Skip to Content

Olmesartan Medoxomil

Class: Angiotensin II Receptor Antagonists
VA Class: CV805
Chemical Name: Cyclic 2,3 carbonate 2,3-dihydroxy-2-butenyl-4-(1-hydroxy-1-methylethyl)-1-propyl-1-[p-(o-1H-tetrazol-5-ylphenyl)benzyl]imidazole-5-carboxylate
Molecular Formula: C29H30N6O6
CAS Number: 144689-63-4
Brands: Azor (combination), Benicar

Medically reviewed on Nov 5, 2018

Warning

  • May cause fetal and neonatal morbidity and mortality if used during pregnancy.1 31 42 43 44 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

  • If pregnancy is detected, discontinue as soon as possible.1 31 43 44

Introduction

Olmesartan is an angiotensin II type 1 (AT1) receptor antagonist (i.e., angiotensin II receptor blocker, ARB).1 2 3 16 28 31 44 139

Uses for Olmesartan Medoxomil

Hypertension

Management of hypertension (alone or in combination with other classes of antihypertensive agents);1 2 3 8 9 28 31 44 139 1200 may be used in fixed combination with amlodipine and/or hydrochlorothiazide when such combined therapy is indicated.31 44 139

Angiotensin II receptor antagonists are recommended as one of several preferred agents for the initial management of hypertension according to current evidence-based hypertension guidelines; other preferred options include ACE inhibitors, calcium-channel blockers, and thiazide diuretics.501 502 503 504 1200 While there may be individual differences with respect to recommendations for initial drug selection and use in specific patient populations, current evidence indicates that these antihypertensive drug classes all generally produce comparable effects on overall mortality and cardiovascular, cerebrovascular, and renal outcomes.501 502 503 504 1200 1213

Individualize choice of therapy; consider patient characteristics (e.g., age, ethnicity/race, comorbidities, cardiovascular risk) as well as drug-related factors (e.g., ease of administration, availability, adverse effects, cost).501 502 503 504 515 1200 1201

A 2017 ACC/AHA multidisciplinary hypertension guideline classifies BP in adults into 4 categories: normal, elevated, stage 1 hypertension, and stage 2 hypertension.1200 (See Table 1.)

Source: Whelton PK, Carey RM, Aronow WS et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018;71:e13-115.

Individuals with SBP and DBP in 2 different categories (e.g., elevated SBP and normal DBP) should be designated as being in the higher BP category (i.e., elevated BP).

Table 1. ACC/AHA BP Classification in Adults1200

Category

SBP (mm Hg)

DBP (mm Hg)

Normal

<120

and

<80

Elevated

120–129

and

<80

Hypertension, Stage 1

130–139

or

80–89

Hypertension, Stage 2

≥140

or

≥90

The goal of hypertension management and prevention is to achieve and maintain optimal control of BP.1200 However, the BP thresholds used to define hypertension, the optimum BP threshold at which to initiate antihypertensive drug therapy, and the ideal target BP values remain controversial.501 503 504 505 506 507 508 515 523 526 530 1200 1201 1207 1209 1222 1223 1229

The 2017 ACC/AHA hypertension guideline generally recommends a target BP goal (i.e., BP to achieve with drug therapy and/or nonpharmacologic intervention) of <130/80 mm Hg in all adults regardless of comorbidities or level of atherosclerotic cardiovascular disease (ASCVD) risk.1200 In addition, an SBP goal of <130 mm Hg is recommended for noninstitutionalized ambulatory patients ≥65 years of age with an average SBP of ≥130 mm Hg.1200 These BP goals are based upon clinical studies demonstrating continuing reduction of cardiovascular risk at progressively lower levels of SBP.1200 1202 1210

Previous hypertension guidelines generally have based target BP goals on age and comorbidities.501 504 536 Guidelines such as those issued by the JNC 8 expert panel generally have targeted a BP goal of <140/90 mm Hg regardless of cardiovascular risk and have used higher BP thresholds and target BPs in elderly patients501 504 536 compared with those recommended by the 2017 ACC/AHA hypertension guideline.1200

Some clinicians continue to support previous target BPs recommended by JNC 8 due to concerns about the lack of generalizability of data from some clinical trials (e.g., SPRINT study) used to support the current ACC/AHA hypertension guideline and potential harms (e.g., adverse drug effects, costs of therapy) versus benefits of BP lowering in patients at lower risk of cardiovascular disease.1222 1223 1224 1229

Consider potential benefits of hypertension management and drug cost, adverse effects, and risks associated with the use of multiple antihypertensive drugs when deciding a patient’s BP treatment goal.1200 1220 1229

For decisions regarding when to initiate drug therapy (BP threshold), the 2017 ACC/AHA hypertension guideline incorporates underlying cardiovascular risk factors.1200 1207 ASCVD risk assessment recommended by ACC/AHA for all adults with hypertension.1200

ACC/AHA currently recommend initiation of antihypertensive drug therapy in addition to lifestyle/behavioral modifications at an SBP ≥140 mm Hg or DBP ≥90 mm Hg in adults who have no history of cardiovascular disease (i.e., primary prevention) and a low ASCVD risk (10-year risk <10%).1200

For secondary prevention in patients with known cardiovascular disease or for primary prevention in those at higher risk for ASCVD (10-year risk ≥10%), ACC/AHA recommend initiation of antihypertensive drug therapy at an average SBP ≥130 mm Hg or an average DBP ≥80 mm Hg.1200

Adults with hypertension and diabetes mellitus, chronic kidney disease (CKD), or age ≥65 years are assumed to be at high risk for cardiovascular disease; ACC/AHA state that such patients should have antihypertensive drug therapy initiated at a BP ≥130/80 mm Hg.1200

In stage 1 hypertension, experts state that it is reasonable to initiate drug therapy using the stepped-care approach in which one drug is initiated and titrated and other drugs are added sequentially to achieve the target BP.1200 Initiation of antihypertensive therapy with 2 first-line agents from different pharmacologic classes recommended in adults with stage 2 hypertension and average BP >20/10 mm Hg above BP goal.1200

Black hypertensive patients generally tend to respond better to monotherapy with calcium-channel blockers or thiazide diuretics than to angiotensin II receptor antagonists.501 504 1200 However, the combination of an ACE inhibitor or an angiotensin II receptor antagonist with a calcium-channel blocker or thiazide diuretic produces similar BP lowering in black patients as in other racial groups.1200

Angiotensin II receptor antagonists or ACE inhibitors may be particularly useful in hypertensive patients with diabetes mellitus or CKD; angiotensin II receptor antagonists also may be preferred, as an alternative to ACE inhibitors, in hypertensive patients with heart failure or ischemic heart disease and/or post-MI.501 502 504 523 524 527 534 535 536 543 1200 1214 1215

Diabetic Nephropathy

A recommended agent in the management of patients with diabetes mellitus and persistent albuminuria who have modestly elevated (30–300 mg/24 hours) or higher (>300 mg/24 hours) levels of urinary albumin excretion; slows rate of progression of renal disease in such patients.535 536 1232

Heart Failure

Angiotensin II receptor antagonists have been used in the management of heart failure.524 528 800

Because of their established benefits, ACE inhibitors have been the preferred drugs for inhibition of the renin-angiotensin-aldosterone (RAA) system in patients with heart failure and reduced left ventricular ejection fraction (LVEF); 524 however, some evidence indicates that therapy with an ACE inhibitor (enalapril) may be less effective than angiotensin receptor-neprilysin inhibitor (ARNI) therapy (e.g., sacubitril/valsartan) in reducing cardiovascular death and heart failure-related hospitalization.701 702 703 800

Angiotensin II receptor antagonists may be used as an alternative for those patients in whom an ACE inhibitor or ARNI is inappropriate.524 800

No additional therapeutic benefit when angiotensin II receptor antagonist used in combination with an ACE inhibitor.1

ACCF, AHA, and the Heart Failure Society of America (HFSA) recommend that patients with chronic symptomatic heart failure and reduced LVEF (NYHA class II or III) who are able to tolerate an ACE inhibitor or angiotensin II receptor antagonist be switched to therapy containing an ARNI to further reduce morbidity and mortality.800

Olmesartan Medoxomil Dosage and Administration

General

BP Monitoring and Treatment Goals

  • Monitor BP regularly (i.e., monthly) during therapy and adjust dosage of the antihypertensive drug until BP controlled.1200

  • If unacceptable adverse effects occur, discontinue drug and initiate another antihypertensive agent from a different pharmacologic class.1216

  • If adequate BP response not achieved with a single antihypertensive agent, either increase dosage of single drug or add a second drug with demonstrated benefit and preferably a complementary mechanism of action (e.g., calcium-channel blocker, thiazide diuretic).1200 1216 Many patients will require at least 2 drugs from different pharmacologic classes to achieve BP goal; if goal BP still not achieved with 2 antihypertensive agents, add a third drug.1200 1216 1220

Administration

Oral Administration

Administer olmesartan orally once daily without regard to meals.1 2

May administer as extemporaneously prepared oral suspension in pediatric patients unable to swallow tablets.1

Reconstitution

Preparation of extemporaneous suspension containing olmesartan medoxomil 2 mg/mL: Add 50 mL of purified water to an amber polyethylene terephthalate (PET) bottle containing twenty 20-mg tablets of olmesartan medoxomil; allow contents to stand for ≥5 minutes.1 Shake container for ≥1 minute and allow to stand for ≥1 minute; repeat this alternating shaking and standing step 4 additional times.1 Dilute concentrated suspension with 100 mL of syrup (Ora-Sweet) and 50 mL of suspending vehicle (Ora-Plus) and shake well for ≥1 minute to disperse ingredients.1 Shake suspension well before dispensing each dose.1

Dosage

Olmesartan is available as olmesartan medoxomil; dosage expressed in terms of the salt.1 31 44

Pediatric Patients

Hypertension
Oral

Pediatric patients 6–16 years of age who weigh 20 to <35 kg: Initially, 10 mg once daily; may increase to maximum of 20 mg once daily after 2 weeks.1 137 1150

Pediatric patients 6–16 years of age who weigh ≥35 kg: Initially, 20 mg once daily; may increase to maximum of 40 mg once daily after 2 weeks.1 137 1150

Adults

Hypertension
Olmesartan Therapy
Oral

Initially, 20 mg once daily as monotherapy in adults without intravascular volume depletion.1

Usual dosage: 20–40 mg once daily; no additional therapeutic benefit with higher dosages or with twice-daily dosing.1 28 1200

Olmesartan/Amlodipine Fixed-combination Therapy
Oral

Fixed-combination olmesartan/amlodipine tablets may be used for initial treatment of hypertension in patients likely to require combination therapy with multiple antihypertensive agents to control BP.144

If the patient’s baseline BP is 160/100 mm Hg, the estimated probability of achieving SBP control (SBP <140 mm Hg) is 48, 46, or 68% and of achieving DBP control (DBP <90 mm Hg) is 51, 60, or 85% with olmesartan medoxomil (40 mg daily) alone, amlodipine (10 mg daily) alone, or amlodipine combined with olmesartan medoxomil (same dosages), respectively.144

If BP is not adequately controlled by monotherapy with olmesartan (or another angiotensin II receptor antagonist) or amlodipine (or another dihydropyridine-derivative calcium-channel blocker), can switch to olmesartan/amlodipine fixed combination.144

Can use the fixed combination as a substitute for the individually titrated drugs.144 Can switch to the fixed-combination preparation containing the corresponding individual doses of olmesartan and amlodipine; alternatively, can increase the dosage of one or both components for additional antihypertensive effects.144

Adjust dosage of olmesartan/amlodipine fixed combination, up to a maximum of olmesartan medoxomil 40 mg and amlodipine 10 mg once daily, according to patient’s response after ≥2 weeks at the current dosage.144

When used for initial therapy of hypertension in patients likely to require combination therapy with multiple antihypertensive agents, recommended initial dosage is olmesartan medoxomil 20 mg and amlodipine 5 mg once daily.144 May increase dosage after 1–2 weeks for additional BP control, up to maximum of olmesartan medoxomil 40 mg and amlodipine 10 mg once daily.144

Olmesartan/Hydrochlorothiazide Fixed-combination Therapy
Oral

Manufacturer states fixed-combination preparation should not be used for initial antihypertensive therapy.31

If BP is not adequately controlled by monotherapy with olmesartan or hydrochlorothiazide, can switch to fixed-combination olmesartan/hydrochlorothiazide tablets.31 In patients already receiving olmesartan, initiate hydrochlorothiazide at dosage of 12.5 mg once daily; in those receiving hydrochlorothiazide, consider reducing hydrochlorothiazide dosage to 12.5 mg and initiate olmesartan medoxomil at dosage of 20 mg once daily.31 Increase dosages to olmesartan medoxomil 40 mg and hydrochlorothiazide 25 mg once daily, if needed, to control BP.31

If BP is controlled with olmesartan and hydrochlorothiazide (administered separately), can switch to the fixed-combination preparation containing the corresponding individual doses for convenience.31

Adjust dosage of olmesartan/hydrochlorothiazide fixed combination according to patient’s response after 2–4 weeks at the current dosage.31

Olmesartan/Amlodipine/Hydrochlorothiazide Fixed-combination Therapy
Oral

Manufacturer states fixed-combination preparation should not be used for initial antihypertensive therapy.139

Can switch to fixed-combination olmesartan/amlodipine/hydrochlorothiazide tablets if BP is not adequately controlled by combined therapy with any 2 of the following drug classes at maximally tolerated, labeled, or usual dosages: angiotensin II receptor antagonists, calcium-channel blockers, or diuretics.139

In patients who experience dose-limiting adverse effects to olmesartan, amlodipine, or hydrochlorothiazide while receiving any dual combination of these drugs, may switch to the triple fixed-combination preparation containing a lower dose of that component.139

Can use the fixed combination as a substitute for the individually titrated drugs.139

May increase dosage of the fixed combination after 2 weeks if additional BP control is needed (up to maximum of olmesartan medoxomil 40 mg, amlodipine 10 mg, and hydrochlorothiazide 25 mg once daily).139

Special Populations

The following information addresses dosage of olmesartan in special populations. Dosages of drugs administered in fixed combination with olmesartan also may require adjustment in certain patient populations; the need for such dosage adjustments must be considered in the context of cautions, precautions, and contraindications specific to that population and drug.31 44

Hepatic Impairment

No adjustment of initial olmesartan dosage necessary in patients with moderate to severe hepatic impairment.1 31

Amount of amlodipine in olmesartan/amlodipine fixed combinations exceeds the recommended initial dosage of amlodipine (2.5 mg daily) in patients with hepatic impairment.44 139

Renal Impairment

Manufacturer states that no adjustment of initial olmesartan dosage is necessary in patients with moderate to severe renal impairment (Clcr <40 mL/minute).1 31 44 However, some clinicians recommend lower initial dosage in patients with Clcr <20 mL/minute, with maximum dosage of 20 mg once daily in such patients.10

Dosage of olmesartan in patients with end-stage renal disease not determined.29

Fixed combinations containing hydrochlorothiazide are not recommended in patients with severe renal impairment (Clcr ≤30 mL/minute).31 139 Loop diuretics are preferred to thiazides in these patients.31 139

Geriatric Patients

No adjustment of initial olmesartan dosage is necessary.1 31

Amount of amlodipine in olmesartan/amlodipine fixed combinations exceeds the recommended initial dosage of amlodipine (2.5 mg daily) in patients ≥75 years of age.44 139

Volume- and/or Salt-depleted Patients

Correct volume and/or salt depletion prior to initiation of olmesartan therapy or initiate therapy under close medical supervision using lower initial dosage.1 31 44

Cautions for Olmesartan Medoxomil

Contraindications

  • Concomitant therapy with aliskiren in patients with diabetes mellitus.1 139 (See Specific Drugs under Interactions.)

Warnings/Precautions

Warnings

Fetal/Neonatal Morbidity and Mortality

Possible reduction in fetal renal function and increase in fetal and neonatal morbidity and mortality when drugs that act on the renin-angiotensin system (e.g., angiotensin II receptor antagonists, ACE inhibitors, aliskiren) are used during the second and third trimesters of pregnancy.1 31 43 44 (See Boxed Warning.) ACE inhibitors also may increase the risk of major congenital malformations when administered during the first trimester of pregnancy.56 57 Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations.1 Potential neonatal effects include skull hypoplasia, anuria, hypotension, renal failure, and death.1

Discontinue olmesartan as soon as possible when pregnancy is detected, unless continued use is considered lifesaving.1 31 42 43 44 Nearly all women can be transferred successfully to alternative therapy for the remainder of their pregnancy.13

Sensitivity Reactions

Anaphylactoid reactions and/or angioedema possible with angiotensin II receptor antagonists;1 2 7 14 extreme caution recommended in patients with a history of angioedema associated with2 7 45 or unrelated to ACE inhibitor or angiotensin II receptor antagonist therapy.15

Other Warnings and Precautions

Infant Morbidity

Olmesartan must not be used for treatment of hypertension in infants <1 year of age; drugs that act directly on the RAA system can affect the development of immature kidneys.1 (See Pediatric Use under Cautions.)

Hypotension

Possible symptomatic hypotension with olmesartan, particularly in volume- and/or salt-depleted patients (e.g., those treated with diuretics).1 31 44 (See Volume- and/or Salt-Depleted Patients under Dosage and Administration.)

Transient hypotension is not a contraindication to additional doses; may reinstate olmesartan therapy cautiously after BP is stabilized (e.g., with volume expansion).1 31 44

Malignancies

In July 2010, FDA initiated a safety review of angiotensin II receptor antagonists after a published meta-analysis found a modest but statistically significant increase in risk of new cancer occurrence in patients receiving an angiotensin II receptor antagonist compared with control.120 121 123 126 However, subsequent studies, including a larger meta-analysis conducted by FDA, have not shown such risk.126 127 128 129 Based on currently available data, FDA has concluded that angiotensin II receptor antagonists do not increase the risk of cancer.126

Renal Effects

Possible oliguria, progressive azotemia and, rarely, acute renal failure and/or death in patients with severe heart failure.1 31 44

Increases in BUN and Scr possible in patients with unilateral or bilateral renal artery stenosis.1 31 44

Sprue-like Enteropathy

Risk of sprue-like enteropathy, an intestinal condition characterized by severe chronic diarrhea with substantial weight loss; intestinal biopsy may reveal villous atrophy.1 133 134 135 139 Can occur months to years after initiating olmesartan.1 133 134 139 Clinical improvement is expected after the drug is discontinued.133 134 135

Not associated with other angiotensin II receptor antagonists to date; not considered to be a class effect of the drugs.133

If symptoms of sprue-like enteropathy develop, exclude other etiologies (e.g., celiac disease); if no other causative factor can be identified, consider drug discontinuance.1 133 139

Increased Cardiovascular Risk in Patients with Diabetes

Findings from several studies have prompted concerns of an increased risk of cardiovascular death (e.g., fatal MI, sudden cardiac death) in patients with diabetes mellitus receiving high-dose olmesartan.1 124 132 140 Following review of all the available data, FDA has concluded that the collective evidence to date does not clearly demonstrate such an association and that the benefits of olmesartan in hypertensive patients continue to outweigh potential risks.1 124 138 140 141 142 143

Use of Fixed Combinations

When olmesartan is used in fixed combination with amlodipine and/or hydrochlorothiazide, consider cautions, precautions, contraindications, and interactions associated with the concomitant agent(s).31 44 139 Consider cautionary information applicable to specific populations (e.g., pregnant or nursing women, individuals with hepatic or renal impairment, geriatric patients) for each drug in the fixed combination.31 44 139

Specific Populations

Pregnancy

Category D.1 (See Boxed Warning.)

May cause fetal and neonatal morbidity and mortality when administered to a pregnant woman.1 Discontinue as soon as possible when pregnancy is detected.1 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Lactation

Olmesartan is distributed into milk in rats; not known whether olmesartan is distributed into human milk.1 31 44 Discontinue nursing or the drug.1 31 44

Pediatric Use

If oliguria or hypotension occurs in neonates with a history of in utero exposure to olmesartan, support BP and renal function; exchange transfusions or dialysis may be required.1 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Safety and efficacy of olmesartan in fixed combination with amlodipine and/or hydrochlorothiazide not established.31 44 139

Safety and efficacy of olmesartan established in pediatric patients 6–16 years of age with hypertension.1 136 Although evaluated in pediatric patients 1–5 years of age, statistically significant reductions in BP were not observed.1

Not evaluated in infants <1 year of age; because of the possibility of abnormal kidney development, do not use in this age group.1

Adverse effects in pediatric patients appear to be similar to those observed in adults.1

Geriatric Use

No overall differences in safety or efficacy of olmesartan alone or in fixed combination with amlodipine and/or hydrochlorothiazide relative to younger adults, but increased sensitivity cannot be ruled out.1 44 139 In general, select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.31

Hepatic Impairment

Systemic exposure to olmesartan may be increased.1 31 44 (See Absorption: Special Populations, under Pharmacokinetics.)

Renal Impairment

Systemic exposure to olmesartan may be increased.1 31 44 (See Absorption: Special Populations, under Pharmacokinetics and also see Renal Impairment under Dosage and Administration.)

Use of olmesartan in fixed combination with hydrochlorothiazide is not recommended in patients with Clcr ≤30 mL/minute.31 139

Deterioration of renal function may occur.1 31 44 (See Renal Effects under Cautions.)

Black Patients

BP reduction with olmesartan may be smaller in black patients than in patients of other races.1 5 31 1200 (See Hypertension under Uses.)

Common Adverse Effects

Dizziness,1 2 3 back pain,1 bronchitis,1 2 12 diarrhea,1 headache,1 2 3 12 hematuria,1 hyperglycemia,1 hypertriglyceridemia,1 influenza-like symptoms,1 2 12 pharyngitis,1 rhinitis,1 sinusitis,1 upper respiratory tract infection.2 3 12

Interactions for Olmesartan Medoxomil

Olmesartan is not metabolized by and does not inhibit or induce CYP isoenzymes.1 2

Specific Drugs

Drug

Interaction

Comments

ACE inhibitors

Increased risk of renal impairment, hyperkalemia, and hypotension1

Generally avoid concomitant use; monitor BP, renal function, and electrolytes if used concomitantly1

Aliskiren

Increased risk of renal impairment, hyperkalemia, and hypotension1 550

Generally avoid concomitant use; monitor BP, renal function, and electrolytes if used concomitantly1 550

Concomitant use contraindicated in patients with diabetes mellitus1 550

Avoid concomitant use in patients with GFR <60 mL/minute1 550

Angiotensin II receptor antagonists

Increased risk of renal impairment, hyperkalemia, and hypotension1

Generally avoid concomitant use; monitor BP, renal function, and electrolytes if used concomitantly1

Antacids

Pharmacokinetic interactions unlikely1 2 28

Colesevelam

Decreased AUC and peak plasma concentrations of olmesartan1

Consider administering olmesartan at least 4 hours before colesevelam1

Digoxin

Pharmacokinetic interactions unlikely1 2 28

Hydrochlorothiazide

Pharmacokinetic interactions unlikely2 28

Lithium

Increased serum lithium concentrations and lithium toxicity1

Carefully monitor serum lithium concentrations 1

NSAIAs, including selective cyclooxygenase-2 (COX-2) inhibitors

Possible deterioration of renal function, including possible acute renal failure, in geriatric, volume-depleted, or renally impaired patients1

Possible decreased hypotensive effect1

Monitor renal function periodically1

Warfarin

Pharmacokinetic interaction unlikely1 2 28

Olmesartan Medoxomil Pharmacokinetics

Absorption

Bioavailability

Olmesartan medoxomil (prodrug) is rapidly and completely hydrolyzed to olmesartan during absorption in the GI tract.1 31 44

Absolute bioavailability of olmesartan is about 26%.1 31 44 Bioavailability of the extemporaneously prepared suspension (see Reconstitution under Dosage and Administration) is similar to that of olmesartan tablets.1

Peak plasma olmesartan concentration generally reached 1–2 hours following oral administration.1 31 44

Onset

Antihypertensive effect of olmesartan is evident within 2 weeks, with maximum BP reduction after 4–6 weeks.1 3

Food

Food does not affect bioavailability of olmesartan.1 31 44

Special Populations

In patients with moderate hepatic impairment, peak plasma concentration of olmesartan is increased; AUC increased by about 60%.1 31 44

In patients with severe renal impairment (Clcr <20 mL/minute), plasma concentrations and AUC of olmesartan are increased.1 31 44 After repeated dosing, AUC values are approximately triple those in patients with normal renal function.1 31 44

In women, peak plasma concentration and AUC of olmesartan are about 10–15% higher than values in men.1 31 44

Distribution

Extent

Olmesartan crosses the placenta and is distributed in the fetus in animals.1 31 44

Olmesartan crosses the blood-brain barrier poorly, if at all, in animals.1 31 44

Olmesartan is distributed into milk in rats; not known whether olmesartan is distributed into human milk.1 31 44

Plasma Protein Binding

Olmesartan: 99%.1 31 44

Elimination

Metabolism

Olmesartan medoxomil undergoes rapid and complete ester hydrolysis to olmesartan.1 2 28 31 44 Virtually no further metabolism of olmesartan occurs; not metabolized by CYP isoenzymes.1 2 28 31 44

Elimination Route

Olmesartan is eliminated mainly in urine (35–50%) and feces (via bile).1 2 31 44

Half-life

Biphasic; terminal half-life of olmesartan is approximately 13 hours.1 31 44

Special Populations

Clearance (adjusted for body weight) in pediatric patients 1–16 years of age is similar to that in adults.1

In geriatric patients, renal clearance of olmesartan is decreased by approximately 30%.1 31 44

Stability

Storage

Oral

Extemporaneous Suspension

2-mg/mL preparation of olmesartan medoxomil in a mixture of syrup (Ora-Sweet) and suspending vehicle (Ora-Plus) (see Reconstitution under Dosage and Administration): Up to 4 weeks at 2–8°C.1

Tablets

Olmesartan or olmesartan/hydrochlorothiazide fixed combination: 20–25°C.1 31

Olmesartan/amlodipine or olmesartan/amlodipine/hydrochlorothiazide fixed combination: 25ºC (may be exposed to 15–30ºC).44 139

Actions

  • Olmesartan medoxomil (prodrug) has little pharmacologic activity until hydrolyzed to olmesartan during absorption.1 2 31 44

  • Olmesartan blocks the physiologic actions of angiotensin II, including vasoconstrictor and aldosterone-secreting effects.1 31 44

  • Olmesartan does not interfere with response to bradykinins and substance P.1 31 44

  • Olmesartan does not share the ACE inhibitor common adverse effect of dry cough.1

Advice to Patients

  • When olmesartan is used in fixed combination with hydrochlorothiazide and/or amlodipine, importance of advising patients of important precautionary information about the concomitant agent(s).31 44 139

  • Importance of advising women of childbearing age about the risks of use during pregnancy.1 31 42 43 44

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.1 31 44

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1 31 44

  • Importance of informing patients of other important precautionary information.1 31 44 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Olmesartan Medoxomil

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

5 mg

Benicar

Sankyo

20 mg

Benicar

Sankyo

40 mg

Benicar

Sankyo

Olmesartan Medoxomil Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

20 mg with Amlodipine Besylate 5 mg (of amlodipine)

Azor

Daiichi Sankyo

20 mg with Amlodipine Besylate 10 mg (of amlodipine)

Azor

Daiichi Sankyo

40 mg with Amlodipine Besylate 5 mg (of amlodipine)

Azor

Daiichi Sankyo

40 mg with Amlodipine Besylate 10 mg (of amlodipine)

Azor

Daiichi Sankyo

Tablets, film-coated

20 mg with Amlodipine Besylate 5 mg (of amlodipine) and Hydrochlorothiazide 12.5 mg

Tribenzor

Daiichi Sankyo

20 mg with Hydrochlorothiazide 12.5 mg

Benicar HCT

Daiichi Sankyo

40 mg with Amlodipine Besylate 5 mg (of amlodipine) and Hydrochlorothiazide 12.5 mg

Tribenzor

Daiichi Sankyo

40 mg with Amlodipine Besylate 5 mg (of amlodipine) and Hydrochlorothiazide 25 mg

Tribenzor

Daiichi Sankyo

40 mg with Amlodipine Besylate 10 mg (of amlodipine) and Hydrochlorothiazide 12.5 mg

Tribenzor

Daiichi Sankyo

40 mg with Amlodipine Besylate 10 mg (of amlodipine) and Hydrochlorothiazide 25 mg

Tribenzor

Daiichi Sankyo

40 mg with Hydrochlorothiazide 12.5 mg

Benicar HCT

Daiichi Sankyo

40 mg with Hydrochlorothiazide 25 mg

Benicar HCT

Daiichi Sankyo

AHFS DI Essentials™. © Copyright 2019, Selected Revisions November 5, 2018. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Daiichi SankyoParsippany, NJ; 2016 Nov.

2. Song JC, White CM. Olmesartan medoxomil (CS-866): an angiotensin II receptor blocker for treatment of hypertension. Formulary. 2001; 36:487-99.

3. Neutel JM. Clinical studies of CS-866, the newest angiotensin II receptor antagonist. Am J Cardiol. 2001; 87(Suppl):37-43C.

5. Anon. Drugs for hypertension. Med Lett Drugs Ther. 2001; 43:17-22. http://www.ncbi.nlm.nih.gov/pubmed/11242494?dopt=AbstractPlus

7. Warner KK, Visconti JA, Tschampel MM. Angiotensin II receptor blockers in patients with ACE inhibitor-induced angioedema. Ann Pharmacother. 2000; 34:526-8. http://www.ncbi.nlm.nih.gov/pubmed/10772441?dopt=AbstractPlus

8. Oparil S, Williams D, Chrysant SG et al. Comparative efficacy of olmesartan, losartan, valsartan, and irbesartan in the control of essential hypertension. J Clin Hypertens (Greenwich). 2001; 3:283-91, 318. http://www.ncbi.nlm.nih.gov/pubmed/11588406?dopt=AbstractPlus

9. Ball KJ, Williams PA, Stumpe KO. Relative efficacy of an angiotensin II antagonist compared with other antihypertensive agents. Olmesartan medoxomil versus antihypertensives. J Hypertens. 2001; 19(Suppl 1):S49-56.

10. von Bergmann K, Laeis P, Puchler K et al. Olmesartan medoxomil: influence of age, renal and hepatic function on the pharmacokinetics of olmesartan medoxomil. J Hypertens. 2001; 19(Suppl 1):S33-40.

11. Walser M. Angiotensin-Receptor Blockers, Type 2 Diabetes, and Renoprotection. N Engl J Med. 2002; 346:706.

12. Puchler K, Laeis P, Stumpe KO. Blood pressure response, but not adverse event incidence, correlates with dose of angiotensin II antagonist. J Hypertens. 2001; 19(Suppl 1):S41-8.

13. US Food and Drug Administration. Dangers of ACE inhibitors during second and third trimesters of pregnancy. FDA Med Bull. 1992; 22:2.

14. Mazzolai L, Burnier M. Comparative safety and tolerability of angiotensin II receptor antagonists. Drug Safety. 1999; 21:23-33. http://www.ncbi.nlm.nih.gov/pubmed/10433351?dopt=AbstractPlus

15. Kirk JK. Therapy with angiotensin II receptor antagonists. Clin Geriatrics. From the MultiMedia Health Care website. http://www.mmhc.com

16. Sankyo Pharma, New York, NY: Personal communication.

17. AstraZeneca, Wayne, PA: personal communication on Candesartan 24:32.08.

19. Brenner BM, Cooper ME, de Zeeuw D et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001; 345:861-9. http://www.ncbi.nlm.nih.gov/pubmed/11565518?dopt=AbstractPlus

20. Lewis EJ, Hunsicker LG, Claarke WR et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med. 2001; 345:851-60. http://www.ncbi.nlm.nih.gov/pubmed/11565517?dopt=AbstractPlus

21. DA, Bakris GL. Type 2 diabetes: RENAAL and IDNT-the emergence of new treatment options. J Clin Hypertens (Greenwich). 2002; 4:52-7. http://www.ncbi.nlm.nih.gov/pubmed/11821641?dopt=AbstractPlus

22. Parving HH, Brenner BM, Cooper ME et al. [Effect of losartan on renal and cardiovascular complications of patients with type 2 diabetes and nephropathy.] (Danish; with English abstract.) Ugeskr Laeger. 2001; 163:5514-9.

23. Weekers L, Krzesinski JM. [Clinical study of the month. Nephroprotective role of angiotensin II receptor antagonists in type 2 diabetes: results of IDNT and RENAAL trials.] (French with English abstract.) Rev Med Liege. 2001; 56:723-6.

24. Parving HH, Lehnert H, Brochner-Mortensen J et al and the Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria Study Group. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med. 2001; 345:870-8. http://www.ncbi.nlm.nih.gov/pubmed/11565519?dopt=AbstractPlus

25. Walser M. Angiotensin-Receptor Blockers, Type 2 Diabetes, and Renoprotection. N Engl J Med. 2002; 346:706.

26. Unger T. Significance of angiotensin type 1 receptor blockade: why are angiotensin II receptor blockers different? Am J Cardiol. 1999; 84:9-15S.

27. Martineau P, Goulet J. New competition in the realm of renin-angiotensin axis inhibition; the angiotensin II receptor antagonists in congestive heart failure. Ann Pharmacother. 2001; 35:71-84. http://www.ncbi.nlm.nih.gov/pubmed/11197588?dopt=AbstractPlus

28. Warner GT, Jarvis B. Olmesartan medoxomil. Drugs. 2002; 62:1345-53. http://www.ncbi.nlm.nih.gov/pubmed/12076183?dopt=AbstractPlus

29. Sankyo Pharma, New York, NY: Personal communication.

31. Daiichi Sankyo, Inc. Benicar HCT (olmesartan medoxomil and hydrochlorothiazide) tablets prescribing information. Parsippany, NJ; 2016 Feb.

35. Appel LJ. The verdict from ALLHAT—thiazide diuretics are the preferred initial therapy for hypertension. JAMA. 2002; 288:3039-60. http://www.ncbi.nlm.nih.gov/pubmed/12479770?dopt=AbstractPlus

36. The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002; 288:2981-97. http://www.ncbi.nlm.nih.gov/pubmed/12479763?dopt=AbstractPlus

37. Izzo JL, Levy D, Black HR. Importance of systolic blood pressure in older Americans. Hypertension. 2000; 35:1021-4. http://www.ncbi.nlm.nih.gov/pubmed/10818056?dopt=AbstractPlus

38. Frohlich ED. Recognition of systolic hypertension for hypertension. Hypertension. 2000; 35:1019-20. http://www.ncbi.nlm.nih.gov/pubmed/10818055?dopt=AbstractPlus

39. Bakris GL, Williams M, Dworkin L et al. Preserving renal function in adults with hypertension and diabetes: a consensus approach. Am J Kidney Dis. 2000; 36:646-61. http://www.ncbi.nlm.nih.gov/pubmed/10977801?dopt=AbstractPlus

42. Cooper WO, Hernandez-Diaz S, Arbogast PG et al. Major congenital malformations after first-trimester exposure to ACE inhibitors. N Engl J Med. 2006; 354:2443-51. http://www.ncbi.nlm.nih.gov/pubmed/16760444?dopt=AbstractPlus

43. Food and Drug Administration. FDA public health advisory: angiotensin-converting enzyme inhibitor (ACE inhibitor) drugs and pregnancy. From FDA website. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm102981.htm

44. Daiichi Sankyo, Inc. Azor (amlodipine and olmesartan medoxomil) tablets prescribing information. Parsippany, NJ; 2008 Oct.

45. Howes LG, Tran D. Can angiotensin receptor antagonists be used safely in patients with previous ACE inhibitor-induced angioedema? Drug Saf. 2002; 25:73-6.

56. Cooper WO, Hernandez-Diaz S, Arbogast PG et al. Major congenital malformations after first-trimester exposure to ACE inhibitors. N Engl J Med. 2006; 354:2443-51. http://www.ncbi.nlm.nih.gov/pubmed/16760444?dopt=AbstractPlus

57. Food and Drug Administration. FDA public health advisory: angiotensin-converting enzyme inhibitor (ACE inhibitor) drugs and pregnancy. From FDA website. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm102981.htm

120. Food and Drug Administration. FDA drug safety communication: ongoing safety review of the angiotensin receptor blockers and cancer. Rockville, MD; 2010 Jul 15. From FDA website (http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm218845.htm).

121. Sipahi I, Debanne SM, Rowland DY et al. Angiotensin-receptor blockade and risk of cancer: meta-analysis of randomised controlled trials. Lancet Oncol. 2010; 11:627-36. http://www.ncbi.nlm.nih.gov/pubmed/20542468?dopt=AbstractPlus

122. Nissen SE. Angiotensin-receptor blockers and cancer: urgent regulatory review needed. Lancet Oncol. 2010; 11:605-6. http://www.ncbi.nlm.nih.gov/pubmed/20542469?dopt=AbstractPlus

123. Sica DA. Angiotensin receptor blockers and the risk of malignancy: a note of caution. Drug Saf. 2010; 33:709-12. http://www.ncbi.nlm.nih.gov/pubmed/20701404?dopt=AbstractPlus

124. Food and Drug Administration. FDA drug safety communication: ongoing safety review of Benicar and cardiovascular events. Rockville, MD; 2010 June 11. From FDA website (http://www.fda.gov/drugs/drugsafety/postmarketdrugsafetyinformationforpatientsandproviders/ucm215222.htm).

125. Imai E, Ito S, Haneda M et al. Olmesartan reducing incidence of endstage renal disease in diabetic nephropathy trial (ORIENT): rationale and study design. Hypertens Res. 2006; 29:703-9. http://www.ncbi.nlm.nih.gov/pubmed/17249526?dopt=AbstractPlus

126. Food and Drug Administration. FDA drug safety communication: No increase in risk of cancer with certain blood pressure drugs-angiotensin receptor blockers (ARBs). Rockville, MD; 2011 Jun 2. Available from FDA website. Accessed 2011 Jun 15. http://www.fda.gov/Drugs/DrugSafety/ucm257516.htm

127. Bangalore S, Kumar S, Kjeldsen SE et al. Antihypertensive drugs and risk of cancer: network meta-analyses and trial sequential analyses of 324,168 participants from randomised trials. Lancet Oncol. 2011; 12:65-82. http://www.ncbi.nlm.nih.gov/pubmed/21123111?dopt=AbstractPlus

128. ARB Trialists Collaboration. Effects of telmisartan, irbesartan, valsartan, candesartan, and losartan on cancers in 15 trials enrolling 138,769 individuals. J Hypertens. 2011; 29:623-35. http://www.ncbi.nlm.nih.gov/pubmed/21358417?dopt=AbstractPlus

129. Pasternak B, Svanström H, Callréus T et al. Use of angiotensin receptor blockers and the risk of cancer. Circulation. 2011; 123:1729-36. http://www.ncbi.nlm.nih.gov/pubmed/21482967?dopt=AbstractPlus

130. Volpe M, Morganti A. 2010 Position Paper of the Italian Society of Hypertension (SIIA): Angiotensin Receptor Blockers and Risk of Cancer. High Blood Press Cardiovasc Prev. 2011; 18:37-40. http://www.ncbi.nlm.nih.gov/pubmed/21612311?dopt=AbstractPlus

131. Siragy HM. A current evaluation of the safety of angiotensin receptor blockers and direct renin inhibitors. Vasc Health Risk Manag. 2011; 7:297-313. http://www.ncbi.nlm.nih.gov/pubmed/21633727?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=3104607&blobtype=pdf

132. Haller H, Viberti GC, Mimran A et al. Preventing microalbuminuria in patients with diabetes: rationale and design of the Randomised Olmesartan and Diabetes Microalbuminuria Prevention (ROADMAP) study. J Hypertens. 2006; 24:403-8. http://www.ncbi.nlm.nih.gov/pubmed/16508590?dopt=AbstractPlus

133. Food and Drug Administration. FDA drug safety communication: FDA approves label changes to include intestinal problems (sprue-like enteropathy) linked to blood pressure medicine olmesartan medoxomil. Rockville, MD; 2013 July 3. From FDA website. http://www.fda.gov/Drugs/DrugSafety/ucm359477.htm

134. Rubio-Tapia A, Herman ML, Ludvigsson JF et al. Severe spruelike enteropathy associated with olmesartan. Mayo Clin Proc. 2012; 87:732-8. http://www.ncbi.nlm.nih.gov/pubmed/22728033?dopt=AbstractPlus

135. Dreifuss SE, Tomizawa Y, Farber NJ et al. Spruelike enteropathy associated with olmesartan: an unusual case of severe diarrhea. Case Rep Gastrointest Med. 2013; 2013:618071. http://www.ncbi.nlm.nih.gov/pubmed/23573432?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=3610358&blobtype=pdf

136. Hazan L, Hernández Rodriguez OA, Bhorat AE et al. A double-blind, dose-response study of the efficacy and safety of olmesartan medoxomil in children and adolescents with hypertension. Hypertension. 2010; 55:1323-30. http://www.ncbi.nlm.nih.gov/pubmed/20385971?dopt=AbstractPlus

137. Salazar DE, Song SH, Shi J et al. The use of modeling and simulation to guide clinical development of olmesartan medoxomil in pediatric subjects. Clin Pharmacol Ther. 2012; 91:250-6. http://www.ncbi.nlm.nih.gov/pubmed/22205195?dopt=AbstractPlus

138. Food and Drug Administration. FDA drug safety communication: Safety review update of Benicar (olmesartan) and cardiovascular events. Rockville, MD; 2011 April 14. From FDA website. http://www.fda.gov/Drugs/DrugSafety/ucm251268.htm

139. Daiichi Sankyo, Inc. Tribenzor (olmesartan medoxomil, amlodipine, hydrochlorothiazide) tablets prescribing information. Parsippany, NJ; 2017 Jan.

140. Food and Drug Administration. FDA drug safety communication: FDA review of cardiovascular risks for diabetics taking hypertension drug olmesartan not conclusive; label updates required. Rockville, MD; 2014 Jun 24. Available from FDA website. Accessed 2014 Aug 11. http://www.fda.gov/Drugs/DrugSafety/ucm402323.htm

141. Graham DJ, Zhou EH, McKean S et al. Cardiovascular and mortality risk in elderly Medicare beneficiaries treated with olmesartan versus other angiotensin receptor blockers. Pharmacoepidemiol Drug Saf. 2014; 23:331-9. http://www.ncbi.nlm.nih.gov/pubmed/24277678?dopt=AbstractPlus

142. Zhou EH, Gelperin K, Levenson MS et al. Risk of acute myocardial infarction, stroke, or death in patients initiating olmesartan or other angiotensin receptor blockers - a cohort study using the Clinical Practice Research Datalink. Pharmacoepidemiol Drug Saf. 2014; 23:340-7. http://www.ncbi.nlm.nih.gov/pubmed/24285502?dopt=AbstractPlus

143. Walker AM, Liang C, Clifford CR et al. Cardiac mortality in users of olmesartan, other angiotensin-receptor blockers and angiotensin-converting enzyme inhibitors. Pharmacoepidemiol Drug Saf. 2014; 23:348-56. http://www.ncbi.nlm.nih.gov/pubmed/24375940?dopt=AbstractPlus

144. Daiichi Sankyo, Inc. Azor (amlodipine and olmesartan medoxomil) tablets prescribing information. Parsippany, NJ; 2017 Jan.

501. James PA, Oparil S, Carter BL et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014; 311:507-20. http://www.ncbi.nlm.nih.gov/pubmed/24352797?dopt=AbstractPlus

502. Mancia G, Fagard R, Narkiewicz K et al. 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2013; 31:1281-357. http://www.ncbi.nlm.nih.gov/pubmed/23817082?dopt=AbstractPlus

503. Go AS, Bauman MA, Coleman King SM et al. An effective approach to high blood pressure control: a science advisory from the American Heart Association, the American College of Cardiology, and the Centers for Disease Control and Prevention. Hypertension. 2014; 63:878-85. http://www.ncbi.nlm.nih.gov/pubmed/24243703?dopt=AbstractPlus

504. Weber MA, Schiffrin EL, White WB et al. Clinical practice guidelines for the management of hypertension in the community: a statement by the American Society of Hypertension and the International Society of Hypertension. J Clin Hypertens (Greenwich). 2014; 16:14-26. http://www.ncbi.nlm.nih.gov/pubmed/24341872?dopt=AbstractPlus

505. Wright JT, Fine LJ, Lackland DT et al. Evidence supporting a systolic blood pressure goal of less than 150 mm Hg in patients aged 60 years or older: the minority view. Ann Intern Med. 2014; 160:499-503. http://www.ncbi.nlm.nih.gov/pubmed/24424788?dopt=AbstractPlus

506. Mitka M. Groups spar over new hypertension guidelines. JAMA. 2014; 311:663-4. http://www.ncbi.nlm.nih.gov/pubmed/24549531?dopt=AbstractPlus

507. Peterson ED, Gaziano JM, Greenland P. Recommendations for treating hypertension: what are the right goals and purposes?. JAMA. 2014; 311:474-6. http://www.ncbi.nlm.nih.gov/pubmed/24352710?dopt=AbstractPlus

508. Bauchner H, Fontanarosa PB, Golub RM. Updated guidelines for management of high blood pressure: recommendations, review, and responsibility. JAMA. 2014; 311:477-8. http://www.ncbi.nlm.nih.gov/pubmed/24352759?dopt=AbstractPlus

511. JATOS Study Group. Principal results of the Japanese trial to assess optimal systolic blood pressure in elderly hypertensive patients (JATOS). Hypertens Res. 2008; 31:2115-27. http://www.ncbi.nlm.nih.gov/pubmed/19139601?dopt=AbstractPlus

515. Thomas G, Shishehbor M, Brill D et al. New hypertension guidelines: one size fits most?. Cleve Clin J Med. 2014; 81:178-88. http://www.ncbi.nlm.nih.gov/pubmed/24591473?dopt=AbstractPlus

516. Wright JT, Bakris G, Greene T et al. Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the AASK trial. JAMA. 2002; 288:2421-31. http://www.ncbi.nlm.nih.gov/pubmed/12435255?dopt=AbstractPlus

522. Patel A, ADVANCE Collaborative Group, MacMahon S et al. Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial. Lancet. 2007; 370:829-40. http://www.ncbi.nlm.nih.gov/pubmed/17765963?dopt=AbstractPlus

523. Fihn SD, Gardin JM, Abrams J et al. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation. 2012; 126:e354-471. http://www.ncbi.nlm.nih.gov/pubmed/23166211?dopt=AbstractPlus

524. WRITING COMMITTEE MEMBERS, Yancy CW, Jessup M et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2013; 128:e240-327. http://www.ncbi.nlm.nih.gov/pubmed/23741058?dopt=AbstractPlus

525. Smith SC, Benjamin EJ, Bonow RO et al. AHA/ACCF Secondary Prevention and Risk Reduction Therapy for Patients with Coronary and other Atherosclerotic Vascular Disease: 2011 update: a guideline from the American Heart Association and American College of Cardiology Foundation. Circulation. 2011; 124:2458-73. http://www.ncbi.nlm.nih.gov/pubmed/22052934?dopt=AbstractPlus

526. Kernan WN, Ovbiagele B, Black HR et al. Guidelines for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2014; :. http://www.ncbi.nlm.nih.gov/pubmed/24788967?dopt=AbstractPlus

527. O'Gara PT, Kushner FG, Ascheim DD et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013; 127:e362-425. http://www.ncbi.nlm.nih.gov/pubmed/23247304?dopt=AbstractPlus

528. Pfeffer MA, Swedberg K, Granger CB et al. Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme. Lancet. 2003; 362:759-66. http://www.ncbi.nlm.nih.gov/pubmed/13678868?dopt=AbstractPlus

530. Myers MG, Tobe SW. A Canadian perspective on the Eighth Joint National Committee (JNC 8) hypertension guidelines. J Clin Hypertens (Greenwich). 2014; 16:246-8. http://www.ncbi.nlm.nih.gov/pubmed/24641124?dopt=AbstractPlus

531. . Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Heart Outcomes Prevention Evaluation Study Investigators. Lancet. 2000; 355:253-9. http://www.ncbi.nlm.nih.gov/pubmed/10675071?dopt=AbstractPlus

534. Qaseem A, Hopkins RH, Sweet DE et al. Screening, monitoring, and treatment of stage 1 to 3 chronic kidney disease: A clinical practice guideline from the American College of Physicians. Ann Intern Med. 2013; 159:835-47. http://www.ncbi.nlm.nih.gov/pubmed/24145991?dopt=AbstractPlus

535. Taler SJ, Agarwal R, Bakris GL et al. KDOQI US commentary on the 2012 KDIGO clinical practice guideline for management of blood pressure in CKD. Am J Kidney Dis. 2013; 62:201-13. http://www.ncbi.nlm.nih.gov/pubmed/23684145?dopt=AbstractPlus

536. Kidney Disease: Improving Global Outcomes (KDIGO) Blood Pressure Work Group. KDIGO clinical practice guideline for the management of blood pressure in chronic kidney disease. Kidney Int Suppl. 2012: 2: 337-414.

541. Perk J, De Backer G, Gohlke H et al. European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts). Eur Heart J. 2012; 33:1635-701. http://www.ncbi.nlm.nih.gov/pubmed/22555213?dopt=AbstractPlus

543. National Kidney Foundation Kidney Disease Outcomes Quality Initiative. K/DOQI Clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease (2002). From National Kidney Foundation website. http://www.kidney.org/professionals/kdoqi/guidelines_commentaries.cfm

550. US Food and Drug Administration. FDA Drug Safety Communication: new warning and contraindication for blood pressure medicines containing aliskiren (Tekturna). Rockville, MD; 2012 April 4. From FDA website. http://www.fda.gov/Drugs/DrugSafety/ucm300889.htm

701. Ponikowski P, Voors AA, Anker SD et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016; :. http://www.ncbi.nlm.nih.gov/pubmed/27206819?dopt=AbstractPlus

702. McMurray JJ, Packer M, Desai AS et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014; 371:993-1004. http://www.ncbi.nlm.nih.gov/pubmed/25176015?dopt=AbstractPlus

703. Ansara AJ, Kolanczyk DM, Koehler JM. Neprilysin inhibition with sacubitril/valsartan in the treatment of heart failure: mortality bang for your buck. J Clin Pharm Ther. 2016; 41:119-27. http://www.ncbi.nlm.nih.gov/pubmed/26992459?dopt=AbstractPlus

800. Yancy CW, Jessup M, Bozkurt B et al. 2016 ACC/AHA/HFSA Focused Update on New Pharmacological Therapy for Heart Failure: An Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation. 2016; :. http://www.ncbi.nlm.nih.gov/pubmed/27208050?dopt=AbstractPlus

1150. Flynn JT, Kaelber DC, Baker-Smith CM et al. Clinical practice guideline for screening and management of high blood pressure in children and adolescents. Pediatrics. 2017; 140 http://www.ncbi.nlm.nih.gov/pubmed/28827377?dopt=AbstractPlus

1200. Whelton PK, Carey RM, Aronow WS et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018; 71:el13-e115. http://www.ncbi.nlm.nih.gov/pubmed/29133356?dopt=AbstractPlus

1201. Bakris G, Sorrentino M. Redefining hypertension - assessing the new blood-pressure guidelines. N Engl J Med. 2018; 378:497-499. http://www.ncbi.nlm.nih.gov/pubmed/29341841?dopt=AbstractPlus

1202. Carey RM, Whelton PK, 2017 ACC/AHA Hypertension Guideline Writing Committee. Prevention, detection, evaluation, and management of high blood pressure in adults: synopsis of the 2017 American College of Cardiology/American Heart Association hypertension guideline. Ann Intern Med. 2018; 168:351-358. http://www.ncbi.nlm.nih.gov/pubmed/29357392?dopt=AbstractPlus

1207. Burnier M, Oparil S, Narkiewicz K et al. New 2017 American Heart Association and American College of Cardiology guideline for hypertension in the adults: major paradigm shifts, but will they help to fight against the hypertension disease burden?. Blood Press. 2018; 27:62-65. http://www.ncbi.nlm.nih.gov/pubmed/29447001?dopt=AbstractPlus

1209. Qaseem A, Wilt TJ, Rich R et al. Pharmacologic treatment of hypertension in adults aged 60 years or older to higher versus lower blood pressure targets: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med. 2017; 166:430-437. http://www.ncbi.nlm.nih.gov/pubmed/28135725?dopt=AbstractPlus

1210. SPRINT Research Group, Wright JT, Williamson JD et al. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015; 373:2103-16. http://www.ncbi.nlm.nih.gov/pubmed/26551272?dopt=AbstractPlus

1213. Reboussin DM, Allen NB, Griswold ME et al. Systematic review for the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2018; 71:2176-2198. http://www.ncbi.nlm.nih.gov/pubmed/29146534?dopt=AbstractPlus

1214. American Diabetes Association. 9. Cardiovascular disease and risk management: standards of medical care in diabetes 2018. Diabetes Care. 2018; 41:S86-S104. http://www.ncbi.nlm.nih.gov/pubmed/29222380?dopt=AbstractPlus

1215. de Boer IH, Bangalore S, Benetos A et al. Diabetes and hypertension: a position statement by the American Diabetes Association. Diabetes Care. 2017; 40:1273-1284. http://www.ncbi.nlm.nih.gov/pubmed/28830958?dopt=AbstractPlus

1216. Taler SJ. Initial treatment of hypertension. N Engl J Med. 2018; 378:636-644. http://www.ncbi.nlm.nih.gov/pubmed/29443671?dopt=AbstractPlus

1218. Messerli FH, Bangalore S, Bavishi C et al. Angiotensin-converting enzyme inhibitors in hypertension: to use or not to use?. J Am Coll Cardiol. 2018; 71:1474-1482. http://www.ncbi.nlm.nih.gov/pubmed/29598869?dopt=AbstractPlus

1219. Karmali KN, Lloyd-Jones DM. Global risk assessment to guide blood pressure management in cardiovascular disease prevention. Hypertension. 2017; 69:e2-e9. http://www.ncbi.nlm.nih.gov/pubmed/28115516?dopt=AbstractPlus

1220. Cifu AS, Davis AM. Prevention, detection, evaluation, and management of high blood pressure in adults. JAMA. 2017; 318:2132-2134. http://www.ncbi.nlm.nih.gov/pubmed/29159416?dopt=AbstractPlus

1222. Bell KJL, Doust J, Glasziou P. Incremental benefits and harms of the 2017 American College of Cardiology/American Heart Association high blood pressure guideline. JAMA Intern Med. 2018; 178:755-7. http://www.ncbi.nlm.nih.gov/pubmed/29710197?dopt=AbstractPlus

1223. LeFevre M. ACC/AHA hypertension guideline: What is new? What do we do?. Am Fam Physician. 2018; 97(6):372-3. http://www.ncbi.nlm.nih.gov/pubmed/29671534%20?dopt=AbstractPlus

1224. Brett AS. New hypertension guideline is released. From NEJM Journal Watch website. Accessed 2018 Jun 18. https://www.jwatch.org/na45778/2017/12/28/nejm-journal-watch-general-medicine-year-review-2017

1229. Ioannidis JPA. Diagnosis and treatment of hypertension in the 2017 ACC/AHA guidelines and in the real world. JAMA. 2018; 319(2):115-6. http://www.ncbi.nlm.nih.gov/pubmed/29242891?dopt=AbstractPlus

1232. American Diabetes Association. 10. Microvascular complications and foot care: standards of medical care in diabetes 2018. Diabetes Care. 2018; 41:S105-S118. http://www.ncbi.nlm.nih.gov/pubmed/29222381%20?dopt=AbstractPlus

Hide