Olmesartan medoxomil, amlodipine, and hydrochlorothiazide (Tribenzor): A new 3-drug combination product for the treatment of hypertension

Combination olmesartan medoxomil, amlodipine, and hydrochlorothiazide 20 mg/5 mg/12.5 mg, 40 mg/5 mg/12.5 mg, 40 mg/5 mg/25 mg, 40 mg/10 mg/12.5 mg, and 40 mg/10 mg/25 mg tablets have been recently approved by FDA as an initial therapy to treat hypertension in patients likely to need multiple drugs to achieve their blood pressure goals. In addition, olmesartan medoxomil, amlodipine, hydrochlorothiazide may be used to provide additional blood pressure lowering for patients not adequately controlled on maximally tolerated, labeled, or usual doses of any 2 of the following antihypertensive classes: angiotensin II receptor blockers, calcium channel blockers, and diuretics or as a substitute for its individually titrated components. The active ingredients of olmesartan medoxomil, amlodipine, hydrochlorothiazide target 3 separate mechanisms involved in blood pressure regulation. Amlodipine blocks the contractile effects of calcium on cardiac and vascular smooth muscle cells; olmesartan medoxomil blocks the vasoconstriction and sodium retaining effects of angiotensin II on cardiac, vascular smooth muscle, and adrenal and renal cells; and hydrochlorothiazide directly promotes the excretion of sodium and chloride in the kidney leading to reductions in intravascular volume.

Efficacy. The antihypertensive efficacy of olmesartan medoxomil, amlodipine, hydrochlorothiazide was studied in a double-blind, active-controlled trial of 2,492 hypertensive patients. Patients with hypertension (mean baseline blood pressure 169/101 mmHg) received olmesartan medoxomil/amlodipine/hydrochlorothiazide 40/10/25 mg (627 patients), olmesartan medoxomil/amlodipine 40/10 mg (628 patients), olmesartan medoxomil/hydrochlorothiazide 40/25 mg (637 patients), or amlodipine/hydrochlorothiazide 10/25 mg (600 patients). After 8 weeks of treatment, the triple combination therapy produced greater reductions in both systolic and diastolic blood pressures (P<.0001) compared to each of the 3 dual combination therapies.

Safety. In the controlled trial of olmesartan medoxomil, amlodipine, hydrochlorothiazide, 574 patients with hypertension received the combination drugs (40 mg/10 mg/25 mg) for 8 weeks. During the trial, discontinuation of therapy due to a clinical adverse event occurred in 4% of patients. The most common adverse reactions (incidence ≥2%) occurring during the trial were dizziness, peripheral edema, headache, fatigue, nasopharyngitis, muscle spasms, nausea, upper respiratory tract infection, diarrhea, urinary tract infection, and joint swelling. Because olmesartan medoxomil, amlodipine, hydrochlorothiazide contains olmesartan, a drug that acts directly on the renin-angiotensin-aldosterone system, it can cause injury or death to a developing fetus.