Uses
Hypertension
Management of hypertension (alone or in combination with other classes of antihypertensive agents).
One of several preferred initial therapies in hypertensive patients with heart failure, postmyocardial infarction, high coronary disease risk, diabetes mellitus, chronic renal failure, and/or cerebrovascular disease.
Can be used as monotherapy for initial management of uncomplicated hypertension; however, thiazide diuretics are preferred by JNC 7.
CHF
Management of symptomatic CHF†, usually in conjunction with cardiac glycosides, diuretics, and β-adrenergic blocking agents.
Diabetic Nephropathy
A first-line agent in the treatment of diabetic nephropathy† in hypertensive patients with type 2 diabetes mellitus.
Dosage and Administration
Administration
Oral Administration
Administer orally once or twice daily without regard to meals. In clinical studies, administration in 2 divided doses was only slightly more effective than once-daily dosing.
Dosage
Available as perindopril erbumine; dosage expressed in terms of perindopril erbumine.
Adults
Hypertension
Oral
Initially, 4 mg once daily as monotherapy. Adjust dosage at approximately monthly intervals (more aggressively in high-risk patients) to achieve BP control.
In patients currently receiving diuretic therapy, discontinue diuretic, if possible, 2–3 days before initiating perindopril. May cautiously resume diuretic therapy if BP not controlled adequately with perindopril alone. If diuretic cannot be discontinued, initiate therapy at 2–4 mg daily (given in 1 dose or 2 divided doses) under close medical supervision for several hours until BP has stabilized.
Usual dosage: 4–8 mg once daily.
Prescribing Limits
Adults
Hypertension
Oral
Maximum 16 mg daily.
Special Populations
Renal Impairment
Hypertension
Initially, 2 mg daily in patients with renal impairment (Clcr >30 mL/minute); titrate until BP is controlled or to maximum of 8 mg daily. (See Renal Impairment under Cautions.)
Geriatric Patients
Hypertension
Initially, 4 mg daily, given in 1 dose or 2 divided doses. Adjust dosage to achieve BP control. Administer dosages >8 mg daily with caution and under close medical supervision.
Cautions
Contraindications
Warnings/Precautions
Warnings
Hypotension
Possible symptomatic hypotension, particularly in volume- and/or salt-depleted patients (e.g., those treated with diuretics). Risk of marked hypotension, sometimes associated with oliguria, azotemia, and, rarely, acute renal failure and death in patients with CHF with or without associated renal insufficiency. Severe hypotension may result in MI or stroke in patients with ischemic cardiovascular or cerebrovascular disease.
Hypotension may occur in patients undergoing surgery or during anesthesia with agents that produce hypotension; recommended treatment is fluid volume expansion.
To minimize potential for hypotension, correct volume and/or salt depletion (e.g., by withholding diuretic therapy, increasing sodium intake) prior to initiation of perindopril. (See Dosage under Dosage and Administration.)
In patients at risk of excessive hypotension, initiate therapy under close medical supervision; monitor closely for first 2 weeks following initiation of perindopril or any increase in perindopril or diuretic dosage.
If excessive hypotension occurs, immediately place patient in supine position and, if necessary, administer IV infusion of 0.9% sodium chloride injection. Perindopril therapy usually can be continued following restoration of volume and BP.
Hematologic Effects
Neutropenia and agranulocytosis reported with captopril; risk appears to depend principally on presence of renal impairment and/or presence of collagen vascular disease (e.g., systemic lupus erythematosus, scleroderma); risk with perindopril is unknown.
Fetal/Neonatal Morbidity and Mortality
Possible fetal and neonatal morbidity and mortality when used during pregnancy. (See Boxed Warning.)
Possible fetal and neonatal morbidity and mortality when used during pregnancy. (See Boxed Warning.) Such potential risks occur throughout pregnancy, especially during the second and third trimesters.
Also may increase the risk of major congenital malformations when administered during the first trimester of pregnancy.
Discontinue as soon as possible when pregnancy is detected, unless continued use is considered lifesaving. Nearly all women can be transferred successfully to alternative therapy for the remainder of their pregnancy.
Hepatic Effects
Clinical syndrome that usually is manifested initially by cholestatic jaundice and may progress to fulminant hepatic necrosis (occasionally fatal) reported rarely with ACE inhibitors.
If jaundice or marked elevation of liver enzymes occurs, discontinue drug and monitor patient.
Sensitivity Reactions
Anaphylactoid reactions and/or head and neck angioedema possible; angioedema associated with tongue, glottis, or larynx may be fatal. If angioedema occurs, promptly discontinue perindopril and observe patient until swelling disappears. Immediate medical intervention (e.g., epinephrine) for involvement of tongue, glottis, or larynx.
Intestinal angioedema possible; consider in differential diagnosis of patients who develop abdominal pain.
Anaphylactoid reactions reported in patients receiving ACE inhibitors while undergoing LDL apheresis with dextran sulfate absorption or following initiation of hemodialysis that utilized high-flux membrane.
Life-threatening anaphylactoid reactions reported in at least 2 patients receiving ACE inhibitors while undergoing desensitization treatment with hymenoptera venom.
Contraindicated in patients with a history of angioedema associated with ACE inhibitors.
General Precautions
Renal Effects
Transient increases in BUN and Scr possible, especially in patients with preexisting renal impairment or those receiving concomitant diuretic therapy. Possible increases in BUN and Scr in patients with unilateral or bilateral renal artery stenosis; generally reversible following discontinuance of therapy.
Possible oliguria, progressive azotemia, and, rarely, acute renal failure and/or death in patients with severe CHF.
Closely monitor renal function for the first few weeks of therapy in hypertensive patients with unilateral or bilateral renal-artery stenosis. Some patients may require dosage reduction or discontinuance of ACE inhibitor or diuretic.
Hyperkalemia
Possible hyperkalemia, especially in patients with renal impairment or diabetes mellitus and those receiving drugs that can increase serum potassium concentration (e.g., potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes). (See Specific Drugs under Interactions.)
Monitor serum potassium concentration carefully in these patients.
Cough
Persistent and nonproductive cough; resolves after drug discontinuance.
Specific Populations
Pregnancy
Category C (1st trimester); Category D (2nd and 3rd trimesters). (See Boxed Warning.)
Lactation
Distributed into milk in rats; not known whether perindopril is distributed into milk in humans. Caution if used in nursing women.
Pediatric Use
Safety and efficacy not established in pediatric patients.
Geriatric Use
Possible lesser effect on BP in those >60 years of age than in younger patients. Increased plasma concentrations of perindopril and perindoprilat. Dizziness and possibly rash may occur more frequently in geriatric patients.
Renal Impairment
Deterioration of renal function may occur (see Renal Effects under Cautions). Systemic exposure to perindoprilat may be increased with decreasing renal function.
Initial dosage adjustment recommended in patients with renal impairment. (See Renal Impairment under Dosage and Administration.) Safety and efficacy not established in patients with Clcr <30 mL/minute.
Hepatic Impairment
Increased bioavailability of perindoprilat.
Blacks
BP reduction may be smaller in black patients compared with nonblack patients; however, no apparent population difference during combined therapy with ACE inhibitor and thiazide diuretic. Use in combination with a diuretic.
Higher incidence of angioedema reported with ACE inhibitors (as monotherapy) in blacks compared with other races.
Common Adverse Effects
Cough, proteinuria, palpitation, sinusitis, viral infection, dyspepsia, fever, upper extremity pain, hypertonia.
Dizziness reported at a rate similar to that with placebo, but incidence increases with increased dosage, suggesting causal relation to the drug.
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