Trade Names:Aceon- Tablets 2 mg- Tablets 4 mg- Tablets 8 mgApo-Perindopril (Canada)Coversyl (Canada)
Competitively inhibits angiotensin I–converting enzyme, resulting in prevention of angiotensin I conversion to angiotensin II, a potent vasoconstrictor that also stimulates aldosterone release. Clinical consequences are a decrease in BP, reduced sodium resorption, and potassium retention.
Rapid absorption. Bioavailability is approximately 75% (perindopril) and approximately 25% (active metabolite perindoprilat). Food reduces bioavailability 35%. Steady state is 3 to 6 days. T max is approximately 1 h (perindopril) and 3 to 7 h (active metabolite perindoprilat).
Protein binding is 60% (perindopril) and 10% to 20% (active metabolite perindoprilat).
Extensively metabolized in liver to active metabolite perindoprilat and other metabolites by glucuronidation and cyclization via dehydration.
Urine (4% to 12% unchanged, 4.5% to 22% as metabolites). Mean total body Cl is 219 to 362 mL/min and mean renal Cl is 23.3 to 28.6 mL/min (perindopril). The t ½ is 0.8 to 1 h (perindopril). Apparent mean t ½ is 30 to 120 h (metabolite perindoprilat).
CrCl is 30 to 80 mL/min; metabolite AUC is approximately doubled.Hepatic Function Impairment
Bioavailability of metabolite is increased, and plasma concentrations are approximately 50% higher.Elderly
Plasma concentrations of perindopril and metabolite are approximately twice those observed in younger patients; renal excretion of metabolite decreases (70 yr of age and older).Heart failure patients
Metabolite Cl is reduced in CHF, resulting in 40% higher dose interval AUC.
Reduce risk of CV mortality or nonfatal MI in patients with stable coronary artery disease; treatment of essential hypertension.
Hypersensitivity or history of angioedema related to ACE inhibitor treatment.
PO Initial dose is 2 mg/day (max, 8 mg/day).Stable Coronary Artery DiseaseAdults
PO Initial dosage 4 mg once daily for 2 wk; then increase as tolerated to a maintenance dosage of 8 mg once daily. In patients older than 70 yr of age, start with 2 mg once daily for the first week, followed by 4 mg once daily the second week, and 8 mg once daily for maintenance as tolerated.Uncomplicated HypertensionAdults
PO Initial dosage 4 mg once daily; then titrate upward until BP, measured just before the next dose, is controlled (max, 16 mg/day). Usual maintenance dose is 4 to 8 mg/day.Patients older than 65 yr of age
PO Initial dose 4 mg/day in 1 or 2 divided doses; then titrate upward until BP, measured just before the next dose, is controlled (max, 8 mg/day).Use with Concomitant DiureticsAdults
PO If BP is not adequately controlled with perindopril alone, a diuretic may be added. In patients being treated with a diuretic, to reduce the likelihood of the occurrence of symptomatic hypotension, discontinue the diuretic 2 to 3 days prior to beginning perindopril. If the diuretic cannot be discontinued, use an initial dose of perindopril 2 to 4 mg/day and titrate the dose as previously described.
Administer without regard to meals. Administer with food if GI upset occurs.
Store tablets at controlled room temperature (68° to 77°F). Protect from moisture.
May increase cough.Digoxin
May cause increased or decreased digoxin levels.Diuretics
Increased risk of excessive BP reduction.Drugs capable of increasing serum potassium (eg, cyclosporine, heparin, indomethacin), potassium-sparing diuretics (eg, spironolactone), potassium supplements
Increased risk of hyperkalemia.Indomethacin
May reduce hypotensive effects, especially in low-renin or volume-dependent hypertensive patients.Lithium
Increased risk of lithium toxicity.Loop diuretics
Effects of loop diuretics may be decreased.Phenothiazines
Enhanced hypotensive effects.Salicylates (eg, aspirin)
The hypotensive and vasodilator effects of perindopril may be reduced.
None well documented.
Dizziness (8%); cerebrovascular accident (0.2%).
Sinusitis (5%); ear infection (1%).
Cough (12%); pulmonary fibrosis (less than 0.1%).
Back pain (6%); hypertonia, upper extremity pain, viral infection (3%); fever (2%); anaphylactoid reactions (0.3% to 1%); angioedema (0.1%).
When used in pregnancy during the second and third trimesters, ACE inhibitors can cause injury and even death to the developing fetus. When pregnancy is detected, discontinue therapy as soon as possible.
In hypertensive patients with unilateral or bilateral renal artery stenosis, increases in BUN and serum creatinine may occur; therefore, monitor renal function during the first few weeks of therapy.
Category C (first trimester); Category D (second and third trimesters).
Safety and efficacy not established.
Changes in renal function may occur in susceptible individuals.
May occur and is potentially fatal if laryngeal edema occurs. Use drug with extreme caution in patients with history of angioedema.
In CHF patients, where renal function may depend on renin angiotensin-aldosterone system activity, perindopril treatment may be associated with oliguria and progressive azotemia, and, rarely, acute renal failure or death.
Chronic nonproductive cough may occur.
Hepatic failure has occurred rarely with other ACE inhibitors.
Symptomatic hypotension may occur.
Has occurred rarely with other ACE inhibitors; risk appears greater with renal function impairment, heart failure, or immunosuppression. Ensure that CBC with differential is evaluated prior to starting therapy, at 2-wk intervals for 3 mo and then periodically thereafter in patients at risk.
Circulatory arrest, death, hypotension, hypothermia.
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