TRIBENZOR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TRIBENZOR (TRIBENZOR).
TRIBENZOR is a fixed-dose combination of olmesartan, an angiotensin II receptor blocker that inhibits the vasopressor and aldosterone-secreting effects of angiotensin II, and amlodipine, a dihydropyridine calcium channel blocker that inhibits calcium ion influx across cardiac and vascular smooth muscle cells, resulting in vasodilation.
| Metabolism | Olmesartan is metabolized by the liver via glucuronidation; amlodipine is extensively metabolized by cytochrome P450 3A4 (CYP3A4) to inactive metabolites. |
| Excretion | Renal: 50-60% as unchanged drug and metabolites; Biliary/Fecal: 40-50% |
| Half-life | Terminal half-life 9-11 hours; supports once-daily dosing |
| Protein binding | Highly protein bound (olmesartan ~99%, amlodipine ~93%, hydrochlorothiazide ~68%) primarily to albumin |
| Volume of Distribution | Olmesartan: 17 L; Amlodipine: 21 L/kg; Hydrochlorothiazide: 3-5 L/kg |
| Bioavailability | Olmesartan: 26% (oral); Amlodipine: 64-90% (oral); Hydrochlorothiazide: 65-75% (oral) |
| Onset of Action | Oral: 2-4 hours for peak antihypertensive effect |
| Duration of Action | Oral: 24 hours; allows once-daily dosing with sustained BP reduction |
Tribenzor (olmesartan medoxomil/amlodipine/hydrochlorothiazide) is available in fixed-dose combinations. Typical adult dose: one tablet orally once daily. Starting dose depends on prior antihypertensive therapy; maximum recommended dose is olmesartan 40 mg/amlodipine 10 mg/HCTZ 25 mg per day.
| Dosage form | TABLET |
| Renal impairment | Contraindicated in anuria and severe renal impairment (CrCl <30 mL/min). For CrCl 30-60 mL/min, use with caution; no specific dose adjustment provided. Monitor renal function. |
| Liver impairment | Child-Pugh Class A: No adjustment necessary. Child-Pugh Class B: Use with caution; limited data. Child-Pugh Class C: Contraindicated due to HCTZ component; avoid use. |
| Pediatric use | Safety and efficacy in pediatric patients (<18 years) have not been established. Not recommended. |
| Geriatric use | Elderly patients may be more sensitive to hypotension and electrolyte imbalances. Start at the lowest dose (olmesartan 20 mg/amlodipine 5 mg/HCTZ 12.5 mg) and titrate cautiously. Monitor renal function and electrolytes. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TRIBENZOR (TRIBENZOR).
| Breastfeeding | Hypertension during lactation is treated with alternative agents, as TRIBENZOR is not recommended. Olmesartan is excreted in human milk in low amounts (M/P ratio unknown), but effects on the nursing infant are unknown. Amlodipine is excreted in breast milk; the M/P ratio is approximately 1.0, with infant doses estimated at 3-7% of maternal weight-adjusted dose. Hydrochlorothiazide is excreted in breast milk in low amounts (M/P ratio ~0.6-1.0) but may suppress lactation. Due to potential for adverse effects in the infant, especially with hydrochlorothiazide, avoid breastfeeding while on TRIBENZOR. |
| Teratogenic Risk | TRIBENZOR (olmesartan/amlodipine/hydrochlorothiazide) is contraindicated in pregnancy, especially during the second and third trimesters. Drugs acting directly on the renin-angiotensin system (RAAS) can cause fetal renal dysfunction, oligohydramnios, skull ossification defects, and neonatal anuria/hypotension. First trimester exposure carries a slightly increased risk of congenital malformations, though the absolute risk is low. Hydrochlorothiazide may cause neonatal thrombocytopenia, electrolyte imbalances, and jaundice. Amlodipine has shown fetal toxicity in animal studies at high doses but human data are limited. |
■ FDA Black Box Warning
None
| Common Effects | Blisters Skin peeling Swelling Application site irritation |
| Serious Effects |
["Concomitant use with aliskiren in patients with diabetes","Known hypersensitivity to any component of the product"]
| Precautions | ["Avoid use in pregnancy; discontinue as soon as possible if pregnancy is detected","Symptomatic hypotension may occur, particularly in volume-depleted patients","Monitor renal function; acute renal failure may occur","Worsening angina or myocardial infarction can occur with initiation of amlodipine","Hepatic impairment may affect drug clearance"] |
Loading safety data…
| Fetal Monitoring | If exposure occurs, monitor fetal ultrasound for amniotic fluid volume, renal function, and skull ossification. Neonates should be monitored for hypotension, oliguria, hyperkalemia, and electrolyte imbalances. Monitor maternal blood pressure, renal function, and electrolytes (especially potassium, sodium, and bicarbonate) throughout pregnancy. Serial fetal growth assessments recommended. |
| Fertility Effects | Olmesartan and other RAAS inhibitors may impair fertility in women of reproductive age by unknown mechanisms; reversible upon discontinuation. Amlodipine and hydrochlorothiazide have no known significant effects on fertility. In animal studies, high doses of olmesartan reduced fertility indices, but clinical significance is unclear. |