ATENOLOL- atenolol tablet 
REMEDYREPACK INC.

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CESSATION OF THERAPY WITH ATENOLOL

Patients with coronary artery disease, who are being treated with atenolol, should be advised against abrupt discontinuation of therapy. Severe exacerbation of angina and the occurrence of myocardial infarction and ventricular arrhythmias have been reported in angina patients following the abrupt discontinuation of therapy with beta blockers. The last two complications may occur with or without preceding exacerbation of the angina pectoris. As with other beta blockers, when discontinuation of atenolol is planned, the patients should be carefully observed and advised to limit physical activity to a minimum. If the angina worsens or acute coronary insufficiency develops, it is recommended that atenolol be promptly reinstituted, at least temporarily. Because coronary artery disease is common and may be unrecognized, it may be prudent not to discontinue atenolol therapy abruptly even in patients treated only for hypertension. (See

DOSAGE AND ADMINISTRATION).

DESCRIPTION

CLINICAL PHARMACOLOGY

INDICATIONS & USAGE

Hypertension

Atenolol tablets are indicated in the management of hypertension. They may be used alone or concomitantly with other antihypertensive agents, particularly with a thiazide-type diuretic.

Angina Pectoris Due to Coronary Atherosclerosis Atenolol tablets are indicated for the long-term management of patients with angina pectoris.

Acute Myocardial Infarction

Atenolol tablets are indicated in the management of hemodynamically stable patients with definite or suspected acute myocardial infarction to reduce cardiovascular mortality. Treatment can be initiated as soon as the patientclinical condition allows. (See

DOSAGE AND ADMINISTRATION, CONTRAINDICATIONS, and WARNINGS). In general, there is no basis for treating patients like those who were excluded from the ISIS-1 trial (blood pressure less than 100 mm Hg systolic, heart rate less than 50 bpm) or have other reasons to avoid beta blockade. As noted above, some subgroups (e.g., elderly patients with systolic blood pressure below 120 mm Hg) seemed less likely to benefit.

CONTRAINDICATIONS

Atenolol tablets are contraindicated in sinus bradycardia, heart block greater than first degree, cardiogenic shock, and overt cardiac failure. (See

WARNINGS).

Atenolol tablets are contraindicated in those patients with a history of hypersensitivity to the atenolol or any of the drug product's components.

WARNINGS

Cardiac Failure

Sympathetic stimulation is necessary in supporting circulatory function in congestive heart failure, and beta blockade carries the potential hazard of further depressing myocardial contractility and precipitating more severe failure.

In patients with acute myocardial infarction, cardiac failure which is not promptly and effectively controlled by 80 mg of intravenous furosemide or equivalent therapy is a contraindication to beta blocker treatment.

In Patients Without a History of Cardiac Failure Continued depression of the myocardium with beta-blocking agents over a period of time can, in some cases, lead to cardiac failure. At the first sign or symptom of impending cardiac failure, patients should be treated appropriately according to currently recommended guidelines, and the response observed closely. If cardiac failure continues despite adequate treatment, atenolol should be withdrawn. (See

DOSAGE AND ADMINISTRATION).

CESSATION OF THERAPY WITH ATENOLOL

Patients with coronary artery disease, who are being treated with atenolol, should be advised against abrupt discontinuation of therapy. Severe exacerbation of angina and the occurrence of myocardial infarction and ventricular arrhythmias have been reported in angina patients following the abrupt discontinuation of therapy with beta blockers. The last two complications may occur with or without preceding exacerbation of the angina pectoris. As with other beta blockers, when discontinuation of atenolol is planned, the patients should be carefully observed and advised to limit physical activity to a minimum. If the angina worsens or acute coronary insufficiency develops, it is recommended that atenolol be promptly reinstituted, at least temporarily. Because coronary artery disease is common and may be unrecognized, it may be prudent not to discontinue atenolol therapy abruptly even in patients treated only for hypertension. (See

DOSAGE AND ADMINISTRATION).

Concomitant Use of Calcium Channel Blockers

Bradycardia and heart block can occur and the left ventricular end diastolic pressure can rise when beta-blockers are administered with verapamil or diltiazem. Patients with pre-existing conduction abnormalities or left ventricular dysfunction are particularly susceptible. (See

PRECAUTIONS).

Bronchospastic Diseases

PATIENTS WITH BRONCHOSPASTIC DISEASE SHOULD, IN GENERAL, NOT RECEIVE BETA BLOCKERS. Because of its relative beta1 selectivity, however, atenolol may be used with caution in patients with bronchospastic disease who do not respond to, or cannot tolerate, other antihypertensive treatment. Since beta1 selectivity is not absolute, the lowest possible dose of atenolol should be used with therapy initiated at 50 mg and a beta2-stimulating agent (bronchodilator) should be made available. If dosage must be increased, dividing the dose should be considered in order to achieve lower peak blood levels.

Major Surgery

Chronically administered beta-blocking therapy should not be routinely withdrawn prior to major surgery; however, the impaired ability of the heart to respond to reflex adrenergic stimuli may augment the risks of general anesthesia and surgical procedures

Diabetes and Hypoglycemia

Atenolol should be used with caution in diabetic patients if a beta-blocking agent is required. Beta blockers may mask tachycardia occurring with hypoglycemia, but other manifestations such as dizziness and sweating may not be significantly affected. At recommended doses, atenolol does not potentiate insulin-induced hypoglycemia and, unlike non-selective beta-blockers, does not delay recovery of blood glucose to normal levels.

Thyrotoxicosis

Beta-adrenergic blockade may mask certain clinical signs (e.g., tachycardia) of hyperthyroidism. Abrupt withdrawal of beta blockade might precipitate a thyroid storm; therefore, patients suspected of developing thyrotoxicosis from whom atenolol therapy is to be withdrawn should be monitored closely. (See

DOSAGE AND ADMINISTRATION).

Untreated Pheochromocytoma

Atenolol tablets should not be given to patients with untreated pheochromocytoma.

Pregnancy and Fetal Injury

Atenolol can cause fetal harm when administered to a pregnant woman. Atenolol crosses the placental barrier and appears in cord blood. Administration of atenolol, starting in the second trimester of pregnancy, has been associated with the birth of infants that are small for gestational age. No studies have been performed on the use of atenolol in the first trimester and the possibility of fetal injury cannot be excluded. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.

Neonates born to mothers who are receiving atenolol at parturition or breast-feeding may be at risk for hypoglycemia and bradycardia. Caution should be exercised when atenolol is administered during pregnancy or to a woman who is breast-feeding. (See

PRECAUTIONS,Nursing Mothers.)

Atenolol has been shown to produce a dose-related increase in embryo/fetal resorptions in rats at doses equal to or greater than 50 mg/kg/day or 25 or more times the maximum recommended human antihypertensive dose.

1Although similar effects were not seen in rabbits, the compound was not evaluated in rabbits at doses above 25 mg/kg/day or 12.5 times the maximum recommended human antihypertensive dose.

Based on the maximum dose of 100 mg/day in a 50 kg patient. on the maximum dose of 100 mg/day in a 50 kg patient.

PRECAUTIONS

ADVERSE REACTIONS

Most adverse effects have been mild and transient.

The frequency estimates in the following table were derived from controlled studies in hypertensive patients in which adverse reactions were either volunteered by the patient (U.S. 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 of atenolol and placebo is similar, causal relationship to atenolol is uncertain.

Volunteered

(U.S. Studies)

Total-Volunteered

and Elicited

(Foreign + U.S. Studies)

Atenolol

(n = 164)

Placebo

(n = 206)

Atenolol

(n = 399)

Placebo

(n = 407)

CARDIOVASCULARBradycardia3030Cold Extremities00.5125Postural Hypotension2145Leg Pain00.531CENTRAL NERVOUS SYSTEM/NEUROMUSCULARDizziness41136Vertigo20.520.2Light Headedness1030.7Tiredness0.60.52613Fatigue3165Lethargy1030.7Drowsiness0.6020.5Depression0.60.5129Dreaming0031GASTROINTESTINALDiarrhea2032Nausea4131RESPIRATORY (see

WARNINGS)

Wheeziness0033Dyspnea0.6164

In a series of investigations in the treatment of acute myocardial infarction, bradycardia and hypotension occurred more commonly, as expected for any beta blocker, in atenolol-treated patients than in control patients. However, these usually responded to atropine and/or to withholding further dosage of atenolol. The incidence of heart failure was not increased by atenolol. Inotropic agents were infrequently used. The reported frequency of these and other events occurring during these investigations is given in the following table.

In a study of 477 patients, the following adverse events were reported during either intravenous and/or oral atenolol administration:

Conventional

Therapy Plus

Atenolol

(n = 244)

Conventional

Therapy

Alone

(n = 233)

Bradycardia43(18%)24(10%)Hypotension60(25%)34(15%)Bronchospasm3(1.2%)2(0.9%)Heart Failure46(19%)56(24%)Heart Block11(4.5%)10(4.3%)BBB + Major Axis Deviation16(6.6%)28(12%)Supraventricular Tachycardia28(11.5%)45(19%)Atrial Fibrillation12(5%)29(11%)Atrial Flutter4(1.6%)7(3%)Ventricular Tachycardia39(16%)52(22%)Cardiac Reinfarction0(0%)6(2.6%)Total Cardiac Arrests4(1.6%)16(6.9%)Nonfatal Cardiac Arrests4(1.6%)12(5.1%)Deaths7(2.9%)16(6.9%)Cardiogenic Shock1(0.4%)4(1.7%)Development of Ventricular Septal Defect0(0%)2(0.9%)Development of Mitral Regurgitation0(0%)2(0.9%)Renal Failure1(0.4%)0(0%)Pulmonary Emboli3(1.2%)0(0%)

In the subsequent International Study of Infarct Survival (ISIS-1) including over 16,000 patients of whom 8,037 were randomized to receive atenolol treatment, the dosage of intravenous and subsequent oral atenolol was either discontinued or reduced for the following reasons:

Full dosage was 10 mg and some patients received less than 10 mg but more than 5 mg.

Reasons for Reduced Dosage

IV Atenolol

Reduced Dose

Partial Dose

Hypotension/Bradycardia105(1.3%)1168(14.5%)Cardiogenic Shock4(0.04%)35(0.44%)Reinfarction0(0%)5(0.06%)Cardiac Arrest5(0.06%)28(0.34%)Heart Block (> first degree)5(0.06%)143(1.7%)Cardiac Failure1(0.01%)233(2.9%)Arrhythmias3(0.04%)22(0.27%)Bronchospasm1(0.01%)50(0.62%)

During postmarketing experience with atenolol, 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 disturbance, sick sinus syndrome, and dry mouth. Atenolol, like other beta blockers, has been associated with the development of antinuclear antibodies (ANA), lupus syndrome and Raynaud's phenomenon.

POTENTIAL ADVERSE EFFECTS

In addition, a variety of adverse effects have been reported with other beta-adrenergic blocking agents, and may be considered potential adverse effects of atenolol.

Hematologic

Agranulocytosis.

Allergic

Fever, combined with aching and sore throat, laryngospasm, and respiratory distress

Central Nervous System

Reversible mental depression progressing to catatonia; an acute reversible syndrome characterized by disorientation of time and place; short-term memory loss; emotional lability with slightly clouded sensorium; and, decreased performance on neuropsychometrics.

Gastrointestinal

Mesenteric arterial thrombosis, ischemic colitis.

Other

Erythematous rash.

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 (see

DOSAGE AND ADMINISTRATION).

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.

OVERDOSAGE

DOSAGE & ADMINISTRATION

Hypertension

The initial dose of atenolol is 50 mg given as one tablet a day either alone or added to diuretic therapy. The full effect of this dose will usually be seen within one to two weeks. If an optimal response is not achieved, the dosage should be increased to atenolol 100 mg given as one tablet a day. Increasing the dosage beyond 100 mg a day is unlikely to produce any further benefit.

Atenolol may be used alone or concomitantly with other antihypertensive agents including thiazide-type diuretics, hydralazine, prazosin, and alpha-methyldopa.

Angina Pectoris

The initial dose of atenolol is 50 mg given as one tablet a day. If an optimal response is not achieved within one week, the dosage should be increased to atenolol 100 mg given as one tablet a day. Some patients may require a dosage of 200 mg once a day for optimal effect.

Twenty-four hour control with once daily dosing is achieved by giving doses larger than necessary to achieve an immediate maximum effect. The maximum early effect on exercise tolerance occurs with doses of 50 to 100 mg, but at these doses the effect at 24 hours is attenuated, averaging about 50% to 75% of that observed with once a day oral doses of 200 mg.

Acute Myocardial Infarction

In patients with definite or suspected acute myocardial infarction, treatment with atenolol I.V. injection should be initiated as soon as possible after the patientarrival in the hospital and after eligibility is established. Such treatment should be initiated in a coronary care or similar unit immediately after the patienthemodynamic condition has stabilized. Treatment should begin with the intravenous administration of 5 mg atenolol over 5 minutes followed by another 5 mg intravenous injection 10 minutes later. Atenolol I.V. injection should be administered under carefully controlled conditions including monitoring of blood pressure, heart rate, and electrocardiogram. Dilutions of atenolol I.V. injection in Dextrose Injection USP, Sodium Chloride Injection USP, or Sodium Chloride and Dextrose Injection may be used. These admixtures are stable for 48 hours if they are not used immediately.

In patients who tolerate the full intravenous dose (10 mg), atenolol tablets 50 mg should be initiated 10 minutes after the last intravenous dose followed by another 50 mg oral dose 12 hours later. Thereafter, atenolol can be given orally either 100 mg once daily or 50 mg twice a day for a further 6 to 9 days or until discharge from the hospital. If bradycardia or hypotension requiring treatment or any other untoward effects occur, atenolol should be discontinued. (See full prescribing information prior to initiating therapy with atenolol tablets).

Data from other beta blocker trials suggest that if there is any question concerning the use of IV beta blocker or clinical estimate that there is a contraindication, the IV beta blocker may be eliminated and patients fulfilling the safety criteria may be given atenolol tablets 50 mg twice daily or 100 mg once a day for at least seven days (if the IV dosing is excluded).

Although the demonstration of efficacy of atenolol is based entirely on data from the first seven postinfarction days, data from other beta blocker trials suggest that treatment with beta blockers that are effective in the post-infarction setting may be continued for one to three years if there are no contraindications.

Atenolol is an additional treatment to standard coronary care unit therapy.

Elderly Patients or Patients with Renal Impairment

Atenolol is excreted by the kidneys; consequently dosage should be adjusted in cases of severe impairment of renal function. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Evaluation of patients with hypertension or myocardial infarction should always include assessment of renal function. Atenolol excretion would be expected to decrease with advancing age.

No significant accumulation of atenolol occurs until creatinine clearance falls below 35 mL/min/1.73m2. Accumulation of atenolol and prolongation of its half-life were studied in subjects with creatinine clearance between 5 and 105 mL/min. Peak plasma levels were significantly increased in subjects with creatinine clearances below 30 mL/min.

The following maximum oral dosages are recommended for elderly, renally-impaired patients and for patients with renal impairment due to other causes:

Creatinine Clearance

(mL/min/1.73m2)

Atenolol

Elimination

Half-Life (h)

Maximum Dosage

15-3516-2750 mg daily< 15> 2725 mg daily

Some renally-impaired or elderly patients being treated for hypertension may require a lower starting dose of atenolol: 25 mg given as one tablet a day. If this 25 mg dose is used, assessment of efficacy must be made carefully. This should include measurement of blood pressure just prior to the next dose (blood pressure) to ensure that the treatment effect is present for a full 24 hours.

Although a similar dosage reduction may be considered for elderly and/or renally-impaired patients being treated for indications other than hypertension, data are not available for these patient populations.

Patients on hemodialysis should be given 25 mg or 50 mg after each dialysis; this should be done under hospital supervision as marked falls in blood pressure can occur.

Cessation of Therapy in Patients with Angina Pectoris

If withdrawal of atenolol therapy is planned, it should be achieved gradually and patients should be carefully observed and advised to limit physical activity to a minimum.

HOW SUPPLIED

Atenolol tablets, USP for oral administration, are supplied as:

25 mg:round, white, unscored tablets debossed GG L7 on one side and plain on the reverse side, and supplied as:

NDC 0781-1078-01 bottles of 100

NDC 0781-1078-05 bottles of 500

NDC 0781-1078-10 bottles of 1000

50 mg:round, white, scored tablets debossed GG 263 on one side and plain on the reverse side, and supplied as:

NDC 0781-1506-01 bottles of 100

NDC 0781-1506-05 bottles of 500

NDC 0781-1506-10 bottles of 1000

NDC 0781-1506-13 unit dose packages of 100

100 mg:round, white, unscored tablets debossed GG 264 on one side and plain on the reverse side, and supplied as:

NDC 0781-1507-01 bottles of 100

NDC 0781-1507-05 bottles of 500

NDC 0781-1507-10 bottles of 1000

NDC 0781-1507-13 unit dose packages of 100

STORAGE AND HANDLING

Store at 20-25 C (68-77 F) (see USP Controlled Room Temperature).

Dispense in a tight, light-resistant container.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL SECTION

DRUG: Atenolol

GENERIC: ATENOLOL

DOSAGE: TABLET

ADMINSTRATION: ORAL

NDC: 52125-166-02

STRENGTH:50 mg

COLOR: white

SHAPE: ROUND

SCORE: Two even pieces

SIZE: 7 mm

IMPRINT: 30

QTY: 30

MM2

ATENOLOL 
atenolol tablet
Product Information
Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC:52125-166(NDC:0781-1506)
Route of AdministrationORAL
Active Ingredient/Active Moiety
Ingredient NameBasis of StrengthStrength
ATENOLOL (UNII: 50VV3VW0TI) (ATENOLOL - UNII:50VV3VW0TI) ATENOLOL50 mg
Inactive Ingredients
Ingredient NameStrength
CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U)  
MAGNESIUM STEARATE (UNII: 70097M6I30)  
SILICON DIOXIDE (UNII: ETJ7Z6XBU4)  
SODIUM STARCH GLYCOLATE TYPE A POTATO (UNII: 5856J3G2A2)  
Product Characteristics
ColorwhiteScore2 pieces
ShapeROUND (TABLET) Size7mm
FlavorImprint Code GG263
Contains    
Packaging
#Item CodePackage DescriptionMarketing Start DateMarketing End Date
1NDC:52125-166-0230 in 1 BLISTER PACK; Type 0: Not a Combination Product08/22/201201/27/2017
Marketing Information
Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
ANDAANDA07302508/22/201201/27/2017
Labeler - REMEDYREPACK INC. (829572556)

Revised: 1/2017
 
REMEDYREPACK INC.