ZESTRIL Tablet Ref.[6956] Active ingredients: Lisinopril

Zestril should be administered orally in a single daily dose. As with all other medication taken once daily, Zestril should be taken at approximately the same time each day. The absorption of Zestril tablets is not affected by food.

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

Hypertension

Zestril may be used as monotherapy or in combination with other classes of antihypertensive therapy (see sections 4.3, 4.4, 4.5 and 5.1).

Starting dose

In patients with hypertension the usual recommended starting dose is 10 mg. Patients with a strongly activated reninangiotensin-aldosterone system (in particular, renovascular hypertension, salt and/or volume depletion, cardiac decompensation, or severe hypertension) may experience an excessive blood pressure fall following the initial dose. A starting dose of 2.5-5 mg is recommended in such patients and the initiation of treatment should take place under medical supervision. A lower starting dose is required in the presence of renal impairment (see Table 1 below).

Maintenance dose

The usual effective maintenance dosage is 20 mg administered in a single daily dose. In general, if the desired therapeutic effect cannot be achieved in a period of 2 to 4 weeks on a certain dose level, the dose can be further increased. The maximum dose used in long-term, controlled clinical trials was 80 mg/day.

Diuretic-treated patients

Symptomatic hypotension may occur following initiation of therapy with Zestril. This is more likely in patients who are being treated currently with diuretics. Caution is recommended therefore, 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 Zestril. In hypertensive patients in whom the diuretic cannot be discontinued, therapy with Zestril should be initiated with a 5 mg dose. Renal function and serum potassium should be monitored. The subsequent dosage of Zestril should be adjusted according to blood pressure response. If required, diuretic therapy may be resumed (see section 4.4 and section 4.5).

Dosage adjustment in renal impairment

Dosage in patients with renal impairment should be based on creatinine clearance as outlined in Table 1 below.

Table 1. Dosage adjustment in renal impairment:

* Dosage and/or frequency of administration should be adjusted depending on the blood pressure response.

The dosage may be titrated upward until blood pressure is controlled or to a maximum of 40 mg daily.

Use in hypertensive paediatric patients aged 6–16 years

The recommended initial dose is 2.5 mg once daily in patients 20 to <50 kg, and 5 mg once daily in patients ≥50 kg. The dosage should be individually adjusted to a maximum of 20 mg daily in patients weighing 20 to <50 kg, and 40 mg in patients ≥50 kg. Doses above 0.61 mg/kg (or in excess of 40 mg) have not been studied in paediatric patients (see section 5.1).

In children with decreased renal function, a lower starting dose or increased dosing interval should be considered.

Heart failure

In patients with symptomatic heart failure, Zestril should be used as adjunctive therapy to diuretics and, where appropriate, digitalis or beta-blockers. Zestril may be initiated at a starting dose of 2.5 mg once a day, which should be administered under medical supervision to determine the initial effect on the blood pressure. The dose of Zestril should be increased:

• By increments of no greater than 10 mg.
• At intervals of no less than 2 weeks.
• To the highest dose tolerated by the patient up to a maximum of 35 mg once daily.

Dose adjustment should be based on the clinical response of individual patients.

Patients at high risk of symptomatic hypotension, e.g. patients with salt depletion with or without hyponatraemia, patients with hypovolaemia or patients who have been receiving vigorous diuretic therapy should have these conditions corrected, if possible, prior to therapy with Zestril. Renal function and serum potassium should be monitored (see section 4.4).

Posology in Acute myocardial infarction

Patients should receive, as appropriate, the standard recommended treatments such as thrombolytics, aspirin, and betablockers. Intravenous or transdermal glyceryl trinitrate may be used together with Zestril.

Starting dose (first 3 days after infarction)

Treatment with Zestril may be started within 24 hours of the onset of symptoms. Treatment should not be started if systolic blood pressure is lower than 100 mmHg. The first dose of Zestril is 5 mg given orally, followed by 5 mg after 24 hours, 10 mg after 48 hours and then 10 mg once daily. Patients with a low systolic blood pressure (120 mmHg or less) when treatment is started or during the first 3 days after the infarction should be given a lower dose – 2.5 mg orally (see section 4.4).

In cases of renal impairment (creatinine clearance <80 ml/min), the initial Zestril dosage should be adjusted according to the patient’s creatinine clearance (see Table 1).

Maintenance dose

The maintenance dose is 10 mg once daily. If hypotension occurs (systolic blood pressure less than or equal to 100 mmHg) a daily maintenance dose of 5 mg may be given with temporary reductions to 2.5 mg if needed. If prolonged hypotension occurs (systolic blood pressure less than 90 mm Hg for more than 1 hour) Zestril should be withdrawn.

Treatment should continue for 6 weeks and then the patient should be re-evaluated. Patients who develop symptoms of heart failure should continue with Zestril (see section 4.2).

Renal complications of diabetes mellitus

In hypertensive patients with type 2 diabetes mellitus and incipient nephropathy, the dose is 10 mg Zestril once daily which can be increased to 20 mg once daily, if necessary, to achieve a sitting diastolic blood pressure below 90 mmHg.

In cases of renal impairment (creatinine clearance <80 ml/min), the initial Zestril dosage should be adjusted according to the patient’s creatinine clearance (see Table 1).

Paediatric population

There is limited efficacy and safety experience in hypertensive children >6 years old, but no experience in other indications (see section 5.1). Zestril is not recommended in children in other indications than hypertension.

Zestril is not recommended in children below the age of 6, or in children with severe renal impairment (GFR <30ml/min/1.73m²) (see section 5.2).

Elderly

In clinical studies, there was no age-related change in the efficacy or safety profile of the drug. When advanced age is associated with decrease in renal function, however, the guidelines set out in Table 1 should be used to determine the starting dose of Zestril. Thereafter, the dosage should be adjusted according to the blood pressure response.

Use in kidney transplant patients

There is no experience regarding the administration of Zestril in patients with recent kidney transplantation. Treatment with Zestril is therefore not recommended.

Limited data are available for overdose in humans. Symptoms associated with overdosage of ACE inhibitors may include hypotension, circulatory shock, electrolyte disturbances, renal failure, hyperventilation, tachycardia, palpitations, bradycardia, dizziness, anxiety and cough.

The recommended treatment of overdose is intravenous infusion of normal saline solution. If hypotension occurs, the patient should be placed in the shock position. If available, treatment with angiotensin II infusion and/or intravenous catecholamines may also be considered. If ingestion is recent, take measures aimed at eliminating Zestril (e.g. emesis, gastric lavage, administration of absorbents and sodium sulphate). Zestril may be removed from the general circulation by haemodialysis (see section 4.4). Pacemaker therapy is indicated for therapy-resistant bradycardia. Vital signs, serum electrolytes and creatinine concentrations should be monitored frequently.

4 years.

Do not store above 30°C.

5 mg Tablets:

Aluminium/PVC-PVDC or Aluminium/PVC foil blister packs of 14, 20, 28, 28x1, 30, 42, 50, 56, 60, 84, 98, 100, 400 and 500 tablets.

Aluminium/PVC-PVDC or Aluminium/PVC foil blister calendar packs of 14, 28, 42, 56, 84 and 98 tablets.

HDPE bottle packs of 20, 30, 50, 100 and 400 tablets.

10 mg Tablets:

Aluminium/PVC-PVDC or Aluminium/PVC foil blister packs of 14, 20, 28, 30, 50, 56, 84, 98, 100 and 400 tablets.

Aluminium/PVC-PVDC or Aluminium/PVC foil blister calendar packs of 14, 28, 56, 84 and 98 tablets.

HDPE bottle packs of 20, 30, 50, 100 and 400 tablets.

20 mg Tablets:

Aluminium/PVC-PVDC or Aluminium/PVC foil blister packs of 14, 20, 28, 30, 42, 50, 56, 56x1, 60, 84, 98, 100, 400 and 500 tablets.

Aluminium/PVC-PVDC or Aluminium/PVC foil blister calendar packs of 14, 28, 42, 56, 84 and 98 tablets.

HDPE bottle packs of 20, 30, 50, 100 and 400 tablets.

Not all pack sizes may be marketed.

No special requirements.