Index Terms

 Perindopril Erbumine

Dosage Forms
Excipient information presented when available (limited, particularly for generics);
consult specific product labeling.

Tablet, Oral, as erbumine:

Aceon: 4 mg, 8 mg [scored]

Generic: 2 mg, 4 mg, 8 mg

Brand Names: U.S.

 Aceon

Pharmacologic Category
 Angiotensin-Converting Enzyme (ACE) Inhibitor
 Antihypertensive

Pharmacology
Perindopril is a prodrug for perindoprilat, which acts as a competitive inhibitor of
angiotensin-converting enzyme (ACE); prevents conversion of angiotensin I to
angiotensin II, a potent vasoconstrictor; results in lower levels of angiotensin II which,
in turn, causes an increase in plasma renin activity and a reduction in aldosterone
secretion

Metabolism

Hydrolyzed hepatically to active metabolite, perindoprilat (~17% to 20% of a dose)

and other inactive metabolites

Excretion

Urine (75%, 4% to 12% as unchanged drug)

Onset of Action
Peak effect: 1-2 hours

Time to Peak

Chronic therapy: Perindopril: 1 hour; Perindoprilat: 3-7 hours (maximum perindoprilat

serum levels are 2-3 times higher and Tmax is shorter following chronic therapy); CHF:
Perindoprilat: 6 hours

Half-Life Elimination

Parent drug: 1.5-3 hours; Metabolite: Effective: 3-10 hours, Terminal: 30-120 hours

Protein Binding

Perindopril: 60%; Perindoprilat: 10% to 20%

Special Populations: Renal Function Impairment

At CrCl of 30 to 80 mL/min, perindoprilat AUC is approximately doubled.

Special Populations: Hepatic Function Impairment

Bioavailability of perindoprilat is increased, and plasma concentrations are
approximately 50% higher.

Special Populations: Elderly

Plasma concentrations of perindopril and perindoprilat in patients older than 70 y are
approximately twice those observed in younger patients; renal excretion of
perindoprilat decreases.

Special Populations Note

Heart failure: Clearance is reduced, resulting in a 40% higher dose-interval AUC.

Use: Labeled Indications

Treatment of hypertension; reduction of cardiovascular mortality or nonfatal
myocardial infarction in patients with stable coronary artery disease
Guideline recommendations:

Hypertension: The 2014 guideline for the management of high blood pressure in
adults (Eighth Joint National Committee [JNC 8]) recommends initiation of
pharmacologic treatment to lower blood pressure for the following patients:

• Patients ≥60 years of age with systolic blood pressure (SBP) ≥150 mm Hg or
diastolic blood pressure (DBP) ≥ 90 mm Hg. Goal of therapy is SBP <150 mm Hg and
DBP <90 mm Hg.

• Patients <60 years of age with SBP ≥140 mm Hg or DBP is ≥90 mm Hg. Goal of
therapy is SBP <140 mm Hg and DBP <90 mm Hg.

• Patients ≥18 years of age with diabetes and SBP ≥140 mm Hg or DBP ≥90 mm Hg.
Goal of therapy is SBP <140 mm Hg and DBP <90 mm Hg.

• Patients ≥18 years of age with chronic kidney disease (CKD) and SBP ≥140 mm Hg
or DBP ≥90 mm Hg. Goal of therapy is SBP <140 mm Hg and DBP <90 mm Hg.

Chronic kidney disease (CKD) and hypertension: Regardless of race or diabetes

status, the use of an ACE inhibitor (ACEI) or angiotensin receptor blocker (ARB) as
initial therapy is recommended to improve kidney outcomes. In the general nonblack
population (without CKD) including those with diabetes, initial antihypertensive
treatment should consist of a thiazide-type diuretic, calcium channel blocker, ACEI, or
ARB. In the general black population (without CKD) including those with diabetes,
initial antihypertensive treatment should consist of a thiazide-type diuretic or a
calcium channel blocker instead of an ACEI or ARB.

Coronary artery disease (CAD) and hypertension: The American Heart Association,
American College of Cardiology, and American Society of Hypertension
(AHA/ACC/ASH) 2015 scientific statement for the treatment of hypertension in
patients with CAD recommends the use of an ACE inhibitor (or an ARB) as part of a
regimen in patients with hypertension and chronic stable angina if there is prior MI,
LV systolic dysfunction, diabetes mellitus, or CKD. A BP target of <140/90 mm Hg is
reasonable for the secondary prevention of cardiovascular events. A lower target BP
(<130/80 mm Hg) may be appropriate in some individuals with CAD, previous MI,
stroke or transient ischemic attack, or CAD risk equivalents (AHA/ACC/ASH
[Rosendorff 2015]).

Heart failure: The ACCF/AHA 2013 heart failure guidelines recommend the use of
ACE inhibitors, along with other guideline-directed medical therapies, to prevent HF
in patients with a reduced ejection fraction who have a history of MI (stage B HF), to
prevent HF in any patient with a reduced ejection fraction (stage B HF), or to treat
those with HF and reduced ejection fraction (stage C HFrEF) (ACCF/AHA [Yancy
2013])
Contraindications
Hypersensitivity to perindopril, any other ACE inhibitor, or any component of the
formulation; angioedema related to previous treatment with an ACE inhibitor; history
of hereditary/idiopathic angioedema; concomitant use with aliskiren in patients with
diabetes mellitus

Canadian labeling: Additional contraindications (not in US labeling): Concomitant use

with aliskiren in patients with moderate-to-severe renal impairment (GFR <60
mL/minute/1.73 m2); women who are pregnant, planning to become pregnant, or
nursing; hereditary problems of galactose intolerance, glucose-galactose
malabsorption, or the Lapp lactase deficiency (formulation contains lactose)

Dosing: Adult
Heart failure (off-label use): Oral: Initial: 2 mg once daily with gradual dose
titration to a target dose of 8 to 16 mg once daily (ACCF/AHA [Yancy, 2013]).

Hypertension: Oral: Initial: 4 mg/day but may be titrated to response; usual range: 4
to 8 mg/day (may be given in 2 divided doses); increase at 1- to 2-week intervals
(maximum: 16 mg/day).

Concomitant therapy with diuretics: To reduce the risk of hypotension, discontinue

diuretic, if possible, 2 to 3 days prior to initiating perindopril. If unable to stop
diuretic, initiate perindopril at 2 to 4 mg/day (given in 1 to 2 divided doses) and
monitor blood pressure closely for the first 2 weeks of therapy, and after any dose
adjustment of perindopril or diuretic.

Stable coronary artery disease: Oral: Initial: 4 mg once daily for 2 weeks; then
increase as tolerated to 8 mg once daily.

Dosing: Geriatric
Hypertension: >65 years: Oral: Initial: 4 mg/day; ACCF/AHA recommends
consideration of lower initial doses with titration per response (Aronow 2011);
Experience with doses >8 mg/day is limited; may be given in 1 to 2 divided doses.

Stable coronary artery disease: >70 years: Oral: Initial: 2 mg/day for 1 week; then
increase as tolerated to 4 mg/day for 1 week; then increase as tolerated to 8 mg/day.

Dosing: Renal Impairment

CrCl >30 mL/minute: Initial: 2 mg/day; maintenance dosing not to exceed 8 mg/day
CrCl <30 mL/minute: Safety and efficacy not established; 2 mg once every 48 hours
has been recommended for patients with CrCl 15 to 30 mL/minute (Coversyl
Canadian product labeling 2014).

Hemodialysis: 2 mg on dialysis days (given after dialysis) has been recommended

(Coversyl Canadian product labeling 2014). Perindopril and its metabolites are
dialyzable.

Dosing: Hepatic Impairment

No dosage adjustment provided in manufacturer's labeling. However, perindoprilat
bioavailability is increased with hepatic impairment.

Administration
Oral: Administer prior to a meal.

Storage
Store at room temperature of 20°C to 25°C (68°F to 77°F). Protect from moisture.