RAMACE Tablet Ref.[50300] Active ingredients: Ramipril

Essential Hypertension

Dosage of RAMACE (ramipril) must be individualized. Initiation of therapy requires consideration of recent antihypertensive drug treatment, the extent of blood pressure elevation and salt restriction. The dosage of other antihypertensive agents being used with RAMACE may need to be adjusted.

Monotherapy

The recommended initial dosage of RAMACE in patients not on diuretics is 2.5mg once daily. Dosage should be adjusted according to blood pressure response, generally, at intervals of at least two weeks. The usual dose range is 2.5 to 10mg once daily. A daily dose of 20mg should not be exceeded.

In some patients treated once daily, the antihypertensive effect may diminish towards the end of the dosing interval. This can be evaluated by measuring blood pressure 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 blood pressure is not controlled with RAMACE alone, a diuretic may be added. After the addition of a diuretic, it may be possible to reduce the dose of RAMACE.

Concomitant Diuretic Therapy

Symptomatic hypotension occasionally may occur following the initial dose of RAMACE and is more likely in patients who are currently being treated with a diuretic. The diuretic should, if possible, be discontinued for two to three days before beginning therapy with RAMACE to reduce the likelihood of hypotension (see WARNINGS). If the diuretic cannot be discontinued, an initial dose of 1.25 mg RAMACE should be used with careful medical supervision for several hours and until blood pressure has stabilized. The dosage of RAMACE should subsequently be titrated (as described above) to the optimal response.

Use in renal impairment

For patients with a creatinine clearance below 40ml/min/1.73m² (serum creatinine above 2.5mg/dL), the recommended initial dose is 1.25mg RAMACE once daily. Dosage may be titrated upward until blood pressure is controlled or to a maximum total daily dose of 5mg. In patients with severe renal impairment (creatinine clearance below 10ml/min/1.73m²) the maximum total daily dose of 2.5mg RAMACE should not be exceeded.

Treatment Following Acute Myocardial Infarction

Dosage of RAMACE (ramipril) must be individualized. Initiation of therapy requires consideration of concomitant medication and baseline blood pressure and should be instituted under close medical supervision, usually in a hospital, three to ten days following an acute myocardial infarction in haemodynamically stable patients with clinical signs of heart failure.

The recommended initial dosage of RAMACE is 2.5 mg given twice a day (b.i.d.), one in the morning and one in the evening. If tolerated, and depending on the patient’s response, dosage may be increased by doubling at intervals of one to three days. The maximum daily dose of RAMACE should not exceed 5 mg twice daily (b.i.d.).

After the initial dose of RAMACE, the patient should be observed under medical supervision for at least two hours and until blood pressure has stabilized for at least an additional hour. If a patient becomes hypotensive at this dosage, it is recommended that the dosage be lowered to 1.25 mg b.i.d. following effective management of the hypotension (see WARNINGS – Hypotension).

Patients who have been fluid or salt depleted, or treated with diuretics are at an increased risk of hypotension (see WARNINGS-Hypotension). An excessive fall in blood pressure may occur particularly in the following: after the initial dose of RAMACE ; after every first increase of dose of RAMACE; after the first dose of a concomitant diuretic and/or when increasing the dose of the concomitant diuretic. If appropriate, the dose of any concomitant diuretic should be reduced which may diminish the likelihood of hypotension (see PRECAUTIONS – Drug Interactions ). Consideration should be given to reducing the initial dose to 1.25 mg of RAMACE in these patients.

Use in renal impairment

In patients with impaired renal function (creatinine clearance of 20-50 mL/min/1.73 m² body surface area), the initial recommended dosage is generally 1.25 mg of RAMACE once daily. This dosage may be increased with caution up to 1.25 mg of RAMACE twice daily, depending upon clinical response and tolerability.

Insufficient data is available concerning the use of ramipril following acute myocardial infarction in patients with heart failure and severe renal failure. (see ACTION & CLINICAL PHARMACOLOGY – Pharmacokinetics & Metabolism, PRECAUTIONS – Renal Impairment).

Use in hepatic impairment

Insufficient data is available concerning the use of ramipril following acute myocardial infarction in patients with heart failure and hepatic dysfunction. Dose reduction and careful monitoring of these patients is required (see ACTIONS & CLINICAL PHARMACOLOGY- Pharmacokinetics & Metabolism, PRECAUTIONS – Patients with Impaired Liver Function).

Management of Patients at Increased Risk of Cardiovascular Events

Recommended initial dose: 2.5 mg of RAMACE once daily. Depending on the tolerability, the dose is gradually increased. It is recommended to double the dose after one week of treatment and – after another three weeks – to increase it to 10 mg. Usual maintenance dose: 10 mg of RAMACE daily (see ACTION AND CLINICAL PHARMACOLOGY, WARNINGS and PRECAUTIONS).

Dosage recommendations for special risk groups such as patients with renal or hepatic impairment, or at an increased risk of hypotension (fluid or salt depletion, treated with diuretics) are to be followed as previously described (SEE WARNINGS and PRECAUTIONS).

Limited data are available regarding overdosage of RAMACE (ramipril) in humans. Two 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. It is not known if ramipril or ramiprilat can be removed from the body by hemodialysis.