Hydrochlorothiazide and Valsartan

Diovan HCT (valsartan and hydrochlorothiazide, USP) is indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular 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 hydrochlorothiazide and the angiotensin II receptor blocker (ARB) class to which valsartan principally belongs. There are no controlled trials demonstrating risk reduction with Diovan HCT. 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 1 drug to achieve blood pressure goals.

Angiotensin II is formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme (ACE, kininase II). Angiotensin II is the principal pressor agent of the renin-angiotensin system, with effects that include vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation, and renal reabsorption of sodium. Valsartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT 1 receptor in many tissues, such as vascular smooth muscle and the adrenal gland. Its action is therefore independent of the pathways for angiotensin II synthesis. There is also an AT 2 receptor found in many tissues, but AT 2 is not known to be associated with cardiovascular homeostasis. Valsartan has much greater affinity (about 20,000-fold) for the AT 1 receptor than for the AT 2 receptor.

Dose once daily. Titrate as needed to a maximum dose of 320/25mg. May be used as add-on/switch therapy for patients not adequately controlled on any of the components (valsartan or HCTZ). May be substituted for titrated components.

Diovan HCT (valsartan and hydrochlorothiazide, USP) is contraindicated in patients who are hypersensitive to any component of this product. Because of the hydrochlorothiazide component, this product is contraindicated in patients with anuria or hypersensitivity to other sulfonamide-derived drugs. Do not coadminister aliskiren with Diovan HCT in patients with diabetes. Anuria, Hypersensitivity to any sulfonamide-derived drugs or any component, Do not coadminister aliskiren with Diovan HCT in patients with diabetes.

Boxed warning (fetal toxicity): When pregnancy is detected, discontinue Diovan HCT as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. Hypotension: Correct volume depletion prior to initiation. Observe for signs of fluid or electrolyte imbalance. Monitor renal function and potassium in susceptible patients. Exacerbation or activation of systemic lupus erythematosus. Acute angle-closure glaucoma

The most common reasons for discontinuation of therapy with Diovan HCT were headache and dizziness. The only adverse experience that occurred in ≥ 2% of patients treated with Diovan HCT and at a higher incidence than placebo was nasopharyngitis (2.4% vs. 1.9%).

Valsartan-Hydrochlorothiazide: Lithium: Increases in serum lithium concentrations and lithium toxicity have been reported during concomitant administration of lithium with angiotensin II receptor antagonists or thiazides. Monitor lithium levels in patients taking Diovan HCT. Valsartan: Agents Increasing Serum Potassium: Concomitant use of valsartan with other agents that block the renin-angiotensin system, potassium-sparing diuretics (e.g., spironolactone, triamterene, amiloride), potassium supplements, salt substitutes containing potassium or other drugs that may increase potassium levels (e.g., heparin) may lead to increases in serum potassium and in heart failure patients to increases in serum creatinine. If co-medication is considered necessary, monitoring of serum potassium is advisable.

Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (59°F and 86°F). Protect from moisture.