AMILORIDE TABLETS BP 5mg

Each tablet contains Amiloride Hydrochloride BP equivalent to 5mg anhydrous amiloride hydrochloride.

Yellow uncoated tablets.

Potassium-conserving agent; diuretic. Although amiloride may be used alone, its principal indication is as concurrent therapy with thiazides or more potent diuretics to conserve potassium during periods of vigorous diuresis and during long-term maintenance therapy. It is indicated for use in:

1) Congestive heart failure.

2) Hypertension.

3) Hepatic cirrhosis with ascites.

Monotherapy: Initially 10mg which may be given as a single or divided dose. This may be increased if necessary to a maximum of 20mg daily. When diuresis has been achieved, the dosage may be reduced by 5mg increments to the least amount required.

In conjunction with other diuretic therapy: When amiloride is used with a diuretic which is given on an intermittent basis, it should be given at the same time as the diuretic.

Congestive heart failure: Initially 5-10mg daily, together with the usual dosage of the diuretic concurrently employed. Where diuresis is not achieved dosage of both agents may be increased if necessary, however, the maximum dose for amiloride is 20mg a day. Once diuresis is achieved, reduction in dosage of both agents may be attempted for maintenance therapy. The dosage of both drugs is determined by diuresis and the level of plasma potassium.

Hypertension: 5-10mg daily, together with the usual antihypertensive dosage of the thiazide concurrently employed. It is not usually necessary to exceed 10mg of amiloride daily; in any event, not more than 20mg a day should be given.

Hepatic cirrhosis with ascites: When used in conjunction with another diuretic, treatment should be commenced with a small amiloride dose of 5mg, plus a low dosage of the other diuretic agent. If necessary, dosage of both agents may gradually be increased until there is effective diuresis. The maximum dose for amiloride is 20mg daily. Maintenance doses may be lower than those required to initiate diuresis; reduction in the daily dosage should therefore be attempted when the patient's weight is stabilised.

Elderly: Dosage in the elderly should be carefully adjusted according to renal function, blood electrolytes and diuretic response. The elderly are more susceptible to electrolyte imbalance and more likely to experience hyperkalaemia since renal reserve may be reduced.

Children: The use of amiloride in children is contraindicated.

For oral administration.

Hyperkalaemia (plasma potassium over 5.5mmol/l); other potassium-conserving agents or potassium supplements; anuria, acute renal failure, severe progressive renal disease, diabetic nephropathy; known sensitivity to amiloride; use in children as safety has not been established.

Diabetes mellitus: To minimise the risk of hyperkalaemia in known or suspected diabetic patients, the status of renal function should be determined before initiating therapy. Amiloride should be discontinued for at least three days before a glucose-tolerance test.

Metabolic or respiratory acidosis: Potassium-conserving therapy should be initiated only with caution in severely ill patients in whom metabolic or respiratory acidosis may occur, eg patients with cardiopulmonary disease of decompensated diabetes. Shifts in acid-base balance alter the balance of extracellular-intracellular potassium, and the development of acidosis may be associated with rapid increase in plasma potassium.

Hyperkalaemia: This has been observed in some patients receiving amiloride, alone or with other diuretics. These patients should be observed carefully for clinical, laboratory, and ECG evidence of hyperkalaemia. Some deaths have been reported in this group of patients. Hyperkalaemia has been noted particularly in the elderly and in hospital patients with hepatic cirrhosis or cardiac oedema who have known renal involvement, who were seriously ill, or were undergoing vigorous diuretic therapy.

Neither potassium-conserving agents nor a diet rich in potassium should be used with amiloride except in severe and/or refractory cases of hypokalaemia. If the combination is used, plasma potassium levels must be continuously monitored.

Treatment of hyperkalaemia: If hyperkalaemia occurs, amiloride should be discontinued immediately and, if necessary, active measures taken to reduce the plasma potassium level.

Impaired renal function: Patients with blood urea over 10mmol/l, serum creatinine over 130µmol/l, or with diabetes mellitus require careful monitoring of serum electrolytes and blood urea levels. In renal impairment, use of a potassium-conserving agent may result in rapid development of hyperkalaemia.

Electrolyte imbalance and blood urea increases: Hyponatraemia and hypochloraemia may occur when amiloride is used with other diuretics. Reversible increases in blood urea levels have been reported accompanying vigorous diuresis, especially when diuretics were used in seriously ill patients, such as those with hepatic cirrhosis with ascites and metabolic alkalosis, or those with resistant oedema. Careful monitoring of serum electrolytes and blood urea levels should therefore be carried out when amiloride is given with oral diuretics to such patients.

Cirrhotic patients: Oral diuretic therapy is more frequently accompanied by side-effects in patients with hepatic cirrhosis with or without ascites, because these patients are intolerant of acute shifts in electrolyte balance, and because they often already have hypokalaemia as a result of associated aldosteronism.

Reports suggest that patients with pre-existing severe liver disease treated with diuretics, including amiloride hydrochloride, may experience hepatic encephalopathy, manifested by tremors, confusion and coma, and increased jaundice.

Lithium should not generally be given with diuretics because they reduce it renal clearance and add a high risk of lithium toxicity.

When combined with thiazide diuretics, amiloride can act synergistically with chlorpropamide to increase the risk of hyponatraemia.

When amiloride is administered concurrently with an angiotensin-converting enzyme inhibitor, NSAIDs or ciclosporin the risk of hyperkalaemia may be increased. Therefore, if concomitant use of these agents is indicated because of demonstrated hypokalaemia, they should be used with caution and with frequent monitoring of serum potassium.In patients receiving amiloride with NSAIDs or ciclosporin the risk of nephrotoxcity may also be increased.

Amiloride is not recommended for use during pregnancy due to limited clinical experience. The potential benefits must be weighed against the possible hazard to the foetus if administered to a woman of childbearing age.

The routine use of diuretics in otherwise healthy pregnant women with or without mild oedema is not indicated because they may be associated with hypovolaemia, increased blood viscosity and decreased placental perfusion. Foetal and neonatal jaundice, foetal bone depression and thrombocytopenia have also been described.

It is not known whether amiloride is excreted in human milk. Therefore, due to the risk that it may take this route of excretion, and possibly cause serious adverse reactions to the nursing infant, the mother should either stop breast-feeding or cease taking the drug.

None known.

Amiloride is usually well tolerated, although minor side-effects are reported relatively frequently. Apart from hyperkalaemia, significant adverse reactions have been infrequently reported. Nausea/anorexia, abdominal pain, flatulence and mild skin rash are probably due to amiloride; but other side-effects are generally associated with diuresis or with the underlying disease being treated.

Body as a whole: Headache, weakness, fatigue, back pain, chest pain, neck/shoulder ache, pain in the extremities.

Cardiovascular: Angina pectoris, orthostatic hypotension, arrhythmias, palpitation, one patient with partial heart block developed complete heart block.

Digestive: Anorexia, nausea, vomiting, diarrhoea, constipation, abdominal pain, GI bleeding, jaundice, thirst, dyspepsia, flatulence.

Metabolic: Elevated plasma potassium levels above 5.5mmol/l, hyponatraemia.

Musculoskeletal: Muscle cramps, joint pain.Serum uric acid levels may rise during treatment with amiloride and acute attacks of gout may be precipitated.

Nervous: Dizziness, vertigo, paraesthesia, tremors, encephalopathy.

Psychiatric: nervousness, mental confusion, insomnia, decreased libido, depression, somnolence.

Respiratory: Cough, dyspnoea.

Special senses: Nasal congestion, visual disturbances, increased intra-ocular pressure, tinnitus.

Urogenital: Impotence, polyuria, dysuria, bladder spasms, frequency of micturition.

Reactions in which no causal relationship could be established were activation of probable pre-existing peptic ulcer, aplastic anaemia, neutropenia and abnormal liver function tests. In a few cirrhotic patients, jaundice associated with the underlying disease has deepened, but the drug relationship is unknown.

No data are available; it is not known whether the drug is dialysable. No specific antidote is available.

The most likely signs and symptoms are dehydration and electrolyte imbalance which should be treated by established methods. Therapy should be discontinued and the patient closely observed. Emesis should be induced or gastric lavage performed if ingestion is recent. Treatment is symptomatic and supportive. If hyperkalaemia occurs, active measures should be taken to reduce plasma potassium levels.

Amiloride hydrochloride is a diuretic.

Amiloride is incompletely absorbed from the gastrointestinal tract. Peak serum concentrations are achieved about 3-4 hours after administration by mouth. It is excreted unchanged in the urine. Amiloride has been estimated to have a serum half-life of about 6 hours.

Not applicable.

Also contains: lactose, magnesium stearate, maize starch, E172, E460.

None known.

Shelf-life

Three years from the date of manufacture.

Shelf-life after dilution/reconstitution

Not applicable.

Shelf-life after first opening

Not applicable.

Store below 25°C in a dry place.

Protect from light.

The product containers are rigid injection moulded polypropylene or injection blow-moulded polyethylene tablet containers with and snap-on polyethylene lids; in case any supply difficulties should arise the alternative is amber glass bottles with screw caps and polyfoam wad or cotton wool.

The product may also be supplied in blister packs in cartons:

a) Carton: Printed carton manufactured from white folding box board.

b) Blister pack: (i) 250µm white rigid PVC. (ii) Surface printed 20µm hard temper aluminium foil with 5-7g/M² PVC and PVdC compatible heat seal lacquer on the reverse side.

Pack sizes: 28s, 30s, 56s, 60s, 84s, 90s, 100s, 112s, 120s, 168s, 180s, 250s, 500s, 1000s

Product may also be supplied in bulk packs, for reassembly purposes only, in polybags contained in tins, skillets or polybuckets filled with suitable cushioning material.

Maximum size of bulk packs: 50,000.

Not applicable.

Name or style and permanent address of registered place of business of the holder of the Marketing Authorisation:

Actavis UK Limited

(Trading style: Actavis)

Whiddon Valley

BARNSTAPLE

N Devon EX32 8NS

PL 0142/0210

August 1986; August 1991

May 2007