Posology
It is recommended that Apo Ramipril is taken each day at the same time of the day.
Apo Ramipril can be taken before, with or after meals, because food intake does not modify its bioavailability.
Apo 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 Apo 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 Apo Ramipril.
In hypertensive patients in whom the diuretic is not discontinued, therapy with Apo Ramipril should be initiated with a 1.25 mg dose. Renal function and serum potassium should be monitored. The subsequent dose of Apo Ramipril should be adjusted according to blood pressure target.
Hypertension
The dose should be individualised according to the patient profile and blood pressure control.
Apo Ramipril may be used in monotherapy or in combination with other classes of antihypertensive medicinal products.
Starting dose
Apo 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.
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 Apo 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 Apo 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 Apo 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 Apo 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 Apo 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 Apo Ramipril after one or two weeks and then to 10 mg Apo 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 Apo 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
Apo 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 :
- 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
In patients with hepatic impairment, treatment with Apo Ramipril must be initiated only under close medical supervision and the maximum daily dose is 2.5 mg Apo 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.1, 5.2 & 5.3 but no specific recommendation on posology can be made.
Method of administration
Oral use.
