Adult: Available preparations:
Atenolol 50 mg and chlortalidone 12.5 mg tab
Atenolol 50 mg and chlortalidone 25 mg tab
Atenolol 100 mg and chlortalidone 25 mg tab
In patients who do not adequately respond to monotherapy: Initially, 1 tab of 50 mg atenolol/25 mg chlortalidone once daily, may increase to 1 tab of 100 mg atenolol/25 mg chlortalidone once daily if the optimal blood pressure response is not achieved. Individualise dosage. Elderly: Initiate at lower doses.
Renal Impairment
CrCl (mL/min)
Dosage
<15
Max dose of atenolol component: 50 mg every other day.
15-35
Max dose of atenolol component: 50 mg once daily.
Contraindications
Hypersensitivity to atenolol, chlortalidone or sulfonamide derivatives. Sick sinus syndrome, bradycardia, 2nd- or 3rd-degree heart block, cardiogenic shock, hypotension, overt cardiac failure, severe peripheral arterial circulatory disorders, uncontrolled heart failure, anuria, metabolic acidosis, untreated phaeochromocytoma.
Special Precautions
Patient with history of severe anaphylaxis to allergens; bronchospastic disease, bronchial asthma, COPD, conduction abnormality, left ventricular dysfunction, 1st-degree heart block, controlled heart failure, Prinzmetal’s angina, cerebrovascular disease; prediabetes or diabetes mellitus, history of gout, hypercholesterolaemia, myasthenia gravis, peripheral vascular disease (e.g. intermittent claudication), Raynaud’s disease, psoriasis, thyroid disease, cirrhosis. Patient undergoing major surgery. Avoid abrupt withdrawal (particularly in patients with coronary artery disease). Renal and hepatic impairment. Elderly. Pregnancy and lactation.
Adverse Reactions
Significant: Hypersensitivity reactions (e.g. angioedema, urticaria), bradycardia, electrolyte disturbances (e.g. hypokalaemia, hypochloraemic alkalosis, hyponatraemia), bronchospasm, masked warning signs of hypoglycaemia or hyperthyroidism (e.g. tachycardia); activation or exacerbation of SLE, precipitation of gout or azotaemia, hyperuricaemia, photosensitivity. Ear and labyrinth disorders: Vertigo. Gastrointestinal disorders: Nausea, diarrhoea, gastrointestinal disturbance. General disorders and administration site conditions: Fatigue, lethargy. Investigations: Transaminase level elevations. Metabolism and nutrition disorders: Impaired glucose tolerance. Musculoskeletal and connective tissue disorders: Muscle fatigue. Nervous system disorders: Dizziness, drowsiness, headache. Psychiatric disorders: Sleep disturbances, depression. Respiratory, thoracic and mediastinal disorders: Wheezing, dyspnoea. Skin and subcutaneous tissue disorders: Rarely, rash, exacerbated psoriasis. Vascular disorders: Cold extremities, orthostatic hypotension.
This drug may cause dizziness, if affected, do not drive or operate machinery. Avoid excessive exposure to sunlight or UV light.
Monitoring Parameters
Monitor blood pressure, heart rate, fluid and electrolyte balance, and renal function tests regularly during treatment. Observe for symptoms of gout, fluid or electrolyte imbalance; worsening of heart failure (in at-risk patients).
Overdosage
Symptoms: Lethargy, wheezing, sinus pause, bradycardia, hypotension, CHF, bronchospasm, hypoglycaemia; nausea, weakness, dizziness and electrolyte balance disturbance. Management: Symptomatic and supportive treatment. Perform gastric lavage, administer activated charcoal or induce emesis to remove any unabsorbed drug. May give atropine or glucagon IV bolus for bradycardia; isoproterenol or transvenous pacemaker for 2nd- or 3rd-degree heart block; vasopressors (e.g. dopamine, norepinephrine) or dobutamine for hypotension; β2-stimulants (e.g. isoproterenol, terbutaline, aminophylline) for bronchospasm; IV glucose for hypoglycaemia. May administer digitalis and diuretic for CHF. Initiate measures to maintain hydration and electrolytes. Monitor blood pressure, electrolyte levels and renal function. Atenolol may be removed by haemodialysis, if necessary.
Drug Interactions
May increase the atrioventricular conduction time or cause arrhythmias with digitalis glycosides. Antihypertensive effect may be enhanced by baclofen. May reduce the hypotensive and diuretic effects with NSAIDs (e.g. ibuprofen, indometacin).
Atenolol: May increase risk of postural hypotension with α-blockers (e.g. prazosin, alfuzosin). May diminish reflex tachycardia and increase the risk of hypotension with anaesthetic drugs. May enhance the bradycardic effect with disopyramide and amiodarone. May intensify blood sugar-lowering effects and mask signs of hypoglycaemia with insulin and oral antidiabetics. May cause severe hypotension, bradycardia and cardiac failure with Ca channel blockers (e.g. nifedipine, diltiazem, verapamil). Increased risk of rebound hypertension after the withdrawal of clonidine. May antagonise effects with sympathomimetic agents (e.g. epinephrine). Ampicillin may decrease the bioavailability of atenolol.
Chlortalidone: May decrease the renal clearance resulting in increased serum levels of lithium. May potentiate the action of antihypertensives (e.g. ACE inhibitors). May potentiate hypokalaemic effects with corticosteroids, β2-agonists, amphotericin B. May increase bioavailability with anticholinergic agents (e.g. atropine, biperiden). May reduce absorption with colestyramine. May increase risk of hypersensitivity reactions with allopurinol. May enhance the hypotensive effect with diazoxide. May reduce renal excretion and potentiate myelosuppressive effects of antineoplastic agents (e.g. cyclophosphamide, methotrexate). May decrease the excretion and increase the effects of Ca salts and vitamin D.
Food Interaction
Chlortalidone: Enhanced orthostatic hypotensive effects with alcohol.
Lab Interference
May result in false-positive aldosterone/renin ratio (ARR). Chlortalidone may reduce the serum protein-bound iodine (with no signs of thyroid disturbance).
Action
Description: Mechanism of Action: Atenolol and chlortalidone combination results in additive antihypertensive action.
Atenolol, a β-blocker, selectively and competitively inhibits the response on the β1-adrenergic receptors in the heart.
Chlortalidone is a sulfonamide-derived thiazide-like diuretic that reduces blood pressure by inhibiting Na and chloride reabsorption in the distal convoluted tubule.
Synonym: Chlortalidone: chlorthalidone. Onset: Atenolol: β-blocking effect: ≤1 hour.
Chlortalidone: Diuretic effect: Approx 2.6 hours. Duration: Atenolol: β-blocking effect: 12-24 hours; antihypertensive effect: 24 hours.
Chlortalidone: 24-48 hours (single dose); 48-72 hours (long-term dosing). Pharmacokinetics: Absorption: Atenolol: Rapid and consistent but incompletely absorbed (approx 50%) from the gastrointestinal tract. Time to peak plasma concentration: 2-4 hours.
Chlortalidone: Consistent but incompletely absorbed (approx 60%) from the gastrointestinal tract. Bioavailability: Approx 65%. Time to peak plasma concentration: Approx 12 hours. Distribution: Atenolol: Poorly penetrates tissues due to low lipid solubility. Crosses the placenta and enters breast milk. Plasma protein binding: 6-16%.
Chlortalidone: Crosses the placenta and enters breast milk. Plasma protein binding: Approx 75%, 58% to albumin. Metabolism: Atenolol: Limited metabolism in the liver.
Chlortalidone: Metabolised in the liver. Excretion: Atenolol: Via faeces (50%); urine (40% as unchanged drug). Elimination half-life: 6-7 hours.
Chlortalidone: Via urine (mainly as unchanged drug). Elimination half-life: 40 hours (single dose); 45-60 hours (long-term dosing).
Chemical Structure
Atenolol Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 2249, Atenolol. https://pubchem.ncbi.nlm.nih.gov/compound/Atenolol. Accessed May 26, 2022.
Chlortalidone Source: National Center for Biotechnology Information. PubChem Database. Chlorthalidone, CID=2732, https://pubchem.ncbi.nlm.nih.gov/compound/Chlorthalidone (accessed on Jan. 21, 2020)
Storage
Store between 20-25°C. Protect from light and moisture.
C07BB03 - atenolol and thiazides ; Belongs to the class of selective beta-blocking agents in combination with thiazides. Used in the treatment of cardiovascular diseases. C07DB01 - atenolol, thiazides and other diuretics ; Belongs to the class of selective beta-blocking agents in combination with thiazides and other diuretics. Used in the treatment of cardiovascular diseases.
References
Anon. Atenolol and Chlorthalidone. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 21/07/2020.Anon. Atenolol. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 21/07/2020.Anon. Chlorthalidone. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 21/07/2020.Atenolol and Chlorthalidone Tablet (Northstar Rx LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 21/07/2020.Atenolol; Chlorthalidone. Gold Standard Drug Database in ClinicalKey [online]. Elsevier Inc. https://www.clinicalkey.com/. Accessed 16/09/2020.Co-tenidone 100/25 mg Tablets (Special Concept Development Ltd T/A RxFarma). MHRA. https://products.mhra.gov.uk/. Accessed 21/07/2020.Co-tenidone 50/12.5 mg Tablets BP (Medreich PLC). MHRA. https://products.mhra.gov.uk/. Accessed 21/07/2020.Target Tablet (Lisapharma). MIMS Malaysia. http://www.mims.com/malaysia. Accessed 21/07/2020 .Tenoretic Tablets (AstraZeneca UK Limited). MIMS Philippines. http://www.mims.com/philippines. Accessed 21/07/2020.
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