Amlodipine, Hydrochlorothiazide and Olmesartan

Tribenzor is indicated for the treatment of hypertension, alone or with other antihypertensive agents, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular (CV) events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including the class to which this drug principally belongs. There are no controlled trials demonstrating risk reduction with Tribenzor. Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals.

The active ingredients of Tribenzor target three separate mechanisms involved in blood pressure regulation. Specifically, 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, adrenal and renal cells, and hydrochlorothiazide directly promotes the excretion of sodium and chloride in the kidney leading to reductions in intravascular volume. For a more detailed description of the mechanisms of action for each individual component, see below. Olmesartan medoxomil. Angiotensin II is formed from angiotensin I in a reaction catalyzed by ACE, kininase II.

Dose once daily. Dosage may be increased in 2-week intervals, as needed. The maximum recommended dose of Tribenzor is 40/10/25 mg. Dose selection should be individualized based on previous therapy. Dose once daily. Dosage may be increased after 2 weeks to a maximum dose of 40 /10 /25 mg once daily.

Because of the hydrochlorothiazide component, Tribenzor is contraindicated in patients with anuria, hypersensitivity to any component, or hypersensitivity to other sulfonamide-derived drugs. Do not co-administer aliskiren with Tribenzor in patients with diabetes. Anuria: Hypersensitivity to sulfonamide-derived drugs.

Boxed warning (fetal toxicity): When pregnancy is detected, discontinue Tribenzor as soon as possible. Drugs that act directly on the renin-angiotensin system (RAS) can cause injury and death to the developing fetus. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. Hypotension: Correct volume or salt depletion prior to administration. Monitor renal function and potassium in susceptible patients Increased angina or myocardial infarction with calcium channel blockers may occur upon dosage initiation or increase. Observe for signs of fluid or electrolyte imbalance. Exacerbation or activation of systemic lupus erythematosus. Acute angle-closure glaucoma. Sprue-like enteropathy has been reported. Consider discontinuation of Tribenzor in cases where no other etiology is found.

Most common adverse reactions (incidence ≥2%) are dizziness, peripheral edema, headache, fatigue, nasopharyngitis, muscle spasms, nausea, upper respiratory tract infection, diarrhea, urinary tract infection, and joint swelling.

Olmesartan medoxomil: Nonsteroidal anti-inflammatory drugs (NSAIDS): May lead to increased risk of renal impairment and loss of antihypertensive effect. Dual inhibition of the renin-angiotensin system: Increased risk of renal impairment, hypotension, and hyperkalemia. Colesevelam hydrochloride: Consider administering olmesartan at least 4 hours before colesevelam hydrochloride dose. Lithium: Increases in serum lithium concentrations and lithium toxicity. Amlodipine: Limit simvastatin to 20 mg daily when coadministered. Increased exposure to cyclosporin and tacrolimus. Increased amlodipine exposure when coadministered with CYP3A inhibitors Hydrochlorothiazide: Antidiabetic drugs: Dosage adjustment of antidiabetic may be required. Cholestyramine and colestipol: Reduced absorption of thiazides.

Store at 25ºC (77ºF), excursions permitted to 15ºC-30ºC (59ºF-86ºF).