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Perindopril Erbumine


Pronunciation: per-IN-doe-pril ER-bue-meen
Class: ACE inhibitor

Trade Names

- Tablets, oral 2 mg
- Tablets, oral 4 mg
- Tablets, oral 8 mg

- Tablets, oral 2 mg
- Tablets, oral 4 mg
- Tablets, oral 8 mg

Apo-Perindopril (Canada)
Coversyl (Canada)


Competitively inhibits angiotensin I–converting enzyme, resulting in prevention of angiotensin I conversion to angiotensin II, a potent vasoconstrictor that also stimulates aldosterone release. Clinical consequences are a decrease in BP, reduced sodium resorption, and potassium retention.

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Bioavailability is approximately 75% (perindopril) and approximately 25% (active metabolite, perindoprilat). Food reduces bioavailability by 43%. Steady state is 3 to 6 days. T max is approximately 1 h (perindopril) and 3 to 7 h (active metabolite, perindoprilat).


Protein binding is 60% (perindopril) and 10% to 20% (active metabolite, perindoprilat).


Extensively metabolized in liver to active metabolite, perindoprilat, and other metabolites by glucuronidation and cyclization via dehydration.


Urine (4% to 12% unchanged). The half-life is 0.8 to 1 h (perindopril). Apparent mean half-life is 3 to 10 h (perindoprilat). Cl is almost exclusively renal.

Special Populations

Renal Function Impairment

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

Hepatic Function Impairment

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


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

Heart failure patients

Perindoprilat Cl is reduced in CHF patients, resulting in a 40% higher dose-interval AUC.

Indications and Usage

Reduce risk of CV mortality or nonfatal MI in patients with stable coronary artery disease; treatment of essential hypertension.


Hypersensitivity to ACE inhibitors; hereditary or idiopathic angioedema.

Dosage and Administration

Hypertension (uncomplicated)

PO Initial dosage of 4 mg once daily, then titrate as needed (max, 16 mg/day). Usual maintenance dosage is 4 to 8 mg/day in 1 or 2 divided doses.


PO Initial dosage is 4 mg/day in 1 or 2 divided doses. Doses above 8 mg should be administered with careful BP monitoring and dose titration.

Stable Coronary Artery Disease

PO Initial dosage of 4 mg once daily for 2 wk, then increase as tolerated to a maintenance dosage of 8 mg once daily.

Elderly (older than 70 y)

PO Start with 2 mg once daily for the first week, followed by 4 mg once daily the second week, and 8 mg once daily for maintenance as tolerated.

Renal Function Impairment
Adults CrCl 30 mL/min or more

PO Initial dosage is 2 mg/day (max, 8 mg/day).

CrCl less than 30 mL/min

Not recommended.

General Advice

Administer without regard to meals. Administer with food if GI upset occurs.


Store between 68° and 77°F. Protect from moisture.

Drug Interactions

Angiotensin II receptor antagonists (eg, telmisartan)

Coadministration may increase the risk of renal dysfunction. Coadministration is not recommended.


Increased risk of excessive BP reduction. Consider decreasing the diuretic dose, discontinuing the diuretic, or increasing salt intake prior to initiating treatment with perindopril. If this is not possible, use the initial dosage with close medical supervision for at least 2 h and until BP has stabilized.

Drugs capable of increasing serum potassium (eg, aldosterone, aliskiren, cyclosporine, heparin, indomethacin), potassium-sparing diuretics (eg, spironolactone), potassium supplements, trimethoprim

Increased risk of hyperkalemia. Frequent monitoring of serum potassium is warranted.


The risk of angioedema may be increased. If an interaction is suspected, stop one or both drugs.


Administration of perindopril with food does not lower the rate or extent of perindopril absorption relative to the fasted state. However, the extent of biotransformation of perindopril to the active metabolite, perindoprilat, is reduced, resulting in a reduction in the AUC, which is probably not clinically important. In clinical trials, perindopril was generally administered in a nonfasting state.

Gold salts (eg, sodium aurothiomalate)

Nitritoid reactions (eg, facial flushing, nausea, vomiting, hypotension) have been reported rarely in patients coadministered injectable gold and perindopril.


Increased risk of lithium toxicity. Frequently monitor lithium concentrations.

NSAIDs (eg, indomethacin)

The hypotensive effect of perindopril may be reduced. This effect is more prominent in low-renin or volume-dependent hypertensive patients; concomitant use may further deteriorate renal function. Monitor blood pressure and renal function. In addition, the risk of hyperkalemia may be increased. Frequently monitor serum potassium.

Salicylates (eg, aspirin)

The hypotensive and vasodilator effects of perindopril may be reduced; monitor BP. Consider increasing the perindopril dose or stopping the salicylate if BP control or renal function deteriorates. A decreased dose of salicylates may avoid the interaction.

Sulfonylureas (eg, glyburide)

The risk of hypoglycemia may be increased. Close clinical and laboratory monitoring is warranted.


The pharmacologic effect of perindopril may be increased, resulting in severe hypotension. Use with caution and closely monitor BP. If hypotension occurs, supportive treatment may be necessary.

Adverse Reactions


Orthostatic hypotension (1%); cardiac arrest (postmarketing).


Bullous pemphigoid, exfoliative dermatitis, pemphigus, psoriasis (postmarketing).


Acute pancreatitis (postmarketing).


Acute renal failure, nephritis (postmarketing).


Anemia (including hemolytic and aplastic), neutropenia/agranulocytosis, pancytopenia, thrombocytopenia (postmarketing).


Elevated ALT (2%); elevated AST (1%); hepatic failure, jaundice (hepatocellular or cholestatic) (postmarketing).


Cough (12%); eosinophilic pneumonitis (postmarketing).


Back pain (6%); falls, hyponatremia, syndrome complex that may include arthralgia/arthritis, fever, myalgia, serositis, vasculitis, rash or other dermatologic manifestations, a positive antinuclear antibody, leukocytosis, eosinophilia or an elevated erythrocyte sedimentation rate (postmarketing).




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


In hypertensive patients with unilateral or bilateral renal artery stenosis, increases in BUN and serum creatinine may occur; therefore, monitor renal function during the first few weeks of therapy. Periodically monitor patients' serum potassium. Closely monitor patients for the first 2 wk of treatment and whenever the dose and/or diuretic is increased. Monitor elderly patients for dizziness because of potential for falls.


Category D .


Undetermined. American Academy of Pediatrics classifies perindopril as compatible with breast-feeding.


Safety and efficacy not established.

Renal Function

Changes in renal function may occur in susceptible individuals.

Anaphylactoid reactions

Presumably because ACE inhibitors affect the metabolism of eicosanoids and polypeptides, including endogenous bradykinin, patients receiving ACE inhibitors may be subject to a variety of adverse reactions.


May occur. Use with extreme caution in patients with hereditary angioedema. Angioedema of the tongue, glottis, or larynx may cause airway obstruction; consider use of subcutaneous epinephrine. Consider intestinal angioedema in differential diagnosis of patients on ACE inhibitor therapy who present with abdominal pain.


In patients with CHF, where renal function may depend on renin angiotensin-aldosterone system activity, perindopril treatment may be associated with oliguria and progressive azotemia, and, rarely, acute renal failure or death.


Chronic, nonproductive cough may occur.

Fetal/Neonatal morbidity and mortality

May occur. Discontinue perindopril as soon as possible if patient becomes pregnant.

Hepatic failure

Rarely, ACE inhibitors have been associated with a syndrome that starts with cholestatic jaundice and progresses to fulminant hepatic necrosis and, sometimes, death.


Elevations of serum potassium have been observed in some patients treated with ACE inhibitors.


Symptomatic hypotension may occur, especially in salt- or volume-depleted patients.

Neutropenia and agranulocytosis

May occur; risk appears greater in patients with renal impairment, especially patients with a collagen vascular disease, such as systemic lupus erythematosus or scleroderma.


Risk of hypotension may be increased.



Circulatory arrest, death, hypotension, hypothermia.

Patient Information

  • Advise patient to take once or twice daily as prescribed, without regard to meals, but to take with food if stomach upset occurs.
  • Advise patient to try to take each dose at about the same time each day.
  • Inform patient that drug controls, but does not cure, hypertension and to continue taking drug as prescribed, even when BP is not elevated.
  • Caution patient not to change the dose or stop taking unless advised by health care provider.
  • Instruct patient to continue taking other BP medications as prescribed by health care provider.
  • Instruct patient in BP and pulse measurement skills.
  • Advise patient to monitor and record BP and pulse at home and to inform health care provider if abnormal measurements are noted. Also advise patient to take record of BP and pulse to each follow-up visit.
  • Caution patient to avoid sudden position changes to prevent orthostatic hypotension.
  • Instruct patient to lie or sit down if experiencing dizziness or light-headedness when standing.
  • Emphasize importance of the following other modalities on BP control: moderate intake of alcohol and salt, regular exercise, smoking cessation, and weight control.
  • Caution patient that inadequate fluid intake, excessive perspiration, diarrhea, or vomiting can lead to excessive fall in BP, resulting in light-headedness or fainting.
  • Advise patient that medication may cause dizziness or light-headedness, and to use caution while driving or performing other tasks requiring mental alertness until tolerance is determined.
  • Caution patient to avoid unnecessary exposure to UV light (eg, sunlight, tanning booths) and to use sunscreen and wear protective clothing when exposed to UV light to avoid photosensitivity reaction.
  • Instruct patient to stop taking drug and immediately report any of the following symptoms to health care provider: chest pains; difficulty breathing; fainting; fever; irregular heartbeat; sore throat; swelling of the hands or feet; swelling of the face, lips, eyelids, or tongue.
  • Instruct patient to inform health care provider if a persistent cough develops while taking medication.
  • Caution patient not to take any prescription or OTC medications, potassium-containing salt substitutes, potassium supplements, herbal preparations, or dietary supplements unless advised by health care provider.
  • Tell patients to immediately report signs or symptoms suggesting angioedema (swelling of face, extremities, eyes, lips, tongue; hoarseness; or difficulty in swallowing or breathing) and to take no more of the drug before consulting a health care provider.
  • Inform women of childbearing age that drugs such as perindopril that act on the renin-angiotensin system may cause serious problems in the fetus and infant if they are used during pregnancy. Tell patients to report pregnancies to their health care provider as soon as possible.
  • Tell patients to report promptly any indication of infection (eg, sore throat, fever), which could be a sign of neutropenia.

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