Amiloride Hcl

Drug overview for AMILORIDE HCL (amiloride hcl):

Generic name: AMILORIDE HCL (a-MIL-oh-ride)
Drug class: Diuretics
Therapeutic class: Cardiovascular Therapy Agents

Amiloride hydrochloride is a potassium-sparing diuretic.

No enhanced Uses information available for this drug.

DRUG IMAGES

AMILORIDE HCL 5 MG TABLET

The following indications for AMILORIDE HCL (amiloride hcl) have been approved by the FDA:

Indications:
Edema
Hypertension
Peripheral edema due to chronic heart failure

Professional Synonyms:
Edematous sodium retaining conditions
Elevated blood pressure
Essential hypertension
Hyperpiesia
Hyperpiesis
Hypertensive disorder
Peripheral edema due to CHF
Peripheral edema due to congestive heart failure
Systemic arterial hypertension

Dosing information for AMILORIDE HCL
DRUG LABEL	DOSING TYPE	DOSING INSTRUCTIONS
AMILORIDE HCL 5 MG TABLET	Maintenance	Adults take 1 tablet (5 mg) by oral route once daily with food

Generic dosing information for AMILORIDE HCL
DRUG LABEL	DOSING TYPE	DOSING INSTRUCTIONS
AMILORIDE HCL 5 MG TABLET	Maintenance	Adults take 1 tablet (5 mg) by oral route once daily with food

The following drug interaction information is available for AMILORIDE HCL (amiloride hcl):

Contraindicated
Severe
Moderate

There are 0 contraindications.

There are 4 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
Potassium Supplements/Potassium Sparing Diuretics SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Decreased renal excretion of potassium, resulting from administration of a potassium sparing diuretic. CLINICAL EFFECTS: May observe hyperkalemia which may be severe or even fatal. PREDISPOSING FACTORS: Renal function impairment. PATIENT MANAGEMENT: If both drugs are administered, monitor potassium levels. Adjust the dose of the drugs accordingly. This combination should probably be avoided if possible. DISCUSSION: The interaction is well documented. Patients with decreased renal function are especially at risk of developing hyperkalemia from this drug combination. A commonly held belief is that a potassium sparing diuretic formulated in combination with a thiazide diuretic, such as Dyazide, will not exhibit this interaction. Although the likelihood of hyperkalemia occurring may be reduced somewhat, a danger still exists.	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
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
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)	ALDACTONE, CAROSPIR, EPLERENONE, INSPRA, KERENDIA, SPIRONOLACTONE, SPIRONOLACTONE-HCTZ
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

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
Triamterene; Amiloride/Selected NSAIDs 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 triamterene or amiloride- induced nephrotoxicity or hyperkalemia to occur in some patients. CLINICAL EFFECTS: Possible renal failure or hyperkalemia. PREDISPOSING FACTORS: Preexisting renal impairment. PATIENT MANAGEMENT: When possible, avoid concurrent therapy with triamterene or amiloride with NSAIDs. If these agents are used concurrently, monitor renal function and serum electrolytes. If decreased renal function or hyperkalemia develops, discontinue both agents. DISCUSSION: Acute renal failure and hyperkalemia have been reported in patients receiving concurrent therapy with therapeutic doses of triamterene or amiloride with NSAIDs. Although a majority of these reports have involved indomethacin, other NSAIDs have been implicated (diclofenac, flurbiprofen, and ibuprofen).	ARTHROTEC 50, ARTHROTEC 75, CALDOLOR, CAMBIA, COMBOGESIC, COMBOGESIC IV, DICLOFENAC, DICLOFENAC POTASSIUM, DICLOFENAC SODIUM, DICLOFENAC SODIUM ER, DICLOFENAC SODIUM MICRONIZED, DICLOFENAC SODIUM-MISOPROSTOL, FLURBIPROFEN, HYDROCODONE-IBUPROFEN, IBU, IBUPAK, IBUPROFEN, IBUPROFEN LYSINE, IBUPROFEN-FAMOTIDINE, INDOCIN, INDOMETHACIN, INDOMETHACIN ER, INFLAMMACIN, INFLATHERM(DICLOFENAC-MENTHOL), LOFENA, LURBIPR, NEOPROFEN, TOXICOLOGY SALIVA COLLECTION, TRESNI, ZIPSOR, ZORVOLEX
Triamterene; Amiloride/Selected 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 triamterene or amiloride- induced nephrotoxicity or hyperkalemia to occur in some patients. CLINICAL EFFECTS: Possible renal failure or hyperkalemia. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: When possible, avoid concurrent therapy with triamterene or amiloride with NSAIDs. If these agents are used concurrently, monitor renal function and serum electrolytes. If decreased renal function or hyperkalemia develops, discontinue both agents. 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. Patients receiving diuretics are at an increased risk of NSAID-induced renal failure.	ACETYL SALICYLIC ACID, ANAPROX DS, ANJESO, ASA-BUTALB-CAFFEINE-CODEINE, ASCOMP WITH CODEINE, ASPIRIN, BISMUTH SUBSALICYLATE, BROMFENAC SODIUM, BUPIVACAINE-KETOROLAC-KETAMINE, BUTALBITAL-ASPIRIN-CAFFEINE, CARISOPRODOL-ASPIRIN, CARISOPRODOL-ASPIRIN-CODEINE, CELEBREX, CELECOXIB, CHOLINE MAGNESIUM TRISALICYLAT, CONSENSI, COXANTO, DAYPRO, DIFLUNISAL, DISALCID, DOLOBID, EC-NAPROSYN, ELYXYB, ETODOLAC, ETODOLAC ER, FELDENE, FENOPROFEN CALCIUM, FENOPRON, KETOPROFEN, KETOPROFEN MICRONIZED, KETOROLAC TROMETHAMINE, KIPROFEN, LODINE, MB CAPS, MECLOFENAMATE SODIUM, MEFENAMIC ACID, MELOXICAM, NABUMETONE, NABUMETONE MICRONIZED, NALFON, NAPRELAN, NAPROSYN, NAPROTIN, NAPROXEN, NAPROXEN SODIUM, NAPROXEN SODIUM CR, NAPROXEN SODIUM ER, NAPROXEN-ESOMEPRAZOLE MAG, NORGESIC, NORGESIC FORTE, ORPHENADRINE-ASPIRIN-CAFFEINE, ORPHENGESIC FORTE, OXAPROZIN, PHENYL SALICYLATE, PHENYLBUTAZONE, PIROXICAM, R.E.C.K.(ROPIV-EPI-CLON-KETOR), RELAFEN DS, ROPIVACAINE-CLONIDINE-KETOROLC, ROPIVACAINE-KETOROLAC-KETAMINE, SALSALATE, SODIUM SALICYLATE, SPRIX, SULINDAC, SUMATRIPTAN SUCC-NAPROXEN SOD, SYMBRAVO, TOLECTIN 600, TOLMETIN SODIUM, TORONOVA II SUIK, TORONOVA SUIK, TREXIMET, URELLE, URETRON D-S, URIBEL TABS, URIMAR-T, URNEVA, URO-MP, URO-SP, VIMOVO, VIVLODEX
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
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. 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 AMILORIDE HCL (amiloride hcl):

Overview
Contraindicated
Severe
Moderate

Drug contraindication overview.

No enhanced Contraindications information available for this drug.

There are 1 contraindications. Absolute contraindication.

Contraindication List
Hyperkalemia

There are 3 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

Severe List
Diabetic nephropathy
Disease of liver
Kidney disease with reduction in glomerular filtration rate (GFr)

There are 3 moderate contraindications. Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.

Moderate List
Acidosis
Diabetes mellitus
Hyponatremia

The following adverse reaction information is available for AMILORIDE HCL (amiloride hcl):

Overview
Severe
Less Severe

Adverse reaction overview.

No enhanced Common Adverse Effects information available for this drug.

There are 13 severe adverse reactions.

More Frequent	Less Frequent
Hyperkalemia	Encephalopathy

Rare/Very Rare
Abnormal hepatic function tests Anaphylaxis Angina Aplastic anemia Cardiac arrhythmia Dyspnea Gastrointestinal hemorrhage Jaundice Neutropenic disorder Ocular hypertension Orthostatic hypotension

There are 46 less severe adverse reactions.

More Frequent	Less Frequent
None.	Abnormal sexual function Acute abdominal pain Anorexia Constipation Cough Cramps Diarrhea Dizziness Erectile dysfunction Fatigue Flatulence Gastrointestinal irritation General weakness Headache disorder Hyponatremia Nausea Vomiting

Rare/Very Rare
Acute cognitive impairment Alopecia Arthralgia Back pain Bladder irritability Chest pain Depression Drowsy Dysuria Gynecomastia Heartburn Increased urinary frequency Insomnia Leg pain Libido changes Nasal congestion Neck pain Nervousness Palpitations Paresthesia Polydipsia Polyuria Pruritus of skin Skin rash Tinnitus Tremor Vertigo Visual changes Xerostomia

The following precautions are available for AMILORIDE HCL (amiloride hcl):

Pediatric
Pregnant
Lactation
Geriatric

No enhanced Pediatric Use information available for this drug.

Contraindicated

None

Severe Precaution

None

Management or Monitoring Precaution

None

Amiloride has been shown to cross the placenta in animals. Following administration of a single 10-mg/kg oral dose of radiolabeled amiloride to rats, traces of drug crossed the placenta. Reproduction studies in rabbits and mice using oral amiloride doses up to 20 and 25 times the maximum daily human dose, respectively, have not revealed evidence of harm to the fetus.

Reproduction studies in rats and rabbits using amiloride dosages up to 8 mg/kg daily have revealed evidence of reduced maternal growth rate in rats, maternal weight loss in rabbits, and adverse effects on growth and survival of rat offspring. There are no adequate and controlled studies to date using amiloride in pregnant women, and the drug should be used during pregnancy only when clearly needed.

It is not known if amiloride is distributed into human milk; however, amiloride is distributed into the milk of lactating animals. Because of the potential for serious adverse reactions from amiloride in nursing infants, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.

No enhanced Geriatric Use information available for this drug.

The following icd codes are available for AMILORIDE HCL (amiloride hcl)'s list of indications:

Edema
R60	Edema, not elsewhere classified
R60.0	Localized edema
R60.1	Generalized edema
R60.9	Edema, unspecified
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
Peripheral edema due to chronic heart failure
R60	Edema, not elsewhere classified
R60.9	Edema, unspecified