(i) ROUTE OF ADMINISTRATION
Oral
DOSAGE AND ADMINISTRATION

The absorption of Health 2000 Lisinopril 10 mg is unaffected by food.
Hypertension
The need for dosage titration should be determined by measurement of the blood pressure just before the next dose.
Treatment should be started with 2.5 mg once daily and titrated upwards to achieve optimal blood pressure control. The usual effective dosage range is 10-20 mg once daily. The maximum recommended dose is 40 mg daily.
Diuretic-treated patients In hypertensive patients who are on diuretics, symptomatic hypotension may occur occasionally following the initial dose. The diuretic should be discontinued two or three days before beginning therapy with Health 2000 Lisinopril 10 mg and may be resumed later if required. If the diuretic cannot be discontinued, an initial dose of 5 mg should be used under medical supervision for at least two hours and until blood pressure has stabilised for at least another hour.
Congestive heart failure Health 2000 Lisinopril 10 mg may be used as adjunctive therapy with non-potassium sparing diuretics and where appropriate, digitalis.
Treatment should be initiated in hospital under close medical supervision, with a recommended starting dose of 2.5 mg with subsequent dose titration. If possible, the dose of diuretic should be reduced before beginning treatment. The dose should be gradually increased, depending on the patient's response, to the usual maintenance dose (520 mg). This dose adjustment may be performed over a two to four week period or more rapidly if clinically indicated.
Blood pressure and renal function should be monitored closely both before and during treatment.
Acute myocardial infarction Treatment may be started within 24 hours of symptom onset. The first dose is 5 mg, followed by 5 mg after 24 hours, 10 mg after 48 hours and then 10 mg once daily. Dosing should continue for 6 weeks. Dosage should be decreased to 2.5 mg in patients with systolic blood pressure > 120mm Hg. If hypotension develops (SBP < 100mm Hg), the daily maintenance dosage may be 5 mg, with a temporary decrease to 2.5 mg if required. Persistent hypotension (SBP < 90mm Hg for > 1 hour) necessitates lisinopril discontinuation.
In impaired renal function Health 2000 Lisinopril 10 mg is excreted by the kidney, and should be used with caution in patients with renal insufficiency (See also Warnings and Precautions).
Renal status Creatinine clearance ml/min Initial dose mg/day
Normal renal function to mild impairment > 30 10
Moderateto severe impairment > 10 to < 30 5
Dialysis patients < 10 2.5*
· Dosage or dosing interval should be adjusted according to the blood pressure response.

(ii) THERAPEUTIC / DIAGNOSTIC CLAIMS

HYPERTENSION
Health 2000 Lisinopril 10 mg is indicated in the treatment of all grades of essential hypertension and renovascular hypertension, alone as initial therapy or concomitantly with other classes of antihypertensive agents, in the treatment of congestive heart failure as adjunctive therapy with non-potassium sparing diuretics and digitalis, and in acute myocardial infarction

(iii) DESCRIPTION OF DOSAGE FORM

Lisinopril is a longacting angiotensin-converting enzyme (ACE) inhibitor. Lisinopril is a specific inhibitor of angiotensin converting enzyme, which catalyses the conversion of the inactive decapeptide angiotensin I to the active angiotensin II, a very powerful vasoconstric-tor agent. As a consequence, blood pressure may be reduced in hypertensive patients and cardiac workload may be reduced in patients with congestive heart failure.

(iv) CONTRAINDICATIONS

Hypersensitivity to this product, patients with a history of angioedema related to previous treatment with an angiotensin-converting enzyme inhibitor and patients with aortic stenosis, cor pulmonale or outflow tract obstruction.

WARNING AND PRECAUTIONS
DRUG INTERACTIONS
Diuretics: Patients on diuretics may occasionally experience an excessive reduction of blood pressure after initiation of therapy with Health 2000 Lisinopril 10 mg. The possibility of hypotensive effects with Health 2000 Lisinopril 10 mg can be minimised by either discontinuing the diuretic or increasing the salt intake prior to initiation of treatment (See also Dosage and Administration).
Agents increasing serum potassium: Attenuate potassium loss caused by thiazidetype diuretics. If concomitant use of these agents is indicated, they should be used with caution, and with frequent monitoring of serum potassium.
Indomethacin may reduce the antihypertensive efficacy of lisinopril.
ACUTE MYOCARDIAL INFARCTION PATIENTS WITH EVIDENCE OF RENAL DYSFUNCTION OR AT RISK OF SERIOUS HEMODYNAMIC DETERIORATION
The drug should be used with caution in these patients.
PREGNANCY
When used in pregnancy, during the second and third trimesters, ACE inhibitors can cause injury and death to the developing foetus. When pregnancy is detected the drug should be discontinued.

NURSING MOTHERS It is not known whether lisinopril is secreted in breast milk. Hence caution should be exercised if administered to lactating women.
PAEDIATRIC USE Safety and effectiveness in children have not been established.
IN THE ELDERLY Pharmacokinetic studies indicate that maximum blood levels and area under the plasma concentration time curve, (AUC), are doubled in older patients so that dosage adjustments should be made with particular caution.
IN IMPAIRED RENAL FUNCTION These patients may require lower maintenance doses. As a consequence of inhibiting the renin-angiotensin-aldosterone system (RAAS), changes in renal function may be anticipated in susceptible individuals. In patients with severe congestive heart failure whose renal function may depend on the activity of RAAS, treatment with ACE inhibitors may be associated with oliguria and/or progressive azotemia and rarely acute renal failure.
In hypertensive patients with unilateral or bilateral renal artery stenosis, increases in blood urea nitrogen and serum creatinine may occur which is usually reversible.
Hence evaluation of patients with hypertension or heart failure should always include assessment of renal function.
Health 2000 Lisinopril 10 mg is dialysable.
SYMPTOMATIC HYPOTENSION Symptomatic hypotension was seen rarely in uncomplicated hypertensive patients. Patients should be cautioned to report light-headedness especially during the first few days of therapy.
COUGH
Cough has been reported with the use of ACE inhibitors. Characteristically, the cough is non-productive, persistent and resolves after discontinuation of therapy.
(v) SIDE EFFECTS
Angioneurotic oedema has been reported with ACE inhibitors. In such cases Health 2000 Lisinopril 10 mg Tablets should be discontinued immediately.
Other adverse reactions which have been observed are dizziness, headache, diarrhoea, cough, fatigue, nausea, rash, palpitation, chest pain and asthenia. Increases in blood urea and creatinine may occur.

(vi) TOXIC EFFECTS
CARCINOGENICITY
Studies in male and female rats for 105 weeks at doses up to 56 times the maximum recommended human daily dose (based on a patient weight of 50 kg) and in male and female mice for 92 weeks at doses up to 84 times the maximum recommended human daily dose (based on a patient weight of 50 kg) found no evidence of tumorigenicity.
MUTAGENICITY

No evidence of mutagenicity was found in tests including the Ames bacterial assay with or without metabolic activation, forward mutation assay using Chinese hamster lung cells, in vitro alkaline elution rat hepatocyte assay, and chromosomal aberration studies in vitro in Chinese hamster ovary cells and in vivo in mouse bone marrow

PREGNANCY/REPRODUCTION

No adverse effects on reproductive performance were found in male and female rats given doses up to 300 mg/kg per day of lisinopril.