Dosing and uses of Tribenzor (olmesartan/amlodipine/hydrochlorothiazide)
Adult dosage forms and strengths
olmesartan/amlodipine/hydrochlorothiazide
tablet
- 20mg/5mg/12.5mg
- 40mg/5mg/12.5mg
- 40mg/5mg/25mg
- 40mg/10mg/12.5mg
- 40mg/10mg/25mg
Hypertension
Indicated treatment of hypertension in patients who have been previously titrated on the individual components, olmesartan, amlodipine, and hydrochlorothiazide
May be used as add-on/switch therapy to provide additional blood pressure lowering for patient not adequately controlled on agents from 2 of the antihypertensive classes (ie, ARBs, CCBs, diuretics)
Not for initial therapy
Administer once daily
Add-on/switch/replacement therapy: 5-10 mg amlodipine, 20-40 mg olmesartan, 12.5-25 mg hydrochlorothiazide daily; dosage may be increased at 2-week intervals; titrate by increasing 1 component at a time; not to exceed 40 mg olmesartan/10 mg amlodipine/25 mg hydrochlorothiazide qDay
Renal Impairment
CrCl >30 mL/min: No dosage adjustment required
CrCl 30 mL/min or less: Avoid use; loop diuretics are preferred to thiazides with severe renal impairment; thiazides may precipitate azotemia
CrCl 20 mL/min or less: Olmesartan AUC approximately tripled
Hepatic Impairment
Mild-to-moderate impairment: Use caution; not studied
Severe hepatic impairment: Do not use; requires starting amlodipine at 2.5 mg, which is not available with Tribenzor
Pediatric dosage forms and strengths
Safety and efficacy not established
Geriatric dosage forms and strengths
No overall differences in efficacy or safety observed in elderly; however, greater sensitivity of some older individuals cannot be ruled out
>75 years: Do not use; severe hepatic impairment requires starting amlodipine at 2.5 mg, which is not available with combination product Tribenzor
Tribenzor (olmesartan/amlodipine/hydrochlorothiazide) adverse (side) effects
1-10%
Dizziness (5.8-8.9%)
Peripheral edema (7.7%)
Fatigue (4%)
Headache (6.4%)
Nausea (3%)
Muscle spasms (3.1%)
Nausea (3%)
Diarrhea (2.6%)
Joint swelling (2.1%)
Syncope (1%)
Urinary tract infection (2%)
Nasopharyngitis (4%)
Upper respiratory tract infection (3%)
Warnings
Black box warnings
Discontinue as soon as possible when pregnancy is detected; affects renin-angiotensin system causing oligohydramnios, which may result in fetal injury and/or death
Contraindications
Hypersensitivity to any drug component or sulfonamide-derived drug
Anuria
Condomitant use with aliskiren in patients with diabetes mellitus
Pregnancy (2nd and 3rd trimesters): significant risk of fetal/neonatal morbidity and mortality
Cautions
Angioedema, severe CHF, surgery/anesthesia, volume depletion (consider lower dose)
Discontinue STAT if pregnant: potential risk of congenital malformations (see Black box warnings)
Risk of hypotension, especially in patients with volume/salt depletion; correct volume-depletion prior to administration
Increased angina or myocardial infarction with calcium channel blockers may occur upon dosage initiation or increase
Risk of hyperkalemia
Dual blockade of the renin angiotensin system with ARBs, ACE inhibitors, or aliskiren associated with increased risk for hypotension, hyperkalemia, and renal function changes (including acute renal failure) compared to monotherapy; closely monitor blood pressure
Intestinal problems (ie, sprue-like enteropathy) reported with olmesartan; symptoms may include severe, chronic diarrhea with substantial weight loss
Avoid with severe renal impairment (<30 mL/min)
Withhold/discontinue if progressive renal impairment occurs
Thiazides: use with caution with mild/moderate liver impairment or progressive liver disease; avoid in patients with severe liver impairment
Monitor for fluid/electrolyte imbalance
Use caution in heart failure, severe aortic stenosis (amlodipine), hepatic impairment, renal artery stenosis, or hypertrophic cardiomyopathy
Thiazide diuretics may exacerbate or activate SLe
Acute transient myopia and acute angle-closure glaucoma has been reported, particularly with history of sulfonamide or penicillin allergy (hydrochlorothiazide is a sulfonamide)
Caution in aortic mitral stenosis, hepatic impairment, hypercholesterolemia, hypercalcemia, parathyroid disease, pre-existing renal insufficiency, systemic lupus erythematosus, bilateral renal artery stenosis or anuria
Pregnancy and lactation
Pregnancy category: C (1st trimester); D (2nd/3rd trimesters)
Lactation: Unknown whether olmesartan or amlodipine distributed in breast milk; hydrochlorothiazide secreted at low concentration in breastmilk; potential for adverse effects on nursing infant
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Tribenzor (olmesartan/amlodipine/hydrochlorothiazide)
Mechanism of action
Olmesartan: Blocks binding of angiotensin II to type 1 angiotensin II receptors; blocks vasoconstrictive and aldosterone-secretion properties of angiotensin II; elicits natriuresis and kaliuresis
Amlodipine: Dihydropyridine calcium channel blocker; inhibits extracellular Ca ions across the membranes of myocardial cells and vascular smooth muscle cells, without changing serum calcium concentrations; this results in inhibition of cardiac and vascular smooth muscle contraction, thereby dilating the main coronary and systemic arteries
Hydrochlorothiazide: Thiazide diuretic; Inhibits Na reabsorption in distal renal tubules resulting in increased Na and water excretion; lowers blood pressure and decreases edema
Pharmacokinetics
Olmesartan
- Half-Life: 13 hr
- Bioavailability: 26% (olmesartan medoxomil); rapidly and completely bioactivated by ester hydrolysis from olmesartan medoxomil to olmesartan
- Vd: 17 L
- Peak Plasma Time: 1-2 hr
- Metabolism: Olmesartan medoxomil is hydrolyzed in GI tract to active olmesartan
- Onset: >90% effective at 24 hr
- Protein Bound: 99%
- Clearance: 1.3 L/hr (plasma); 0.6 L/hr (renal)
- Excretion: Feces (50-65%); urine (35-50%)
Amlodipine
- Half-Life: 30-50 hr
- Bioavailability: 64-90%
- Vd: 21L/kg
- Duration of antihypertensive effects: 24 hr
- Absorption: Well absorbed
- Peak plasma time: 6-12 hr
- Protein Bound: 93-98%
- Metabolism: Liver (>90% converted to inactive metabolites via hepatic metabolism)
- Excretion: Urine (10% parent compound and 60% metabolites within 24 hr)
Hydrochlorothiazide
- Half-Life: 6-15 hr
- Bioavailability: 70%
- Onset: 2 hr (diuresis); 4-6 hr (peak effect)
- Duration: 6-12 hr (diuresis); 1 wk (HTN)
- Vd: 3.6-7.8 L/kg
- Peak Plasma:1.5-2.5 hr
- Protein Bound: 68%
- Metabolism: Minimally metabolized
- Clearance: 335 mL/min
- Excretion: Urine 50-70%
- Dialyzable: No
