RAMIPRIL

Capsules should be swallowed whole. DO NOT open, divide, crush or chew the capsules. Recommended Dose and Dosage Adjustment Essential Hypertension Dosage of ramipril must be individualized. Initiation of therapy requires consideration of recent antihypertensive drug treatment, the extent of blood pressure (BP) elevation and salt restriction.

The dosage of other antihypertensive agents being used with ramipril may need to be adjusted. 5 mg once daily. Dosage should be adjusted according to BP response, generally, at intervals of ≥ 2 weeks. 5 - 10 mg once daily. The maximum daily dose is 20 mg.

In some patients treated once daily, the antihypertensive effect may diminish towards the end of the dosing interval. This can be evaluated by measuring BP just prior to dosing to determine whether satisfactory control is being maintained for 24 hours.

If it is not, either twice daily administration with the same total daily dose, or an increase in dose should be considered. If BP is not controlled with ramipril alone, a diuretic may be added. After the addition of a diuretic, it may be possible to reduce the dose of ramipril.

Concomitant Diuretic Therapy Symptomatic hypotension occasionally may occur following the initial dose of ramipril and is more likely in patients who are currently being treated with a diuretic. The diuretic should, if possible, be discontinued for 2-3 days before beginning therapy with Ramipril to reduce the likelihood of hypotension (see WARNINGS AND PRECAUTIONS).

25 mg ramipril should be used with careful medical supervision for several hours and until BP has stabilized. The dosage of Ramipril should subsequently be titrated (as described above) to the optimal response. 25 mg ramipril once daily.

Dosage may be titrated upward until BP is controlled or to a maximum total daily dose of 5 mg. 5 mg ramipril. Use in hepatic impairment The response to the treatment with ramipril may be either increased or reduced. Treatment in these patients must therefore be initiated only under close medical supervision.

5 mg. OVERDOSAGE Ramipril - Product Monograph Page 19 of 37 Limited data are available regarding overdosage with ramipril in humans; only 2 cases of overdosage have been reported. In the case of an overdose with ramipril, the most likely clinical manifestation would be symptoms attributable to severe hypotension, which should normally be treated by intravenous volume expansion with normal saline.

Overdosage may cause excessive peripheral vasodilatation (with marked hypotension, shock), bradycardia, electrolyte disturbances, and renal failure. For management of a suspected drug overdose, contact your regional Poison Control Centre.

Management Primary detoxification by, for example, gastric lavage, administration of adsorbents, sodium sulfate; (if possible during the first 30 minutes). g. norepinephrine, dopamine) or angiotensin II (angiotensinamide), which is usually available only in scattered research laboratories, must be considered in addition to volume and salt substitution.

No experience is available concerning the efficacy of forced diuresis, alteration in urine pH, haemofiltration, or dialysis in speeding up the elimination of ramipril or ramiprilat. If dialysis or haemofiltration is nevertheless considered, see also WARNINGS AND PRECAUTIONS, Immune, Anaphylactoid reactions during membrane exposure section.

ACTION AND CLINICAL PHARMACOLOGY Mechanism of Action Ramipril is an angiotensin converting enzyme (ACE) inhibitor. Following oral administration, ramipril is rapidly hydrolyzed to ramiprilat, its principal active metabolite. ACE catalyzes the conversion of angiotensin I to the vasoconstrictor substance, angiotensin II.

Angiotensin II also stimulates aldosterone secretion by the adrenal cortex. Inhibition of ACE activity leads to decreased levels of angiotensin II thereby resulting in decreased vasoconstriction and decreased aldosterone secretion. The latter decrease may result in a small increase in serum potassium (see WARNINGS AND PRECAUTIONS, Endocrine and Metabolism, Hyperkalemia and Potassium-Sparing Diuretics).

Decreased levels of angiotensin II and the accompanying lack of negative feedback on renal renin secretion result in increases in plasma renin activity. ACE is identical to kininase II. Thus, ramipril may also block the degradation of the vasodepressor peptide bradykinin, which may contribute to its therapeutic effect.

Pharmacodynamics Administration of ramipril to patients with mild to moderate essential hypertension results in a reduction of both supine and standing BP usually with little or no orthostatic change or change in heart rate. Symptomatic postural hypotension is infrequent, although this may occur in Ramipril - Product Monograph Page 20 of 37 patients who are salt-and/or volume-depleted (see WARNINGS AND PRECAUTIONS).

In single dose studies, doses of 5-20 mg ramipril lowered BP within 1-2 hours, with peak reductions achieved 3-6 hours after dosing. At recommended doses given once daily, antihypertensive effects have persisted over 24 hours. The effectiveness of ramipril appears to be similar in the elderly (> 65 years of age) and younger adult patients given the same daily doses.

In studies comparing the same daily dose of ramipril given as a single morning dose or as a twice daily dose, BP reductions at the time of morning trough blood levels were greater with the divided regimen. While […]