Losartan Potassium and Hydrochlorothiazide Tablets, USP 100 mg/12.5 mg

DESCRIPTION

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displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3

 Losartan Potassium and Hydrochlorothiazide 50 mg/12.5 mg, Losartan Potassium and Hydrochlorothiazide 100 mg/12.5 mg and Losartan Potassium and Hydrochlorothiazide 100 mg/25 mg combine an angiotensin II receptor (type AT₁) antagonist and a diuretic, hydrochlorothiazide.     Losartan potassium, a non-peptide molecule, is chemically described as 2-butyl-4-chloro-1-[p-(o–1H-tetrazol-5-ylphenyl)benzyl]imidazole-5-methanol monopotassium salt. Its empirical formula is C₂₂H₂₂ClKN₆O, and its structural formula is:     Losartan potassium, USP is a white to off-white free-flowing crystalline powder with a molecular weight of 461.01. It is freely soluble in water, soluble in alcohols, and slightly soluble in common organic solvents, such as acetonitrile and methyl ethyl ketone.      Oxidation of the 5-hydroxymethyl group on the imidazole ring results in the active metabolite of losartan.     Hydrochlorothiazide is 6-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide. Its empirical formula is C₇H₈ClN₃O₄S₂ and its structural formula is:     Hydrochlorothiazide, USP is a white, or practically white, crystalline powder with a molecular weight of 297.74, which is slightly soluble in water, but freely soluble in sodium hydroxide solution.     Losartan Potassium and Hydrochlorothiazide Tablets, USP are available for oral administration in three tablet combinations of losartan and hydrochlorothiazide. Losartan Potassium and Hydrochlorothiazide Tablets, USP 50 mg/12.5 mg contain 50 mg of losartan potassium USP and 12.5 mg of hydrochlorothiazide USP. Losartan Potassium and Hydrochlorothiazide Tablets, USP 100 mg/12.5 mg contain 100 mg of losartan potassium USP and 12.5 mg of hydrochlorothiazide USP. Losartan Potassium and Hydrochlorothiazide Tablets, USP 100 mg/25 mg contain 100 mg of losartan potassium USP and 25 mg of hydrochlorothiazide USP. Inactive ingredients are colloidal silicon dioxide, hydroxypropyl cellulose, hypromellose, lactose anhydrous, magnesium stearate, microcrystalline cellulose, pregelatinized starch, talc and titanium dioxide. Losartan Potassium and Hydrochlorothiazide Tablets, USP 50 mg/12.5 mg and Losartan Potassium and Hydrochlorothiazide Tablets, USP 100 mg/25 mg also contain D&C yellow No. 10 lake.      Losartan Potassium and Hydrochlorothiazide Tablets, USP 50 mg/12.5 mg contain 4.24 mg (0.108 mEq) of potassium, Losartan Potassium and Hydrochlorothiazide Tablets, USP 100 mg/12.5 mg contain 8.48 mg (0.216 mEq) of potassium, and Losartan Potassium and Hydrochlorothiazide Tablets, USP 100 mg/25 mg contain 8.48 mg (0.216 mEq) of potassium.

INDICATIONS AND USAGE

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displayName: INDICATIONS & USAGE SECTION
FDA Article Code: 34067-9

Hypertension      Losartan Potassium and Hydrochlorothiazide Tablets are indicated for the treatment of hypertension. 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 PHARMACOLOGY, Pharmacodynamics and Clinical Effects, and DOSAGE AND ADMINISTRATION). Hypertensive Patients with Left Ventricular Hypertrophy      Losartan Potassium and Hydrochlorothiazide Tablets are 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 PRECAUTIONS, Race, CLINICAL PHARMACOLOGY, Pharmacodynamics and Clinical Effects, Losartan Potassium, Reduction in the Risk of Stroke, Race, and DOSAGE AND ADMINISTRATION).

CONTRAINDICATIONS

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displayName: CONTRAINDICATIONS SECTION
FDA Article Code: 34070-3

Losartan Potassium and Hydrochlorothiazide Tablets are contraindicated in patients who are hypersensitive to any component of this product.     Because of the hydrochlorothiazide component, this product is contraindicated in patients with anuria or hypersensitivity to other sulfonamide-derived drugs.

ADVERSE REACTIONS

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displayName: ADVERSE REACTIONS SECTION
FDA Article Code: 34084-4

      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. In clinical trials with losartan potassium-hydrochlorothiazide, no adverse experiences peculiar to this combination have been observed. Adverse experiences have been limited to those that were reported previously with losartan potassium and/or hydrochlorothiazide. The overall incidence of adverse experiences reported with the combination was comparable to placebo.      In general, treatment with losartan potassium-hydrochlorothiazide was well tolerated. For the most part, adverse experiences have been mild and transient in nature and have not required discontinuation of therapy. In controlled clinical trials, discontinuation of therapy due to clinical adverse experiences was required in only 2.8% and 2.3% of patients treated with the combination and placebo, respectively.      In these double-blind controlled clinical trials, the following adverse experiences reported with losartan-hydrochlorothiazide occurred in ≥1 percent of patients, and more often on drug than placebo, regardless of drug relationship:

OVERDOSAGE

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displayName: OVERDOSAGE SECTION
FDA Article Code: 34088-5

Losartan Potassium          Significant lethality was observed in mice and rats after oral administration of 1000 mg/kg and 2000 mg/kg, respectively, about 44 and 170 times the maximum recommended human dose on a mg/m² basis.      Limited data are available in regard to overdosage in humans. The most likely manifestation of overdosage would be hypotension and tachycardia; bradycardia could occur from parasympathetic (vagal) stimulation. If symptomatic hypotension should occur, supportive treatment should be instituted.      Neither losartan nor its active metabolite can be removed by hemodialysis. Hydrochlorothiazide      The oral LD₅₀ of hydrochlorothiazide is greater than 10 g/kg in both mice and rats. The most common signs and symptoms observed are those caused by electrolyte depletion (hypokalemia, hypochloremia, hyponatremia) and dehydration resulting from excessive diuresis. If digitalis has also been administered, hypokalemia may accentuate cardiac arrhythmias. The degree to which hydrochlorothiazide is removed by hemodialysis has not been established.

DOSAGE AND ADMINISTRATION

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displayName: DOSAGE & ADMINISTRATION SECTION
FDA Article Code: 34068-7

Hypertension

     Dosing must be individualized. The usual starting dose of losartan is 50 mg once daily, with 25 mg recommended for patients with intravascular volume depletion (e.g., patients treated with diuretics) (see WARNINGS, Hypotension ─ Volume-Depleted Patients ) and patients with a history of hepatic impairment (see WARNINGS, Impaired Hepatic Function ). Losartan can be administered once or twice daily at total daily doses of 25 to 100 mg. If the antihypertensive effect measured at trough using once-a-day dosing is inadequate, a twice-a-day regimen at the same total daily dose or an increase in dose may give a more satisfactory response.         Hydrochlorothiazide is effective in doses of 12.5 to 50 mg once daily and can be given at doses of 12.5 to 25 mg as Losartan Potassium and Hydrochlorothiazide Tablets.     To minimize dose-independent side effects, it is usually appropriate to begin combination therapy only after a patient has failed to achieve the desired effect with monotherapy.     The side effects (see WARNINGS) of losartan are generally rare and apparently independent of dose; those of hydrochlorothiazide are a mixture of dose-dependent (primarily hypokalemia) and dose-independent phenomena (e.g., pancreatitis), the former much more common than the latter. Therapy with any combination of losartan and hydrochlorothiazide will be associated with both sets of dose-independent side effects.

HOW SUPPLIED

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displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5

Losartan Potassium and Hydrochlorothiazide Tablets, USP 100 mg/12.5 mg are white to off white colored, oval shaped, biconvex film coated tablets, debossed with “1117” on one side and plain on other side. Bottles of 30                                           NDC 21695-966-30   Storage     Store at 20° to 25°C (68° to 77°F) (See USP controlled room temperature). Protect from light. Keep container tightly closed.

Principal Display Panel

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displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4