SUMMARY OF PRODUCT CHARACTERISTICS

1.    NAME OF THE MEDICINAL PRODUCT

Neo-Naclex-K 2.5mg/630mg Tablets

2.    QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 2.5mg Bendroflumethiazide in the white layer and 630mg Potassium chloride in the pink layer, providing 330mg elemental potassium (8.4 mEq).

3. PHARMACEUTICAL FORM

Film coated, two-layered white and pink tablet.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Essential hypertension

The mechanism whereby the thiazides exert their antihypertensive effect has not been clearly established. In non-oedematous patients there may be little noticeable diuretic effect. Neo-Naclex-K may be used as the sole antihypertensive agent, or as an adjunct to other anti-hypertensive drugs whose action may be enhanced.

Oedema.

Neo-Naclex-K inhibits the renal tubular absorption of salt and water by its action at the beginning of the distal convoluted tubule. Sodium and chloride ions are excreted in equivalent proportions. Because potassium excretion is promoted, metabolic alkalosis may occur secondary to hypokalaemia. There is no important effect upon carbonic anhydrase. Neo-Naclex-K causes a steady diuresis lasting about 12 hours. It is indicated in the treatment of oedema associated with conditions such as congestive heart failure, nephrotic syndrome and cirrhosis of the liver.

4.2 Posology and method of administration

Neo-Naclex-K tablets should be swallowed whole with water.

Adults:

When Neo-Naclex-K is added to other antihypertensive drugs, the dosage of the latter can usually be reduced as the Neo-Naclex-K takes effect.

Essential hypertension

1    tablet once daily, alone or in conjunction with other anti-hypertensive agents.

Oedema:

2    tablets once daily in the morning usually produce the desired effect without diuresis interfering with sleep. The dose can be increased to 4 tablets, if required. During the first few days of treatment, there is usually a large increase in urinary volume, which diminishes as treatment continues..

Maintenance-Many patients will respond adequately to a daily dose of 1 to 2 tablets on

only two or three days in a week.

Elderly:

See precautions.

Children:

Neo-Naclex-K is not recommended for children.

Route of administration:

Oral.

Neo-Naclex-K K tablets should be swallowed whole with water

4.3. Contraindications

Severe renal or hepatic failure. Hypersensitivity to the product or other sulphonamide-like drugs. Addisons’s disease, diabetic keto-acidosis, hyperkalaemia and hypercalaemia. Neo-Naclex-K is a solid potassium-containing preparation and is therefore contraindicated in conditions of the gastrointestinal tract where strictures may form. Neo-Naclex-K should not be administered concurrently with lithium carbonate.

4.4 Special warnings and precautions for use

When treatment is prolonged and intensive, potassium depletion can develop insidiously. Periodic serum electrolyte determinations should be done. Neo-Naclex-K tablets usually provide sufficient potassium to maintain the serum concentration in hypertension, but it is sometimes advisable to give potassium chloride in addition to that contained in Neo-Naclex-K. If the patient is vomiting, has diarrhoea, or is suffering from an acute febrile or chronic illness (especially cirrhosis of the liver or heart failure), supplementary potassium may be particularly important. Additional potassium chloride to prevent hypokalaemia and the danger of arrhythmias, and other ECG changes is strongly recommended if patients receiving digitalis require prolonged treatment. Hypocalaemia may increase toxicity of glycosides and antagonise the effects of anti-arrhythmic drugs. In concurrent therapy with carbenoxolone or corticosteroids, additional potassium supplements are recommended. Patients at risk of myocardial infarction, and patients admitted for cardiac surgery also need potassium supplements.

Potassium depletion may cause polyuria, malaise, muscle weakness or cramp, decreased tendon reflexes, anorexia, dizziness, nausea or vomiting, also increased sensitivity to digitalis may increase and signs of overdosage appear.

Prolonged potassium depletion may induce chronic pyelonephritis. Renal function should be monitored. Neo-Naclex-K and additional potassium supplements must not be given in renal insufficiency complicated by hyperkalaemia.

In addition, in prolonged therapy it is necessary to test for glycosuria and investigate polyuria. In renal insufficiency, renal function should be monitored. The possibility of magnesium depletion should also be considered. In cirrhosis of the liver, thiazides may participate hepatic encephalopathy.

Thiazides may aggravate existing diabetes mellitus and causes symptoms in patients with latent disease. Neo-Naclex-K may impair control of diabetes in patients receiving sulphonylureas. Thiazides should be used with caution in systemic lupus erythematosus. Serum uric acid levels may be raised, with or without gout, in some patients. Thiazides may cause or aggravate hyperlipidaemia; pancreatitis may occur. The elderly are sensitive to the effects of thiazides on blood pressure and electrolyte. Administration of supplementary potassium is particularly important in the elderly. Patients with prostatic hypertrophy may develop acute urinary retention.

4.5 Interaction with other medicinal products and other forms of interaction

Diabetes mellitus: Thiazides may impair control in diabetics receiving sulphonylureas.

Lithium toxicity:-the renal clearance of lithium carbonate is reduced: concomitant use is contraindicated.

Anaesthesia: - The hypotensive effect of Halothane is increased by thiazides. Sensitivity to Tubocurarine is increased in hypokalaemia. Plasma potassium should be monitored prior to its use in patients treated with thiazides. The action of lidocaine is antagonised by hypokalaemia.

Antagonism and hypokalaemia:    Carbenoxolone, indomethacin,

phenylbutazone and corticosteroids may both antagonise the hypotensive effect of thiazides and increase potassium loss. Monitoring and potassium supplements are recommended.

Hypotension: Enhanced hypotensive effects may follow the concomitant use of thiazides and barbiturates, alcohol, other antihypertensives, (e.g. beta blocking agents, ACE inhibitors, calcium antagonists), MAOI’s or narcotics.

Cardiac Toxicity(increased QT Interval): Due to disopyramide, flecainide, sotalol, atomoxetine, pimozide and sertindole is increased if hypokalemia occurs.

Hypersensitivity: Use of Allopurinal and a thiazide in patients with renal dysfunction should be avoided; severe hypersensitivity vasculitis has been reported.

Cardiac glycosides: Hypokalaemia may increase the toxicity of glycosides and antagonize the effects of anti-arrhythmic drugs.

Potassium imbalance: - Caution is required in the use of Neo-Naclex-K with any drug or disease state which has a potential for producing potassium imbalance.

Vitamin B12: Potassium chloride, as in Neo-Naclex-K, may reduce absorption of oral Vitamin B12.

4.6. Pregnancy and lactation

Pregnancy:

Diuretics are best avoided in the management of oedema of pregnancy or hypertension of pregnancy, as their use may be associated with hypovolaemia, increased blood viscosity and reduced placental perfusion. There is inadequate evidence of safety in human pregnancy, there are reports of foetal and neonatal bone depression, thrombocytopoenia, electrolyte imbalance, hypoglycaemia and jaundice.

Expectant mothers who receive thiazide diuretics may be at increased risk from acute haemorrhagic pancreatitis. In parturition, thiazides may cause uterine inertia and delay the onset of labour.

Thiazides are only indicated in pregnancy if oedema complicates a pathological lesion and, even then, after assessing risk versus benefit including the undesirability of administering drugs in the first trimester.

Lactation:

As thiazides diuretics are secreted in mother’s milk, breast feeding should be avoided.

4.7.    Effects on ability to drive and use machines

When driving vehicles or operating machines it should be taken into account that dizziness may occur

4.8.    Undesirable effects

If abdominal pain, distension, nausea, vomiting or gastro-intestinal bleeding occur during the administration of tablets containing potassium salts, they should be discontinued immediately. Small bowel lesions are usually associated with enteric coated tablets and are less likely to occur with Neo-Naclex-K. The following have been reported: Disturbance of electrolyte, acid-base balance, lipids, glucose and uric acid levels; thirst, polyuria, weakness, dizziness, muscle cramps and reversible impotence: nausea, vomiting, mild anorexia, gastric irritation, diarrhoea or constipation; rashes, skin reactions, purpura and blood dyscrasias including thrombocytopoenia, hypocalciuria, precipitation of gout, pancreatitis, hepatic encephalopathy and postural hypotension.

4.9. Overdose

CNS depression (e.g. drowsiness, lethargy and coma) may occur without cardiovascular or respiratory depression. Hypovolaemia, hyperkalaemia, and mild hypoglycaemia are likely to be present.

In the case of recent ingestion, gastric lavage should be carried out; activated charcoal may help reduce absorption.

Treatment should be symptomatic, directed at fluid and electrolyte replacement.

Severe hyperkalaemia following overdose with potassium-containing thiazide combinations is rare. Lethargy, confusion, muscle weakness, paralysis, arrhythmia or cardiac arrest may occur. Measurement of plasma potassium, ECG monitoring and correction of any abnormalities are required. Other treatment depends on plasma potassium concentration. When this is less than 6.5mEq/l, fluid replacement with oral calcium polystyrene sulphonate is recommended. For levels of 6.5mEq/l, or greater, urgent treatment is required with intravenous insulin, glucose, sodium bicarbonate and/or calcium gluconate, oral calcium polystyrene sulphonate and possibility haemodialysis.

5. PHARMACOLOGICAL PROPERTIES

5.1. Pharmacodynamic properties

Neo-Naclex-K contains Bendroflumethiazide, a thiazide diuretic. Thiazide diuretics inhibit sodium and chloride reabsorption in the renal tubules and produce a corresponding increase in potassium excretion.. The mechanism whereby the thiazides exert their antihypertensive effect has not been clearly established.

Neo-Naclex-K also contains potassium chloride as a potassium supplement to offset the potassium-losing effect of Bendroflumethiazide

5.2. Pharmacokinetic properties

Not supplied.

5.3. Preclinical safety data

No further data of relevance.

6. PHARMACEUTICAL PARTICULARS

Film coat

Hydroxypropylmethylcellulose Ethylcellulose 50 Acetylated monoglyceride Propylene glycol Polysorbate 80 Methylene Chloride Isopropyl alcohol

6.2.    Incompatibilities

None

6.3.    Shelf life

24 months

6.4.    Special precautions for storage

Securitainer:

Store below 30C and protect from light and moisture.

Blister:

Store below 25C and protect from light and moisture.

6.5    Nature and contents of container

Tamper-evident, polypropylene container with low-density polyethylene lid, containing 30,100, 250 and 500 Neo-Naclex-K tablets.

PVC/PVdC blisters with aluminium foil backing containing 28,56,112 tablets.

6.6. Instructions for use, handling, (and disposal)

None.

7    MARKETING AUTHORISATION HOLDER

Mercury Pharma Group Ltd Capital House, 85 King William Street,

London EC4N 7BL, UK

MARKETING AUTHORISATION NUMBER(S)

PL: 10972/0001.

9. DATE OF FIRST AUTHORISATION/RENEWAL OF AUTHORISATION

12^th January 1993.

10 DATE OF REVISION OF THE TEXT

09/05/2014