Perindopril erbumine .............................. 4 mg
Indapamide ....................................... 1.25 mg
Excipients q.s ..................................... 1 tablet
(Lactose, avicel, PVP K30, sodium starch glycolate, magnesium stearate).
PRESENTATION: Box of 1 blister x 30 tablets.
PHARMACODYNAMICS: Perindopril is an ACE (Angiotensin Converting Enzyme) inhibitor and gives its action through perindoprilat activity. Perindopril catalyzes conversion of angiotensin I into angiotensin II, a potent vasoconstrictor. Inhibition of ACE results in a reduction of angiotensin II in the plasma, which leads to increased plasma renin activity and reduced secretion of aldosterone. The latter results in natriuresis and may be associated with a small increase of serum potassium. Since ACE inactivates bradykinin, inhibition of ACE also results in an increased activity of circulating and local Kallikrein-Kinin systems and thus also activation of the prostaglandin system. This mechanism contributes to blood pressure-lowering action. In patients with hypertension, perindopril reduces peripheral vascular resistance, leading to blood pressure reduction. Perindopril often causes arteriectasia and phlebectasia.
Indapamide is a sulfonamide diuretic. Indapamide has diuretic and antihypertensive effects. Indapamide inhibits the reabsorption of sodium ion in the cortical dilution segment. It increases the urinary excretion of sodium and chloride, thereby increasing urine output. Indapamide gives a response of blood vessel to vasoconstrictive amines returning normally, reduces peripheral arterial resistance. The antihypertensive effect is still maintained by indapamide in patients with no renal function.
The drug is quickly absorbed after oral administration and extensively metabolized in the liver. Perindopril is metabolized to active perindoprilat. As ingestion of food decreases biological conversion to perindoprilat, hence bioavailability. The drug is excreted mainly in the urine. Indapamide is not removed from the circulation by hemodialysis.
The drug is indicated in treatment of primary hypertension in patients whose blood pressure is not controlled by monotherapy.
The drug is contraindicated in: Patients known to be hypersensitive to perindopril, indapamide, and sulfonamide-derived drugs. Patients with a history of angioedema related to previous treatment with an ACE inhibitor. Patients with recent cerebral vascular accident, anuria. Patients with severe renal impairment (creatinine clearance < 30 ml/min.) Pediatric patients (No study on them has now been reported).
Linked to perindopril: Perindopril is used with caution in patients with heart failure, loss of water-salt, risk of hypotension and/or renal impairment, renal artery stenosis; in those with hemodialysis, renal insufficiency, hypertension caused by renal blood vessels, congestive heart failure, surgical procedures, diabetes, stable angina, and old ages.
Linked to indapamide: Indapamide is used with caution in patients with severe kidney disease, impaired hepatic function or progressive liver disease, hyperparathyroidism or thyroid gland diseases, synpathectomy. Glucose concentration should be periodically determined, particularly in patients suffered from or doubting of diabetes.
The drug is contraindicated in pregnant and nursing women.
Use with caution because the drug may cause headache, dizziness.
INTERACTIONS: Use of nonsteroidal anti-inflammatory drugs, corticoids, tetracosactide reduces the effect of perindopril. Patients on diuretics, and
especially those started recently, may occasionally experience an excessive reduction of blood pressure after initiation of perindopril therapy. Combination of perindopril with tranquillizers and imipramine
antidepressant has been reported to increase risk of orthostatic hypotension. Perindopril increases the hypoglycemic effect of insulin and oral hypoglycemic agents. Concomitant use of perindopril and potassium-sparing diuretics, potassium supplements may lead to significant increases in serum potassium, particularly in patients with renal insufficiency. Increased serum lithium has been reported in patients receiving concomitant lithium and perindopril therapy.
Use of indapamide combined with other diuretics should not be recommended because of hypokalemia and hyperuricemia. Risk of lithium toxicity has been reported during concomitant administration of lithium with indapamide. Indapamide may decrease arterial response to a vasoconstrictor e.g. noradrenaline, but this diminution is not sufficient to preclude effectiveness of noradrenaline.
Linked to perindopril: headache, temper and/or sleep disorders, asthenia; taste disturbances, dizziness, cramp; skin rash; irritation-like dry cough; impotence, dry mouth; mild decrease in hemoglobin; hyperkalemia; angioedema on face, head of limb, lips, tongue, glottis and/ or larynx.
Linked to indapamide: disturbances of electrolyte balance, hypokalemia, hyponatremia or alkaline infections caused by hypochloremia; lassitude, muscle weakness; headache, vertigo, dizziness; anorexia, nausea, vomiting; orthostatic hypotension, palpitation; eruption, itching, urticaria; thrombocytopenia, agranulocytosis; acute short-sightedness, cramp.
Inform your physician about any adverse effects occur during the treatment.
OVERDOSAGE: Linked to indapamide: Symptoms include disturbances of electrolyte balance, hypotension, muscle weakness, gastrointestinal disorders, nausea, vomiting, depressed respiration. Treatment of overdosage is symptomatic treatment; there is no specific antidote. If acute overdosage occurs, an evacuation of the stomach is recommended by emesis and gastric lavage after which the electrolyte and fluid balance should be evaluated carefully. Supportive treatment should be given to maintain respiratory and circulatory function.
Linked to perindopril: Symptom is associated to hypotension. Treatment of overdosage: Gastric lavage, intravenous infusion of isotonic saline should be given. Perindopril can be removed from the blood by hemodialysis (70 ml per min.)
Coperil Plus is taken in the morning and before a meal.
Dosage in hypertensive patients: The recommended dose is 1 tablet of Coperil Plus daily (perindopril 4 mg/ indapamide 1.25 mg).
Dosage in patients with renal impairment: In patients with creatinine clearance greater than 60 ml/minute, no dose modification is required. In patients with creatinine clearance 30-60 ml/minute, it is recommended to start treatment with the adequate dosage of the free combination (the recommended dose of perindopril is 2 mg daily). No recommendation in breaking a tablet in half; another dosage form should be applied.
Dosage in elderly patients: Treatment should be initiated after considering blood pressure response, especially in case of salt and water diminution to avoid the sudden beginning of hypotensive attacks.
Or as directed by the physician.
Read the directions carefully before use. 
Consult the physician for more information.
The drug is for prescription only. 
Shelf-life: 36 months from the manufacturing date.
Storage conditions:
Store in dry places, not exceeding 30oC, protect from light.
Specifications: Manufacturer's.


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