Aceon

Generic Name: Perindopril Erbumine
Class: Angiotensin-Converting Enzyme Inhibitors
VA Class: CV800
Chemical Name: (2S - (1(R*(R*)),2α,3aβ,7aβ)) - 1 - (2 - ((1 - (Ethoxycarbonyl)butyl)amino) - 1 - oxopropyl)octahydro - 1H - indole - 2 - carboxylic acid
Molecular Formula: C₁₉H₃₂N₂O₅
CAS Number: 82834-16-0

• 
  

  May cause fetal and neonatal morbidity and mortality if used during pregnancy.^{1 42 43} (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

  
  


• 
  

  If pregnancy is detected, discontinue perindopril as soon as possible.^{1 43}

  
  

Introduction

Nonsulfhydryl ACE inhibitor.¹

Uses for Aceon

Hypertension

Management of hypertension (alone or in combination with other classes of antihypertensive agents).^{1 2}

One of several preferred initial therapies in hypertensive patients with heart failure, postmyocardial infarction, high coronary disease risk, diabetes mellitus, chronic renal failure, and/or cerebrovascular disease.²¹

Can be used as monotherapy for initial management of uncomplicated hypertension; however, thiazide diuretics are preferred by JNC 7.²¹

CHF

Management of symptomatic CHF†, usually in conjunction with cardiac glycosides, diuretics, and β-adrenergic blocking agents.^{20 23 24 25 26 27}

Diabetic Nephropathy

A first-line agent in the treatment of diabetic nephropathy† in hypertensive patients with type 2 diabetes mellitus.^{6 31 32 33 34 35 36 37 38}

Aceon Dosage and Administration

Administration

Oral Administration

Administer orally once or twice daily¹ without regard to meals.² In clinical studies, administration in 2 divided doses was only slightly more effective than once-daily dosing.¹

Dosage

Available as perindopril erbumine; dosage expressed in terms of perindopril erbumine.¹

Adults

Hypertension

Oral

Initially, 4 mg once daily as monotherapy.¹ Adjust dosage at approximately monthly intervals (more aggressively in high-risk patients) to achieve BP control.^{6 21}

In patients currently receiving diuretic therapy, discontinue diuretic, if possible, 2–3 days before initiating perindopril.¹ May cautiously resume diuretic therapy if BP not controlled adequately with perindopril alone.¹ If diuretic cannot be discontinued, initiate therapy at 2–4 mg daily (given in 1 dose or 2 divided doses) under close medical supervision for several hours until BP has stabilized.¹

Usual dosage: 4–8 mg once daily.^{1 2 21}

Prescribing Limits

Adults

Hypertension

Oral

Maximum 16 mg daily.¹

Special Populations

Renal Impairment

Hypertension

Initially, 2 mg daily in patients with renal impairment (Cl_cr >30 mL/minute); titrate until BP is controlled or to maximum of 8 mg daily. (See Renal Impairment under Cautions.)¹

Geriatric Patients

Hypertension

Initially, 4 mg daily, given in 1 dose or 2 divided doses.¹ Adjust dosage to achieve BP control.¹ Administer dosages >8 mg daily with caution and under close medical supervision.¹

Cautions for Aceon

Contraindications

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  Known hypersensitivity (e.g., history of angioedema) to perindopril or another ACE inhibitor.¹

  
  

Warnings/Precautions

Warnings

Hypotension

Possible symptomatic hypotension, particularly in volume- and/or salt-depleted patients (e.g., those treated with diuretics).^{1 13} Risk of marked hypotension, sometimes associated with oliguria, azotemia, and, rarely, acute renal failure and death in patients with CHF with or without associated renal insufficiency.¹ Severe hypotension may result in MI or stroke in patients with ischemic cardiovascular or cerebrovascular disease.¹

Hypotension may occur in patients undergoing surgery or during anesthesia with agents that produce hypotension; recommended treatment is fluid volume expansion.¹

To minimize potential for hypotension, correct volume and/or salt depletion (e.g., by withholding diuretic therapy, increasing sodium intake) prior to initiation of perindopril.¹ (See Dosage under Dosage and Administration.)

In patients at risk of excessive hypotension, initiate therapy under close medical supervision; monitor closely for first 2 weeks following initiation of perindopril or any increase in perindopril or diuretic dosage.¹

If excessive hypotension occurs, immediately place patient in supine position and, if necessary, administer IV infusion of 0.9% sodium chloride injection.¹ Perindopril therapy usually can be continued following restoration of volume and BP.¹

Hematologic Effects

Neutropenia and agranulocytosis reported with captopril; risk appears to depend principally on presence of renal impairment and/or presence of collagen vascular disease (e.g., systemic lupus erythematosus, scleroderma); risk with perindopril is unknown.¹

Fetal/Neonatal Morbidity and Mortality

Possible fetal and neonatal morbidity and mortality when used during pregnancy.¹ (See Boxed Warning.)

Possible fetal and neonatal morbidity and mortality when used during pregnancy.^{1 43} (See Boxed Warning.) Such potential risks occur throughout pregnancy, especially during the second and third trimesters.⁴³

Also may increase the risk of major congenital malformations when administered during the first trimester of pregnancy.^{42 43}

Discontinue as soon as possible when pregnancy is detected, unless continued use is considered lifesaving.^{1 42 43} Nearly all women can be transferred successfully to alternative therapy for the remainder of their pregnancy.¹³

Hepatic Effects

Clinical syndrome that usually is manifested initially by cholestatic jaundice and may progress to fulminant hepatic necrosis (occasionally fatal) reported rarely with ACE inhibitors.¹

If jaundice or marked elevation of liver enzymes occurs, discontinue drug and monitor patient.¹

Sensitivity Reactions

Anaphylactoid reactions and/or head and neck angioedema possible; angioedema associated with tongue, glottis, or larynx may be fatal.¹ If angioedema occurs, promptly discontinue perindopril and observe patient until swelling disappears.¹ Immediate medical intervention (e.g., epinephrine) for involvement of tongue, glottis, or larynx.¹

Intestinal angioedema possible; consider in differential diagnosis of patients who develop abdominal pain.¹

Anaphylactoid reactions reported in patients receiving ACE inhibitors while undergoing LDL apheresis with dextran sulfate absorption or following initiation of hemodialysis that utilized high-flux membrane.¹

Life-threatening anaphylactoid reactions reported in at least 2 patients receiving ACE inhibitors while undergoing desensitization treatment with hymenoptera venom.¹

Contraindicated in patients with a history of angioedema associated with ACE inhibitors.¹

General Precautions

Renal Effects

Transient increases in BUN and S_cr possible, especially in patients with preexisting renal impairment or those receiving concomitant diuretic therapy.¹ Possible increases in BUN and S_cr in patients with unilateral or bilateral renal artery stenosis; generally reversible following discontinuance of therapy.¹

Possible oliguria, progressive azotemia, and, rarely, acute renal failure and/or death in patients with severe CHF.¹

Closely monitor renal function for the first few weeks of therapy in hypertensive patients with unilateral or bilateral renal-artery stenosis.¹ Some patients may require dosage reduction or discontinuance of ACE inhibitor or diuretic.¹

Hyperkalemia

Possible hyperkalemia, especially in patients with renal impairment or diabetes mellitus and those receiving drugs that can increase serum potassium concentration (e.g., potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes).¹ (See Specific Drugs under Interactions.)

Monitor serum potassium concentration carefully in these patients.¹

Cough

Persistent and nonproductive cough; resolves after drug discontinuance.¹

Specific Populations

Pregnancy

Category C (1st trimester); Category D (2nd and 3rd trimesters).¹ (See Boxed Warning.)

Lactation

Distributed into milk in rats; not known whether perindopril is distributed into milk in humans.¹ Caution if used in nursing women.¹

Pediatric Use

Safety and efficacy not established in pediatric patients.¹

Geriatric Use

Possible lesser effect on BP in those >60 years of age than in younger patients.¹ Increased plasma concentrations of perindopril and perindoprilat.¹ Dizziness and possibly rash may occur more frequently in geriatric patients.¹

Renal Impairment

Deterioration of renal function may occur (see Renal Effects under Cautions).¹ Systemic exposure to perindoprilat may be increased with decreasing renal function.¹

Initial dosage adjustment recommended in patients with renal impairment.¹ (See Renal Impairment under Dosage and Administration.) Safety and efficacy not established in patients with Cl_cr <30 mL/minute.¹

Hepatic Impairment

Increased bioavailability of perindoprilat.¹

Blacks

BP reduction may be smaller in black patients compared with nonblack patients;^{1 5 6} however, no apparent population difference during combined therapy with ACE inhibitor and thiazide diuretic.^{5 6} Use in combination with a diuretic.^{5 6}

Higher incidence of angioedema reported with ACE inhibitors (as monotherapy) in blacks compared with other races.^{1 19 21}

Common Adverse Effects

Cough, proteinuria, palpitation, sinusitis, viral infection, dyspepsia, fever, upper extremity pain, hypertonia.¹

Dizziness reported at a rate similar to that with placebo, but incidence increases with increased dosage, suggesting causal relation to the drug.¹

Interactions for Aceon

Specific Drugs

Drug	Interaction	Comments
Digoxin	No effect on digoxin concentrations; effect on perindopril/perindoprilat concentrations has not been excluded1
Diuretics	Increased hypotensive effect1	If possible, discontinue diuretic before initiating perindopril1 (see Dosage under Dosage and Administration)
Diuretics, potassium-sparing (amiloride, spironolactone, triamterene)	Enhanced hyperkalemic effect1	Use with caution; monitor serum potassium concentrations frequently1
Gentamicin	Possible interaction based on animal data; no studies in humans1	Use with caution1
Lithium	Increased serum lithium concentrations; possible toxicity1	Use with caution; monitor serum lithium concentrations frequently1
Potassium supplements or potassium-containing salt substitutes	Enhanced hyperkalemic effect1	Use with caution; monitor serum potassium concentrations frequently1

Aceon Pharmacokinetics

Absorption

Bioavailability

Absolute bioavailability of perindopril is 75%; mean bioavailability of perindoprilat is 25%.¹

Peak plasma concentrations of perindopril and perindoprilat are achieved within 1 and 3–7 hours, respectively.¹

Onset

Antihypertensive effects occur promptly, with effects increasing slightly over several weeks.¹

Duration

Maximal antihypertensive effect (inhibition of 80–90% of ACE activity) persists for about 10–12 hours; at 24 hours, only 60% of ACE activity is blocked.¹

Food

Food does not affect rate or extent of absorption of perindopril but reduces bioavailability of perindoprilat by about 35%.¹

Special Populations

In patients with hepatic impairment, increased perindoprilat bioavailability.¹

In patients with renal impairment, increased perindoprilat concentrations with decreasing renal function.¹

In patients >70 years of age, increased plasma perindopril and perindoprilat concentrations (resulting from increased conversion of perindopril to perindoprilat and decreased renal excretion of perindoprilat).¹

Distribution

Extent

Appears to cross the blood-brain barrier only slightly in rats.¹

Crosses the placenta and is distributed into milk in rats.¹

Plasma Protein Binding

Perindopril: 60%.¹

Perindoprilat: 10–20%.¹

Elimination

Metabolism

Extensively metabolized in the liver to 6 metabolites, including an active metabolite, perindoprilat.¹

Elimination Route

Eliminated principally in urine (as metabolites).¹

Removed by renal dialysis.¹

Half-life

Perindopril: 0.8–1 hour.¹

Perindoprilat: 3–10 hours.¹

Special Populations

In patients with CHF, decreased clearance and increased AUC of perindoprilat.¹

Stability

Storage

Oral

Tablets

20–25°C.¹ Protect from moisture.¹

ActionsActions

• 
  

  Prodrug; not pharmacologically active until hydrolyzed in the liver to perindoprilat.^{1 2}

  
  


• 
  

  Suppresses the renin-angiotensin-aldosterone system.¹

  
  

Advice to Patients

• 
  

  Risk of angioedema, anaphylactoid reactions, or other sensitivity reactions.¹ Importance of reporting sensitivity reactions (e.g., edema of face, eyes, lips, tongue, or extremities; hoarseness; swallowing or breathing with difficulty) immediately to clinician and of discontinuing the drug.¹

  
  


• 
  

  Importance of reporting signs of infection (e.g., sore throat, fever).¹

  
  


• 
  

  Risk of hypotension.¹ Importance of informing clinicians promptly if lightheadedness or fainting occurs.¹

  
  

  Importance of adequate fluid intake; risk of volume depletion with excessive perspiration, dehydration, vomiting, or diarrhea.¹

  
  


• 
  

  Risks of use during pregnancy.¹ (See Boxed Warning.)

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs (including salt substitutes containing potassium).¹

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹

  
  


• 
  

  Importance of advising patients of other important precautionary information.¹ (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Perindopril Erbumine

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets	2 mg	Aceon (scored)	Solvay
		4 mg	Aceon (scored)	Solvay
		8 mg	Aceon (scored)	Solvay

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Aceon 2MG Tablets (SOLVAY): 100/$199 or 200/$383.98

Aceon 4MG Tablets (SOLVAY): 30/$77.99 or 90/$207.97

Aceon 8MG Tablets (SOLVAY): 100/$273.98 or 200/$547.95

Perindopril Erbumine 2MG Tablets (AUROBINDO PHARMA): 100/$75.99 or 300/$199.98

Perindopril Erbumine 4MG Tablets (AUROBINDO PHARMA): 100/$79.99 or 300/$209.97

Perindopril Erbumine 8MG Tablets (AUROBINDO PHARMA): 100/$85.99 or 300/$219.96

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions April 2008. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Solvay Pharmaceuticals. Aceon (perindopril erbumine) tablets prescribing information. Marietta, GA; 2003 Mar.

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).

5. Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. The fifth report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC V). Arch Intern Med. 1993; 153:154-83. [IDIS 309043] [PubMed 8422206]

6. National Heart, Lung, and Blood Institute National High Blood Pressure Education Program. The sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI). Bethesda, MD: National Institutes of Health; 1997 Nov. (NIH publication No. 98-4080.)

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.

9. Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. The 1984 Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. Arch Intern Med. 1984; 144:1045-57. [IDIS 184763] [PubMed 6143542]

10. Anon. Drugs for hypertension. Med Lett Drugs Ther. 1984; 26:107-12. [PubMed 6150424]

11. Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. The 1988 Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. Arch Intern Med. 1988; 148:1023-38. [IDIS 242588] [PubMed 3365073]

12. Lapostolle F, Borron SW, Bekka R et al. Lingual angioedema after perindopril use. Am J Cardiol. 1998; 81:523. [IDIS 401641] [PubMed 9485152]

13. Bagger JP. Adverse event with first-dose perindopril in congestive heart failure. Lancet. 1997; 349:1671-2. [IDIS 387024] [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. [IDIS 452007] [PubMed 10977801]

17. Associated Press (American Diabetes Association). Diabetics urged: drop blood pressure. Chicago, IL; 2000 Aug 29. Press Release from web site ().

18. Appel LJ. The verdict from ALLHAT—thiazide diuretics are the preferred initial therapy for hypertension. JAMA. 2002; 288:3039-60. [IDIS 490723] [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. [IDIS 490721] [PubMed 12479763]

20. Anon. Consensus recommendations for the management of chronic heart failure. On behalf of the membership of the advisory council to improve outcomes nationwide in heart failure. Part II. Management of heart failure: approaches to the prevention of heart failure. Am J Cardiol. 1999; 83:9A-38A.

21. National Heart, Lung, and Blood Institute National High Blood Pressure Education Program. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VII) Express. Bethesda, MD: May 14 2003. From NIH website. (). (Also published in JAMA. 2003; 289.

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.

28. American Diabetes Association. Treatment of hypertension in adults with diabetes. Diabetes Care. 2003; 26(Suppl 1):S80-2.

29. Guidelines Committee. 2003 European Society of Hypertension–European Society of Cardiology guidelines for the management of arterial hypertension. J Hypertension. 2003; 21:1011-53.

30. Novartis. Diovan (valsartan) tablets prescribing information. East Hanover, NJ; 2002 Aug.

31. American Diabetes Association. Treatment of hypertension in adults with diabetes. Diabetes Care. 2002; 25:134-47. [IDIS 479088] [PubMed 11772914]

32. American Diabetes Association. Standards of medical care for patients with diabetes mellitus. Diabetes Care. 2002; 25(Suppl 1):S33-43.

33. American Diabetes Association. Clinical Practice Recommendations 2002. Position Statement. Diabetic nephropathy. Diabetes Care. 2002; 25(Suppl 1):S85-9.

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. [IDIS 321612] [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. [IDIS 365188] [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. [IDIS 324307] [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. [IDIS 531054] [PubMed 15811979]

40. Neaton JD, Kuller LH. Diuretics are color blind. JAMA. 2005; 293:1663-6. [IDIS 531056] [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 ().

44. Sibai BM. Treatment of hypertension in pregnant women. N Engl J Med. 1996; 335:257-65. [IDIS 369138] [PubMed 8657243]

45. US Food and Drug Administration. Dangers of ACE inhibitors during pregnancy. FDA Med Bull. 1992; 22:2.

More Aceon resources

• Aceon Side Effects (in more detail)
• Aceon Dosage
• Aceon Use in Pregnancy & Breastfeeding
• Drug Images
• Aceon Drug Interactions
• Aceon Support Group
• 0 Reviews for Aceon - Add your own review/rating

• Aceon Prescribing Information (FDA)


• Aceon Consumer Overview


• Aceon Advanced Consumer (Micromedex) - Includes Dosage Information


• Aceon MedFacts Consumer Leaflet (Wolters Kluwer)


• Perindopril Prescribing Information (FDA)

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