Dapril Special Precautions

Dual Blockade of the Renin-Angiotensin-Aldosterone System (RAAS): There is evidence that the concomitant use of angiotensin-converting enzyme angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers or aliskiren increases the risk of hypotension, hyperkalaemia and decreased renal function (including acute renal failure). Dual blockade of RAAS through the combined use of ACE inhibitors, angiotensin II receptor blockers or aliskiren is therefore not recommended (see Interactions).
If dual blockade therapy is considered absolutely necessary, this should only occur under specialist supervision and subject to frequent close monitoring of renal function, electrolytes and blood pressure.
Angiotensin-converting enzyme-inhibitors and angiotensin II receptor blockers should not be used concomitantly in patients with diabetic nephropathy.
Symptomatic Hypotension: Symptomatic hypotension was seen rarely in uncomplicated hypertensive patients. In hypertensive patients receiving Dapril, hypotension is more likely to occur if the patient has been volume-depleted eg, by diuretic therapy, dietary salt restriction, dialysis, diarrhoea or vomiting (see Side Effects).
In patients with congestive heart failure, with or without associated renal insufficiency, symptomatic hypotension has been observed. This is most likely to occur in those patients with more severe degrees of heart failure, as reflected by the use of high doses of loop diuretics, hyponatremia or functional renal impairment. In these patients, therapy should be started under medical supervision and the patients should be monitored closely whenever the dose of Dapril and/or diuretic is adjusted. If hypotension occurs, the patient should be placed in the supine position and, if necessary, should receive an IV infusion of normal saline.
A transient hypotensive response is not a contraindication to further doses, which can be given usually without difficulty once the blood pressure has increased after volume expansion.
In some patients with congestive heart failure who have normal or low blood pressure, additional lowering of systemic blood pressure may occur with Dapril. This effect is anticipated and is not usually a reason to discontinue treatment. If hypotension becomes symptomatic, a reduction of dose or discontinuation of Dapril may be necessary.
Renal Function Impairment: In patients with congestive heart failure, hypotension following the initiation of therapy with ACE inhibitors may lead to some further impairment in renal function. Acute renal failure, usually reversible, has been reported in this situation.
In some patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney, who have been treated with ACE inhibitors, increases of blood urea and serum creatinine, reversible upon discontinuation of therapy have been seen. This is especially likely in patients with renal insufficiency.
Some hypertensive patients with no apparent preexisting renal vascular disease have developed increases in blood urea and serum creatinine, usually minor and transient, especially when Dapril has been given concomitantly with a diuretic.
This is more likely to occur in patients with preexisting renal impairment. Dosage reduction of Dapril and/or discontinuation of the diuretic may be required.
Hypersensitivity/Angioneurotic Oedema: Angioneurotic oedema of the face, extremities, lips, tongue, glottis and/or larynx has been reported rarely in patients treated with ACE inhibitors, including Dapril. In such cases, Dapril should be discontinued promptly and the patient observed carefully until the swelling disappears. In those instances where swelling has been confined to the face and lips, the condition generally resolved without treatment, although antihistamines have been useful in relieving symptoms.
Angioneurotic oedema associated with laryngeal oedema may be fatal. Where there is involvement of the tongue, glottis and larynx, likely to cause airway obstruction, SC adrenaline solution 1:1000 (0.3-0.5 mL) should be administered promptly, and other appropriate therapy instituted.
Surgery/Anaesthesia: In patients undergoing major surgery or during anaesthesia with agents that produce hypotension, Dapril may block angiotensin II formation secondary to compensatory rennin release. If hypotension occurs and is considered to be due to this mechanism, it can be corrected by volume expansion.
Further Information: Where Dapril replaces a β-adrenoceptor blocking agent, the β-adrenoceptor blocker should be withdrawn gradually; the dose should be titrated down after commencing Dapril therapy.
Use in pregnancy: When used in pregnancy during the 2nd and 3rd trimesters, ACE inhibitors can cause injury and even death to the developing foetus. When pregnancy is detected, Dapril should be discontinued as soon as possible.
Use in lactation: It is not known whether Dapril is secreted in human milk. Because many drugs are secreted in human milk, caution should be exercised if Dapril is given to a nursing mother.
Use in children: Safety and effectiveness of Dapril in children have not been established.
Use in the elderly: In clinical studies, there was no age-related change in the efficacy or safety profile of Dapril. When advanced age is associated with decrease in renal function, however, the guidelines set out in the table (see Dosage & Administration) should be used to determine the starting dose of Dapril. Thereafter, the dosage should be adjusted according to the blood pressure response.