perindopril (Rx)

Brand and Other Names:Aceon
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet

  • 2mg
  • 4mg
  • 8mg
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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

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Interactions

Interaction Checker

and perindopril

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    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            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%)

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            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

            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)

            Pregnancy (2nd and 3rd trimesters): significant risk of fetal/neonatal morbidity and mortality

            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

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            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.

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            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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            Formulary

            FormularyPatient Discounts

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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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