ZOFENIL Film-coated tablet Ref.[49805] Active ingredients: Zofenopril

Posology

Hypertension

Adults

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.

Patients without volume or salt depletion

Treatment should be started with 15 mg once daily and titrated upwards to achieve optimal blood pressure control.

The usual effective dose is 30 mg once daily.

The maximum dose is 60 mg 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).

Patients suspected of volumeor salt depletion

First-dose hypotension may occur in high risk patients (see Special warnings and precautions for use). 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 15 mg 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.

Renal impairment and dialysis

In hypertensive patients with mild renal impairment (creatinine clearance >45 ml/min.) the same dose level and once-daily regimen for ZOFENIL can be employed as for patients with normal renal function. Patients with moderate to severe impairment (creatinine clearance <45 ml/min.) should be given one-half the therapeutic dose of ZOFENIL; the once-daily dosage regimen does not require modification.

The starting dose and the dosage regimen of ZOFENIL 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 Special warnings and precaution for use).

Elderly (over 65 years)

In the elderly with normal creatinine clearance no adjustment is necessary.

In the elderly with reduced creatinine clearance (less than 45 ml/min) half of the daily dose is recommended. Creatinine clearance may be estimated from serum creatinine by the following formula:

Clearance Creatinine (ml/min) = (140 – age) X weight (Kg) / Serum Cr. (mg/dl) X 72

The above method provides creatinine clearance in males. For females the value obtained should be multiplied by 0.85.

Hepatic impairment

In hypertensive patients with mild to moderate hepatic impairment, the starting dose of ZOFENIL is half of the dose for patients with normal hepatic function. In hypertensive patients with severe liver impairment ZOFENIL is contraindicated

Paediatric population

The safety and efficacy of ZOFENIL in children and adolescents below 18 years has not been established. Therefore its use is not recommended.

Acute myocardial infarction

Adults

Treatment with ZOFENIL 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:

1^st and 2^nd day: 7.5 mg every 12 hours

3^rd and 4^th day: 15 mg every 12 hours

from 5^th day and onwards: 30 mg 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), ZOFENIL 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.

Elderly (over 65 years)

ZOFENIL should be used with caution in myocardial infarction patients who are more than 75 years of age.

Renal impairment and dialysis

The efficacy and safety of ZOFENIL in myocardial infarction patients with renal impairment or who are undergoing dialysis has not been established. Therefore, ZOFENIL should not be used in these patients.

Hepatic impairment

The efficacy and safety of ZOFENIL in myocardial infarction patients with hepatic impairment has not been established. Therefore, it should not be used in these patients.

Method of administration

Zofenil can be taken before, during or after meals. Dosage must be titrated according to the therapeutic response of the patient.

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.

Blister PVDC /PVC/aluminium or Aclar/Aluminium or PVC/PE/PVDC/Aluminium, packs of: 12, 14, 15, 28, 30, 48, 50, 50 unit doses, 56, 56 unit doses, 90 or 100 film coated tablets.

Not all pack sizes may be marketed.

No special requirements.