Diuretics

AcetaZOLAMIDE is not a mercurial diuretic. Rather, it is a nonbacteriostatic sulfonamide possessing a chemical structure and pharmacological activity distinctly different from the bacteriostatic sulfonamides.

AcetaZOLAMIDE is an enzyme inhibitor that acts specifically on carbonic anhydrase, the enzyme that catalyzes the reversible reaction involving the hydration of carbon dioxide and the dehydration of carbonic acid. In the eye, this inhibitory action of acetaZOLAMIDE decreases the secretion of aqueous humor and results in a drop in intraocular pressure, a reaction considered desirable in cases of glaucoma and even in certain nonglaucomatous conditions. Evidence seems to indicate that acetaZOLAMIDE has utility as an adjuvant in the treatment of certain dysfunctions of the central nervous system (e.g., epilepsy). Inhibition of carbonic anhydrase in this area appears to retard abnormal, paroxysmal, excessive discharge from central nervous system neurons. The diuretic effect of acetaZOLAMIDE is due to its action in the kidney on the reversible reaction involving hydration of carbon dioxide and dehydration of carbonic acid. The result of renal loss of HCO3 ion, which carries out sodium, water, and potassium. Alkalinization of the urine and promotion of diuresis are thus affected. Alteration in ammonia metabolism occurs due to increased reabsorption of ammonia by the renal tubules as a result of urinary alkalinization.

Placebo-controlled clinical trials have shown that prophylactic administration of acetaZOLAMIDE at a dose of 250 mg every eight to 12 hours (or a 500 mg controlled-release capsule once daily) before and during rapid ascent to altitude results in fewer and/or less severe symptoms (such as headache, nausea, shortness of breath, dizziness, drowsiness, and fatigue) of acute mountain sickness (AMS). Pulmonary function (e.g., minute ventilation, expired vital capacity and peak flow) is greater in the acetaZOLAMIDE treated group, both in subjects with AMS and asymptomatic subjects. The acetaZOLAMIDE treated climbers also had less difficulty in sleeping.

INDICATIONS AND USAGE
For adjunctive treatment of: edema due to congestive heart failure; drug-induced edema; centrencephalic epilepsies (petit mal, unlocalized seizures); chronic simple (open-angle) glaucoma, secondary glaucoma, and preoperatively in acute angle-closure glaucoma where delay of surgery is desired in order to lower intraocular pressure. AcetaZOLAMIDE is also indicated for the prevention or amelioration of symptoms associated with acute mountain sickness in climbers attempting rapid ascent and in those who are very susceptible to acute mountain sickness despite gradual ascent

Dosing (adults):
Note: I.M. administration is not recommended because of pain secondary to the alkaline pH
Glaucoma:
Chronic simple (open-angle): Oral: 250 mg 1-4 times/day or 500 mg sustained release capsule twice daily
Secondary, acute (closed-angle): I.V.: 250-500 mg, may repeat in 2-4 hours to a maximum of 1 g/day

Edema: Oral, I.V.: 250-375 mg once daily

Epilepsy: Oral: 8-30 mg/kg/day in 1-4 divided doses; sustained release capsule is not recommended for treatment of epilepsy

Mountain sickness: Oral: 250 mg every 8-12 hours (or 500 mg extended release capsules every 12-24 hours)
Therapy should begin 24-48 hours before and continue during ascent and for at least 48 hours after arrival at the high altitude

Urine alkalinization (unlabeled use): Oral: 5 mg/kg/dose repeated 2-3 times over 24 hours

Respiratory stimulant in COPD (unlabeled use): Oral, I.V.: 250 mg twice daily

Elderly: Oral: Initial: 250 mg twice daily; use lowest effective dose

Dosing adjustment in renal impairment:
Clcr 10-50 mL/minute: Administer every 12 hours
Clcr<10 mL/minute: Avoid use (ineffective)
Hemodialysis: Moderately dialyzable (20% to 50%)
Peritoneal dialysis: Supplemental dose is not necessary

Administration
Oral: May cause an alteration in taste, especially carbonated beverages; short-acting tablets may be crushed and suspended in cherry or chocolate syrup to disguise the bitter taste of the drug, do not use fruit juices, alternatively submerge tablet in 10 mL of hot water and add 10 mL honey or syrup

[Supplied:: 125, 250 mg tablet. 500mg SR capsule. 500mg powder for injection.]

[Supplied: 5 mg tab]

[Supplied: 5mg amiloride/50mg(hctz) tablet]

Adult (usual) Edema: initial, up to 20 mg po daily (divided once or twice daily). Maint: 2.5-5 mg po qd. Hypertension: initial, 5 to 20 mg orally daily (divided once or twice daily). Maint: 2.5-15 mg orally qd. Avoid use in patients with SCR >2.5 mg/dl.

[Supplied: 2.5, 5, 10 mg tablet]

Potassium excretion is also increased by bumetanide, in a dose-related fashion.

Bumetanide may have an additional action in the proximal tubule. Since phosphate reabsorption takes place largely in the proximal tubule, phosphaturia during bumetanide-induced diuresis is indicative of this additional action. This is further supported by the reduction in the renal clearance of bumetanide by probenecid, associated with diminution in the natriuretic response. This proximal tubular activity does not seem to be related to an inhibition of carbonic anhydrase. Bumetanide does not appear to have a noticeable action on the distal tubule.

Bumetanide decreases uric acid excretion and increases serum uric acid. Following oral administration of bumetanide the onset of diuresis occurs in 30 to 60 minutes. Peak activity is reached between 1 and 2 hours. At usual doses (1 to 2 mg) diuresis is largely complete within 4 hours; with higher doses, the diuretic action lasts for 4 to 6 hours.

Several pharmacokinetic studies have shown that bumetanide, administered orally or parenterally, is eliminated rapidly in humans, with a half-life of between 1 and 1 1/2 hours. Plasma protein-binding is in the range of 94% to 96%.

Oral administration of carbon-14 labeled bumetanide to human volunteers revealed that 81% of the administered radioactivity was excreted in the urine, 45% of it as unchanged drug. Urinary and biliary metabolites identified in this study were formed by oxidation of the N-butyl side chain. Biliary excretion of bumetanide amounted to only 2% of the administered dose.

INDICATIONS AND USAGE
Bumetanide tablets are indicated for the treatment of edema associated with congestive heart failure, hepatic and renal disease, including the nephrotic syndrome. Almost equal diuretic response occurs after oral and parenteral administration of bumetanide. Therefore, if impaired gastrointestinal absorption is suspected or oral administration is not practical, bumetanide should be given by the intramuscular or intravenous route.

Successful treatment with bumetanide following instances of allergic reactions to furosemide suggests a lack of cross-sensitivity.

CONTRAINDICATIONS
Bumetanide is contraindicated in anuria. Although bumetanide can be used to induce diuresis in renal insufficiency, any marked increase in blood urea nitrogen or creatinine, or the development of oliguria during therapy of patients with progressive renal disease, is an indication for discontinuation of treatment with bumetanide. Bumetanide is also contraindicated in patients in hepatic coma or in states of severe electrolyte depletion until the condition is improved or corrected. Bumetanide is contraindicated in patients hypersensitive to this drug.

WARNINGS
1. Volume and electrolyte depletion. The dose of bumetanide should be adjusted to the patient’s need. Excessive doses or too frequent administration can lead to profound water loss, electrolyte depletion, dehydration, reduction in blood volume and circulatory collapse with the possibility of vascular thrombosis and embolism, particularly in elderly patients.

2. Hypokalemia. Hypokalemia can occur as a consequence of bumetanide administration. Prevention of hypokalemia requires particular attention in the following conditions: patients receiving digitalis and diuretics for congestive heart failure, hepatic cirrhosis and ascites, states of aldosterone excess with normal renal function, potassium-losing nephropathy, certain diarrheal states, or other states where hypokalemia is thought to represent particular added risks to the patient, i.e., history of ventricular arrhythmias.

In patients with hepatic cirrhosis and ascites, sudden alterations of electrolyte balance may precipitate hepatic encephalopathy and coma. Treatment in such patients is best initiated in the hospital with small doses and careful monitoring of the patient’s clinical status and electrolyte balance. Supplemental potassium and/or spironolactone may prevent hypokalemia and metabolic alkalosis in these patients.

3. Ototoxicity. In cats, dogs and guinea pigs, bumetanide has been shown to produce ototoxicity. In these test animals bumetanide was 5 to 6 times more potent than furosemide and, since the diuretic potency of bumetanide is about 40 to 60 times furosemide, it is anticipated that blood levels necessary to produce ototoxicity will rarely be achieved. The potential exists, however, and must be considered a risk of intravenous therapy, especially at high doses, repeated frequently in the face of renal excretory function impairment. Potentiation of aminoglycoside ototoxicity has not been tested for bumetanide. Like other members of this class of diuretics, bumetanide probably shares this risk.

4. Allergy to sulfonamides. Patients allergic to sulfonamides may show hypersensitivity to bumetanide.

5. Thrombocytopenia. Since there have been rare spontaneous reports of thrombocytopenia from postmarketing experience, patients should be observed regularly for possible occurrence of thrombocytopenia

Dosing (adults):
Oral, I.M., I.V.:
Edema:
Oral: 0.5-2 mg/dose (maximum dose: 10 mg/day) 1-2 times/day.
 I.M., I.V.: 0.5-1 mg/dose; may repeat in 2-3 hours for up to 2 doses if needed (maximum dose: 10 mg/day) .
Continuous I.V. infusion: 0.9 to 1 mg/hour.

Hypertension: Oral: 0.5 mg daily (maximum dose: 5 mg/day); usual dosage range (JNC 7): 0.5-2 mg/day in 2 divided doses

Administration
Administer I.V. slowly, over 1-2 minutes; an alternate-day schedule or a 3-4 daily dosing regimen with rest periods of 1-2 days in between may be the most tolerable and effective regimen for the continued control of edema; reserve I.V. administration for those unable to take oral medications

Supplied
Injection, solution: 0.25 mg/mL (2 mL, 4 mL, 10 mL) [contains benzyl alcohol]
Tablet (Bumex®): 0.5 mg, 1 mg, 2 mg

Dosing (adults):
Hypertension: Oral: 500 mg to 2 g/day divided in 1-2 doses (manufacturer labeling); doses of 125-500 mg/day have also been recommended

Edema: Oral, I.V.: 500 mg to 1 g once or twice daily. Intermittent treatment (ie, therapy on alternate days) may be appropriate for some patients.

Elderly: Oral: 500 mg once daily or 1 g 3 times/week

Supplied
Injection, powder for reconstitution, as sodium: 500 mg
Suspension, oral: 250 mg/5 mL (237 mL) [contains alcohol 0.5% and benzoic acid]
Tablet: 250 mg, 500 mg

The drug produces copious diuresis with greatly increased excretion of sodium and chloride. At maximal therapeutic dosage, chlorthalidone is approximately equal in its diuretic effect to comparable maximal therapeutic doses of benzothiadiazine diuretics. The site of action appears to be the cortical diluting segment of the ascending limb of Henle's loop of the Nephron.

INDICATIONS AND USAGE
Diuretics such as chlorthalidone are indicated in the management of hypertension either as the sole therapeutic agent or to enhance the effect of other antihypertensive drugs in the more severe forms of hypertension.

Chlorthalidone is indicated as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy.

Chlorthalidone has also been found useful in edema due to various forms of renal dysfunction, such as nephrotic syndrome, acute glomerulonephritis, and chronic renal failure

Dosing (adults)
Oral:  25-100 mg/day or 100 mg 3 times/week; usual dosage range (JNC 7): 12.5-25 mg/day

Elderly: Initial: 12.5-25 mg/day or every other day; there is little advantage to using doses >25 mg/day

Dosage adjustment in renal impairment: Clcr<10 mL/minute: Administer every 48 hours

Supplied
Tablet: 25 mg, 50 mg, 100 mg

[Supplied: 50 mg tablet]

Mechanism of Action
Eplerenone binds to the mineralocorticoid receptor and blocks the binding of aldosterone, a component of the renin-angiotensin-aldosterone-system (RAAS). Aldosterone synthesis, which occurs primarily in the adrenal gland, is modulated by multiple factors, including angiotensin II and non-RAAS mediators such as adrenocorticotropic hormone (ACTH) and potassium. Aldosterone binds to mineralocorticoid receptors in both epithelial (e.g., kidney) and nonepithelial (e.g., heart, blood vessels and brain) tissues and increases blood pressure through induction of sodium reabsorption and possibly other mechanisms.

Eplerenone has been shown to produce sustained increases in plasma renin and serum aldosterone, consistent with inhibition of the negative regulatory feedback of aldosterone on renin secretion. The resulting increased plasma renin activity and aldosterone circulating levels do not overcome the effects of eplerenone.

Eplerenone selectively binds to recombinant human mineralocorticoid receptors relative to its binding to recombinant human glucocorticoid, progesterone and androgen receptors.

Dosing (adults)
Oral:
Hypertension: Initial: 50 mg once daily; may increase to 50 mg twice daily if response is not adequate; may take up to 4 weeks for full therapeutic response. Doses >100 mg/day are associated with increased risk of hyperkalemia and no greater therapeutic effect.

Concurrent use with moderate CYP3A4 inhibitors: Initial: 25 mg once daily

Congestive heart failure (post-MI): Initial: 25 mg once daily; dosage goal: titrate to 50 mg once daily within 4 weeks, as tolerated

Dosage adjustment per serum potassium concentrations for CHF:
<5.0 mEq/L:
Increase dose from 25 mg every other day to 25 mg daily or
Increase dose from 25 mg daily to 50 mg daily

5.0-5.4 mEq/L: No adjustment needed

5.5-5.9 mEq/L:
Decrease dose from 50 mg daily to 25 mg daily or
Decrease dose from 25 mg daily to 25 mg every other day or
Decrease does from 25 mg every other day to withhold medication

>/= 6.0 mEq/L: Withhold medication until potassium <5.5 mEq/L, then restart at 25 mg every other day

Dosage adjustment in renal impairment:
Patients with hypertension with Clcr<50 mL/minute or serum creatinine >2.0 mg/dL in males or >1.8 mg/dL in females: Use is contraindicated; risk of hyperkalemia increases with declining renal function

Patients with CHF post-MI: Use with caution
Supplied
Tablet [film coated]: 25 mg, 50 mg

Edema (adult):
Oral: 50-100 mg/day in 1-2 divided doses; may increase in increments of 25-50 mg at intervals of several days to a maximum of 400 mg/24 hours. (ELDERLY — Oral: Initial: 25-50 mg/day.)
IV: Usual: 50mg x 1 (0.5-1 mg/kg/dose). Maximum: 100 mg/dose. Usually only one dose has been necessary; occasionally a second dose at a new injection site, to avoid possible thrombophlebitis, may be required. A single intravenous dose not exceeding 100 mg has been used in critical situations.

Preparation: Dilute in D5W or NS (1 mg/mL) and infuse over several minutes.

[Supplied: 50 MG powder for inj. 25, 50mg tablet]

Dosing (adults)
Edema/CHF: initial: 20-40 mg IV/IM over 1-2 min. May repeat in 1 to 2 hours or may be increased by 20 mg until desired response. This individually determined dose may be given once or twice daily.
Edema (oral): initial: 20-80 mg orally qd- may repeat in 6-8 hrs. Maximum: 600 mg/day.

HTN: initial: 80 mg po daily (divided twice daily).

Acute pulmonary edema: usual dose - 40 mg IV over 1-2 minutes. If not adequate, may increase dose to 80 mg.

Continuous I.V. infusion: Initial IV bolus dose of 0.1 mg/kg followed by continuous I.V. infusion doses of 0.1 mg/kg/hour doubled q2h to a maximum of 0.4 mg/kg/hour if urine output is <1 ml/kg/hour. Other studies have used a rate of 4 mg/minute as a continuous IV infusion.

Elderly: Oral, IM, IV: Initial: 20 mg/day; increase slowly to desired response.

Acute renal failure: High doses (up to 1-3 g/day - oral/IV) have been used to initiate desired response. Avoid use in oliguric states.

Administration: IV injections should be given slowly over 1-2 minutes. Maximum rate of administration for IVPB or infusion: 4 mg/minute. Replace parenteral therapy with oral therapy as soon as possible.
[Supplied 10 mg/ml, 40 mg/5 ml oral soln. 10 mg/ml soln for inj. 20,40, 50, 80mg tablet]

Dosing (adults)
Edema: 25-100 mg po daily in single or divided doses.
Hypertension (HTN): initial, 12.5-25 mg po once daily. Titration: allow 2-3 weeks to achieve optimum antihypertensive effect. Usual maintenance dose: 12.5 - 50mg/day. Maximum 50mg/day.

Renal Dosing: GFR less than 15-25 mL/min, use not recommended. Patients with edema may respond to intermittent therapy (ie, administer on alternate days or 3-5 days / week).

[Supplied: 25, 50, 100mg tablet. 12.5 mg capsule. 50mg/5 ml solution]

Dosing (adults)
 HTN: initial, 1 tab or capsule (25 mg hydrochlorothiazide/37.5 mg triamterene) po qd. Allow 2-3 weeks to achieve optimum antihypertensive effect. May increase to maximum dose of 50/75 mg po qd (higher doses increase the risk of electrolyte imbalance and renal dysfunction).

[Supplied  25 mg-37.5 mg capsule/tablet. 50 mg-75 mg tablet].

Dosing (adults)
Edema: usual - 50 to 100 mg daily initially. Doses of 25 or 200 mg daily are used for maintenance therapy. HTN: usual adult dose - 12.5 to 50 mg daily.

[Supplied: 50mg tablet]

Management of mild to moderate hypertension; treatment of edema in congestive heart failure and nephrotic syndrome

Adults: Oral:
Edema: 2.5-5 mg/day. Note: There is little therapeutic benefit to increasing the dose >5 mg/day; there is, however, an increased risk of electrolyte disturbances

Hypertension: 1.25 mg in the morning, may increase to 5 mg/day by increments of 1.25-2.5 mg; consider adding another antihypertensive and decreasing the dose if response is not adequate

[Supplied 1.25, 2.5 mg tablet]

Methazolamide's inhibitory action on carbonic anhydrase decreases the secretion of aqueous humor and results in a decrease in intraocular pressure. The onset of the decrease in intraocular pressure generally occurs within two to four hours, has a peak effect in six to eight hours, and a total duration of ten to eighteen hours.

Methazolamide is a sulfonamide derivative; however, it does not have any clinically significant antimicrobial properties. Although methazolamide achieves a high concentration in the cerebrospinal fluid, it is not considered an effective anticonvulsant.

Methazolamide has a weak and transient diuretic effect, therefore use results in an increase in urinary volume, with excretion of sodium, potassium and chloride. The drug should not be used as a diuretic. Inhibition of renal bicarbonate reabsorption produces an alkaline urine. Plasma bicarbonate decreases, and a relative, transient metabolic acidosis may occur due to a disequilibrium in carbon dioxide transport in the red cell. Urinary citrate excretion is decreased by approximately 40% after doses of 100 mg every 8 hours. Uric acid output has been shown to decrease 36% in the first 24 hour period.

INDICATIONS AND USAGE
Methazolamide is indicated in the treatment of ocular conditions where lowering intraocular pressure is likely to be of therapeutic benefit, such as chronic open-angle glaucoma, secondary glaucoma, and preoperatively in acute angle-closure glaucoma where lowering the intraocular pressure is desired before surgery.

CONTRAINDICATIONS
Methazolamide therapy is contraindicated in situations in which sodium and/or potassium serum levels are depressed, in cases of marked kidney or liver disease or dysfunction, in adrenal gland failure, and in hyperchloremic acidosis. In patients with cirrhosis, use may precipitate the development of hepatic encephalopathy.

Long-term administration of methazolamide is contraindicated in patients with angle-closure glaucoma, since organic closure of the angle may occur in spite of lowered intraocular pressure.

Dosage - Adults:
Oral: 50-100 mg 2-3 times/day
Glaucoma: 50-100 mg po bid - tid.
Altitude sickness: 150-200 mg po daily.

[Supplied: 25, 50 mg tablet]

[Supplied: 2.5, 5mg tablet]

CLINICAL PHARMACOLOGY
Metolazone is a quinazoline diuretic, with properties generally similar to the thiazide diuretics. The actions of metolazone result from interference with the renal tubular mechanism of electrolyte reabsorption. Metolazone acts primarily to inhibit sodium reabsorption at the cortical diluting site and to a lesser extent in the proximal convoluted tubule. Sodium and chloride ions are excreted in approximately equivalent amounts. The increased delivery of sodium to the distal tubular exchange site results in increased potassium excretion. Metolazone does not inhibit carbonic anhydrase. A proximal action of metolazone has been shown in humans by increased excretion of phosphate and magnesium ions and by a markedly increased fractional excretion of sodium in patients with severely compromised glomerular filtration. This action has been demonstrated in animals by micropuncture studies.

When metolazone tablets are given, diuresis and saluresis usually begin within one hour and may persist for 24 hours or more. For most patients, the duration of effect can be varied by adjusting the daily dose. High doses may prolong the effect. A single daily dose is recommended. When a desired therapeutic effect has been obtained, it may be possible to reduce dosage to a lower maintenance level.

The diuretic potency of metolazone at maximum therapeutic dosage is approximately equal to thiazide diuretics. However, unlike thiazides, metolazone may produce diuresis in patients with glomerular filtration rates below 20 mL/min.

Metolazone and furosemide administered concurrently have produced marked diuresis in some patients where edema or ascites was refractory to treatment with maximum recommended doses of these or other diuretics administered alone. The mechanism of this interaction is unknown (see WARNINGS and PRECAUTIONS: Drug Interactions).

Maximum blood levels of metolazone are found approximately eight hours after dosing. A small fraction of metolazone is metabolized. Most of the drug is excreted in the unconverted form in the urine.

INDICATIONS AND USAGE
Metolazone tablets are indicated for the treatment of salt and water retention including:

edema accompanying congestive heart failure;
edema accompanying renal diseases, including the nephrotic syndrome and states of diminished renal function.
Metolazone tablets are also indicated for the treatment of hypertension, alone or in combination with other antihypertensive drugs of a different class. Mykrox® tablets, a more rapidly available form of metolazone, are intended for the treatment of new patients with mild to moderate hypertension. A dose titration is necessary if Mykrox® tablets are to be substituted for Zaroxolyn® tablets and other formulations of metolazone that share its slow and incomplete bioavailability, in the treatment of hypertension.

Adults: Oral:
Edema: 5-20 mg/dose every 24 hours

Hypertension (Zaroxolyn®): 2.5 to 5 mg/dose every 24 hours

Hypertension (Mykrox®): 0.5 mg/day; if response is not adequate, increase dose to maximum of 1 mg/day

[Supplied: Mykrox® 0.5 mg tablet. Zaroxolyn®: 2.5, 5, 10mg tablet]

[Supplied: 1, 2, 4 mg tablet]

Mechanisms of Action
Spironolactone is a specific pharmacologic antagonist of aldosterone, acting primarily through competitive binding of receptors at the aldosterone-dependent sodium-potassium exchange site in the distal convoluted renal tubule. Spironolactone causes increased amounts of sodium and water to be excreted, while potassium is retained. Spironolactone acts both as a diuretic and as an antihypertensive drug by this mechanism. It may be given alone or with other diuretic agents which act more proximally in the renal tubule.

Aldosterone antagonist activity
Increased levels of the mineralocorticoid, aldosterone, are present in primary and secondary hyperaldosteronism. Edematous states in which secondary aldosteronism is usually involved include congestive heart failure, hepatic cirrhosis, and the nephrotic syndrome. By competing with aldosterone for receptor sites, spironolactone provides effective therapy for the edema and ascites in those conditions. Spironolactone counteracts secondary aldosteronism induced by the volume depletion and associated sodium loss caused by active diuretic therapy.

Spironolactone is effective in lowering the systolic and diastolic blood pressure in patients with primary hyperaldosteronism. It is also effective in most cases of essential hypertension, despite the fact that aldosterone secretion may be within normal limits in benign essential hypertension.

Through its action in antagonizing the effect of aldosterone, spironolactone inhibits the exchange of sodium for potassium in the distal renal tubule and helps to prevent potassium loss.

Spironolactone has not been demonstrated to elevate serum uric acid, to precipitate gout, or to alter carbohydrate metabolism.

Adults: Oral:
To reduce delay in onset of effect, a loading dose of 2 or 3 times the daily dose may be administered on the first day of therapy.

Edema, hypokalemia: 25-200 mg/day in 1-2 divided doses

Hypertension (JNC 7): 25-50 mg/day in 1-2 divided doses

Diagnosis of primary aldosteronism: 100-400 mg/day in 1-2 divided doses

Acne in women (unlabeled use): 25-200 mg once daily

Hirsutism in women (unlabeled use): 50-200 mg/day in 1-2 divided doses

CHF, severe (with ACE inhibitor and a loop diuretic ± digoxin): 25 mg/day, increased or reduced depending on individual response and evidence of hyperkalemia

Elderly: Initial: 25-50 mg/day in 1-2 divided doses, increasing by 25-50 mg every 5 days as needed.

Dosing interval in renal impairment:
Clcr 10-50 mL/minute: Administer every 12-24 hours.
Clcr<10 mL/minute: Avoid use.

Supplied
Tablet: 25 mg, 50 mg, 100 mg

[Supplied: 25/25mg and 50/50mg tablets].

(HTN): initial 5 mg po qd. Allow 4-6wk to achieve optimum antihypertensive effect. May increase to 10 mg po qd.
[Supplied: 10 mg/ml injection. 5, 10, 20 , 100mg tablet]

[Supplied: 4 mg tablet]

Adults: Oral: 100-300 mg/day in 1-2 divided doses; maximum dose: 300 mg/day; usual dosage range (JNC 7): 50-100 mg/day

Dosing interval in renal impairment:
 Clcr<10 mL/minute: Avoid use.

Dosing adjustment in hepatic impairment: Dose reduction is recommended in patients with cirrhosis.

[Supplied: 50, 100mg capsule].