EXFORGE- amlodipine besylate and valsartan tablet, film coated
Novartis Pharmaceuticals Corporation
WARNING: FETAL TOXICITY
When pregnancy is detected, discontinue Exforge as soon as possible.
Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus.
Exforge is fixed combination of amlodipine and valsartan.
Exforge contains the besylate salt of amlodipine, dihydropyridine calcium-channel blocker (CCB). Amlodipine besylate is white to pale yellow crystalline powder, slightly soluble in water and sparingly soluble in ethanol. Amlodipine besylate?s chemical name is 3-Ethyl-5-methyl(4RS)-2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate benzenesulphonate.
Valsartan is nonpeptide, orally active, and specific angiotensin II antagonist acting on the AT1 receptor subtype. Valsartan is white to practically white fine powder, soluble in ethanol and methanol and slightly soluble in water. Valsartan?s chemical name is N-(1-oxopentyl)-N-[[2?-(1H-tetrazol-5-yl) [1,1?-biphenyl]-4-yl]methyl]-L-valine
Mechanism of Action
Amlodipine is dihydropyridine calcium channel blocker that inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle. Experimental data suggest that amlodipine binds to both dihydropyridine and nondihydropyridine binding sites. The contractile processes of cardiac muscle and vascular smooth muscle are dependent upon the movement of extracellular calcium ions into these cells through specific ion channels. Amlodipine inhibits calcium ion influx across cell membranes selectively, with greater effect on vascular smooth muscle cells than on cardiac muscle cells. Negative inotropic effects can be detected in vitro but such effects have not been seen in intact animals at therapeutic doses. Serum calcium concentration is not affected by amlodipine. Within the physiologic pH range, amlodipine is an ionized compound (pKa=8.6), and its kinetic interaction with the calcium channel receptor is characterized by gradual rate of association and dissociation with the receptor binding site, resulting in gradual onset of effect.
Angiotensin II is formed from angiotensin in 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 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.
1 INDICATIONS AND USAGE
Figure 1: Probability of Achieving Systolic Blood Pressure <140 mmHg at Week 8Figure 2: Probability of Achieving Diastolic Blood Pressure <90 mmHg at Week 8Figure 3: Probability of Achieving Systolic Blood Pressure <130 mmHg at Week 8Figure 4: Probability of Achieving Diastolic Blood Pressure <80 mmHg at Week 8
Exforge (amlodipine and valsartan) 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 wide variety of pharmacologic classes, including amlodipine and the ARB class to which valsartan principally belongs. There are no controlled trials demonstrating risk reduction with Exforge.
DOSAGE AND ADMINISTRATION
2.1 General Considerations
Dose once daily. The dosage can be increased after to weeks of therapy to maximum of one 10/320 mg tablet once daily as needed to control blood pressure. The majority of the antihypertensive effect is attained within weeks after initiation of therapy or change in dose.
Exforge may be administered with or without food.
Exforge may be administered with other antihypertensive agents.
3 DOSAGE FORMS AND STRENGTHS
5/160 mg tablets, debossed with NVR/ECE (side 1/side 2)
10/160 mg tablets, debossed with NVR/UIC
5/320 mg tablets, debossed with NVR/CSF
10/320 mg tablets, debossed with NVR/LUF
Pregnancy Category D