Meda Health Sales

Prestim 10mg/2. 5 mg Tablets

For a full list of excipients, see section 6.1

Tablet.

White, flat, oval shaped tablets with a single score line on one face and engraved on the other side with "V PRE".

Prestim tablets are indicated for the treatment of mild to moderate hypertension.

Prestim tablets are for oral administration.

Initiate treatment with 1 tablet daily and thereafter adjust according to response.

The recommended dosage range is from one to two tablets daily. The initial dose will be one tablet daily, increasing, where necessary after two weeks to a maximum of two tablets daily. Most patients are maintained on one or two tablets, taken as a single dose in the morning or as divided doses morning and evening.

If blood pressure control is not achieved on two tablets daily, consideration should be given to titrating timolol and bendroflumethiazide separately or adding another hypotensive agent.

Special populations

Elderly:

There are no special dosing recommendations.

Patients with hepatic I renal impairment:

When Prestim is administered to patients with hepatic or renal impairment, the dosage may require adjustment (see section 4.4, Special warnings and precautions for use).

Children:

There is no experience in children.

o Hypersensitivity to the active substances or to any of the excipients in Prestim Tablets

o History of bronchospasm, bronchial asthma, chronic obstructive pulmonary disease

o Anuria

o Renal failure

o Addison's disease

o Cardiogenic shock

o Second and third degree atrioventricular block

o Marked bradycardia

o Uncontrolled heart failure. Use in patients who have received verapamil intravenously within 48 hours

o Concurrent use with lithium salts (see section 4.5, Interaction with other medicinal products and other forms of interaction)

o Sick sinus syndrome (including sino-atrial block)

o Prinzmetal 's angina

o Severe peripheral arterial disease

o Untreated phaeochromocytoma

o Hypotension

o Metabolic acidosis

o Anaesthesia with agents that produce myocardial depression such as chloroform and ether

o Hypokalaemia

o Use in the presence of digitalis intoxication

Cardiac failure

The continued depression of sympathetic drive through beta-blockade may lead to cardiac failure. All patients should be observed for evidence of cardiac failure.

Bradycardia

If marked bradycardia develops, Prestim should be discontinued.

Treatment discontinuation in patients with ischaemic heart disease

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

Fluid and electrolyte disturbances

Prestim should be used with caution in patients with fluid and electrolyte disturbances.

Patients who are being treated with Prestim require regular supervision with monitoring of fluid balance and electrolyte state to avoid-electrolyte disturbance, particularly hypokalaemia or excessive loss of fluid.

Elderly and patients with impaired hepatic or renal function

Prestim should be used with caution in elderly patients and in those with impaired hepatic or renal function (see section 4.2, Posology and method of administration).

Metabolism

Beta-blockers may mask the symptoms of thyrotoxicosis and hypoglycaemia.

Caution should be exercised in patients with diabetes mellitus, or spontaneous hypoglycaemia. In these patients the dose ofhypoglycaemic agent may need adjustment.

Skin rashes/ocular disturbances

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

Patients with a history of psoriasis should take beta-blockers only after careful consideration.

Concomitant medications

Caution should be exercised with patients on myocardial depressants, anti-arrhythmic agents, and a or -adrenoceptor stimulant such as monoamine oxidase inhibitors and tricyclic antidepressants.

If Prestim and clonidine are given concurrently, clonidine should not be discontinued until several days after the withdrawal of Prestim.

In the event of a patient receiving Prestim requiring anaesthesia the anaesthetist should be informed of the use of the medication prior to the use of a general anaesthetic.

Lithium

As with other diuretics, Prestim should not be administered concurrently with lithium salts. Diuretics can reduce lithium clearance resulting in high serum levels of lithium.

Antiarrhythmic agents

The depressant effect of beta-blocking drugs on myocardial contractility and on intracardiac conduction may be increased by concomitant use with other drugs having similar effects. Serious effects have been reported with verapamil, disopyramide, lignocaine and tocainide and may be anticipated with diltiazem, quinidine, amiodarone and any of the class 1 antiarrhythmic agents. Special care is necessary when any of these agents are given intravenously in patients who are receiving beta-blockers.

Concurrent administration of digitalis glycosides may increase the atrio-ventricular conduction time.

Antihypertensive agents

Concomitant administration of antihypertensive agents including vasodilators such as dihydropyridine derivatives (e.g. nifedipine) or catecholamine depleting drugs (e.g. reserpine and guanethidine) may increase the blood pressure lowering effect of Prestim.

Antidepressants

Concomitant administration ofadrenergenic drugs (e.g. tricyclic antidepressants, monoamine oxidase inhibitors), barbiturates and phenothiazines may increase the blood pressure lowering effect of Prestim.

Antidiabetic medicines

Beta-blockers may intensify the blood sugar lowering effect of insulin and oral antidiabetic drugs.

Anaesthesia

Anaesthetic agents causing myocardial depression such as ether, cyclopropane and trichloroethylene should not be used in patients receiving beta-blockers.

Local anaesthetics with added vasoconstrictors, e.g. adrenaline, should be avoided.

Prostaglandin synthetase inhibiting medicines

Some prostaglandin synthetase inhibiting medicines have been shown to impair the antihypertensive effect of beta-blocking drugs.

Sympathomimetic agents

The effect of sympathomimetic agents, e.g. isoprenaline, salbutamol, will be reduced by concomitant use of beta blockers. In addition, sympathomimetics may counteract the effect of beta-blocking agents.

Other

The bioavailability of beta-blockers will be increased by co-administration with cimetidine or hydralazine and reduced with rifampicin.

Prestim should not be given during pregnancy or lactation unless it is considered essential by the physician

Beta-blockers reduce placental perfusion, which may result in intrauterine foetal death, intrauterine growth retardation and premature deliveries, particularly if used in the first trimester. However these data are not conclusive. In addition, adverse effects (especially hypoglycaemia and bradycardia) may occur in foetus and neonate. Data specifically on timolol during pregnancy are not available.

Lactation

Both constituents cross the placenta and appear in breast milk therefore breast-feeding is not recommended. There have been reports of neonatal jaundice, thrombocytopenia, and electrolyte imbalances following feeding with milk from mothers on treatment with thiazides.

Prestim has no known influence on the ability to drive or operate machines. When driving vehicles or operating machines it should be taken into account that occasionally dizziness or fatigue may occur (see section 4.8, Undesirable effects).

Adverse drug reactions that have been observed with Prestim tablets

Metabolism and nutrition disorders: hyperuricaemia. Gout may be precipitated by thiazide-associated hyperuricaemia.

Psychiatric disorders: insomnia, depression.

Nervous system disorders: dizziness

Eye disorders: visual disturbance such as blurred vision, dry eye

Cardiac disorders: bradycardia

Vascular disorders: hypotension

Respiratory, thoracic and mediastinal disorders: dyspnoea, bronchospasm

Gastrointestional disorders: Gastrointestinal disorders such as acute pancreatitis, vomiting, diarrhoea and nausea.

Skin and subcutaneous tissue disorders: rash

Musculoskeletal, connective tissue and bone disorders: myalgia

Renal and urinary disorders: oliguria

General disorders and administration site conditions: asthenia, fatigue, thirst, peripheral coldness

Investigations: increased blood urea

Adverse drug reactions that have been associated with the use of other thiazide diuretics or beta-blockers and may be observed with Prestim tablets:

Blood and lymphatic system disorders: blood disorders such as blood dyscrasias

Metabolism and nutrition disorders: electrolyte (potassium) depletion and dehydration, hyperglycaemia (in diabetic and other susceptible patients)

Nervous system disorders: coma (may be precipitated in hepatic cirrhosis)

Cardiac disorders: worsening cardiac failure, atrioventricular block

Vascular disorders: necrotising vasculitis

Skin and subcutaneous tissue disorders: photosensitivity reaction

Renal and urinary disorders: glycosuria (in diabetic and other susceptible patients)

The most common signs of overdosage are bradycardia, hypotension, bronchospasm and acute cardiac failure.

Suggested treatments are as follows:

General methods should be taken to restore blood volume, maintain blood pressure and correct electrolyte imbalance.

Pharmacotherapeutic group: timolol and thiazides, ATC code: C07BA06

Timolol maleate is a non-selective -adrenoceptor antagonist with marked hypotensive activity. Bendroflumethiazide is a thiazide diuretic which has a moderate duration of activity. It has been shown that beta-blocking agents used in combination with a thiazide diuretic, potentiates the effects of this diuretic giving an enhanced antihypertensive effect. This may be due to the inhibition of renin release or concomitant regional haemodynamic changes.

Timolol maleate is well absorbed, extensively metabolised in the liver and eliminated through the kidney with a half- life of 2.5 to 5 hours (the biological half-life is somewhat longer). The beta-blocking effect of timolol is apparent within 30 minutes of administration and has been shown to last for up to 24 hours. It has low to moderate lipid solubility. Protein binding is reported to be low. It crosses the placenta and appears in breast milk.

Bendroflumethiazide has been reported to be completely absorbed from the gastro-intestinal tract and to have a plasma half-life of about 3 or 4 hours. It is highly bound to plasma protein. There is evidence that bendroflumethiazide is fairly extensively metabolised; about 30% is excreted unchanged in the urine. The diuretic effect of bendroflumethiazide is usually complete in 12-18 hours.

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

Microcrystalline cellulose

Maize starch

Magnesium stearate

Not applicable.

3 years.

Do not store above 25°C.

Amber glass bottles of 30 tablets and 100 tablets.

Not all pack sizes may be marketed.

No special requirements.

Meda Health Sales Ireland Limited

Unit 34/35, Block A,

Dunboyne Business Park

Dunboyne, Co Meath,

Ireland

PA1332/36/1

Date of first authorisation: 09 February 1997

Date of last renewal: 09 February 2007

February 2011