Perindopril: Drug information

(For additional information see "Perindopril: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)

ALERT: US Boxed Warning

Fetal toxicity:

When pregnancy is detected, discontinue perindopril as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus.

Brand Names: Canada

AG-Perindopril;
AG-Perindopril Erbumine;
APO-Perindopril;
Auro-Perindopril;
BIO-Perindopril;
Coversyl;
JAMP-Perindopril;
JAMP-Perindopril Erbumine;
M-Perindopril Erbumine;
MAR-Perindopril;
MINT-Perindopril;
NRA-Perindopril;
PMS-Perindopril;
Priva-Perindopril Erbumine [DSC];
RIVA-Perindopril;
SANDOZ Perindopril Erbumine;
TEVA-Perindopril

Pharmacologic Category

Angiotensin-Converting Enzyme (ACE) Inhibitor;
Antihypertensive

Dosing: Adult

Heart failure with reduced ejection fraction

Heart failure with reduced ejection fraction (off-label use):

Note: If tolerated, an angiotensin II receptor-neprilysin inhibitor is generally preferred over an angiotensin-converting enzyme inhibitor (Ref).

Oral: Initial: 2 mg once daily; increase dose (eg, double) as tolerated every ≥1 to 2 weeks to a target dose of 8 to 16 mg once daily (Ref). In hospitalized patients, may titrate more rapidly as tolerated (Ref).

Hypertension, chronic

Hypertension, chronic:

Note: For patients who warrant combination therapy (BP >20/10 mm Hg above goal or suboptimal response to initial monotherapy), may use with another appropriate agent (eg, long-acting dihydropyridine calcium channel blocker or thiazide diuretic) (Ref).

Oral: Initial: 4 mg once daily; evaluate response after ~2 to 4 weeks and titrate dose (eg, increase the daily dose by doubling) as needed up to 16 mg once daily; if additional blood pressure control is needed, consider combination therapy. Patients with severe asymptomatic hypertension and no signs of acute end organ damage should be evaluated for medication titration within 1 week (Ref).

Stable coronary artery disease

Stable coronary artery disease:

Note : Initiate as a component of an appropriate medical regimen, which may include antiplatelet agent(s), a beta-blocker, and a statin. Continue indefinitely for patients with concurrent diabetes, left ventricular ejection fraction ≤40% post–myocardial infarction, hypertension, stable chronic kidney disease, or history of ST-elevation myocardial infarction (Ref).

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

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

Kidney impairment prior to treatment initiation:

Altered kidney function (Ref): Oral:

CrCl >80 mL/minute: No dosage adjustment necessary.

CrCl ≥30 to ≤80 mL/minute: Initial: 2 mg/day; maximum maintenance dose: 8 mg/day.

CrCl <30 mL/minute: Use is generally not recommended; however, an initial dose of 2 mg every 48 hours may be considered (Ref); titrate cautiously based on tolerability and response, not to exceed 4 mg/day (Ref).

Hemodialysis, intermittent (thrice weekly): Dialyzable (perindopril [% unknown] and perindoprilat [~60%]) (Ref): Oral: Initial: 2 mg 3 times per week after dialysis on dialysis days (Ref); titrate cautiously based on tolerability and response, not to exceed 4 mg/day (Ref).

Peritoneal dialysis: Oral: Use generally not recommended (has not been studied); however, if use is necessary, an initial dose of 2 mg every 48 hours may be considered; titrate cautiously based on tolerability and response, not to exceed 4 mg/day (Ref).

CRRT: Oral: Use generally not recommended (has not been studied); however, if use is necessary, an initial dose of 2 mg every 48 hours may be considered; titrate cautiously based on tolerability and response, not to exceed 4 mg/day (Ref). Avoid use if an AN69 hemofilter is used (associated with anaphylactoid reaction) (Ref).

PIRRT (eg, sustained, low-efficiency diafiltration): Oral: Use generally not recommended (has not been studied); however, if use is necessary, an initial dose of 2 mg every 48 hours may be considered; titrate cautiously based on tolerability and response, not to exceed 4 mg/day (Ref). Avoid use if an AN69 hemofilter is used (associated with anaphylactoid reaction) (Ref).

Kidney impairment during therapy:

Small, transient increases in serum creatinine are expected within 4 weeks following initiation of therapy or an increase in dose. If serum creatinine increases by >30%, review for possible etiologies (eg, acute kidney injury, volume depletion, concomitant medications, renal artery stenosis), then determine if dose reduction or discontinuation of perindopril therapy should be considered (Ref).

Dosage adjustment for toxicity:

Hyperkalemia: Assess for alternative or contributing factors (eg, diet, concomitant medications) of increased potassium, then determine if dose reduction or discontinuation of perindopril therapy should be considered (Ref).

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling; use with caution (perindoprilat bioavailability is increased with hepatic impairment). Use with caution, particularly in patients with ascites due to cirrhosis (Ref).

Dosing: Older Adult

Hypertension, chronic: >65 years of age: Oral: Initial: 4 mg/day in 1 or 2 divided doses; consider lower initial doses with titration per response (Ref). Experience with doses >8 mg/day is limited.

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

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

1% to 10%:

Cardiovascular: Chest pain (2%), ECG abnormality (2%), palpitations (1%)

Dermatologic: Dermatologic disorder (4%), diaphoresis (1%)

Endocrine & metabolic: Hyperkalemia (2%)

Gastrointestinal: Abdominal pain (3%), diarrhea (2%), dyspepsia (2%), flatulence (1%), nausea (≤4%), stomach pain (≤4%), upper abdominal pain (≤4%), vomiting (≤4%)

Genitourinary: Erectile dysfunction (1%), proteinuria (1%), urinary tract infection (3%)

Hepatic: Increased serum alanine aminotransferase (2%)

Infection: Viral infection (3%)

Nervous system: Asthenia (5% to 7%), depression (1%), drowsiness (1%), headache (3%), hypertonia (2%), nervousness (1%), paresthesia (2%), sleep disorder (2%)

Neuromuscular & skeletal: Arm and/or wrist pain (3%), arthralgia (1%), arthritis (1%), back pain (7%), lower extremity pain (5%), muscle cramps (2%), myalgia (1%), neck pain (1%)

Otic: Tinnitus (1%)

Respiratory: Cough (2% to 6%), pharyngitis (4%), rhinitis (5%), sinusitis (5%)

Miscellaneous: Fever (2%)

<1%:

Cardiovascular: Acute myocardial infarction, bradycardia, cardiac arrhythmia, cardiac conduction disorder, cold extremity, edema, flushing, heart murmur, hypotension, intermittent claudication, orthostatic hypotension, peripheral edema, peripheral vascular disease, premature ventricular contractions, syncope, vasodilation

Dermatologic: Alopecia, dermatitis, ecchymoses, erythema of skin, hyperhidrosis, pemphigus, pruritus, purpuric rash, skin infection, skin rash, Stevens-Johnson syndrome, tinea, urticaria, xeroderma

Endocrine & metabolic: Change in libido, fluid retention, increased thirst, menstrual disease

Gastrointestinal: Anorexia, constipation, dysgeusia, gastroenteritis, gastrointestinal hemorrhage, hematemesis, increased appetite, mesenteric ischemia, mucous membrane abnormality, stomatitis, xerostomia

Genitourinary: Hematuria, nocturia, oliguria, pollakiuria, polyuria, scrotal edema, urinary incontinence, urinary retention, vaginitis

Hematologic & oncologic: Hematoma, hemolytic anemia, leukopenia, neutropenia, thrombocytopenia

Hypersensitivity: Anaphylaxis, angioedema

Infection: Herpes simplex infection

Nervous system: Abnormal dreams, agitation, amnesia, anxiety, cerebrovascular accident, cognitive dysfunction (including perceptual distortion), confusion, feeling hot, illusion, malaise, memory impairment, migraine, mood changes, myasthenia, pain, psychological disorder (psychosexual disorder), rigors, sciatica, sensation of cold, speech disturbance, tremor, vertigo

Neuromuscular & skeletal: Gout, hyperkinetic muscle activity, ostealgia

Ophthalmic: Conjunctivitis, increased lacrimation, visual disturbance

Otic: Otalgia

Renal: Flank pain, increased blood urea nitrogen, increased serum creatinine, kidney impairment, nephrolithiasis

Respiratory: Asthma, bronchitis, bronchospasm, dyspnea, epistaxis, hoarseness, pneumonia, post nasal drip, pulmonary fibrosis, rhinorrhea, sneezing, throat irritation

Frequency not defined:

Endocrine & metabolic: Hypercholesterolemia, increased serum glucose

Hepatic: Increased serum bilirubin

Postmarketing:

Cardiovascular: Angina pectoris, Raynaud disease, tachycardia

Dermatologic: Eczema, erythema multiforme, exacerbation of psoriasis, pemphigoid, psoriasis (Song 2021), skin photosensitivity

Endocrine & metabolic: Hypoglycemia, hyponatremia, SIADH

Gastrointestinal: Intestinal angioedema (Parreira 2020), pancreatitis

Genitourinary: Anuria

Hematologic & oncologic: Agranulocytosis, decreased hematocrit, decreased hemoglobin, eosinophilia, pancytopenia

Hepatic: Hepatitis (cholestatic and cytolytic hepatitis)

Nervous system: Dizziness, falling, visual hallucination (Doane 2013)

Renal: Acute kidney injury

Respiratory: Eosinophilic pneumonia, pneumonitis (Benard 1996)

Contraindications

Hypersensitivity (eg, angioedema) to perindopril, other ACE inhibitors, or any component of the formulation; hereditary/idiopathic angioedema; concomitant use with aliskiren in patients with diabetes mellitus; concomitant use or within 36 hours of switching to or from a neprilysin inhibitor (eg, sacubitril).

Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Canadian labeling: Additional contraindications (not in US labeling): Concomitant use with aliskiren in patients with moderate to severe kidney impairment (GFR <60 mL/minute/1.73 m²); while pregnant, planning to become pregnant, or patients of childbearing potential not using adequate contraception; breastfeeding; hereditary problems of galactose intolerance, glucose-galactose malabsorption, or the congenital lactase deficiency; concomitant use with sacubitril/valsartan; extracorporeal treatments leading to contact of blood with negatively charged surfaces; unilateral or bilateral renal artery stenosis

Warnings/Precautions

Concerns related to adverse effects:

• Angioedema: At any time during treatment (especially following first dose), angioedema may occur rarely with ACE inhibitors; it may involve the head and neck (potentially compromising airway) or the intestine (presenting with abdominal pain). Black patients and patients with idiopathic or hereditary angioedema or previous angioedema associated with ACE inhibitor therapy may be at an increased risk. Risk may also be increased with concomitant use of mTOR inhibitor (eg, everolimus) or neprilysin inhibitor (eg, sacubitril) therapy. Prolonged frequent monitoring may be required especially if tongue, glottis, or larynx are involved as they are associated with airway obstruction. Patients with a history of airway surgery may have a higher risk of airway obstruction. Aggressive early and appropriate management is critical. Use in patients with previous angioedema associated with ACE inhibitor therapy is contraindicated.

• Cholestatic jaundice: A rare toxicity associated with ACE inhibitors includes cholestatic jaundice, which may progress to fulminant hepatic necrosis (some fatal); discontinue if marked elevation of hepatic transaminases or jaundice occurs.

• Cough: An ACE inhibitor cough is a dry, hacking, nonproductive one that usually occurs within the first few months of treatment and should generally resolve within 1 to 4 weeks after discontinuation of the ACE inhibitor. Other causes of cough should be considered (eg, pulmonary congestion in patients with heart failure) and excluded prior to discontinuation.

• Hematologic effects: Another ACE inhibitor, captopril, has been associated with neutropenia with myeloid hypoplasia and agranulocytosis; anemia and thrombocytopenia have also occurred. Patients with kidney impairment are at high risk of developing neutropenia. Patients with both kidney impairment and collagen vascular disease (eg, systemic lupus erythematosus) are at an even higher risk of developing neutropenia. Periodically monitor CBC with differential in these patients.

• Hypersensitivity reactions: Anaphylactic/anaphylactoid reactions can occur with ACE inhibitors. Severe anaphylactoid reactions may be seen during hemodialysis (eg, CVVHD) with high-flux dialysis membranes (eg, AN69), and rarely, during low density lipoprotein apheresis with dextran sulfate cellulose. Rare cases of anaphylactoid reactions have been reported in patients undergoing sensitization treatment with hymenoptera (bee, wasp) venom while receiving ACE inhibitors.

• Hypotension/syncope: Symptomatic hypotension with or without syncope can occur (usually with the first several doses); effects are most often observed in volume-depleted patients; correct volume depletion prior to initiation; close monitoring of patient is required especially with initial dosing and dosing increases; BP must be lowered at a rate appropriate for the patient's clinical condition. Although dose reduction may be necessary, hypotension is not a reason for discontinuation of future ACE inhibitor use especially in patients with heart failure where a reduction in systolic BP is a desirable observation.

• Kidney function deterioration: May be associated with deterioration of kidney function and/or increases in BUN and serum creatinine, particularly in patients with low renal blood flow (eg, renal artery stenosis, heart failure) whose GFR is dependent on efferent arteriolar vasoconstriction by angiotensin II; deterioration may result in oliguria, acute kidney failure, and progressive azotemia. Small increases in serum creatinine may occur following initiation; consider discontinuation only in patients with progressive and/or significant deterioration in kidney function (Bakris 2000).

Disease-related concerns:

• Aortic stenosis: Use with caution in patients with severe aortic stenosis; may reduce coronary perfusion resulting in ischemia.

• Ascites: Generally, avoid use in patients with ascites due to cirrhosis or refractory ascites; if use cannot be avoided in patients with ascites due to cirrhosis, monitor BP and kidney function carefully to avoid rapid development of kidney failure (AASLD [Runyon 2013]).

• Cardiovascular disease: Initiation of therapy in patients with ischemic heart disease or cerebrovascular disease warrants close observation due to the potential consequences posed by falling BP (eg, MI, stroke). Fluid replacement, if needed, may restore BP; therapy may then be resumed. Discontinue therapy in patients whose hypotension recurs.

• Collagen vascular disease: Use with caution in patients with collagen vascular disease especially with concomitant kidney impairment; may be at increased risk for hematologic toxicity.

• Hepatic impairment: Use with caution in patients with hepatic impairment.

• Hypertrophic cardiomyopathy with left ventricular outflow tract obstruction: Use with caution in patients with hypertrophic cardiomyopathy and left ventricular outflow tract obstruction since reduction in afterload may worsen symptoms associated with this condition (AHA/ACC [Ommen 2020]).

• Renal artery stenosis: Use with caution in patients with unstented unilateral/bilateral renal artery stenosis. When unstented unilateral or bilateral renal artery stenosis is present, use is generally avoided due to the elevated risk of deterioration in kidney function unless possible benefits outweigh risks.

• Kidney impairment: Use with caution in patients with kidney impairment; dosage adjustment may be needed. Avoid rapid dosage escalation which may lead to further kidney impairment.

Special populations:

• Race/Ethnicity: In Black patients, the BP-lowering effects of ACE inhibitors may be less pronounced. The exact mechanism is not known; differences in the renin-angiotensin-aldosterone system, low renin levels, and salt sensitivity more commonly found in Black patients may contribute (Brewster 2013; Helmer 2018).

• Surgical patients: In patients on chronic ACE inhibitor therapy, intraoperative hypotension may occur with induction and maintenance of general anesthesia; use with caution before, during, or immediately after major surgery. Cardiopulmonary bypass, intraoperative blood loss, or vasodilating anesthesia increases endogenous renin release. Use of ACE inhibitors perioperatively will blunt angiotensin II formation and may result in hypotension. However, discontinuation of therapy prior to surgery is controversial. If continued preoperatively, avoidance of hypotensive agents during surgery is prudent (Hillis 2011). Based on current research and clinical guidelines in patients undergoing noncardiac surgery, continuing ACE inhibitors is reasonable in the perioperative period. If ACE inhibitors are held before surgery, it is reasonable to restart postoperatively as soon as clinically feasible (ACC/AHA [Fleisher 2014]).

Dosage form specific issues:

• Lactose: Some formulations may contain lactose.

Dosage Forms: US

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

Tablet, Oral, as erbumine:

Generic: 2 mg, 4 mg, 8 mg

Generic Equivalent Available: US

Yes

Pricing: US

Tablets (Perindopril Erbumine Oral)

2 mg (per each): $1.97

4 mg (per each): $0.88 - $2.30

8 mg (per each): $2.80

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

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

Tablet, Oral, as erbumine:

Coversyl: 2 mg, 4 mg, 8 mg

Generic: 2 mg, 4 mg, 8 mg

Use: Labeled Indications

Hypertension, chronic: Management of hypertension.

Stable coronary artery disease: To reduce the risk of cardiovascular mortality or nonfatal myocardial infarction in patients with stable coronary artery disease.

Use: Off-Label: Adult

Heart failure with reduced ejection fraction

Medication Safety Issues

International issues:

The brand name Coversyl represents different salt forms of perindopril (ie, erbumine/tert-butylamine or arginine) in multiple international markets

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Aliskiren: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Aliskiren may enhance the hypotensive effect of Angiotensin-Converting Enzyme Inhibitors. Aliskiren may enhance the nephrotoxic effect of Angiotensin-Converting Enzyme Inhibitors. Management: Aliskiren use with ACEIs or ARBs in patients with diabetes is contraindicated. Combined use in other patients should be avoided, particularly when CrCl is less than 60 mL/min. If combined, monitor potassium, creatinine, and blood pressure closely. Risk D: Consider therapy modification

Allopurinol: Angiotensin-Converting Enzyme Inhibitors may enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Risk C: Monitor therapy

Alteplase: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Alteplase. Specifically, the risk for angioedema may be increased. Risk C: Monitor therapy

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider therapy modification

Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Angiotensin II: Angiotensin-Converting Enzyme Inhibitors may enhance the therapeutic effect of Angiotensin II. Risk C: Monitor therapy

Angiotensin II Receptor Blockers: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Angiotensin II Receptor Blockers may increase the serum concentration of Angiotensin-Converting Enzyme Inhibitors. Management: Use of telmisartan and ramipril is not recommended. It is not clear if any other combination of an ACE inhibitor and an ARB would be any safer. Consider alternatives when possible. Monitor blood pressure, renal function, and potassium if combined. Risk D: Consider therapy modification

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy

Aprotinin: May diminish the antihypertensive effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Arginine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

AzaTHIOprine: Angiotensin-Converting Enzyme Inhibitors may enhance the myelosuppressive effect of AzaTHIOprine. Risk C: Monitor therapy

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Brigatinib: May diminish the antihypertensive effect of Antihypertensive Agents. Brigatinib may enhance the bradycardic effect of Antihypertensive Agents. Risk C: Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination

Dapoxetine: May enhance the orthostatic hypotensive effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Dexmethylphenidate: May diminish the therapeutic effect of Antihypertensive Agents. Risk C: Monitor therapy

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Dipeptidyl Peptidase-IV Inhibitors: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk of angioedema may be increased. Risk C: Monitor therapy

Drospirenone-Containing Products: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy

Eplerenone: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Everolimus: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk of angioedema may be increased. Risk C: Monitor therapy

Ferric Gluconate: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Ferric Gluconate. Risk C: Monitor therapy

Ferric Hydroxide Polymaltose Complex: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Ferric Hydroxide Polymaltose Complex. Specifically, the risk for angioedema or allergic reactions may be increased. Risk C: Monitor therapy

Finerenone: Angiotensin-Converting Enzyme Inhibitors may enhance the hyperkalemic effect of Finerenone. Risk C: Monitor therapy

Flunarizine: May enhance the therapeutic effect of Antihypertensive Agents. Risk C: Monitor therapy

Gelatin (Succinylated): Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Gelatin (Succinylated). Specifically, the risk of a paradoxical hypotensive reaction may be increased. Risk C: Monitor therapy

Grass Pollen Allergen Extract (5 Grass Extract): Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Grass Pollen Allergen Extract (5 Grass Extract). Specifically, ACE inhibitors may increase the risk of severe allergic reaction to Grass Pollen Allergen Extract (5 Grass Extract). Risk X: Avoid combination

Heparin: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Heparins (Low Molecular Weight): May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Herbal Products with Blood Pressure Increasing Effects: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Herbal Products with Blood Pressure Lowering Effects: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy

Icatibant: May diminish the antihypertensive effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Indoramin: May enhance the hypotensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Iron Dextran Complex: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Iron Dextran Complex. Specifically, patients receiving an ACE inhibitor may be at an increased risk for anaphylactic-type reactions. Risk C: Monitor therapy

Lanthanum: May decrease the serum concentration of Angiotensin-Converting Enzyme Inhibitors. Management: Administer angiotensin-converting enzyme (ACE) inhibitors at least two hours before or after lanthanum. Risk D: Consider therapy modification

Levodopa-Foslevodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Foslevodopa. Risk C: Monitor therapy

Lithium: Angiotensin-Converting Enzyme Inhibitors may increase the serum concentration of Lithium. Management: Lithium dosage reductions will likely be needed following the addition of an ACE inhibitor. Monitor for increased concentrations/toxic effects of lithium if an ACE inhibitor is initiated/dose increased, or if switching between ACE inhibitors. Risk D: Consider therapy modification

Loop Diuretics: May enhance the hypotensive effect of Angiotensin-Converting Enzyme Inhibitors. Loop Diuretics may enhance the nephrotoxic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nicorandil: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the combination may result in a significant decrease in renal function. Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents (Topical): May diminish the therapeutic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider therapy modification

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Polyethylene Glycol-Electrolyte Solution: Angiotensin-Converting Enzyme Inhibitors may enhance the nephrotoxic effect of Polyethylene Glycol-Electrolyte Solution. Risk C: Monitor therapy

Potassium Salts: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Potassium-Sparing Diuretics: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Prazosin: Antihypertensive Agents may enhance the hypotensive effect of Prazosin. Risk C: Monitor therapy

Pregabalin: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Pregabalin. Specifically, the risk of angioedema may be increased. Risk C: Monitor therapy

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Racecadotril: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk for angioedema may be increased with this combination. Risk C: Monitor therapy

Ranolazine: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Sacubitril: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Sacubitril. Specifically, the risk of angioedema may be increased with this combination. Risk X: Avoid combination

Salicylates: May enhance the nephrotoxic effect of Angiotensin-Converting Enzyme Inhibitors. Salicylates may diminish the therapeutic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Silodosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Sirolimus Products: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk for angioedema may be increased. Risk C: Monitor therapy

Sodium Phosphates: Angiotensin-Converting Enzyme Inhibitors may enhance the nephrotoxic effect of Sodium Phosphates. Specifically, the risk of acute phosphate nephropathy may be enhanced. Risk C: Monitor therapy

Sparsentan: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Risk X: Avoid combination

Tacrolimus (Systemic): Angiotensin-Converting Enzyme Inhibitors may enhance the hyperkalemic effect of Tacrolimus (Systemic). Risk C: Monitor therapy

Temsirolimus: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk of angioedema may be increased. Risk C: Monitor therapy

Terazosin: Antihypertensive Agents may enhance the hypotensive effect of Terazosin. Risk C: Monitor therapy

Thiazide and Thiazide-Like Diuretics: May enhance the hypotensive effect of Angiotensin-Converting Enzyme Inhibitors. Thiazide and Thiazide-Like Diuretics may enhance the nephrotoxic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Tolvaptan: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Trimethoprim: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Urapidil: May interact via an unknown mechanism with Angiotensin-Converting Enzyme Inhibitors. Management: Avoid concomitant use of urapidil and angiotensin-converting enzyme (ACE) inhibitors. Risk D: Consider therapy modification

Urokinase: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk of angioedema may be increased. Risk C: Monitor therapy

Food Interactions

Perindopril active metabolite concentrations may be lowered if taken with food. Management: Administer prior to a meal.

Reproductive Considerations

Medications considered acceptable for the treatment of chronic hypertension during pregnancy may generally be used in patients trying to conceive. Angiotensin-converting enzyme (ACE) inhibitors are fetotoxic. Transition patients prior to conception to an agent preferred for use during pregnancy unless treatment with an ACE inhibitor is absolutely necessary (ACC/AHA [Whelton 2018]; ACOG 2019; NICE 2019). Closely monitor pregnant patients on ACE inhibitors with serial ultrasounds.

ACE inhibitors are not recommended for the treatment of heart failure in patients planning to become pregnant (AHA/ACC/HFSA [Heidenreich 2022]).

Pregnancy Considerations

Drugs that act on the renin-angiotensin system can cause injury and death to the developing fetus. Exposure to an angiotensin-converting enzyme (ACE) inhibitor during the first trimester of pregnancy may be associated with an increased risk of fetal malformations (ACOG 2019; ESC [Regitz-Zagrosek 2018]). Following exposure during the second or third trimesters, drugs that act on the renin-angiotensin system are associated with oligohydramnios. Oligohydramnios, due to decreased fetal renal function, may lead to fetal lung hypoplasia and skeletal malformations. Oligohydramnios may not appear until after an irreversible fetal injury has occurred. ACE inhibitor use during pregnancy is also associated with anuria, hypotension, renal failure, skull hypoplasia, and death in the fetus/neonate. Monitor infants exposed to an ACE inhibitor in utero for hyperkalemia, hypotension, and oliguria. Exchange transfusions or dialysis may be required to reverse hypotension or improve renal function.

Chronic maternal hypertension is also associated with adverse events in the fetus/infant. Chronic maternal hypertension may increase the risk of birth defects, low birth weight, premature delivery, stillbirth, and neonatal death. Actual fetal/neonatal risks may be related to the duration and severity of maternal hypertension. Untreated chronic hypertension may also increase the risks of adverse maternal outcomes, including gestational diabetes, preeclampsia, delivery complications, stroke, and myocardial infarction (ACOG 2019).

Discontinue ACE inhibitors as soon as possible once pregnancy is detected. Agents other than ACE inhibitors are recommended for the treatment of chronic hypertension during pregnancy (ACOG 2019; ESC [Cífková 2020]; SOGC [Magee 2022]). Consider the use of ACE inhibitors only for pregnant patients with hypertension refractory to other medications (ACOG 2019). Closely monitor pregnant patients on ACE inhibitors with serial ultrasounds.

ACE inhibitors are not recommended for the treatment of heart failure during pregnancy (AHA/ACC/HFSA [Heidenreich 2022]; ESC [Regitz-Zagrosek 2018]).

Breastfeeding Considerations

Perindopril and perindoprilat are present in breast milk.

Data related to the presence of perindopril and perindoprilat in breast milk are available from a study evaluating a method to measure their concentrations for lactation studies. Oral perindopril erbumine 10 mg twice daily was administered to 1 breastfeeding mother for 2 weeks. One breast milk sample was obtained 9 hours after the dose, providing concentrations of perindopril 0.9 ng/mL and perindoprilat 22.5 ng/mL (Lwin 2017). Following this study, breast milk was sampled in 10 lactating mothers between 8 and 119 days postpartum taking an equivalent of perindopril arginine 5 to 20 mg once daily. Dosing in all patients started within 3 days of delivery. Maximum breast milk concentrations of perindopril were 0.03 to 4.1 ng/mL occurring 2 to 4 hours after the maternal dose. The mean concentration of perindoprilat in breast milk ranged from 0.41 to 36.83 ng/mL with the maximum breast milk concentrations occurring 3 to 7 hours after the dose. Perindopril and perindoprilat were undetectable in some samples. A single serum sample was obtained from three exclusively breastfed full-term infants at approximately the time of maternal peak plasma concentrations. Perindopril was measurable in the serum of 3 infants (0.44 to 1.12 ng/mL) and perindoprilat was present in 2 infants (5.28 ng/mL and 10.14 ng/mL). Authors of the study calculated the estimated daily infant dose via breast milk to be 0.00045 to 0.18 µg/kg/day for perindopril and 0.032 to 5.4 μg/kg/day for perindoprilat, providing a relative infant dose (RID) of 0.0005 to 0.2% and 0.03 to 4.6% for perindopril and perindoprilat, respectively (Leggett 2020). In general, breastfeeding is considered acceptable when the RID of a medication is <10% (Anderson 2016; Ito 2000).

The manufacturer recommends that caution be exercised when administering perindopril to a person who is breastfeeding. When postpartum treatment with an angiotensin-converting enzyme (ACE) inhibitor is needed, consider use of an agent other than perindopril (AHA/ACC/HFSA [Heidenreich 2022]; ESC [Cífková 2020]). Avoid breastfeeding if high maternal doses of an ACE inhibitor are needed (ACOG 2019).

Monitoring Parameters

Blood pressure; BUN; serum creatinine; electrolytes (eg, potassium [especially in patients on concomitant potassium-sparing diuretics, potassium supplements, and/or potassium-containing salts]); if patient has collagen vascular disease and/or kidney impairment, periodically monitor CBC with differential. If angioedema is suspected, assess risk of airway obstruction (eg, involvement of tongue, glottis, larynx, and/or history of airway surgery).

Mechanism of Action

Perindopril is a prodrug for perindoprilat, which acts as a competitive inhibitor of 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.

Pharmacokinetics (Adult Data Unless Noted)

Onset of action: Peak effect: 1 to 2 hours

Protein binding: Perindopril: ~60%; Perindoprilat: 10% to 20%

Metabolism: Hepatically hydrolyzed to active metabolite, perindoprilat (~17% to 20% of a dose) and other inactive metabolites

Bioavailability: Perindopril: ~75%; Perindoprilat ~25% (~16% with food)

Half-life elimination: Parent drug: 1.5 to 3 hours; Metabolite: Effective: 3 to 10 hours, Terminal: 30 to 120 hours

Time to peak: Chronic therapy: Perindopril: ~1 hour; Perindoprilat: 3 to 7 hours (maximum perindoprilat serum levels are 2 to 3 times higher and T_max is shorter following chronic therapy); CHF: Perindoprilat: 6 hours

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

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Altered kidney function: At CrCl of 30 to 80 mL/minute, perindoprilat AUC is approximately doubled.

Hepatic function impairment: Bioavailability of perindoprilat is increased, and plasma concentrations are ~50% higher.

Older adult: Plasma concentrations of perindopril and perindoprilat in patients >70 years of age are approximately twice those observed in younger patients; renal excretion of perindoprilat decreases.

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

Brand Names: International

International Brand Names by Country

For country code abbreviations (show table)

(AE) United Arab Emirates: Coversyl | Heartopril;
(AR) Argentina: Coverene | Coverene cardio;
(AT) Austria: Coversum;
(AU) Australia: Apo perindopril | Coversyl | Genrx Perindopril | Idaprex | Indopril | Indosyl mono | Noumed perindopril | Ozapace | Perindo | Perindopril | Perindopril actavis | Perindopril an | Perindopril Ga | Perindopril generichealth | Perindopril-DP | Prexum;
(BD) Bangladesh: Cadnyl | Coversyl | Pendoril | Peripril;
(BE) Belgium: Coversyl | Mariper | Perindocyl | Perindopodimyl | Perindopril krka | Perindopril Mylan | Perindopril pfizer | Perindopril ratiopharm | Perindopril Teva;
(BF) Burkina Faso: Panoprist;
(BG) Bulgaria: Myden | Paxene | Prenessa | Prestarium | Prinopril | Stopress;
(BR) Brazil: Coversyl | Pericor | Perindopril erbumina;
(CH) Switzerland: Coversum | Perindopril actavis | Perindopril Helvepharm | Perindopril sandoz | Perindopril spirig | Perindopril-Mepha;
(CI) Côte d'Ivoire: Cardosyl | Panoprist;
(CL) Chile: Coversyl;
(CN) China: Acertil;
(CO) Colombia: Coversyl;
(CZ) Czech Republic: Apo Perindo | Coverex | Gleperil | Perinalon | Perindopril krka | Perindopril Pmcs | Perindopril ratiopharm | Pinbarix | Prenessa | Prestarium | Pricoron | Vidotin;
(DE) Germany: Coversum | Coversum cor | Perindopril erbumin 1 A Pharma | Perindopril erbumin glenmark;
(DO) Dominican Republic: Coversyl;
(EC) Ecuador: Coversil;
(EE) Estonia: Coverex | Perindobax | Prenessa | Prestarium | Stopress;
(EG) Egypt: Adwipril | Coversyl | Normafasten | Protectopril;
(ES) Spain: Coversyl | Perindopril actavis | Perindopril aurobindo | Perindopril krka | Perindopril Pharmacia | Perindopril ranbaxy | Perindopril Tecnigen | Perindopril Teva;
(FI) Finland: Acertil | Asyntilsan | Coversyl | Perindopril actavis | Perindopril Bmm Pharma | Perindopril glenmark | Perindopril krka | Perindopril orion | Perindopril pfizer | Perindopril ranbaxy | Perindopril ratiopharm;
(FR) France: Coversyl | Perindopril | Perindopril actavis | Perindopril arrow | Perindopril Biogaran | Perindopril Dci | Perindopril EG | Perindopril krka | Perindopril Mylan | Perindopril phr | Perindopril ranbaxy | Perindopril ratiopharm | Perindopril sandoz | Perindopril Teva Sante | Perindopril Winthrop | Perindopril Zydus;
(GB) United Kingdom: Coversyl | Perindopril | Perindopril Kent | Perindopril krka | Perindopril Teva;
(GR) Greece: Coversyl;
(HK) Hong Kong: Acertil | Apo perindopril | Covinace | Perindal;
(HR) Croatia: Perineva | Prexanil;
(HU) Hungary: Acetens | Armix | Coverex | Levenor | Perindan | Perindep | Perindopril actavis | Perindopril pfizer | Perindopril pharma vim | Perindopril ratiopharm | Perindopril sandoz | Perineva | Prenessa;
(ID) Indonesia: Prexum;
(IE) Ireland: Coversyl | Percarnil | Perindopril krka | Prindace;
(IN) India: Conape | Coversyl | Eviper | Perigard | Perihart;
(IT) Italy: Coversyl | Perindopril | Perindopril almus | Perindopril Doc | Perindopril EG | Perindopril Myl | Perindopril Mylan | Perindopril Pensa | Perindopril Ran | Perindopril sandoz | Perindopril Teva | Perindopril zentiva | Prenessa;
(JO) Jordan: Coversyl;
(JP) Japan: Cobathrow | Coversyl | Gopron | Perindopril | Perinsyl;
(KR) Korea, Republic of: Acerpril | Acertil;
(KW) Kuwait: Coversyl;
(LB) Lebanon: Acepril | Coversyl;
(LT) Lithuania: Coverex | Perindobax | Perindopril | Perindopril Bmm Pharma | Prestarium | Prindex | Stopress;
(LU) Luxembourg: Coversyl;
(LV) Latvia: Coverex | Perindalon | Perindobax | Perindopril pfizer | Perineva | Prestarium | Pricoron | Stopress | Vidotin;
(MA) Morocco: Acepril | Coeril | Coversyl | Inopril | Zynara;
(MX) Mexico: Coversyl;
(MY) Malaysia: Covapril | Coversyl | Covinace | Hiten 4 | Hiten 8 | Multipril | Perinace | Perindosyl | Provinace;
(NL) Netherlands: Coversyl | Perindopril tert butylamine | Perindopril tert butylamine Aurobindo | Perindopril tert butylamine Glenmark | Perindopril tert-Butylamine | Perindopril tert-butylamine A | Perindopril tert-butylamine Actavis | Perindopril tert-butylamine ratiopharm | Perindopril tert-butylamine Sandoz;
(NZ) New Zealand: Apo perindopril | Coversyl;
(PH) Philippines: Benace | Cadoril | Hypergo | Peridil | Peripil;
(PK) Pakistan: Coversyl | Perinace;
(PL) Poland: Cardipen | Coversyl | Erbugen | Lextril | Perindanor | Perindopril pfizer | Perindoran | Prenessa | Prestarium | Stopress;
(PT) Portugal: Coversyl | Perind | Perindopril | Perindopril aurobindo | Perindopril Aurovitas | Perindopril Bluepharma | Perindopril krka | Perindopril Labesfal | Perindopril ratiopharm | Perindopril sandoz | Perindopril vitoria | Perindopril Wynn | Perindopril zentiva;
(QA) Qatar: Coversyl Arginine | Hiten;
(RO) Romania: Ernyom | Perindopril Teva | Prenessa | Vidotin;
(RU) Russian Federation: Arentopres | Coverex | Gypernik | Parnavel | Perindopril | Perindopril Avexima | Perindopril FPO | Perindopril pfizer | Perindopril Richter | Perindopril sz | Perindopril TAD | Perineva | Perinpress | Piristar | Prenessa | Prestarium;
(SA) Saudi Arabia: Coversyl;
(SG) Singapore: Coversyl | Perinace | Perindopril Hexal | Provinace;
(SI) Slovenia: Percarnil | Perindopril Teva | Perineva | Prenessa | Prexanil | Voxin;
(SK) Slovakia: Perindopril pfizer | Perindopril Pmcs | Perindopril ratiopharm | Perindopril saneca | Prestarium | Prindex | Stopress | Valperal | Vidotin;
(TH) Thailand: Coversyl;
(TN) Tunisia: Cardosyl | Coversyl | Perindopril;
(TR) Turkey: Aceper | Coversyl | Periday | Serperil;
(TW) Taiwan: Acertil | Acetec | Perindopril | Prinwin;
(UA) Ukraine: Aliter | Coverex | Hiten | Perindopres | Perindopril | Perindopril darnitsa | Perindopril sandoz | Peripril | Prenelia | Prenesa | Prestarium | Stopress;
(UY) Uruguay: Miprilan;
(VE) Venezuela, Bolivarian Republic of: Coversyl | Perigard;
(VN) Viet Nam: Comegim | Coperil | Coversyl | Savidopril;
(ZA) South Africa: Acti Prex | Auro perindopril | Bindace | Cipla-perindopril | Ciplasyl | Circator | Coversyl | Pearinda | Perindopril unicorn | Peristar | Prexum | Spec Perindopril | Vectoryl | Zydus Perindopril;
(ZM) Zambia: Pearinda | Perigard

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Topic 9758 Version 342.0

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Perindopril: Drug information