COMPOSITION
Each tablet contains Lisinopril 5mg and 10mg
ACTIONS
Lisinopril in kuinopril Tablet is a competitive inhibitor of angiotensin-converting enzymes (ACE); this prevents conversion of angiotensin I to angitotensin II, a potent vasoconstrictor, results in lower levels of angiotensin II which causes an increase in plasma renin activity and a reduction in aldosterone secretion. A Central Nervous System (CNS) mechanism may also be involved in the hypotensive effect as angiotensin 11 increases adrenergic outflow from the system (CNS); vasoactive kallilkreins may be decreased in conversion to active hormones by angiotensin-converting enzymes (ACE) inhibitors, thus reducing blood pressure.
INDICATIONS
-Kuinopril® is indicated in the treatment of all grades of essential hypertension and renovascular hypertension. Kuinopril® may be used alone or in combination with other antihypertensive agents.
-Kuinopril® is also indicated as an adjunctive therapy in the treatment of congestive heart
failure (after load reduction)
-Treatment of haemodynamically stable patients within 24 hours of acute myocardial infarction,
to improve survival, treatment of left ventricular dysfunction after myocardial infarction.
-Kuinpril® is indicated in normotensive insulin-dependent and hypertensive non-insulin dependent
diabetes mellitus patients who have incipient nephropathy characterized by microalbuminuria.
kuinopril® reduces urinary albumin excretion rate.
CONTRAINDICATION
Kuinopril® is contraindicated:-
-In pregnancy and should be stopped if pregnancy is suspected.
-In patients who are hypersensitive to any component of this product.
-In patients with a history of angioneurotic oedema relating to previous angiotensin-converting
enzyme inhibitor therapy and in patients with hereditary or idiopathic angioedema.
WARNINGS/PRECAUTIONS
Assessment of renal function
Evaluation of the patients should include assessment of renal function to inititation of therapy during treatment.
Impaired renal function
Kuniopril® should be used with caution in patients with renal insufficiency, as they may require reduced or less frequent doses. Close monitoring of renal function during therapy should be performed as deemed appropriate in those with renal insfficiency.
In majority, renal function will not alter or may improve.
In acute Myocardial infarction
Treatment with Lisinopril should not be initiated in patients with evidence of renal dysfunction, dedined as serum creatinine concentration exceeding 177 micromol/L and or proteinuria exceeding 500mg/24hous. If renal dysfunction develops during treatment withLlisinopril (serum creatinine concentration exceeding 265micromol/l or a doubling from the pretreatment value) then the physician should consider withdrawal of kuinopril®.
Haemodialysis patients
A high incidence of anaphylactoid reactions has been reported in patients dialysed with high-flux membrances (e.g. AN 69) and treated concomitantly with an ACE inhibitor. This combination should therefore be avoided
Symptomatic Hypotension
Symptomatic hypotension was seen rarely in uncomplicated hypertensive patients. It is more likely to occur in patients who have been volume-depleted by diuretic therapy, dietary salt restriction, dialysis, diarrhoea, or vomiting. In these patients, by discontinuing diuretic therapy or significantly reducing the diuretic dose 2 to 3 prior to initiating kuinopril® the possibility of this occurrence is reduced.
kuinopril® should be given with caution to patients with aortic stenosis or hypertrophic cardiomyopathy.
Hypotension in acute myocardial infaration
Treatment with lisinopril must not be initated in acute myocardial infarction patients who are at risk of further seriuos haemodynamic deterioration after treatment with a vasodilator.
These are patients with systolic blood pressure of 100mmHg or cardogenic shock.
During the first 3 days following the infarction, the dose should be reduced if the systolic blood pressure is 120mmHg or lower.
Maintenance doses should be reduced to 5mg or temporarily to 2.5mg if systolic blood pressure is 100mmHg or lower.
If hypotension persists (systolic blood pressure less than 90mmHg for more than 1 hour) then kuinopril® should be withdrawn.
Hypersentivity/Angioedema
Angioneurotic ocedema has been reported with angiotensin coverting enzymes inhibitors, including Lisinopril. In such cases Lisinopril should be discontinued immediately and the patients observed. Where swelling is confined to the face, lips and mouth, the condition will usually resolve without further treatment, although antihistamines may be useful in relieving symptoms.These patients should be followed carefully until the swelling has resolved.
However, angioedema associated with laryngeal oedema may be fatal. Where there is involvement of the tongue, glottis, or larynx, likely to cause airways obstruction, emergency therapy should be administered promptly. This may include the administration of adrenaline and /or the maintenance of a patient airway. The patients should be under close medical supervision until complete and sustained resolution of symptoms has occurred.
KEEP OUT OF THE REACH OF CHILDREN!
SIDE/ADVERSE EFFECTS
Lisinopril in kuinopril is usually well tolerated in clinical studies, side effects have usually been mild and transient and in most instances have not required interruption of therapy. The side effects includes: orthostatic effects, hypotension, headache, dizziness, fatigue, weakness, rash, hyperkaelemia, diarrhea, nausea, vomiting, abdominal pain, impotent, decreased haemoglobin, chest pain, increased serum creatinine (often transient),Increased BUN, and renal function (in patients with bilateral renal artery stensis or hypovolemia).
DRUG INTERACTIONS
– Combination with other antihypertensive agents such as beta-blockers and diuretics may
increase the antihypertensive efficacy. Lisinopril minimizes the development of thiazide-induced hypokaelamia and hyperuricaemia.
– Indomethacin may reduce the antihypertensive efficacy of Kuinopril®
– Lisinopril in kuinopril ® may reduce the elimination of lithium, serum levels of lithium should
be monitored if lithium salts are administered.
– Plasma potassium: usually remains within normal limits. If kuinopril® is given with a diuretic, the likelihood of diuretic induced hypokalaemia may be lessened. Kuinopril® may elevate plasma potassium supplements, potassium-sparing diuretics and potassium containing salt substitutes are not recommended.
DOSAGE AND ADMINISTRATION
Since aborption of Lisnopril in Kuinopril® is not affected by food, the tablets may be administered before, during or after meals. Kuinopril® should be administred in a single daily dose. Kuinopril® should be taken at approximately the same time each day.
Hypertension:
Adults
Essential Hypertension
The usual dosage is one tablet (10mg) administered once daily. Increase doses 5-10mg/day at 1 to 2 weeks intervals, maximum daily dose: 40mg.
Renovascular Hypertension
Treatment should be started with 2.5mg once daily and adjusted to achieve optimal blood pressure control is achieved
Elderly
The initial dose is 2.5-5mg/day; increase doses2.5-5mg/day at 1 to 2 weeks intervals.
Maximum daily dose: 40mg
Patients taking diuretics should have them discontinued 2-3days prior to initiating Kuinopril® if possible.
Restart diuretic after blood pressure is stable if needed. If diuretic cannot be discontinued prior to therapy, begin with 5mg with close supervision until stable blood pressure.
In patients with hyponatremia (<130 Eq/L), start dose at 2.5mg/day.
Congestive heart failure:
Treatment should be intiated, under close medical supervision,with a recommended starting dose of 2.5mg with subsequent dose titration. The dose should be gradually increased, depending on the patient’s response, to the usual maintenance dose (5-20mg). Dose adjustment should be based on the clinical response of individual patients. Patients should start/continue standard therapy, including diuretics, beta-blockers and digoxin as indicated.
Acute Myocardial Infarction:
(Within 24hours in hemodynamically patients), 5mg immediately, then 5mg at 24hours, 10mg at 48hours and 10mg everyday thereafter for 6 weeks. Patients should continue to receive standard treatment such as thrombolytics, aspirin and beta –blockers. Patients with a low systolic blood pressure (120mmHg or less) should be given a lower dose- 2.5mg orally. If hypotension occurs (systolic blood pressure less than or equal to 100mmHg), a daily maintenance dose of 5mg may be given with temporary reductions to 2.5mg if needed. If prolonged hypotension occurs (systolic blood pressure less than 90mmHg for more than 1hour) lisinopril should be withdrawn. The benefit appears to be greatest in patients with large myocardial infarctions and evidence of impaired left ventricular function. Patients should continue to receive standard treatment such as thrombolytics, aspirin and beta blockers lisinopril in Kuinopril® is compatible with intravenous or transdermal glyceryl trinitrate.
Renal Complication of diabetes Mellitus:
Treatment should be started with 2.5mg once daily and titrated to achieve the target dose. In normotensive insulin dependent diabetes mellitus patients, the dose is 10mg lisinopril once daily, which can be increased to 20mg once daily if necessary to achieve a sitting diastolic blood pressure below 75mmHg. In hypertensive non – insulin – dependent diabetes mellitus patients, the dose schedule is as above to achieve a sitting diastolic blood pressure below 90mmHg.
Dosing adjustment in renal impairment:
Clcr 10 -50ml/ minute: Administer 50% to 75% of normal dose.
Clcr < 10ml/minute: Administer 25% to 50% of normal dose.
Hemodialysis: Dialyzable (50%).
STORAGE
Store in a cool dry place below 30oC.
PRESENTATION
Kuinopril® is available as tablets containing10mg lisinopril in a blister pack of 3 x10’s.