Plot 1 Junaid Dosunmu Street,Central Business District, Alausa, P.0. Box 3560 Ikeja, Lagos, Nigeria.
Tel: + 234-1-774-1205
AstraZeneca, Silk Court, Silk Road Business Park, Macclesfield, Cheshire SK10 2NA, England
Dosage Form, Composition & NAFDAC Registration Number (NRN)
Tablet (NRN: 04-1768): Atenolol PhEur 100 mg, Chlorthalidone PhEur 25 mg.
How to identify the Product: Film-coated tablets.
Tablet (NRN: 04-2001): Atenolol 50 mg, Chlorthalidone 12.5 mg.
How to identify the Product: Film-coated tablets
Tenoretic combines the antihypertensive activity of two agents, a beta-blocker (atenolol) and a diuretic (chlorthalidone). Atenolol predominantly blocks beta1 receptors and does not posses membrane stabilising or intrinsic sympathomimetic (partial agonist) activities. The mechanism of the antihypertensive effect of atenolol has not been established.
Chlorthalidone, a monosulfonamyl diuretic, increases excretion of sodium and chloride. Natriuresis is accompanied by some loss of potassium. The mechanism by which chlorthalidone reduces blood pressure is not fully known but may be related to the excretion and redistribution of body sodium.
Chlorthalidone usually does not decrease normal blood pressure. The combination of atenolol with thiazide-like diuretics has been shown to be compatible and generally more effective than either drug used alone as antihypertensive agent.
Co-administration of chlorthalidone and atenolol has little effect on the pharmacokinetics of either. Approximately 50% of an oral dose of atenolol and 60% of an oral dose of chlorthalidone is absorbed from the gastro-intestinal tract. Atenolol is only poorly bound to plasma proteins.
Chlorthalidone is 75% plasma protein bound. The Tmax for atenolol is 3 hours and the Tmaxfor chlorthalidone is 12 hours. Metabolism of atenolol occurs to only a very minor extent and both atenolol and chlorthalidone are excreted predominantly via the kidney.
A pharmacologically active metabolite of atenolol is present in urine of man but represents only 2% of the dose. This metabolite is not detected in plasma. Information is not available on chlorthalidone. The elimination half-life of atenolol is 6-9 hours and that for chlorthalidone is approximately 50 hours
Management of hypertension
Presence of second or third degree heart block; Patients with cardiogenic shock
Special care should be taken with patients whose cardiac reserve is poor. Beta-blockers should be avoided in overt heart failure. However, they may be used in patients whose signs of failure have been controlled. One of the pharmacological actions of beta-blockers is to reduce heart rate. In the rare instance when symptoms may be attributable to the slow heart rate, the dose may be reduced. Tenoretic modifies the tachycardia of hypoglycaemia.
Tenoretic contains the cardioselective beta-blocker atenolol and may be used with caution in patients with chronic obstructive airways disease. However, some increase in airways resistance may occur occasionally in asthmatic patients. This can usually be reversed by commonly used dosage of bronchodilators such as salbutamol or isoprenaline. In patients suffering from ischaemic heart disease, as with other beta-blockers, treatment should not be discontinued abruptly. Tenoretic may aggravate peripheral arterial circulatory disorders.
While taking beta-blockers, patients with a history of anaphylactic reaction to a variety of allergen may have a more severe reaction on repeated challenge. Such patients may be unresponsive to the usual doses of adrenaline used to treat the allergic reactions.
Pregnancy & Lactation: Not recommended.
Anaesthesia: Care should be taken when using anaesthetic agents with Tenoretic. The anaesthetist should be informed and the choice of anaesthetic should be the agent with as little negative inotropic activity as possible.
Effect on ability to drive or operate machinery: Unlikely to cause any impairment of the ability of patients to drive or operate machinery.
Care should be taken in prescribing a beta-blocker with Class I anti-arrythmic agents such as disopyramide. Combined use of beta-blockers and calcium channel blockers with negative inotropic effects e.g. verapamil, diltiazem can lead to an exaggeration of these effects, particularly in patients with impaired ventricular function and/or SA or AV conduction abnormalities. This may result in severe hypotension, bradycardia and cardiac failure. Neither the beta-blocker nor the calcium channel blocker should be administered intravenously within 48 hours of discontinuing the other.
Beta-blockers may exacerbate the rebound hypertension which can follow the withdrawal of clonidine. If the two drugs are co-administered, the beta-blocker should be withdrawn several days before discontinuing clonidine. If replacing clonidine by beta-blocker therapy, the introduction of beta-blockers should be delayed for several days after clonidine administration has stopped.
As with other combinations of beta-blockers and diuretics, Tenoretic may be associated with minor changes in potassium status. Measurement of potassium levels is appropriate especially in the older patient, those receiving digitalis preparations for cardiac failure, taking an abnormal (low in potassium) diet or suffering from gastro-intestinal complaints. Potassium depletion may be dangerous in patients receiving digitalis.
Diuretics may cause hyperuricaemia. Tenoretic is generally associated with only a minor increase in serum uric acid. In cases of prolonged elevation the concurrent use of a uricosuric agent will reverse the hyperuricaemia. Because Tenoretic contains chlorthalidone, care should be taken in patients with severe renal failure or with a history of sensitivity to chlorthalidone. Chlorthalidone may decrease glucose tolerance. Care is necessary when Tenoretic is administered to patients with a known predisposition to diabetes. Preparations containing lithium generally should not be given with diuretics because they may reduce its renal clearance.
Minor side effects include cold extremities, fatigue, gastro-intestinal disturbance and, in isolated cases, bradycardia. Headache, mood changes, dizziness and deterioration in heart failure may occasionally occur. Sleep disturbances of the type noted with other beta-blockers, postural hypotension which may be associated with syncope alopecia, thrombocytopenia, purpura, psoriasiform skin reactions, exacerbation of psoriasis, visual disturbances, psychoses, hallucinations and precipitation of heart block in susceptible patients have rarely been reported.
There have been reports of skin rashes and/or dry eye associated with the use of beta-blockers. 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. Nausea and dizziness have been reported occasionally with chlorthalidone and idiosyncratic drug reactions such as thrombocytopenia and leucopenia have occurred rarely.
Dosage & Administration
Adults: One tablet daily. Most patients with hypertension will give a satisfactory response to a single tablet daily of Tenoretic. There is little or no further fall in blood pressure with increased dosage and, where necessary, another antihypertensive drug, such as vasodilator, can be added.
Elderly Patients: Dosage requirements are often lower in this age group.
Children: There is no paediatric experience with Tenoretic, therefore this preparation is not recommended for children.
Renal Failure: In patients with severe renal impairment a reduction in daily dose or in frequency of administration may be necessary.
Excessive bradycardia can be countered with atropine 1-2 mg intravenously. 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 response. If no response to glucagon occurs or if glucagon is unavailable, a beta-adrenoceptor stimulant such as dobutamine 2.5 to 10 micrograms/kg/minute by intravenous infusion or isoprenaline 10 to 25 micrograms given as an infusion at a rate not exceeding 5 micrograms/minute may be given.
It is likely that these doses would be inadequate to reverse the cardiac effects of beta-blockade if a large overdose has been taken. The dose of dobutamine or isoprenaline should therefore be increased if necessary to achieve the required response according to the clinical condition of the patient.
There is a possibility of hypotension occurring following the use of beta-adrenoceptor agonists but this will be reduced by the use of the more selective agent dobutamine. Excessive diuresis should be countered by maintaining normal fluid and electrolyte balance.
Store at room temperature, protected from light and moisture.