CO-AMILOZIDE

Posology Hypertension: initially 1 tablet daily, increasing if necessary to a maximum of 2 tablets daily or in divided doses. Congestive heart failure: initially 1 tablet daily, increasing if necessary to a maximum of 4 tablets daily.

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.

Oedema and ascites in cirrhosis of the liver: initially 2 tablets daily, increasing if necessary to a maximum of 4 tablets daily; dose should be reduced for maintenance if possible. 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.

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. 3). Method of administration Oral use

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:

Body as a whole: anaphylactic reaction, headache , weakness , fatigue, malaise, chest pain, back pain, syncope. Cardiovascular: arrhythmias, tachycardia, digitalis toxicity, orthostatic hypotension, angina pectoris. Digestive: anorexia , nausea , vomiting, diarrhoea, constipation, abdominal pain, GI bleeding, appetite changes, abdominal fullness, flatulence, thirst, hiccups.

4 ‘special warnings and precautions for use’), gout, dehydration, symptomatic hyponatraemia. Integumentary: rash , pruritis, flushing, diaphoresis. Musculoskeletal: leg ache, muscle cramps, joint pain. Nervous: dizziness , vertigo, paraesthesia, stupor.

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

* Side effects that have been reported most frequently during controlled clinical trials with Co- amilozide Additional side effects that have been reported with the individual components and may be potential side effects of Co-Amilozide are listed below: Amiloride: Body as a whole: neck/shoulder ache, pain in extremities.

Digestive: abnormal liver function, activation of probable pre-existing peptic ulcer, dyspepsia, jaundice. Integumentary: dry mouth, alopecia. Nervous: tremors, encephalopathy. Haematological: aplastic anaemia, neutropenia. Cardiovascular: one patient with partial heart block developed complete heart block, palpitation.

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 clearance falls 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, hypochloremic 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); 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; anuria; acute renal failure, severe progressive renal disease, 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, or those with serum creatinine over 130 μmol/l in whom serum electrolyte and blood urea levels cannot be monitored carefully and frequently.

In renal impairment, use of a potassium – conserving agent may result in rapid development of hyperkalaemia. Because the safety of amiloride hydrochloride for use in children has not been established, Co- Amilozide is not recommended for children.

For ‘Use in pregnancy’ and ‘Use in breast-feeding mothers’, see ‘Pregnancy and Lactation’.