Tenoric Atenolol and Chlortalidone Tablets


Co-Tenidone Tablets BP


For the use only of a Registered Medical Practitioner or a Hospital or a Laboratory



Tenoric tablets (atenolol and chlortalidone) are used for the treatment of hypertension. Tenoric combines the antihypertensive activity of two agents: a hydrophilic and selective beta1-blocking (cardioselective) agent (atenolol) and a monosulfonamyl diuretic (chlortalidone). Atenolol is 4-[2’-hydroxy-3’-[(1- methylethyl) amino] propoxy] benzeneacetamide. Chlortalidone is 2-chloro-5-(1-hydroxy-3-oxo-1 – isoindolinyl) benzene sulfonamide.




Each film-coated tablet contains:

Atenolol EP 50mg

Chlortalidone EP 12.5mg


Each film-coated tablet contains:

Atenolol EP 100mg

Chlortalidone EP 25mg



Atenolol and chlortalidone have been used singly and concomitantly for the treatment of hypertension. Therefore, this combination provides a convenient formulation for the concomitant administration of these two entities. The combination of atenolol with thiazide like diuretics has been shown to be compatible and generally more effective than either drug used alone. In patients with more severe hypertension, Tenoric may be administered with other antihypertensives such as vasodilators.




Atenolol is a beta1-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 beta2 – adrenoreceptors, chiefly located in the bronchial and vascular musculature.

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 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 beta1-selectivity of atenolol has been shown by its reduced ability to reverse the beta2– 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.

Atenolol produced a significantly smaller decrease of FEV1 than, 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.

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 with prolonged use.



Chlortalidone is a monosulfonamyl diuretic. 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 sodium and chloride. Natriuresis is accompanied by some loss of potassium. The diuretic effects of chlortalidone lead to decreased extracellular fluid volume, plasma volume, cardiac output, total exchangeable sodium, glomerular filtration rate, and renal plasma flow. The mechanism by which chlortalidone reduces blood pressure is not fully known but may be related to the excretion and redistribution of body sodium. The site of action appears to be the cortical diluting segment of the ascending limb of Henle’s loop of the nephron.




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. It has very low lipid solubility. Atenolol undergoes little or no metabolism by the liver, and the absorbed portion is eliminated primarily by renal excretion. 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. Only small amounts are reported to cross the blood brain barrier.

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 glomerular filtration rate; but significant accumulation does not occur until the creatinine clearance falls below 35 mL/min/1.73m2.


Chlortalidone is erratically absorbed from the gastrointestinal tract. Absorption of chlortalidone following oral dosing is consistent but incomplete (approximately 60%) with peak plasma concentrations occurring about 12 hours after dosing. It has a prolonged elimination half life from plasma and blood of 40 to 60 hours and is highly bound to red blood cells; the receptor to which it is bound has beeen identified as carbonic anhydrase. Plasma protein binding is high (approximately 75%). Chlortalidone is mainly excreted unchanged in the urine. It crosses the placental barrier and is distributed into breast milk.

Co-administration of chlortalidone and atenolol has little effect on the pharmacokinetics of either.

The combination is effective for at least 24 hours after a single oral daily dose. This simplicity of dosing facilitates compliance by its acceptability to patients.



Tenoric is 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.



Tenoric is contraindicated in patients with: sinus bradycardia; heart block greater than first degree; cardiogenic shock; overt cardiac failure; anuria; hypotension; metabolic acidosis; severe peripheral arterial circulatory disturbances; sick sinus syndrome; hypersensitivity to this product or to sulfonamide- derived drugs.



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 who have congestive heart failure controlled by digitalis and/or diuretics, Tenoric should be administered cautiously. Both digitalis and atenolol slow AV conduction.

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, Tenoric should be withdrawn.

Renal and hepatic disease and electrolyte disturbances

Since atenolol is excreted via the kidneys, the drug should be used with caution in patients with impaired renal function.

In patients with renal disease, thiazides may precipitate azotemia. Since cumulative effects may develop in the presence of impaired renal function, if progressive renal impairment becomes evident, Tenoric should be discontinued.

In patients with impaired hepatic function or progressive liver disease, minor alterations in fluid and electrolyte balance may precipitate hepatic coma. Tenoric should be used with caution in these patients.

Ischemic heart disease

Following abrupt cessation of therapy with certain beta-blocking agents in patients with coronary artery disease, exacerbations of angina pectoris and, in some cases, myocardial infarction have been reported. Therefore, such patients should be cautioned against interruption of therapy without the physician’s advice. Even in the absence of overt angina pectoris, when discontinuation of Tenoric is planned, the patient, should be carefully observed and should be advised to limit physical activity to a minimum. Tenoric should be reinstated if withdrawal symptoms occur. Because coronary artery disease is common and may be unrecognized, it may be prudent not to discontinue Tenoric therapy abruptly even in patients treated only for hypertension.

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.

Bronchospastic diseases

Patients with bronchospastic disease should, in general, not receive beta blockers. Because of its relative beta1-selectivity, however Tenoric 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 Tenoric should be used 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.

Anesthesia and major surgery

It is not advisable to withdraw beta-adrenoreceptor blocking drugs prior to surgery in the majority of patients. However, care should be taken when using anesthetic agents such as those, which may depress the myocardium. Vagal dominance, if it occurs, may be corrected with atropine (1-2mg IV). Beta blockers are competitive inhibitors of beta-receptor agonists and their effects on the heart can be reversed by administration of such agents; e.g. dobutamine or isoproterenol with caution.

Caution should be observed when using anesthetic agents with Tenoric, The anesthetist should be informed and the choice of anesthetic should be an agent with as little negative inotropic activity as possible. Use of beta-adrenoceptor blocking drugs with anesthetic drugs may result in attenuation of the reflex tachycardia and increase the risk of hypotension. Anesthetic agents causing myocardial depression are best avoided.

Metabolic and endocrine effects

Tenoric may be used with caution in diabetic patients. 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 nonselective beta blockers, does not delay recovery of blood glucose to normal levels.

Insulin requirements in diabetic patients may be increased, decreased or unchanged; latent diabetes mellitus may became manifest during chlortalidone administration.

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 Tenoric therapy is to be withdrawn should be monitored closely.

Because calcium excretion is decreased by thiazides, Tenoric should be discontinued before carrying out tests for parathyroid function. Pathologic changes in the parathyroid glands, with hypercalcemia and hypophosphatemia, have been observed in a few patients on prolonged thiazide therapy; however, the common complications of hyperparathyroidism such as renal lithiasis, bone resorption, and peptic ulceration have not been seen.

Hyperuricemia may occur, or acute gout may be precipitated in certain patients receiving thiazide therapy.

Untreated pheochromocytoma

The drug should not be given to patients with untreated pheochromocytoma.




Tenoric may aggravate peripheral arterial circulatory disorders.

Electrolyte and fluid balance status

Periodic determination of serum electrolytes to detect possible electrolyte imbalance should be performed at appropriate intervals.

Patients should be observed for clinical signs of fluid or electrolyte imbalance; i.e., hyponatremia, hypochloremic alkalosis, and hypokalemia. Serum and urine electrolyte determinations are particularly important when the patient is vomiting excessively or receiving parenteral fluids. Warning signs or symptoms of fluid and electrolyte imbalance include dryness of the mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, and gastrointestinal disturbances such as nausea and vomiting.

Measurement of potassium levels is appropriate especially in elderly patients, those receiving digitalis preparations for cardiac failure, patients whose dietary intake of potassium is abnormally low, or those suffering from gastrointestinal complaints.

Hypokalemia may develop especially with brisk diuresis, when severe cirrhosis is present, or during concomitant use of corticosteroids or ACTH.

Interference with adequate oral electrolyte intake will also contribute to hypokalemia. Hypokalemia can sensitize or exaggerate the response of the heart to the toxic effects of digitalis (e.g. increased ventricular irritability). Hypokalemia may be avoided or treated by use of potassium supplements or foods with a high potassium content.

Any chloride deficit during thiazide therapy is generally mild and usually does not require specific treatment except under extraordinary circumstances (as in liver disease or renal disease). Dilutional hyponatremia may occur in edematous patients in hot weather; appropriate therapy is water restriction rather than administration of salt except in rare instances when the hyponatremia is life-threatening. In actual salt depletion, appropriate replacement is the therapy of choice.

Other precautions

In patients receiving thiazides, sensitivity reactions may occur with or without a history of allergy or bronchial asthma. The possible exacerbation or activation of systemic lupus erythematosus has been reported. The antihypertensive effects of thiazides may be enhanced in the postsympathectomy patient.

Effect on ability to drive and use machines

Use is unlikely to result in any impairment of the ability of patients to drive or operate machinery. However, it should be taken into account that occasionally dizziness or fatigue may occur.

Usage in pregnancy and lactation

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.

Thiazides cross the placental barrier and appear in cord blood. The use of chlortalidone and related drugs in pregnant women requires that the anticipated benefits of the drug be weighed against possible hazards to the fetus. These hazards include fetal or neonatal jaundice, thrombocytopenia and possibly other adverse reactions which have occurred in the adult.

Atenolol is excreted in human breast milk at a ratio of 15 to 68 when compared to the concentration in plasma. Caution should be exercised when atenolol is administered to a nursing woman. Clinically significant bradycardia has been reported in breast fed infants.

Premature infants, or infants with impaired renal function may be more likely to develop adverse effects.

Usage in paediatrics

Safety and effectiveness in paediatric patients have not been established.

Usage in geriatics

Though clinical experience has not identified differences in responses between the elderly and younger patients, in general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant disease or other drug therapy.


Drug Interactions

The drug may potentiate the action of other antihypertensive agents used concomitantly. Patients treated with Tenoric plus a catecholamine depletory (e.g. reserpine) should be closely observed for evidence of hypotension and/or marked bradycardia, which may produce vertigo, syncope or postural hypotension.

Concomittant therapy with dihydropyridines e.g. nifedine, may increase the risk of hypotension, and cardiac failure may occur in patients with latent cardiac insufficiency.

Calcium channel blockers may also have an additive effect when given with the drug.

Digitalis glycosides, in association with beta-adrenoceptor blocking drugs, may increase atrio-ventricular conduction time.

Caution must be exercised when prescribing a beta-adrenoceptor blocking drug with Class 1 antiarrhythmic agent such as disopyramide.

Concomittant use of sympathomimetic agents, e.g. adrenaline, may counteract the effect of beta-adrenoceptor blocking drugs.

Thiazides may decrease arterial responsiveness to norepinephrine. This diminution is not sufficient to preclude the therapeutic effectiveness of norepinephrine. Thiazides may increase the responsiveness to tubocurarine.

Concomitant use with insulin and oral antidiabetic drugs may lead to the intensification of the blood sugar lowering effects of these drugs.

Concomittant use of prostaglandin synthase inhibiting drugs, e.g. indomethacin, ibuprofen, may decrease the hypotensive effects of beta-blockers.

Lithium generally should not be given with diuretics because they reduce its renal clearance and add a high risk of lithium toxicity.

Beta blockers may exacerbate the rebound hypertension which can follow the withdrawal of clonidine. If the two drugs are coadministered, the beta- blocker should be withdrawn several days before the gradual withdrawal of clonidine. If replacing clonidine by beta-blocker therapy, the introduction of beta-blockers should be delayed for several days after clonidine administration has stopped.

While taking beta blockers, patients with a history of anaphylactic reaction to a variety of allergens may have a more severe reaction on repeated challenge, either accidental, diagnostic or therapeutic. Such patients may be unresponsive to the usual doses of epinephrine used to treat the allergic reaction.



The drug is usually well tolerated in properly selected patients. Most adverse effects have been mild and transient. The adverse effects observed are essentially the same as those seen with the individual components.


The adverse effects include:


Bradycardia, cold extremities, posturaI hypotension, leg pain.

Central nervous system/neuromuscular

Dizziness, vertigo, light-headedness, tiredness, fatigue, lethargy, drowsiness, depression, dreaming.


Diarrhea, nausea.


Wheezing, dyspnea.


The following adverse reactions 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. The combination, 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 not observed 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, decreased performance on neuropsychometrics.


Intensification of AV block.


Mesenteric arterial thrombosis, ischemic colitis.




Erythematous rash, fever and sore throat, laryngospasm and respiratory distress.


There have been reports of skin rashes and/or dry eyes associated with the use of beta-adregenic 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.




Orthostatic hypotension.


Anorexia, gastric irritation, vomiting, cramping, constipation, jaundice (intrahepatic cholestatic jaundice), pacreatitis.


Vertigo, paresthesia, xanthopsia.


Leukopenia, agranulocytosis, thrombocytopenia, aplastic anemia.


Purpura, photosensitivity, rash, urticaria, necrotizing angiitis (vasculitis) (cutaneous vasculitis), Lyell’s syndrome (toxic epidermal necrolysis).


Hyperglycemia, glycosuria, hyperuricemia, muscle spasm, weakness, restlessness.

Clinical laboratory test findings

Clinically important changes in standard laboratory parameters were rarely associated with the administration of the drug. 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.



Dosage must be individualized.

Chlortalidone 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 Tenoric 50 tablet given once a day. If an optimal response is not achieved, the dosage should be increased to one Tenoric 100 tablet 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.

The lowest effective dose of Tenoric is recommended for patients with mild renal insufficiency. Since chlortalidone lose its diuretic effect when the creatinine clearance is <30ml/min, Tenoric should not be used in patients with creatinine clearance<30ml/min.



The symptoms of overdosage may include bradycardia, hypotension, acute cardiac insufficiency and bronchospasm.

General treatment should include: close supervision, treatment in an intensive care ward, the use of gastric lavage, activated charcoal and a laxative to prevent absorption of any drug still present in the gastrointestinal tract, the use of plasma or plasma substitutes to treat hypotension and shock. The possible use of haemodialysis or haemoperfusion may be considered.

Excessive bradycardia may be countered with atropine 1-2 mg intravenously and/or a cardiac pacemaker. If necessary; this may be followed by a bolus dose of glucagon 10 mg intravenously. If required, this may be repeated or followed by an intravenous infusion of glucagon 1-10 mg/hour depending on the response. If no response to glucagon occurs or glucagon is unavailable, a beta-adrenoceptor stimulant such as dobutamine 2.5 to 10 micrograms/kg/minute by intravenous infusion may be given. Dobutamine, because of its positive inotropic effect, could also be used to treat hypotension and acute cardiac insufficiency.

It is likely that these doses would be inadequate to reverse the cardiac effects of beta-adrenoceptor blockade if a large overdose has been taken. The dose of dobutamine should therefore be increased if necessary to achieve the required response according to the clinical condition of the patient.

Bronchospasm can usually be reversed by brochodilators.

Excessive diuresis should be countered by maintaining normal fluid and electrolyte balance.



Blister strip of 14 tablets.






Made in India by

Ipca Laboratories Ltd.

Regd. Off.: 48, Kandivli Ind. Estate,

Mumbai 400 067

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