SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Co-tenidone 50/12.5 mg Film-coated Tablets BP

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains

Atenolol 50 mg

Chlortalidone 12.5 mg

For full list of excipients, see section 6.1

3 PHARMACEUTICAL FORM

Film-coated tablet

Co-tenidone 50/12.5 mg Film-coated Tablets are brownish pink, round, biconvex film-coated tablets marked CT/50 on one side and plain on the other.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Management of hypertension.

4.2 Posology and method of administration

Oral administration.

Adults:

One tablet daily containing 50 mg atenolol and 12.5 mg chlortalidone.

Elderly:

One tablet daily.

Children:

There is no experience of using Co-tenidone in children. Therefore it is not recommended.

Renal impairment:

In patients with renal impairment, a reduction in daily dose or infrequency of administration may be necessary.

4.3 Contraindications

Co-tenidone should not be used in patients with known hypersensitivity to atenolol or chlortalidone. Like other beta-blocker-diuretic combinations, Co-tenidone should not be used in patients with second or third degree heart block, cardiogenic shock or severe peripheral circulatory disturbances. It should not be used in patients with severe renal or hepatic failure; sick sinus syndrome (including sino-atrial block); untreated phaeochromocytoma; metabolic acidosis;bradycardia (<45-50 bpm); hypotension.

Although cardioselective beta-blockers may have less effect on lung function than non-selective beta-blockers, they should be avoided in patients with reversible obstructive airways disease unless there are compelling reasons for their use.

4.4 Special warnings and precautions for use

Care should be taken when using beta-blockers in patients with poor cardiac reserve. Atenolol should be avoided in overt heart failure but may be used in patients whose signs of failure have been adequately controlled.

Atenolol reduces heart rate. In instances when symptoms may be attributable to the slow heart rate, the dose should be reduced. In patients suffering from ischaemic heart disease, treatment should not be discontinued abruptly.

If the use of Co-tenidone in patients with asthma or a history of obstructive airways disease is unavoidable, the risk of inducing bronchospasm should be appreciated and appropriate precautions taken. If bronchospasm occurs, this can usually be reversed by administration of commonly used bronchodilators such as salbutamol or isoprenaline.

Atenolol modifies the tachycardia of hypoglycaemia. Chlortalidone may decrease glucose tolerance in diabetes. During prolonged therapy, regular tests for glycosuria should be carried out.

All patients treated with diuretics should have their fluid and electrolyte status monitored, especially the elderly, patients with potassium-depleting gastrointestinal disturbances, on low potassium diets or taking cardiac glycosides. Hypokalaemia or hypomagnesaemia may occur.

Co-tenidone should be used with caution in patients with a predisposition to uricaemia or gout since chlortalidone may cause a rise in serum uric acid levels. Prolonged elevation can be corrected by the use of a uricosuric agent.

The product label will state 'Do not take this medicine if you have a history of wheezing or asthma'.

In patients with peripheral circulatory disorders (Raynaud’s disease or syndrome, intermittent claudication), Co-tenidone should be used with great caution as aggravation of these disorders may occur.

Due to the negative effect on conduction time by atenolol, Co-tenidone should only be given with caution to patients with first degree heart block.

Atenolol may mask the symptoms of thyrotoxicosis.

Beta-blockers may increase the number and the duration of anginal attacks in patients with Prinzmetal’s angina due to unopposed alpha-receptor mediated coronary artery vasoconstriction. As atenolol is a beta-1-slective blocker the use of Co-tenidone may be considered in such patients but only used with utmost care.

Patients with anamnestically known psoriasis should take atenolol only after careful consideration.

Atenolol may increase both the sensitivity toward allergens and the seriousness of anaphylactic reactions.

4.5 Interaction with other medicinal products and other forms of interaction

In general, beta-adrenoceptor-blocking agents should not be given concomitantly with adrenaline, amphetamines, sympathomimetic amines, ergotamine, local anaesthetic-type anti-arrhythmic agents, clonidine and calcium channel blocking agents such as nifedipine and verapamil. Reduced absorption may occur if calcium or aluminium hydroxide is administered concurrently. Calcium antagonists eg verapamil in combination with atenolol have a negative influence on contractility and atrioventricular conduction.

Co-administration of beta-blockers with digitalis glycosides may cause an increase in atrio-ventricular conduction time.

Care should be exercised in prescribing a beta blocking drug together with class 1 anti-arrhythmic drugs (i.e. local anaesthetic-type anti-arrhythmics) (eg disopyramide) and amiodarone due to a potentiating effect in atrial-conduction time and induction of a negative inotropic effect.

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.

Beta-blockers may enhance the effects of anti-diabetic agents and mask the warning signs of hypoglycaemia such as tremor and tachycardia.

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

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

Like other thiazide diuretics, chlortalidone may potentiate bone marrow suppression caused by cancer chemotherapy and may impair the control of diabetes mellitus by diet and oral hypoglycaemic agents. Hypokalaemia may precipitate digitalis toxicity. Lithium should not be administered concurrently because lithium clearance may be significantly reduced causing lithium toxicity. Aminoglycoside nephrotoxicity may be potentiated. Concurrent administration of indomethacin can reduce the hypotensive effects of both atenolol and chlortalidone.

Care should be taken when using anaesthetic agents with Co-tenidone; hypokalaemia can prolong the effects of tubocurarine. Also the choice of anaesthetic should be an agent with as little negative inotropic activity as possible.

4.6 Fertility, pregnancy and lactation

Both atenolol and chlortalidone cross the placenta and enter the breast milk. Co-tenidone should not be used in pregnant or lactating women.

4.7 Effects on ability to drive and use machines

The use of Co-tenidone is unlikely to result in any impairment of the ability to drive or operate machinery as there are only rare reports of beta-adrenoceptor blocking drugs causing symptomatic hypotension and bradycardia.

Undesirable effects

Side-effects reported include cold extremities, isolated cases of bradycardia and muscular fatigue, sleep disturbances of the type reported with other beta- blockers have rarely been reported. There have been reports of skin rashes and/or dry eyes associated with the use of beta-adrenergic blocking drugs. Withdrawal of the drug should be considered if any such reaction is not otherwise explicable. Discontinuation of therapy with a beta-blocker should be gradual.

Chlortalidone is associated with occasional reports of gastrointestinal disturbances and slight dizziness; there are rare reports of neutropenia, thrombocytopenia and hyponatraemia.

4.9 Overdose

Symptoms: extreme bradycardia and hypotension with nausea, weakness, dizziness and disturbances of electrolyte balance.

Excessive bradycardia may be countered by atropine 1-2 mg intravenously followed if necessary 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-adrenoceptor 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.

Any risk of hypotension occurring following the use of beta adrenoceptor agonists will be reduced by the use of the more selective agent, dobutamine.

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

Pharmacodynamic properties

Pharmacotherapeutic Group: Atenolol and other diuretics -ATC Code: C07CB03.

Atenolol is a cardiovascular beta-adrenoceptor antagonist with no membrane stabilising activity and no partial agonist activity.

Chlortalidone is a long-acting thiazide-like diuretic.

5.2 Pharmacokinetic properties

Atenolol: After an oral dose about 50% is absorbed. Peak serum concentration occurs 2-4 hours after administration. Atenolol is poorly protein bound. Plasma half life is 68 hours but can rise to 140 hours in severe renal impairment. There is no liver metabolism. 90% of absorbed drug is excreted unchanged in the urine. The remainder is metabolised either by hydroxylation or by conjugation with glucuronic acid or is excreted in the bile.

Atenolol crosses the placenta and enters the breast milk.

Chlortalidone: After an oral dose about 65% is absorbed. Peak serum levels are reached 2-6 hours after administration. Most of the absorbed dose (98%) is bound to red cell carbonic anhydrase. The plasma half life is 50-90 hours during long term treatment 30-60% of the dose is excreted unchanged in the urine and up to 10% is excreted in the faeces. No metabolites have been identified.

5.3 Preclinical safety data

There are no pre-clinical data of relevance to the prescriber, which are additional to those already included in other sections of the SmPC.

PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Tablet core:

Maize starch

Calcium hydrogen phosphate dihydrate Microcrystalline cellulose Povidone K30

Sodium starch glycolate Type A Magnesium stearate

Film Coat:

Hypromellose (E464)

Titanium dioxide (E171)

Iron oxide red (E172)

Macrogol

Iron oxide yellow (E172)

Iron oxide black (E172)

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

36 months

6.4 Special precautions for storage

Do not store above 25°C.

Store in the original package to protect from light and moisture.

6.5 Nature and contents of container

Blister packs of white opaque PVC film and hard tempered aluminium foil. Pack sizes: 28, 30, 56, 60.

6.6 Special precautions for disposal

None stated.

7 MARKETING AUTHORISATION HOLDER

Activase Pharmaceuticals Limited,

11 Boumpoulinas, 3^rd Floor,

PC. 1060 Nicosia.

Cyprus

8    MARKETING AUTHORISATION NUMBER(S)

PL 28444/0101

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION 10/04/2014

10 DATE OF REVISION OF THE TEXT

10/04/2014