Losartan and hydrochlorothiazide: uses, appearance and warnings

Losartan potassium and hydrochlorothiazide tablet is a combination of losartan, an angiotensin II receptor blocker (ARB) and hydrochlorothiazide, a diuretic indicated for: Treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. ( 1.1) Reduction of the risk of stroke in patients with hypertension and left ventricular hypertrophy. There is evidence that this benefit does not apply to Black patients. ( 1.2 ) 1.1 Hypertension Losartan potassium and hydrochlorothiazide tablet is indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure lowers the risk of fatal and non-fatal cardiovascular (CV) events, primarily strokes and myocardial infarction. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including losartan and hydrochlorothiazide. Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than 1 drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program's Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC). Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly. Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal. Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in Black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy. 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 blood pressure control exceeds the risk of initiating combination therapy in these patients [see CLINICAL STUDIES ( 14 ) and DOSAGE AND ADMINISTRATION ( 2.1 )]. Losartan potassium and hydrochlorothiazide tablet may be administered with other antihypertensive agents. 1.2 Hypertensive Patients with Left Ventricular Hypertrophy Losartan potassium and hydrochlorothiazide tablet is indicated to reduce the risk of stroke in patients with hypertension and left ventricular hypertrophy, but there is evidence that this benefit does not apply to Black patients. [See USE IN SPECIFIC POPULATIONS ( 8.6 ), CLINICAL PHARMACOLOGY ( 12.3 ), and DOSAGE AND ADMINISTRATION ( 2.2 ).]

Losartan potassium and hydrochlorothiazide tablets USP 50 mg/12.5 mg are yellow, capsule shaped, biconvex, film-coated tablets, debossed with 'LU' on one side and 'M41' on the other side. Losartan potassium and hydrochlorothiazide tablets USP 100 mg/12.5 mg are white, oval shaped, biconvex, film-coated tablets, debossed with 'LU' on one side and 'M42' on the other side. Losartan potassium and hydrochlorothiazide tablets USP 100 mg /25 mg are yellow, tear drop shaped, biconvex, film-coated tablets, debossed with 'LU' on one side and 'M43' on the other side. Tablets (losartan potassium/hydrochlorothiazide content): 50/12.5 mg; 100/12.5 mg; and 100/25 mg. ( 3 )

Losartan potassium and hydrochlorothiazide tablet USP is supplied as a film-coated tablet. Losartan/ Hydrochlorothiazide Color Shape Engraving NDC 68180-xxx-xx One side Other side Bottle/30 Bottle/90 50 mg/12.5 mg Yellow Capsule shaped biconvex LU M41 215-06 215-09 100 mg/12.5 mg White Oval shaped biconvex LU M42 216-06 216-09 100 mg/25 mg Yellow Tear drop shaped biconvex LU M43 217-06 217-09 Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Keep container tightly closed. Protect from light.

Losartan potassium and hydrochlorothiazide tablet is contraindicated: In patients who are hypersensitive to any component of this product. In patients with anuria For coadministration with aliskiren in patients with diabetes Hypersensitivity to any component of losartan potassium and hydrochlorothiazide tablets. ( 4 ) Anuria. ( 4 ) Coadministration with aliskiren in patients with diabetes. ( 4 )

Hypotension: Correct volume or salt depletion prior to administration of losartan potassium and hydrochlorothiazide tablets. ( 5.2 ) Monitor renal function and potassium in susceptible patients. ( 5.3 ) Observe for clinical signs of fluid or electrolyte imbalance. ( 5.5 ) Acute angle-closure glaucoma. ( 5.6 ) Exacerbation of systemic lupus erythematosus. ( 5.7 ) 5.1 Fetal Toxicity Losartan potassium and hydrochlorothiazide tablets can cause fetal harm when administered to a pregnant woman. Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected, discontinue losartan potassium and hydrochlorothiazide tablets as soon as possible. Thiazides cross the placental barrier and appear in cord blood. Adverse reactions include fetal or neonatal jaundice, thrombocytopenia [see USE IN SPECIFIC POPULATIONS ( 8.1 )]. 5.2 Hypotension in Volume- or Salt-Depleted Patients In patients with an activated renin-angiotensin system, such as volume- or salt-depleted patients (e.g., those being treated with high doses of diuretics), symptomatic hypotension may occur after initiation of treatment with losartan potassium and hydrochlorothiazide tablets. Correct volume or salt depletion prior to administration of losartan potassium and hydrochlorothiazide tablets. Do not use losartan potassium and hydrochlorothiazide tablets as initial therapy in patients with intravascular volume depletion. 5.3 Impaired Renal Function Changes in renal function including acute renal failure can be caused by drugs that inhibit the renin angiotensin system and by diuretics. Patients whose renal function may depend in part on the activity of the renin-angiotensin system (e.g., patients with renal artery stenosis, chronic kidney disease, severe congestive heart failure, or volume depletion) may be at particular risk of developing acute renal failure on losartan potassium and hydrochlorothiazide tablets .Monitor renal function periodically in these patients. Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on losartan potassium and hydrochlorothiazide tablets [see DRUG INTERACTIONS ( 7.3 ) and USE IN SPECIFIC POPULATIONS ( 8.8 )]. 5.4 Hypersensitivity Hypersensitivity reactions to hydrochlorothiazide may occur in patients with or without a history of allergy or bronchial asthma but are more likely in patients with such a history [see ADVERSE REACTIONS ( 6.2 )] . 5.5 Electrolyte and Metabolic Effects In double-blind clinical trials of various doses of losartan potassium and hydrochlorothiazide, the incidence of hypertensive patients who developed hypokalemia (serum potassium <3.5 mEq/L) was 6.7% versus 3.5% for placebo; the incidence of hyperkalemia (serum potassium >5.7 mEq/L) was 0.4% versus 0% for placebo. Losartan potassium and hydrochlorothiazide tablet contains hydrochlorothiazide which can cause hypokalemia, hyponatremia and hypomagnesemia. Hypomagnesemia can result in hypokalemia which may be difficult to treat despite potassium repletion. Losartan potassium and hydrochlorothiazide tablet also contains losartan which can cause hyperkalemia. Monitor serum electrolytes periodically [see DRUG INTERACTIONS ( 7.1 )]. Concomitant use of other drugs that may increase serum potassium may lead to hyperkalemia [see DRUG INTERACTIONS ( 7.1 )]. Hydrochlorothiazide may alter glucose tolerance and raise serum levels of cholesterol and triglycerides. Hyperuricemia may occur or frank gout may be precipitated in patients receiving thiazide therapy. Because losartan decreases uric acid, losartan in combination with hydrochlorothiazide attenuates the diuretic-induced hyperuricemia. Hydrochlorothiazide decreases urinary calcium excretion and may cause elevations of serum calcium. Monitor calcium levels. 5.6 Acute Myopia and Secondary Angle-Closure Glaucoma Hydrochlorothiazide, a sulfonamide, can cause an idiosyncratic reaction, resulting in acute transient myopia and acute angle-closure glaucoma. Symptoms include acute onset of decreased visual acuity or ocular pain and typically occur within hours to weeks of drug initiation. Untreated acute angle-closure glaucoma can lead to permanent vision loss. The primary treatment is to discontinue hydrochlorothiazide as rapidly as possible. Prompt medical or surgical treatments may need to be considered if the intraocular pressure remains uncontrolled. Risk factors for developing acute angle-closure glaucoma may include a history of sulfonamide or penicillin allergy. 5.7 Systemic Lupus Erythematosus Thiazide diuretics have been reported to cause exacerbation or activation of systemic lupus erythematosus.

Most common adverse reactions (incidence ≥2% and greater than placebo) are dizziness, upper respiratory infection, cough, and back pain. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Lupin Pharmaceuticals, Inc. at 1-800-399-2561 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Losartan potassium-hydrochlorothiazide has been evaluated for safety in 858 patients treated for essential hypertension and 3889 patients treated for hypertension and left ventricular hypertrophy. Most adverse reactions have been mild and transient in nature and have not required discontinuation of therapy. …

Agents increasing serum potassium: Risk of hyperkalemia. ( 7.1 ) Lithium: Risk of lithium toxicity. ( 7.2 ) Non-Steroidal Anti-Inflammatory Drugs (NSAIDs): increased risk of renal impairment and reduced diuretic, natriuretic, and antihypertensive effects. ( 7.3 ) Dual inhibition of the renin-angiotensin system: increased risk of renal impairment, hypotension, syncope, and hyperkalemia. ( 7.4 ) Antidiabetic drugs: dosage adjustment of antidiabetic may be required. ( 7.5 ) Cholestyramine and colestipol: Reduced absorption of thiazides. ( 7.5 ) 7.1 Agents Increasing Serum Potassium Coadministration of losartan with other drugs that raise serum potassium levels may result in hyperkalemia. Monitor serum potassium in such patients. …