Eplerenone

Drug overview for EPLERENONE (eplerenone):

Generic name: EPLERENONE (eh-PLER-en-own)
Drug class: Diuretics
Therapeutic class: Cardiovascular Therapy Agents

Eplerenone is considered a relatively selective competitive mineralocorticoid (aldosterone) receptor antagonist.

No enhanced Uses information available for this drug.

DRUG IMAGES

EPLERENONE 50 MG TABLET
EPLERENONE 25 MG TABLET

The following indications for EPLERENONE (eplerenone) have been approved by the FDA:

Indications:
Chronic heart failure following myocardial infarction
Hypertension

Professional Synonyms:
CHF following MI
Congestive heart failure resulting from myocardial infarction
Elevated blood pressure
Essential hypertension
Hyperpiesia
Hyperpiesis
Hypertensive disorder
Systemic arterial hypertension

Dosing information for EPLERENONE
DRUG LABEL	DOSING TYPE	DOSING INSTRUCTIONS
EPLERENONE 25 MG TABLET	Maintenance	Adults take 1 tablet (25 mg) by oral route once daily
EPLERENONE 50 MG TABLET	Maintenance	Adults take 1 tablet (50 mg) by oral route once daily

Generic dosing information for EPLERENONE
DRUG LABEL	DOSING TYPE	DOSING INSTRUCTIONS
EPLERENONE 25 MG TABLET	Maintenance	Adults take 1 tablet (25 mg) by oral route once daily
EPLERENONE 50 MG TABLET	Maintenance	Adults take 1 tablet (50 mg) by oral route once daily

The following drug interaction information is available for EPLERENONE (eplerenone):

Contraindicated
Severe
Moderate

There are 1 contraindications. These drug combinations generally should not be dispensed or administered to the same patient. A manufacturer label warning that indicates the contraindication warrants inclusion of a drug combination in this category, regardless of clinical evidence or lack of clinical evidence to support the contraindication.

Drug Interaction	Drug Names
Eplerenone/Strong CYP3A4 Inhibitors; Protease Inhibitors SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Strong inhibitors of CYP3A4 and protease inhibitors may inhibit the metabolism of eplerenone.(1-3) CLINICAL EFFECTS: Concurrent use of eplerenone with a strong inhibitor of CYP3A4 or a protease inhibitor may result in 5-fold increases in eplerenone concentrations and toxicity (e.g. hyperkalemia, hypotension).(1-3) PREDISPOSING FACTORS: Severe renal disease increases the risk for hyperkalemia. PATIENT MANAGEMENT: The manufacturer of eplerenone states that the concurrent use of strong CYP3A4 inhibitors is contraindicated.(1) The US Department of Health and Human Services HIV guidelines state that protease inhibitors are contraindicated with eplerenone.(3) The US manufacturer of itraconazole states that concurrent use of eplerenone is contraindicated during and two weeks after itraconazole treatment.(4) The starting dose of eplerenone for hypertension should be reduced to 25 mg in patients receiving moderate CYP3A4 inhibitors.(1) In all patients taking eplerenone who start taking a moderate CYP3A4 inhibitor, check serum potassium and creatinine levels after 3-7 days of concurrent therapy.(1) DISCUSSION: Ketoconazole (200 mg BID) increased the maximum concentration (Cmax) and area-under-curve (AUC) of a single dose of eplerenone (100 mg) by 1.7-fold and 5.4-fold, respectively.(1) The concurrent use of eplerenone with less potent CYP3A4 inhibitors (erythromycin 500 mg BID, fluconazole 200 mg daily, saquinavir 1200 mg TID, and verapamil 240 mg daily) increased the Cmax of eplerenone by 1.4-fold to 1.6-fold and the AUC of eplerenone by 2.0-fold and 2.9-fold.(1) Strong inhibitors of CYP3A4 and protease inhibitors linked to this monograph include: adagrasib, amprenavir, atazanavir, boceprevir, ceritinib, clarithromycin, cobicistat, darunavir, fosamprenavir, idelalisib, indinavir, itraconazole, josamycin, ketoconazole, lonafarnib, lopinavir, mibefradil, mifepristone, nefazodone, nelfinavir, nirmatrelvir/ritonavir, paritaprevir, posaconazole, ribociclib, saquinavir, telaprevir, telithromycin, tipranavir, troleandomycin, tucatinib, and voriconazole.(1,2)	APTIVUS, ATAZANAVIR SULFATE, CLARITHROMYCIN, CLARITHROMYCIN ER, DARUNAVIR, EVOTAZ, FOSAMPRENAVIR CALCIUM, GENVOYA, ITRACONAZOLE, ITRACONAZOLE MICRONIZED, KALETRA, KETOCONAZOLE, KISQALI, KORLYM, KRAZATI, LANSOPRAZOL-AMOXICIL-CLARITHRO, LOPINAVIR-RITONAVIR, MIFEPREX, MIFEPRISTONE, NEFAZODONE HCL, NOXAFIL, OMECLAMOX-PAK, PAXLOVID, POSACONAZOLE, PREZCOBIX, PREZISTA, RECORLEV, REYATAZ, SPORANOX, STRIBILD, SYMTUZA, TOLSURA, TUKYSA, TYBOST, VFEND, VFEND IV, VIRACEPT, VOQUEZNA TRIPLE PAK, VORICONAZOLE, ZOKINVY, ZYDELIG, ZYKADIA

Drug Interaction

Drug Names

Eplerenone/Strong CYP3A4 Inhibitors; Protease Inhibitors

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Strong inhibitors of CYP3A4 and protease inhibitors may inhibit the metabolism of eplerenone.(1-3)

CLINICAL EFFECTS: Concurrent use of eplerenone with a strong inhibitor of CYP3A4 or a protease inhibitor may result in 5-fold increases in eplerenone concentrations and toxicity (e.g. hyperkalemia, hypotension).(1-3)

PREDISPOSING FACTORS: Severe renal disease increases the risk for hyperkalemia.

PATIENT MANAGEMENT: The manufacturer of eplerenone states that the concurrent use of strong CYP3A4 inhibitors is contraindicated.(1) The US Department of Health and Human Services HIV guidelines state that protease inhibitors are contraindicated with eplerenone.(3) The US manufacturer of itraconazole states that concurrent use of eplerenone is contraindicated during and two weeks after itraconazole treatment.(4)

The starting dose of eplerenone for hypertension should be reduced to 25 mg in patients receiving moderate CYP3A4 inhibitors.(1) In all patients taking eplerenone who start taking a moderate CYP3A4 inhibitor, check serum potassium and creatinine levels after 3-7 days of concurrent therapy.(1)

DISCUSSION: Ketoconazole (200 mg BID) increased the maximum concentration (Cmax) and area-under-curve (AUC) of a single dose of eplerenone (100 mg) by 1.7-fold and 5.4-fold, respectively.(1)

The concurrent use of eplerenone with less potent CYP3A4 inhibitors (erythromycin 500 mg BID, fluconazole 200 mg daily, saquinavir 1200 mg TID, and verapamil 240 mg daily) increased the Cmax of eplerenone by 1.4-fold to 1.6-fold and the AUC of eplerenone by 2.0-fold

and 2.9-fold.(1) Strong inhibitors of CYP3A4 and protease inhibitors linked to this monograph include: adagrasib, amprenavir, atazanavir, boceprevir, ceritinib, clarithromycin, cobicistat, darunavir, fosamprenavir, idelalisib, indinavir, itraconazole, josamycin, ketoconazole, lonafarnib, lopinavir, mibefradil, mifepristone, nefazodone, nelfinavir, nirmatrelvir/ritonavir, paritaprevir, posaconazole, ribociclib, saquinavir, telaprevir, telithromycin, tipranavir, troleandomycin, tucatinib, and voriconazole.(1,2)

APTIVUS, ATAZANAVIR SULFATE, CLARITHROMYCIN, CLARITHROMYCIN ER, DARUNAVIR, EVOTAZ, FOSAMPRENAVIR CALCIUM, GENVOYA, ITRACONAZOLE, ITRACONAZOLE MICRONIZED, KALETRA, KETOCONAZOLE, KISQALI, KORLYM, KRAZATI, LANSOPRAZOL-AMOXICIL-CLARITHRO, LOPINAVIR-RITONAVIR, MIFEPREX, MIFEPRISTONE, NEFAZODONE HCL, NOXAFIL, OMECLAMOX-PAK, PAXLOVID, POSACONAZOLE, PREZCOBIX, PREZISTA, RECORLEV, REYATAZ, SPORANOX, STRIBILD, SYMTUZA, TOLSURA, TUKYSA, TYBOST, VFEND, VFEND IV, VIRACEPT, VOQUEZNA TRIPLE PAK, VORICONAZOLE, ZOKINVY, ZYDELIG, ZYKADIA

There are 6 severe interactions. These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.

Drug Interaction	Drug Names
Cyclosporine;Tacrolimus/Potassium-Sparing Diuretics SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Concurrent use of cyclosporine(1) or tacrolimus(2) with a potassium-sparing diuretic may result in additive or synergistic effects on potassium levels. CLINICAL EFFECTS: Concurrent use of cyclosporine(1) or tacrolimus(2) with a potassium-sparing diuretic may result in severe hyperkalemia. PREDISPOSING FACTORS: Renal impairment increases the risk for hyperkalemia. PATIENT MANAGEMENT: The US manufacturers of cyclosporine(1) and tacrolimus(2) state that potassium-sparing diuretics should not be used during therapy with these agents. DISCUSSION: Hyperkalemia has been reported with cyclosporine, therefore, the US manufacturer states that potassium-sparing diuretics should not be used with cyclosporine.(1) In tacrolimus clinical trials, mild to severe hyperkalemia was reported in 31% of kidney transplant patients, 45% of US liver transplant patients, and 13% of European liver transplant patients. The manufacturer of tacrolimus states that potassium levels should be closely monitored in all patients maintained on tacrolimus and that potassium-sparing diuretics should be avoided during tacrolimus therapy.(2)	ASTAGRAF XL, CYCLOSPORINE, CYCLOSPORINE MODIFIED, ENVARSUS XR, GENGRAF, NEORAL, PROGRAF, SANDIMMUNE, TACROLIMUS, TACROLIMUS XL
Eplerenone/Potassium Supplements SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Eplerenone increases serum potassium levels.(1) CLINICAL EFFECTS: Concurrent use of eplerenone with a potassium supplement may result in hyperkalemia.(1) PREDISPOSING FACTORS: Renal impairment. PATIENT MANAGEMENT: The manufacturer of eplerenone states that the use of eplerenone for the treatment of hypertension in patients receiving potassium supplements is contraindicated.(1) DISCUSSION: The main risk of eplerenone therapy is hyperkalemia. The risk of hyperkalemia can be reduced by avoiding potassium supplements during eplerenone therapy.(1)	CLINIMIX E, DEXTROSE 5%-ELECTROLYTE #48, EFFER-K, K-PHOS NO.2, K-PHOS ORIGINAL, KABIVEN, KCL-D5W-0.2% NACL, KCL-D5W-0.225% NACL, KCL-D5W-0.45% NACL, KCL-D5W-0.9% NACL, KLOR-CON, KLOR-CON 10, KLOR-CON 8, KLOR-CON M10, KLOR-CON M15, KLOR-CON M20, KLOR-CON-EF, POKONZA, POTASSIUM ACETATE, POTASSIUM CHLORIDE, POTASSIUM CHLORIDE IN D5LR, POTASSIUM CHLORIDE-0.45% NACL, POTASSIUM CHLORIDE-0.9% NACL, POTASSIUM CHLORIDE-DEXTROSE 5%, POTASSIUM CHLORIDE-WATER, POTASSIUM CITRATE, POTASSIUM CITRATE ER, POTASSIUM CL-LIDOCAINE-NS, POTASSIUM GLUCONATE, POTASSIUM PHOSPHATE, POTASSIUM PHOSPHATE-0.9% NACL, POTASSIUM PHOSPHATES, UROCIT-K
Aldosterone Receptor Antagonists/Potassium Sparing Diuretics SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Aldosterone receptor antagonists increase serum potassium levels, as do potassium-sparing diuretics.(1-3) CLINICAL EFFECTS: Concurrent use of aldosterone receptor antagonists with a potassium sparing diuretic may result in hyperkalemia.(1-3) PREDISPOSING FACTORS: Renal impairment PATIENT MANAGEMENT: The manufacturer of eplerenone states that the use of eplerenone for the treatment of hypertension in patients receiving potassium-sparing diuretics is contraindicated.(1) The US manufacturer of spironolactone states that spironolactone should not be used with potassium-sparing diuretics.(2) The US manufacturer of finerenone states that more frequent monitoring of potassium may be necessary in patients on concomitant medications that impair potassium excretion or increase serum potassium levels.(3) DISCUSSION: The one of the main risks of aldosterone receptor antagonist therapy is hyperkalemia. The risk of hyperkalemia can be reduced by avoiding potassium sparing diuretics during therapy.(1-3)	AMILORIDE HCL, AMILORIDE-HYDROCHLOROTHIAZIDE, DYRENIUM, TRIAMTERENE, TRIAMTERENE-HYDROCHLOROTHIAZID
Eplerenone/Selected Moderate CYP3A4 Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Moderate inhibitors of CYP3A4 may inhibit the metabolism of eplerenone.(1) CLINICAL EFFECTS: Concurrent use of moderate inhibitors of CYP3A4 may result in a 2-fold increase in eplerenone concentration and toxicity (e.g. hyperkalemia, hypotension).(1) PREDISPOSING FACTORS: Severe renal disease increases the risk for hyperkalemia. PATIENT MANAGEMENT: The starting dose of eplerenone for hypertension should be reduced to 25 mg in patients receiving moderate CYP3A4 inhibitors. For inadequate blood pressure response, dosing may be increased to a maximum of 25 mg twice daily. Do not exceed 25 mg once daily in post-MI CHF patients receiving a moderate CYP3A4 inhibitor.(1) In all patients taking eplerenone who start taking a moderate CYP3A4 inhibitor, check serum potassium and creatinine levels after 3-7 days of concurrent therapy.(1) DISCUSSION: Ketoconazole (200 mg BID) increased the maximum concentration (Cmax) and area-under-curve (AUC) of a single dose of eplerenone (100 mg) by 1.7-fold and 5.4-fold, respectively.(1) The concurrent use of eplerenone with less potent CYP3A4 inhibitors (erythromycin 500 mg BID, fluconazole 200 mg daily, saquinavir 1200 mg TID, and verapamil 240 mg daily) increased the Cmax of eplerenone by 1.4-fold to 1.6-fold and the AUC of eplerenone by 2.0-fold and 2.9-fold.(1) Moderate inhibitors of CYP3A4 include: aprepitant, avacopan, berotralstat, clofazimine, conivaptan, crizotinib, diltiazem, duvelisib, erythromycin, fedratinib, fluconazole, fluvoxamine, fosnetupitant, imatinib, isavuconazonium, lefamulin, lenacapavir, letermovir, netupitant, nilotinib, nirogacestat, schisandra, treosulfan and verapamil.(1-3)	AKYNZEO, APONVIE, APREPITANT, CARDIZEM, CARDIZEM CD, CARDIZEM LA, CARTIA XT, CINVANTI, CLOFAZIMINE, CONIVAPTAN-D5W, COPIKTRA, CRESEMBA, DANZITEN, DIFLUCAN, DILT-XR, DILTIAZEM 12HR ER, DILTIAZEM 24HR ER, DILTIAZEM 24HR ER (CD), DILTIAZEM 24HR ER (LA), DILTIAZEM 24HR ER (XR), DILTIAZEM HCL, DILTIAZEM HCL-0.7% NACL, DILTIAZEM HCL-0.9% NACL, DILTIAZEM HCL-NACL, DILTIAZEM-D5W, E.E.S. 200, E.E.S. 400, EMEND, ERY-TAB, ERYPED 200, ERYPED 400, ERYTHROCIN LACTOBIONATE, ERYTHROCIN STEARATE, ERYTHROMYCIN, ERYTHROMYCIN ESTOLATE, ERYTHROMYCIN ETHYLSUCCINATE, ERYTHROMYCIN LACTOBIONATE, FLUCONAZOLE, FLUCONAZOLE-NACL, FLUVOXAMINE MALEATE, FLUVOXAMINE MALEATE ER, GLEEVEC, GRAFAPEX, IMATINIB MESYLATE, IMKELDI, INREBIC, MATZIM LA, NILOTINIB HCL, OGSIVEO, ORLADEYO, PREVYMIS, SUNLENCA, TASIGNA, TAVNEOS, TIADYLT ER, TIAZAC, TRANDOLAPRIL-VERAPAMIL ER, VAPRISOL-5% DEXTROSE, VERAPAMIL ER, VERAPAMIL ER PM, VERAPAMIL HCL, VERAPAMIL SR, XALKORI, XENLETA
Sodium Phosphate Bowel Cleanser/Diuretics SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Bowel cleansing with sodium phosphate causes dehydration, decreased intravascular volume and hyperphosphatemia, which increases phosphate levels in the renal tubules. Abnormally high levels of calcium and phosphate in the renal tubules may precipitate out, resulting in renal injury.(1) CLINICAL EFFECTS: Use of sodium phosphate for bowel cleansing in patients maintained on diuretics may increase the risk of acute phosphate nephropathy, which is an acute kidney injury associated with deposits of calcium phosphate crystal in the renal tubules that may result in permanent renal function impairment. Acute phosphate nephropathy presents as acute kidney injury with minimal proteinuria and a bland urine sediment.(2) Use of oral sodium phosphate products at laxative doses has not been associated with acute kidney injury.(3) PREDISPOSING FACTORS: Patients who may be at an increased risk of acute phosphate nephropathy include those who are over age 55; are hypovolemic or have decreased intravascular volume; have baseline kidney disease, bowel obstruction, or active colitis; and who are using medications that affect renal perfusion or function (such as diuretics, angiotensin converting enzyme (ACE) inhibitors, angiotension receptor blockers (ARBs) and possibly nonsteroidal anti-inflammatory drugs (NSAIDs).(2) PATIENT MANAGEMENT: If possible, use an alternative agent for bowel cleansing.(1) Use sodium phosphate products with caution in patients taking medications that affect kidney function or perfusion, such as diuretics. Obtain baseline and post-procedure labs (electrolytes, calcium, phosphate, BUN, creatinine, and [in smaller, frail individuals] glomerular filtration rate). Instruct patients to drink sufficient quantities of clear fluids before, during, and after bowel cleansing and to avoid other laxatives that contain sodium phosphate. Consider hospitalization and intravenous hydration during bowel cleansing to support frail patients who may be unable to drink an appropriate volume of fluid or who may be without assistance at home.(2) Use of an electrolyte solution for rehydration may decrease the risk of acute phosphate nephropathy.(4,5) DISCUSSION: Since May 2006, the FDA has received 20 reports of acute phosphate nephropathy associated with the use of Osmo Prep. Concomitant medications included ACE inhibitors or ARBs (11), diuretics (6), and NSAIDs (4).(2) In a retrospective review of colonoscopy patients, simultaneous use of ACE inhibitors or ARBs significantly increased the risk of acute kidney injury from oral sodium phosphate. Diuretic use was also a risk factor.(6) In a case series study of 21 cases of acute phosphate nephropathy in patients who had used oral sodium phosphate, 14 patients received an ACE inhibitor or ARB, 4 used a diuretic, and 3 used an NSAID.(7) Cases have also been reported with rectal products.(8)	MB CAPS, SODIUM PHOSPHATE DIBASIC, URIMAR-T, URNEVA
Aldosterone Receptor Antagonists/Trimethoprim SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Eplerenone, finerenone, spironolactone, and trimethoprim have all been proven to increase serum potassium levels.(1-7) The increase is achieved by reduction in potassium elimination by trimethoprim(4,5) and inhibition of aldosterone by eplerenone, finerenone, and spironolactone.(2,3,8) The use of these medications in combination can have an additive effect on serum potassium resulting in potentially dangerous levels.(9) CLINICAL EFFECTS: Concurrent use of trimethoprim and aldosterone antagonists may result in increased serum potassium levels(9) and risk of sudden death.(10) PREDISPOSING FACTORS: Interaction risk appears to be greater in patients with renal insufficiency, heart failure, when receiving other drugs associated with hyperkalemia risk (e.g. ACE Inhibitors, non-steroidal antiinflammatory agents(NSAIDs), angiotensin II receptor antagonists), and/or in older patients.(1,2,3,6,9,10) PATIENT MANAGEMENT: Alternative antibiotic therapy should be considered for patients who have renal impairment, heart failure, or take other meds associated with hyperkalemia risk.(1,2,9,10) Patients using trimethoprim and an aldosterone antagonist concurrently should have their serum potassium monitored at baseline and during treatment. Peak potassium increase is delayed and generally occurs after 4 or more days of therapy.(6) DISCUSSION: A nested case-control study of elderly patients chronically treated with spironolactone evaluated hospital admissions due to hyperkalemia within 14 days of receiving a prescription for SMX-TMP, amoxicillin, norfloxacin, or nitrofurantion. 248 patients were identified. Two thirds of the patients with hyperkalemia on admission had received SMX-TMP, a 12-fold increased risk compared to patients receiving amoxicillin or norfloxacin.(9) A nested case-control study of elderly patients chronically treated with spironolactone evaluated sudden death within 14 days of receiving a prescription for SMX-TMP, amoxicillin, ciprofloxacin, norfloxacin, or nitrofurantion. 328 patients were identified and matched to up to 4 case controls. Compared with amoxicillin, use of SMX-TMP was associated with a more than 2-fold (2.46 adjusted OR) increased risk of death.(10)	BACTRIM, BACTRIM DS, PRIMSOL, SULFAMETHOXAZOLE-TRIMETHOPRIM, SULFATRIM, TRIMETHOPRIM, TRIMETHOPRIM MICRONIZED

There are 10 moderate interactions. The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.

Drug Interaction	Drug Names
Angiotensin II Receptor Blocker (ARB)/K+ Sparing Diuretics SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Angiotensin II receptor blockers (ARBs) may decrease the renal excretion of potassium. CLINICAL EFFECTS: Concurrent use of potassium sparing diuretics with an ARB may result in hyperkalemia. PREDISPOSING FACTORS: Impaired renal function; diabetes mellitus. PATIENT MANAGEMENT: Monitor serum potassium and adjust the dosage accordingly in patients receiving concurrent therapy with a potassium sparing diuretic and an ARB. In all patients taking eplerenone who start taking an an ARB, check serum potassium and creatinine levels after 3-7 days of concurrent therapy. DISCUSSION: In a nested case-control study of heart failure patients receiving continuous ACE inhibitor/ARB therapy (n = 1,491,894), the risk of hyperkalemia was significantly associated with spironolactone use (odds ratio (OR) = 13.59; confidence interval (CI) = 11.63-15.88).(20) In a systemic literature review and meta-analysis of 20 randomized controlled studies, it was found that treatment with spironolactone and ACEI/ARB combination therapy compared to ACEI/ARB therapy alone increased the mean serum potassium concentration by 0.19 mEq/L (95% CI, 0.12-0.26 mEq/L).(21) A retrospective cohort study in patients with hypertension, diabetes, and albuminuria between 2008 and 2018 examined the efficacy and safety of mineralocorticoid receptor antagonists eplerenone and spironolactone in combination with ACEI/ARB compared to ACEI/ARB alone. Hyperkalemia was more frequent in combination therapy patients (n=1,282) versus monotherapy (n=5,484) (22.3 vs 10.9 per 100 person-years for combination and monotherapy, respectively; HR = 1.78, 95% CI: 1.42, 2.24).(22) Several studies have indicated that serum potassium levels increase when ACE inhibitors and ARB therapy is initiated and decrease when the drug is lowered. There are case reports of hyperkalemia during concurrent therapy with ARBs and spironolactone and with aliskiren and spironolactone. Based on this data, serum potassium levels should be monitored in patients receiving concomitant ARBs with potassium sparing diuretics.	AMLODIPINE-OLMESARTAN, AMLODIPINE-VALSARTAN, AMLODIPINE-VALSARTAN-HCTZ, ARBLI, ATACAND, ATACAND HCT, AVALIDE, AVAPRO, AZOR, BENICAR, BENICAR HCT, CANDESARTAN CILEXETIL, CANDESARTAN-HYDROCHLOROTHIAZID, COZAAR, DIOVAN, DIOVAN HCT, EDARBI, EDARBYCLOR, ENTRESTO, ENTRESTO SPRINKLE, EPROSARTAN MESYLATE, EXFORGE, EXFORGE HCT, FILSPARI, HYZAAR, IRBESARTAN, IRBESARTAN-HYDROCHLOROTHIAZIDE, LOSARTAN POTASSIUM, LOSARTAN-HYDROCHLOROTHIAZIDE, MICARDIS, MICARDIS HCT, OLMESARTAN MEDOXOMIL, OLMESARTAN-AMLODIPINE-HCTZ, OLMESARTAN-HYDROCHLOROTHIAZIDE, TELMISARTAN, TELMISARTAN-AMLODIPINE, TELMISARTAN-HYDROCHLOROTHIAZID, TRIBENZOR, VALSARTAN, VALSARTAN-HYDROCHLOROTHIAZIDE
Drospirenone/Potassium Sparing Diuretics SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Drospirenone has antimineralocorticoid activity and may cause hyperkalemia. Potassium sparing diuretics may also increase potassium levels.(1) CLINICAL EFFECTS: Concurrent use of drospirenone and potassium sparing diuretics may result in hyperkalemia.(1) PREDISPOSING FACTORS: Renal insufficiency, hepatic dysfunction, adrenal insufficiency, and use of potassium supplements, ACE inhibitors, angiotensin II receptor antagonists, heparin, and NSAIDs may increase potassium levels.(1) PATIENT MANAGEMENT: Patients receiving drospirenone with a potassium sparing diuretic should have their serum potassium level checked during the first treatment cycle.(1) DISCUSSION: Drospirenone has antimineralocorticoid activity comparable to 25 mg of spironolactone and may result in hyperkalemia. Concurrent use of potassium sparing diuretics may also increase potassium levels.(1)	ANGELIQ, BEYAZ, DROSPIRENONE-ETH ESTRA-LEVOMEF, DROSPIRENONE-ETHINYL ESTRADIOL, JASMIEL, LO-ZUMANDIMINE, LORYNA, NEXTSTELLIS, NIKKI, OCELLA, SAFYRAL, SLYND, SYEDA, VESTURA, YASMIN 28, YAZ, ZARAH, ZUMANDIMINE
Zoledronic Acid/Diuretics SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Concurrent use of zoledronic acid and a diuretic may have adverse effects on the renal system.(1,2) CLINICAL EFFECTS: Concurrent use of zoledronic acid and a diuretic may result in renal dysfunction. Deterioration in renal function, acute renal failure requiring dialysis, and death have been reported.(1) PREDISPOSING FACTORS: The interaction may be more likely in elderly patients, patients who are taking other drugs that impact renal function, patients with pre-existing renal compromise, and patients who are dehydrated.(1) PATIENT MANAGEMENT: Patients should be adequately hydrated with 500 ml (2 glasses of water) before and after zoledronic acid administration.(1) Creatinine clearance should be monitored before and after therapy and zoledronic acid should not be administered in patients with a creatinine clearance less than 35 ml/min.(1,3) DISCUSSION: Zoledronic acid has been associated with renal dysfunction, including deterioration in renal function, acute renal failure requiring dialysis, and death. Risk factors include advanced age, concomitant nephrotoxic agents, and dehydration.(1) The FDA has received 16 reports of fatal acute renal failure and 9 reports of renal injury requiring dialysis following the administration of Reclast (zoledronic acid).(3)	RECLAST, ZOLEDRONIC ACID
Lithium/Aldosterone Receptor Antagonists SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Aldosterone receptor antagonists, including eplerenone, finerenone and spironolactone, bind to mineralocorticoid receptors, blocking the action of aldosterone. The subsequent increase in sodium and water excretion may lead to reduced renal clearance of lithium.(1-3) CLINICAL EFFECTS: Lithium has a narrow therapeutic range. Unintended increases in lithium concentrations may lead to lithium toxicity. Early symptoms of lithium toxicity may include: lethargy, muscle weakness or stiffness, new onset or coarsening of hand tremor, vomiting, diarrhea, confusion, ataxia, blurred vision, tinnitus and nystagmus. Severe toxicity may produce multiple organ dysfunction (e.g. seizures, coma, renal failure, cardiac arrhythmias, cardiovascular collapse) and may be fatal.(4) PREDISPOSING FACTORS: Risk factors for lithium toxicity include: renal impairment or worsening of existing renal disease, dehydration, low sodium diet, and concomitant use of multiple medications which may impair renal elimination of lithium (e.g. ARBs, ACE Inhibitors, NSAIDs, diuretics).(4) Patients who require higher therapeutic lithium levels to maintain symptom control are particularly susceptible to these factors. PATIENT MANAGEMENT: Evaluate renal function and most recent lithium levels. If renal function is not stable or if the lithium level is in the high therapeutic range, then consider lowering the lithium dose when an aldosterone antagonist is started, or consider withholding the aldosterone antagonist until renal function is stable. If renal function is stable and baseline lithium concentrations are in the therapeutic range, recheck lithium levels 5 to 7 days after initiation of eplerenone, finerenone, or spironolactone. Adjust the lithium dose as necessary based on lithium serum levels and patient response. If an interacting drug is discontinued, the lithium level may fall. Monitor lithium concentration and adjust dose if needed.(4) Counsel patient to assure they know signs and symptoms of lithium toxicity and understand the importance of follow-up laboratory testing. DISCUSSION: Although the magnitude and frequency of this specific diuretic interaction is not clear, manufacturer product information for spironolactone and lithium state that lithium patients should generally not receive diuretics.(2,3) The manufacturer of eplerenone recommends frequent monitoring of lithium levels in patients who receive concomitant therapy.(1)	LITHIUM CARBONATE, LITHIUM CARBONATE ER, LITHIUM CITRATE, LITHIUM CITRATE TETRAHYDRATE, LITHOBID
Aldosterone Receptor Antagonists/NSAIDs; Salicylates SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The exact mechanism is unknown; however, nonsteroidal anti-inflammatory (NSAID) inhibition of prostaglandins may allow eplerenone, finerenone, or spironolactone-induced nephrotoxicity or hyperkalemia to occur in some patients.(1-3) In some patients, NSAIDs may reduce the diuretic, natriuretic and antihypertensive effects of eplerenone, finerenone, or spironolactone.(1-3) CLINICAL EFFECTS: Concurrent use of eplerenone, finerenone, or spironolactone with NSAIDs may result in renal failure or hyperkalemia. The effects of the diuretic, natriuretic, or antihypertensive effects of eplerenone, finerenone, or spironolactone may be decreased.(1-3) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: When possible, avoid concurrent therapy with eplerenone, finerenone, or spironolactone with NSAIDs. If these agents are used concurrently, monitor renal function and serum electrolytes. If decreased renal function or hyperkalemia develops, discontinue both agents. The manufacturer of eplerenone recommends checking serum potassium and serum creatinine within 3-7 days of concurrent therapy with NSAIDs.(1) The manufacturer of spironolactone states concurrent use with NSAIDs may lead to severe hyperkalemia and extreme caution should be used during concurrent therapy.(2) DISCUSSION: Although acute renal failure and hyperkalemia have only been reported in studies and case reports involving indomethacin, diclofenac, flurbiprofen, and ibuprofen with either triamterene or amiloride, the proposed mechanism suggests that all nonsteroidal anti-inflammatory agents may be capable of this interaction with all potassium-sparing diuretics. Patients receiving diuretics are at an increased risk of NSAID-induced renal failure.	ACETYL SALICYLIC ACID, ANAPROX DS, ANJESO, ARTHROTEC 50, ARTHROTEC 75, ASA-BUTALB-CAFFEINE-CODEINE, ASCOMP WITH CODEINE, ASPIRIN, BISMUTH SUBSALICYLATE, BROMFENAC SODIUM, BUTALBITAL-ASPIRIN-CAFFEINE, CALDOLOR, CAMBIA, CARISOPRODOL-ASPIRIN, CARISOPRODOL-ASPIRIN-CODEINE, CELEBREX, CELECOXIB, CHOLINE MAGNESIUM TRISALICYLAT, COMBOGESIC, COMBOGESIC IV, CONSENSI, COXANTO, DAYPRO, DICLOFENAC, DICLOFENAC POTASSIUM, DICLOFENAC SODIUM, DICLOFENAC SODIUM ER, DICLOFENAC SODIUM MICRONIZED, DICLOFENAC SODIUM-MISOPROSTOL, DIFLUNISAL, DISALCID, DOLOBID, EC-NAPROSYN, ELYXYB, ETODOLAC, ETODOLAC ER, FELDENE, FENOPROFEN CALCIUM, FENOPRON, FLURBIPROFEN, HYDROCODONE-IBUPROFEN, IBU, IBUPAK, IBUPROFEN, IBUPROFEN LYSINE, IBUPROFEN-FAMOTIDINE, INDOCIN, INDOMETHACIN, INDOMETHACIN ER, INFLAMMACIN, INFLATHERM(DICLOFENAC-MENTHOL), KETOPROFEN, KETOPROFEN MICRONIZED, KETOROLAC TROMETHAMINE, KIPROFEN, LODINE, LOFENA, LURBIPR, MECLOFENAMATE SODIUM, MEFENAMIC ACID, MELOXICAM, NABUMETONE, NABUMETONE MICRONIZED, NALFON, NAPRELAN, NAPROSYN, NAPROTIN, NAPROXEN, NAPROXEN SODIUM, NAPROXEN SODIUM CR, NAPROXEN SODIUM ER, NAPROXEN-ESOMEPRAZOLE MAG, NEOPROFEN, NORGESIC, NORGESIC FORTE, ORPHENADRINE-ASPIRIN-CAFFEINE, ORPHENGESIC FORTE, OXAPROZIN, PHENYL SALICYLATE, PHENYLBUTAZONE, PIROXICAM, RELAFEN DS, SALSALATE, SODIUM SALICYLATE, SULINDAC, SUMATRIPTAN SUCC-NAPROXEN SOD, SYMBRAVO, TOLECTIN 600, TOLMETIN SODIUM, TORONOVA II SUIK, TORONOVA SUIK, TRESNI, TREXIMET, URELLE, URETRON D-S, URIBEL TABS, URIMAR-T, URO-MP, URO-SP, VIMOVO, VIVLODEX, ZIPSOR, ZORVOLEX, ZYNRELEF
Tizanidine/Selected Antihypertensives SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Tizanidine is an alpha-2 agonist. Concurrent use with antihypertensive agents may result in additive effects on blood pressure.(1) CLINICAL EFFECTS: Concurrent use of antihypertensives and tizanidine may result in hypotension.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Patients receiving concurrent therapy should be monitored for hypotension. The risk of hypotension may be decreased by careful titration of tizanidine dosages and monitoring for hypotension prior to dose advancement. Counsel patients about the risk of orthostatic hypotension.(1) DISCUSSION: Severe hypotension has been reported following the addition of tizanidine to existing lisinopril therapy.(2-4)	TIZANIDINE HCL, ZANAFLEX
Aliskiren/Potassium Sparing Diuretics SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Aliskiren may decrease the renal excretion of potassium. CLINICAL EFFECTS: Concurrent use of potassium sparing diuretics with aliskiren may result in hyperkalemia. PREDISPOSING FACTORS: Impaired renal function; diabetes mellitus. PATIENT MANAGEMENT: Monitor serum potassium and adjust the dosage accordingly in patients receiving concurrent therapy with a potassium sparing diuretic and aliskiren. In all patients taking eplerenone who start taking aliskiren, check serum potassium and creatinine levels after 3-7 days of concurrent therapy. DISCUSSION: Several studies have indicated that serum potassium levels increase when ACE inhibitors and ARB therapy is initiated and decrease when the drug is lowered. There are case reports of hyperkalemia during concurrent therapy with ARBs and spironolactone and with aliskiren and spironolactone. Based on this data, serum potassium levels should be monitored in patients receiving concomitant aliskiren with potassium sparing diuretics.	ALISKIREN, TEKTURNA
Moexipril/Selected Potassium Sparing Diuretics SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: ACE inhibitors such as moexipril may decrease the renal excretion of potassium. CLINICAL EFFECTS: Concurrent use of potassium sparing diuretics with an ACE inhibitor such as moexipril may result in hyperkalemia. PREDISPOSING FACTORS: Impaired renal function; diabetes mellitus. PATIENT MANAGEMENT: Monitor serum potassium and adjust the dosage accordingly in patients receiving concurrent therapy with a potassium sparing diuretic and an ACE inhibitor such as moexipril. In all patients taking eplerenone who start taking moexipril, check serum potassium and creatinine levels after 3-7 days of concurrent therapy. DISCUSSION: In a nested case-control study of heart failure patients receiving continuous ACE inhibitor/ARB therapy (n = 1,491,894), the risk of hyperkalemia was significantly associated with spironolactone use (odds ratio (OR) = 13.59; confidence interval (CI) = 11.63-15.88).(20) Several studies have indicated that serum potassium levels increase when ACE inhibitors and ARB therapy is initiated and decrease when the drug is lowered. There are case reports of hyperkalemia during concurrent therapy with ARBs and spironolactone and with aliskiren and spironolactone. Based on this data, serum potassium levels should be monitored in patients receiving concomitant moexipril with potassium sparing diuretics.	MOEXIPRIL HCL
Selected ACE Inhibitors/Potassium Sparing Diuretics SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: ACE inhibitors may decrease the renal excretion of potassium. CLINICAL EFFECTS: Concurrent use of potassium sparing diuretics with an ACE inhibitor may result in hyperkalemia. PREDISPOSING FACTORS: Impaired renal function; diabetes mellitus. PATIENT MANAGEMENT: Monitor serum potassium and adjust the dosage accordingly in patients receiving concurrent therapy with a potassium sparing diuretic and an ACE inhibitors. In all patients taking eplerenone who start taking an ACE inhibitor, check serum potassium and creatinine levels after 3-7 days of concurrent therapy. DISCUSSION: In a nested case-control study of heart failure patients receiving continuous ACE inhibitor/ARB therapy (n = 1,491,894), the risk of hyperkalemia was significantly associated with concomitant spironolactone use (odds ratio (OR) = 13.59; confidence interval (CI) = 11.63-15.88).(20) In a systemic literature review and meta-analysis of 20 randomized controlled studies, it was found that treatment with spironolactone and ACEI/ARB combination therapy compared to ACEI/ARB therapy alone increased the mean serum potassium concentration by 0.19 mEq/L (95% CI, 0.12-0.26 mEq/L).(21) A retrospective cohort study in patients with hypertension, diabetes, and albuminuria between 2008 and 2018 examined the efficacy and safety of mineralocorticoid receptor antagonists eplerenone and spironolactone in combination with ACEI/ARB compared to ACEI/ARB alone. Hyperkalemia was more frequent in combination therapy patients (n=1,282) versus monotherapy (n=5,484) (22.3 vs 10.9 per 100 person-years for combination and monotherapy, respectively; HR = 1.78, 95% CI: 1.42, 2.24).(22) Several studies have indicated that serum potassium levels increase when ACE inhibitors and ARB therapy is initiated and decrease when the drug is lowered. There are case reports of hyperkalemia during concurrent therapy with ARBs and spironolactone and with aliskiren and spironolactone. Based on this data, serum potassium levels should be monitored in patients receiving concomitant ACE inhibitors with potassium sparing diuretics. Selected ACE inhibitors linked to this monograph include: benazepril, captopril, enalapril, fosinopril, lisinopril, perindopril, quinapril, ramipril, and trandolapril.	ACCUPRIL, ACCURETIC, ALTACE, AMLODIPINE BESYLATE-BENAZEPRIL, BENAZEPRIL HCL, BENAZEPRIL-HYDROCHLOROTHIAZIDE, CAPTOPRIL, CAPTOPRIL-HYDROCHLOROTHIAZIDE, ENALAPRIL MALEATE, ENALAPRIL-HYDROCHLOROTHIAZIDE, ENALAPRILAT, EPANED, FOSINOPRIL SODIUM, FOSINOPRIL-HYDROCHLOROTHIAZIDE, LISINOPRIL, LISINOPRIL-HYDROCHLOROTHIAZIDE, LOTENSIN, LOTENSIN HCT, LOTREL, PERINDOPRIL ERBUMINE, PRESTALIA, QBRELIS, QUINAPRIL HCL, QUINAPRIL-HYDROCHLOROTHIAZIDE, RAMIPRIL, TRANDOLAPRIL, TRANDOLAPRIL-VERAPAMIL ER, VASERETIC, VASOTEC, ZESTORETIC, ZESTRIL
Apomorphine/Selected Antihypertensives and Vasodilators SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Apomorphine causes dose-dependent decreases in blood pressure. Concurrent use with antihypertensive agents may result in additive effects on blood pressure.(1) CLINICAL EFFECTS: Concurrent use of antihypertensives and apomorphine may result in orthostatic hypotension with or without dizziness, nausea, or syncope.(1) PREDISPOSING FACTORS: The risk of orthostatic hypotension may be increased during dose escalation of apomorphine and in patients with renal or hepatic impairment.(1) PATIENT MANAGEMENT: Patients receiving concurrent therapy should be monitored for hypotension. Counsel patients about the risk of orthostatic hypotension.(1) DISCUSSION: Healthy volunteers who took sublingual nitroglycerin (0.4 mg) concomitantly with apomorphine experienced a mean largest decrease in supine systolic blood pressure (SBP) of 9.7 mm Hg and in supine diastolic blood pressure (DBP) of 9.3 mm Hg, and a mean largest decrease in standing SBP and DBP of 14.3 mm Hg and 13.5 mm Hg, respectively. The maximum decrease in SBP and DBP was 65 mm Hg and 43 mm Hg, respectively. When apomorphine was taken alone, the mean largest decrease in supine SBP and DBP was 6.1 mm Hg and 7.3 mm Hg, respectively, and in standing SBP and DBP was 6.7 mm Hg and 8.4 mm Hg, respectively.(1)	APOKYN, APOMORPHINE HCL, ONAPGO

The following contraindication information is available for EPLERENONE (eplerenone):

Overview
Contraindicated
Severe
Moderate

Drug contraindication overview.

Eplerenone is contraindicated in patients with serum potassium concentrations exceeding 5.5 mEq/L at initiation of therapy, in those with creatinine clearance of 30 mL/minute or less, and in those receiving concomitant therapy with potent inhibitors of cytochrome P-450 (CYP) isoenzyme 3A4 (e.g., ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, nelfinavir) or any agent described as a potent CYP3A4 inhibitor in its prescribing information. In addition, when used for hypertension, the drug is contraindicated in patients with type 2 diabetes mellitus with microalbuminuria; serum creatinine concentrations exceeding 2 or 1.8

mg/dL in males or females, respectively; creatinine clearance less than 50 mL/minute; and in those receiving potassium supplements or potassium-sparing diuretics (e.g., amiloride, spironolactone, triamterene).

There are 5 contraindications. Absolute contraindication.

Contraindication List
Chronic kidney disease stage 3A (moderate) GFR 45-59 ml/min
Chronic kidney disease stage 3B (moderate) GFR 30-44 ml/min
Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min
Chronic kidney disease stage 5 (failure) GFr<15 ml/min
Hyperkalemia

There are 0 severe contraindications.

There are 1 moderate contraindications. Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.

Moderate List
Disease of liver

The following adverse reaction information is available for EPLERENONE (eplerenone):

Overview
Severe
Less Severe

Adverse reaction overview.

Adverse effects occurring in 2% or more of patients receiving eplerenone for the management of congestive heart failure following acute MI, but occurring at greater incidence in patients receiving the drug than in those receiving placebo, include hyperkalemia, increased serum creatinine concentrations, urinary tract disorders, adverse CNS effects, and adverse GI effects. Adverse effects reported in 1% or more of patients receiving eplerenone for the management of hypertension are dizziness, fatigue, flu-like symptoms, cough, diarrhea, abdominal pain, hyperkalemia, decreased serum sodium concentrations, abnormal vaginal bleeding, gynecomastia, hypercholesterolemia, hypertriglyceridemia, mastodynia, or albuminuria.

There are 7 severe adverse reactions.

More Frequent	Less Frequent
Hyperkalemia	Dizziness Headache disorder Kidney disease with reduction in glomerular filtration rate (GFr)

Rare/Very Rare
Acute myocardial infarction Angina Angioedema

There are 3 less severe adverse reactions.

More Frequent	Less Frequent
None.	Abnormal vaginal bleeding Gynecomastia

Rare/Very Rare
Skin rash

The following precautions are available for EPLERENONE (eplerenone):

Pediatric
Pregnant
Lactation
Geriatric

Safety and efficacy have not been established in children younger than 18 years of age. For information on overall principles and expert recommendations for treatment of hypertension in pediatric patients, see Uses: Hypertension in Pediatric Patients, in the Thiazides General Statement 40:28.20.

Contraindicated

None

Severe Precaution

None

Management or Monitoring Precaution

None

Category B. (See Users Guide.)

Eplerenone is distributed into milk in rats; a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.

No substantial differences in safety and efficacy have been observed in geriatric patients relative to younger adults. Geriatric patients 75 years of age and older with congestive heart failure following an acute MI did not benefit from the addition of eplerenone to standard medical therapy. Because geriatric patients may have decreased renal function (reduced creatinine clearance), the incidence of hyperkalemia may be increased in geriatric patients (65 years of age and older). (See Endocrine, Electrolyte, and Metabolic Effects under Warnings/Precautions: Warnings, in Cautions.)

The following icd codes are available for EPLERENONE (eplerenone)'s list of indications:

Chronic heart failure following myocardial infarction
I50.22	Chronic systolic (congestive) heart failure
I50.32	Chronic diastolic (congestive) heart failure
I50.42	Chronic combined systolic (congestive) and diastolic (congestive) heart failure
I50.812	Chronic right heart failure
Hypertension
I10	Essential (primary) hypertension
I11	Hypertensive heart disease
I11.0	Hypertensive heart disease with heart failure
I11.9	Hypertensive heart disease without heart failure
I12	Hypertensive chronic kidney disease
I12.0	Hypertensive chronic kidney disease with stage 5 chronic kidney disease or end stage renal disease
I12.9	Hypertensive chronic kidney disease with stage 1 through stage 4 chronic kidney disease, or unspecified chronic kidney disease
I13	Hypertensive heart and chronic kidney disease
I13.0	Hypertensive heart and chronic kidney disease with heart failure and stage 1 through stage 4 chronic kidney disease, or unspecified chronic kidney disease
I13.1	Hypertensive heart and chronic kidney disease without heart failure
I13.10	Hypertensive heart and chronic kidney disease without heart failure, with stage 1 through stage 4 chronic kidney disease, or unspecified chronic kidney disease
I13.11	Hypertensive heart and chronic kidney disease without heart failure, with stage 5 chronic kidney disease, or end stage renal disease
I13.2	Hypertensive heart and chronic kidney disease with heart failure and with stage 5 chronic kidney disease, or end stage renal disease
I15.1	Hypertension secondary to other renal disorders