DESCRIPTION                                

Fineron contains finerenone a nonsteroidal mineralocorticoid receptor antagonist

Finerenone chemical name is (4S)-4(4-cyano-2-methoxyphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide.

INDICATIONS

Fineron is indicated to reduce risk of sustained eGFR decline and stage kidney

Disease, cardiovascular death, nonfatal myocardial infarction and hospitalization

For heart failure in adults patients, with chronic kidney disease (CKD) associated

With type 2 diabetes.

DOSAGE AND ADMINISTRATION

Prior to initiation of fineron: measure serum potassium levels and estimated

Glomerular filtration rate (eGFR) before initiation. Do not initiate treatment if

Serum potassium is>5.0 mEq/L.

Recommended starting dosage: The recommeded starting dose of fineron

Is base on eGFR and is presented in table

eGFR (mL/min/1.73m2)	Starting dosage
≥60	20mg once daily
≥25 to<60	10mg once daily
>25	Initiation is not recommended

Monitoring and dose adjustment The target daily daily dose of fineron is 20mg. Measure serum potassium 4 weeks after initiating treatment and adjust dose. If serum potassium levels are >4.8 to 5.0 mEq/L, initiation of Fineron treatment may be considered with additional serum potassium monitoring within

First 4 weeks base on clinical judgment and serum potassium levels. Monitor serum potassium 4 weeks after a dose adjustment and throughout treatment and adjust of the dose as needed.

		Current Fineron Dose
		10mg once daily	20mg once daily
Current serum potassium (mEq/L.	≤ 4.8	Increase the dose to 20mg once daily	Maintain 20mg once daily
	˃ 4.8 – 5.5	Maintain 10mg once daily	Maintain 20mg once daily
	˃ 5.5	Withhold fineron . Consider restarting at 10mg once daily when serum potassium ≤ 5.0 mEq/L.	Withhold Fineron. Restart at 10mg once daily when serum potassium ≤ 5.0 mEq/L.

CLINICAL PHARMACOLOGY

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 bocks MR mediated sodium rabsorption and MR overactivation in both epithelial (e.g., kidney) and nonepethelial (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.

 Pharmacokinetics Finwerenone exposuire increased proportionally over a dose range of 1.25 to 80mg (0.06 to 4 time the maximum approved recommended dosage). Steady state geometric mean C_max,md was 160 µg/L and steady state geometric mean AUCJ md was 686 µg.h/L following administration of finerenone 20mg to patients.

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

Distribution The volium e 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 25L/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% and approximately 20% in feces (<0.2% as unchanged).

CONTRAINDICATIONS

Fineron is contraindicated in patients

● Who are receiving concomitant treatment with Strong CYP3A4 inhibitors.

● With adrenal insufficiency.

WARNINGS AND PRECAUTIONS:

Hyperkalemia

Finerenone can cause hyperkalemia . The risk for developing hyperkalemia increases with decreasing kidney function and is greater in patients with higher baseline potassium levels or other risk factors for hyperkalemia. Measure serum potassium and eGFR in all patients before initiation of treatment with Finerenone and dose accordingly. Do not initiate Finerenone if  serum potassium is > 5.0 mEq/L. Measure serum potassium periodically during treatment with Finerenone and adjust dose accordingly. More frequent monitoring may be necessary for patients at risk for hyperkalemia, including those on concomitant medications that impair potassium excretion or increase serum potassium.

SIDE EFFECTS

The following are the side effects as described below:

● Hyperkalemia

●Hypotension

●Hyponatremia

DRUG INTERACTIONS

CYP3A4 Inhibitors and inducers

Strong CYP3A4 Inhibitors Finerenone is a CYP3A4 substrate. Concomnitant use with a strong CYP3A4 inhibitor increases finerenone exposure, which may increase the risk of finerenone adverse reactions. Concomitant use of finerenone with strong CYP3A4 inhibitors is contraindicated. Avoid concomitant intake of grapefruit or grapefruit juice.

Moderate and Weak CYP3A4 Inhibitors Finerenone is a CYP3A4 substrate.

Concomitant use with a moderate or weak CYP3A4 inhibitor increases Finerenone exposure, which may increase the risk of Finerenone adverse reactions. Monitor serum potassium during drug initiation or dosage adjustment of either Finerenone or the moderate or weak CYP3A4 inhibitor, and adjust Finerenone dosage as appropriate.

Strong and Moderate CYP3A4 Inducers Finerenone is a CYP3A4 substrate. Concomitant use of Finerenone with a strong or moderate CYP3A4 inducer decreases Finerenone exposure, which may reduce the efficacy of Finerenone. Avoid concomitant use of Finerenone with strong or moderate CYP3A4 inducers.

Drugs That Affect Serum Potassium More frequent serum potassium monitoring is warranted in patients receiving concomitant therapy with drugs or supplements that increase serum potassium.

OVERDOSE In the event of suspected overdose immediately interrupt finerenone 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%.

INSTRUCTIONS

Store below 30⁰C protect from heat light and moisture. Keep out of the reach of children.

PRESENTATION

Fineron 10mg tablets are available in pack size of 14’s.

Fineron 20mg tablets are available in pack size of 14’s.

Manufactured by

NABIQASIM INDUSTRIES (PVT.) LTD.

17/24,Korangi industrial Area, Karachi Pakistan