Aceon

Name: Aceon

What is perindopril?

Perindopril is an ACE inhibitors. ACE stands for angiotensin converting enzyme.

Perindopril is used to treat high blood pressure (hypertension) and to prevent heart attack in people with coronary artery disease.

Perindopril may also be used for purposes not listed in this medication guide.

What should I discuss with my healthcare provider before taking perindopril?

You should not use this medicine if you are allergic to perindopril or if:

  • you have hereditary angioedema; or

  • you are allergic to any other ACE inhibitor, such as benazepril, captopril, enalapril, fosinopril, lisinopril, moexipril, quinapril, ramipril, or trandolapril.

If you have diabetes, do not use perindopril together with any medication that contains aliskiren (Amturnide, Tekturna, Tekamlo).

You may also need to avoid taking perindopril with aliskiren if you have kidney disease.

You should not use perindopril if you have hereditary angioedema.

To make sure perindopril is safe for you, tell your doctor if you have:

  • kidney disease (or if you are on dialysis);

  • liver disease;

  • heart disease or congestive heart failure;

  • diabetes; or

  • a connective tissue disease such as Marfan syndrome, Sjogren's syndrome, lupus, scleroderma, or rheumatoid arthritis.

Do not use if you are pregnant. If you become pregnant, stop taking this medicine and tell your doctor right away. Perindopril can cause injury or death to the unborn baby if you take the medicine during your second or third trimester.

It is not known whether perindopril passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

Uses for Aceon

Hypertension

Management of hypertension (alone or in combination with other classes of antihypertensive agents);1 2 46 500 may be used in fixed combination with amlodipine when such combined therapy is indicated.46

ACE inhibitors are recommended as one of several preferred drugs for the initial management of hypertension; other options include angiotensin II receptor antagonists, calcium-channel blockers, and thiazide diuretics.501 502 503 504 While there may be individual differences with respect to specific outcomes, these antihypertensive drug classes all produce comparable effects on overall mortality and cardiovascular, cerebrovascular, and renal outcomes.500 501 502 504 Individualize choice of therapy; consider patient characteristics (e.g., age, ethnicity/race, comorbidities, cardiovascular risk) as well as drug-related factors (e.g., ease of administration, availability, adverse effects, cost).500 501 502 503 504 515

ACE inhibitors may be preferred in hypertensive patients with heart failure, ischemic heart disease, diabetes mellitus, chronic kidney disease, or cerebrovascular disease or post-MI.500 501 502 504 520 523 524 525 526 527 534 535 536 543

Black hypertensive patients generally tend to respond better to monotherapy with calcium-channel blockers or thiazide diuretics than to ACE inhibitors.1 18 19 39 40 500 501 504 However, diminished response to an ACE inhibitor is largely eliminated when administered concomitantly with a calcium-channel blocker or thiazide diuretic.500 504

The optimum BP threshold for initiating antihypertensive drug therapy is controversial.501 504 505 506 507 508 515 523 530 Further study needed to determine optimum BP thresholds/goals; individualize treatment decisions.501 503 507 515 526 530

JNC 7 recommends initiation of drug therapy in all patients with uncomplicated hypertension and BP ≥140/90 mm Hg;500 JNC 8 panel recommends SBP threshold of 150 mm Hg for patients ≥60 years of age.501 Although many experts agree that SBP goal of <150 mm Hg may be appropriate for patients ≥80 years of age,502 504 505 530 application of this goal to those ≥60 years of age is controversial, especially for those at higher cardiovascular risk.501 502 505 506 508 511 515

In the past, initial antihypertensive drug therapy was recommended for patients with diabetes mellitus or chronic kidney disease who had BP ≥130/80 mm Hg;500 503 current hypertension management guidelines generally recommend a BP threshold of 140/90 mm Hg for these individuals (same as for the general population of patients without these conditions), although a goal of <130/80 mm Hg may still be considered.501 502 503 504 520 530 535 536 541

Heart Failure

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

Some evidence indicates that therapy with an ACE inhibitor (enalapril) may be less effective than angiotensin receptor-neprilysin inhibitor (ARNI) therapy (e.g., sacubitril/valsartan) in reducing cardiovascular death and heart failure-related hospitalization.702 800

ACCF, AHA, and the Heart Failure Society of America (HFSA) recommend that patients with chronic symptomatic heart failure and reduced left ventricular ejection fraction (LVEF) (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

Diabetic Nephropathy

A recommended agent in the management of patients with diabetes mellitus and persistent albuminuria† who have modestly elevated (30–300 mg/24 hours) or higher (>300 mg/24 hours) levels of urinary albumin excretion; slows rate of progression of renal disease in such patients.34 35 36 37 38 520 535 536

Cautions for Aceon

Contraindications

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

Warnings/Precautions

Warnings

Fetal/Neonatal Morbidity and Mortality

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

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

Other Warnings/Precautions

Use of Fixed Combinations

When used in fixed combination with amlodipine, consider the cautions, precautions, contraindications, and interactions associated with amlodipine.46 Consider cautionary information applicable to specific populations (e.g., pregnant or nursing women, individuals with hepatic or renal impairment, geriatric patients) for each drug in the fixed combination.46

Hypotension

Possible symptomatic hypotension, particularly in volume- and/or salt-depleted patients (e.g., those treated with diuretics, undergoing dialysis, with diarrhea or vomiting).1 2 13

Risk of marked hypotension, sometimes associated with oliguria, azotemia, and, rarely, acute renal failure and death in patients with heart failure 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, decreasing diuretic dosage, increasing sodium intake) prior to initiation of perindopril.1 600 (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

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

Renal Effects

Transient increases in BUN and Scr possible, especially in patients with preexisting renal impairment or those receiving concomitant diuretic therapy.1 Possible increases in BUN and Scr 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 heart failure.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 and use not recommended in patients with Clcr <30 mL/minute.1 600

Hepatic Impairment

Increased bioavailability of perindoprilat.1

Black Patients

BP reduction may be smaller in black patients compared with patients of other races.1 500 504 (See Hypertension under Uses and see Perindopril Arginine/Amlodipine Fixed-combination Therapy under Dosage and Administration.)

Higher incidence of angioedema reported with ACE inhibitors (as monotherapy) in black patients compared with other races.1 19 500

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

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 heart failure, decreased clearance and increased AUC of perindoprilat.1

Stability

Storage

Oral

Tablets

Perindopril erbumine: 20–25°C.1 Protect from moisture.1

Perindopril arginine/amlodipine fixed combination: 25ºC (may be exposed to 15–30ºC); protect from moisture.46

What are some side effects that I need to call my doctor about right away?

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of kidney problems like unable to pass urine, change in how much urine is passed, blood in the urine, or a big weight gain.
  • Signs of a high potassium level like a heartbeat that does not feel normal; change in thinking clearly and with logic; feeling weak, lightheaded, or dizzy; feel like passing out; numbness or tingling; or shortness of breath.
  • Very bad dizziness or passing out.
  • Cough that does not go away.
  • Very bad belly pain.
  • Very upset stomach or throwing up.
  • Liver problems have happened with drugs like this one. Sometimes, this has been deadly. Call your doctor right away if you have signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.

Consumer Information Use and Disclaimer

  • If your symptoms or health problems do not get better or if they become worse, call your doctor.
  • Do not share your drugs with others and do not take anyone else's drugs.
  • Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
  • Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about this medicine, please talk with your doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take Aceon (perindopril) or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to Aceon. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

Clinical Studies

Hypertension

In placebo-controlled studies of perindopril monotherapy (2 mg to 16 mg once daily) in patients with a mean blood pressure of about 150/100 mm Hg, 2 mg had little effect, but doses of 4 mg to 16 mg lowered blood pressure. The 8 mg and 16 mg doses were indistinguishable, and both had a greater effect than the 4 mg dose. In these studies, doses of 8 mg and 16 mg per day gave supine, trough blood pressure reductions of 9 to 15/5 to 6 mm Hg. When once daily and twice daily dosing were compared, the twice daily dosing regimen was generally slightly superior, but by not more than about 0.5 mm Hg to 1 mm Hg. After 2 mg to 16 mg doses of perindopril, the trough mean systolic and diastolic blood pressure effects were about 75 to 100% of peak effects.

Perindopril's effects on blood pressure were similar when given alone or on a background of 25 mg hydrochlorothiazide In general, the effect of perindopril occurred promptly, with effects increasing slightly over several weeks.

Formal interaction studies of Aceon® (perindopril erbumine) have not been carried out with antihypertensive agents other than thiazides. Limited experience in controlled and uncontrolled trials coadministering Aceon with a calcium channel blocker, a loop diuretic or triple therapy (beta-blocker, vasodilator and a diuretic), does not suggest any unexpected interactions. In general, ACE inhibitors have less than additive effects when given with beta-adrenergic blockers, presumably because both work in part through the renin angiotensin system.

In uncontrolled studies in patients with insulin-dependent diabetes, perindopril did not appear to affect glycemic control. In long-term use, no effect on urinary protein excretion was seen in these patients.

The effectiveness of Aceon was not influenced by sex and it was less effective in black patients than in nonblack patients. In elderly patients (greater than or equal to 60 years), the mean blood pressure effect was somewhat smaller than in younger patients, although the difference was not significant.

Stable Coronary Artery Disease

The EURopean trial On reduction of cardiac events with Perindopril in stable coronary Artery disease (EUROPA) was a multicenter, randomized, double-blind and placebo-controlled study conducted in 12,218 patients who had evidence of stable coronary artery disease without clinical heart failure. Patients had evidence of coronary artery disease documented by previous myocardial infarction more than 3 months before screening, coronary revascularization more than 6 months before screening, angiographic evidence of stenosis (at least 70% narrowing of one or more major coronary arteries), or positive stress test in men with a history of chest pain. After a run-in period of 4 weeks during which all patients received perindopril 2 mg to 8 mg, the patients were randomly assigned to perindopril 8 mg once daily (n=6,110) or matching placebo (n=6,108). The mean follow-up was 4.2 years. The study examined the long-term effects of perindopril on time to first event of cardiovascular mortality, nonfatal myocardial infarction, or cardiac arrest in patients with stable coronary artery disease.

The mean age of patients was 60 years; 85% were male, 92% were taking platelet inhibitors, 63% were taking β blockers, and 56% were taking lipid-lowering therapy. The EUROPA study showed that perindopril significantly reduced the relative risk for the primary endpoint events (Table 1). This beneficial effect is largely attributable to a reduction in the risk of nonfatal myocardial infarction. This beneficial effect of perindopril on the primary outcome was evident after about one year of treatment (Figure 1). The outcome was similar across all predefined subgroups by age, underlying disease or concomitant medication (Figure 2).

Table 1. Primary Endpoint and Relative Risk Reduction
CI=confidence interval; RRR: relative risk reduction; MI: myocardial infarction
  Perindopril
(N = 6,110)
Placebo
(N = 6,108)
RRR
(95% CI)
P
Combined Endpoint        
  Cardiovascular mortality, nonfatal MI or cardiac arrest 488 (8%) 603 (9.9%) 20% (9 to 29) 0.0003
Component Endpoint        
  Cardiovascular mortality 215 (3.5%) 249 (4.1%) 14% (-3 to 28) 0.107
  Nonfatal MI 295 (4.8%) 378 (6.2%) 22% (10 to 33) 0.001
  Cardiac arrest 6 (0.1%) 11 (0.2%) 46% (-47 to 80) 0.22

Figure 1. Time to First Occurrence of Primary Endpoint

Figure 2. Beneficial Effect of Perindopril Treatment on Primary Endpoint in Predefined Subgroups

Side Effects of Aceon

Serious side effects have been reported with Aceon. See "Drug Precautions" section.

Common side effects include:

  • cough
  • back pain
  • headache
  • upper respiratory infection (flu or common cold)
  • weakness
  • dizziness

This is not a complete list of Aceon side effects. Ask your doctor or pharmacist for more information.

 

 

Inform MD

Before taking Aceon, tell your doctor about all of your medical conditions. Especially tell your doctor if you:

  • have a history of angioedema (swelling under the skin)
  • have diabetes (high blood sugar) and you are taking aliskiren (Tekturna; also in Amturnide, Tekamlo, Tekturna HCT). Your doctor will probably tell you not to take Aceon if you have diabetes and you are also taking aliskiren.
  • have or have ever had heart or kidney disease or diabetes
  • have liver disease
  • are having surgery, including dental surgery. Inform the doctor or dentist that you are taking perindopril.
  • are using salt substitutes containing potassium. If your doctor prescribes a low-salt or low-sodium diet, follow these instructions carefully.
  • are pregnant or breastfeeding

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include feeling extremely dizzy or light-headed, or fainting.

In Summary

Common side effects of Aceon include: cough. See below for a comprehensive list of adverse effects.

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