Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/842
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Verapamil Hydrochloride (Tablet, Film Coated, Extended Release)
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| dailymed-instance:dosage |
Essential Hypertension: The dose of verapamil extended-release tablets should be individualized by titration and the drug should be administered with food. Initiate therapy with 180 mg of verapamil hydrochloride extended-release tablets given in the morning. Lower initial doses of 120 mg a day may be warranted in patients who may have an increased response to verapamil (e.g., the elderly or small people). Upward titration should be based on therapeutic efficacy and safety evaluated weekly and approximately 24 hours after the previous dose. The antihypertensive effects of verapamil hydrochloride extended-release tablets are evident within the first week of therapy. If adequate response is not obtained with 180 mg of verapamil hydrochloride extended-release tablets, the dose may be titrated upward in the following manner: When switching from verapamil hydrochloride immediate-release tablets to verapamil hydrochloride extended-release tablets, the total daily dose in milligrams may remain the
same.
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| dailymed-instance:descripti... |
Verapamil hydrochloride is a calcium ion influx inhibitor (slow channel blocker or calcium ion antagonist). The tablets are designed for extended-release of the drug in the gastrointestinal tract; extended-release characteristics are not altered when the tablet is divided in half. The structural formula of verapamil hydrochloride is given below: CHNO���HClM.W. = 491.07 (��)-5-[(3,4-Dimethoxyphenethyl)methylamino]-2-(3,4-dimethoxyphenyl)-2-isopropylvaleronitrilemonohydrochloride Verapamil hydrochloride is an almost white, crystalline powder, practically free of odor, with a bitter taste. It is soluble in water, chloroform and methanol. Verapamil hydrochloride
is not chemically related to other cardioactive drugs. Each extended-release tablet, for oral administration, contains 120 mg, 180 mg or 240 mg of verapamil hydrochloride. In addition, each tablet contains the following inactive ingredients: hypromellose, magnesium stearate, microcrystalline cellulose, polydextrose, polyethylene
glycol, povidone, sodium alginate, sodium lauryl sulfate, titanium dioxide, triacetin, and FD&C Blue #1 aluminum lake. Verapamil Hydrochloride Extended-release Tablets, USP 120 mg meet USP Dissolution Test 1. Verapamil Hydrochloride Extended-release Tablets, USP 180 mg and 240 mg meet USP Dissolution Test 3.
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Verapamil hydrochloride is a calcium ion influx inhibitor (slow channel blocker or calcium ion antagonist) that exerts its pharmacologic effects by modulating the influx of ionic calcium across the cell membrane of the arterial smooth muscle as well as in conductile and contractile myocardial cells.<br/>Mechanism of Action:<br/>Essential Hypertension: Verapamil exerts antihypertensive effects by decreasing systemic vascular resistance, usually without orthostatic decreases in blood pressure or reflex tachycardia; bradycardia (rate less than 50 beats/min) is uncommon (1.4%). During isometric or dynamic exercise verapamil does not alter systolic cardiac function in patients with normal ventricular function. Verapamil does not alter total serum calcium levels. However, one report suggested that calcium levels above the normal range may alter the therapeutic effect of verapamil. Other pharmacologic actions of verapamil hydrochloride include the following: Verapamil dilates the main coronary arteries and coronary arterioles, both in normal and ischemic regions, and is a potent inhibitor of coronary artery spasm, whether spontaneous or ergonovine-induced. This property increases myocardial oxygen delivery in patients with coronary artery spasm, and is responsible for the effectiveness of verapamil in vasospastic (Prinzmetal's or variant) as well as unstable angina at rest. Whether this effect plays any role in classical effort angina is not clear, but studies of exercise tolerance have not shown an increase in the maximum exercise rate-pressure product, a widely accepted measure of oxygen utilization. This suggests that, in general, relief of spasm or dilation of coronary arteries is not an important factor in classical angina. Verapamil regularly reduces the total systemic resistance (afterload) against which the heart works both at rest and at a given level of exercise by dilating peripheral arterioles. Electrical activity through the AV node depends, to a significant degree, upon calcium influx through the slow channel. By decreasing the influx of calcium, verapamil prolongs
the effective refractory period within the AV node and slows AV conduction in a rate-related manner. Normal sinus rhythm is usually not affected, but in patients with sick sinus syndrome, verapamil may interfere with sinus-node impulse generation and may induce sinus arrest or sinoatrial block. Atrioventricular block can occur in patients without preexisting conduction defects . Verapamil does not alter the normal atrial action potential or intraventricular conduction time, but depresses amplitude, velocity of depolarization, and conduction in depressed atrial fibers. Verapamil may shorten the antegrade effective refractory period of the accessory
bypass tract. Acceleration of ventricular rate and/or ventricular fibrillation has been reported in patients with atrial flutter or atrial fibrillation and a coexisting accessory AV pathway following administration of verapamil . Verapamil has a local anesthetic action that is 1.6 times that of procaine on an equimolar basis. It is not known whether this action is important at the doses used in man.<br/>Pharmacokinetics and Metabolism: With the immediate-release formulation, more than 90% of the orally administered dose of verapamil hydrochloride is absorbed. Because of rapid biotransformation of verapamil during its first pass through the portal circulation, bioavailability ranges from 20% to 35%. Peak plasma concentrations are reached between 1 and 2 hours after oral administration. Chronic oral administration of 120 mg of verapamil hydrochloride every 6 hours resulted in plasma levels of verapamil ranging from 125 to 400 ng/mL, with higher values reported occasionally. A nonlinear correlation between the verapamil dose administered and verapamil plasma levels does exist. In early dose titration with verapamil a relationship exists between verapamil plasma concentration and prolongation of the PR interval. However, during chronic administration this relationship may disappear. The mean elimination
half-life in single-dose studies ranged from 2.8 to 7.4 hours. In these same studies, after repetitive dosing, the half-life increased to a range from 4.5 to 12 hours (after less than 10 consecutivedoses given 6 hours apart). Half-life of verapamil may increase during titration. No relationship has been established between the plasma concentration of verapamil and a reduction in blood pressure. Aging may affect the pharmacokinetics of verapamil. Elimination half-life may be prolonged in the elderly. In multiple dose studies under fasting conditions, the bioavailability measured by AUC of verapamil hydrochloride extended-release tablets was similar to verapamil hydrochloride immediate-release tablets; rates of absorption were, of course, different. In randomized, single-dose, crossover studies using healthy volunteers, administration of verapamil hydrochloride extended-release tablets with food produced lower peak concentrations, delayed time to peak, and lesser total absorption (AUC), than when the product was administered to fasting subjects. Similar results were demonstrated for plasma norverapamil. Food thus produces decreased bioavailability (AUC) but a narrower peak-to-trough ratio. Good correlation of dose and response is not available, but controlled studies of extended-release verapamil have shown effectiveness of doses similar to the effective doses of immediate-release verapamil. In healthy men, orally administered verapamil hydrochloride undergoes extensive metabolism in the liver. Twelve metabolites have been identified in plasma; all except norverapamil are present in trace amounts only. Norverapamil can reach steady-state plasma concentrations approximately equal to those of verapamil itself. The cardiovascular activity of norverapamil appears to be approximately 20% that of verapamil. Approximately 70% of an administered dose is excreted as metabolites in the urine and 16% or more in the feces within 5 days. About 3% to 4% is excreted in the urine as unchanged drug. Approximately 90% is bound to plasma proteins. In patients with hepatic insufficiency, metabolism of immediate-release verapamil is delayed and elimination half-life prolonged up to 14 to 16 hours ; the volume of distribution is increased and plasma clearance reduced to about 30% of normal. Verapamil clearance values suggest that patients with liver dysfunction may attain therapeutic verapamil plasma concentrations with one-third of the oral daily dose required for patients with normal liver function. After four weeks of oral dosing (120 mg q.i.d.), verapamil and norverapamil levels were noted in the cerebrospinal fluid with estimated partition coefficient of 0.06 for verapamil and 0.04 for norverapamil. In ten healthy males, administration of oral verapamil (80 mg every 8 hours for 6 days) and a single dose of ethanol (0.8 g/kg) resulted in a 17% increase in mean peak ethanol concentrations (106.45��21.40 to 124.23��24.74 mg���hr/dL) compared to placebo. The area under the blood ethanol concentration versus time curve (AUC over 12 hours) increased by 30% (365.67��93.52 to 475.07��97.24 mg���hr/dL). Verapamil AUCs were positively correlated (r = 0.71) to increased ethanol blood AUC values.<br/>Hemodynamics and Myocardial Metabolism: Verapamil reduces afterload and myocardial contractility. Improved left ventricular diastolic function in patients with IHSS and those with coronary heart disease has also been observed with verapamil. In most patients, including those with organic cardiac disease, the negative inotropic action of verapamil is countered by reduction of afterload, and cardiac index is usually not reduced. However, in patients with severe left ventricular dysfunction, (e.g., pulmonary wedge pressure above 20 mmHg or ejection fraction less than 30%), or in patients taking beta-adrenergic blocking agents or other cardiodepressant drugs, deterioration of ventricular function may occur .<br/>Pulmonary Function: Verapamil does not induce bronchoconstriction and hence, does not impair ventilatory function.
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Verapamil hydrochloride is contraindicated in:
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| dailymed-instance:supply |
Verapamil Hydrochloride Extended-release Tablets, USP 120 mg are supplied
as blue, oval, unscored, film-coated tablets containing 120 mg of verapamil hydrochloride. The tablet is debossed with MYLAN on one side and 244 on the reverse side. They are available as follows: NDC 0378-1120-01bottles of 100 tablets Verapamil Hydrochloride Extended-release Tablets, USP 180 mg are supplied as blue, oval, scored, film-coated tablets containing 180 mg of verapamil hydrochloride. The tablet is debossed with M312 on one side and is blank on the reverse side. They are available as follows: NDC 0378-1180-01bottles of 100 tablets NDC 0378-1180-05bottles of 500 tablets Verapamil Hydrochloride Extended-release Tablets, USP 240 mg are supplied as blue, modified capsule shaped, scored, film-coated tablets containing 240 mg of verapamil
hydrochloride. The tablet is debossed withM411 on the scored side and is blank on the reverse side. They are available as follows: NDC 0378-0411-01bottles of 100 tablets NDC 0378-0411-05bottles of 500 tablets STORE BETWEEN 15��AND 25��C (59��AND 77��F). PROTECT FROM LIGHT AND MOISTURE. Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.
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dailymed-ingredient:FD&C_Blue_#1_aluminum_lake,
dailymed-ingredient:hypromellose,
dailymed-ingredient:magnesium_stearate,
dailymed-ingredient:microcrystalline_cellulose,
dailymed-ingredient:polydextrose,
dailymed-ingredient:polyethylene_glycol,
dailymed-ingredient:povidone,
dailymed-ingredient:sodium_alginate,
dailymed-ingredient:sodium_lauryl_sulfate,
dailymed-ingredient:titanium_dioxide,
dailymed-ingredient:triacetin
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| dailymed-instance:genericMe... |
Verapamil Hydrochloride
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Verapamil Hydrochloride (Tablet, Film Coated, Extended Release)
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| dailymed-instance:adverseRe... |
Serious adverse reactions are uncommon when verapamil therapy is initiated with upward dose titration within the recommended single and total daily dose. See WARNINGS for discussion of heart failure, hypotension, elevated liver enzymes, AV block, and rapid ventricular response. Reversible (upon discontinuation of verapamil) non-obstructive, paralytic ileus has been infrequently reported in association with the use of verapamil. The following reactions to orally administered verapamil occurred at rates greater than 1% or occurred at lower rates but appeared clearly drug-related in clinical trials in 4,954 patients. In clinical trials related to the control of ventricular response in digitalized patients who had atrial fibrillation or flutter, ventricular rates below 50/min at rest occurred in 15% of patients and asymptomatic hypotension occurred in 5% of patients. The following reactions, reported in 1% or less of patients, occurred under conditions (open trials, marketing experience) where a causal relationship is uncertain; they are listed
to alert the physician to a possible relationship.<br/>Treatment of Acute Cardiovascular Adverse Reactions: The frequency of cardiovascular adverse reactions that require therapy is rare; hence, experience with their treatment is limited. Whenever severe hypotension or complete AV block occurs following oral administration of verapamil, the appropriate emergency measures should be applied immediately, e.g., intravenously administered norepinephrine bitartrate, atropine sulfate, isoproterenol HCl (all in the usual doses), or calcium gluconate (10% solution). In patients with hypertrophic cardiomyopathy (IHSS), alpha-adrenergic agents (phenylephrine HCl, metaraminol bitartrate, or methoxamine HCl) should be used to maintain blood pressure, and isoproterenol and norepinephrine should be avoided. If further support is necessary, dopamine HCl or dobutamine HCl may be administered. Actual treatment and dosage should depend on the severity of the clinical situation and the judgment and experience of the treating physician.
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| dailymed-instance:indicatio... |
Verapamil hydrochloride extended-release tablets are indicated for the management of essential hypertension.
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| dailymed-instance:name |
Verapamil Hydrochloride
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