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Amiloride hydrochloride and hydrochlorothiazide in:
5mg/50mg tablet: A pale yellow, circular, flat, bevel-edged tablet having a diameter of 8mm. One face is embossed with 5/50, whilst the other has the company logo (dp).
Amiloride is a weak diuretic with its primary site of action being in the distal nephron where it inhibits sodium reabsorption while causing retention of potassium and hydrogen ions. It does not inhibit aldosterone or carbonic anhydrase. The greatest benefit of its potassium sparing effect is obtained when combined with thiazide or loop diuretics. In chronic diuretic therapy where hypokaliemia and alkalosis are common, amiloride acts to correct the alkalosis and reduce potassium loss thereby maintaining normal plasma potassium levels.
Hydrochlorothiazide is a thiazide diuretic and acts to reduce the reabsorption of electrolytes from the renal tubules thereby increasing the excretion of sodium, chloride, water and potassium to a lesser extent. A small reduction in carbonic anhydrase activity leads to some increase in sodium bicarbonate. The acid-base balance and pH of the urine are not altered appreciably.
Absorption of amiloride from the GI tract is incomplete, peak serum concentrations being achieved 3 to 4 hours after administration. This correlates with the onset of action of amiloride, however, the natriuresis and anti-kaluresis continues for up to 24 hours after a single dose. It is excreted unchanged in the urine with no enterohepatic cycling occurring. The serum half-life is said to be six hours.
Hydrochlorothiazide is incompletely but fairly rapidly absorbed from the gastrointestinal tract. Peak plasma concentrations occur between 60 and 120 minutes. Absorption is enhanced when given with food. Hydrochlorothiazide appears to preferentially bind to red blood cells. It also crosses the placental barrier and is excreted into breast milk. Excretion is principally renal with little into the bile. The serum half-life is estimated to be in the range of 3-4 hours with a biological half-life of 12 hours. In treating hypotension, the antihypertensive effect takes 3-4 days to appear and may last up to several days after discontinuation of chronic therapy.
HYDROZIDE tablets are indicated for the treatment of hypertension, cardiac oedema and hepatic cirrhosis with ascites and oedema.
Hypertension: 1-2 HYDROZIDE tablets daily.
Cardiac oedema: The dosage is determined according to the diuretic response and plasma potassium levels.
Initially 1-2 HYDROZIDE tablets daily. If adequate diuresis is not achieved, the dose may be gradually increased, however, a dose of 4 tablets daily should not be exceeded. The maintenance dosage may be smaller than that necessary to initiate diuresis.
Hepatic cirrhosis - with ascites and oedema: Initially 1 HYDROZIDE tablet daily. The dosage is gradually increased until effective diuresis is achieved to a maximum of 4 tablets a day. When the patients weight is established, a reduction in dosage may be attempted. Gradual weight reduction is desirable to avoid untoward effects associated with diuretic therapy.
Hyperkaliemia (plasma potassium over 5.5meq/ l) anuria, acute renal failure, severe progressive renal disease, diabetic nephropathy. Raised serum creatinine (over 130micromol/l), urea nitrogen levels (over 21mmol/l) or urea levels (over 10mmol/l) if serum electrolytes and renal function cannot be adequately controlled. Hypersensitivity to amiloride or hydrochlorothiazide.
Use in children: the safety of amiloride in paediatric use has not been established. If HYDROZIDE is to be used the potential benefit must be weighed against the potential risk.
Use in pregnancy: the safety of amiloride during pregnancy and lactation has not been established, therefore, use of HYDROZIDE requires that the potential benefit must be weighed against the potential risk.
General: Amiloride should not be given concomitantly with potassium or other potassium sparing diuretics. Diabetes has been precipitated in patients receiving thiazides. Metabolic or respiratory acidosis may cause rapid alterations in intracellular and extracellular potassium. Rapid electrolyte alteration may also occur in hepatic cirrhosis. Combinations of amiloride and hydrochlorothiazide may raise serum creatinine, urea and urate levels.
To avoid orthostatic hypotension developing, the dosage of other antihypertensives, especially that of methyldopa, guanethidine or other ganglionic blocking medicines, should be reduced. Care is required and plasma potassium should be monitored if HYDROZIDE is to be used in: elderly patients, patients with hepatic cirrhosis, cardiac oedema or renal insufficiency, as well as in patients receiving concomitant digitalis therapy.
Routine plasma potassium measurements are recommended even without specific indications after about one month of therapy and, thereafter, about once a year.
Diabetic patients, especially those with nephropathy, are at high risk of developing electrolyte disturbances during amiloride therapy. Amiloride may alter insulin and sulphonylurea requirements in diabetic patients. Hydrochlorothiazide may precipitate attacks of gout in susceptible patients.
Gastrointestinal symptoms, anorexia, nausea, vomiting, abdominal pain, constipation or diarrhoea may occur. Diuresis may cause dry mouth, thirst, paresthesis, dizziness, fatigue, muscle cramps or orthostatic hypotension. Hyperkaliemia, hyperglycaemia and hyperuricaemia, as well as hyponatraemia and hypochloraemia, have been reported.
In patients with liver disease, hepatic encephalopathy may be aggravated. Skin rash, pruritus and minor psychiatric disturbances may occur. Erythema multiforme has been reported with hydrochlorothiazide alone. Thrombocytopenia, leukemia, agranulocytosis and aplastic anaemia have also been reported during therapy with hydrochlorothiazide.
Lithium should not be administered to patients receiving long term thiazide therapy because of a risk of lithium toxicity due to reduced lithium clearance. Thiazides may antagonise the hypoglycaemic effects of insulin and of sulphonylureas in diabetic patients. The hyperglycaemic, hypotensive and hyperuricaemic effects of diazoxide may be potentiated by hydrochlorothiazide.
Alcohol, barbiturates and narcotic drugs have been reported to increase the postural hypotensive effects of thiazide diuretics. Hydrochlorothiazide may enhance the toxicity of digitalis glycosides by depleting serum potassium. The neuromuscular blocking action of non-polarising muscle relaxants may be enhanced. Hydrochlorothiazide may interfere with tests for parathyroid function. Amiloride may interfere with glucose tolerance tests and should be discontinued before such a test is performed.
Overdosage is rare and results in hypotension and electrolyte imbalance. Treatment is symptomatic and gastric lavage may be useful in cases of recent overdosage.
Protect from light and moisture. Keep out of reach of children.
Prescription Medicine.
HYDROZIDE: 100s
Amiloride HCl is N-Amidino-3,5-diamino-6-chloropyrazine-2-carboxamide hydrochloride dihydrate. Its molecular formula and weight are C6H8ClN7O,HCl,2H2O and 302.1 respectively.
Hydrochlorothiazide is 6-chloro-3,4-dihydro-2H1,2,4-benzothiaziadine-7-sulphonamide 1,1-dioxide. Its molecular formula and weight are C7H8ClN3O4S2 and 297.7 respectively.
Other ingredients of the tablets are: Maize cornflour, Microcrystalline cellulose, Sodium stearyl fumarate, Polyvinylpyrrolidinone and D&C Yellow No 10.
HYDROZIDE tablets have a shelf-life of 3 years when stored at room temperature.
Douglas Pharmaceuticals Ltd
P.O. Box 45-027
AUCKLAND 8
New Zealand
Ph: (09) 835-0660
Fax: (09) 835-0665
4 May 1999