Source: European Medicines Agency (EU)
Zofenopril is indicated for the treatment of mild to moderate essential hypertension.
Zofenopril is indicated for the treatment initiated within the first 24 hours of patients with acute myocardial infarction with or without signs and symptoms of heart failure, who are haemodynamically stable and have not received thrombolytic therapy.
The need for dosage titration should be determined by measurement of blood pressure just before the next dose. The dose should be increased at an interval of four weeks.
Treatment should be started with 15mg once daily and titrated upwards to achieve optimal blood pressure control.
The usual effective dose is 30mg once daily. The maximum dose is 60mg per day administered in a single or two divided doses. In case of inadequate response, other antihypertensive agents such as diuretics may be added (see sections 4.3, 4.4, 4.5 and 5.1).
First-dose hypotension may occur in high risk patients (see section 4.4). Initiation of therapy with ACE inhibitors requires correction of salt and/or volume deficiencies, discontinuation of an existing diuretic therapy for two to three days before ACE inhibition and a starting dose of 15mg daily. If this is not possible, the initial dose should be 7.5 mg daily.
Patients at high risk for severe acute hypotension should be monitored closely preferably in hospital, for as long as the maximal effect is expected after administration of the first dose and whenever the dose of ACE inhibitor and/or diuretic is increased. This also applies to patients with angina pectoris or cerebrovascular disease in whom excessive hypotension could result in a myocardial infarction or cerebrovascular accident.
In hypertensive patients with mild renal impairment (creatinine clearance > 45ml/min) the same dose level and once-daily regimen for zofenopril can be employed as for patients with normal renal function. Patients with moderate to severe impairment (creatinine clearance < 45ml/min) should be given one-half the therapeutic dose of zofenopril; the once-daily dosage regimen does not require modification.
The starting dose and the dosage regimen of zofenopril for hypertensive patients maintained on dialysis should be one-quarter the dose used for patients with normal renal function.
Recent clinical observations have shown a high incidence of anaphylactoid-like reactions in patients on ACE inhibitors during haemodialysis with high-flux dialysis membranes or during LDL apheresis (see section 4.4).
In older people with normal creatinine clearance no adjustment is necessary. In tolder people with reduced creatinine clearance (< 45ml/min) half of the daily dose is recommended.
Creatinine clearance may be estimated from serum creatinine by the following formula:
Creatininr clearance (ml/min) = (140 – age) X weigth (kg) / Serum creatine (mg/dl) X 72
The above method provides creatinine clearance in males. For females the value obtained should be multiplied by 0.85.
In hypertensive patients with mild to moderate hepatic impairment, the starting dose of zofenopril is half of the dose for patients with normal hepatic function.
In hypertensive patients with severe liver impairment zofenopril is contraindicated.
The safe or effective use of zofenopril in children and adolescents below the age of 18 years has not been established. Therefore, it should not be used in children.
Treatment with zofenopril should begin within 24 hours after the onset of symptoms of acute myocardial infarction and continued for six weeks.
The posology should be as follows:
1st and 2nd day: 7.5mg every 12 hours
3rd and 4th day: 15mg every 12 hours
from 5th day and onwards: 30mg every 12 hours
In the event of low systolic blood pressure (≤120mmHg) at the start of treatment or during the first three days following myocardial infarction, the daily dose should not be increased. In the event of hypotension (≤100mmHg), the treatment can be continued with the dose that was previously tolerated. In the event of severe hypotension (systolic blood pressure lower than 90mmHg in two consecutive measurement at least one hour apart), zofenopril should be discontinued.
After 6 weeks treatment patients must be re-evaluated and the treatment should be discontinued in patients without signs of left ventricular dysfunction or cardiac failure. If these signs are present, treatment might be continued long term.
Patients should also receive, as appropriate, the standard treatment such as nitrates, aspirin or β-blockers.
Zofenopril should be used with caution in myocardial infarction patients who are more than 75 years of age.
The efficacy and safety of zofenopril in myocardial infarction patients with renal impairment or who are undergoing dialysis has not been established. Therefore, zofenopril should not be used in these patients.
The efficacy and safety of zofenopril in myocardial infarction patients with hepatic impairment has not been established. Therefore, it should not be used in these patients.
Zofenopril can be taken before, during or after meals. Dosage must be titrated according to the therapeutic response of the patient.
NOTE: Please be aware that not all recommended dosages can be administered with this product, since the lowest dose achievable with this product is 15 mg (half a tablet).
Symptoms of overdosage are severe hypotension, shock, stupor, bradycardia, electrolyte disturbances and renal failure.
After ingestion of an overdose, the patients should be kept under close supervision, preferably in an intensive care unit. Serum electrolytes and creatinine should be monitored frequently.
Therapeutic measures depend on the nature and severity of the symptoms. If the ingestion is recent, measures to prevent absorption such as gastric lavage and administration of adsorbents and sodium sulphate may be implemented. If hypotension occurs, the patient should be placed in shock position and the judicious use of volume expanders and/or treatment with angiotensin II considered. Bradycardia or extensive vagal reactions should be treated by administering atropine. The use of a pacemaker may be considered. ACE inhibitors may be removed from the circulation by hemodialysis. The use of high-flux polyacrylonitrile membranes should be avoided.
3 years.
No special precautions for storage.
PVC/PVDC/Aluminium foil blisters in cartons of 14, 28, 30 and 56 film-coated tablets.
Not all pack sizes may be marketed.
No special requirements.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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