Gleperil

Uses

Gleperil is a long-acting ACE (Angiotensin Converting Enzyme) inhibitor and is used for Essential hypertension, Stable coronary artery disease, Congestive heart failure.

Gleperil is also used to associated treatment for these conditions: Cardiovascular Events, Diabetic Nephropathy, High Blood Pressure (Hypertension), Hypertension,Essential, Myocardial Infarction, NYHA Class I Congestive heart failure, Stroke, Chronic heart failure with reduced ejection fraction (NYHA Class II), Chronic heart failure with reduced ejection fraction (NYHA Class III)

How Gleperil works

There are two isoforms of ACE: the somatic isoform, which exists as a glycoprotein comprised of a single polypeptide chain of 1277; and the testicular isoform, which has a lower molecular mass and is thought to play a role in sperm maturation and binding of sperm to the oviduct epithelium. Somatic ACE has two functionally active domains, N and C, which arise from tandem gene duplication. Although the two domains have high sequence similarity, they play distinct physiological roles. The C-domain is predominantly involved in blood pressure regulation while the N-domain plays a role in hematopoietic stem cell differentiation and proliferation. ACE inhibitors bind to and inhibit the activity of both domains, but have much greater affinity for and inhibitory activity against the C-domain. Gleperilat, the active metabolite of perindopril, competes with ATI for binding to ACE and inhibits and enzymatic proteolysis of ATI to ATII. Decreasing ATII levels in the body decreases blood pressure by inhibiting the pressor effects of ATII as described in the Pharmacology section above. Gleperil also causes an increase in plasma renin activity likely due to a loss of feedback inhibition mediated by ATII on the release of renin and/or stimulation of reflex mechanisms via baroreceptors.

Dosage

Gleperil dosage

Hypertension: One Gleperil 4 tablet once daily preferably in the morning. If necessary, the dose may be increased to 8 mg after 1 month of treatment. Gleperil should be taken before food.

Stable coronary artery disease: Gleperil 4 once daily for two weeks, then increased to 8 mg once daily, depending on renal function and provided that the 4 mg dose is well tolerated. Elderly patients should receive Gleperil 2 mg once daily for one week, then Gleperil 4 once daily the next week, before increasing the dose up to 8 mg once daily, depending on renal, function. The dose should be increased only if the previous lower dose is well tolerated.

Congestive heart failure: Gleperil should be started under close medical supervision at a starting dose of 2 mg in the morning. If necessary dose may be increased to 4 mg.

Elderly patients: Start treatment at Gleperil 2 mg daily.

Side Effects

Rare and mild: usually at the start of treatment cough, fatigue, asthenia, headache, disturbances of mood and/or sleep have been reported.

Less often: Taste impairment, epigastric discomfort, nausea, abdominal pain and rash. Reversible increase in blood urea and creatinine may be observed. Proteinuria has occurred in some patients.

Rarely: Angioneurotic edema and decrease in hemoglobin, red cells and platelets have been reported.

Toxicity

The most likely symptom of overdose is severe hypotension. The most common adverse effects observed in controlled clinical trials include cough, digestive symptoms, fatigue, headache, and dizziness.

Precaution

In the following cases, Gleperil should be used with caution:

• Renovascular hypertension
• Surgery/Anesthesia
• Renal failure: The dose should be cautiously adjusted in accordance with the creatinine clearance
• Symptomatic hypotension is rarely seen, but is more likely in volume-depleted patients, those receiving diuretics, or with the first two doses
• In diuretic-treated patients: stop the diuretic 3 days before starting Gleperil. A diuretic may later be given in combination if necessary; potassium-sparing diuretics are not recommended
• Combination with neuroleptics or imipramine-type drugs may increase the hypotensive effect. Serum lithium concentrations may rise during lithium therapy

Interaction

May enhance hypotensive effect with diuretics. Additive hyperkalaemic effect with K supplements, K-sparing diuretics, and other drugs (e.g. ciclosporin, heparin, indometacin). May increase serum levels and toxicity of lithium. Antihypertensive effect may be reduced by aspirin or other NSAIDs. Coadministration with NSAIDs may also increase the risk of renal impairment. Increased risk of hypoglycaemia with antidiabetic agents. Rarely, nitritoid reactions occur with concomitant use of gold (Na aurothiomalate).

Food Interaction

• Avoid hypertensive herbs (e.g. bayberry, blue cohosh, cayenne, ephedra, and licorice).
• Avoid potassium-containing products. Potassium products increase the risk of hyperkalemia.
• Limit salt intake. Salt may attenuate the antihypertensive effect.
• Take with or without food. The absorption is unaffected by food.

[Moderate] GENERALLY AVOID: Moderate-to-high dietary intake of potassium can cause hyperkalemia in some patients who are using angiotensin converting enzyme (ACE) inhibitors.

In some cases, affected patients were using a potassium-rich salt substitute.

ACE inhibitors can promote hyperkalemia through inhibition of the renin-aldosterone-angiotensin (RAA) system.

MANAGEMENT: It is recommended that patients who are taking ACE inhibitors be advised to avoid moderately high or high potassium dietary intake.

Particular attention should be paid to the potassium content of salt substitutes.

Gleperil Drug Interaction

Moderate: aspirin, aspirin, aspirin, celecoxib, furosemide, pregabalin, nitroglycerinUnknown: rosuvastatin, duloxetine, apixaban, omega-3 polyunsaturated fatty acids, atorvastatin, metoprolol, esomeprazole, acetaminophen, clopidogrel, levothyroxine, cyanocobalamin, ascorbic acid, cholecalciferol

Gleperil Disease Interaction

Major: angioedema, bone marrow suppression, CHF, hemodialysis, hyperkalemia, hypotensionModerate: liver disease, renal dysfunction, hepatic impairment

Elimination Route

Rapidly absorbed with peak plasma concentrations occurring approximately 1 hour after oral administration. Bioavailability is 65-75%. Following absorption, perindopril is hydrolyzed to perindoprilat, which has an average bioavailability of 20%. The rate and extent of absorption is unaffected by food. However, food decreases the extent of biotransformation to peridoprilat and reduces its bioavailability by 35%.

Half Life

Gleperil, 1.2 hours; Peridoprilat, 30-120 hours. The long half life of peridoprilat is due to its slow dissociation from ACE binding sites.

Clearance

• 219 - 362 mL/min [oral administration]

Elimination Route

Gleperil is extensively metabolized following oral administration, with only 4 to 12% of the dose recovered unchanged in the urine.

Pregnancy & Breastfeeding use

Gleperil should not be used during pregnancy & lactation.

Contraindication

Gleperil is contraindicated in patients with a history of hypersensitivity to Gleperil. This drug is contraindicated in case of management of hypertension of Children, during Pregnancy & Lactation.

Acute Overdose

Symptoms: Hypotension, bradycardia, circulatory shock, renal failure, hyperventilation, electrolyte disturbances, tachycardia, palpitations, dizziness, anxiety, and cough.

Management: Symptomatic and supportive. IV infusion of NaCl 0.9%. Treatment with angiotensin II infusion and/or IV catecholamines may also be considered. Haemodialysis may be beneficial.

Storage Condition

Keep away from the reach of children. Store in a cool & dry place, protect from light and moisture.

Innovators Monograph

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