‘DYAZIDE’Tablets
SCHEDULING STATUS:
S3
PROPRIETARY NAME
(and dosage form):
‘DYAZIDE’Tablets
COMPOSITION:
Each ‘Dyazide’tablet contains 50 mg triamterene and 25 mg hydrochlorothiazide.
Triamterene is 2,4,7-triamino-6-phenylpteridine.
Hydrochlorothiazide is 6-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7sulfonamide-1,1-dioxide.
PHARMACOLOGICAL CLASSIFICATION:
A.18.1 Diuretics.
PHARMACOLOGICAL ACTION:
‘Dyazide’ is an oral diuretic, antihypertensive agent. Its hydrochlorothiazide component blocks reabsorption of sodium (and attendant chloride anions). Its triamterene component acts by a different mechanism - it interferes with the exchange of sodium ions for potassium and hydrogen ions.
Diuretic activity following a single dose is evident within the first hour, reaches a peak at 2 to 3 hours, and tapers off during subsequent 7 to 9 hours.
Because of the potassium-conserving effect of its triamterene component, ‘Dyazide’ reduces the risk of hypokalaemia when seen with other diuretics. Therefore, it is of particular value in patients who might otherwise suffer from hypokalaemia and resultant side effects. The need for potassium supplements is virtually eliminated with the use of ‘Dyazide’. Hypochloraemic alkalosis, sometimes a problem with thiazides alone, has not been reported with ‘Dyazide’.
INDICATIONS:
‘Dyazide’is indicated in the treatment of oedema associated with congestive heart failure, cirrhosis of the liver, the nephrotic syndrome and in steroid-.induced oedema and idiopathic oedema.
‘Dyazide’is useful in patients whose response to other diuretic therapy is inadequate and in cases where sodium retaining steroids are present.
‘Dyazide’is also indicated in the treatment of mild to moderate hypertension. (Triamterene alone has little or no antihypertensive effect.) The usefulness of ‘Dyazide’ derives from the antihypertensive effect of the hydrochlorothiazide component and the potassium-sparing effect of triamterene.
CONTRA-INDICATIONS:
‘Dyazide’ is contra-indicated for further use in patients who exhibit progressive renal dysfunction, including increasing oliguria and increasing azotaemia or in patients who develop hyperkalaemia while on the drug. ‘Dyazide’ should not be used in patients with pre-existing elevated serum potassium, as is sometimes seen in patients with impaired renal function. Increasing hepatic dysfunction in patients on ‘Dyazide’ contra-indicates further use of the preparation. Hypersensitivity to either drug in the preparation is a contra-indication.
‘Dyazide’should not be used together with spironolactone as this may result in severe hyperkalaemia.
DOSAGE AND DIRECTIONS FOR USE:
Oedema:
The usual adult starting dosage is one tablet twice daily after meals. When adequate control of oedema has been achieved, the patient may be maintained on one tablet daily. In some patients, one tablet every other day may be sufficient. The maximum daily dosage should not exceed four tablets per day.
Hypertension:
The usual starting dosage is one tablet twice daily after meals. Subsequently, the dosage may be adjusted to the patient’s needs.
Since ‘Dyazide’has an antihypertensive effect, its use with antihypertensive drugs requires reduced dosage of the latter agent. When ‘Dyazide’ is added to an antihypertensive agent already being used as therapy, the dosage of the other antihypertensive drug should be reduced - particularly if it is a ganglionic agent. Subsequent adjustments of dosage should be made as required.
SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Side-effects ordinarily mild, include: Muscle cramps, weakness, dizziness, headache and dry mouth, rash, urticaria, purpura with or without thrombocytopenia, neutropenia and agranulocytosis have occurred, and other dermatological conditions; nausea and vomiting, diarrhoea, constipation and other gastrointestinal disturbances. (Such nausea can usually be prevented by giving the drug after meals). It is seldom necessary to discontinue therapy because of side-effects.
It should be noted that symptoms of nausea and vomiting can also be indicative of electrolyte imbalance. (See Precautions.)
Precautions:
Electrolyte imbalance when encountered in such diseases as heart failure, renal disease, or cirrhosis of the liver, may also be aggravated or caused independently by a diuretic agent including ‘Dyazide’.
Since ‘Dyazide’ is a combination of two potent diuretics, the possibility of electrolyte imbalance should be kept in mind when using high doses for prolonged periods or in patients on a salt-restricted diet. Periodic serum electrolyte determinations should be performed during therapy.
‘Dyazide’can cause mild to moderate nitrogen retention which is reversible upon withdrawal of the drug and is seldom observed with intermittent (every other-day) therapy. Upon evidence of increasing azotaemia, however, the drug should be discontinued. Cirrhotics with splenomegaly may have marked variations in their blood pictures - including thrombocyte and leukocyte levels - which are not related to drug therapy. Periodic blood studies in these patients are recommended.
Cases of thrombocytopenic purpura and megaloblastic anaemia have been reported with triamterene; thiazides alone have caused jaundice, acute pancreatitis and blood dyscrasias including agranulocytosis, thrombocytopenia and leucopenia.
Since ‘Dyazide’has an antihypertensive effect, its use with another antihypertensive drug requires reduced dosage of the latter agent. When ‘Dyazide’ is added to another antihypertensive already being used as therapy, the dose of the other antihypertensive drug should be reduced - particularly if it is a ganglionic blocking agent. Subsequently adjustment of dosage should be made as required.
‘Dyazide’because of its hydrochlorothiazide component may cause hyperglycaemia and glycosuria. In diabetics, the insulin requirement may be altered. Also, hyperuricaemia may be observed occasionally, with possible occurrence of gout. However, ‘Dyazide’does not appear to offer greater liability than that reported for hydrochlorothiazide alone.
Triamterene component may cause a decreasing alkali reserve with the possibility of metabolic acidosis. In cases of hypokalaemia, increased sensitivity to digitalis may occur, precipitating digitalis intoxication.
Hyperkalaemia has been reported ranging in incidence from 4 % in patients less than 60 years of age and higher in patients 60 years and older.
Because of potassium-conserving effects of triamterene, hypokalaemia is an uncommon occurrence with the use of ‘Dyazide’. Patients should not be placed on dietary potassium supplements or potassium salts in conjunction with ‘Dyazide’unless they develop hypokalaemia or their dietary intake of potassium is markedly impaired. Thiazides have been shown to decrease arterial responsiveness to norepinephrine and to increase the paralyzing effect of tubocurarine; consequently caution should be observed in patients undergoing surgery.
Periodic BUN and serum potassium determination should be made to check kidney function, especially in elderly patients and in patients with suspected or confirmed renal insufficiency or hepatic insufficiency.
Usage in Pregnancy:
Clinical experience and foetal studies in animals have shown no evidence to suggest that the preparation may be a cause of congenital abnormalities. Nevertheless, thiazides have been shown to pass through the placenta and also into breast milk. Cases of thrombocytopenia which may be a manifestation of bone-marrow depression, which may sometimes be fatal, pancreatitis, or hypoglycaemia have been reported in newborn infants of mothers treated with thiazides. The use of ‘Dyazide’in pregnant or nursing mothers should therefore be avoided.
KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
In the event of overdosage, it can be theorized that electrolyte imbalance would be the major concern.
Other symptoms might be nausea and vomiting, other gastrointestinal disturbances, and weakness.
Hypotension may occur and, if profound, pressor agents such as levaterenol may be used to maintain blood pressure levels. As with overdosage of any drug, immediate evacuation of the stomach should be induced through emesis and gastric lavage. Careful eva luation of the electrolyte pattern and fluid balance should be made. There is no specific antidote.
IDENTIFICATION:
‘Dyazide’tablets are peach coloured, round, flat-faced, bevel-edged compressed tablets with a single score on one side, and a SKF plus code E93 embossed on the other.
PRESENTATION:
‘Dyazide’tablets are available in securitainers of 250 and 1000, and calendarised blisterpacks of 28.
STORAGE INSTRUCTIONS:
Store below 25° C in a dry place.
KEEP OUT OF REACH OF CHILDREN.
REGISTRATION NUMBER:
G/18.1/71.
NAME AND BUSINESS ADDRESS OF THE APPLICANT:
SmithKline Beecham Pharmaceuticals (Pty) Ltd.
6 Carey Street, Wynberg Ext. 6,
Johannesburg 2090.
DATE OF PUBLICATION OF THIS PACKAGE INSERT:
26.4.1982.
PO194 |
