CO-AMILOZIDE

Posology Adults:

Hypertension Initially half a tablet is given once a day. If necessary, increase to one tablet given once a day or in divided doses. Congestive heart failure Initially half a tablet a day, subsequently adjusted if required but not exceeding 2 tablets a day.

The optimal dose is determined by the diuretic response and the plasma potassium level. Once an initial diuresis has been achieved, reduction in dosage may be attempted for maintenance therapy. Maintenance therapy may be on an intermittent basis.

Hepatic cirrhosis with ascites Initiate therapy with a low dose. A single daily dose of one tablet may be increased gradually until there is an effective diuresis. Dosage should not exceed 2 tablets a day. Maintenance dosages may be lower than those required to initiate diuresis; dosage reduction should therefore be attempted when the patient’s weight is stabilised.

A gradual weight reduction is especially desirable in cirrhotic patients to reduce the likelihood of untoward reactions associated with diuretic therapy. 3). Elderly Particular caution is needed in the elderly because of their susceptibility to electrolyte imbalance; the dosage should be carefully adjusted to renal function and clinical response.

Method of administration For oral administration

Although minor side effects are relatively common, significant side effects are infrequent. Reported side effects are generally associated with diuresis, thiazide therapy, or with the underlying disease. No increase in the risk of adverse reactions has been seen over those of the individual components.

The following side effects have been reported with Co-amilozide:

General disorders and administration site conditions: anaphylactic reaction, headache *weakness *, fatigue, malaise, chest pain, back pain, syncope Cardiac Disorders: arrhythmias, tachycardia, digitalis toxicity, orthostatic hypotension, angina pectoris Gastrointestinal disorders: anorexia*, nausea*, vomiting, diarrhoea, constipation, abdominal pains, GI bleeding, changes in appetite, abdominal fullness, flatulence, thirst, hiccups.

4 'Special warnings and precautions for use'), gout, dehydration, symptomatic hyponatraemia. Blood and lymphatic system disorders: agranulocytosis, aplastic anaemia, haemolytic anaemia, leucopenia, neutropenia, purpura and thrombocytopenia.

Skin and subcutaneous tissue disorder: diaphoresis, rash*, pruritus, flushing. Musculoskeletal and connective tissue disorders: leg ache, muscle cramps, joint pains. Nervous system disorders: dizziness*, vertigo, paraesthesiae, stupor.

Psychiatric disorders: insomnia, nervousness, mental confusion, depression, sleepiness. Respiratory, thoracic and mediastinal disorders: dyspnoea Special senses: bad taste, nasal congestion, visual disturbance. Renal and urinary disorders: impotence, dysuria, nocturia, incontinence, renal dysfunction including renal failure.

Additional side effects that have been reported with the individual components and may be potential side effects of Co-amilozide are listed below: Amiloride: General disorders and administration site conditions: neck/shoulder ache, pain in extremities.

Hyperkalaemia has been observed in patients receiving amiloride hydrochloride, either alone or with other diuretics, particularly in the aged or in hospital patients with hepatic cirrhosis or congestive heart failure with renal involvement, who were seriously ill, or were undergoing vigorous diuretic therapy.

Such patients should be carefully observed for clinical, laboratory, and ECG evidence of hyperkalaemia (not always associated with an abnormal ECG). Neither potassium supplements nor a potassium-rich diet should be used with Co-amilozide except under careful monitoring in severe and/or refractory cases of hypokalaemia.

Some deaths have been reported in this group of patients.

Treatment of hyperkalaemia:

Should hyperkalaemia develop, discontinue treatment immediately and, if necessary, take active measures to reduce the plasma potassium to normal.

Impaired renal function:

Renal function should be monitored because the use of Co-amilozide in impaired renal function may result in the rapid development of hyperkalaemia. Thiazide diuretics become ineffective when creatinine levels fall below 30 ml/min.

Electrolyte imbalance:

Although the likelihood of electrolyte imbalance is reduced by Co-amilozide, careful check should be kept for such signs of fluid and electrolyte imbalance as hyponatraemia, hypochloraemic alkalosis, hypokalaemia and hypomagnesaemia.

It is particularly important to make serum and urine electrolyte determinations when the patient is vomiting excessively or receiving parenteral fluids. Warning signs or symptoms of fluid or electrolyte imbalance include: dryness of the mouth, weakness, lethargy, drowsiness, restlessness, seizures, confusion, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, and gastro-intestinal disturbances such as nausea and vomiting.

5 mmol/l) • is taking other potassium conserving diuretics or potassium supplements or potassium-rich food (except in severe and/or refractory cases of hypokalaemia under careful monitoring) • is having concomitant treatment with spironolactone or triamterene • has anuria • has acute renal failure or severe progressive renal disease • has severe hepatic failure or precoma associated with hepatic cirrhosis • has Addison’s disease • has hypercalcaemia • has concurrent lithium therapy • has diabetic nephropathy • has blood urea over 10 mmol/l, diabetes mellitus, or serum creatinine over 130 μmol/l where serum electrolyte and blood urea cannot be monitored carefully and frequently.

• In renal impairment, use of a potassium-conserving agent may result in rapid development of hyperkalaemia. • Co-amilozide is not recommended for children under 18 years old. 6 'Fertility, pregnancy and lactation'.