ADCO-RETIC tablets

SCHEDULING STATUS:
S3

PROPRIETARY NAME
(and dosage form):

ADCO-RETIC tablets

COMPOSITION:
Each tablet contains 5 mg amiloride hydrochloride, and 50 mg hydrochlorothiazide.

PHARMACOLOGICAL CLASSIFICATION:
A 18.1 Diuretics

PHARMACOLOGICAL ACTION:
ADCO-RETIC Tablets have diuretic and antihypertensive effects, combining the natriuretic action of hydrochlorothiazide, with the potassium conserving property of amiloride hydrochloride. The mild diuretic action of amiloride hydrochloride is additive to the natriuretic and diuretic activity of the thiazide.

INDICATIONS:
ADCO-RETIC Tablets are indicated in the treatment of patients with oedema of cardiac decompensation or associated with hepatic cirrhosis and corticosteroid therapy. They are also indicated in the treatment of patients with essential hypertension.

CONTRA-INDICATIONS:
Hyperkalaemia:
ADCO-RETIC Tablets should not be used in the presence of elevated plasma potassium levels (interpreted as over 5,5 mmol per L).
Antikaliuretic Therapy or Potassium Supplementation:
Other antikaliuretic agents and potassium supplements are contra-indicated in patients receiving ADCO-RETIC Tablets due to the potassium-sparing effect of amiloride hydrochloride (such combination therapy is commonly associated with rapid increases in plasma potassium levels).
Impaired Renal Function:
Anuria, acute renal failure, severe progressive renal disease and diabetic nephropathy are contra-indications to the use of ADCO-RETIC Tablets. Patients with increases in blood urea nitrogen (BUN) over 5 mmol/L, in serum creatinine levels over 130 umol/L, or in whole blood urea values over 10 mmol/L should not receive the drug without careful, frequent monitoring of serum electrolytes and BUN levels. Potassium retention in the presence of renal impairment is accentuated by the addition of an antikaliuretic agent and may result in the rapid development of hyperkalaemia.
In Children:
The safety of the use of amiloride hydrochloride in children has not been established; therefore, ADCO-RETIC Tablets are not recommended in the paediatric age group.
Sensitivity to the Drug:
Hypersensitivity to either component is a contra-indication to the use of ADCO-RETIC Tablets.
Contra-indicated in pregnancy and lactation.

DOSAGE AND DIRECTIONS FOR USE:
Potassium supplements should not be given with ADCO-RETIC Tablets.
Oedema:
The usual dosage is one or two tablets a day. The optimal dosage is determined by the diuretic response and the serum potassium level. Once an initial diuresis has been achieved, reduction in dosage should be attempted for maintenance therapy.
Hypertension:
The usual dosage is one ADCO-RETIC Tablet daily. Some patients may require half a tablet daily. ADCO-RETIC Tablets may be used alone or as an adjunct to other antihypertensive medicines.
ADCO-RETIC Tablets may add to or potentiate the action of other antihypertensive agents. If ADCO-RETIC Tablets are added to therapy with other antihypertensive agents, dosage reduction of such agents may be necessary in order to reduce the risk of an excessive drop in blood pressure.

SIDE EFFECTS AND SPECIAL PRECAUTIONS:
The side-effects of amiloride hydrochloride include: orthostatic hypotension, abnormal liver function, activation of peptic ulcer, nausea, vomiting, diarrhoea, or constipation, abdominal pain, thirst and gastrointestinal bleeding. Dry mouth, skin rash, pruritus, aplastic anaemia, neutropenia, elevated serum potassium levels (>5,5 mmol per L), muscle cramps, dizziness, weakness, vertigo, paraesthesia, confusion, minor psychiatric changes, and visual disturbances may occur. Patients with partial heart block may develop complete heart block.
Rises in blood urea nitrogen concentrations may occur, as well as abnormalities in liver function tests.
Amiloride hydrochloride may cause hepatic encephalopathy manifested by tremors, confusion and coma. Patients with liver disease should be observed for this complication when ADCO-RETICTablets are administered. In cirrhotic patients, jaundice associated with the underlying disease process may deepen.
In diabetic patients, hyperkalaemia may occur with amiloride hydrochloride administration, particularly if chronic renal disease or pre-renal azotaemia is present. Before initiating therapy in diabetic or suspected diabetic patients, the renal function status should be known.
Amiloride hydrochloride should be given with care to patients likely to develop acidosis, such as severely ill patients with cardiopulmonary disease and with decompensated diabetes.
The side-effects of hydrochlorothiazide include: anaphylactic-type reactions, fever, headache, weakness, fatigue, necrotizing angiitis (vasculitis, cutaneous vasculitis), Stevens-Johnson Syndrome (erythema multiforme), digitalis toxicity, orthostatic hypotension, jaundice (intrahepatic cholestatic jaundice), pancreatitis, thirst, glycosuria, hyperglycaemia, hyperuricaemia, gout, photosensitivity, sialadenitis, urticaria, rash and pruritus. Restlessness, mental confusion, respiratory distress including pneumonitis, transient blurred vision, xanthopsia, agranulocytosis, aplastic anaemia, haemolytic anaemia, leukopenia, purpura, thrombocytopenia, muscle cramps, dizziness, vertigo and paraesthesia may occur.
Hyperparathyroidism and changes in serum lipids may also occur. Pathological changes in the parathyroid gland with hypercalcaemia and hypophosphataemia may occur with prolonged treatment with hydrochlorothiazide.
The following side-effects may also occur:
Malaise, chest pain, back pain, arrythmias, tachycardia, angina pectoris, anorexia, nausea, vomiting, diarrhoea or constipation, appetite changes, abdominal fullness, flatulence, hiccups, flushing, leg ache, joint pain, stupor, insomnia, nervousness, depression, sleepiness, dyspnoea, bad taste, nasal congestion, impotence, dysuria, nocturia and incontinence.
Hydrochlorothiazide should be used with caution in patients with impaired hepatic or renal function, or with diabetes mellitus or adrenal disease. Insulin requirements in diabetic patients may be increased, decreased, or unchanged due to hydrochlorothiazide. Diabetes mellitus which has been latent may become manifest during thiazide administration. Blood-glucose concentrations should be monitored in patients taking antidiabetic agents since their requirements of these agents may change.
Use in Nursing Mothers: Hydrochlorothiazide appears in breast milk. If use of the drug is deemed essential, the patient should stop nursing.
Hydrochlorothiazide crosses the placental barrier and appears in the cord blood.
Electrolyte Imbalance and Reversible BUN Increases:
Hydrochlorothiazide may produce hypomagnesaemia, hyponatraemia, hypochloraemia and hypokalaemia. Hyponatraemia may occur in patients with congestive heart failure who are very oedematous, particularly with large doses in conjunction with restricted salt in the diet. Hypokalaemia intensifies the effect of digitalis on cardiac muscle and administration of digitalis or its glycosides may have to be temporarily suspended. Urinary calcium excretion may be decreased in patients receiving hydrochlorothiazide. All patients should be carefully observed for signs of fluid and electrolyte imbalance, especially in the presence of vomiting or during parenteral fluid therapy. The potassium depleting effects of hydrochlorothiazide may be enhanced by corticosteroids, corticotrophin and carbenoxalone.
If increasing azotaemia and oliguria occur during treatment ADCO-RETIC Tablets should be discontinued.
Hydrochlorothiazide potentiates the action of other antihypertensive drugs. Therefore, the dosage of these agents, especially the ganglion blockers, may need to be reduced when ADCO-RETIC Tablets are added to the regimen.
Lithium should generally not be given to patients receiving hydrochlorothiazide since the risk of lithium toxicity is very high in such patients.
Hydrochlorothiazide may increase the neuromuscular blocking action of nondepolarising muscle relaxants like tubocurarine. The antihypertensive effect of ADCO-RETIC Tablets may be enhanced in the postsympathectomy patient.
Hydrochlorothiazide may decrease arterial responsiveness to norepinephrine. This diminution is not sufficient to preclude the effectiveness of the pressor agent for therapeutic use.
Orthostatic hypotension due to hydrochlorothiazide may be potentiated by alcohol, barbiturates or narcotics.
Hydrochlorothiazide may interfere with a number of diagnostic tests, including tests for parathyroid function; serum concentrations of protein-bound iodine may increase without signs of thyroid disturbance. ADCO-RETIC Tablets should be discontinued before carrying out tests for parathyroid function.
Effects Related to Diuresis in Cirrhotic Patients:
Oral diuretic therapy is more frequently accompanied by adverse reactions in patients with hepatic cirrhosis and ascites because these patients are intolerant of acute shifts in electrolyte balance, and because they often have pre-existing hypokalaemia as a result of associated aldosteronism.
Sensitivity reactions to ADCO-RETIC Tablets may occur in patients with or without a history of allergy or bronchial asthma.
The possibility of exacerbation or activation of systemic lupus erythematosus may occur.
Patients should be observed regularly for the possible occurrence of liver dysfunction, idiosyncratic reactions, or blood dyscrasias.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
For symptoms see "Side-effects and Special Precautions". Treatment is symptomatic and supportive.
Empty the stomach by emesis or lavage and give symptomatic treatment. Restore fluid and acid-base balance as indicated.

IDENTIFICATION:
Peach coloured, diamond-shaped tablet with ‘ACDO’Eembossed on one side and a breakline on either side.

PRESENTATION:
ADCO-RETIC Tablets are supplied in securitainers and bottles of 30, 100 and 1000 tablets.

STORAGE INSTRUCTIONS:
Store below 25°C. Protect from light and moisture. Keep out of reach of children.

REGISTRATION NUMBER:
V/18.1/260

NAME AND BUSINESS ADDRESS OF THE APPLICANT:
Adcock Ingram Limited
Adcock Ingram Park
17 Harrison Avenue
Bryanston
Private Bag X69, Bryanston, 2021

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
24 October 1988