Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/2337
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Atenolol and Chlorthalidone (Tablet)
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DOSAGE MUST BE INDIVIDUALIZED . Chlorthalidone is usually given at a dose of 25 mg daily; the usual initial dose of atenolol is 50 mg daily. Therefore, the initial dose should be one atenolol and chlorthalidone tablet 50 mg/25 mg given once a day. If an optimal response is not achieved, the dosage should be increased to one atenolol and chlorthalidone tablet 100 mg/25 mg given once a day. When necessary, another antihypertensive agent may be added gradually beginning with 50 percent of the usual recommended starting dose to avoid an excessive fall in blood pressure. Since atenolol is excreted via the kidneys, dosage should be adjusted in cases of severe impairment of renal function. No significant accumulation of atenolol occurs until creatinine clearance falls below 35 mL/min/1.73m(normal range is 100���150 mL/min/1.73m); therefore, the following maximum dosages are recommended for patients with renal impairment.
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| dailymed-instance:descripti... |
Atenolol and chlorthalidone tablets, USP are for the treatment of hypertension. They combine the antihypertensive activity of two agents: a beta-selective (cardioselective) hydrophilic blocking agent (atenolol) and a monosulfonamyl diuretic (chlorthalidone). Atenolol, USP is Benzeneacetamide, 4-[2'-hydroxy-3'-[(1-methylethyl)amino]propoxy]-. Its structural formula is: Atenolol (free base) is a relatively polar hydrophilic compound with a water solubility of 26.5 mg/mL at 37��C. It is freely soluble in 1N HCl (300 mg/mL at 25��C) and less soluble in chloroform (3 mg/mL at 25��C). Chlorthalidone, USP is 2-Chloro-5-(1-hydroxy-3-oxo-1-isoindolinyl) benzene sulfonamide. Its structural formula is: Chlorthalidone has a water solubility of 12 mg/100 mL at 20��C. Each tablet, for oral administration, contains: 50 mg of atenolol and 25 mg ofchlorthalidone or 100 mg of atenolol and 25 mg ofchlorthalidone. In addition, each tablet contains the following inactive ingredients: colloidal silicon dioxide, magnesium stearate, microcrystalline cellulose, pregelatinized starch, sodium lauryl sulfate, sodium starch glycolate and stearic acid.
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Atenolol and Chlorthalidone: Atenolol and chlorthalidone have been used singly and concomitantly for the treatment of hypertension. The antihypertensive effects of these agents are additive, and studies have shown that there is no interference with bioavailability when these agents are given together in the single combination tablet. Therefore, this combination providesa convenient formulation for the concomitant administration of these two entities. In patients with more severe hypertension, atenolol and chlorthalidone may be administered with other antihypertensives such as vasodilators.<br/>Atenolol: Atenolol is a beta-selective (cardioselective) beta-adrenergic receptor blocking agent without membrane stabilizing or intrinsic sympathomimetic (partial agonist) activities. This preferential effect is not absolute, however, and at higher doses, atenolol inhibits beta-adrenoreceptors, chiefly located in the bronchial and vascular musculature.<br/>Pharmacodynamics: In standard animal or human pharmacological tests, beta-adrenoreceptor blocking activity of atenolol has been demonstrated by: (1) reduction in resting and exercise heart rates and cardiac output, (2) reduction of systolic and diastolic blood pressure at rest and on exercise, (3) inhibition of isoproterenol induced tachycardia and (4) reduction in reflex orthostatic tachycardia. A significant beta-blocking effect of atenolol, as measured by reduction of exercise tachycardia, is apparent within one hour following oral administration of a single dose. This effect is maximal at about 2 to 4 hours and persists for at least 24 hours. The effect at 24 hours is dose related and also bears a linear relationship to the logarithm of plasma atenolol concentration. However, as has been shown for all beta-blocking agents, the antihypertensive effect does not appear to be related to plasma level. In normal subjects, the beta-selectivity of atenolol has been shown by its reduced ability to reverse the beta-mediated vasodilating effect of isoproterenol as compared to equivalent beta-blocking doses of propranolol. In asthmatic patients, a dose of atenolol producing a greater effect on resting heart rate than propranolol resulted in much less increase in airway resistance. In a placebo controlled comparison of approximately equipotent oral doses of several beta blockers, atenolol produced a significantly smaller decrease of FEVthan nonselective beta blockers, such as propranolol and unlike those agents did not inhibit bronchodilation in response to isoproterenol. Consistent with its negative chronotropic effect due to beta blockade of the SA node, atenolol increases sinus cycle length and sinus node recovery time. Conduction in the AV node is also prolonged. Atenolol is devoid of membrane stabilizing activity, and increasing the dose well beyond that producing beta blockade does not further depress myocardial contractility. Several studies have demonstrated a moderate (approximately 10%) increase in stroke volume at rest and exercise. In controlled clinical trials, atenolol given as a single daily dose, was an effective antihypertensive agent providing 24-hour reduction of blood pressure. Atenolol has been studied in combination with thiazide-type diuretics and the blood pressure effects of the combination are approximately additive. Atenolol is also compatible with methyldopa, hydralazine and prazosin, the combination resulting in a larger fall in blood pressure than with the single agents. The dose range of atenolol is narrow, and increasing the dose beyond 100 mg once daily is not associated with increased antihypertensive effect. The mechanisms of the antihypertensive effects of beta-blocking agents have not been established. Several mechanisms have been proposed and include: (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. The results from long-term studies have not shown any diminution of the antihypertensive efficacy of atenolol and prolonged use.<br/>Pharmacokinetics and Metabolism: In man, absorption of an oral dose is rapid and consistent but incomplete. Approximately 50% of an oral dose is absorbed from the gastrointestinal tract, the remainder being excreted unchanged in the feces. Peak blood levels are reached between 2 and 4 hours after ingestion. Unlike propranolol or metoprolol, but like nadolol, hydrophilic atenolol undergoes little or no metabolism by the liver, and the absorbed portion is eliminated primarily by renal excretion. Atenolol also differs from propranolol in that only a small amount (6���16%) is bound to proteins in the plasma. This kinetic profile results in relatively consistent plasma drug levels with about a fourfold interpatient variation. There is no information as to the pharmacokinetic effect of atenolol on chlorthalidone. The elimination half-life of atenolol is approximately 6 to 7 hours and there is no alteration of the kinetic profile of the drug by chronic administration. Following doses of 50 mg or 100 mg, both beta-blocking and antihypertensive effects persist for at least 24 hours. When renal function is impaired, elimination of atenolol is closely related to the glomerularfiltration rate; but significant accumulation does not occur until the creatinine clearance falls below 35 mL/min/1.73m(see prescribing information for atenolol).<br/>Atenolol Geriatric Pharmacology: In general, elderly patients present higher atenolol plasma levels with total clearance values about 50% lower than younger subjects. The half-life is markedly longer in the elderly compared to younger subjects. The reduction in atenolol clearance follows the general trend that elimination of renally excreted drugs is decreased with increasing age.<br/>Chlorthalidone: Chlorthalidone is a monosulfonamyl diuretic which differs chemically from thiazide diuretics in that a double ring system is incorporated in its structure. It is an oral diuretic with prolonged action and low toxicity. The diuretic effect of the drug occurs within 2 hours of an oral dose. It produces diuresis with greatly increased excretion of sodium and chloride. At maximal therapeutic dosage, chlorthalidone is approximately equal in its diuretic effect to comparable maximal therapeutic doses of benzothiadiazine diuretics. The site of action appears to be the cortical diluting segment of the ascending limb of Henle's loop of the nephron.
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Atenolol and chlorthalidone tablets are contraindicated in patients with: sinus bradycardia; heart block greater than first degree; cardiogenic shock; overt cardiac failure ; anuria; hypersensitivity to this product or to sulfonamide-derived drugs.
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| dailymed-instance:supply |
Atenolol and Chlorthalidone Tablets, USP are available containing: 50 mg of atenolol and 25 mg of chlorthalidone or 100 mg of atenolol and 25 mg of chlorthalidone The 50 mg/25 mg tablets are white, round, scored tablets debossed with M over 63 on the scored side. They are available as follows: NDC 0378-2063-01bottles of 100 tablets The 100 mg/25 mg tablets are white, round, unscored tablets debossed with M over 64. They are available as follows: NDC 0378-2064-01bottles of 100 tablets Store at 20��to 25��C (68��to 77��F). [See USP for Controlled Room Temperature.] Protect from light. Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.
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| dailymed-instance:genericMe... |
Atenolol and Chlorthalidone
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| dailymed-instance:fullName |
Atenolol and Chlorthalidone (Tablet)
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| dailymed-instance:adverseRe... |
Atenolol and chlorthalidone is usually well tolerated in properly selected patients. Most adverse effects have been mild and transient. The adverse effects observed for atenolol and chlorthalidone are essentially the same as those seen with the individual components.<br/>Atenolol: The frequency estimates in the following table were derived from controlled studies in which adverse reactions were either volunteered by the patient (US studies) or elicited, e.g., by checklist (foreign studies). The reported frequency of elicited adverse effects was higher for both atenolol and placebo-treated patients than when these reactions were volunteered. Where frequency of adverse effects for atenolol and placebo is similar, causal relationship to atenolol is uncertain. During postmarketing experience, the following have been reported in temporal relationship to the use of the drug: elevated liver enzymes and/or bilirubin, hallucinations, headache, impotence, Peyronie's disease, postural hypotension which may be associated with syncope, psoriasiform rash or exacerbation of psoriasis, psychoses, purpura, reversible alopecia, thrombocytopenia, visual disturbances, sick sinus syndrome and dry mouth. Atenolol and chlorthalidone, like other beta blockers, has been associated with the development of antinuclear antibodies (ANA), lupus syndrome and Raynaud's phenomenon.<br/>Chlorthalidone: Cardiovascular: orthostatic hypotension. Gastrointestinal: anorexia, gastric irritation, vomiting, cramping, constipation, jaundice (intra-hepatic cholestatic jaundice), pancreatitis. CNS: vertigo, paresthesias, xanthopsia. Hematologic: leukopenia, agranulocytosis, thrombocytopenia, aplastic anemia. Hypersensitivity: purpura, photosensitivity, rash, urticaria, necrotizing angiitis (vasculitis) (cutaneous vasculitis), Lyell's syndrome (toxic epidermal necrolysis). Miscellaneous: hyperglycemia, glycosuria, hyperuricemia, muscle spasm, weakness, restlessness. Clinical trials of atenolol and chlorthalidone conducted in the United States (89 patients treated with atenolol and chlorthalidone) revealed no new or unexpected adverse effects.<br/>Potential Adverse Effects: In addition, a variety of adverse effects not observed in clinical trials with atenolol but reported with other beta-adrenergic blocking agents should be considered potential adverse effects of atenolol. Nervous System: Reversible mental depression progressing to catatonia; an acute reversible syndrome characterized by disorientation for time and place, short-term memory loss, emotional lability, slightly clouded sensorium, and decreased performance on neuropsychometrics. Cardiovascular: Intensification of AV block . Gastrointestinal: Mesenteric arterial thrombosis, ischemic colitis. Hematologic: Agranulocytosis. Allergic: Erythematous rash, fever combined with aching and sore throat, laryngospasm and respiratory distress. Miscellaneous: There have been reports of skin rashes and/or dry eyes associated with the use of beta-adrenergic blocking drugs. The reported incidence is small, and, in most cases, the symptoms have cleared when treatment was withdrawn. Discontinuance of the drug should be considered if any such reaction is not otherwise explicable. Patients should be closely monitored following cessation of therapy. The oculomucocutaneous syndrome associated with the beta blocker practolol has not been reported with atenolol. Furthermore, a number of patients who had previously demonstrated established practolol reactions were transferred to atenolol therapy with subsequent resolution or quiescence of the reaction.<br/>Clinical Laboratory Test Findings: Clinically important changes in standard laboratory parameters were rarely associated with the administration of atenolol and chlorthalidone. The changes in laboratory parameters were not progressive and usually were not associated with clinical manifestations. The most common changes were increases in uric acid and decreases in serum potassium.
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| dailymed-instance:indicatio... |
Atenolol and chlorthalidone tablets are indicated in the treatment of hypertension. This fixed dose combination drug is not indicated for initial therapy of hypertension. If the fixed dose combination represents the dose appropriate to the individual patient's needs, it may be more convenient than the separate components.
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Atenolol and Chlorthalidone
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