CO-AMILOZIDE

Posology The rate of loss of weight and the serum electrolyte levels should determine the dosage. 0 kg/day. Hypertension Initially half a Co-amilozide 5mg/50mg tablet given once a day. If necessary, an increase to one Co-amilozide 5mg/50mg tablet given once a day or in divided doses.

Co-amilozide may be used alone or as an adjunct to other antihypertensive drugs, but since the antihypertensive effect of these agents may be enhanced, their dosage may need to be reduced in order to reduce the risk of an excessive drop in pressure.

Congestive heart failure Initially half a Co-amilozide 5mg/50mg tablet a day, subsequently adjusted if required, but not exceeding two Co-amilozide 5mg/50mg tablets a day. Optimal dosage 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. Patients with hepatic cirrhosis with ascites Initiate therapy with a low dose.

A single daily dose of one Co-amilozide 5mg/50mg tablet may be increased gradually until there is an effective diuresis. Dosage should not exceed two Co-amilozide 5mg/50mg 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 patients 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.

(See also Special Warnings & Precautions, subsections - Hyperkalaemia, Electrolyte imbalance). Method of administration Oral use.

, Electrolyte Imbalance). Hypokalaemia may develop, especially as a result of brisk diuresis, after prolonged therapy or when severe cirrhosis is present. g. increased ventricular irritability). A potassium chloride supplement is recommended in these circumstances, however, 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.

Potassium conserving therapy should be initiated with caution in severely ill patients in whom metabolic or respiratory acidosis may occur, eg patients with decompensated diabetes or cardiopulmonary disease. Shifts in acid base balance alter the balance of extracellular/intracellular potassium.

The development of acidosis may be associated with rapid increases in serum potassium. Potassium replacement or conservation is also likely to be necessary in patients at risk from the cardiac effects of hypokalaemia such as those with severe heart disease, those taking cardiac glycosides preparations or high doses of diuretics and in patients with severe liver disease.

Potassium supplements should not be given in renal insufficiency complicated by hyperkalaemia. Potassium supplementation alone may not be sufficient to correct hypokalaemia in patients who are also deficient in magnesium. Magnesium depletion has also been implicated as a risk factor for arrhythmias.

Some patients may be particularly susceptible to hyponatraemia, including the elderly and those with severe heart failure who are very oedematous, particularly with large doses of thiazides in conjunction with restricted salt in the diet.

Diuretic-induced hyponatraemia is usually mild and asymptomatic. It may become severe and symptomatic in a few patients who will then require immediate attention and appropriate treatment. Thiazides may decrease urinary calcium excretion.

Thiazides may cause intermittent and slight elevation of serum calcium in the absence of known disorders of calcium metabolism. Therapy should be discontinued before carrying out tests for parathyroid function. In seriously ill patients, reversible increases in blood urea have been reported accompanying vigorous diuresis, hepatic cirrhosis, ascites and metabolic alkalosis or those with resistant oedema.

Serum electrolyte and blood urea levels should be carefully monitored in these patients. Co-amilozide should be used with caution in patients with renal impairment. 3 Contraindications). Uraemia may be precipitated or increased by hydrochlorothiazide.

Cumulative effects of the drug may develop in patients with impaired renal function. If increasing uraemia and oliguria develop during treatment, Co- amilozide should be discontinued. 3 'Contraindications'), since minor alterations of fluid and electrolyte balance may precipitate hepatic coma.

8 Undesirable Effects). 8 Undesirable Effects, Metabolic subsection). Thiazides may impair glucose tolerance. 3 'Contraindications'). Dosage adjustment of antidiabetic agents, including insulin, may be required. Increases in cholesterol and triglyceride levels may be associated with thiazide diuretic therapy.

To minimise the risk of hyperkalaemia in diabetic or suspected diabetic patients, the status of renal function should be determined before initiating therapy with Co-amilozide. Therapy should be discontinued at least three days before giving a glucose tolerance test.

, patients with cardiopulmonary disease or patients with inadequately controlled diabetes. Shifts in acid-base balance alter the balance of extracellular/intracellular potassium, and the development of acidosis may be associated with rapid increases in plasma potassium.

Sensitivity reactions:

The possibility that thiazides may activate or exacerbate systemic lupus erythematosus has been reported. Sensitivity reactions to thiazides may occur in patients with or without a history of allergy or bronchial asthma. Caution is required in patients with severe asthma, as hypokalaemia associated with beta 2 -agonist therapy can be potentiated by concurrent use of diuretics.

Non-melanoma skin cancer:

An increased risk of non-melanoma skin cancer (NMSC) [basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)] with increasing cumulative dose of hydrochlorothiazide exposure has been observed in two epidemiological studies based on the Danish National Cancer Registry.

Photosensitizing actions of hydrochlorothiazide could act as a possible mechanism for NMSC. Patients taking hydrochlorothiazide should be informed of the risk of NMSC and advised to regularly check their skin for any new lesions and promptly report any suspicious skin lesions.

Possible preventive measures such as limited exposure to sunlight and UV rays and, in case of exposure, adequate protection should be advised to the patients in order to minimise the risk of skin cancer. Suspicious skin lesions should be promptly examined […]

Hyperkalaemia has been observed in patients receiving amiloride hydrochloride, either alone or with other diuretics, particularly in the aged and in diabetics. It has been reported in seriously ill hospital patients with hepatic cirrhosis or congestive heart failure with renal impairment, 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). Some deaths have been reported in this group of patients Treatment of hyperkalaemia: Should hyperkalaemia develop, discontinue Co-amilozide treatment immediately and, if necessary, take active measures taken to reduce the serum potassium to normal.

Impaired renal function:

Renal function should be monitored carefully for serum electrolytes and blood urea levels, as should seriously ill patients, such as those with hepatic cirrhosis with ascites and metabolic alkalosis or those with resistant oedema who are also taking diuretics because the use of Co- amilozide in impaired renal function may result in the rapid development of hyperkalaemia.

Thiazide diuretics become ineffective when creatinine clearance falls below 30 ml/min.

Electrolyte imbalance and blood urea increases:

Although the likelihood of electrolyte imbalance is reduced with Co-amilozide, careful check should be kept for such signs of fluid and electrolyte imbalance as hyponatraemia, hypochloraemic alkalosis, hypokalaemia and hypomagnesaemia, particularly in the elderly and in patients receiving long-term therapy.

It is particularly important to make serum and urine electrolyte determinations when the patient is vomiting excessively or receiving parenteral fluids. 8 Undesirable Effects, Electrolyte Imbalance). Hypokalaemia may develop, especially as a result of brisk diuresis, after prolonged therapy or when severe cirrhosis is present.

g. increased ventricular irritability). A potassium chloride supplement is recommended in these circumstances, however, 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.

Potassium conserving therapy should be initiated with caution in severely ill patients in whom metabolic or respiratory acidosis may occur, eg patients with decompensated diabetes or cardiopulmonary disease. Shifts in acid base balance alter the balance of extracellular/intracellular potassium.

The development of acidosis may be associated with rapid increases in serum potassium. Potassium replacement or conservation is also likely to be necessary in patients at risk from the cardiac effects of hypokalaemia such as those with severe heart disease, those taking cardiac glycosides preparations or high doses of diuretics and in patients with severe liver disease.

Potassium supplements should not be given in renal insufficiency complicated by hyperkalaemia. Potassium supplementation alone may not be sufficient to correct hypokalaemia in patients who are also deficient in magnesium. Magnesium depletion has also been implicated as a risk factor for arrhythmias.

Some patients may be particularly susceptible to hyponatraemia, including the elderly and those with severe heart failure who are very oedematous, particularly with large doses of thiazides in conjunction with restricted salt in the diet.

Diuretic-induced hyponatraemia is usually mild and asymptomatic. It may become severe and symptomatic in a few patients who will then require immediate attention and appropriate treatment. Thiazides may decrease urinary calcium excretion.

Thiazides may cause intermittent and slight elevation of serum calcium in the absence of known disorders of calcium metabolism. Therapy should be discontinued before carrying out tests for parathyroid function. In seriously ill patients, reversible increases in blood urea have been reported accompanying vigorous diuresis, hepatic cirrhosis, ascites and metabolic alkalosis or those with resistant oedema.

Serum electrolyte and blood urea levels should be carefully monitored in these patients. Co-amilozide should be used with caution in patients with renal impairment. 3 Contraindications). Uraemia may be precipitated or increased by hydrochlorothiazide.

Cumulative effects of the drug may develop in patients with impaired renal function. If increasing uraemia and oliguria develop during treatment, Co- amilozide should be discontinued. 3 'Contraindications'), since minor alterations of fluid and electrolyte balance may precipitate hepatic coma.

8 Undesirable Effects). 8 Undesirable Effects, Metabolic subsection). Thiazides may impair glucose tolerance. 3 'Contraindications'). Dosage adjustment of antidiabetic agents, […]

5 mmol/1); other potassium- conserving diuretics. Potassium supplements or potassium-rich food (except in severe and/or refractory cases of hypokalaemia under careful monitoring); • Concomitant use with spironolactone or triamterene; • Severe hepatic failure, precoma associated with hepatic cirrhosis: • Addison's disease; • Hypercalcaemia; • Concurrent lithium therapy; • Diabetic nephropathy, patients with blood urea over 10 mmol/l, patients with diabetes mellitus; • Severe renal impairment; severe progressive renal disease; acute renal failure; anuria; use of potassium conserving agents may result in rapid development of hyperkalaemia in patients with renal impairment; patients with blood urea over10 mmol/l or those with serum creatinine over 130 μmol/l in whom serum electrolyte and blood urea levels cannot be monitored carefully and frequently; • The safety of amiloride hydrochloride for use in children under 18 years of age has not been established.

Co-amilozide is not recommended for children. 6 (Pregnancy and lactation).