Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/74
| Predicate | Object |
|---|---|
| rdf:type | |
| rdfs:label |
Verapamil Hydrochloride (Capsule, Extended Release)
|
| dailymed-instance:dosage |
Essential Hypertension: The dose of verapamil hydrochloride extended-release should be individualized by titration. The usual daily dose of extended-release verapamil hydrochloride in clinical trials has been 240 mg given by mouth once daily in the morning. However, initial doses of 120 mg a day may be warranted in patients who may have an increased response to verapamil (e.g., elderly, small people, etc.). Upward titration should be based on therapeutic efficacy and safety evaluated approximately 24 hours after dosing. The antihypertensive effects of verapamil hydrochloride extended-release are evident within the first week of therapy. If adequate response is not obtained with 120 mg of verapamil hydrochloride extended-release, the dose may be titrated upward in the following manner: Verapamil extended-release capsules are for once-a-day administration. When switching from immediate-release verapamil to verapamil hydrochloride extended-release capsules, the same total daily dose of verapamil hydrochloride extended-release capsules can be used. As with immediate-release verapamil, dosages of verapamil hydrochloride extended-release capsules should be individualized and titration may be needed in some patients.<br/>Sprinkling the Capsule Contents on Food: Verapamil Hydrochloride Extended-release Bead Filled Capsules may also be administered by carefully opening the capsule and sprinkling the beads on a spoonful of applesauce. The applesauce should be swallowed immediately without chewing and followed with a glass of cool water to ensure complete swallowing of the beads. The applesauce used should not be hot, and it should be soft enough to be swallowed without chewing. Any bead/applesauce mixture should be used immediately and not stored for future use. Subdividing the contents of a verapamil hydrochloride extended-release capsule is not recommended.
|
| dailymed-instance:descripti... |
Verapamil hydrochloride extended-release is a calcium ion influx inhibitor (slow channel blocker or calcium ion antagonist). Verapamil hydrochloride extended-release is available for oral administration as a 120 mg hard gelatin capsule, a 180 mg hard gelatin capsule and a 240 mg hard gelatin capsule. These bead filled capsules provide an extended-release of the drug in the gastrointestinal tract. The structural formula of verapamil hydrochloride is given below: CHNO���HCl M.W. 491.07 Chemical name: (��)-5-[(3,4-Dimethoxyphenethyl) methylamino]-2-(3,4-dimethoxyphenyl)-2-isopropylvaleronitrile monohydrochloride. 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 structurally related to other cardioactive drugs. In addition to verapamil hydrochloride, verapamil hydrochloride extended-release capsules contain the following inactive ingredients: ammonium hydroxide, colloidal silicon dioxide, D&C yellow no. 10 aluminum lake, dibutyl sebacate, diethyl phthalate, ethylcellulose, FD&C blue no. 2 aluminum lake, FD&C blue no. 1 aluminum lake, FD&C green #3, FD&C red no. 40 aluminum lake, gelatin, hypromellose, isopropyl alcohol, maltodextrin, methacrylic acid copolymer, n-butyl alcohol, oleic acid, pharmaceutical glaze, polyethylene glycol, povidone, propylene glycol, SDA-3A alcohol, silicon dioxide, sodium lauryl sulfate, sugar spheres, synthetic black iron oxide, talc, and titanium dioxide.In addition the 180 mg capsule contains D&C yellow #10.
|
| dailymed-instance:clinicalP... |
Verapamil hydrochloride extended-release is a calcium ion influx inhibitor (slow channel blocker or calcium ion antagonist) which 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. Normal sinus rhythm is usually not affected by verapamil hydrochloride. However in patients with sick sinus syndrome, verapamil hydrochloride 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 hydrochloride 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 hydrochloride may shorten the antegrade effective refractory period of accessory bypass tracts. 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 hydrochloride 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/>Mechanism of Action:<br/>Essential Hypertension: Verapamil hydrochloride exerts antihypertensive effects by decreasing systemic vascular resistance, usually without orthostatic decreases in blood pressure or reflex tachycardia; bradycardia (rate less than 50 beats/minute is uncommon). Verapamil hydrochloride regularly reduces arterial pressure at rest and at a given level of exercise by dilating peripheral arterioles and reducing the total peripheral resistance (afterload) against which the heart works.<br/>Pharmacokinetics and Metabolism: With the immediate-release formulations, more than 90% of the orally administered dose is absorbed, and peak plasma concentrations of verapamil are observed 1 to 2 hours after dosing. Because of rapid biotransformation of verapamil during its first pass through the portal circulation, the absolute bioavailability ranges from 20% to 35%. Chronic oral administration of the highest recommended dose (120 mg every 6 hours) resulted in plasma verapamil levels ranging from 125 to 400 ng/mL with higher values reported occasionally. A nonlinear correlation between the verapamil hydrochloride dose administered and verapamil plasma levels does exist. During initial dose titration with verapamil a relationship exists between verapamil plasma concentrations and the prolongation of the PR interval. However, during chronic administration this relationship may disappear. The quantitative relationship between plasma verapamil concentrations and blood pressure reduction has not been fully characterized. In a multiple dose pharmacokinetic study, peak concentrations for a single daily dose of verapamil hydrochloride extended-release 240 mg were approximately 65% of those obtained with an 80 mg t.i.d. dose of the conventional immediate-release tablets, and the 24-hour post-dose concentrations were approximately 30% higher. At a total daily dose of 240 mg, verapamil hydrochloride extended-release was shown to have a similar extent of verapamil bioavailability based on the AUC-24 as that obtained with the conventional immediate-release tablets. Inthis same study verapamil hydrochloride extended-release doses of 120 mg, 240 mg and 360 mg once daily were compared after multiple doses. The ratios of the verapamil and norverapamil AUCs for verapamil hydrochloride extended-release 120 mg, 240 mg and 360 mg once daily doses are 1 (565 ng���hr/mL):3 (1660 ng���hr/mL):5 (2729 ng���hr/mL) and 1 (621 ng���hr/mL):3 (1614 ng���hr/mL):4 (2535 ng���hr/mL), respectively, indicating that the AUC increased non-proportionately with increasing doses. Food does not affect the extent or rate of the absorption of verapamil from the verapamil hydrochloride extended-release capsule. The verapamil hydrochloride extended-release 240 mg capsule when administered with food had a Cof 77 ng/mL which occurred 9.0 hours after dosing, and an AUC(0���inf) of 1387 ng���hr/mL. Verapamil hydrochloride extended-release 240 mg under fasting conditions had a Cof 77 ng/mL which occurred 9.8 hours after dosing, and an AUC(0���inf) of 1541 ng���hr/mL. The bioequivalence of verapamil hydrochloride extended-release 240 mg, administered as the beads sprinkled on applesauce and as the intact capsule, was demonstrated in a single-dose, cross-over study in 32 healthy adults. Comparative ratios (sprinkled/intact) of verapamil were 0.95, 1.02, and 1.01 for C, T, and AUC(0���inf) respectively. Similar results were observed with norverapamil. The time to reach maximum verapamil concentrations (T) with verapamil hydrochloride extended-release has been found to be approximately 7 to 9 hours in each of the single dose (fasting), single dose (fed), the multiple dose (steady-state) studies, and dose proportionality pharmacokinetic studies. Similarly the apparent half-life (t) has been found to be approximately 12 hours independent of dose. Aging may affect the pharmacokinetics of verapamil. Elimination half-life may be prolonged in the elderly. In healthy man, 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 biologic activity of norverapamil appears to be approximately 20% that of verapamil. Approximately 70% of an administered dose of verapamil hydrochloride 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 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 10 healthy males, administration of oral verapamil (80 mg every 8 hours for 6 days) and a single oral 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/dL) compared with 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 hydrochloride 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 hydrochloride therapy. In most patients, including those with organic cardiac disease, the negative inotropic action of verapamil hydrochloride is countered by reduction of afterload and cardiac index is usually not reduced. In patients with severe left ventricular dysfunction however, (e.g., pulmonary wedge pressure above 20 mm Hg or ejection fraction lower than 30%), or in patients on beta-adrenergic blocking agents or other cardiodepressant drugs, deterioration of ventricular function may occur.<br/>Pulmonary Function: Verapamil hydrochloride does not induce bronchoconstriction and hence, does not impair ventilatory function.
|
| dailymed-instance:activeIng... | |
| dailymed-instance:contraind... |
Verapamil hydrochloride is contraindicated in:
|
| dailymed-instance:supply |
Verapamil Hydrochloride Extended-release Capsules, are available in 120 mg, 180 mg and 240 mg capsules. The 120 mg capsules have a bluish green opaque cap and white opaque body that are radially printed with MYLAN over 6320 in black ink. They are available as follows: NDC 0378-6320-01bottles of 100 capsulesNDC 0378-6320-05bottles of 500 capsules The 180 mg capsules have a bluish green opaque cap and light green opaque body that are radially printed with MYLAN over 6380 in black ink. They are available as follows: NDC 0378-6380-01bottles of 100 capsulesNDC 0378-6380-05bottles of 500 capsules The 240 mg capsule is an elongated capsule with a bluish green opaque cap and bluish green opaque body that are radially printed with MYLAN over 6440 in black ink. They are available as follows: NDC 0378-6440-01bottles of 100 capsulesNDC 0378-6440-05bottles of 500 capsules STORE AT ROOM TEMPERATURE 15��to 25��C (59��to 77��F). Brief digressions above 25��C while not detrimental, should be avoided. AVOID EXCESSIVE HEAT.PROTECT FROM MOISTURE. Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.
|
| dailymed-instance:activeMoi... | |
| dailymed-instance:inactiveI... |
dailymed-ingredient:D&C_yellow_no._10_aluminum_lake,
dailymed-ingredient:FD&C_blue_no._1_aluminum_lake,
dailymed-ingredient:FD&C_blue_no._2_aluminum_lake,
dailymed-ingredient:FD&C_green_#3,
dailymed-ingredient:FD&C_red_no._40_aluminum_lake,
dailymed-ingredient:SDA-3A_alcohol,
dailymed-ingredient:ammonium_hydroxide,
dailymed-ingredient:colloidal_silicon_dioxide,
dailymed-ingredient:dibutyl_sebacate,
dailymed-ingredient:diethyl_phthalate,
dailymed-ingredient:ethylcellulose,
dailymed-ingredient:gelatin,
dailymed-ingredient:hypromellose,
dailymed-ingredient:isopropyl_alcohol,
dailymed-ingredient:maltodextrin,
dailymed-ingredient:methacrylic_acid_copolymer,
dailymed-ingredient:n-butyl_alcohol,
dailymed-ingredient:oleic_acid,
dailymed-ingredient:pharmaceutical_glaze,
dailymed-ingredient:polyethylene_glycol,
dailymed-ingredient:povidone,
dailymed-ingredient:propylene_glycol,
dailymed-ingredient:silicon_dioxide,
dailymed-ingredient:sodium_lauryl_sulfate,
dailymed-ingredient:sugar_spheres,
dailymed-ingredient:synthetic_black_iron_oxide,
dailymed-ingredient:talc,
dailymed-ingredient:titanium_dioxide
|
| dailymed-instance:genericMe... |
Verapamil Hydrochloride
|
| dailymed-instance:fullName |
Verapamil Hydrochloride (Capsule, Extended Release)
|
| dailymed-instance:adverseRe... |
Serious adverse reactions are uncommon when verapamil hydrochloride 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. In clinical trials involving 285 hypertensive patients on verapamil hydrochloride extended-release for greater than 1 week the following adverse reactions were reported in greater than 1% of the patients: In clinical trials of other formulations of verapamil hydrochloride (N=4,954) the following reactions have occurred at rates greater than 1%: In clinical trials related to the control of ventricular response in digitalized patients who had atrial fibrillation or atrial flutter, ventricular rate 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: Cardiovascular: angina pectoris, atrioventricular dissociation, chest pain, claudication, myocardial infarction, palpitations, purpura (vasculitis), syncope. Digestive System: diarrhea, dry mouth, gastrointestinal distress, gingival hyperplasia. Hemic and Lymphatic: ecchymosis or bruising. Nervous System: cerebrovascular accident, confusion, equilibrium disorders, insomnia, muscle cramps, paresthesia, psychotic symptoms, shakiness, somnolence. Respiratory: dyspnea. Skin: arthralgia and rash, exanthema, hair loss, hyperkeratosis, maculae, sweating, urticaria, Stevens-Johnson syndrome, erythema multiforme. Special Senses: blurred vision, tinnitus. Urogenital: gynecomastia, impotence, increased urination, spotty menstruation.<br/>Treatment of Acute Cardiovascular Adverse Reactions: The frequency of cardiovascular adverse reactions which 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 isoproterenol hydrochloride, norepinephrine, atropine (all in the usual doses), or calcium gluconate (10% solution). In patients with hypertrophic cardiomyopathy (IHSS), alpha-adrenergic agents (phenylephrine, metaraminol bitartrate or methoxamine) should be used to maintain blood pressure,and isoproterenol and levarterenol should be avoided. If further support is necessary, inotropic agents (dopamine or dobutamine) may be administered. Actual treatment and dosage should depend on the severity and the clinical situation and the judgment and experience of the treating physician.
|
| dailymed-instance:indicatio... |
Verapamil hydrochloride extended-release capsules are indicated for the management of essential hypertension.
|
| dailymed-instance:represent... | |
| dailymed-instance:routeOfAd... | |
| dailymed-instance:name |
Verapamil Hydrochloride
|