ACE Inhibitor

Aka: ACE Inhibitor, Angiotensin Converting Enzyme Inhibitor, Captopril, Capoten, Lisinopril, Prinivil, Zestril, Enalapril, Vasotec, Fosinopril, Monopril, Benzapril, Lotensin, Moexipril, Univasc, Perindopril, Aceon, Quinapril, Accupril, Ramipril, Altace, Trandopril, Mavik

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II. Contraindications

  1. Absolute Contraindications
    1. Angioedema history
      1. Regardless of cause (even if not due to ACE Inhibitor)
    2. Pregnancy (serious Teratogenicity - black box warning)
    3. Renal Artery Stenosis
    4. ACE Inhibitor related Allergic Reaction
  2. Relative Contraindications
    1. Aortic Stenosis
    2. Hypertrophic Cardiomyopathy

III. Indications

  1. Hypertension
    1. Useless in low renin patients (esp. Black ethnicity)
    2. Low renin patients respond better to Diuretics
  2. Myocardial Infarction
    1. Early ACE Inhibitor in acute Myocardial Infarction
      1. Started within 24 hours of Anterior MI
      2. Significant reduction in CHF and death
      3. Significantly lower mortality at 1 year
    2. Reference
      1. Ambrosioni (1995) N Engl J Med 332:80-5 [PubMed]
      2. Stenestrand (2001) JAMA 285:430-6 [PubMed]
  3. Congestive Heart Failure
    1. Left ventricle Systolic Dysfunction
  4. Diabetic Nephropathy
  5. Renal Insufficiency

IV. Mechanism

  1. Renin-Angiotensin System

V. Safety

  1. Pregnancy: Category D
    1. Category C if stopped in first trimester
    2. Serious Teratogenicity risk to fetus if continued into second or third trimester
  2. Lactation
    1. Unknown
    2. Risk of Hypotension in newborns

VI. Preparations (Choose once daily dosing if possible)

  1. Benzapril (Lotensin)
    1. Hypertension: 10 mg orally daily (target 20-40 mg/day)
    2. Maximum: 80 mg/day
    3. Renal Dosing
      1. GFR <30: Start at 5 mg
    4. Primarily renal excretion (as benzeprilat)
    5. Available as unscored generic tablets: 5, 10, 20 and 40 mg
  2. Captopril (Capoten)
    1. Hypertension: 25 mg orally twice to three times daily (maximum 450 mg/day)
    2. CHF: 6.25 - 12.5 mg orally three times daily (maximum 450 mg/day)
    3. Primarily Renal Dosing
    4. Available as scored generic tablets: 12.5, 25, 50 and 100 mg
  3. Enalapril (Vasotec)
    1. Hypertension: 5 mg orally daily (maximum 40 mg/day)
    2. CHF, GFR<30: 2.5 mg orally daily to twice daily (maximum 40 mg/day)
    3. IV (Hypertensive Emergency): 1.25 mg IV every 6 hours
    4. Excretion both renal and hepatic
    5. Available as scored tablets: 2.5, 5, 10 and 20 mg
  4. Fosinopril (Monopril)
    1. Hypertension: 10 mg orally daily (target 40 mg/day)
    2. CHF: 10 mg orally daily (target 20-40 mg/day)
    3. Renal Impairment: 5 mg orally daily at start
    4. Maximum: 80 mg/day
    5. Excretion both renal and hepatic
    6. Available as scored tablets (10 mg) and unscored tablets (20 and 40 mg)
  5. Lisinopril (Prinivil, Zestril)
    1. Hypertension: 10 mg orally daily (target 20-40 mg/day)
    2. CHF: 5 mg orally daily (target 20 mg/day)
    3. Acute MI: 5 mg orally daily for 2 days then 10 mg orally daily
    4. Renal Dosing
      1. GFR 10-30: 2.5 to 5 mg orally daily to start
      2. GFR <10: 2.5 mg orally daily to start
    5. Maximum 40 mg/day
    6. Primarily renal excretion
    7. Available as generic/Prinivil scored tablets (10, 20 and 40 mg)
    8. Available as generic/Zestril unscored tabs (2.5, 5, 10, 20, 30 and 40 mg)
  6. Moexipril (Univasc): Take one hour before meals
    1. Hypertension: 7.5 mg orally daily (maximum 30 mg/day)
    2. Primarily hepatic metabolism
    3. Available as generic scored tablets (7.5, 15 mg)
  7. Perindopril (Aceon)
    1. Hypertension: 4 mg orally daily (target 4-8 mg/day)
    2. Maximum 16 mg/day
    3. Primarily renal metabolism
    4. Available as generic unscored tablets (2, 4, 8 mg)
  8. Quinapril (Accupril)
    1. Hypertension: 10 mg orally daily (target 20-40 mg/day)
    2. CHF: 2.5 mg to 5 mg orally twice daily
      1. Low dose is especially important if concurrent Diuretic use
      2. Titrating weekly to 20-40 mg/day
    3. Renal Dosing
      1. GFR 30-60: 5 mg orally daily to start
      2. GFR 10-30: 2.5 mg orally daily to start
    4. Maximum: 80 mg/day (no benefit above 40 mg/day)
    5. Excretion is 50-60% renal
    6. Available as generic scored tablets (5 mg) and unscored tablets (10,20 and 40 mg)
  9. Ramipril (Altace)
    1. Hypertension: 2.5 mg orally daily (target 2.5-20 mg orally daily)
    2. CHF or MI: 2.5 mg orally twice daily (target 5 mg orally twice daily)
    3. Renal Impairment or Diuretic use: 1.25 mg orally daily to start
    4. Maximum 20 mg/day
    5. Excretion both renal and hepatic
    6. Available as generic capsule (1.25, 2.5, 5, 10 mg)
  10. Trandopril (Mavik)
    1. Hypertension: 1 mg orally daily (target 2 to 4 mg orally daily)
    2. CHF: 0.5 to 1 mg orally daily (target 4 mg orally daily)
    3. Maximum: 8 mg/day
    4. Excretion 66% hepatic and 33% renal
    5. Available as generic scored tablet (1 mg) and unscored tablet (2 and 4 mg)

VII. Adverse Effects

  1. Cough (dry and irritating)
    1. Characteristics
      1. Occurs in 5 to 20% of patients
        1. More common in women
        2. More common in black patients
      2. Not dose related
      3. Stops within 4 days of medication cessation
    2. Alternative medications
      1. Angiotensin Receptor Blocker (e.g. Losartan)
    3. Inhalers may relieve cough
      1. Tilade 2 puffs inhaled four times daily
      2. Cromolyn 20 mg inhaled four times daily
  2. Hyperkalemia (5% of patients)
    1. See Drug Interactions below
    2. Asociated with Renal Insufficiency, Diabetes Mellitus
  3. Teratogenicity in second or third trimester
    1. Fetal injury or death
    2. Pregnancy Class C if discontinued in first trimester
  4. Renal Insufficiency
    1. Renal Artery Stenosis (see monitoring below)
    2. No Creatinine level is absolute contraindication
    3. Baseline Serum Creatinine <3.0 mg/dl is safe
  5. Hypotension
    1. Restart ACE Inhibitor at half prior dose
    2. Decrease or hold dose of any concurrent Diuretic
  6. Angioedema
    1. ACE inhibitor Induced Angioedema is not an Allergic Reaction (unlike typical Angioedema)
      1. Related to bradykinin accumulation
      2. Does not respond to typical Angioedema management (e.g. Corticosteroids, Antihistamines)
    2. Occurs in 1 of 300 patients
      1. More common in african american patients by factor of 2-4 fold
    3. Reaction can occur months to years after starting an ACE Inhibitor
    4. Treatment is withdrawal of medication and supportive care
      1. See Angioedema for management
      2. Reactions may be severe and life threatening with complete airway closure
      3. May respond to agents used for Hereditary Angioedema (e.g. Icatibant, Berinert)
    5. Do not re-challenge with ACE Inhibitor
      1. ACE Inhibitor Angioedema will recur with ARB agents in 8% of patients
      2. Avoid Angiotensin Receptor Blocker (ARB) unless a very compelling reason exists
        1. If ARB is used, wait at least 4 weeks after ACE Inhibitor has been discontinued
        2. Avoid using ARB in moderate to severe ACE Inhibitor Angioedema episode
  7. Rare Adverse Reactions
    1. Rash
    2. Agranulocytosis
    3. Neutropenia
      1. Associated with comorbid Renal Insufficiency
      2. Associated with comorbid Collagen vascular disease

VIII. Drug Interactions

  1. Increases Lithium levels (follow levels)
  2. Decreased ACE Inhibitor levels with concurrent Antacids
  3. Decreased Renal Function with concurrent NSAID use
  4. Agents predisposing to Hyperkalemia
    1. Bactrim
    2. Potassium supplements or salt substitute
    3. Beta Blockers
    4. NSAIDs
    5. Potassium sparing Diuretics
      1. Triamterene
      2. Spironolactone

IX. Monitoring

  1. Serum Potassium (if patient at risk)
  2. Serum Creatinine
    1. Timing
      1. Baseline
      2. Recheck in 4 days to 2 weeks
    2. Expect an increase in Chronic Kidney Disease
      1. Despite this, renal protective effect outweighs mild to moderate Creatinine increase
    3. Indication to consider stopping ACE Inhibitor
      1. Serum Creatinine increased >20% in 4 days
    4. Additional precautions when increasing dose
      1. Serum Creatinine should not increase >30%

X. References

  1. (1987) N Engl J Med 316(23):1429-35 [PubMed]
  2. Bicket (2002) Am Fam Physician 66(3):461-73 [PubMed]
  3. Pfeffer (1992) N Engl J Med 327(10):669-77 [PubMed]
  4. Yeun (2001) Postgrad Med 110(5):39-40 [PubMed]

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Related Studies

Cost: Medications

captopril (on 11/23/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
CAPTOPRIL 100 MG TABLET Generic $1.38 each
CAPTOPRIL 12.5 MG TABLET Generic $0.45 each
CAPTOPRIL 25 MG TABLET Generic $0.38 each
CAPTOPRIL 50 MG TABLET Generic $0.68 each
lisinopril (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
LISINOPRIL 10 MG TABLET Generic $0.02 each
LISINOPRIL 2.5 MG TABLET Generic $0.02 each
LISINOPRIL 20 MG TABLET Generic $0.02 each
LISINOPRIL 30 MG TABLET Generic $0.06 each
LISINOPRIL 40 MG TABLET Generic $0.05 each
LISINOPRIL 5 MG TABLET Generic $0.01 each
LISINOPRIL-HYDROCHLOROTHIAZIDE 10-12.5 MG TAB Generic $0.03 each
LISINOPRIL-HYDROCHLOROTHIAZIDE 20-12.5 MG TAB Generic $0.05 each
LISINOPRIL-HYDROCHLOROTHIAZIDE 20-25 MG TAB Generic $0.05 each
enalapril (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
ENALAPRIL 1 MG/ML ORAL SOLN Generic $1.89 per ml
ENALAPRIL MALEATE 10 MG TAB Generic $0.11 each
ENALAPRIL MALEATE 2.5 MG TAB Generic $0.10 each
ENALAPRIL MALEATE 20 MG TAB Generic $0.13 each
ENALAPRIL MALEATE 5 MG TABLET Generic $0.11 each
ENALAPRIL-HYDROCHLOROTHIAZIDE 10-25 MG TABLET Generic $0.17 each
ENALAPRIL-HYDROCHLOROTHIAZIDE 5-12.5 MG TAB Generic $0.15 each
fosinopril (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
FOSINOPRIL SODIUM 10 MG TAB Generic $0.17 each
FOSINOPRIL SODIUM 20 MG TAB Generic $0.17 each
FOSINOPRIL SODIUM 40 MG TAB Generic $0.21 each
moexipril (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
MOEXIPRIL HCL 15 MG TABLET Generic $0.75 each
MOEXIPRIL HCL 7.5 MG TABLET Generic $0.97 each
perindopril (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
PERINDOPRIL ERBUMINE 4 MG TAB Generic $0.47 each
PERINDOPRIL ERBUMINE 8 MG TAB Generic $0.50 each
quinapril (on 2/23/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
QUINAPRIL 10 MG TABLET Generic $0.07 each
QUINAPRIL 20 MG TABLET Generic $0.09 each
QUINAPRIL 40 MG TABLET Generic $0.11 each
QUINAPRIL 5 MG TABLET Generic $0.08 each
QUINAPRIL-HYDROCHLOROTHIAZIDE 10-12.5 MG TAB Generic $0.31 each
QUINAPRIL-HYDROCHLOROTHIAZIDE 20-12.5 MG TAB Generic $0.36 each
QUINAPRIL-HYDROCHLOROTHIAZIDE 20-25 MG TAB Generic $0.34 each
ramipril (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
RAMIPRIL 1.25 MG CAPSULE Generic $0.09 each
RAMIPRIL 10 MG CAPSULE Generic $0.07 each
RAMIPRIL 2.5 MG CAPSULE Generic $0.06 each
RAMIPRIL 5 MG CAPSULE Generic $0.07 each
FPNotebook does not benefit financially from showing this medication data or their pharmacy links. This information is provided only to help medical providers and their patients see relative costs. Insurance plans negotiate lower medication prices with suppliers. Prices shown here are out of pocket, non-negotiated rates. See Needy Meds for financial assistance information. GoodRx is another tool for finding lower drug prices.

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