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 |
| Molecular Weight | 558.5 g/mol (olmesartan medoxomil: 558.59 Da; valsartan: 435.52 Da; hydrochlorothiazide: 297.74 Da; combined: not applicable) |
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 | Increased risk of fetal renal dysfunction, oligohydramnios, and skull ossification defects. Use only if no alternative. |
| 2nd trimester | Fetal toxicity including oligohydramnios, renal impairment, and hypotension. Avoid use. |
| 3rd trimester | Same as T2; may cause neonatal renal failure, hypotension, and hyperkalemia. Contraindicated. |
Clinical note
Comprehensive clinical and safety monograph for TRIBENZOR (TRIBENZOR).
| Placental transfer | Valsartan and hydrochlorothiazide cross the placenta. Olmesartan is likely transferred based on animal data. |
| Breastfeeding | Hydrochlorothiazide and valsartan are excreted in breast milk. Olmesartan excretion is unknown. Use with caution due to potential for adverse effects in the infant (e.g., hypotension, renal impairment). |
■ FDA Black Box Warning
None
| Common Effects | Blisters Skin peeling Swelling Application site irritation |
| Serious Effects |
Pregnancy (second and third trimesters)AnuriaHypersensitivity to any componentSevere hepatic impairmentConcomitant use with aliskiren in patients with diabetesHistory of angioedema with previous ARB therapy
| 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 |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they can increase amlodipine levels and risk of side effects. Avoid high-potassium foods (e.g., bananas, oranges, spinach) and potassium supplements, as HCTZ may cause potassium loss but olmesartan can cause potassium retention. Avoid excessive salt intake. Take with or without food, but be consistent. |
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| Lactation Rating |
| L3: Moderately Safe |
| 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. |
| 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. |
| Clinical Pearls | TRIBENZOR (olmesartan/amlodipine/hydrochlorothiazide) is a fixed-dose combination for hypertension not controlled on dual therapy. Avoid in pregnancy; can cause fetal harm. Monitor renal function, electrolytes, and blood pressure. Use cautiously in patients with severe renal impairment (CrCl <30 mL/min) as HCTZ is ineffective. Amlodipine may cause peripheral edema, especially at higher doses. Olmesartan may cause sprue-like enteropathy; discontinue if severe diarrhea with weight loss occurs. |
| Patient Advice | Take exactly as prescribed; do not change dose or stop without consulting your doctor. · Avoid pregnancy; use effective contraception. Stop drug and notify doctor if you become pregnant. · Rise slowly from sitting or lying to reduce dizziness. · Report persistent diarrhea with significant weight loss to your doctor. · Stay hydrated; avoid excessive sweating or dehydration. · Avoid salt substitutes containing potassium without medical advice. · Limit alcohol intake as it may lower blood pressure further. |