Lopressor HCT®
metoprolol tartrate USP and hydrochlorothiazide USP
50/25 Tablets
100/25 Tablets
100/50 Tablets
Beta Blocker/Diuretic Antihypertensive
Rx only
Prescribing Information
Ischemic Heart Disease: Following abrupt cessation of therapy with certain beta-blocking agents, exacerbations of angina pectoris and, in some cases, myocardial infarction have been reported. Even in the absence of overt angina pectoris, when discontinuing therapy, Lopressor should not be withdrawn abruptly, and patients should be cautioned against interruption of therapy without the physician’s advice (see PRECAUTIONS, Information for Patients).
DESCRIPTION
Lopressor HCT has the antihypertensive effect of Lopressor®, metoprolol tartrate, a selective beta1-adrenoreceptor blocking agent, and the antihypertensive and diuretic actions of hydrochlorothiazide. It is available as tablets for oral administration. The 50/25 tablets contain 50mg of metoprolol tartrate USP and 25mg of hydrochlorothiazide USP; the 100/25 tablets contain 100mg of metoprolol tartrate USP and 25mg of hydrochlorothiazide USP; and the 100/50 tablets contain 100mg of metoprolol tartrate USP and 50mg of hydrochlorothiazide USP. Metoprolol tartrate USP is (±)-1-(Isopropylamino)-3-[p-(2-methoxyethyl)phenoxy]-2-propanol L-(+)-tartrate (2:1) salt, and its structural formula is
Metoprolol tartrate USP is a white, crystalline powder. It is very soluble in water; freely soluble in methylene chloride, in chloroform, and in alcohol; slightly soluble in acetone; and insoluble in ether. Its molecular weight is 684.82.
Hydrochlorothiazide is 6-chloro-3, 4-dihydro-2 H-1,2,4-benzothiadiazine-7- sulfonamide 1,1-dioxide, and its structural formula is
Hydrochlorothiazide USP is a white, or practically white, practically odorless, crystalline powder. It is freely soluble in sodium hydroxide solution, in n-butylamine, and in dimethylformamide; sparingly soluble in methanol; slightly soluble in water; and insoluble in ether, in chloroform, and in dilute mineral acids. Its molecular weight is 297.73.
Inactive Ingredients: Cellulose compounds, colloidal silicon dioxide, D&C Yellow No. 10 (100/50-mg tablets), FD&C Blue No. 1 (50/25-mg tablets), FD&C Red No. 40 and FD&C Yellow No. 6 (100/25-mg tablets), lactose, magnesium stearate, povidone, sodium starch glycolate, corn starch, stearic acid, and sucrose.
CLINICAL PHARMACOLOGY
Lopressor
Lopressor is a beta-adrenergic receptor blocking agent. In vitro and in vivo animal studies have shown that it has a preferential effect on beta1 adrenoreceptors, chiefly located in cardiac muscle. This preferential effect is not absolute, however, and at higher doses, Lopressor also inhibits beta2 adrenoreceptors, chiefly located in the bronchial and vascular musculature.
Clinical pharmacology studies have confirmed the beta-blocking activity of metoprolol in man, as shown by (1)reduction in heart rate and cardiac output at rest and upon exercise, (2)reduction of systolic blood pressure upon exercise, (3)inhibition of isoproterenol-induced tachycardia, and (4)reduction of reflex orthostatic tachycardia.
Relative beta1 selectivity has been confirmed by the following: (1)In normal subjects, Lopressor is unable to reverse the beta2-mediated vasodilating effects of epinephrine. This contrasts with the effect of nonselective (beta1 plus beta2) beta blockers, which completely reverse the vasodilating effects of epinephrine. (2)In asthmatic patients, Lopressor reduces FEV1 and FVC significantly less than a nonselective beta blocker, propranolol at equivalent beta1-receptor blocking doses.
Lopressor has no intrinsic sympathomimetic activity and only weak membrane-stabilizing activity. Lopressor crosses the blood-brain barrier and has been reported in the CSF in a concentration 78% of the simultaneous plasma concentration. Animal and human experiments indicate that Lopressor slows the sinus rate and decreases AV nodal conduction.
In controlled clinical studies, Lopressor has been shown to be an effective antihypertensive agent when used alone or as concomitant therapy with thiazide-type diuretics, at dosages of 100-450mg daily. In controlled, comparative, clinical studies, Lopressor has been shown to be as effective an antihypertensive agent as propranolol, methyldopa, and thiazide-type diuretics, and to be equally effective in supine and standing positions.
The mechanism of the antihypertensive effects of beta-blocking agents has not been elucidated. However, several possible mechanisms have been proposed: (1)competitive antagonism of catecholamines at peripheral (especially cardiac) adrenergic neuron sites, leading to decreased cardiac output; (2)a central effect leading to reduced sympathetic outflow to the periphery; and (3)suppression of renin activity.
Pharmacokinetics
In man, absorption of Lopressor is rapid and complete. Plasma levels following oral administration, however, approximate 50% of levels following intravenous administration, indicating about 50% first-pass metabolism.
Plasma levels achieved are highly variable after oral administration. Only a small fraction of the drug (about 12%) is bound to human serum albumin. Metoprolol is a racemic mixture of R- and S-enantiomers. Less than 5% of an oral dose of Lopressor is recovered unchanged in the urine; the rest is excreted by the kidneys as metabolites that appear to have no clinical significance. The systemic availability and half-life of Lopressor in patients with renal failure do not differ to a clinically significant degree from those in normal subjec |
