RAMIPRIL Capsule, hard Ref.[7067] Active ingredients: Ramipril

Posology

It is recommended that Ramipril is taken each day at the same time of the day. Ramipril can be taken before, with or after meals, because food intake does not modify its bioavailability (see section 5.2). Ramipril has to be swallowed with liquid. It must not be chewed or crushed.

Adults

Diuretic-Treated patients

Hypotension may occur following initiation of therapy with Ramipril; this is more likely in patients who are being treated concurrently with diuretics. Caution is therefore recommended since these patients may be volume and/or salt depleted.

If possible, the diuretic should be discontinued 2 to 3 days before beginning therapy with Ramipril (see section 4.4).

In hypertensive patients in whom the diuretic is not discontinued, therapy with Ramipril should be initiated with a 1.25 mg dose. Renal function and serum potassium should be monitored. The subsequent dosage of Ramipril should be adjusted according to blood pressure target.

Hypertension

The dose should be individualised according to the patient profile (see section 4.4) and blood pressure control.

Ramipril may be used in monotherapy or in combination with other classes of antihypertensive medicinal products (see sections 4.3, 4.4, 4.5 and 5.1).

Starting dose:

Ramipril should be started gradually with an initial recommended dose of 2.5 mg daily.

Patients with a strongly activated renin-angiotensin-aldosterone system may experience an excessive drop in blood pressure following the initial dose. A starting dose of 1.25 mg is recommended in such patients and the initiation of treatment should take place under medical supervision (see section 4.4).

Titration and maintenance dose:

The dose can be doubled at interval of two to four weeks to progressively achieve target blood pressure; the maximum permitted dose of Ramipril is 10 mg daily. Usually the dose is administered once daily.

Cardiovascular prevention

Starting dose:

The recommended initial dose is 2.5 mg of Ramipril once daily.

Titration and maintenance dose:

Depending on the patient’s tolerability to the active substance, the dose should be gradually increased. It is recommended to double the dose after one or two weeks of treatment and – after another two to three weeks – to increase it up to the target maintenance dose of 10 mg Ramipril once daily.

See also posology on diuretic treated patients above.

Treatment of renal disease

In patients with diabetes and microalbuminuria:

Starting dose:

The recommended initial dose is 1.25 mg of Ramipril once daily.

Titration and maintenance dose:

Depending on the patient’s tolerability to the active substance, the dose is subsequently increased. Doubling the once daily dose to 2.5 mg after two weeks and then to 5 mg after a further two weeks is recommended.

In patients with diabetes and at least one cardiovascular risk:

Starting dose:

The recommended initial dose is 2.5 mg of Ramipril once daily.

Titration and maintenance dose:

Depending on the patient’s tolerability to the active substance, the dose is subsequently increased. Doubling the daily dose to 5 mg Ramipril after one or two weeks and then to 10 mg Ramipril after a further two or three weeks is recommended. The target daily dose is 10 mg.

In patients with non-diabetic nephropathy as defined by macroproteinuria ≥3 g/day:

Starting dose:

The recommended initial dose is 1.25 mg of Ramipril once daily.

Titration and maintenance dose:

Depending on the patient’s tolerability to the active substance, the dose is subsequently increased. Doubling the once daily dose to 2.5 mg after two weeks and then to 5 mg after a further two weeks is recommended.

Symptomatic heart failure

Starting dose:

In patients stabilized on diuretic therapy, the recommended initial dose is 1.25 mg daily.

Titration and maintenance dose:

Ramipril should be titrated by doubling the dose every one to two weeks up to a maximum daily dose of 10 mg. Two administrations per day are preferable.

Secondary prevention after acute myocardial infarction and with heart failure

Starting dose:

After 48 hours, following myocardial infarction in a clinically and haemodynamically stable patient, the starting dose is 2.5 mg twice daily for three days. If the initial 2.5 mg dose is not tolerated a dose of 1.25 mg twice a day should be given for two days before increasing to 2.5 mg and 5 mg twice a day. If the dose cannot be increased to 2.5 mg twice a day the treatment should be withdrawn.

See also posology on diuretic treated patients above.

Titration and maintenance dose:

The daily dose is subsequently increased by doubling the dose at intervals of one to three days up to the target maintenance dose of 5 mg twice daily.

The maintenance dose is divided in 2 administrations per day where possible.

If the dose cannot be increased to 2.5 mg twice a day treatment should be withdrawn. Sufficient experience is still lacking in the treatment of patients with severe (NYHA IV) heart failure immediately after myocardial infarction. Should the decision be taken to treat these patients, it is recommended that therapy be started at 1.25 mg once daily and that particular caution be exercised in any dose increase.

Special populations

Patients with renal impairment

Daily dose in patients with renal impairment should be based on creatinine clearance (see section 5.2):

• if creatinine clearance is ≥60 ml/min, it is not necessary to adjust the initial dose (2.5 mg/day); the maximal daily dose is 10 mg;
• if creatinine clearance is between 30-60 ml/min, it is not necessary to adjust the initial dose (2.5 mg/day); the maximal daily dose is 5 mg;
• if creatinine clearance is between 10-30 ml/min, the initial dose is 1.25 mg/day and the maximal daily dose is 5 mg;
• in haemodialysed hypertensive patients: ramipril is slightly dialysable; the initial dose is 1.25 mg/day and the maximal daily dose is 5 mg; the medicinal product should be administered few hours after haemodialysis is performed.

Patients with hepatic impairment (see section 5.2)

In patients with hepatic impairment, treatment with Ramipril must be initiated only under close medical supervision and the maximum daily dose is 2.5 mg Ramipril.

Elderly

Initial doses should be lower and subsequent dose titration should be more gradual because of greater chance of undesirable effects especially in very old and frail patients. A reduced initial dose of 1.25 mg ramipril should be considered.

Paediatric population

The safety and efficacy of ramipril in children has not yet been established.

Currently available data for ramipril are described in sections 4.8, 5.1, 5.2 and 5.3 but no specific recommendation on posology can be made.

Method of administration

Oral use.

Symptoms

Symptoms associated with overdosage of ACE inhibitors may include excessive peripheral vasodilatation (with marked hypotension, shock), bradycardia, electrolyte disturbances, and renal failure.

Management

The patient should be closely monitored and the treatment should be symptomatic and supportive. Suggested measures include primary detoxification (gastric lavage, administration of adsorbents) and measures to restore haemodynamic stability, including, administration of alpha 1 adrenergic agonists or angiotensin II (angiotensinamide) administration. Ramiprilat, the active metabolite of ramipril is poorly removed from the general circulation by haemodialysis.

2 years.

Do not store above 25°C.

Keep the blister in the outer carton. Keep the container tightly closed.

Store in the original package to protect from moisture.

Ramipril capsules are available in Clear PVC/ PE/ PVdC- Aluminium blister pack and white opaque HDPE bottle pack.

Pack size:

Blister pack: 7, 10, 14, 20, 21, 28, 30, 42, 50, 56, 60, 90, 98 & 100 capsules.

Bottle pack: 30, 100, 500 & 1000 capsules.

Not all pack sizes may be marketed.

No special requirements.