Kuinopril® (10 & 20) plus Tablets (LISINOPRIL 10mg + HYDROCHLOROTHIAZIDE 12.5mg) (LISINOPRIL 20mg + HYDROCHLOROTHIAZIDE 12.5mg)
COMPOSITION
Each tablet contains Lisinopril 10mg and Hydrochlorothiazide 12.5mg
Each tablet contains Lisinopril 20mg and Hydrochlorothiazide 12.5mg
CLINICAL PHARMACOLOGY
Pharmacodynamic:
Lisinopril in Kuinopril®– plus is a competitive inhibitor of Angiotensin Converting Enzymes (ACE); this prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor; and results in lower levels of angiotensin II which causes an increase in plasma rennin activity and a reduction in aldosterone secretion. A Central Nervous System (CNS) mechanism may also be involved in the hypotensive effect as angiotensin. It increases adrenergic outflow from the system (CNS); vasoactive kailitrens may be decreased in conversion to active hormones by Angiotensin-Converting Enzymes (ACE) inhibitors, thus reducing blood pressure.
Hydrochlorothiazide is a diuretic and an antihypertensive agent. It affects the distal renal tubular mechanism of electrolyte reabsorption and increases excretion of sodium and chloride in approximately equivalent amount. The mechanism of the antihypertensive effect of the thiazides is unknown.
Pharmacokinetics:
Concomitant administration of lisinopril and hydrochlorothiazide has little or no effect on the bioavailability of either drug. The combination tablet is bioequivalent to concomitant administration of the separate entities.
Lisinopril:
Following oral administration of Lisinopril, peak serum concentrations occur within about 7 hours. On multiple dosing Lisinopril has an effective half life of accumulation of 12.6 hours. Lisinopril is excreted unchanged in the urine.
Hydrochlorothiazide:
When plasma levels have been followed to at least 24 hours, the plasma half-life has been observed to vary between 5-6 and 14.3 hours. At least 61% of the dose is eliminated unchanged within 24 hours. After oral hydrochlorothiazide, diuresis begins within 2 hours, peaks in about 4 hours and lasts 6 to 12 hours. Hydrochlorothiazide crosses the placenta but not blood-brain barrier.
INDICATIONS
Kuinopril®– Plus is indicated for the management of essential hypertension for patients in whom combination therapy is appropriate.
CONTRAINDICATIONS
Kuinopril®– plus is contraindicated in patients with anuria.
-In patients with a history of angioneurotic oedema relating to previous treatment with angiotensin-converting enzyme inhibitor
-In patients with hereditary or idiopathic angioedema
-In patients who are hypersensitive to other sulphonamide-derived drugs
-In patients who are hypersensitive to any component of this product.
DRUG INTERACTION
-Indomethacin may reduce the antihypertensive efficacy of Kuinopril®-plus.
-The antihypertensive effect of Kuinopril®-plus may be potentiated when given concomitantly with other agents likely to cause postural hypotension
-Thiazides may increase the responsiveness to tubocurarine.
WARNINGS/PRECAUTIONS
-Hypotension and Electrolyte/Fluid imbalance in patients at increase risk of symptomatic hypotension, initiation of therapy and dose adjustment should be monitored under close medical supervision.
Renal Function Impairment: Thiazides may not be appropriate diuretics for use in patients with renal impairment and are ineffective at creatinine clearance value of 30ml/minute or below (i.e. moderate or severe renal insufficiency).
Kuinopril® -plus should not be administered to patients with renal insufficiency (creatinine clearance < 80ml/min) until titration of the individual components has shown the need for the doses present in the combination tablets.
Hepatic Disease: Thiazides should be used with caution in patients with impaired hepatic function or progressive liver disease since minor alterations of fluid and electrolyte balance may precipitate hepatic coma.
Metabolic and Endocrine Effects: Thiazide therapy may impair glucose tolerance. Dosage adjustment of antidiabetic agents including insulin may be required. Increases in cholesterol and triglyceride levels may be associated with thiazide diuretic-therapy.
Hypersensitivity/Angioneurotic Oedema: Angioeurotic Oedema of the face, extremities, lips, tongue, glottis and/or larynx has been reported rarely in patients treated with angiotensin converting enzyme inhibitors including lisinopril in such cases.
Kuinopril®-plus should be discontinued promptly and appropriate monitoring should be instituted to ensure complete resolution of symptoms prior to dismissing the patient.
PREGNANCY AND LACTATION: Kuinopril®-plus is contraindicated in pregnancy and treatment should be stopped if pregnancy is suspected. Angiotensin Converting Enzyme inhibitors (ACE) can cause foetal and neonatal morbidity and mortality when administered to pregnant women during the second and third trimesters.
It is not known whether lisinopril is secreted in human milk; however thiazides do appear in human milk. Because of the potential for serious reactions in breast-fed infants; a decision should be made whether to discontinue Kuinopril®-plus, taking into account the importance of the drug to the mother.
KEEP OUT OF THE REACH OF CHILDREN!
ADVERSE REACTIONS / SIDE EFFECTS
Kuinopril®-plus tablets 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. One of the most common clinical side effects was dizziness, which generally responded to dosage reduction and seldom required discontinuation of therapy. Other side effects were headache, dry cough, fatigue and hypotension.
SYMPTOMS OF OVERDOSAGE AND ANTIDOTE
The Lisinopril most likely features of overdosage would be hypotension, electrolyte disturbance and renal failure. If severe hypotension occurs, the patient should be placed in the shock position and an intravenous infusion of normal saline should be given rapidly. Angiotensin Converting Enzyme Inhibitors may be removed from the general circulation by haemodialysis.
Hydrochlorothiazide
The most common signs and symptoms observed are those caused by electrolyte depletion (hypokalaemia, hypochloraemia, hyponatraemia) and dehydration resulting from excessive diuresis.
DOSAGE AND ADMINISTRATION
Kuinopril® 10 plus tablets should be administered once daily.
Kuinopril® 20 plus tablets should be administered once daily.
Kuinopril®-plus should be taken at approximately the same time each day. If the desired therapeutic effect can not be achieved in a period of 2 to 4 weeks at the dose level, the dose can be increased to two tablets once daily.
STORAGE
Store in a cool dry below 30oC.
PRESENTATION
Kuinopril®-plus is available as 20mg Lisinopril and 12.5mg Hydrochlorothiazide/tablet, in blister packs of 3×10’s.