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Look Up > Drugs > Perindopril Erbumine
Perindopril Erbumine
Pronunciation
U.S. Brand Names
Generic Available
Pharmacological Index
Use
Pregnancy Risk Factor
Pregnancy/Breast-Feeding Implications
Contraindications
Warnings/Precautions
Adverse Reactions
Overdosage/Toxicology
Drug Interactions
Mechanism of Action
Pharmacodynamics/Kinetics
Usual Dosage
Monitoring Parameters
Cardiovascular Considerations
Mental Health: Effects on Mental Status
Mental Health: Effects on Psychiatric Treatment
Dental Health: Local Anesthetic/Vasoconstrictor Precautions
Dental Health: Effects on Dental Treatment
Patient Information
Nursing Implications
Dosage Forms

Pronunciation
(per IN doe pril er BYOO meen)

U.S. Brand Names
Aceon®

Generic Available

No


Pharmacological Index

Angiotensin-Converting Enzyme (ACE) Inhibitors


Use

Treatment of stage I or II hypertension and congestive heart failure treatment of left ventricular dysfunction after myocardial infarction


Pregnancy Risk Factor

D (especially during 2nd and 3rd trimesters)


Pregnancy/Breast-Feeding Implications

Breast-feeding/lactation: Only small amounts are excreted in breast milk


Contraindications

Hypersensitivity to perindopril or any component; angioedema related to previous treatment with an ACE inhibitor; bilateral renal artery stenosis; primary hyperaldosteronism; pregnancy (2nd and 3rd trimesters)


Warnings/Precautions

Anaphylactic reactions can occur. Angioedema can occur at any time during treatment (especially following first dose). Careful blood pressure monitoring with first dose (hypotension can occur especially in volume depleted patients). Dosage adjustment needed in renal impairment. Use with caution in hypovolemia; collagen vascular diseases; valvular stenosis (particularly aortic stenosis); hyperkalemia; or before, during, or immediately after anesthesia. Avoid rapid dosage escalation, which may lead to renal insufficiency. Neutropenia/agranulocytosis with myeloid hyperplasia can rarely occur. If patient has renal impairment then a baseline WBC with differential and serum creatinine should be evaluated and monitored closely during the first 3 months of therapy. Hypersensitivity reactions may be seen during hemodialysis with high-flux dialysis membranes (eg, AN69). Use with caution in unilateral renal artery stenosis and pre-existing renal insufficiency.


Adverse Reactions

>10% Central nervous system: Headache (23%)

1% to 10%:

Cardiovascular: edema (3.9%), chest pain (2.4%)

Central nervous system: Dizziness (8.2%), sleep disorders (2.5%), depression (2%), fever (1.5%), weakness (7.9%), nervousness (1%)

Dermatologic: Rash (2.3%)

Endocrine and metabolic: Hyperkalemia (1.4%), increased triglycerides (1.3%)

Gastrointestinal: Nausea (2.3%), diarrhea (4.3%), vomiting (1.5%), dyspepsia (1.9%), abdominal pain (2.7%), flatulence (1%)

Genitourinary: Sexual dysfunction (male: 1.4%)

Hepatic: Increased ALT (1.7%)

Neuromuscular & skeletal: Back pain (5.8%), upper extremity pain (2.8%), lower extremity pain (4.7%), paresthesia (2.3%), joint pain (1.1%), myalgia (1.1%), arthritis (1%)

Renal: Proteinuria (1.5%)

Respiratory: Cough (incidence is higher in women, 3:1) (12%), sinusitis (5.2%), rhinitis (4.8%), pharyngitis (3.3%)

Otic: Tinnitus (1.5%)

Miscellaneous: Viral infection (3.4%)

Note: Some reactions occurred at an incidence >1% but less than or equal to placebo:

<1% (Limited to important or life-threatening symptoms): Angioedema (0.1%), anaphylaxis, facial edema, malaise, pain, chills, orthostatic hypotension, constipation, xerostomia, increased appetite, gastroenteritis, bronchitis, rhinorrhea, dyspnea, sneezing, epistaxis, pulmonary fibrosis (<0.1%), vaginitis, nephrolithiasis, urinary frequency, urinary retention, flank pain, hypotension, ventricular extrasystole, myocardial infarction, vasodilation, syncope, conduction abnormalities, gout, hematoma, bruising, arthralgia, migraine, amnesia, vertigo, cerebral vascular accident (0.2%), anxiety, psychosocial disorder, sweating, tines, pruritus, dry skin, erythema,purpura (0.1%), conjunctivity, earache, hypokalemia, decreased uric acid, increased alkaline phosphatase, increased serum creatinine, increased AST, hematuria, and hyperglycemia.

Additional adverse effects associated with with ACE inhibitors include agranulocytosis (especially in patients with renal impairment or collagen vascular disease), neutropenia, decreases in creatinine clearance in some elderly hypertensive patients or those with chronic renal failure, and worsening of renal function in patients with bilateral renal artery stenosis or hypovolemic patients (diuretic therapy). In addition, a syndrome which may include fever, myalgia, arthralgia, interstitial nephritis, vasculitis, rash, eosinophilia and positive ANA, and elevated ESR has been reported with ACE inhibitors.


Overdosage/Toxicology

Mild hypotension has been the only toxic effect seen with acute overdose. Bradycardia may also occur; hyperkalemia occurs even with therapeutic doses, especially in patients with renal insufficiency and those taking NSAIDs.

Following initiation of essential overdose management, toxic symptom treatment and supportive treatment should be initiated. Hypotension usually responds to I.V. fluids or Trendelenburg positioning.


Drug Interactions

Alpha1 blockers: Hypotensive effect increased.

Aspirin and NSAIDs may decrease ACE inhibitor efficacy and/or increase risk of renal effects.

Diuretics: Hypovolemia due to diuretics may precipitate acute hypotensive events or acute renal failure.

Insulin: Risk of hypoglycemia may be increased.

Lithium: Risk of lithium toxicity may be increased; monitor lithium levels, especially the first 4 weeks of therapy.

Mercaptopurine: Risk of neutropenia may be increased.

Potassium-sparing diuretics (amiloride, spironolactone, triamterene): Increased risk of hyperkalemia.

Potassium supplements may increase the risk of hyperkalemia.

Trimethoprim (high dose) may increase the risk of hyperkalemia.


Mechanism of Action

Competitive inhibitor of angiotensin-converting enzyme (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


Pharmacodynamics/Kinetics

Peak concentrations: 1-2 hours

Distribution: Small amounts of the drug are excreted into breast milk

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

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

Bioavailability: Perindopril: 65% to 95%

Half-life: Parent drug: 1.5-3 hours; Metabolite: 25-30 hours

Time to peak: Occurs in 1 and 3-4 hours for perindopril and perindoprilat, respectively after chronic therapy; (maximum perindoprilat serum levels are 2-3 times higher and Tmax is shorter following chronic therapy); in CHF, the peak of perindoprilat is prolonged to 6 hours

Elimination: 75% of an oral dose is recovered in urine (10% as unchanged drug)


Usual Dosage

Adults: Oral:

Hypertension: Initial: 4 mg/day but may be titrated to response; usual range: 4-8 mg/day, maximum: 16 mg/day

Dosing adjustment in renal impairment:

Clcr >60 mL/minute: Administer 4 mg/day.

Clcr 30-60 mL/minute: Administer 2 mg/day.

Clcr 15-29 mL/minute: Administer 2 mg every other day.

Clcr <15 mL/minute: Administer 2 mg on the day of dialysis.

Hemodialysis: Perindopril and its metabolites are dialyzable

Dosing adjustment in hepatic impairment: None needed

Dosing adjustment in geriatric patients: Due to greater bioavailability and lower renal clearance of the drug in elderly subjects, dose reduction of 50% is recommended.


Monitoring Parameters

Serum creatinine, electrolytes, and WBC with differential initially and repeated at 2-week intervals for at least 90 days


Cardiovascular Considerations

ACE inhibitors decrease morbidity and mortality in patients with asymptomatic and symptomatic left ventricular dysfunction. In this situation, they decrease hospitalizations for, and retard progression to, congestive heart failure. ACE inhibitors are also indicated in patients postmyocardial infarction in whom left ventricular ejection fraction is <40%. When used in patients with heart failure the maximum, or maximum tolerated dose, should be achieved, if possible. Lower daily doses of ACE inhibitors have not demonstrated the same cardioprotective effects. ACE inhibitors have renal protective effects in patients with proteinuria and possibly cardioprotective effects in high-risk patients.


Mental Health: Effects on Mental Status

May cause dizziness or fatigue; may rarely cause sedation, insomnia, or depression


Mental Health: Effects on Psychiatric Treatment

May cause neutropenia; use caution with clozapine and carbamazepine; may decrease lithium clearance resulting in an increase in serum lithium levels and potential lithium toxicity; monitor serum lithium levels


Dental Health: Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions


Dental Health: Effects on Dental Treatment

<1%: Taste disturbances


Patient Information

This medication does not replace the need to follow exercise and diet recommendations for hypertension. Take as directed; do not miss doses, alter dosage, or discontinue without consulting prescriber. Consult prescriber for appropriate diet. Change position slowly when rising from sitting or lying. May cause transient drowsiness; avoid driving or engaging in tasks that require alertness until response to drug is known. Small frequent meals may help reduce any nausea, vomiting, or epigastric pain. You may experience persistent cough; contact prescriber. Report unusual weight gain or swelling of ankles and hands; persistent fatigue; dry cough; difficulty breathing; palpitations; or swelling of face, eyes, or lips. Pregnancy/breast-feeding precautions: Do not get pregnant while taking this medication - use appropriate barrier contraceptive measures. Consult prescriber if breast-feeding.


Nursing Implications

A reduction in clinical signs of congestive heart failure (dyspnea, orthopnea, cough) and an improvement in exercise duration are indicative of therapeutic response; a reduction of supine diastolic blood pressure of 10 mm Hg or to 90 mm Hg is indicative of excellent therapeutic response in patients with hypertension; observe for cough, difficulty breathing/swallowing, perioral swelling and signs and symptoms of agranulocytosis; monitor for 6 hours after initial dosing for profound hypotension or first-dose phenomenon


Dosage Forms

Tablet: 2 mg, 4 mg, 8 mg


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