Composition

Valvas HCT 10/160/12.5 mg Tablet: Each tablet contains 13.86 mg Amlodipine Besilate BP equivalent to 10 mg Amlodipine, 160 mg Valsartan USP & 12.5 mg Hydrochlorothiazide BP.

Valvas HCT 10/160/25 mg Tablet: Each tablet contains 13.86 mg Amlodipine Besilate BP equivalent to 10 mg Amlodipine, 160 mg Valsartan USP & 25 mg Hydrochlorothiazide BP.

Clinical Pharmacology

The 3 components Amlodipine, Valsartan, Hydrochlorothiazide lower the blood pressure through complementary mechanisms, each working at a separate site and blocking different effect or pathways.

Amlodipine is a dihydropyridine calcium channel blocker that inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle. Valsartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 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. Amlodipine and Valsartan has been shown to be effective in lowering blood pressure. Both Amlodipine and Valsartan lower blood pressure by reducing peripheral resistance, but calcium influx blockade and reduction of angiotensin II vasoconstriction are complementary mechanisms.

Hydrochlorothiazide is a thiazide diuretic. Thiazides affect the renal tubular mechanisms of electrolyte reabsorption, directly increasing excretion of sodium and chloride in approximately equivalent amounts. Indirectly, the diuretic action of hydrochlorothiazide reduces plasma volume, with consequent increases in plasma renin activity, increases in aldosterone secretion, increases in urinary potassium loss, and decreases in serum potassium. The renin-aldosterone link is mediated by angiotensin II, so coadministration of an angiotensin II receptor antagonist tends to reverse the potassium loss associated with these diuretics.

 

Indications

Amlodipine, Valsartan and Hydrochlorothiazide combination is indicated for the treatment of hypertension. This fixed combination drug is not indicated for the initial therapy of hypertension

 

Dosage and Administrations

General Considerations: Dose is once-daily. The dosage may be increased after 2 weeks of therapy. The full blood pressure lowering effect was achieved 2 weeks after being on the maximal dose of combination of Amlodipine, Valsartan & Hydrochlorothiazide. The maximum recommended dose of combination of Amlodipine, Valsartan & Hydrochlorothiazide is 10/320/25 mg. Add-on I Switch Therapy: Combination of Amlodipine, Valsartan & Hydrochlorothiazide may be used for patients not adequately controlled on any 2 of the following antihypertensive classes: calcium channel blockers, angiotensin receptor blockers, and diuretics. A patient who

experiences dose-limiting-adverse reactions to an individual component while on any dual combination of the components of Combination of Amlodipine, Valsartan r

Hydrochlorothiazide may be switched to Combination of Amlodipine, Valsartan & Hydrochlorothiazide containing a lower dose of that component to achieve similar blood pressure reductions.

Replacement Therapy: Combination of Amlodipine, Valsartan & Hydrochlorothiazide may be substituted for the individually titrated components.

Use with Other Antihypertensive Drugs: Combination of Amlodipine, Valsartan & Hydrochlorothiazide may be administered with other antihypertensive agents.

 

Side Effects

Combination of Amlodipine, Valsartan & Hydrochlorothiazide can cause side effects to

Sodium and/or volume-depleted patients, Patients with unilateral or bilateral renal artery stenosis or stenosis to a solitary kidney since blood urea and serum creatinine

and electrolyte may increase, Angioedema.

Thiazide diuretics, including hydrochlorothiazide, may alter glucose tolerance and raise

serum levels of cholesterol, triglyceride des and uric acid. In diabetic patients’ dosage adjustments of insulin or oral hypoglycemic i agents i may be required. Thiazides reduce

urinary calcium excretion and may cause intermittent and slight elevation of serum calcium in the absence of known disorders of calcium metabolism. Photosensitivity: Cases of photosensitivity reactions have been reported with thiazide diuretics. Acute angle-closure glaucoma: Hydrochlorothiazide, a sulphonamide, has been associated with an idiosyncratic reaction resulting in acute transient myopia and acute angle-closure glaucoma.

 

Contraindications

Renal impairment: Due to the hydrochlorothiazide component, Combination of Amlodipine, Valsartan & Hydrochlorothiazide is contraindicated for use in patients with

anuria or diabetes mellitus with severe renal impairment {glomerular filtration rate {GFR) <30 ml/min/1. 73 m2). Due to the valsartan component, combination of

Amlodipine, Valsartan & Hydrochlorothiazide is contraindicated in patients with severe hepatic impairment, biliary cirrhosis or cholestasis. Due to the hydrochlorothiazide

component, combination is contraindicated in symptomatic hyperuricemia.

Heart failure and coronary artery disease: There is limited experience with the use of

Combination of Amlodipine, Valsartan & Hydrochlorothiazide, particularly at the maximum dose, in patients with heart failure and coronary artery disease. Severe hypotension. Hemodynamically unstable heart failure after acute myocardial infarction. Shock {including cardiogenic shock). Obstruction of the outflow tract of the left ventricle (e.g. hypertrophic obstructive cardiomyopathy and high-grade aortic stenosis).

Hypersensitivity to the active substances, to other sulphonamide derivatives, to dihydropyridine derivatives, or to any of the excipients.

Second and third trimesters of pregnancy, Refractory hypokalemia, hyponatremia, hypercalcemia, and symptomatic hyperuricemia.

Elderly {age 65 years or over): Caution, including more frequent monitoring of blood pressure, is recommended in elderly patients, particularly at the maximum dose.