Hyzaar (hydrochlorothiazide/losartan potassium)
D/C when pregnancy is detected. Drugs that act directly on the renin-angiotensin system (RAS) can cause injury/death to the developing fetus.
Angiotensin II receptor blocker (ARB) /thiazide diuretic
Treatment of HTN. Reduce the risk of stroke in patients with HTN and left ventricular hypertrophy (LVH) (may not apply to black patients).
Usual: 50mg/12.5mg qd
Max: 100mg/25mg qd
Combination may be substituted for titrated components
Initial: 50mg/12.5mg qd
Titrate: If inadequate response after 2-4 weeks, increase to 100mg/25mg qd
Max: 100mg/25mg qd
Hypertension with Left Ventricular Hypertrophy
Reduction in Risk of Stroke:
Initial: Losartan 50mg qd
Titrate: If inadequate BP reduction, add 12.5mg HCTZ or substitute w/ losartan-HCTZ 50mg/12.5mg
If additional BP reduction needed, substitute w/ losartan 100mg and HCTZ 12.5mg or losartan-HCTZ 100mg/12.5mg, followed by losartan 100mg and HCTZ 25mg or losartan-HCTZ 100mg/25mg
This may not apply to black patients
Take w/ or w/o food
Tab: (Losartan/HCTZ) 50mg/12.5mg, 100mg/12.5mg, 100mg/25mg
Anuria, sulfonamide-derived drug hypersensitivity. Coadministration with aliskiren in patients with diabetes.
Not indicated for initial therapy of HTN. Symptomatic hypotension may occur in intravascularly volume-depleted patients (eg, treated with diuretics); correct volume depletion before therapy. Not recommended with hepatic impairment requiring losartan titration. Not recommended with severe renal impairment (CrCl ≤30mL/min). Angioedema reported (rare). HCTZ: Caution with impaired hepatic function or progressive liver disease; may precipitate hepatic coma. Hypersensitivity reactions may occur. May cause exacerbation or activation of systemic lupus erythematosus (SLE). May cause idiosyncratic reaction, resulting in acute transient myopia and acute angle-closure glaucoma; d/c as rapidly as possible. Observe for clinical signs of fluid or electrolyte imbalance (hyponatremia, hypochloremic alkalosis, and hypokalemia). Hypokalemia may develop, especially with brisk diuresis, severe cirrhosis, or after prolonged therapy. Hypokalemia may cause cardiac arrhythmia and may sensitize/exaggerate the response of the heart to the toxic effects of digitalis. Hyperuricemia may occur or frank gout may be precipitated. May cause hyperglycemia, hypomagnesemia, hypercalcemia, and manifestations of latent diabetes mellitus (DM). D/C prior to parathyroid function tests. Enhanced effects in postsympathectomy patients. Consider withholding or discontinuing therapy if progressive renal impairment becomes evident. Increased cholesterol and TG levels reported. May precipitate azotemia in patients with renal disease. Losartan: Oliguria and/or progressive azotemia and acute renal failure and/or death (rare) may occur in patients whose renal function is dependent on the activity of the RAS (eg, severe congestive heart failure [CHF]). May increase SrCr and BUN levels in patients with renal artery stenosis.
Hypokalemia, dizziness, URI.
See Contraindications. NSAIDs, including selective COX-2 inhibitors, may decrease effects of diuretics and angiotensin II receptor antagonists and may deteriorate renal function. May reduce lithium clearance and increase risk of lithium toxicity; avoid concurrent use. Monitor serum lithium levels during concomitant use. HCTZ: Potentiation of orthostatic hypotension may occur with alcohol, barbiturates, or narcotics. Dose adjustment of antidiabetic drugs (oral agents, insulin) may be required. May cause additive effect or potentiation with other antihypertensives. Anionic exchange resins (eg, cholestyramine, colestipol) may impair absorption. Corticosteroids, adrenocorticotropic hormone, or glycyrrhizin (found in liquorice) may intensify electrolyte depletion, particularly hypokalemia. May decrease response to pressor amines (eg, norepinephrine). May increase response to nondepolarizing skeletal muscle relaxants (eg, tubocurarine). Losartan: Dual blockade of the RAS is associated with increased risks of hypotension, syncope, hyperkalemia, and changes in renal function (including acute renal failure); closely monitor BP, renal function, and electrolytes with concomitant agents that affect the RAS. Avoid with aliskiren in patients with renal impairment (GFR <60mL/min). Rifampin may reduce levels. Fluconazole may decrease levels of the active metabolite and increase levels of losartan. May increase serum K+ with K+-sparing diuretics (eg, spironolactone, triamterene, amiloride), K+ supplements, or salt substitutes containing K+.
PREGNANCY AND LACTATION
Category D, not for use in nursing.
MECHANISM OF ACTION
Losartan: Angiotensin II receptor antagonist; blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to AT1 receptor in many tissues (eg, vascular smooth muscle, adrenal gland). HCTZ: Thiazide diuretic; has not been established. Affects the renal tubular mechanisms of electrolyte reabsorption, directly increasing excretion of Na+ and Cl- in approximately equivalent amounts.
Absorption: Losartan: Well-absorbed. Systemic bioavailability (33%); Tmax=1 hr, 3-4 hrs (active metabolite). Distribution: Losartan: Vd=34L, 12L (active metabolite); plasma protein binding (98.7%, 99.8% active metabolite). HCTZ: Crosses placenta; found in breast milk. Metabolism: Losartan: CYP2C9, 3A4; carboxylic acid (active metabolite). Elimination: Losartan: Urine (35%, 4% unchanged, 6% active metabolite), feces (60%); T1/2=2 hrs, 6-9 hrs (active metabolite). HCTZ: Kidney (≥61% unchanged); T1/2=5.6-14.8 hrs.
Assess for hypersensitivity to the drug and its components, anuria, sulfonamide-derived drug hypersensitivity, history of penicillin allergy, volume/salt depletion, SLE, DM, CHF, hepatic/renal function, postsympathectomy status, cirrhosis, renal artery stenosis, pregnancy/nursing status, and possible drug interactions. Obtain baseline BP.
Monitor for signs/symptoms of fluid/electrolyte imbalance, exacerbation/activation of SLE, idiosyncratic reaction, latent DM, precipitation of gout, hypersensitivity reactions, and other adverse reactions. Monitor BP, serum electrolytes, renal/hepatic function, cholesterol, and TG levels periodically.
Inform females of childbearing potential of the consequences of exposure during pregnancy and of the treatment options for women planning to become pregnant. Instruct to report pregnancy to the physician as soon as possible. Counsel that lightheadedness may occur, especially during the 1st days of therapy; instruct to report to physician. Instruct to d/c therapy and consult physician if syncope occurs. Caution that inadequate fluid intake, excessive perspiration, diarrhea, or vomiting may lead to an excessive fall in BP, with the same consequences of lightheadedness and possible syncope. Instruct not to use K+ supplements or salt substitutes containing K+ without consulting physician.
25°C (77°F); excursions permitted to 15-30°C (59-86°F). Protect from light.
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