Lisa E Ruohoniemi, PharmD

approved in adults with type 2 diabetes mellitus-mediated chronic kidney disease

 (CKD) to reduce the risk of renal disease progression and cardiovascular events.

Approved by the FDA in 2021, finerenone is the only non-steroidal mineralocorticoid receptor antagonist for this purpose.

 Diabetes is the leading cause of CKD and renal failure in the United States, putting patients at risk for disturbances in fluid balance, electrolytes, and normal renal elimination.

In clinical trials, finerenone demonstrated efficacy related to renal and cardiovascular outcomes, regardless of patients’ history of atherosclerotic cardiovascular disease.

Finerenone selectively inhibits sodium reabsorption mediated by mineralocorticoid receptors.

 It also blocks mineralocorticoid receptor overexpression in kidney, heart, and blood vessel tissue; this mineralocorticoid receptor overexpression contributes to fibrosis and inflammation.

Of note, finerenone has no clinically relevant effects on androgen, progesterone, estrogen, and glucocorticoid receptors, unlike other currently available mineralocorticoid receptor antagonists.

Finerenone is indicated in patients with type 2 diabetes mellitus-mediated CKD to reduce the risk of:

It is available as both 10 mg and 20 mg oral tablets; the recommended starting dose is based on the patient’s eGFR as indicated in 

The target daily dose of finerenone is 20 mg, but clinicians should adjust doses based on both the patient’s current serum potassium concentration and finerenone dose.

 Finrenone’s package insert presents providers with guidance on this dose escalation.

Patients unable to swallow whole tablets may crush finerenone and mix it with water or soft foods, such as applesauce, immediately prior to oral administration.

The randomized, double-blind, placebo-controlled, multicenter phase 3 study FIDELIO-DKD evaluated finerenone’s efficacy and safety.

 A total of 4674 patients participated in the study, with 2833 patients randomized to the finerenone group and 2841 to the placebo group.

Researchers followed patients from the study for a median of 2.6 years.

 The mean age of participants was 66 years of age, 70% of patients were male, and mean eGFR at baseline was 44mL/min/1.73m.

Further, 99.8% of the patients at baseline were also on an ACE inhibitor or ARB.

Finerenone demonstrated a reduction in the incidence of a sustained decline in eGFR of at least 40%, and of cardiovascular death, non-fatal myocardial infarction, and hospitalization for heart failure.

 In FIDELIO-DKD, 17.7% of patients in the finerenone group had at least 1 of these events, compared to 21.1% of patients in the placebo group.

The FDA granted finerenone both priority review and fast track designations for its application.

Contraindications, Warnings, and Precautions

Finerenone is primarily metabolized via CYP3A4; its concomitant use is contraindicated in patients on strong CYP3A4 inhibitors. Finererone is also contraindicated in patients with adrenal insufficiency.

Hyperkalemia is a risk associated with finerenone.Patients with elevated baseline potassium levels and decreasing renal function are at higher risk for developing hyperkalemia while taking finerenone.

Clinicians should monitor serum potassium and eGFR in all patients before initiating finerenone and periodically thereafter.

 Clinicians should also avoid initiating finerenone in patients with a serum potassium greater than 5 mEq/L.

In the FIDELIO-DKD clinical trial, hyperkalemia was the most frequently reported AE associated with finerenone (≥10%), followed by hypotension (4.8%) and hyponatremia (1.4%).

In patients with a serum potassium greater than 5.5 mEq/mL, clinicians should withhold finerenone.

 Patients previously on a 20 mg dose should restart finerenone at 10 mg daily when serum potassium is 5 mEq/mL or less.

For patients on a 10 mg dose who develop hyperkalemia, clinicians may also consider re-initiating at the same dose once serum potassium has normalized.

There are no data on the use of finerenone in pregnancy. Clinicians should advise women that breastfeeding is not recommended at the time of treatment with finerenone and for one day following treatment.

Lisa E Ruohoniemi, PharmD, is a clinical staff pharmacist at LewisGale Hospital- Montgomery in Blacksburg, VA.

FDA approves drug for chronic kidney disease. U.S. Food and Drug Administration. 

https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-drug-reduce-risk-serious-kidney-and-heart-complications-adults-chronic-kidney-disease

. Published July 9, 2021. Accessed March 7, 2022.

Kerendia. Prescribing Information. Bayer; 2021. Accessed March 7, 2022. 

https://labeling.bayerhealthcare.com/html/products/pi/Kerendia_PI.pdf

Filippatos G, Anker SD, Agarwal R, et al. Finerenone and Cardiovascular Outcomes in Patients With Chronic Kidney Disease and Type 2 Diabetes. 

. 2021;143(6):540-552. doi:10.1161/CIRCULATIONAHA.120.051898

Articles

Approved by the FDA in 2021, finerenone is the only non-steroidal mineralocorticoid receptor antagonist that reduces the risk of renal disease progression and cardiovascular events in adults with type 2 diabetes mellitus-mediated chronic kidney disease.

Clinical Overview: Finerenone for Chronic Kidney Disease Associated With Type 2 Diabetes

Niraparib (Zejula; Glaxosmithkline) is an oral PARP inhibitor approved in adult patients with ovarian cancer or with fallopian tube or primary peritoneal cancers.

Although the mainstay of treatment for newly diagnosed advanced epithelial ovarian cancer involves surgery and platinum-taxane chemotherapy, up to 85% of patients with advanced ovarian cancer will have disease recurrence after treatment.

 In these patients, niraparib is associated with increased progression-free survival (PFS), regardless of the presence or absence of BRCA gene mutations.

Niraparib is indicated as a first-line maintenance therapy for patients with either advanced or recurrent ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy.

Additionally, niraparib is indicated as a primary treatment for patients with advanced ovarian, fallopian tube, or primary peritoneal cancer in patients who meet the following criteria

They have been treated with 3 or more prior chemotherapy regimens.

They have cancer associated with homologous recombination deficiency (HRD)-positive status defined by either a deleterious or suspected deleterious 

 gene mutation or genomic instability accompanied by disease progression more than 6 months after response to the last platinum-based chemotherapy.

Lastly, to determine eligibility for treatment with niraparib, providers must use an FDA-approved companion diagnostic tool for the selection process.

The table details niraparib dosing based on indication.

Patients may take niraparib with or without food. Upon the occurrence of adverse reactions, patients should consider interruption of treatment, dose reduction, or dose discontinuation. The package insert includes additional information on these dosage modifications for reference.

Lastly, the treatment dose of niraparib for patients with hepatic impairment is 200 mg by mouth once daily.

Niraparib exerts genotoxic activity by targeting rapidly dividing cells.

 It inhibits the enzymes PARP1 and PARP2, interfering with DNA repair by causing single- and subsequently double-stranded DNA breaks; this leads to programmed cell death.

The FDA approved niraparib in March 2017 following the phase 3 NOVA trial (NCT01847274), which compared niraparib with placebo in 2 independent cohorts consisting of 553 patients who were enrolled based on their BRCA mutation status.

 During the study, the investigators evaluated PFS as the primary end point.

The findings showed that niraparib was associated with a significantly longer median duration of PFS versus placebo, regardless of the patient’s BRCA mutation or HRD status (21 vs 5.5 months, respectively, in the BRCA cohort; 12.9 vs 3.8 months in the non-

, HRD-deficient cohort; and 9.3 vs 3.9 months in the overall non-BRCA cohort).

The BOX provides an overview of niraparib’s most common adverse reactions at an incidence of 10% or more.

For patients who are or may become pregnant in the future, it is important to know that niraparib can result in fetal harm during pregnancy by causing teratogenicity and/or embryo-fetal death because of its disruption of cell division.

 Similarly, health care providers should advise lactating women not to breastfeed during treatment with niraparib and for 1 month after receiving the final dose.

 is a clinical staff pharmacist at LewisGale Hospital Montgomery in Blacksburg, Virginia.

1. Zejula. Prescribing information. GlaxoSmithKline; 2021. Accessed November 2, 2021. https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Zejula_Capsules/pdf/ZEJULA-CAPSULES-PI-PIL.PDF

2. Gonz lez-Mart n A, Pothuri B, Vergote I, et al; PRIMA/ENGOT-OV26/GOG-3012 Investigators. Niraparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med. 2019;381(25):2391-2402. doi:10.1056/NEJMoa1910962

3. Moore KN, Secord AA, Geller MA, et al. Niraparib monotherapy for late-line treatment of ovarian cancer (QUADRA): a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2019;20(5):636-648. Published correction appears in Lancet Oncol. 2019;20(5):e242. Lancet Oncol. 2019;20(5):636-648.

4. Ison G, Howie LJ, Amiri-Kordestani L, et al. FDA approval summary: niraparib for the maintenance treatment of patients with recurrent ovarian cancer in response to platinum-based chemotherapy. Clin Cancer Res. 2018;24(17):4066-4071. doi:10.1158/1078-0432.CCR-18-0042

5. About Zejula. Zejula HCP. Accessed November 2021. https://www.zejulahcp.com/what-is-zejula/

6. Mirza MR, Monk BJ, Herrstedt J, et al. Niraparib maintenance therapy in platinumsensitive, recurrent ovarian cancer. N Engl J Med. 2016;375(22):2154-2164. doi:10.1056/NEJMoa1611310

The oral PARP inhibitor is associated with increased PFS, regardless of BRCA mutational status.

Niraparib as First-Line Maintenance Treatment of Ovarian, Fallopian Tube, Primary Peritoneal Cancer

Niraparib (Zejula; GlaxoSmithKline) is an oral poly (ADP-ribose) polymerase (PARP) inhibitor approved in adult patients with ovarian cancer in addition to fallopian tube and primary peritoneal cancers.

Whereas the mainstay of treatment for newly diagnosed advanced epithelial ovarian cancer involves surgery and platinum-taxane chemotherapy, up to 85% of patients with advanced ovarian cancer will have disease recurrence after treatment.

 In these patients, niraparib is associated with increased progression-free survival (PFS), regardless of the presence or absence of 

First-line maintenance therapy for either advanced or recurrent ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy.

Primary treatment for advanced ovarian, fallopian tube, or primary peritoneal cancer in patients who meet the following criteria:

Have been treated with 3 or more prior chemotherapy regimens.

Have cancer associated with homologous recombinant deficiency-positive status (defined by either a deleterious 

 gene mutation or genomic instability accompanied by disease progression more than 6 months after response to the last platinum-based chemotherapy).

Providers must use an FDA-approved companion diagnostic for niraparib to identify eligible patients.

 provides niraparib dosing based on indication.

Patients may take niraparib with or without food. For adverse events (AEs), patients should consider interruption of treatment, dose reduction, or dose discontinuation.

 The package insert provides additional information on these dosage modifications.

The dose of niraparib for patients with hepatic impairment is 200 mg by mouth once daily.

 It inhibits the enzymes PARP1 and PARP2, interfering with DNA repair by causing single- and subsequently double-stranded DNA breaks, which leads to programmed tumor cell death.

The FDA approved niraparib in March 2017 following the phase 3 NOVA trial, which compared niraparib with placebo in 2 independent cohorts (consisting of 553 enrolled patients), based on 

The study evaluated progression-free survival as the primary endpoint.

 Niraparib was associated with a significantly longer median duration of PFS compared to the placebo group, regardless of the patient’s 

mutation or HRD status (21 vs. 5.5 months in the 

, HRD-deficient cohort, and 9.3 vs. 3.9 months in the overall non-

 provides niraparib’s most common adverse reactions (incidence of 10% or more).

Niraparib can result in fetal harm in pregnancy by causing teratogenicity and/or embryo-fetal death due to its disruption of cell division.

Similarly, health care providers should advise lactating women not to breastfeed during treatment with niraparib and for 1 month after receiving the final dose because of its risk to a breastfed child.

Lisa E Ruohoniemi, PharmD, is a Clinical Staff Pharmacist at LewisGale Hospital, Montgomery Blacksburg, VA.

Zejula. Prescribing information. GlaxoSmithKline; 2021. Accessed November 2nd, 2021. 

https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Zejula_Capsules/pdf/ZEJULA-CAPSULES-PI-PIL.PDF

González-Martín A, Pothuri B, Vergote I, et al. Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. 

. 2019;381(25):2391-2402. doi:10.1056/NEJMoa1910962

Moore KN, Secord AA, Geller MA, et al. Niraparib monotherapy for late-line treatment of ovarian cancer (QUADRA): a multicentre, open-label, single-arm, phase 2 trial [published correction appears in Lancet Oncol. 2019 May;20(5):e242]. 

. 2019;20(5):636-648. doi:10.1016/S1470-2045(19)30029-4

Ison G, Howie LJ, Amiri-Kordestani L, et al. FDA Approval Summary: Niraparib for the Maintenance Treatment of Patients with Recurrent Ovarian Cancer in Response to Platinum-Based Chemotherapy. 

. 2018;24(17):4066-4071. doi:10.1158/1078-0432.CCR-18-0042

https://www.zejulahcp.com/what-is-zejula/

Mirza MR, Monk BJ, Herrstedt J, et al. Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer. 

. 2016;375(22):2154-2164. doi:10.1056/NEJMoa1611310

Niraparib is associated with increased progression-free survival, regardless of the presence or absence of BRCA gene mutations.

Oncology Overview: Niraparib

is a new-generation oral androgen receptor inhibitor indicated for patients with nonmetastatic castration-resistant prostate cancer.

Although androgen deprivation therapy is the mainstay of care for patients with advanced hormone-sensitive prostate cancer, most patients will subsequently develop castration-resistant prostate cancer.

 In 2019, the FDA approved darolutamide for these patients; the novel molecular structure of darolutamide theoretically results in fewer and less severe toxic adverse effects (AEs) than other androgen receptor inhibitors currently on the market.

Available as a 300-mg oral tablet, darolutamide is recommended to be administered to patients at a dose of 600 mg twice a day with food. Patients on darolutamide should also receive a gonadotropin-releasing hormone analog concurrently or should have had bilateral orchiectomy; patients may continue treatment with darolutamide until disease progression, which would be assessed radiographically, or unacceptable toxicity occurs.

If a patient experiences grade 3 toxicity or higher or an intolerable reaction to darolutamide, it is important to withhold dosing or reduce the dose to 300 mg twice a day until the symptoms improve. Upon symptom improvement, patients can resume the standard regimen of 600 mg twice a day. The manufacturer does not recommend dose reduction below 300 mg twice a day.

In prostate cancer, the primary targets for treatment are androgens and androgen receptor signaling pathways. Darolutamide exerts its effects via competitive inhibition of this androgen binding, leading to the blockade of both the androgen receptor nuclear translocation and the androgen receptor–mediated transcription. This decreases signaling from androgen receptors and reduces overall serum androgen levels.

The FDA's approval of darolutamide was based on a review of the results from the phase 3 multinational, randomized, double-blind, placebo-controlled ARAMIS trial (NCT02200614).

 The study’s primary end point was metastasis-free survival, which is the standard end point in trials involving castration-resistant prostate cancer.

During the study, median metastasis-free survival was 40.4 months in the darolutamide group versus 18.4 months in the placebo group (HR 0.41; 95% CI, 0.34 to 0.50; 

<0.001). Darolutamide reduced the risk of metastasis or death from any cause by 59%, a benefit evident across patient subgroups.

During treatment with darolutamide, the most common AEs experienced by patients are fatigue, pain in extremities, and rash (TABLE).

Serious AEs occurred in 25% of patients receiving darolutamide and in 20% of patients receiving the placebo.

In the ARAMIS trial, investigators reported that the incidence of AEs was generally similar in the darolutamide and placebo groups. Further, after adjustment for treatment duration or observation period, the differences between treatment and placebo groups in the incidences of relevant AEs either decreased or disappeared.

is a clinical staff pharmacist at LewisGale Hospital Montgomery in Blacksburg, Virginia.

Nubeqa. Prescribing Information. Bayer; 2021. Accessed October 28, 2021. http:// labeling.bayerhealthcare.com/html/products/pi/Nubeqa_PI.pdf

Fizazi K, Albiges L, Loriot Y, Massard C. ODM-201: a new-generation androgen receptor inhibitor in castration-resistant prostate cancer. 

. 2015;15(9):1007-1017. doi:10.1586/14737140.2015.1081566

Fizazi K, Shore N, Tammela TL, et al; ARAMIS Investigators. Darolutamide in nonmetastatic, castration-resistant prostate cancer. 

. 2019;380(13):1235-1246. doi:10.1056/ NEJMoa1815671

The drug's novel molecular structure may result in fewer toxic adverse effects.

Using Darolutamide in Nonmetastatic Castration-Resistant Prostate Cancer

Darolutamide (Nubeqa; Bayer) is a new-generation oral androgen receptor (AR) inhibitor indicated for patients with non-metastatic castration-resistant prostate cancer.

 The FDA approved darolutamide in 2019 for these patients. The drug’s novel molecular structure theoretically results in fewer and less severe toxic adverse effects (AEs) than other androgen-receptor inhibitors currently on the market.

Darolutamide is available as a 300 mg oral tablet. The recommended dose is 600 mg administered twice a day with food.

Patients on darolutamide should also receive a gonadotropin-releasing hormone analog concurrently or should have had bilateral orchiectomy. Patients may continue treatment with darolutamide until disease progression (assessed radiographically) or unacceptable toxicity occurs.

If a patient experiences grade 3 toxicity or higher or an intolerable reaction to darolutamide, withhold dosing or reduce the dose to 300 mg twice a day until improvement of symptoms.

 Patients may then resume the standard regimen of 600 mg twice a day. The manufacturer does not recommend dose reduction below 300 mg twice a day.

The primary targets for treatment in prostate cancer are androgens and androgen receptor signaling pathways.

 Darolutamide exerts its effects via competitive inhibition of this androgen binding, leading to blockade of both:

This then decreases signaling from androgen receptors and reduces overall serum androgen levels.

The FDA approved darolutamide after review of the phase 3 multinational, randomized, double-blind, placebo-controlled Androgen Receptor Antagonizing Agent for Metastasis-free Survival (ARAMIS) trial.

 ARAMIS’s primary endpoint was metastasis-free survival, the standard endpoint in trials involving castration-resistant prostate cancer.

Median metastasis-free survival was 40.4 months in the darolutamide group, compared to 18.4 months in the placebo group (95% CI, P<0.001).

 Darolutamide reduced the risk of metastasis or death from any cause by 59%, a benefit evident across patient subgroups.

Darolutamide’s most common adverse reactions are fatigue, pain in extremities, and rash (see 

Serious AEs occurred in 25% of patients receiving darolutamide and 20% of patients receiving the placebo.

In ARAMIS, researchers reported that the incidence of AEs was generally similar in the darolutamide and placebo groups.

 Further, after adjustment for treatment duration or observation period, the differences between treatment and placebo groups in the incidences of relevant AEs either decreased or disappeared.

, is a Clinical Staff Pharmacist at LewisGale Hospital, Montgomery Blacksburg, VA.

Nubeqa. Prescribing Information. Bayer; 2021. Accessed October 28, 2021. 

http://labeling.bayerhealthcare.com/html/products/pi/Nubeqa_PI.pdf

Fizazi K, Albiges L, Loriot Y, Massard C. ODM-201: a new-generation androgen receptor inhibitor in castration-resistant prostate cancer. Expert Rev Anticancer Ther. 2015;15(9):1007-1017. doi:10.1586/14737140.2015.1081566. Published September 2015. Accessed October 26, 2021.

Fizazi K, Shore N, Tammela TL, et al. Darolutamide in Nonmetastatic, Castration-Resistant Prostate Cancer. N Engl J Med. 2019;380(13):1235-1246. doi:10.1056/NEJMoa1815671. Published February 2019. Accessed October 25, 2021.

Darolutamide exerts its effects via competitive inhibition of androgen binding.