VA Class:CV800
Perindopril is a nonsulfhydryl angiotensin-converting enzyme (ACE) inhibitor.1
Perindopril is used alone or in combination with drugs from other classes of antihypertensive agents in the management of hypertension.1, 46, 1200
Because captopril, another angiotensin-converting enzyme (ACE) inhibitor, may cause serious adverse effects (e.g., neutropenia, agranulocytosis), particularly in patients with renal impairment (especially those with collagen vascular disease) or in patients receiving immunosuppressive therapy, the possibility that similar adverse effects may occur with perindopril should be considered since current evidence is insufficient to rule out such risk.1 (See Cautions: Hematologic Effects, in Captopril 24:32.04.)
Perindopril is used alone or in combination with other classes of antihypertensive agents in the management of hypertension.1, 2, 46, 1200 ACE inhibitors are considered one of several preferred antihypertensive drugs for the initial management of hypertension according to current evidence-based hypertension guidelines; other preferred options include angiotensin II receptor antagonists, calcium-channel blockers, and thiazide diuretics.501, 502, 503, 504, 1200 While there may be individual differences with respect to recommendations for initial drug selection and use in specific patient populations, current evidence indicates that these antihypertensive drug classes all generally produce comparable effects on overall mortality and cardiovascular, cerebrovascular, and renal outcomes.501, 502, 504, 1200, 1213 (See Uses: Hypertension, in Captopril 24:32.04.) ACE inhibitors may be particularly useful in the management of hypertension in patients with certain coexisting conditions such as heart failure, ischemic heart disease, diabetes mellitus, chronic kidney disease (CKD), or cerebrovascular disease or following myocardial infarction (MI).501, 502, 504, 523, 524, 525, 526, 527, 534, 535, 536, 543, 1214, 1215 (See Uses: Hypertension, in Captopril 24:32.04 and in Enalaprilat/Enalapril 24:32.04.)
In patients with hypertension and compelling indications (e.g., CKD with albuminuria [urine albumin 300 mg/day or greater, or urine albumin:creatinine ratio of 300 mg/g or equivalent in the first morning void]), angiotensin II receptor antagonists are usually considered an alternative for ACE inhibitor-intolerant patients.1218 However, data indicate no difference in efficacy between ACE inhibitors and angiotensin II receptor antagonists with regard to blood pressure lowering and clinical outcomes (i.e., all-cause mortality, cardiovascular mortality, MI, heart failure, stroke, and end-stage renal disease).1200, 1218 Adverse events (e.g., cough, angioedema) leading to drug discontinuance occur more frequently with ACE inhibitor therapy than with angiotensin II receptor antagonist therapy.1218 Because of similar efficacy and a lower frequency of adverse effects, some experts believe that angiotensin II receptor antagonists should be used instead of an ACE inhibitor for the treatment of hypertension or hypertension with certain compelling indications.1218
Most patients with hypertension, especially black patients, will require at least 2 antihypertensive drugs to achieve adequate blood pressure control.1200 In general, black hypertensive patients tend to respond better to monotherapy with thiazide diuretics or calcium-channel blockers than to monotherapy with ACE inhibitors.1, 18, 19, 39, 40, 501, 504, 1200 Although ACE inhibitors have lowered blood pressure in all races studied, monotherapy with these agents has produced a smaller reduction in blood pressure in black hypertensive patients,1 a population associated with low renin hypertension.7, 8, 18, 19 However, the combination of an ACE inhibitor or an angiotensin II receptor antagonist with a calcium-channel blocker or thiazide diuretic produces similar blood pressure lowering in black patients as in other racial groups.1200 In addition, ACE inhibitors appear to produce a higher incidence of angioedema in black patients than in other races.1, 19, 1200 (See Race under Hypertension: Other Special Considerations for Antihypertensive Drug Therapy, in Uses in Captopril 24:32.04 and in Enalaprilat/Enalapril 24:32.04.)
Efficacy of perindopril alone, in combination with hydrochlorothiazide, or in fixed combination with amlodipine has been established in clinical studies of 6-16 weeks' duration.1, 2, 46
For additional information on the role of ACE inhibitors in the management of hypertension, see Uses in Captopril 24:32.04 and in Enalaprilat/Enalapril Maleate 24:32.04. For information on overall principles and expert recommendations for treatment of hypertension, see Uses: Hypertension in Adults, in the Thiazides General Statement 40:28.20.
ACE inhibitors have been used in the management of heart failure†, usually in conjunction with other agents such as cardiac glycosides, diuretics, and β-adrenergic blocking agents (β-blockers).23, 24, 25, 26, 27, 524, 800
Current guidelines for the management of heart failure in adults generally recommend a combination of drug therapies to reduce morbidity and mortality, including neurohormonal antagonists (e.g., ACE inhibitors, angiotensin II receptor antagonists, angiotensin receptor-neprilysin inhibitors [ARNIs], β-blockers, aldosterone receptor antagonists) that inhibit the detrimental compensatory mechanisms in heart failure.524, 701, 703, 800 Additional agents (e.g., cardiac glycosides, diuretics, sinoatrial modulators [i.e., ivabradine]) added to a heart failure treatment regimen in selected patients have been associated with symptomatic improvement and/or reduction in heart failure-related hospitalizations.524, 800 Experts recommend that all asymptomatic patients with reduced left ventricular ejection fraction (LVEF) (American College of Cardiology Foundation [ACCF]/American Heart Association [AHA] stage B heart failure) receive therapy with an ACE inhibitor and β-blocker to prevent symptomatic heart failure and to reduce morbidity and mortality.524, 800 In patients with prior or current symptoms of chronic heart failure and reduced LVEF (ACCF/AHA stage C heart failure), ACCF, AHA, and the Heart Failure Society of America (HFSA) recommend inhibition of the renin-angiotensin-aldosterone (RAA) system with an ACE inhibitor, angiotensin II receptor antagonist, or ARNI in conjunction with a β-blocker, and an aldosterone antagonist in selected patients, to reduce morbidity and mortality.800 While ACE inhibitors have been the preferred drugs for inhibition of the RAA system because of their established benefits in patients with heart failure and reduced ejection fraction,524 some evidence indicates that therapy with sacubitril/valsartan, an ARNI, may be more effective than ACE inhibitor therapy (enalapril) in reducing cardiovascular death and heart failure-related hospitalization.702, 800 ACCF, AHA, and HFSA recommend that patients with chronic symptomatic heart failure and reduced LVEF (New York Heart Association [NYHA] class II or III) who are able to tolerate an ACE inhibitor or angiotensin II receptor antagonist be switched to therapy containing an ARNI to further reduce morbidity and mortality.800 However, in patients in whom an ARNI is not appropriate, continued use of an ACE inhibitor for all classes of heart failure with reduced ejection fraction remains strongly advised.800 In patients in whom an ARNI or ACE inhibitor is not appropriate, an angiotensin II receptor antagonist may be used.800 For additional information on the use of ACE inhibitors in the management of heart failure, see Uses: Heart Failure, in Captopril 24:32.04 and in Enalaprilat/Enalapril 24:32.04. For further information on the use of ARNIs in patients with heart failure, see Uses: Heart Failure, in Sacubitril and Valsartan 24:32.92.
Both ACE inhibitors and angiotensin II receptor antagonists have been shown to slow the rate of progression of renal disease in patients with diabetes mellitus and persistent albuminuria†, 34, 35, 36, 37, 38, 1232 and use of a drug from either class is recommended in such patients with modestly elevated (30-300 mg/24 hours) or higher (exceeding 300 mg/24 hours) levels of urinary albumin excretion.535, 536, 1232 The usual precautions of ACE inhibitor or angiotensin II receptor antagonist therapy in patients with substantial renal impairment should be observed.30 For additional information on the use of ACE inhibitors in the treatment of diabetic nephropathy, see Diabetic Nephropathy under Uses: Nephropathy, in Captopril 24:32.04.
Perindopril is administered orally once or twice daily1 without regard to meals.2, 46 In clinical studies, administration of the drug in 2 divided doses generally was only slightly more effective than once-daily dosing.1
For the management of uncomplicated hypertension in adults not receiving a diuretic, the initial dosage of perindopril erbumine is 4 mg once daily.1
If therapy is initiated in a patient already receiving a diuretic, symptomatic hypotension may occur following the initial dose of the angiotensin-converting enzyme (ACE) inhibitor.1, 13 The possibility of hypotension can be minimized by discontinuing the diuretic, reducing the diuretic dosage, or increasing salt intake prior to initiation of perindopril therapy.1 If diuretic therapy cannot be altered, perindopril erbumine should be initiated under close medical supervision for at least 2 hours and until blood pressure has stabilized for an additional hour.1
Subsequent dosage of perindopril erbumine should be adjusted according to the patient's blood pressure response until blood pressure measured just prior to the next dose is controlled or the 16-mg daily maximum dosage is reached.1 The manufacturers states that the usual maintenance dosage of perindopril erbumine is 4-8 mg once daily.1, 2 Some experts state that the usual dosage range is 4-16 mg once daily.1200
Perindopril Arginine/Amlodipine Besylate Fixed-combination Therapy
The commercially available preparation containing perindopril arginine in fixed combination with amlodipine besylate may be used in patients receiving amlodipine monotherapy when amlodipine dosages necessary for adequate response have been associated with development of edema.46 In addition, patients who do not respond adequately to monotherapy may be switched to therapy with the fixed combination of perindopril arginine and amlodipine.46 Dosage of the fixed-combination preparation should be adjusted according to the patient's response at intervals of 7-14 days.46
Commercially available preparations containing perindopril arginine in fixed combination with amlodipine may be used for initial treatment of hypertension in patients likely to require combined therapy with multiple antihypertensive drugs to achieve blood pressure control.46 In such patients, therapy with the fixed-combination preparation usually should be initiated at a dosage of 3.5 mg of perindopril arginine and 2.5 mg of amlodipine once daily.46 The decision to use the fixed combination of perindopril arginine and amlodipine for initial management of hypertension should be based on assessment of potential benefits and risks of such therapy, including consideration of whether the patient is likely to tolerate the lowest available dosage of the combined drugs.46 Dosage may be adjusted as needed at intervals of 7-14 days to a maximum dosage of perindopril arginine 14 mg and amlodipine 10 mg once daily.46
In patients whose baseline blood pressure is 170/105 mm Hg, the estimated probability of achieving control of systolic blood pressure (defined as systolic blood pressure of less than 140 mm Hg) is 26, 40, or 50% and of achieving control of diastolic blood pressure (defined as diastolic blood pressure of less than 90 mm Hg) is 31, 46, or 65% with perindopril erbumine (16 mg daily) alone, amlodipine (10 mg daily) alone, or amlodipine (10 mg daily) combined with perindopril arginine (14 mg daily), respectively.46
In black patients and patients with diabetes mellitus, the addition of perindopril arginine (14 mg daily) to amlodipine (10 mg daily) did not provide additional antihypertensive effects beyond those achieved with amlodipine monotherapy.46
Blood Pressure Monitoring and Treatment Goals
Blood pressure should be monitored regularly (i.e., monthly) during therapy and dosage of the antihypertensive drug adjusted until blood pressure is controlled.1200 If an adequate blood pressure response is not achieved with ACE inhibitor monotherapy, the dosage may be increased or another antihypertensive agent with demonstrated benefit and preferably with a complementary mechanism of action (e.g., calcium-channel blocker, thiazide diuretic) may be added; if target blood pressure is still not achieved with the use of 2 antihypertensive agents, a third drug may be added.1200, 1216 (See Uses: Hypertension.) In patients who develop unacceptable adverse effects with perindopril, the drug should be discontinued and another antihypertensive agent from a different pharmacologic class should be initiated.1216
The goal of hypertension management and prevention is to achieve and maintain optimal control of blood pressure.1200 However, the optimum blood pressure threshold for initiating antihypertensive drug therapy and specific treatment goals remain controversial.505, 506, 507, 508, 515, 523, 530, 1201, 1207, 1209, 1222 While other hypertension guidelines have based target blood pressure goals on age and comorbidities,501, 504, 536 a 2017 multidisciplinary hypertension guideline from the American College of Cardiology (ACC), American Heart Association (AHA), and a number of other professional organizations incorporates underlying cardiovascular risk into decision making regarding treatment and generally recommends the same target blood pressure (i.e., less than 130/80 mm Hg) in all adults.1200 Many patients will require at least 2 drugs from different pharmacologic classes to achieve this blood pressure goal; the potential benefits of hypertension management and drug cost, adverse effects, and risks associated with the use of multiple antihypertensive drugs also should be considered when deciding a patient's blood pressure treatment goal.1200, 1220
Hepatic impairment may result in increased perindoprilat serum concentrations, but the manufacturer makes no specific recommendations regarding dosage adjustment.1
The initial dosage of perindopril erbumine in patients with renal impairment (creatinine clearance exceeding 30 mL/minute) is 2 mg daily; dosage should not exceed 8 mg daily because of limited clinical experience.1 Safety and efficacy have not been established in those with creatinine clearance less than 30 mL/minute.1 Perindopril is removed by renal dialysis; clearance of the drug in patients undergoing renal dialysis is similar to that in patients with normal renal function.1
Perindopril erbumine therapy for hypertension in geriatric patients should be initiated at a dosage of 4 mg once daily; increases to dosages exceeding 8 mg daily should occur gradually and only under close medical supervision.1
The manufacturer states that use of preparations containing perindopril arginine in fixed combination with amlodipine besylate is not recommended in geriatric patients or in patients with hepatic impairment, renal impairment with creatinine clearance of less than 60 mL/minute, or heart failure, as insufficient data are available to support dosage recommendations in these populations.46
Known hypersensitivity (e.g., history of angioedema) to perindopril, other angiotensin-converting enzyme (ACE) inhibitors, or any ingredient in the formulation.1
History of hereditary or idiopathic angioedema.1
Concomitant aliskiren therapy in patients with diabetes mellitus.1
Concomitant use (within 36 hours) of a neprilysin inhibitor (e.g., sacubitril).1, 46 (See Drug Interactions: Neprilysin Inhibitors.)
Fetal/Neonatal Morbidity and Mortality
Drugs that act on the renin-angiotensin system (e.g., ACE inhibitors, angiotensin II receptor antagonists) reduce fetal renal function and increase fetal and neonatal morbidity and mortality when used in pregnancy during the second and third trimesters.1 ACE inhibitors also have been reported to increase the risk of major congenital malformations when administered during the first trimester of pregnancy.42, 43 Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations.1 Potential neonatal effects include skull hypoplasia, anuria, hypotension, renal failure, and death.1 ACE inhibitors (e.g., perindopril) should be discontinued as soon as possible when pregnancy is detected, unless continued use is considered life-saving for the mother.1 Nearly all women can be transferred successfully to alternative therapy for the remainder of their pregnancy.44, 45 For additional information on the risk of ACE inhibitors during pregnancy, see Cautions: Pregnancy, Fertility, and Lactation, in Captopril 24:32.04 and in Enalaprilat/Enalapril 24:32.04.
Sensitivity reactions, including anaphylactoid reactions and angioedema (including laryngeal edema), are potentially fatal.1, 12 Head and neck angioedema have occurred in patients receiving an ACE inhibitor and have been reported at a higher rate in black patients compared with patients of other races.1 In addition, concomitant use of an ACE inhibitor and a mammalian target of rapamycin (mTOR) inhibitor or a neprilysin inhibitor (e.g., sacubitril) may increase the risk of angioedema.1 Head and neck angioedema involving the tongue, glottis, or larynx may cause airway obstruction.1 If laryngeal stridor or angioedema of the face, tongue, or glottis occurs, ACE inhibitors (e.g., perindopril) should be discontinued and appropriate therapy (e.g., epinephrine) initiated immediately.1 Caution in patients with history of angioedema unrelated to ACE inhibitor therapy.1
Intestinal angioedema (occasionally without a prior history of facial angioedema or elevated serum levels of complement 1 [C1]) esterase inhibitor) also has been reported in patients receiving ACE inhibitors.1 Intestinal angioedema, which frequently presents as abdominal pain (with or without nausea or vomiting), usually is diagnosed by abdominal CT scan, ultrasound, or surgery;1 manifestations usually have resolved after discontinuance of the ACE inhibitor.1 Intestinal angioedema should be considered in the differential diagnosis of patients who develop abdominal pain during therapy with an ACE inhibitor.1
Life-threatening anaphylactoid reactions have been reported in at least 2 patients receiving ACE inhibitors while undergoing desensitization treatment with hymenoptera venom.1 When ACE inhibitors were temporarily discontinued before desensitization with the venom, anaphylactoid reactions did not recur; however, such reactions recurred after inadvertent rechallenge.1 Anaphylactoid reactions also have been reported following initiation of hemodialysis that used a high-flux membrane in patients receiving an ACE inhibitor.1 In addition, anaphylactoid reactions have been reported in patients undergoing low-density lipoprotein (LDL) apheresis with dextran sulfate absorption.1
Other Warnings and Precautions
Symptomatic hypotension may occur.1, 13 Patients at particular risk include those with volume or salt depletion secondary to salt restriction, prolonged diuretic therapy, dialysis, diarrhea, or vomiting.1, 2 The American College of Cardiology (ACC) and American Heart Association (AHA) recommend that ACE inhibitor therapy be initiated with caution in patients with very low systemic blood pressure (systolic blood pressure less than 80 mm Hg).524
Marked hypotension, which may be associated with oliguria or azotemia and rarely with acute renal failure and death, may occur with ACE inhibitor therapy; excessive hypotension in those with ischemic cardiovascular or cerebrovascular disease may result in myocardial infarction (MI) or stroke.1 To minimize the potential for hypotension, volume and/or salt depletion should be corrected (e.g., by withholding diuretic therapy, decreasing diuretic dosage, increasing sodium intake) prior to initiation of perindopril.1 In patients at risk for excessive hypotension, perindopril therapy should be started under close medical supervision, and patients should be followed closely for the first 2 weeks after initiation of perindopril therapy or any increase in perindopril or diuretic dosage.1
If excessive hypotension occurs, the patient should be placed immediately in the supine position and, if necessary, an IV infusion of 0.9% sodium chloride injection should be administered.1 Perindopril therapy usually can be continued following restoration of volume and blood pressure.1
Neutropenia or agranulocytosis, particularly in those with renal impairment (especially those with a collagen vascular disease such as systemic lupus erythematosus or scleroderma), has been reported with ACE inhibitor therapy.1 (See Cautions: Hematologic Effects, in Captopril 24:32.04.)
Inhibition of the renin-angiotensin-aldosterone (RAA) system may cause renal impairment and, rarely, renal failure and/or death in susceptible patients (e.g., those whose renal function depends on the activity of the RAA system such as patients with severe heart failure).1
Deterioration of renal function, manifested as minor and transient increases in BUN and serum creatinine concentrations, may occur following administration of ACE inhibitor therapy, particularly in hypertensive patients with unilateral or bilateral renal artery stenosis or concomitant diuretic therapy.1 Renal function should be monitored for the first few weeks of therapy in such patients and periodically during perindopril therapy.1
Hyperkalemia can develop,1 especially in those with renal impairment or diabetes mellitus and those receiving drugs or other agents that can increase serum potassium concentration (e.g., potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes).1 Serum potassium concentrations should be monitored periodically in patients receiving perindopril.1 ACE inhibitor therapy should be initiated with caution in patients with elevated serum potassium concentrations (exceeding 5 mEq/L).524
Persistent, nonproductive cough has been reported with ACE inhibitor therapy; cough generally resolves after drug discontinuance.1
Rare ACE inhibitor-associated clinical syndrome manifested initially by cholestatic jaundice; may progress to fulminant hepatic necrosis and is potentially fatal.1 Patients receiving an ACE inhibitor, including perindopril, who develop jaundice or marked elevations of hepatic enzymes should discontinue the drug and receive appropriate medical follow-up.1
Hypotension may occur in patients undergoing surgery or during anesthesia with agents that produce hypotension due to blockade by ACE inhibitors of angiotensin II formation secondary to compensatory renin release.1 Hypotension in such patients may be corrected by volume expansion.1
When perindopril is used in fixed combination with amlodipine, the cautions, precautions, contraindications, and interactions associated with amlodipine must be considered in addition to those associated with perindopril.46
Category D.1 (See Users Guide.) Perindopril can cause fetal and neonatal morbidity and mortality when administered to a pregnant woman.1 (See Fetal/Neonatal Morbidity and Mortality under Warnings/Precautions: Warnings, in Cautions.)
Not known whether perindopril is distributed in milk; caution if used in nursing women.1
If oliguria or hypotension occurs in neonates with a history of in utero exposure to perindopril, blood pressure and renal function should be supported; exchange transfusions or dialysis may be required.1
Safety and efficacy not established in pediatric patients.1, 46 For information on overall principles and expert recommendations for treatment of hypertension in pediatric patients, see Uses: Hypertension in Pediatric Patients, in the Thiazides General Statement 40:28.20.
Perindopril has been reported to have a somewhat lesser effect on blood pressure in those 60 years of age and older than in younger patients.1 Increased plasma concentrations of perindopril and perindoprilat have been reported in geriatric patients compared with younger patients.1 Dizziness and possibly rash may occur more frequently in geriatric patients; such patients should be monitored for dizziness because of the potential for falls.1 (See Dosage and Administration: Special Populations.)
Decreased renal function in susceptible patients. Safety and efficacy not established and use not recommended in patients with creatinine clearance less than 30 mL/minute.1 Use with caution in those with moderate to mild renal impairment.1 (See Dosage and Administration: Special Populations and also see Renal Effects under Warnings/Precautions: Other Warnings and Precautions, in Cautions.)
Use with caution.1 (See Dosage and Administration: Special Populations.)
ACE inhibitors generally are not as effective in black patients compared with other races.1, 504, 1200 (See Uses: Hypertension.)
Adverse effects occurring more commonly with perindopril than with placebo by at least 1% in clinical trials include cough, back pain, sinusitis, viral infection, upper extremity pain, hypertonia, dyspepsia, fever, proteinuria, otic infection, and palpitation.1 Dizziness was reported at a rate similar to that with placebo, but incidence increased with increased dosage, suggesting causal relation to drug use.1 Most common adverse effects resulting in discontinuance include cough, headache, asthenia, and dizziness.1
Agents that Increase Serum Potassium Concentration
Potential pharmacologic interaction (additive hyperkalemic effect) with potassium-sparing diuretics, potassium supplements, salt substitutes, and other agents that can cause hyperkalemia (e.g., cyclosporine, heparin, indomethacin).1 Serum potassium concentrations should be monitored in patients receiving such concomitant therapy.1, 46
Potential pharmacokinetic and pharmacologic interaction (hypotensive effect).1
A pharmacokinetic study revealed no effect on plasma digoxin concentrations when concurrently administered with perindopril.1 However, an effect of digoxin on the plasma concentration of perindopril/perindoprilat cannot be ruled out.1
Drugs that Block the Renin-Angiotensin System
Dual blockade of the renin-angiotensin system with angiotensin receptor blocking agents, angiotensin-converting enzyme (ACE) inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared with monotherapy.1 Most patients receiving the combination of 2 renin-angiotensin system blocking agents do not obtain any additional benefit compared with monotherapy.1 Concomitant use of 2 renin-angiotensin system blocking agents generally should be avoided.1 Blood pressure, renal function, and electrolytes should be closely monitored in patients receiving perindopril and other agents that affect the renin-angiotensin system.1
Potential interaction based on animal data;1 caution advised.1
Nitroid reactions (manifestations include facial flushing, nausea, vomiting, and hypotension) have been reported rarely in patients receiving concomitant therapy with injectable gold (sodium aurothiomalate) and an ACE inhibitor.1
Potential pharmacokinetic interaction (increased lithium concentrations and clinical toxicity).1
Mammalian Target of Rapamycin Inhibitors
Concomitant use of an ACE inhibitor and a mammalian target of rapamycin (mTOR) inhibitor may increase the risk of angioedema.1 Patients receiving such concomitant therapy should be monitored for signs of angioedema.1
Increased risk of angioedema.1 Perindopril should not be administered within 36 hours of switching to or from a neprilysin inhibitor (e.g., sacubitril, commercially available as sacubitril/valsartan).1 (See Sensitivity Reactions under Cautions: Warnings/Precautions.)
Nonsteroidal Anti-inflammatory Agents
In geriatric patients, patients who are volume depleted (including those who are receiving diuretic therapy), or patients with compromised renal function, concomitant use of nonsteroidal anti-inflammatory agents (NSAIAs), including cyclooxygenase-2 (COX-2) inhibitors, and ACE inhibitors may result in the deterioration of renal function, including possible renal failure.1 These effects are usually reversible.1 Renal function should be monitored periodically in patients receiving concomitant perindopril and NSAIA therapy.1
Perindopril is an angiotensin-converting enzyme (ACE) inhibitor that does not contain a sulfhydryl group.1 Perindopril is a prodrug and has little pharmacologic activity until hydrolyzed in the liver to perindoprilat.1, 2 Perindoprilat and its metabolites are excreted principally in urine.1
Risk of angioedema, anaphylactoid reactions, and other sensitivity reactions; importance of discontinuing the drug and immediately reporting suggestive manifestations (e.g., edema of face, eyes, extremities, lips, or tongue; hoarseness; swallowing or breathing with difficulty) to a clinician.1
Risk of hypotension (e.g., lightheadedness, syncope), especially during initial therapy or with volume depletion secondary to excessive perspiration, vomiting, or diarrhea.1 Importance of adequate fluid intake.1 Importance of discontinuing drug and contacting clinician if symptoms of syncope occur.1
Importance of contacting a clinician promptly if manifestations of infection or neutropenia (e.g., sore throat, fever) develop.1
Risk of hyperkalemia.1 Importance of avoiding the use of potassium supplements or salt substitutes containing potassium without consultation with a clinician.1
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1
Importance of women informing clinicians immediately if they are or plan to become pregnant or plan to breast-feed; importance of discussing other options for hypertension treatment if pregnancy occurs.1 Risk of use during first, second and third trimesters of pregnancy.1, 42, 43
Importance of informing patients of other important precautionary information. (See Cautions.)
Additional Information
Overview (see Users Guide). For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Tablets | 2 mg* | Aceon® (scored) | Symplmed |
Perindopril Erbumine Tablets | ||||
4 mg* | Aceon® (scored) | Symplmed | ||
Perindopril Erbumine Tablets | ||||
8 mg* | Aceon® (scored) | Symplmed | ||
Perindopril Erbumine Tablets |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
1. Symplmed. Aceon® (perindopril erbumine) tablets prescribing information. Cincinnati, OH; 2017 Sep.
2. Todd PA, Fitton A. Perinopril: a review of its pharmacological properties and therapeutic use in cardiovascular disorders. Drugs . 1991; 42:90-114. [PubMed 1718688]
3. Bristol-Myers Squibb. Capoten® (captopril) tablets prescribing information. Princeton, NJ; 1996 April.
4. Reviewers' comments in enalapril/enalaprilat (personal observations).
7. Saunders E. Tailoring treatment to minority patients. Am J Med. 1990; 88(Suppl 3B):21-23S.
8. Chrysant SG, Danisa K, Kem DC et al. Racial differances in pressure, volume and renin interrelationships in essential hypertension. Hypertension. 1979; 1:136-41.
10. Anon. Drugs for hypertension. Med Lett Drugs Ther . 1984; 26:107-12. [PubMed 6150424]
12. Lapostolle F, Borron SW, Bekka R et al. Lingual angioedema after perindopril use. Am J Cardiol . 1998; 81:523. [PubMed 9485152]
13. Bagger JP. Adverse event with first-dose perindopril in congestive heart failure. Lancet . 1997; 349:1671-2. [PubMed 9186393]
14. Izzo JL, Levy D, Black HR. Importance of systolic blood pressure in older Americans. Hypertension . 2000; 35:1021-4. [PubMed 10818056]
15. Frohlich ED. Recognition of systolic hypertension for hypertension. Hypertension . 2000; 35:1019-20. [PubMed 10818055]
16. Bakris GL, Williams M, Dworkin L et al. Preserving renal function in adults with hypertension and diabetes: a consensus approach. Am J Kidney Dis . 2000; 36:646-61. [PubMed 10977801]
17. Associated Press (American Diabetes Association). Diabetics urged: drop blood pressure. Chicago, IL; 2000 Aug 29. Press Release from web site ([Web]).
18. Appel LJ. The verdict from ALLHAT—thiazide diuretics are the preferred initial therapy for hypertension. JAMA . 2002; 288:3039-60. [PubMed 12479770]
19. The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA . 2002; 288:2981-97. [PubMed 12479763]
22. Novartis. Lotensin® (benazepril hydrochloride) tablets prescribing information. East Hanover, NJ: 2001 Jul.
23. Merck & Co. Vasotec® tablets (enalapril maleate) prescribing information. Whitehouse Station, NJ; 2002 Jan.
24. Bristol-Myers Squibb. Monopril® (fosinopril sodium) tablets prescribing information. Princeton, NJ; 2002 Feb.
25. Merck. Prinivil® (lisinopril) tablets prescribing information. Whitehouse Station, NJ; 2002 Jan.
26. AstraZeneca. Zestril® (lisinopril) tablets prescribing information. Wilmington, DE: 2002 Jan.
27. Parke Davis. Accupril® (quinapril hydrochloride) tablets prescribing information. Morris Plains, NJ; 2001 Mar.
30. Novartis. Diovan® (valsartan) tablets prescribing information. East Hanover, NJ; 2002 Aug.
34. Lewis EJ, Hunsicker LG, Bain RP et al. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. N Engl J Med . 1993; 329:1456-62. [PubMed 8413456]
35. Remuzzi G. Slowing the progression of diabetic nephropathy. N Engl J Med . 1993; 329:1496-7. [PubMed 8413463]
36. Kaplan NM. Choice of initial therapy for hypertension. JAMA . 1996; 275:1577-80. [PubMed 8622249]
37. Viberti G, Mogensen CE, Groop LC et al. Effect of captopril on progression to clinical proteinuria in patients with insulin-dependent diabetes mellitus and microalbuminuria. JAMA . 1994; 271:275-9. [PubMed 8295285]
38. Fournier A. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. N Engl J Med . 1994; 330:937. [PubMed 8114873]
39. Wright JT, Dunn JK, Cutler JA et al. Outcomes in hypertensive black and nonblack patients treated with chlorthalidone, amlodipine, and lisinopril. JAMA . 2005; 293:1595-607. [PubMed 15811979]
40. Neaton JD, Kuller LH. Diuretics are color blind. JAMA . 2005; 293:1663-6. [PubMed 15811986]
42. Cooper WO, Hernandez-Diaz S, Arbogast PG et al. Major congenital malformations after first-trimester exposure to ACE inhibitors. N Engl J Med . 2006; 354:2443-51. [PubMed 16760444]
43. Food and Drug Administration. FDA public health advisory: angiotensin-converting enzyme inhibitor (ACE inhibitor) drugs and pregnancy. From FDA website ([Web]).
44. Sibai BM. Treatment of hypertension in pregnant women. N Engl J Med . 1996; 335:257-65. [PubMed 8657243]
45. US Food and Drug Administration. Dangers of ACE inhibitors during pregnancy. FDA Med Bull . 1992; 22:2.
46. Symplmed, LLC. Prestalia® (perindopril arginine and amlodipine besylate) tablets prescribing information. Cincinnati, OH; 2015 Jan.
501. James PA, Oparil S, Carter BL et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA . 2014; 311:507-20. [PubMed 24352797]
502. Mancia G, Fagard R, Narkiewicz K et al. 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens . 2013; 31:1281-357. [PubMed 23817082]
503. Go AS, Bauman MA, Coleman King SM et al. An effective approach to high blood pressure control: a science advisory from the American Heart Association, the American College of Cardiology, and the Centers for Disease Control and Prevention. Hypertension . 2014; 63:878-85. [PubMed 24243703]
504. Weber MA, Schiffrin EL, White WB et al. Clinical practice guidelines for the management of hypertension in the community: a statement by the American Society of Hypertension and the International Society of Hypertension. J Clin Hypertens (Greenwich) . 2014; 16:14-26. [PubMed 24341872]
505. Wright JT, Fine LJ, Lackland DT et al. Evidence supporting a systolic blood pressure goal of less than 150 mm Hg in patients aged 60 years or older: the minority view. Ann Intern Med . 2014; 160:499-503. [PubMed 24424788]
506. Mitka M. Groups spar over new hypertension guidelines. JAMA . 2014; 311:663-4. [PubMed 24549531]
507. Peterson ED, Gaziano JM, Greenland P. Recommendations for treating hypertension: what are the right goals and purposes?. JAMA . 2014; 311:474-6. [PubMed 24352710]
508. Bauchner H, Fontanarosa PB, Golub RM. Updated guidelines for management of high blood pressure: recommendations, review, and responsibility. JAMA . 2014; 311:477-8. [PubMed 24352759]
511. JATOS Study Group. Principal results of the Japanese trial to assess optimal systolic blood pressure in elderly hypertensive patients (JATOS). Hypertens Res . 2008; 31:2115-27. [PubMed 19139601]
515. Thomas G, Shishehbor M, Brill D et al. New hypertension guidelines: one size fits most?. Cleve Clin J Med . 2014; 81:178-88. [PubMed 24591473]
523. Fihn SD, Gardin JM, Abrams J et al. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation . 2012; 126:e354-471. [PubMed 23166211]
524. WRITING COMMITTEE MEMBERS, Yancy CW, Jessup M et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation . 2013; 128:e240-327. [PubMed 23741058]
525. Smith SC, Benjamin EJ, Bonow RO et al. AHA/ACCF Secondary Prevention and Risk Reduction Therapy for Patients with Coronary and other Atherosclerotic Vascular Disease: 2011 update: a guideline from the American Heart Association and American College of Cardiology Foundation. Circulation . 2011; 124:2458-73. [PubMed 22052934]
526. Kernan WN, Ovbiagele B, Black HR et al. Guidelines for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke . 2014; :. [PubMed 24788967]
527. O'Gara PT, Kushner FG, Ascheim DD et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation . 2013; 127:e362-425. [PubMed 23247304]
530. Myers MG, Tobe SW. A Canadian perspective on the Eighth Joint National Committee (JNC 8) hypertension guidelines. J Clin Hypertens (Greenwich) . 2014; 16:246-8. [PubMed 24641124]
534. Qaseem A, Hopkins RH, Sweet DE et al. Screening, monitoring, and treatment of stage 1 to 3 chronic kidney disease: A clinical practice guideline from the American College of Physicians. Ann Intern Med . 2013; 159:835-47. [PubMed 24145991]
535. Taler SJ, Agarwal R, Bakris GL et al. KDOQI US commentary on the 2012 KDIGO clinical practice guideline for management of blood pressure in CKD. Am J Kidney Dis . 2013; 62:201-13. [PubMed 23684145]
536. Kidney Disease: Improving Global Outcomes (KDIGO) Blood Pressure Work Group. KDIGO clinical practice guideline for the management of blood pressure in chronic kidney disease. Kidney Int Suppl . 2012: 2: 337-414.
543. National Kidney Foundation Kidney Disease Outcomes Quality Initiative. K/DOQI Clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease (2002). From National Kidney Foundation website. [Web]
701. Ponikowski P, Voors AA, Anker SD et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J . 2016; 37:2129-200. [PubMed 27206819]
702. McMurray JJ, Packer M, Desai AS et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med . 2014; 371:993-1004. [PubMed 25176015]
703. Ansara AJ, Kolanczyk DM, Koehler JM. Neprilysin inhibition with sacubitril/valsartan in the treatment of heart failure: mortality bang for your buck. J Clin Pharm Ther . 2016; 41:119-27. [PubMed 26992459]
800. Yancy CW, Jessup M, Bozkurt B et al. 2016 ACC/AHA/HFSA Focused Update on New Pharmacological Therapy for Heart Failure: An Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation . 2016; 134:e282-93. [PubMed 27208050]
1150. Flynn JT, Kaelber DC, Baker-Smith CM et al. Clinical practice guideline for screening and management of high blood pressure in children and adolescents. Pediatrics . 2017; 140 [PubMed 28827377]
1200. Whelton PK, Carey RM, Aronow WS et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension . 2018; 71:el13-e115. [PubMed 29133356]
1201. Bakris G, Sorrentino M. Redefining hypertension - assessing the new blood-pressure guidelines. N Engl J Med . 2018; 378:497-499. [PubMed 29341841]
1202. Carey RM, Whelton PK, 2017 ACC/AHA Hypertension Guideline Writing Committee. Prevention, detection, evaluation, and management of high blood pressure in adults: synopsis of the 2017 American College of Cardiology/American Heart Association hypertension guideline. Ann Intern Med . 2018; 168:351-358. [PubMed 29357392]
1207. Burnier M, Oparil S, Narkiewicz K et al. New 2017 American Heart Association and American College of Cardiology guideline for hypertension in the adults: major paradigm shifts, but will they help to fight against the hypertension disease burden?. Blood Press . 2018; 27:62-65. [PubMed 29447001]
1209. Qaseem A, Wilt TJ, Rich R et al. Pharmacologic treatment of hypertension in adults aged 60 years or older to higher versus lower blood pressure targets: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med . 2017; 166:430-437. [PubMed 28135725]
1210. SPRINT Research Group, Wright JT, Williamson JD et al. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med . 2015; 373:2103-16. [PubMed 26551272]
1213. Reboussin DM, Allen NB, Griswold ME et al. Systematic review for the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol . 2018; 71:2176-2198. [PubMed 29146534]
1214. American Diabetes Association. 9. Cardiovascular disease and risk management: standards of medical care in diabetes 2018. Diabetes Care . 2018; 41:S86-S104. [PubMed 29222380]
1215. de Boer IH, Bangalore S, Benetos A et al. Diabetes and hypertension: a position statement by the American Diabetes Association. Diabetes Care . 2017; 40:1273-1284. [PubMed 28830958]
1216. Taler SJ. Initial treatment of hypertension. N Engl J Med . 2018; 378:636-644. [PubMed 29443671]
1218. Messerli FH, Bangalore S, Bavishi C et al. Angiotensin-converting enzyme inhibitors in hypertension: to use or not to use?. J Am Coll Cardiol . 2018; 71:1474-1482. [PubMed 29598869]
1220. Cifu AS, Davis AM. Prevention, detection, evaluation, and management of high blood pressure in adults. JAMA . 2017; 318:2132-2134. [PubMed 29159416]
1222. Bell KJL, Doust J, Glasziou P. Incremental benefits and harms of the 2017 American College of Cardiology/American Heart Association high blood pressure guideline. JAMA Intern Med . 2018; 178:755-7. [PubMed 29710197]
1223. LeFevre M. ACC/AHA hypertension guideline: what is new? what do we do?. Am Fam Physician . 2018; 97(6):372-3. [PubMed 29671534]
1224. Brett AS. New hypertension guideline is released. From NEJM Journal Watch website. Accessed 2018 Jun 18. [Web]
1229. Ioannidis JPA. Diagnosis and treatment of hypertension in the 2017 ACC/AHA guidelines and in the real world. JAMA . 2018; 319(2):115-6. [PubMed 29242891]
1232. American Diabetes Association. 10. Microvascular complications and foot care: standards of medical care in diabetes 2018. Diabetes Care . 2018; 41:S105-S118. [PubMed 29222381]