Gerard Laboratories

Atenetic 50mg/12.5 mg Film-coated Tablets

Atenetic 100mg/25 mg Film-coated Tablets

For a full list of excipients, see section 6.1.

Film-coated tablet.

Atenetic 50mg/12.5 mg: white, biconvex, film-coated tablet embossed with 'AC62' on one side and 'G' on the reverse.

Atenetic 100mg/25 mg: white, biconvex, film-coated tablet embossed with 'AC125' on one side and 'G' on the reverse.

Arterial hypertension which cannot be treated sufficiently with monotherapy.

Adults:-

One tablet daily. Most adult patients respond satisfactorily to one tablet daily of Atenetic 50/12.5 mg. Rarely however either two tablets of Atenetic 50/12.5 mg or one tablet of Atenetic 100/25 mg daily may be required. There is little or no further fall in blood pressure with increased dosage. If necessary, another antihypertensive drug such as a vasodilator can be added. Patients can be transferred directly from Atenetic to other anti-hypertensive treatments with the exception of clonidine.

Elderly:-

One tablet daily of Atenetic 50/12.5 mg. Dosage requirements are often lower in this age group. Older patients with hypertension who do not respond to low-dose therapy with a single agent should have a satisfactory response to a single tablet daily of Atenetic 50/12.5 mg. If hypertensive control is not achieved addition of a small dose of another agent, e.g. a vasodilator may be appropriate.

Children:-

There is no paediatric experience with Atenetic, therefore, this preparation is not recommended for children.

Renal failure:

Caution should be exercised in patients with renal failure. In patients with severe renal impairment, a reduction in the daily dose or in frequency of administration may be necessary (see Section 4.4).

Second or 3rd degree atrio-ventricular block.

Severe bradycardia.

Hypotension

Uncontrolled or digitalis/diuretic-refractory heart failure.

Cardiogenic shock.

Use in patients who have received verapamil intravenously within 48 hours.

Use in patients with a known hypersensitivity to chlortalidone or atenolol.

Use of this preparation in the presence of hypokalaemia, precoma associated with hepatic, renal or Addison's disease and in digitalis intoxication.

Severe peripheral arterial circulatory disturbances.

Metabolic acidosis.

Sick sinus syndrome.

Untreated phaeochromocytoma.

Sudden reduction in diastolic blood pressure: the initial treatment of severe malignant hypertension should be so designed as to avoid sudden reduction in diastolic blood pressure with impairment of autoregulatory mechanisms.

Sudden withdrawal of beta-adrenoceptor blocking agents in patients with ischaemic heart disease: it may result in the appearance of anginal attacks of increased frequency or severity or deterioration in cardiac states. Discontinuation of therapy should be gradual.

Congestive cardiac failure: the beta-blocker should only be used with caution in patients with controlled congestive cardiac failure. Evidence of recrudescence of this condition should be regarded as a signal to discontinue therapy.

Asthma: beta-blockers should not be given to patients with bronchospasm or asthma. However Atenetic is a cardioselective beta-blocker, consequently its use may be considered with extreme caution in patients when there is no alternative treatment. If increased airways resistance does occur, it should be discontinued and bronchodilator therapy {e.g. salbutamol} administered if necessary.

Cardiac: special care should be taken with patients whose cardiac reserve is poor. Any signs of failure of myocardial contractility should be controlled with digitalis and diuretics. The product may have a negative effect on conduction time so must be given with caution to patients with first degree heart block. Beta-adrenoceptor blocking drugs should be avoided in overt heart failure. However, they may be used in patients whose signs of failure have been controlled.

Obstructive airways disease: Atenetic may cause an increase in airways resistance. It can be administered with caution to patients with obstructive respiratory disorders provided that adequate supervision is maintained. If increased airways resistance develops, consideration must be given to discontinuation of the drug, depending on the degree of airways resistance and the benefit derived from beta-blockade.

Renal impairment: when this agent is administered to patients in renal failure, the interval between doses may need to be increased or the dosage reduced to avoid accumulation of the drug.

Thyrotoxicosis and hypoglycaemia: the beta-blocker may mask some of the symptoms of thyrotoxicosis and of hypoglycaemia by inhibition of the sympathetic nerve functions. The effects of hypoglycaemic agents may be increased particularly by the non-cardioselective beta-blockers. The tachycardia of hypoglycaemia may be modified.

Anaesthesia: in the event that a patient receiving the beta-blocker requires anaesthesia the anaesthetist should be informed of the use of medication prior to the use of a general anaesthetic to permit his taking the necessary precautions. It is not advisable to withdraw beta-adrenoceptor blocking drugs prior to surgery in the majority of patients. However, care should be taken when using anaesthetic agents such as ether, cyclopropane, and trichloroethylene. Vagal dominance, if it occurs, may be corrected with atropine (1-2 mg iv).

Potassium status: due to its chlortalidone component hypokalaemia may occur. Regular supervision and measurement of potassium level is appropriate, especially in the older patient, those receiving digitalis preparation for cardiac failure, those taking an abnormal (low in potassium) diet or those suffering from gastrointestinal complaints. Hypokalaemia may predispose to arrhythmias in patients receiving digitalis.

Metabolic effect: the metabolic effects of chlortalidone are dose related and, at the low dose contained in the Atenetic tablets, are unlikely to be troublesome. Atenetic has been associated with only minor changes in potassium status. Total body potassium is unaltered on chronic therapy, and changes in serum potassium are minor and probably clinically unimportant. Thus, in cases of uncomplicated hypertension, concurrent potassium supplements should be unnecessary.

Diabetes: care is required when Atenetic is administered to patients with a known disposition to diabetes.

Pulse rate: beta-adrenoreceptor blocking drugs cause a reduction in heart rate. If any symptoms are observed which are attributable to this the dosage may be reduced.

Serum uric acid: the tablets cause only minor increases in the serum uric acid. However, if there is prolonged elevation of the level of uric acid, the use of a uricosuric agent will reduce the hyperuricaemia.

Prinzmetal angina: Atenolol may increase the number and duration of angina attacks in patients with Prinzmetal angina.

Peripheral circulatory disorders: less severe peripheral circulatory disorders may be aggravated by the product.

Allergens: the tablets may cause a more severe reaction to various allergens when given to patients with a history of anaphylactic reaction to suck allergens.

Psoriasis: patients with known psoriasis should take beta-blockers only after careful consideration.

The beta-blocker should only be used with great caution in patients who are receiving concomitant myocardial depressants such as halogenated anaesthetics; class I anti-arrhythmics such as disopyramide, quinidine, procainamide, lignocaine or beta-adrenoceptor stimulants such as noradrenaline or adrenaline.

Adrenergic-neurone blocking agents such as guanethidine, reserpine, diuretics and other antihypertensive agents, including the vasodilator group, will have an additive effect on the hypotensive action of the drug.

Care should be observed in patients using beta-blockers with calcium channel blockers with negative inotropic effects e.g. verapamil and diltiazem in patients with impaired ventricular function and this combination should not be given to patients with 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.

Adjustment of dosage of hypoglycaemic agents may be necessary if given with uncontrolled or 'brittle' diabetes mellitus. Beta-blockers may enhance hypoglycaemic effects of anti-diabetic agents and mask the warning signs of hypoglycaemia such as tremor and tachycardia.

The concomitant administration of this preparation with the cardiac glycosides, or non-depolarising muscle relaxants may necessitate adjustment of the dosage of those drugs. Co-administration of beta-blockers with digital glycosides may cause an increase in atrio-ventricular conduction time.

Like other beta-blockers atenolol, a constituent of Atenetic, can cause rebound hypertension following clonidine withdrawal. If Atenetic and clonidine are given concurrently, the clonidine should not be discontinued until several days after Atenetic withdrawal. If replacing clonidine by beta-blocker therapy, the introduction of beta-blockers should be delayed for several days after clonidine administration has stopped.

Diuretics generally reduce renal clearance of lithium, therefore concurrent therapy is not recommended.

Co-administration of beta-blockers with a dihydropyridine e.g. nifedipine, may increase the risk of hypotension and heart failure may occur in those with latent cardiac insufficiency.

Sympathomimetics e.g. adrenaline may counteract the effects of beta-blocking drugs.

Enzyme inhibitors (e.g. cimetidine) may increase plasma concentrations of the combination.

Alcohol potentiates the action of the product.

Co-administration of the tablets with hydralazine may increase the effect of the product.

Co-administration of prostaglandin synthetase inhibiting drugs e.g. ibuprofen and indomethacin with beta-blockers may decrease the hypotensive effects of the beta-blocker.

The anaesthetist should be informed and the choice of anaesthetic should be an agent with as little negative inotropic activity as possible. Use of beta-blockers with anaesthetic drugs may result in attenuation of the reflex tachycardia and increase the risk of hypotension. Anaesthetic agents causing myocardial depression are best avoided.

The tablets should not be given during pregnancy and when breastfeeding, unless the potential benefits outweigh the risks. Many beta-blockers cross the placenta and administration of beta-blockers to pregnant women shortly before delivery has occasionally resulted in bradycardia and other adverse effects such as hypoglycaemia and hypotension in the neonate.

If a patient experiences dizziness and fatigue while taking Atenetic, they should not drive or operate machinery.

Atenetic Film-coated Tablets are well tolerated. In clinical studies, the undesired events reported are usually attributable to the pharmacologic actions of its component. The following undesired events, listed by body system, have been reported with Atenetic Film-coated Tablets or either of its components:

Discontinuance of Atenetic Film-coated Tablets should be considered if, according to clinical judgement, the wellbeing of the patient is adversely affected by any of the above reactions.

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 prenalterol 5 mg intravenously, followed if necessary by an intravenous infusion of 5 mg/hour or 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, although larger doses may be required.

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 agents, prenalterol and dobutamine. Excessive diuresis may be countered by maintaining normal fluid and electrolyte balance.

Beta-blocking agents, selective and other diuretics

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Atenetic combines the antihypertensive activity of two agents: atenolol and chlortalidone.

Atenolol is a hydrophilic beta-blocker with general properties similar to those of propranolol. Atenolol is classified as cardioselective and is reported to lack intrinsic sympathomimetic activity and membrane stabilising properties.

Chlortalidone is a diuretic which has certain structural similarities to the thiazides and has action as and uses similar to those of chlorothiazide. Diuresis is initiated in about 2 hours and lasts for 46 hours or longer. Its inhibitory action on carbonic anhydrases is only weak.

Atenolol appears to be incompletely absorbed from the gastrointestinal tract and is not significantly metabolised. It is excreted in the urine and its biological half life is not longer than would be anticipated from its plasma half live of about 6-7 hours. Atenolol diffuses across the placenta and is excreted in breast milk. Only small amounts are reported to cross the blood-brain barrier, and it is only about 5% bound to plasma proteins.

Chlortalidone is erratically absorbed from the gastrointestinal tract. Its prolonged terminal half-life of 35 to 54 hours has been reported to be due to its strong binding to red blood cells. During long-term administration 30 to 60% has been reported to be excreted unchanged in urine. It crosses the placental barrier and is excreted unchanged in breast milk.

No significant teratologic and carcinogenic effects have been demonstrated in animal models.

Magnesium carbonate (heavy), Sodium laurilsulfate, Povidone K29/32, Pregelatinised starch, Maize starch, Stearic acid, Magnesium stearate, Sodium starch glycolate (Type A), Hypromellose, Macrogol 400, Titanium dioxide (E171), Talc.

Not applicable.

5 Years.

Do not store above 25°C.

PVC/aluminium foil blister packs of 28 and 98.

Not all pack sizes may be marketed.

No special requirements.

Generics (UK) Limited, Station Close, Potters Bar, Hertfordshire, EN6 1TL, England

PA 405/31/1-2

21^st May 1991 / 21^st May 2006

September 2006