PHARMACOLOGIC CATEGORY
Diuretic, Combination
DOSING: ADULTS — Hypertension, edema: Oral: Initial: 1 tablet/day; may be increased to 2 tablets/day if needed; usually given in a single dose
DOSING: ELDERLY — Oral: Initial: 1/2 to 1 tablet/day
DOSING: RENAL IMPAIRMENT — See individual agents.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet: 5/50: Amiloride hydrochloride 5 mg and hydrochlorothiazide 50 mg
DOSAGE FORMS: CONCISE
Tablet: 5/50: Amiloride 5 mg and hydrochlorothiazide 50 mg
GENERIC EQUIVALENT AVAILABLE — Yes
USE — Potassium-sparing diuretic; antihypertensive
ADVERSE REACTIONS SIGNIFICANT — See individual agents.
WARNINGS / PRECAUTIONS
Boxed warnings: Hyperkalemia: See "Concerns related to adverse effects" below.
Concerns related to adverse effects: Electrolyte disturbances: Hypochloremic alkalosis and hyponatremia can occur. Hyperkalemia: [U.S. Boxed Warning]: Hyperkalemia can occur; patients at risk include those with renal impairment, diabetes, the elderly, and the severely ill. Serum potassium levels must be monitored at frequent intervals especially when dosages are changed or with any illness that may cause renal dysfunction. Photosensitivity: Photosensitization may occur with hydrochlorothiazide. Sulfa allergy: Chemical similarities are present among sulfonamides, sulfonylureas, carbonic anhydrase inhibitors, thiazides, and loop diuretics (except ethacrynic acid). Use in patients with sulfonamide allergy is specifically contraindicated in product labeling, however, a risk of cross-reaction exists in patients with allergy to any of these compounds; avoid use when previous reaction has been severe. Discontinue if signs of hypersensitivity are noted.
Disease-related concerns: Diabetes: Use with extreme caution in patients with diabetes mellitus; may see a change in glucose control. Monitor closely; discontinue amiloride 3 days prior to glucose tolerance testing. Gout: In certain patients with a history of gout, a familial predisposition to gout, or chronic renal failure, gout can be precipitated with hydrochlorothiazide. Hepatic impairment: Use hydrochlorothiazide with caution in patients with severe hepatic dysfunction; in cirrhosis, avoid electrolyte and acid/base imbalances that might lead to hepatic encephalopathy. Hypercholesterolemia: Use hydrochlorothiazide with caution in patients with moderate or high cholesterol concentrations. Metabolic/respiratory acidosis: Use with caution in patients who are at risk for metabolic or respiratory acidosis (eg, cardiopulmonary disease, uncontrolled diabetes). Renal impairment: Avoid use of hydrochlorothiazide in severe renal disease (ineffective). Systemic lupus erythematosus (SLE): Hydrochlorothiazide can cause SLE exacerbation or activation.
DRUG INTERACTIONS
ACE Inhibitors: Potassium-Sparing Diuretics may enhance the hyperkalemic effect of ACE Inhibitors. Risk C: Monitor therapy
ACE Inhibitors: Thiazide Diuretics may enhance the hypotensive effect of ACE Inhibitors. Specifically, postural hypotension which can accompany ACE Inhibitor initiation. Thiazide Diuretics may enhance the nephrotoxic effect of ACE Inhibitors. Risk C: Monitor therapy
Alcohol (Ethyl): May enhance the orthostatic effect of Thiazide Diuretics. Risk C: Monitor therapy
Allopurinol: Thiazide Diuretics may enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Thiazide Diuretics may increase the serum concentration of Allopurinol. Specifically, Thiazide Diuretics may increase the concentration of Oxypurinolol, an active metabolite of Allopurinol. Risk C: Monitor therapy
Amifostine: Antihypertensives may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification
Ammonium Chloride: Potassium-Sparing Diuretics may enhance the adverse/toxic effect of Ammonium Chloride. Specifically the risk of systemic acidosis. Risk D: Consider therapy modification
Analgesics (Opioid): May enhance the orthostatic effect of Thiazide Diuretics. Risk C: Monitor therapy
Angiotensin II Receptor Blockers: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Antidiabetic Agents: Thiazide Diuretics may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Antihypertensives: May enhance the hypotensive effect of other Antihypertensives. Risk C: Monitor therapy
Barbiturates: May enhance the orthostatic effect of Thiazide Diuretics. Risk C: Monitor therapy
Bile Acid Sequestrants: May decrease the absorption of Thiazide Diuretics. The diuretic response is likewise decreased. Risk D: Consider therapy modification
Calcitriol: Thiazide Diuretics may enhance the hypercalcemic effect of Calcitriol. Risk C: Monitor therapy
Calcium Salts: Thiazide Diuretics may decrease the excretion of Calcium Salts. Continued concomitant use can also result in metabolic alkalosis. Risk C: Monitor therapy
Cardiac Glycosides: Potassium-Sparing Diuretics may diminish the therapeutic effect of Cardiac Glycosides. In particular, the inotropic effects of digoxin appear to be diminished. Potassium-Sparing Diuretics may increase the serum concentration of Cardiac Glycosides. This particular effect may be unique to Spironolactone. Risk C: Monitor therapy
Corticosteroids (Orally Inhaled): May enhance the hypokalemic effect of Thiazide Diuretics. Risk C: Monitor therapy
Corticosteroids (Systemic): May enhance the hypokalemic effect of Thiazide Diuretics. Risk C: Monitor therapy
Dofetilide: Thiazide Diuretics may enhance the QTc-prolonging effect of Dofetilide. Thiazide Diuretics may increase the serum concentration of Dofetilide. Risk X: Avoid combination
Drospirenone: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Eplerenone: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Management: This combination is contraindicated in patients receiving eplerenone for treatment of hypertension. Risk D: Consider therapy modification
Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Lithium: Thiazide Diuretics may decrease the excretion of Lithium. Risk D: Consider therapy modification
MAO Inhibitors: May enhance the orthostatic effect of Orthostasis Producing Agents. Risk C: Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Mitotane: Potassium-Sparing Diuretics may diminish the therapeutic effect of Mitotane. High dose diuretics (eg, Cushings syndrome) may present significantly higher risk than low doses (eg, CHF). Risk D: Consider therapy modification
Nonsteroidal Anti-Inflammatory Agents: May diminish the therapeutic effect of Thiazide Diuretics. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May diminish the antihypertensive effect of Potassium-Sparing Diuretics. Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Potassium Salts: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk D: Consider therapy modification
Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
QuiNIDine: Potassium-Sparing Diuretics may diminish the therapeutic effect of QuiNIDine. Risk C: Monitor therapy
RiTUXimab: Antihypertensives may enhance the hypotensive effect of RiTUXimab. Risk D: Consider therapy modification
Tolvaptan: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Yohimbine: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Refer to Hydrochlorothiazide.
LACTATION — Excretion in breast milk unknown/contraindicated
DIETARY CONSIDERATIONS — May be taken with food.
PRICING — (data from drugstore.com)
Tablets (Amiloride-Hydrochlorothiazide)
5-50 mg (100): $27.99
CANADIAN BRAND NAMES — Apo-Amilzide®; Gen-Amilazide; Moduret; Novamilor; Nu-Amilzide
INTERNATIONAL BRAND NAMES — Adco-Retic (ZA); Add-Acten (AE, BF, BH, BJ, CI, CY, EG, ET, GH, GM, GN, IL, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, OM, QA, SA, SC, SD, SL, SN, SY, TN, TZ, UG, YE, ZA, ZM, ZW); Ameride (ES); Amil-Co (GB); Amilco (DK); Amilco Mite (DK); Amilocomp beta (DE); Amiloretic (ZA); Amizide (AU, TW); Amuretic (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Apo-Amilzide (MY); Biduret (IN); Bildiuretic (TH); Co-Amilozide (AU, GB); Hydrozide (NZ); Hyperetic (TH); Kaluril (IL); Lorinid Mite (ID); Mengdaqing (CL); Moduretic (AU, BE, BF, BJ, BR, CH, CI, CO, CZ, DE, EE, ET, FI, GB, GH, GM, GN, GR, HK, IE, IT, KE, LR, MA, ML, MR, MU, MW, MX, MY, NE, NG, NL, PE, PK, PT, PY, SC, SD, SE, SL, SN, TH, TN, TW, TZ, UG, UY, VE, ZA, ZM, ZW); Moure-M (TH); Mourinate (TH); Sefaretic (HK); Sparkal (DK); Tiaden (TW); Uniretic (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Yostiretic (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE)
PHARMACODYNAMICS / KINETICS — See individual agents.
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