Losartan Potassium / Hydrochlorothiazide

Pronunciation

Pronunciation: loe-SAR-tan poe-TAS-ee-um/HYE-droe-KLOR-oh-THYE-a-zide
Class: Antihypertensive combination

Trade Names

Hyzaar
- Tablets, oral losartan 50 mg/hydrochlorothiazide 12.5 mg
- Tablets, oral losartan 100 mg/hydrochlorothiazide 12.5 mg
- Tablets, oral losartan 100 mg/hydrochlorothiazide 25 mg

Hyzaar DS (Canada)

Pharmacology

Losartan

Antagonizes the effect of angiotensin II (vasoconstriction and aldosterone secretion) by blocking the angiotensin II receptor in vascular smooth muscle and the adrenal gland, producing decreased BP.

Slideshow: 2014 Update: First Time Brand-to-Generic Switches

Hydrochlorothiazide

Inhibits reabsorption of sodium and chloride in ascending loop of Henle and early distal tubules.

Indications and Usage

For the treatment of hypertension; to reduce the risk of stroke in patients with hypertension and left ventricular hypertrophy.

Contraindications

Anuria; hypersensitivity to other sulfonamide derivatives or any component of product.

Dosage and Administration

Adults

PO Losartan 50 mg/hydrochlorothiazide 12.5 mg once daily is the usual dosage. May increase dosage to losartan 100 mg/hydrochlorothiazide 25 mg once daily after 3 wk (max, losartan 100 mg/hydrochlorothiazide 25 mg daily).

Conversion
Adults Current losartan users

PO Patients whose BP is not adequately controlled with losartan 100 mg monotherapy may be switched to losartan 100 mg/hydrochlorothiazide 12.5 mg once daily. May increase to losartan 100 mg/hydrochlorothiazide 25 mg daily after 3 wk, if necessary.

Current hydrochlorothiazide users

PO Patients whose BP is inadequately controlled by hydrochlorothiazide 25 mg once daily or who are controlled but who experience hypokalemia with this regimen may be switched to losartan 50 mg/hydrochlorothiazide 12.5 mg once daily. If BP remains uncontrolled after 3 wk of therapy, the dose may be titrated up to losartan 100 mg/hydrochlorothiazide 25 mg once daily if necessary.

General Advice

  • Administer with or without food.
  • May be administered with other antihypertensives.
  • Not recommended for use as initial therapy in patients with intravascular volume depletion (eg, patients treated with diuretics).
  • This fixed-dose combination is not indicated for initial therapy of hypertension, except when the hypertension is severe enough that the value of achieving prompt BP control exceeds the risk of initiating combination therapy in these patients.
  • The combination may be substituted for the titrated components.

Storage/Stability

Store at 59° to 86°F. Protect from light.

Drug Interactions

No drug interaction studies have been conducted between losartan/hydrochlorothiazide and other drugs. The following interactions are based on drug interactions involving each component of the losartan/hydrochlorothiazide combination.

ACE inhibitors (eg, captopril, ramipril)

Concurrent use may be associated with an increased risk of renal dysfunction and hyperkalemia. Consider monotherapy.

Alcohol, barbiturates, narcotics

Potentiation of orthostatic hypotension may occur.

Aliskiren

Renal excretion of potassium may be decreased, resulting in hyperkalemia, particularly in diabetic patients. Coadministration is contraindicated in diabetic patients and should be avoided in patients with moderate to severe renal impairment. If coadministration is undertaken, closely monitor serum potassium concentrations and renal function.

Antihypertensive agents (eg, propranolol)

Additive or potentiation of hypotension effects may occur.

Antineoplastic agents (eg, cyclophosphamide)

Hydrochlorothiazide may prolong antineoplastic-induced myelosuppression. If coadministration cannot be avoided, use with caution.

Cholestyramine, colestipol resins

Hydrochlorothiazide absorption may be impaired. Single doses of either cholestyramine or colestipol resins bind hydrochlorothiazide, reducing GI absorption up to 85% and 43%, respectively. Separate the administration times by at least 4 h. Adjust diuretic dose as needed.

Corticosteroids, corticotropin

Coadministration may cause intensified electrolyte depletion, particularly hypokalemia.

Cyclooxygenase 2 inhibitors (eg, celecoxib), NSAIDs (eg, ibuprofen, indomethacin, ketorolac [nasal])

The diuretic, natriuretic, and antihypertensive effects of hydrochlorothiazide and the antihypertensive effects of losartan may be reduced. In addition, concomitant use may further deteriorate renal function, especially in volume-depleted patients, patients with renal impairment, or elderly patients. The risk of hyperkalemia may also be increased. Monitor BP, renal function, and serum potassium. If an interaction is suspected, it may be necessary to discontinue the NSAID.

Diazoxide

The pharmacologic effects of both drugs may be increased. Hyperglycemia, hyperuricemia, and hypotension may occur. Closely monitor BP, blood glucose, and serum uric acid.

Digoxin

Hydrochlorothiazide-induced electrolyte disturbances may predispose to digitalis-induced arrhythmias. Closely monitor plasma concentrations of potassium and magnesium and monitor patients for signs of digoxin toxicity.

Dofetilide

Plasma concentrations of dofetilide may be increased; prolongation of the QT interval may occur, increasing the risk of torsades de pointes. Coadministration is contraindicated.

Insulin

Insulin requirements may increase or decrease, or remain unchanged. Monitor blood glucose and adjust the insulin dose as needed.

Lithium

Lithium Cl may be decreased, increasing lithium concentrations and the risk of lithium toxicity. Avoid coadministration. If coadministration cannot be avoided, closely monitor serum lithium levels and adjust the dose of lithium as needed.

Loop diuretics (eg, furosemide)

The effects of loop diuretics may be decreased. In contrast, loop diuretics and hydrochlorothiazide have synergistic effects that may result in profound diuresis and electrolyte abnormalities. Monitor fluid status and electrolytes.

Nondepolarizing muscle relaxants (eg, tubocurarine)

A possible increase in responsiveness to the muscle relaxant due to diuretic-induced hypokalemia may occur. If hypokalemia cannot be corrected, a lower dosage of nondepolarizing muscle relaxants may be needed.

Potassium preparations (eg, potassium-sparing diuretics [eg, amiloride, spironolactone], potassium supplements, salt substitutes containing potassium)

Serum potassium concentrations may be increased, decreased, or unchanged. Hyperkalemia, possibly with cardiac arrhythmias or arrest, may occur. Closely monitor serum potassium concentrations. Adjust treatment as needed.

Pressor amines (eg, norepinephrine)

Response to pressor amines may be decreased. Use with caution.

Rifamycins (eg, rifampin)

Rifamycins may decrease plasma concentrations and pharmacologic effects of losartan. Larger doses of losartan/hydrochlorothiazide may be needed.

Sulfonylureas (eg, glyburide)

Hydrochlorothiazide may increase fasting blood glucose and decrease the hypoglycemic action of sulfonylureas. Closely monitor blood glucose and adjust therapy as needed.

Tretinoin

The risk of phototoxicity may be increased if these agents are coadministered. Avoid coadministration.

Trimethoprim

Hyperkalemia, possibly with cardiac arrhythmias or arrest, may occur, especially in elderly patients. Closely monitor serum potassium. Adjust therapy as needed.

Laboratory Test Interactions

Hydrochlorothiazide may decrease serum protein-bound iodine levels without signs of thyroid disturbance. Interrupt therapy for a few days before carrying out tests of parathyroid function.

Adverse Reactions

Cardiovascular

Hypotension, palpitations (1%).

CNS

Dizziness (6%).

GI

Abdominal pain (1%).

Hepatic

Elevated liver enzymes and/or serum bilirubin, hepatitis (postmarketing).

Lab Tests

Increased BUN, increased serum creatinine (1%); decreased Hgb/Hct.

Metabolic

Hypokalemia (7%); hypercalcemia; hyperglycemia; hyperuricemia; hypomagnesemia; hyponatremia; increased triglyceride and cholesterol levels; hyperkalemia (postmarketing).

Respiratory

Upper respiratory tract infection (6%); cough (3%); sinusitis (1%); dry cough (postmarketing).

Miscellaneous

Back pain (2%); edema/swelling, rash (1%); anaphylactic reactions, angioedema, erythroderma, rhabdomyolysis, thrombocytopenia, vasculitis (postmarketing).

Precautions

Warnings

When used in pregnancy during the second and third trimesters, drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. When pregnancy is detected, discontinue therapy as soon as possible.


Monitor

Correct volume and/or salt depletion before initiating therapy. Perform periodic determinations of serum electrolytes and renal function. Observe all patients for clinical signs of fluid or electrolyte imbalance. Monitor BP and pulse on a regular basis. Monitor blood glucose in diabetic patients when the drug is started or the dose is changed.


Pregnancy

Category C (first trimester); Category D (second and third trimesters). Drugs that act directly on the renin-angiotensin system can cause fetal and neonatal morbidity, including hypotension, neonatal skull hypoplasia, anuria, reversible or irreversible renal failure, and death, when administered to pregnant women during the second and third trimesters. Oligohydramnios has also been reported, presumably resulting from decreased fetal renal function, and has been associated with fetal limb contractures, craniofacial deformation, and hypoplastic lung development. Prematurity, intrauterine growth retardation, and patent ductus arteriosus have also been reported, although it is not clear whether these occurrences were due to exposure to the drug. Women whose embryos and fetuses are exposed only during the first trimester should be so informed.

Thiazides cross the placental barrier and appear in cord blood. There is a risk of fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions that have occurred in adults.

Lactation

It is not known if losartan is excreted into breast milk. Thiazides appear in breast milk. A decision should be made whether to discontinue therapy or breast-feeding, taking into account the importance of the drug to the mother.

Children

Safety and efficacy not established.

Elderly

Use with caution; adverse reactions are more frequent in elderly patients.

Hypersensitivity

May occur in patients with or without a history of allergy or bronchial asthma; cross-sensitivity with sulfonamides may also occur.

Renal Function

Not recommended for use in severe renal impairment (CrCl 30 mL/min or less).

Hepatic Function

Not recommended.

Diabetes

Hyperglycemia may occur; latent diabetes mellitus may become manifest.

Electrolyte imbalance

Hypercalcemia, hypochloremic alkalosis, hypokalemia, hypomagnesemia, and hyponatremia may occur.

Hyperuricemia

May occur or frank gout may be precipitated in certain patients receiving thiazide therapy.

Hypotension

Symptomatic hypotension may occur after initiation of therapy in patients who are intravascularly volume depleted (eg, those treated with diuretics). Use with caution in these patients. Correct these conditions prior to administration of losartan/hydrochlorothiazide or start treatment under close medical supervision.

Lipid disorders

Increases in cholesterol and triglyceride levels may occur.

Ocular effects

Hydrochlorothiazide can cause an idiosyncratic reaction, resulting in acute transient myopia and acute angle-closure glaucoma. Symptoms typically occur within hours to weeks of initiation of therapy.

Postsympathectomy

The antihypertensive effects may be enhanced in these patients.

Renal effects

As a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function may be anticipated in susceptible patients. In patients whose renal function may depend on the activity of the renin-angiotensin-aldosterone system (eg, patients with severe CHF), treatment with ACE inhibitors has been associated with oliguria and/or progressive azotemia, and, rarely, acute renal failure and/or death. In addition, increased BUN and serum creatinine may occur.

Systemic lupus erythematosus

Exacerbation or activation may occur with hydrochlorothiazide.

Overdosage

Symptoms

Bradycardia, dehydration, electrolyte depletion (eg, hypochloremia, hypokalemia, hyponatremia), hypotension, tachycardia.

Patient Information

  • Inform female patients of childbearing potential about the consequences of second and third trimester exposure to drugs that act on the renin-angiotensin system. Inform them that these consequences do not appear to have resulted from intrauterine drug exposure that has been limited to the first trimester. Patients should be asked to report pregnancies to their health care providers as soon as possible.
  • Caution patients that light-headedness can occur, especially during the first few days of therapy, and that it should be reported to the prescribing health care provider. Inform patients that if syncope occurs, losartan/hydrochlorothiazide should be discontinued until the health care provider has been consulted.
  • Caution patients that inadequate fluid intake, excessive perspiration, diarrhea, or vomiting can lead to an excessive fall in BP, with the same consequences of light-headedness and possible syncope.
  • Advise patients not to use potassium supplements or salt substitutes containing potassium without consulting their health care provider.

Copyright © 2009 Wolters Kluwer Health.

Hide
(web4)