II. Indications

  1. Intolerance to ACE Inhibitor
  2. See ACE Inhibitor for indications

III. Contraindications

  1. See ACE Inhibitor for contraindications
  2. Angioedema with ACE Inhibitor (relative contraindication)
    1. Bradykinin related reaction that recurs with ARBs in 2% of patients who had Angioedema on ACE Inhibitor
    2. Do not use ARB if ACE inhibitor Induced Angioedema was severe
    3. Precautions given to patient to stop ARB immediately and seak emergency care for signs of Angioedema recurrence
    4. Wait at least 4 weeks between stopping ACE Inhibitor and starting ARB
    5. (2013) J Allergy Clin Immunol 131:1491-3 [PubMed]

IV. Mechanism

V. Preparations: ARB alone

  1. Losartan (Cozaar)
    1. Start: 50 mg orally daily or 25 mg daily if volume depleted (MAX 100 mg/day)
    2. Consider twice daily divided dosing
  2. Irbesartan (Avapro)
    1. Start 150 mg orally daily (max 300 mg/day)
  3. Candesartan (Atacand)
    1. Start 8 mg orally daily (maximum 32 mg/day)
  4. Eprosartan (Teveten)
    1. Start 400 mg orally daily (maximum 800 mg/day)
  5. Telmisartan (Micardis)
    1. Start 40 mg orally daily (maximum 80 mg/day)
  6. Valsartan (Diovan)
    1. Start 80 mg orally daily (maximum 320 mg/day)
  7. Olmesartan (Benicar)
    1. Start 20 mg orally daily (maximum 40 mg/day)
  8. Azilsartan (Edarbi)
    1. Start 40 mg orally daily (maximum 80 mg/day)

VI. Preparations: Combination

  1. Amlodipine (and ARB)
    1. Exforge (Amlodipine and Valsartan)
    2. Azor (Amlodipine and Olmesartan)
  2. Hydrochlorothiazide (and ARB)
    1. Most ARB agents are available in combination with Hydrochlorothiazide (Hctz)
  3. Sacubitril and Valsartan (Entresto)
    1. Indicated in Systolic Dysfunction (consider as an alternative to ACE Inhibitor or mono Angiotensin Receptor Blocker)
    2. Sacubitril (neprilysin inhibitor) increases vasodilation and Sodium excretion
    3. Risk of Hypotension (Number needed to harm 21)
    4. Risk of Angioedema (Number needed to harm 200)
    5. See Systolic Dysfunction for dosing and references

VII. Protocol: Equivalent dosing (switching between agents)

  1. Losartan (Cozaar) 100 mg daily or divided twice daily
  2. Irbesartan (Avapro) 300 mg daily
  3. Candesartan (Atacand) 16 mg daily
  4. Eprosartan (Teveten) 800 mg daily
  5. Telmisartan (Micardis) 40 mg daily
  6. Valsartan (Diovan) 160 mg daily
  7. Olmesartan (Benicar) 20 mg daily
  8. Azilsartan (Edarbi) 40 mg daily

VIII. Efficacy

  1. Peak effect may require 4-6 weeks
  2. Proteinuria control is equivalent to ACE Inhibitors
    1. Kunz (2008) Ann Intern Med 148:30-48. [PubMed]
  3. Evidence as of 2015 shows similar efficacy of ARBs as ACE Inhibitors in Myocardial Infarction prevention
    1. (2016) Presc Lett 23(3): 13
  4. Avoid in combination with ACE Inhibitors
    1. No advantage to combinations in Hypertension, vascular disease, Diabetes Mellitus, Coronary Artery Disease
    2. Moderate benefit of combination therapy in Congestive Heart Failure
    3. (2013) Prescr Lett 20(3): 13
  5. Reduce cardiovascular death, Cerebrovascular Accident and Myocardial Infarction risk
    1. Higher level cardiovascular protection than Atenolol
      1. However Atenolol is not the best Beta Blocker for cardiovascular disease prevention
      2. Dahlof (2002) Lancet 359:995-1003 [PubMed]
    2. ARBs do not effect Angiotensin II type 2 receptors
      1. Results in less effect on fibrosis and Blood Flow
      2. Unlike ACE Inhibitors, ARBs don't effect nitric oxide
      3. (2005) Prescriber's Letter 12:31-2

IX. Adverse Effects

  1. Valsartan (Diovan), Irbesartan (Avapro) and Losartan (Cozaar)
    1. N-Nitrosodimethylamine (NMDA) or N-nitrosodiethylamine (NDEA) product contamination (FDA recall 2018)
      1. https://www.fda.gov/Drugs/DrugSafety/ucm613916.htm
      2. https://www.fda.gov/Safety/Recalls/ucm624593.htm
      3. https://www.fda.gov/Safety/Recalls/ucm625492.htm
      4. Product contamination may have been for as long as 4 years
      5. Cancer risk 1 in 8000 patients taking Valsartan for 8 years at 320 mg/day
      6. (2018) Presc Lett 25(9): 49
  2. Olmesartan (Benicar)
    1. Sprue-like Enteropathy
      1. Presents with progressive, severe Chronic Diarrhea, weight loss and sprue-like intestinal changes
      2. May be a delayed Hypersensitivity Reaction (typically months to years after starting Olmesartan)
      3. Rubio-Tapia (2012) Mayo Clin Proc 87(8):732-8 [PubMed]

Images: Related links to external sites (from Bing)

Related Studies

Cost: Medications

losartan (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
LOSARTAN POTASSIUM 100 MG TAB Generic $0.08 each
LOSARTAN POTASSIUM 25 MG TAB Generic $0.04 each
LOSARTAN POTASSIUM 50 MG TAB Generic $0.05 each
LOSARTAN-HYDROCHLOROTHIAZIDE 100-12.5 MG TAB Generic $0.13 each
LOSARTAN-HYDROCHLOROTHIAZIDE 100-25 MG TAB Generic $0.14 each
LOSARTAN-HYDROCHLOROTHIAZIDE 50-12.5 MG TAB Generic $0.12 each
cozaar (on 1/14/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
COZAAR 100 MG TABLET Generic $0.08 each
COZAAR 50 MG TABLET Generic $0.05 each
irbesartan (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
IRBESARTAN 150 MG TABLET Generic $0.18 each
IRBESARTAN 300 MG TABLET Generic $0.24 each
IRBESARTAN 75 MG TABLET Generic $0.17 each
IRBESARTAN-HYDROCHLOROTHIAZIDE 150-12.5 MG TB Generic $0.19 each
IRBESARTAN-HYDROCHLOROTHIAZIDE 300-12.5 MG TB Generic $0.24 each
avapro (on 1/3/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
AVAPRO 150 MG TABLET Generic $0.18 each
AVAPRO 300 MG TABLET Generic $0.24 each
candesartan (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
CANDESARTAN CILEXETIL 16 MG TB Generic $0.79 each
CANDESARTAN CILEXETIL 32 MG TB Generic $0.96 each
CANDESARTAN CILEXETIL 4 MG TAB Generic $0.80 each
CANDESARTAN CILEXETIL 8 MG TAB Generic $0.77 each
CANDESARTAN-HYDROCHLOROTHIAZIDE 16-12.5 MG TB Generic $1.12 each
CANDESARTAN-HYDROCHLOROTHIAZIDE 32-12.5 MG TB Generic $1.76 each
CANDESARTAN-HYDROCHLOROTHIAZIDE 32-25 MG TAB Generic $1.47 each
telmisartan (on 1/18/2023 at Medicaid.Gov Survey of pharmacy drug pricing)
TELMISARTAN 20 MG TABLET Generic $0.19 each
TELMISARTAN 40 MG TABLET Generic $0.26 each
TELMISARTAN 80 MG TABLET Generic $0.28 each
TELMISARTAN-AMLODIPINE 80-5 MG Generic $3.05 each
TELMISARTAN-HYDROCHLOROTHIAZIDE 40-12.5 MG TB Generic $0.66 each
TELMISARTAN-HYDROCHLOROTHIAZIDE 80-12.5 MG TB Generic $0.86 each
TELMISARTAN-HYDROCHLOROTHIAZIDE 80-25 MG TAB Generic $0.79 each
micardis (on 1/10/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
MICARDIS 80 MG TABLET Generic $0.28 each
valsartan (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
VALSARTAN 160 MG TABLET Generic $0.23 each
VALSARTAN 320 MG TABLET Generic $0.27 each
VALSARTAN 40 MG TABLET Generic $0.16 each
VALSARTAN 80 MG TABLET Generic $0.19 each
VALSARTAN-HYDROCHLOROTHIAZIDE 160-12.5 MG TAB Generic $0.26 each
VALSARTAN-HYDROCHLOROTHIAZIDE 160-25 MG TAB Generic $0.30 each
VALSARTAN-HYDROCHLOROTHIAZIDE 320-12.5 MG TAB Generic $0.34 each
VALSARTAN-HYDROCHLOROTHIAZIDE 320-25 MG TAB Generic $0.34 each
VALSARTAN-HYDROCHLOROTHIAZIDE 80-12.5 MG TAB Generic $0.22 each
diovan (on 7/27/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
DIOVAN 160 MG TABLET Generic $0.23 each
DIOVAN 320 MG TABLET Generic $0.27 each
DIOVAN 80 MG TABLET Generic $0.19 each
olmesartan (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
OLMESARTAN MEDOXOMIL 20 MG TAB Generic $0.08 each
OLMESARTAN MEDOXOMIL 40 MG TAB Generic $0.13 each
OLMESARTAN MEDOXOMIL 5 MG TAB Generic $0.06 each
OLMESARTAN-HYDROCHLOROTHIAZIDE 20-12.5 MG TAB Generic $0.20 each
OLMESARTAN-HYDROCHLOROTHIAZIDE 40-12.5 MG TAB Generic $0.26 each
OLMESARTAN-HYDROCHLOROTHIAZIDE 40-25 MG TAB Generic $0.26 each
benicar (on 1/18/2023 at Medicaid.Gov Survey of pharmacy drug pricing)
BENICAR HCT 40-25 MG TABLET Generic $0.27 each
entresto (on 7/27/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
ENTRESTO 24 MG-26 MG TABLET $10.18 each
ENTRESTO 49 MG-51 MG TABLET $10.18 each
ENTRESTO 97 MG-103 MG TABLET $10.18 each
exforge (on 7/27/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
EXFORGE HCT 10-320-25 MG TAB $12.94 each