Amlodipine + Valsartan

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

Combined antihypertensive preparations

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 have 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.

• Amlodipine is an effective treatment of hypertension in once daily doses of 2.5 mg-10 mg while Valsartan is effective in doses of 80 mg-320 mg. In clinical trials with Amlodipine and Valsartan combination using Amlodipine doses of 5 mg-10 mg and Valsartan doses of 160 mg-320 mg, the antihypertensive effects increased with increasing doses.

No drug interaction studies have been conducted with Amlodipine and Valsartan combination, although studies have been conducted with the individual components.

• Amlodipine and Valsartan combination is contraindicated in patients who are hypersensitive to any compounds of this product.Dose should be titrated slowly in patients with impaired hepatic or severely impaired renal function. In general, calcium channel blockers should be used with caution in patients with heart failure.

• The most common side effects include peripheral edema, vertigo, nasopharyngitis, upper respiratory tract infection and dizziness.

• Pregnancy: Amlodipine and Valsartan combination should not be used in 2nd and 3rd trimester because it can cause fetal death .
• Nursing Mothers: It is not known whether Valsartan and Amlodipine are excreted in human milk. Because of the potential for adverse effects on the nursing infant, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Information on Amlodipine: Single oral doses of amlodipine maleate equivalent to 40 mg/kg and 100 mg/kg amlodipine in mice and rats, respectively, caused deaths. Single oral doses equivalent to 4 or more mg/kg amlodipine in dogs (11 or more times the maximum recommended human dose on a mg/m2 basis) caused a marked peripheral vasodilation and hypotension. Overdosage might be expected to cause excessive peripheral vasodilation with marked hypotension. In humans, experience with intentional overdosage of amlodipine is limited. Marked and potentially prolonged systemic hypotension up to and including shock with fatal outcome have been reported. If massive overdose should occur, initiate active cardiac and respiratory monitoring should be instituted. Frequent blood pressure measurements are essential. Should hypotension occur, cardiovascular support including elevation of the extremities and the judicious administration of fluids should be initiated. If hypotension remains unresponsive to these conservative measures, administration of vasopressors (such as phenylephrine with attention to circulating volume and urine output As amlodipine is highly protein bound, hemodialysis is not likely to be of benefit. Administration of activated charcoal to healthy volunteers immediately or up to two hours after ingestion of amlodipine has been shown to significantly decrease amlodipine absorption. Information on Valsartan Limited data are available related to overdosage in humans. The most likely effect of overdose with valsartan would be peripheral vasodilation, hypotension and tachycardia; bradycardia could occur from parasympathetic (vagal) stimulation. Depressed level of consciousness, circulatory collapse, and shock have been reported. If symptomatic hypotension should occur, supportive treatment should be instituted. Valsartan is not removed from the plasma by hemodialysis. Valsartan was without grossly observable adverse effects at single oral doses up to 2000 mg/kg in rats and up to 1000 mg/kg in marmosets, except for the salivation and diarrhea in the rat and vomiting in the marmoset at the highest dose (60 and 37 times, respectively, the maximum recommended human dose on a mg/m2 basis). (Calculations assume an oral dose of 320 mg/day and a 60-kg patient.)

Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.

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