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
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.
(antihypertensive effect with chronic dosing)
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.
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).
Hepatic Impairment
- PO (Adults): Moderate hepatic impairment — Initiate at 8 mg once daily.
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.
Hepatic Impairment
- PO (Adults): 25 mg once daily initially; may ↑ as tolerated.
- PO (Children >6 yr): Hypertension — 0.7 mg/kg once daily (up to 50 mg/day), may titrate up to 1.4 mg/kg/day (or 100 mg/day).
Renal Impairment
- PO (Children >6 yr): CCr <30 mL/min — Contraindicated.
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).