Atenolol / Chlorthalidone

Pronunciation

Pronunciation: a-TEN-oh-lol/klor-THAL-i-done
Class: Antihypertensive combination

Trade Names

Tenoretic 50
- Tablets, oral atenolol 50 mg/chlorthalidone 25 mg

Tenoretic 100
- Tablets, oral atenolol 100 mg/chlorthalidone 25 mg

Apo-Atenidone (Canada)
Tenoretic (Canada)

Pharmacology

Atenolol

Atenolol is a beta-adrenergic blocking agent that slows heart rate, reduces cardiac output and lowers BP.

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Chlorthalidone

Chlorthalidone is a diuretic agent that reduces body water by increasing urine output.

Indications and Usage

For the treatment of hypertension.

Contraindications

Hypersensitivity to sulfonamide-derived drugs; sinus bradycardia; heart block greater than first degree; cardiogenic shock; overt cardiac failure; anuria.

Dosage and Administration

Adults

PO Atenolol 50 mg/chlorthalidone 25 mg initially. May increase to atenolol 100 mg/chlorthalidone 25 mg daily, if needed.

Renal function impairment
Adults CrCl 15 to 35 mL/min/1.73 m 2

PO Max dose is atenolol 50 mg/chlorthalidone 25 mg daily.

CrCl less than 15 mL/min/1.73 m 2

PO Max dose is atenolol 50 mg/chlorthalidone 25 mg every other day.

General Advice

  • Administer with or without food.
  • Additional antihypertensive may be added if needed; initiate additional medication at half the recommended starting dose to avoid excessive fall in BP.
  • Do not abruptly discontinue therapy; abrupt cessation can cause adverse effects.

Storage/Stability

Store at 68° to 77°F.

Drug Interactions

No drug interaction studies have been conducted between atenolol/chlorthalidone and other drugs. The following interactions are based on drug interactions involving each component of the atenolol/chlorthalidone combination.

ACE inhibitors (eg, captopril)

The risk of acute renal dysfunction may be increased. Closely monitor renal function, especially in elderly patients and in patients with renal impairment.

Antiarrhythmic agents (eg, disopyramide, flecainide, lidocaine, quinidine)

Pharmacologic effects of disopyramide, flecainide, and lidocaine may be increased. Severe bradycardia and cardiac arrest may occur. In addition, quinidine may increase the pharmacologic effects of atenolol/chlorthalidone; hypotension may occur. Use with caution and monitor closely.

Antihypertensive agents

Additive or potentiation of hypotension effects. Closely monitor BP.

Antineoplastic agents (eg, cyclophosphamide)

Thiazides may prolong antineoplastic-induced myelosuppression. Use with caution.

Bile acid sequestrants (eg, cholestyramine, colestipol)

Chlorthalidone absorption may be delayed or decreased. Separate the administration times by at least 4 hours. A higher dose of atenolol/chlorthalidone may be needed.

Bupivacaine

Plasma concentrations and pharmacologic effects of bupivacaine may be increased by atenolol. Reduce the dose of bupivacaine as needed.

Calcium channel blockers (eg, diltiazem, mibefradil, nifedipine, verapamil)

Pharmacologic effects may be increased. Hypotension, bradycardia, cardiac failure, and life-threatening cardiac conduction abnormalities may result. Monitor CV status closely and adjust dosage as needed.

Catecholamine-depleting drugs (eg, reserpine)

Additive effects may occur. Monitor closely for hypotension and/or excessive bradycardia.

Clonidine

The severity of rebound hypertension associated with abrupt withdrawal of clonidine may be more severe. Paradoxical hypertension may also occur. Avoid abrupt withdrawal of clonidine. Discontinue either agent gradually; preferably, discontinue atenolol/chlorthalidone first.

CNS depressants (eg, alcohol, barbiturates, narcotics)

Potentiation of orthostatic hypotension may occur. Monitor BP.

Corticosteroids, corticotropin

Electrolyte depletion may be intensified, particularly hypokalemia. Closely monitor serum potassium.

Diazoxide

The pharmacologic effects of both drugs may be increased. Hyperglycemia, hyperuricemia, and hypotension may occur. Closely monitor BP, blood and urine glucose, and serum uric acid levels.

Digitalis glycosides (eg, digoxin)

The risk of bradycardia is increased because atenolol and digitalis both slow AV conduction and decrease heart rate. Monitor cardiac function and heart rate. In addition, thiazide-induced electrolyte disturbances may predispose to digitalis-induced arrhythmias. Measure plasma concentrations of potassium and magnesium.

Fingolimod

Fingolimod-related bradycardia may be increased. Monitor closely, especially during initiation of fingolimod therapy.

Glucagon

The hyperglycemic effect of glucagon may be blunted by atenolol. Consider administering glucose for a hypoglycemic episode in a patient on atenolol/chlorthalidone.

Hypoglycemic agents, oral (eg, sulfonylureas)

The effect of oral hypoglycemic agents may be increased or decreased; symptoms of hypoglycemia may be masked. In addition, the hypoglycemic effects of sulfonylureas may be decreased by thiazides. Monitor blood glucose and adjust the hypoglycemic dose as needed.

Insulin

Atenolol prolongs and masks symptoms of hypoglycemia. In contrast, thiazides may increase fasting blood glucose and decrease insulin secretion; thus, the effect of insulin may be decreased. Monitor blood glucose and adjust the insulin dosage as needed. Consider a cardioselective beta-blocker.

Lithium

Lithium clearance may be decreased by thiazides, increasing lithium concentrations and the risk of lithium toxicity. In addition, the combination of lithium and atenolol may cause bradycardia. Lithium generally should not be given with diuretics. If concurrent use cannot be avoided, monitor serum lithium levels and adjust the dosage accordingly.

Loop diuretics (eg, furosemide)

Chlorthalidone and furosemide have synergistic effects that may result in profound diuresis and serious electrolyte abnormalities. Monitor patients for dehydration and electrolyte abnormalities during combined therapy.

Mefloquine

Coadministration may cause CV toxicity, including ECG abnormalities, such as AV block or QT interval prolongation. Consider alternatives to mefloquine. If coadministration cannot be avoided, close clinical and ECG monitoring is indicated.

Nondepolarizing muscle relaxants (eg, tubocurarine)

Possible increase responsiveness to the muscle relaxant due to diuretic-induced hypokalemia. If hypokalemia cannot be corrected, a lower dosage of nondepolarizing muscle relaxants may be needed.

NSAIDs (eg, ibuprofen, indomethacin)

The antihypertensive effects of atenolol and the diuretic, natriuretic, and antihypertensive effects of the thiazide diuretic may be reduced. Additionally, acute renal failure has been reported on rare occasions with concomitant use of thiazides and NSAIDs. Avoid coadministration with indomethacin if possible. Monitor BP and the diuretic response.

Pressor amines (eg, norepinephrine)

Response to pressor amines may be decreased. Use with caution.

Quinazolines (eg, prazosin)

Coadministration may enhance the severity and duration of hypotension.

Tretinoin

The risk of phototoxicity may be increased if these agents are coadministered. Avoid coadministration.

Laboratory Test Interactions

Thiazides may decrease serum protein-bound iodine levels without signs of thyroid disturbance. Discontinue thiazides before carrying out tests for parathyroid function.

Adverse Reactions

Cardiovascular

Postural hypotension (4%); bradycardia (3%); orthostatic hypotension, Raynaud phenomena, sick sinus syndrome, syncope (postmarketing).

CNS

Tiredness (26%); dizziness (13%); depression (12%); fatigue (6%); dreaming, lethargy, light-headedness (3%); drowsiness, vertigo (2%); paresthesia; restlessness; weakness; hallucination, headache, psychoses (postmarketing).

Dermatologic

Exacerbation of psoriasis or psoriasiform rash, purpura, reversible alopecia (postmarketing).

GI

Nausea (4%); diarrhea (3%); anorexia; constipation; cramping; gastric irritation; vomiting; dry mouth (postmarketing).

Genitourinary

Impotence, Peyronie disease (postmarketing).

Hematologic

Agranulocytosis; aplastic anemia; leukopenia; thrombocytopenia.

Hepatic

Jaundice (intrahepatic cholestatic jaundice); pancreatitis; elevated liver enzymes and/or bilirubin (postmarketing).

Hypersensitivity

Lyell syndrome (TEN); necrotizing angiitis (vasculitis, cutaneous vasculitis); photosensitivity; purpura; rash; urticaria.

Metabolic

Glycosuria; hyperglycemia; hyperuricemia; hypokalemia.

Musculoskeletal

Leg pain (3%); muscle spasm.

Respiratory

Dyspnea (6%); wheezing (3%).

Special Senses

Visual disturbance; xanthopsia.

Miscellaneous

Cold extremities (12%); antinuclear antibodies, lupus syndrome (postmarketing).

Precautions

Monitor

Observe patients for signs of fluid or electrolyte imbalance (eg, hyponatremia, hypokalemia, hyperkalemia, hypomagnesemia). Periodically determine serum electrolytes at appropriate intervals. Perform periodic BUN and creatinine determinations, especially in elderly patients and patients with confirmed or suspected hepatic or renal insufficiencies. Monitor blood glucose in diabetic patients when the drug is started or dosage is changed.


Pregnancy

Category D . Atenolol can cause fetal harm when administered to pregnant women. Use of atenolol in the second trimester of pregnancy has been associated with birth of infants who are small for gestational age. Both atenolol and chlorthalidone cross the placental barrier and appear in cord blood. Thiazides can cause fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse effects that have occurred in adults. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, apprise the patient of the potential hazard to the fetus.

Lactation

Atenolol is excreted in breast milk and may produce clinically significant effects, including hypoglycemia and bradycardia, in infants. Thiazides are excreted in human milk. Exercise caution when atenolol/chlorthalidone is administered to a breast-feeding woman.

Children

Safety and efficacy not established.

Elderly

Use with caution.

Renal Function

Use with caution in patients with renal disease; thiazides may precipitate azotemia. Cumulative effects may develop in patients with impaired renal function; discontinue if progressive renal function impairment develops.

Hepatic Function

Use with caution in impaired hepatic function or progressive liver disease because minor alternations of fluid and electrolyte balance may precipitate hepatic coma.

Cardiac failure

Continued depression of the myocardium with beta-blocking agents over a period of time can lead to cardiac failure.

Cardiovascular effects

May precipitate or aggravate symptoms of arterial circulatory disorders.

Diabetes mellitus

Use with caution. May mask symptoms of hypoglycemia (eg, tachycardia, BP changes). Latent diabetes may become manifest during administration.

Discontinuation

Abrupt cessation of beta-blocking agents in patients with coronary artery disease can exacerbate angina pectoris, and in some cases, MI has been reported. Do not abruptly discontinue therapy.

Electrolyte imbalance

Hypokalemia, hypochloremic alkalosis, hyponatremia, hypercalcemia, and hypophosphatemia may occur.

Hyperuricemia

Hyperuricemia may occur, or acute gout may be precipitated.

Pheochromocytoma

Do not give to patients with untreated pheochromocytoma.

Postsympathectomy

The antihypertensive effects of hydrochlorothiazide may be enhanced in the postsympathectomy patient.

Respiratory effects

In general, do not give beta-blockers to patients with bronchospastic diseases.

Surgery

The impaired ability of the heart to respond to reflux adrenergic stimuli may augment the risks of general anesthesia and surgical procedures; however, chronically administered beta-blockers should not be routinely withdrawn prior to major surgery.

Systemic lupus erythematosus

Exacerbation or activation may occur.

Thyroid effects

May mask clinical signs (eg, tachycardia) of developing or continuing hyperthyroidism. Abrupt withdrawal may exacerbate symptoms of hyperthyroidism, including thyroid storm.

Patient Information

  • Warn patients, especially those with evidence of coronary artery insufficiency, against interruption or discontinuation of therapy without the health care provider's approval.
  • Advise patients to consult their health care provider at the first sign or symptom of impending cardiac failure.
  • Caution patients that light-headedness can occur, especially during the first days of therapy, and to report symptoms to their health care provider.
  • Caution patients that inadequate fluid intake, excessive perspiration, diarrhea, or vomiting can lead to an excessive fall in BP, resulting in light-headedness or fainting.
  • Instruct diabetic patients to monitor blood glucose more frequently when the drug is started or the dose is changed, and to inform their health care provider of significant changes.
  • Caution patients to avoid unnecessary exposure to ultraviolet (UV) light (sunlight, tanning booths), use sunscreen, and wear protective clothing when exposed to UV light to avoid photosensitivity reaction.
  • Caution patients not to take any prescription or nonprescription medications, potassium salt substitutes, or potassium dietary supplements unless advised by their health care provider.

Copyright © 2009 Wolters Kluwer Health.

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