SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Viskaldix Tablets

Pindolol/Clopamide 10mg/5mg Tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 10mg pindolol and 5mg clopamide.

3    PHARMACEUTICAL FORM

Tablet.

White, uncoated, round, flat, bevelled tablets, marked VISKALDIX on one side and with a score line on the other.

The score line is only to facilitate breaking for ease of swallowing and not to divide into equal doses.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Mild to moderate hypertension.

4.2 Posology and method of administration

One tablet daily in the morning. If blood pressure is not satisfactorily lowered after 2 to 3 weeks then two tablets daily as a single dose in the morning. Maximum dose of three tablets daily, if required.

Children

There is no experience with this medicine in children.

Use in the elderly

There is no evidence that the dosage or tolerability of this medicine is directly affected by advanced age. However, because of the diuretic component, such patients should be carefully supervised as factors sometimes associated with aging, such as poor diet or impaired renal function may indirectly affect the dosage or tolerability.

Method of administration Oral.

4.3    Contraindications

Untreated cardiac failure, sick sinus syndrome (including sino-atrial block), second and third degree heart block, Prinzmetal's angina, history of bronchospasm and bronchial asthma (a warning stating "do not take this medicine if you have a history of wheezing or asthma" will appear on the label), untreated phaeochromocytoma, metabolic acidosis, pronounced bradycardia, obstructive pulmonary disease, cor pulmonale, prolonged fasting hypokalaemia, refractory hypokalaemia, hyponatraemia, hypercalcaemia, Addison's disease, severe renal or hepatic impairment and symptomatic hyperuricaemia. This medicine should not be used with agents which inhibit calcium transport e.g. verapamil.

4.4    Special warnings and precautions for use

Especially in patients with ischaemic heart disease, treatment should not be discontinued suddenly. The dosage should be gradually reduced, i.e. over 1-2 weeks, if necessary at the same time initiating replacement therapy, to prevent exacerbation of angina pectoris.

Patients with a poor cardiac reserve should be stabilised with digitalis before treatment with this medicine to prevent impairment of myocardial contractility.

As with all beta-blockers, this medicine should be used with caution in patients with a history of non-asthmatic chronic obstructive lung disease or recent myocardial infarction.

Patients with spontaneous hypoglycaemia or diabetes should be monitored closely as concomitant use of beta-blockers may intensify the blood sugar lowering effect of insulin and other antidiabetic drugs and also as thiazide diuretics can lower insulin tolerance. Use of beta-blockers may mask the symptoms of hypoglycaemia (tachycardia, tremor). Beta blockers may also mask the symptoms of thyrotoxicosis.

During treatment with this medicine, patients should not undergo anaesthesia with agents causing myocardial depression (e.g. halothane, cyclopropane, trichloroethylene, ether, chloroform). This medicine should be gradually withdrawn before elective surgery. In emergency surgery or cases where withdrawal of this medicine would cause deterioration in cardiac condition, atropine sulphate 1 to 2mg intravenously should be given to prevent severe bradycardia.

If a beta-blocker is indicated in a patient with phaeochromocytoma it must always be given in conjunction with an alpha-blocker. Pre-existing peripheral vascular disorders may be aggravated by beta-blockers. Patients with known psoriasis should take beta-blockers only after careful consideration.

Beta-blockers may increase both the sensitivity towards allergens and the seriousness of anaphylactic reactions.

There have been reports of skin rashes and/or dry eyes associated with the use of beta-adrenoceptor 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. Cessation of therapy with a beta-blocker should be gradual.

In severe renal failure a further impairment of renal function following beta blockade has been reported in a few cases. Potassium levels should be checked in patients with renal or hepatic failure and urate levels should be checked in patients with gout.

Dilutional hyponatraemia may occur in hot weather in oedematous patients on this medicine.

The appropriate therapy is water restriction rather than the administration of salt, except in rare instances when the hyponatraemia is life-threatening. In true salt depletion, appropriate replacement is the treatment of choice.

4.5 Interaction with other medicinal products and other forms of interaction

This medicine should not be used during concomitant administration of lithium, or by patients with known hypersensitivity to sulphonamides.

Calcium-channel blocking agents: This medicine should not be used with calcium-channel blockers with negative inotropic effects e.g. verapamil and to a lesser extent diltiazem. The concomitant use of oral beta-blockers and calcium antagonists of the dihydropyridine type can be useful in hypertension or angina pectoris. However, because of their potential effect on the cardiac conduction system and contractility, the i.v. route must be avoided. The concomitant use with dihydropyridines e.g. nifedipine may increase the risk of hypotension. In patients with cardiac insufficiency, treatment with beta-blocking agents may lead to cardiac failure.

Use of digitalis glycosides in association with beta-blockers may increase atrioventricular conduction time.

Clonidine: when therapy is discontinued in patients receiving a beta-blocker and clonidine concurrently, the beta-blockers should be gradually discontinued several days before clonidine is discontinued, in order to reduce the potential risk of a clonidine withdrawal hypertensive crisis.

MAO inhibitors: concurrent use with beta-blockers is not recommended. Possibly significant hypertension may theoretically occur up to 14 days following discontinuation of the MAO inhibitor.

Caution should be exercised in the concurrent use of beta-blocking agents with class 1 antiarrhythmics (e.g. disopyramide, quinidine) and amiodarone.

Concomitant use of beta-blockers may intensify the blood sugar lowering effect of insulin and other antidiabetic drugs.

Cimetidine, hydralazine and alcohol may induce increased plasma level of beta-blockers.

Prostaglandin synthetase inhibiting drugs may decrease the hypotensive effects of beta-blockers

Sympathomimetics with beta-adrenergic stimulant activity and xanthines: concurrent use with beta-blockers may result in mutual inhibition of therapeutic effects; in addition, beta-blockers may decrease theophylline clearance.

Concomitant use of beta-blockers with tricyclic antidepressants, barbiturates and phenothiazines as well as other anti-hypertensive agents may increase the blood pressure lowering effect.

Reserpine: concurrent use may result in an additive and possibly excessive beta-adrenergic blockade.

4.6    Fertility, pregnancy and lactation

This medicine should not be given to pregnant or lactating women.

4.7    Effects on ability to drive and use machines

Because dizziness or fatigue may occur during initiation of treatment with antihypertensive drugs, patients driving vehicles or operating machinery should exercise caution until their individual reaction to treatment has been determined.

4.8 Undesirable effects

Side-effects associated with beta-blockade: bradycardia, a slowed av-conduction or increase of an existing av-block, hypotension, heart failure, cold and cyanotic extremities, Raynaud's phenomenon, paraesthesia of the extremities, increase of an existing intermittent claudication, fatigue, headaches, impaired vision, hallucinations, psychoses, confusion, impotence, dizziness, sleep disturbances, depression, nightmares. Gastro-intestinal problems, nausea, vomiting, diarrhoea. Bronchospasm in patients with bronchial asthma or a history of asthmatic complaints. Disorder of the skin, especially rash. Dry eyes. Beta-blockers may mask the symptoms of thyrotoxicosis or hypoglycaemia. An increase in ANA (anti-nuclear antibodies) has been seen; its clinical relevance is not clear.

Thiazide diuretics may cause postural hypotension and mild gastrointestinal effects; impotence (reversible on withdrawal of treatment); hypokalaemia, hypomagnesaemia, hyponatraemia, hypercalcaemia, hypochloraemic alkalosis, hyperuricaemia, gout, hyperglycaemia, and increases in plasma cholesterol. Less commonly rashes, photosensitivity; blood disorders (including neutropenia and thrombocytopenia), pancreatitis; intrahepatic cholestatis and hypersensitivity reactions (including pneumonitis, pulmonary oedema, severe skin reactions) have also been reported.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

4.9 Overdose

Overdosage may cause alterations in heart rate, nausea, vomiting, orthostatic disturbances, collapse, hypokalaemia and its accompanying disorders. Treatment by elimination of any unabsorbed drug and general supportive measures.

Plasma electrolytes should be closely monitored. Marked bradycardia, as a result of overdosage (or idiosyncrasy) should be treated with atropine sulphate 1-2mg iv.

If necessary isoprenaline hydrochloride can be administered by slow iv under constant supervision beginning with 25mcg (5mcg/min) until desired effect is achieved. A cardiac pacemaker may be required. i.v glucagon (5 to 10mg) has been reported to overcome some of the features of serious overdosage.

5    PHARMACOLOGICAL PROPERTIES

5.1    Pharmacodynamic properties

This medicine is a combination of pindolol and clopamide, both acting to lower blood pressure, although by two separate mechanisms.

Pindolol is a non-selective beta-adrenergic antagonist which blocks both B1 and B2 adrenoceptors for more than 24 hours following administration. It has negligible membrane stabilising activity. The intrinsic sympathomimetic activity (ISA) provides the heart with basal stimulation similar to that elicited by normal resting sympathetic activity. Thus, resting cardiac output and heart rate are not unduly depressed, subsequently reducing the risk of bradycardia.

Clopamide enhances the elimination of sodium and chloride by inhibiting their reabsorption in the renal tubules which, in turn, leads to increased water excretion.

The mechanistic relationship to the diuretic action and reduced blood pressure is not fully understood, however the diuretic effect is proportional to the dosage. Diuresis is initiated after about 2 hours and can last for up to 24 hours with maximal effect after 3 to 6 hours.

This combination can produce a clear antihypertensive effect after a few days, but, in some cases, to achieve the full effect, two to three weeks treatment may be necessary.

5.2 Pharmacokinetic properties

The pharmacokinetics of the two active ingredients are very similar and are not influenced by their combination or by being taken with food. Both components are rapidly and almost completely absorbed. They show negligible hepatic first-pass metabolism. Thus the bioavailability of both is at least 85%. The maximum plasma concentration of pindolol is reached within one hour after ingestion, and that of clopamide, one or two hours after ingestion. Plasma protein binding is 40% for pindolol, and 46% for clopamide. The volume of distribution is about 2L/Kg for pindolol, and 1.5L/Kg for clopamide. The total body clearance of pindolol is 400ml/min, that of clopamide is 165ml/min. The elimination half-life is 3-4 hours for pindolol, and 6 hours for clopamide. Approximately one third of the dose of both drugs is excreted unchanged in the urine. The excretion of clopamide occurs mainly via the kidneys, whereas pindolol shows a balanced excretion between the renal and hepatic routes.

5.3 Preclinical safety data

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

6 PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Magnesium stearate, maize starch and lactose.

6.2    Incompatibilities

None

6.3    Shelf life

5 years from date of manufacture.

6.4    Special precautions for storage

None

6.5 Nature and contents of container

PVC/PVDC clear blister packs in a cardboard carton containing 28 tablets.

6.6 Special precautions for disposal

None

7    MARKETING AUTHORISATION HOLDER

Amdipharm UK Limited

Regency House

Miles Gray Road

Basildon

Essex

SS14 3AF

United Kingdom.

8    MARKETING AUTHORISATION NUMBER(S)

PL 20072/0021

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

01/01/2005

10 DATE OF REVISION OF THE TEXT

29/01/2014