• Hypertension (as monotherapy or with other antihypertensives).
• Treatment of diabetic nephropathy in patients with type 2 diabetes and hypertension (irbesartan and losartan only).
• Management of HF (New York Heart Association class II-IV) in patients who cannot tolerate ACE inhibitors (candesartan and valsartan only) or in combination with an ACE inhibitor and beta-blocker (candesartan only).
• Prevention of stroke in patients with hypertension and left ventricular hypertrophy (losartan only).
• Reduction of risk of death from cardiovascular causes in patients with left ventricular systolic dysfunction after MI (valsartan only).
• Reduction of risk of myocardial infarction, stroke, or cardiovascular death in patients 55 yr who are at high risk for cardiovascular events and are unable to take ACE inhibitors (telmisartan only).

Contraindicated in:

• Hypersensitivity
• Concurrent use with aliskiren in patients with diabetes or moderate-to-severe renal impairment (CCr <60 mL/min)
• Severe hepatic impairment (candesartan)
• OB: Pregnancy
• Lactation: Lactation.

Use Cautiously in:

• HF (may result in azotemia, oliguria, acute renal failure and/or death)
• Volume- or salt-depleted patients or patients receiving high doses of diuretics (correct deficits before initiating therapy or initiate at lower doses)
• Black patients (may not be effective)
• Impaired renal function due to primary renal disease or HF (may worsen renal function)
• Obstructive biliary disorders (telmisartan) or hepatic impairment (losartan, or telmisartan)
• Severe renal impairment (CCr <30 mL/min) (valsartan)
• Women of reproductive potential
• Pedi: Safety and effectiveness not established in children <18 yr (azilsartan, candesartan, irbesartan, telmisartan), <6 yr (losartan, olmesartan), and <1 yr (valsartan).

CV: hypotension, chest pain, edema, tachycardia.

Derm: rash.

EENT: nasal congestion, pharyngitis, rhinitis, sinusitis.

GI: abdominal pain, diarrhea, drug-induced hepatitis, dyspepsia, nausea, vomiting.

GU: impaired renal function.

F and E: hyperkalemia.

MS: arthralgia, back pain, myalgia.

Neuro: dizziness, anxiety, depression, fatigue, headache, insomnia, weakness.
Misc: ANGIOEDEMA.

Drug-Drug:

• NSAIDs and selective COX-2 inhibitors may blunt the antihypertensive effect and ↑ the risk of renal dysfunction.
• ↑antihypertensive effects with other antihypertensives and diuretics.
• Telmisartan may ↑ serum digoxin levels.
• Concurrent use of potassium-sparing diuretics, potassium-containing salt substitutes, or potassium supplements may ↑ risk of hyperkalemia.
• ↑risk of hyperkalemia, renal dysfunction, hypotension, and syncope with concurrent use of ACE inhibitors or aliskiren; avoid concurrent use with aliskiren in patients with diabetes or CCr <60 mL/min; avoid concurrent use with ACE inhibitors
• Candesartan, valsartan, and irbesartan may ↑ lithium levels.
• Irbesartan and losartan may ↑ effects of amiodarone, fluoxetine, glimepiride, glipizide, phenytoin, rosiglitazone, and warfarin.
• Rifampin may ↓ effects of losartan.
• ↑risk of renal dysfunction when telmisartan used with ramipril (concurrent use not recommended).
• Colesevelam may ↓ olmesartan levels; administer olmesartan 4 hr before colesevelam

Azilsartan

(Generic available)

• Tablets: 40 mg; 80 mg;
• In combination with: chlorthalidone (Edarbyclor); see Appendix [not included in this PDA edition].

Candesartan

(Generic available)

• Tablets: 4 mg; 8 mg; 16 mg; 32 mg;
• In combination with: hydrochlorothiazide (Atacand HCT); see Appendix [not included in this PDA edition].

Irbesartan

(Generic available)

• Tablets: 75 mg; 150 mg; 300 mg;
• In combination with: hydrochlorothiazide (Avalide); see Appendix [not included in this PDA edition].

Losartan

(Generic available)

• Tablets: 25 mg; 50 mg; 100 mg;
• In combination with: hydrochlorothiazide (Hyzaar); see Appendix [not included in this PDA edition].

Olmesartan

(Generic available)

• Tablets: 5 mg; 20 mg; 40 mg;
• In combination with: hydrochlorothiazide (Benicar HCT); amlodipine (Azor); see Appendix [not included in this PDA edition].

Telmisartan

(Generic available)

• Tablets: 20 mg; 40 mg; 80 mg;
• In combination with: hydrochlorothiazide (Micardis HCT); amlodipine; see Appendix [not included in this PDA edition].

Valsartan

(Generic available)

• Tablets: 40 mg; 80 mg; 160 mg; 320 mg;
• In combination with: amlodipine (Exforge); hydrochlorothiazide (Diovan HCT); amlodipine and hydrochlorothiazide (Exforge HCT); see Appendix [not included in this PDA edition].

Azilsartan

• PO (Adults): 80 mg once daily, initial dose may be ↓ to 40 mg once daily if high doses of diuretics are used concurrently.

Candesartan

• PO (Adults): Hypertension — 16 mg once daily; may ↑ up to 32 mg/day in 1–2 divided doses (begin therapy at a lower dose in patients who are receiving diuretics or are volume depleted). HF — 4 mg once daily initially, dose may be doubled at 2 wk intervals up to target dose of 32 mg once daily.
• PO (Children 6–16 yr and >50 kg): 8–16 mg/day (in 1–2 divided doses); may ↑ up to 32 mg/day (in 1–2 divided doses).
• PO (Children 6–16 yr and <50 kg): 4–8 mg/day (in 1–2 divided doses); may ↑ up to 16 mg/day (in 1–2 divided doses).
• PO (Children 1–5 yr): 0.20 mg/kg/day (in 1–2 divided doses); may ↑ up to 0.4 mg/kg/day (in 1–2 divided doses).

Irbesartan

• PO (Adults): Hypertension — 150 mg once daily; may ↑ to 300 mg once daily. Initiate therapy at 75 mg once daily in patients who are receiving diuretics or are volume depleted. Type 2 diabetic nephropathy — 300 mg once daily.

Losartan

• PO (Adults): Hypertension — 50 mg once daily initially (range 25–100 mg/day as a single daily dose or 2 divided doses) (initiate therapy at 25 mg once daily in patients who are receiving diuretics or are volume depleted). Prevention of stroke in patients with hypertension and left ventricular hypertrophy — 50 mg once daily initially; hydrochlorothiazide 12.5 mg once daily should be added and/or dose of losartan ↑ to 100 mg once daily followed by an ↑ in hydrochlorothiazide to 25 mg once daily based on BP response. Type 2 diabetic nephropathy — 50 mg once daily, may ↑ to 100 mg once daily depending on BP response.

Olmesartan

• PO (Adults): 20 mg once daily; may ↑ up to 40 mg once daily (patients who are receiving diuretics or are volume-depleted should be started on lower doses).
• PO (Children 6–16 yr): 35 kg — 20 mg once daily; may ↑ after 2 wk up to 40 mg once daily; 20–34.9 kg — 10 mg once daily; may ↑ after 2 wk up to 20 mg once daily.

Telmisartan

• PO (Adults): Hypertension — 40 mg once daily (volume-depleted patients should start with 20 mg once daily); may be titrated up to 80 mg/day; Cardiovascular risk reduction — 80 mg once daily.

Valsartan

Oral tablets and suspension are NOT interchangeable on a mg-per-mg basis. These dosage forms should not be combined to arrive at a particular dose.

• PO (Adults): Hypertension — 80 mg or 160 mg once daily initially in patients who are not volume-depleted; may ↑ to 320 mg once daily; HF — 40 mg twice daily, may be titrated up to target dose of 160 mg twice daily as tolerated; Post-MI — 20 mg twice daily (may be initiated 12 hr after MI); dose may be titrated up to target dose of 160 mg twice daily, as tolerated.
• PO (Children 1–16 yr): Hypertension — 1 mg/kg once daily (maximum dose = 40 mg/day) (may consider using starting dose of 2 mg/kg once daily if greater BP reduction needed); may ↑ up to 4 mg/kg once daily (maximum dose = 160 mg/day).

azilsartan: Edarbi

candesartan: Atacand

irbesartan: Avapro

losartan: Cozaar

olmesartan: Benicar

telmisartan: Micardis

valsartan: Diovan

• Blocks vasoconstrictor and aldosterone-producing effects of angiotensin II at receptor sites, including vascular smooth muscle and the adrenal glands.

• Lowering of BP.
• Slowed progression of diabetic nephropathy (irbesartan and losartan only).
• Reduced cardiovascular death and hospitalizations due to HF in patients with HF (candesartan and valsartan only).
• Decreased risk of cardiovascular death in patients with left ventricular systolic dysfunction who are post-MI (valsartan only).
• Decreased risk of stroke in patients with hypertension and left ventricular hypertrophy (effect may be less in black patients) (losartan only).

Therapeutic Classification: antihypertensives

Pharmacologic Classification: angiotensin II receptor antagonists

Absorption: Azilsartan — Azilsartan medoxomil is converted to azilsartan, the active component. 60% absorbed; Candesartan — Candesartan cilexetil is converted to candesartan, the active component; 15% bioavailability of candesartan; Irbesartan — 60–80% absorbed after oral administration; Losartan — well absorbed, with extensive first-pass hepatic metabolism, resulting in 33% bioavailability; Olmesartan — Olmesartan medoxomil is converted to olmesartan, the active component; 26% bioavailability of olmesartan; Telmisartan — 42–58% absorbed following oral administration (bioavailability ↑ in patients with hepatic impairment); Valsartan — 10–35% absorbed following oral administration; systemic exposure 60% higher with the suspension compared to tablets.

Distribution: All angiotensin receptor blockers (ARBs) cross the placenta; Candesartan — enters breast milk.

Protein Binding: All ARBs are >90% protein-bound.

Metabolism/Excretion: Azilsartan — 50% metabolized by the liver, primarily by the CYP2C9 enzyme system. 55% eliminated in feces, 42% in urine (15% as unchanged drug); Candesartan — Minor metabolism by the liver; 33% excreted in urine, 67% in feces (via bile); Irbesartan — Some hepatic metabolism; 20% excreted in urine, 80% in feces; Losartan — Undergoes extensive first-pass hepatic metabolism; 14% is converted to an active metabolite. 4% excreted unchanged in urine; 6% excreted in urine as active metabolite; some biliary elimination; Olmesartan — 30–50% excreted unchanged in urine, remainder eliminated in feces via bile; Telmisartan — Excreted mostly unchanged in feces via biliary excretion; Valsartan — Minor metabolism by the liver; 13% excreted in urine, 83% in feces.

Half-life: Azilsartan — 11 hr; Candesartan — 9 hr; Irbesartan — 11–15 hr; Losartan — 2 hr (6–9 hr for metabolite); Olmesartan — 13 hr; Telmisartan — 24 hr; Valsartan — 6 hr.

olmesartan: Olmetec

(antihypertensive effect with chronic dosing)

• Instruct patient to take as medication directed, even if feeling well. Take missed doses as soon as remembered if not almost time for next dose; do not double doses. Instruct patient to take medication at the same time each day. Warn patient not to discontinue therapy unless directed by health care professional.
• Caution patient to avoid salt substitutes containing potassium or food containing high levels of potassium or sodium unless directed by health care professional. See Appendix M.
• Caution patient to avoid sudden changes in position to decrease orthostatic hypotension. Use of alcohol, standing for long periods, exercising, and hot weather may increase orthostatic hypotension.
• May cause dizziness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications, especially NSAIDs and cough, cold, or allergy remedies.
• Instruct patient to notify health care professional of medication regimen prior to treatment or surgery.
• Instruct patient to notify health care professional immediately if swelling of face, eyes, lips, or tongue occurs, or if difficulty swallowing or breathing occurs.
• May cause fetal harm. Advise females of reproductive potential to use contraception and notify health care professional if pregnancy is suspected or planned, or if breast feeding. If pregnancy is detected, discontinue medication as soon as possible. In patients taking during pregnancy, perform serial ultrasound examinations to assess the intra-amniotic environment. Fetal testing may be appropriate, based on the week of gestation. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. If oligohydramnios is observed, consider alternative drug treatment. Closely observe neonates with histories of in utero exposure to valsartan for hypotension, oliguria, and hyperkalemia. In neonates with a history of in utero exposure to valsartan, if oliguria or hypotension occurs, support blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and replacing renal function.
• Emphasize the importance of follow-up exams to evaluate effectiveness of medication.
• Hypertension: Encourage patient to comply with additional interventions for hypertension (weight reduction, low-sodium diet, discontinuation of smoking, moderation of alcohol consumption, regular exercise, stress management). Medication controls but dose not cure hypertension.
  • Instruct patient and family on proper technique for monitoring BP. Advise them to check BP at least weekly and to report significant changes.

azilsartan: a-zill-SAR-tan

candesartan: can-de-SAR-tan

irbesartan: ir-be-SAR-tan

losartan: loe-SAR-tan

olmesartan: ole-me-SAR-tan

telmisartan: tel-mi-SAR-tan

valsartan: val-SAR-tan