP3A4 (90%) and, to a lesser extent, by CYP2C8 (10%). The metabolites are inactive.

Excretion: About 80% of the administered dose is excreted in urine.

There are no data on the use of Kerendia in pregnancy, so its risk of major birth defects, miscarriage or other bad outcomes for the mother or baby can't be judged. Animal studies showed developmental toxicity at exposures about 4 times those expected in humans. Nobody knows yet what this means for people. The background risk of major birth defects and miscarriage for the group of patients this medicine is meant for is also unknown. Every pregnancy carries some background risk of birth defects, pregnancy loss or other adverse outcomes. In the general population of the U.S., the estimated background risk in clinically recognized pregnancies is 2 to 4% for major birth defects and 15 to 20% for miscarriage, respectively.

There are no data on whether finerenone or its metabolite passes into human milk, what it does to a breastfed infant, or how it affects milk production. In a study of rats exposed before and after birth, the pups had higher mortality and lower weight at about 4 times the AUC unbound expected in humans. These findings suggest that finerenone is present in rat milk. When a drug appears in animal milk, it is likely to appear in human milk too. Because breastfed infants could be at risk from exposure to Finerenone, avoid breastfeeding during treatment and for 1 day after treatment.

Pediatric use: The safety and efficacy of Finerenone have not been established in patients below 18 years of age.

Geriatric use: In the FIDELIO-DKD study, 2827 patients received Finerenone. Of these, 58% were 65 years and older, and 15% were 75 years and older. Doctors saw no overall differences in safety or efficacy between these older patients and the younger ones, so no dose adjustment is required.

Hepatic impairment: Avoid Finerenone in patients with severe hepatic impairment (Child Pugh C). No dosage adjustment is recommended for mild or moderate hepatic impairment (Child Pugh A or B). In patients with moderate hepatic impairment (Child Pugh B), consider additional serum potassium monitoring.

If you suspect an overdose of Finerenone, stop the treatment straight away. The most likely effect of an overdose is hyperkalemia (high potassium in the blood). If hyperkalemia develops, it should be treated in the standard way. Hemodialysis is unlikely to remove Finerenone efficiently, because about 90% of the medicine is bound to plasma proteins.

Store Finerenone below 30°C, away from light and moisture. Keep it out of the reach of children.