Finerenone - Uses, Precautions, Side Effects, Dosage, and More

Introduction:

Finerenone is a third-generation non-steroidal mineralocorticoid receptor antagonist (MRAs) manufactured by the German pharmaceutical company Bayer. It was invented and widely used to decrease the risk of worsening kidney disease, nonfatal myocardial infarction, the need for hospitalization in cases of heart failure, deaths due to cardiovascular diseases, and heart attacks in patients suffering from chronic kidney disease (CKD) due to type 2 diabetes. The dosing of this drug is mainly based on the serum potassium levels and the eGFR (estimated glomerular filtration rate) values of the patients.

Finerenone received FDA (Food and Drug Administration) approval in July 2021 and has also been approved by the EMA (European Medicines Agency) recently in March 2022 based on the positive response obtained from the pivotal phase III Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease (FIDELIO-DKD) study. It is available and sold as a film-coated tablet in 10 and 20 mg doses. This tablet is strictly recommended to be prescribed only in adults with chronic kidney disease.

How Does Finerenone Work?

Finerenone works to prevent the progression of chronic kidney disease and the incidence of other complications associated with it in the following manner:

• Finerenone works by binding to the mineralocorticoid receptor.

• Mineralocorticoid receptors are the receptors with a role as the activators of the process that causes inflammation and scarring in the kidneys.

• Finerenone blocks the mineralocorticoid receptor, thereby protecting the kidneys from severe inflammation and scarring.

Uses:

Finerenone reduces the risk of the following complications in patients suffering from chronic kidney disease due to type 2 diabetes:

• Reduces the decline of eGFR.

• Reduces the risk of kidney disease progression to the end-stage.

• Reduces the risk of nonfatal myocardial infarction.

• Reduces the risk of the CKD patient getting hospitalized for heart failure.

• Reduces deaths due to cardiovascular diseases and heart attacks.

Dosage:

• Finerenone is available in tablet form and has two strengths (10 mg and 20 mg).

• A doctor’s prescription is required for the consumption of this drug.

• Before administering this drug, it is always essential to assess the serum potassium level and the eGFR (estimated glomerular filtration rate), as these values determine the dosage of the tablet to be administered.

• If the serum potassium level is more than or equal to 5.0 mEq/L and the eGFR value less than 25 mL/min/1.73m2, it is not recommended to administer Finerenone.

• Depending upon the eGFR value, the dosage is calculated. If eGFR is more than or equal to 60, then 20 mg once daily is the recommended dose, and when the value is more than 25 but less than 60, 10 mg once daily is the recommended dose.

• The tablet can be taken at any time before or after food.

• Also, if the patient is not comfortable taking the tablet as a whole, the tablet can be crushed and mixed with water or other soft foods and taken orally.

Warning:

• In patients suffering from hyperkalemia (higher potassium levels in the blood) and compromised kidney function, it is not safe to administer Finerenone as it could cause complications. So, it is always mandatory to check serum potassium levels before getting prescribed Finerenone.

• It is also unsafe to use Finerenone in patients diagnosed with Addison's disease, a condition in which the body lacks the tendency to produce cortisol and aldosterone.

• Also, caution should be taken when taking other medications along with Finerenone as it could interact with a few drugs when taken together.

For Patients:

What Do You Need to Know About Chronic Kidney Disease?

• Chronic kidney disease is a long-term kidney disorder. Kidneys are the organs responsible for filtering unwanted waste products and purifying the blood. However, in the case of chronic kidney disease, the purifying action of the kidneys is compromised due to which the waste products go unfiltered and accumulate in the body, thereby leading to several other diseases like cardiovascular disorders, stroke, etc.

• The onset of the symptoms of this disease is not specific and can vary with individuals. The symptoms are usually of slow onset and might not show any symptoms in some cases. The symptoms can be as common as nausea, vomiting, weakness, fatigue, appetite changes, changes in urination, etc.

Learn More About Finerenone:

Before Starting Finerenone:

When and Why to Take Finerenone?

Finerenone is a drug recommended for use in adult patients suffering from chronic kidney disease due to type 2 diabetes. It is widely used to decrease the decline of eGFR, the risk of worsening kidney disease, nonfatal myocardial infarction, the need for hospitalization in cases of heart failure, deaths due to cardiovascular diseases, and heart attacks in patients suffering from chronic kidney disease due to type 2 diabetes. A physician’s prescription is mandatory for starting Finerenone therapy. It works by blocking the mineralocorticoid receptors, thereby preventing the progression of kidney diseases.

Before starting Finerenone, it is always recommended to test the serum potassium levels and the eGFR as they determine the dosage of the drug.

How Effective Is Finerenone?

The use of Finerenone has shown markable prevention of CKD progression. It has also reduced the incidence of heart complications in patients suffering from chronic kidney disease due to type 2 diabetes.

Things to Inform Your Doctor Before They Prescribe You Finerenone:

Inform your doctor about the following before getting a prescription for Finerenone:

• Mention if there is any prior history of allergy to a specific drug.

• Do not refrain from mentioning if you suffer from any diseases, specifically adrenal gland-related conditions.

• Mention your drug history, including medications that you are taking currently and those that have been taken in the recent past, as there can be drug interactions with certain drugs.

• If you suffer from any liver-related illnesses or hyperkalemia, it is not recommended to take Finerenone.

• Mention your pregnancy status to the doctor if you are planning a pregnancy, or are already pregnant. This is imperative since the effects of this drug on the baby are unclear.

• Mention if you are breastfeeding, as it is not recommended to breastfeed while taking this medication.

• Mention your exact age to the physician, as this drug is not recommended for consumption in patients under 18 years of age.

Starting Finerenone:

How to Take Finerenone?

It is always important for any drug to be prescribed before you start taking it; the same goes for this drug. When you are prescribed this drug, ask your doctor how to take it. Read the instructions given in the tablet strip and follow them accordingly.

• Finerenone is available in tablet form and should be taken orally.

• It can be taken before having food or after.

• It is recommended to take Finerenone once daily.

• Make sure to take one tablet regularly without fail for the medication to work well.

• The dosage of this drug is customized based on an individual’s requirements and health status.

• The dosage should be taken and altered only under the guidance of a physician. The doctor might initially ask you to start taking the lowest dose and increase the dosage gradually to avoid side effects.

• If you are taking any other medications, inform your doctor and give your medication history to confirm if both the drugs can be taken simultaneously.

Things to Do After You Start Taking Finerenone:

After starting Finerenone, keep track of how long the tablet has been taken, your body’s response to the medication, occurrence of any adverse effects, etc.

• If you find that there are any side effects, report these to your physician immediately. The same goes for the worsening of CKD symptoms.

• Analyze the effects of the drug clearly and report them to the physician.

• It is recommended to avoid taking grapefruit juice when you take Finerenone, as grapefruit juice tends to increase the chance of side effects.

Look Out for Side Effects:

Most patients taking Finerenone do not experience any symptoms as such, but if symptoms occur, it is usually one among the following:

• Dizziness.

• Symptoms of hyperkalemia such as muscle weakness and irregular heartbeat.

• Decrease in sodium levels (hyponatremia).

• Allergic or hypersensitivity reactions that present with symptoms like itching, hives, swollen lips, eyes, etc.

• Low blood pressure or hypotension.

Though these symptoms are possible, symptoms other than those in this list can also occur. So, it is crucial to note down even smaller changes and report them to the physician immediately. As the medication dosage is customized based on the particular patient’s concern, stopping the medication or lowering the dosage is not recommended. In case of the onset of any symptoms, seek medical help immediately.

Dietary Alterations:

It is recommended to avoid taking grapefruit juice and grapefruit-based products when you take Finerenone, as grapefruit juice tends to increase the possibility of side effects occurring. Also, avoid potassium supplements or salt substitutes unless recommended by your physician. There is no known effect on the administration of Finerenone with high fat or high-calorie diets.

What Should Be Done When You Miss a Dose?

Never take the tablet more than once a day. It is strictly not recommended. If you miss a dose, take it as and when you remember on the same day, although it is recommended to be taken at the same time every day. If it is already time for your next dose, skip the missed dose and take the next dose. Do not take the missed dose along with the next day’s dose, as it might lead to an overdose.

What Is the Treatment for Finerenone Overdose?

There is no specific antidote to compensate for an overdose of Finerenone. If you do overdose, seek medical help immediately. Any drug overdose is treated as a medical emergency, and a combination of emergency treatments may be done to reverse or treat the drug overdose.

How to Store Finerenone?

Finerenone should be stored in a tightly sealed container at an optimum room temperature between 20 degrees Celsius to 25 degrees Celsius. Avoid contact with moisture, heat, direct sunlight, and freezing temperatures. Before purchasing the medications, check the manufacturing and expiry dates; avoid buying and taking outdated medications. Regarding the disposal, ask your doctor for advice. Keep Finerenone out of the reach of children. Do not leave the container open or unattended to prevent contamination.

Avoid Self-Medication:

Finerenone is a prescription drug, as the dosage is customized based on the patient’s concern and is recommended only in adults suffering from chronic kidney disease due to type 2 diabetes. Taking this tablet without a prescription is strictly not recommended. Do not share prescriptions or recommend somebody else to take the medication without consulting a physician. Likewise, do not alter or stop the dosage without consulting your doctor.

Staying On Finerenone:

Tips to Stay On Track:

• One tablet of Finerenone should be taken regularly without fail in the dosage recommended by the doctor.

• Stopping or altering the dose by yourself is not recommended.

• It takes a while for any drug to show its effects, so it is important to have patience and not stop the drug in a short span if the anticipated results are not attained.

• Keep track of the improvement of the condition and subsidence of the symptoms.

• Inform your doctor about your reaction to the drug and how well you are tolerating it.

• Do not overdose.

• If any side effects are encountered, seek medical help.

• Follow all the instructions given by your physician.

For Doctors:

Indication:

Finerenone is indicated for use in patients suffering from chronic kidney disease due to type 2 diabetes to prevent the worsening of the condition or to avoid other serious complications.

Pharmacology:

Mechanism of Action:

Finerenone is a selective antagonist of the mineralocorticoid receptor. It regulates the gene transcription and is activated by the hormones aldosterone and cortisol. So, the mechanism of action of Finerenone is by blocking the mineralocorticoid receptor-mediated sodium reabsorption. Mineralocorticoid receptors are the receptors whose overactivation causes inflammation and scarring in the kidneys. Finerenone blocks these mineralocorticoid receptors, thereby protecting the kidneys from severe inflammation and scarring.

Pharmacodynamics:

The following are the significant changes that take place in the body after the intake of Finerenone:

• Reduction in urinary albumin to creatinine ratio (UACR).

• At the end of month one of taking Finerenone, the mean systolic and diastolic pressures decreased by 3 mmHg and 1 to 2 mmHg, respectively, after which they remained stable.

• Finerenone does not prolong the QT interval even when administered in a dosage four times over the recommended dosage.

Pharmacokinetics:

The exposure rate of Finerenone increased with an increase in the dosage from 1.25 mg to 80 mg, and a steady-state was achieved only after administering the dosage steadily for two days.

Ingredients:

Active Ingredient:

The only active ingredient is Finerenone, for which the dosage could be 10 mg or 20 mg.

Inactive Ingredients:

• Lactose monohydrate.

• Microcrystalline cellulose.

• Croscarmellose sodium.

• Hypromellose.

• Magnesium stearate.

• Sodium lauryl sulfate.

Film Coating Ingredients:

• Hypromellose.

• Titanium dioxide.

• Talc.

• Ferric oxide: red (for 10 mg tablets) or yellow (for 20 mg tablets).

Absorption:

• It was found that Finerenone showed complete absorption on oral administration, after which it got metabolized.

• The bioavailability of Finerenone is 44 %.

• Finerenone achieves Cmax (maximum serum concentration) after oral administration within 30 minutes to 1 hour and 15 minutes.

Distribution:

• Vss (volume of distribution at steady-state) for Finerenone is 52.6 L.

• Plasma protein binding (mainly to serum albumin) of Finerenone is 92 %.

Metabolism:

• 90 % of the primary metabolism of Finerenone to inactive metabolites is achieved by CYP3A4, while CYP2C8 takes care of the remaining 10 %.

Elimination:

• The terminal half-life of Finerenone is two to three hours.

• The systemic blood clearance of Finerenone is 25L/h.

Excretion:

It was also observed that the majority of the drug (around 80 %) was excreted in the urine, in which less than 1 % was excreted unchanged, and 20 % of it was excreted in the feces with less than 0.2 % unchanged.

Toxicity:

Finerenone was found to be non-genotoxic in an in-vitro study, and this drug also did not show any significant tumor response in a study in rats. Concerning fertility impairment, no such effect was observed in male rats, while there was impairment of fertility in female rats.

Warnings and Precautions:

• In patients suffering from hyperkalemia (high potassium levels in the blood) along with compromised kidney function, it is not safe to administer Finerenone as it could cause complications. So, it is always mandatory to get the serum potassium levels checked before getting prescribed Finerenone.

• It is also unsafe to use Finerenone in patients diagnosed with Addison's disease, which is a condition in which the body lacks the tendency to produce Cortisol and Aldosterone.

• Also, caution should be taken when taking other medications along with Finerenone as it could interact with a few drugs when taken together.

• The history of any prior allergies to a specific drug, medications history, etc., should be mentioned accurately to the physician as they help the doctor figure out and stay alert in such scenarios.

• Do not avoid mentioning if you suffer from any diseases, specifically adrenal gland-related conditions.

• In cases of severe liver-related illnesses, this drug is not recommended, while in moderate to mild cases, after assessing the serum potassium levels, the doctor decides on the dosage accordingly.

• In hyperkalemia patients, the use of Finereone is not a safe option, so it is always important to mention it to the doctor.

• Mention your pregnancy status to the doctor if you are planning a pregnancy, or are already pregnant. It is important to mention this as the effects of this drug on the baby are not clear.

• Mention if you are breastfeeding, as it is not recommended to breastfeed while taking this medication.

• Mention your exact age to the physician, as this drug is not recommended to be taken by patients under 18 years of age.

• The administration of Finerenone along with or while taking CYP3A4 inhibitors or inducers should be avoided.

Dosage and Forms:

• Finerenone is a film-coated tablet that is recommended to be orally administered.

• The available dosages of Finerenone are 10 mg and 20 mg tablets. The dosage is customized based on the patient’s health status and requirements. Doctors usually start administering this drug at minimal doses and then gradually increase it to look for side effects and patient tolerance.

• It is available as a film-coated, oblong-shaped tablet in two different colors based on the dosage. The 10 mg tablet is pink-colored, whereas the 20 mg one is yellow-colored.

• The tablet is engraved with FI on one side, and the other side shows its dosage (10 or 20).

• Finerenone is available in a bottle containing either 30 tablets or 90 tablets.

• This tablet has a shelf life of about three years.

Administration of the Drug:

• Finerenone is advised to be taken once daily in the dosage as recommended by the physician.

• It can be taken anytime, that is, before or after food.

• If you have difficulty taking the tablet as a whole, the tablet can be crushed, powdered, mixed with water or soft foods, and consumed. But, this should not be done in advance and left to sit for an extended period. Instead, prepare a fresh batch just before taking it.

• The tablet is taken with water.

• It is always better and ideal to take the tablet at the same time every day.

• The dosage should not be altered, and the medication should not be stopped unless recommended by the physician.

• The intake of any grapefruit-based food is not recommended while on this drug.

Considerations for Administration:

It is always mandatory to check the patient’s serum potassium levels and eGFR before administering Finerenone, as the dosage is calculated based on the patient’s reports.

Gather information from the patient on any hepatic disorders, hyperkalemia, pregnancy, or lactation, as the drug is complicated and needs to be evaluated for adverse effects in such cases.

The prescription of this drug is only recommended in patients over 18 years of age with chronic kidney disease due to type 2 diabetes.

Contraindications:

Finerenone is contraindicated in patients who are:

• Less than 18 years of age.

• Hypersensitive to certain drugs.

• Pregnant.

• Suffering from hyperkalemia.

• Suffering from severe hepatic impairment.

Clinical Trials:

• The safety dosage of Finerenone was evaluated by a double-blind, randomized, placebo-controlled, multicentre pivotal phase 3 study titled FIDELIO-DKD (Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease).

• This study was conducted on adult patients suffering from chronic kidney disease due to type 2 diabetes mellitus.

• The study consisted of around 2,827 patients who received Finerenone once daily every day and 2,831 patients who received a placebo. The mean duration of the patients under Finerenone treatment was around two years and two months.

• The average percentage of the population that suffered from side effects in patients who took Finerenone was 32 %, whereas, in the placebo taking population, the side effects were reported in 34 %.

• The most commonly encountered side effect of this drug was hyperkalemia which was also found to be more common among the Finerenone taking group than in the placebo group.

• A laboratory study was conducted to evaluate if Finerenone decreased the eGFR value. The main objective of this study was to assess the effect of Finerenone in eGFR and if it caused kidney-related illnesses like kidney death or kidney failure.

• It was observed that Finerenone had shown a subtle decrease in the eGFR value in the first four weeks of starting Finerenone administration which settled down after a few weeks. Some even showed the eGFR values becoming normal after the discontinuation of the drug.

Drug Interactions:

• The use of Finerenone concomitantly with strong CYP3A4 inhibitors increases the exposure of the drug, thereby leading to adverse effects pertaining to the drug use. So it is always advisable not to take Finerenone along with CYP3A4 inhibitors.

• Avoid intake of grapefruit juice or its derived products along with Finerenone as the concomitant use has shown adverse effects.

• The use of Finerenone with even a moderate to weak CYP3A4 inhibitor has shown to increase its exposure, thereby leading to adverse effects. Therefore, in cases where both these drugs have to be taken together, the serum potassium level is evaluated, and the drug dosage is decreased or is not recommended.

• The use of Finerenone concomitantly with CYP3A4 inducers has shown a decrease in the exposure of Finerenone. This leads to a reduction in the effectiveness of Finerenone. All interactions happen as Finerenone is a CYP3A4 substrate.

• The serum potassium levels should be kept in check frequently in patients who are under drugs that have the potential to increase the serum potassium levels.

Other Specifications:

Finerenone in Pregnant Women:

There is no data on the use of Finerenone in a pregnant human. But studies have been performed on pregnant rats to check for the effects of Finerenone on pregnancy. The results showed increased mortality and other severe side effects in the female rats, which proved the placental transmission of the drug in rats. So, it is advisable not to take this drug if you are pregnant or planning pregnancy.

Finerenone in Lactating Women:

Though the presence of Finerenone in human milk has not been studied yet, a study conducted on female rats has proved its presence in rat milk. Finerenone showed increased mortality and decreased body weight in rat pups, which established the apparent presence of Finerenone in animal milk. It is also anticipated that Finerenone could be present in human milk. So, it is not recommended to take Finerenone while breastfeeding; and it is expressly advised to avoid breastfeeding on the day of taking Finerenone and one day after intake as well.

Finerenone in Pediatric Patients:

Finerenone is a drug specifically designed for treating adults suffering from chronic kidney disease due to type 2 diabetes. So, the use of Finerenone in anyone below 18 years of age is strictly not recommended as it is said to cause adverse effects in such cases.

Finerenone in Geriatric Patients:

No difference was observed in the efficiency and safety of Finerenone in older people compared to younger individuals in a study where more than half the participants were over 85 years of age. So, no specific alteration or dose adjustment is required in the older adults, and the same dose as the younger adults can be administered.

Finerenone in Patients With Hepatic Impairment:

Finerenone is not recommended for administration in adults with severe hepatic impairment, whereas no dose adjustment is required in those with mild to moderate hepatic impairment. However, monitoring the serum potassium levels from time to time in patients with moderate hepatic impairment is advisable.

Finerenone in Patients With Renal Impairment:

Mild renal impairment did not affect the AUC (area under the curve) and Cmax (maximum serum concentration) of Finerenone. Similarly, moderate and severe renal impairment did not affect the Cmax but affected about 34-36 % of patients.

Finerenone in Patients With Low Body Weight:

Reports say that dose adjustment or modification is not required in patients with low body weight as it has been proved that there is no influence of body weight in determining the drug dosage.