CILAZAPRIL

Posology Cilazapril should be administered once daily. As food intake has no clinically significant influence on absorption, Cilazapril can be administered before or after a meal. The dose should always be taken at about the same time of day.

Hypertension The initial dose is 1 mg/day. Blood pressure should be assessed, and dosage adjusted individually in accordance with the blood pressure response. 0 mg once daily. Patients with a strongly activated renin- angiotensin-aldosterone system (in particular, salt and/or volume depletion, cardiac decompensation, or severe hypertension) may experience an excessive blood pressure fall following the initial dose.

5 mg once daily is recommended in such patients and the initiation of treatment should take place under medical supervision. Hypertensive patients receiving diuretics If possible, the diuretic should be discontinued 2 – 3 days before beginning therapy with Cilazapril to reduce the likelihood of symptomatic hypotension.

It may be resumed later if required. 5 mg once daily. 5 mg once daily under close medical supervision. This dose should be maintained for about 1 week. 5 mg. 0 mg. 1). 4). 5 mg once daily < 10ml/min Not recommended If renovascular hypertension is also present there is an increased risk of severe hypotension and renal insufficiency.

In these patients, treatment should be started under close medical supervision with low doses and careful dose titration. Since treatment with diuretics may be a contributory factor, they should be discontinued and renal function should be monitored during the first weeks of Cilazapril therapy.

Results from clinical trials showed that clearance of cilazapril was correlated with creatinine clearance in patients with chronic heart failure. The special dosage recommendation should thus be followed in chronic heart failure patients with impaired renal function.

5 mg/day accompanied by a careful monitoring of the blood pressure, because significant hypotension may occur. 0 mg once daily. Thereafter, the maintenance dose must be adapted to individual tolerability, response and clinical status.

5 mg must be strictly followed.

Paediatric population:

Safety and efficacy in children aged below 18 years have not been established. Therefore, there is no recommendation for administration of cilazapril to children. Method of administration Oral use.

(a) Summary of the safety profile The most frequent drug-attributable adverse events observed in patients taking ACE inhibitors are cough, skin rash and renal dysfunction. Cough is more common in women and non-smokers. Where the patient can tolerate the cough, it may be reasonable to continue treatment.

In some cases, reducing the dose may help. Treatment-related adverse events severe enough to stop treatment occur in less than 5% of patients receiving ACE inhibitors. (b) Tabulated list of adverse reactions The following list of adverse reactions is derived from clinical trials and post- marketing data in association with cilazapril and/or other ACE inhibitors.

Estimates of frequency are based on the proportion of patients reporting each adverse reaction during cilazapril clinical trials that included a total combined population of 7171 patients. Adverse reactions that were not observed during cilazapril clinical trials but have been reported in association with other ACE inhibitors or derived from postmarketing case reports are classified as `rare’.

4). Symptoms of hypotension may include syncope, weakness, dizziness and visual impairment. 4). 4). Hyperkalaemia is most likely to occur in patients with renal impairment and those taking potassium sparing diuretics or potassium supplements.

The events of cerebral ischaemia, transient ischaemic attack and ischaemic stroke reported rarely in association with ACE inhibitors may be related to hypotension in patients with underlying cerebrovascular disease. Similarly, myocardial ischaemia may be related to hypotension in patients with underlying ischaemic heart disease.

Headache is a commonly reported adverse event, although the incidence of headache is greater in patients receiving placebo than in those receiving ACE inhibitors. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

Pregnancy ACE inhibitors should not be initiated during pregnancy. Unless continued ACE inhibitor therapy is considered essential, patients planning pregnancy should be changed to alternative anti-hypertensive treatments which have an established safety profile for use in pregnancy.

6). Hypotension ACE inhibitors may cause severe hypotension, especially when starting treatment. Firstdose hypotension is most likely to occur in patients whose renin-angiotensinaldosterone system is activated, such as in renovascular hypertension or other causes of renal hypoperfusion, sodium or volume depletion, or previous treatment with other vasodilators.

These conditions can co-exist, particularly in severe heart failure. Hypotension should be treated by placing the patient supine and volume expansion. Cilazapril may be continued once the patient is volume replete, but should be given at a lower dose or discontinued if hypotension persists.

At-risk patients should start treatment with cilazapril under medical supervision, with a low initial dose and careful titration. If possible, diuretic therapy should be discontinued temporarily. Similar caution should be taken for patients with angina pectoris or cerebrovascular disease, in whom hypotension can cause myocardial or cerebral ischaemia.

Dual blockade of the renin-angiotensin-aldosterone system (RAAS) There is evidence that the concomitant use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren increases the risk of hypotension, hyperkalaemia and decreased renal function (including acute renal failure).

1). 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. ACE-inhibitors and angiotensin II receptor blockers should not be used concomitantly in patients with diabetic nephropathy.

1). • Concomitant use with sacubitril/valsartan therapy. 5).