The FDA ( Food and Drug Administration ) has approved Tribenzor ( Olmesartan medoxomil, Amlodipine, Hydrochlorothiazide ), a new three-in-one combination product taken once-daily for the treatment of hypertension in patients who are not adequately controlled on any two of the following antihypertensive drug classes: angiotensin receptor blockers, calcium channel blockers and diuretics.
Tribenzor is not indicated for initial therapy.

Approximately 56% of patients taking current blood pressure-lowering therapies do not reach current recommended blood pressure goal of less than 140/90 mmHg or less than 130/80 mmHg for patients with diabetes mellitus, chronic renal disease, or chronic cardiovascular disease.
More than two-thirds of patients with high blood pressure will require two or more antihypertensive medications in order to achieve goal blood pressure control.

Tribenzor combines three widely prescribed antihypertensive medications, each working in a different way, to lower blood pressure. It combines the complementary actions of Olmesartan medoxomil ( which blocks angiotensin II receptors ), Amlodipine ( which inhibits the entrance of calcium into the blood vessel walls ), and Hydrochlorothiazide ( a diuretic which reduces water volume in the blood ).

After eight weeks of treatment, Tribenzor produced highly statistically significantly greater reductions in both systolic and diastolic blood pressures compared to each of the three dual combination therapies. According to the Tribenzor pivotal registration trial that included a total of 2,492 patients with hypertension ( mean baseline blood pressure 168.5/100.9 mmHg ), the switch to Tribenzor 40/10/25 mg from each of the following three dual combination therapies: (i) Amlodipine / Hydrochlorothiazide 10/25 mg, (ii) Olmesartan / Hydrochlorothiazide 40/25 mg, and (iii) Olmesartan / Amlodipine 40/10 mg, yielded a further mean reduction after eight weeks of treatment in systolic blood pressure / diastolic blood pressure of 8.1/5.4 mmHg, 7.6/5.4 mmHg, and 8.4/4.5 mmHg, respectively ( P<0.0001 vs each dual combination therapy ).

The most common adverse reactions ( incidence greater than or equal to 2% ) seen in clinical trials for Tribenzor were dizziness, peripheral edema, headache, fatigue, nasopharyngitis, muscle spasms, nausea, upper respiratory tract infection, diarrhea, urinary tract infection, and joint swelling.

Important safety information

Warning

When pregnancy is detected, discontinue Tribenzor as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and even death to the developing fetus.

Contraindications: Tribenzor is contraindicated in patients with anuria or hypersensitivity to other sulfonamide-derived drugs.

Hypotension in volume- or salt-depleted patients: In patients with an activated renin-angiotensin system, such as volume- and/or salt-depleted patients, symptomatic hypotension due particularly to the Olmesartan component may occur after initiation of treatment with Tribenzor. Treatment should start under close medical supervision.

Increased angina and myocardial infarction - Patients, particularly those with severe obstructive coronary artery disease, may develop increased frequency, duration, or severity of angina or acute myocardial infarction on starting calcium channel blocker therapy or at the time of dosage increase.

Impaired renal function - Avoid use in patients with severely impaired renal function ( creatinine clearance less than or equal to 30 mL/min ). If progressive renal impairment becomes evident, consider withholding or discontinuing Tribenzor.
In studies of Ace inhibitors in patients with unilateral or bilateral renal artery stenosis, increases in serum creatinine or blood urea nitrogen ( BUN ) have been reported. There has been no long-term use of Olmesartan medoxomil in patients with unilateral or bilateral renal artery stenosis, but similar effects would be expected with Tribenzor because of the Olmesartan medoxomil component.
Thiazides may precipitate azotemia in patients with renal disease. Cumulative effects of the drug may develop in patients with impaired renal function.

Hepatic impairment - Avoid use in patients with severely impaired hepatic function. Amlodipine is extensively metabolized by the liver and the plasma elimination half-life ( t1/2 ) is 56 hours in patients with severely impaired hepatic function. Minor alterations of fluid and electrolyte balance due to Hydrochlorothiazide may precipitate hepatic coma.

Electrolyte and metabolic imbalances - Due to the Hydrochlorothiazide component, observe patients for clinical signs of fluid or electrolyte imbalance.

Hypersensitivity reaction - Hypersensitivity reactions to Hydrochlorothiazide may occur in patients with or without a history of allergy or bronchial asthma, but are more likely in patients with such history.

Systemic lupus erythematosus - Thiazide diuretics have been reported to cause exacerbation or activation of systemic lupus erythematosus.

Vasodilation - Although vasodilation attributable to Amlodipine is gradual in onset, acute hypotension has rarely been reported after oral administration. Patients with severe aortic stenosis may be at particular risk.

Lithium Interaction - Lithium generally should not be given with thiazides.

Adverse Reactions - The most frequently reported adverse reaction was dizziness ( 5.8 to 8.9% ). The other most frequent adverse reactions occurring in greater than or equal to 2% of patients treated with Tribenzor are peripheral edema ( 7.7% ), headache ( 6.4% ), fatigue ( 4.2% ), nasopharyngitis ( 3.5% ), muscle spasms ( 3.1% ), nausea ( 3.0% ), upper respiratory tract infection ( 2.8% ), diarrhea ( 2.6% ), urinary tract infection ( 2.4% ), and joint swelling ( 2.1% ).

Source: Daiichi Sankyo, 2010

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