Dosing & Uses
Dosage Forms & Strengths
tablet
- 2mg
- 4mg
- 8mg
Hypertension
4-8 mg PO qDay or divided q12hr
Maximum: 16 mg/day PO divided q12hr
Diuretic may be added; careful initial titration required to avoid symptomatic hypotension
Stable Coronary Artery Disease (CAD)
4 mg PO qDay for 2 weeks, THEN increase as tolerated to 8 mg/day PO divided q12hr
Reduce risk of cardiovascular mortality or MI in patients with stable CAD
Heart Failure (Off-label)
2 mg PO qDay initially to maximum 8-16 mg PO qDay
Dosing Considerations
Beneficial for many patients at risk for heart disease; reduces risk of MI, stroke, diabetic nephropathy , microalbuminuria, new onset DM
Consider starting an ACE inhibitor in high-risk patients, even if no HTN or CHF
May prolong survival in CHF, may preserve renal function in DM
May help to prevent migraine HA
Good choice in hyperlipidemia patients
Requires weeks for full effect; to start, use low dose and titrate q1-2wk
Abrupt discontinuance not associated with rapid increase in BP
Not recommended
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Adverse Effects
>10%
Headache (23%)
Cough (12%)
1-10%
Dizziness (8%)
Back pain (6%)
Lower extremity pain (5%)
Abnormal ECG (2%)
Palpitation (1%)
Depression (2%)
Somnolence (1%)
Menstrual disorder (1%)
Edema (4%)
ALT increased (2%)
Sexual dysfunction (male 1%)
Sleep disorder (3%)
Chest pain (2%)
Nausea/vomiting (2%)
Flatulence (1%)
Rash (2%)
Hyperkalemia (1%)
Tinnitus (2%)
Frequency Not Defined
Intestinal angioedema
Liver failure (rare)
Leukopenia
Pruritus
Stroke
Syncope
Urinary retention
Vertigo
Amnesia
Angioedema, More frequent in black patients (0.1%), Angioedema of lips, More frequent in black patients (0.1%), Angioedema of throat, More frequent in black patients (0.1%)
Warnings
Black Box Warnings
Discontinue as soon as possible when pregnancy is detected; affects renin-angiotensin system causing oligohydramnios, which may result in fetal injury and/or death
Contraindications
Hypersensitivity to perindopril/other ACE inhibitors
History of hereditary or angioedema associated with previous ACE inhibitor treatment
Coadministration of neprilysin inhibitors (eg, sacubitril) with ACE inhibitors may increase angioedema risk; do not administer ACE inhibitors within 36 hr of switching to or from sacubitril/valsartan
Bilateral renal artery stenosis
Do not coadminister with aliskiren in patients with diabetes mellitus or with renal impairment (ie, GFR <60 mL/min/1.73 m²)
Cautions
Apheresis (LDL) with dextran sulfate, hypertrophic cardiomyopathy, collagen vascular disease, excessive hypotension - volume depletion, hemodialysis with high flux membrane, aortic stenosis
ACE inhibition also causes increased bradykinin levels which putatively mediates angioedema
Coadministration with mTOR inhibitors (eg, temsirolimus) may increased risk for angioedema
Dual blockade of the renin angiotensin system with ARBs, ACE inhibitors, or aliskiren associated with increased risk for hypotension, hyperkalemia, and renal function changes (including acute renal failure) compared to monotherapy
Symptomatic hypotension is most likely to occur in patients who have been volume or salt-depleted as a result of prolonged diuretic therapy, dietary salt restriction, dialysis, diarrhea or vomiting; in patients with ischemic heart disease or cerebrovascular disease, an excessive fall in blood pressure could result in a myocardial infarction or a cerebrovascular accident; If excessive hypotension occurs, place patient in a supine position and, if necessary, treat with intravenous infusion of physiological saline; perinopril treatment can usually be continued following restoration of volume and blood pressure
Discontinue immediately if pregnant (see Contrainidications and Black Box Warnings)
Less effective in blacks
Renal impairment may occur
Neutropenia/agranulocytosis reported
Cough may occur within the first few months
Cholestatic jaundice may occur
Renal impairment
Pregnancy & Lactation
Pregnancy Category: D
Discontinue as soon as pregnancy detected; during the second and third trimesters of pregnancy, drugs that act directly on the renin-angiotensin have been associated with fetal injury that includes hypotension, neonatal skull hypoplasia, anuria, reversible or irreversible renal failure, and death
Lactation: not known if distributed into breast milk; use caution
Pregnancy Categories
A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA:Information not available.
Pharmacology
Mechanism of Action
Angiotensin converting enzyme (ACE) inhibitors dilate arteries and veins by competively inhibiting the conversion of angiotensin I to angiotensin II (a potent endogenous vasoconstrictor) and by inhibiting bradykinin metabolism; these actions result in preload and afterload reductions on the heart
ACE inhibitors also promote sodium and water excretion by inhibiting angiotensin-II induced aldosterone secretion; elevation in potassium may also be observed
ACE inhibitors also elicit renoprotective effects through vasodilation of renal arterioles
ACE inhibitors reduce cardiac and vascular remodeling associated with chronic hypertension, heart failure, and myocardial infarction
Pharmacokinetics
Half-Life: 1.5-3 hr (perindopril);3-10 hr (perindoprilat):
Onset: 1-2 hr (peak response PO for HTN)
Peak Plasma Time: 1 hr (PO; perindopril); 3-7 hr (perindoprilat)
Therapeutic concentration range: 80-150 ng/mL
Renal clearance: 1.5 L/h (perindopril), 6-10 L/hr (perindoprilat total body: 21-31 L/h perindopril): 46 L/hr) (perindoprilat)
Excretion: Urine (75%)
Duration: 24 hr
Bioavailability: 75% (perindopril); 20-30% (perindoprilat)
Protein Bound: 60% (perindopril); 10-20% (perindoprilat)
Vd: 0.22 L/kg (perindopril); 0.16 L/kg (perindoprilat)
Metabolism: Liver (88 -96%)
Metabolites: Perindoprilat (active), glucuronide derivatives (inactive)
Dialyzable: HD: yes
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Patient Handout
Formulary
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