Amstan tablets.fh1

Tablets
5 mg +80mg, 5mg+16 0mg & 10 mg +160 mg
DESCRIPTION
of amlodipine and valsartan are equivalent t o t he bioavailability of AMSTAN (Amlodipine + Valsartan) is a fixed combination of amlodipine and valsartan when administered as individual t ablets.
amlodipine and valsartan.
Amlodipine contains the besylate salt of amlodipine, a dihydropyridine c alcium-c hannel block er. Chemi cally, Amlodipine bes ylat e is described as 3-Ethyl-5- methyl (4RS)-2-[(2-aminoet hoxy) methyl] After oral administrat ion of therapeut ic doses of amlodipine alone, 4-(2-chlorophenyl)-6-methyl-1, 4-dihydropyridine-3,5-dicarboxylat e peak plasma concentrations of amlodipine are reached in 6 t o12 benzenesulphonate. The molecular formula is C hours. Abs olute bioavailability has been calc ulat ed as between 64% and 80% . Amlodipine bioavailability is unaffected by foodingest ion.
Distribut ionVolume of distribution is approximately 21 L/kg. Approximately 97.5% of circulating drug is bound to plasma proteins in hypertensive Amlodipine is extensively (approximately 90% ) met abolized in theliver to inactive met abolites.
Valsartan is a nonpeptide, orally act ive and specific angiotensin IIant agonist acting on the AT1 receptor subt ype. Its chemical name i s N-(1-ox openty l)-N-[[ 21-(1H-t etrazol-5-yl) [ 1, 11-bi phenyl] -4 Amlodipine elimination f rom plas ma is biphasic, with a terminal y l] methyl] -L-valine. The molecular formula is C24H29N5O3 and the elimination half-life of approximat ely 30 t o 50 hours. St eady-state plasma levels are reached after cont inuous administration for 7 to 8 days . 10% of the parent compound and 60% of amlodipinemet abolites are excreted in urine.
Following oral administ ration of vals artan alone, peak plas maconcentrations of valsartan are reached in 2 t o 4 hours. Meanabsolute bioavailabilit y is 23% . Food decreases exposure (as measured by AUC) to valsartan by about 40% and peak plasma concentration (Cmax) by about 50%. However, this reduction in AUC Q UALITATIVE & QUANTI TATIVE COMPOSITION
is not accompanied by a clinic ally s ignificant reduction in t he AMSTAN (Amlodipine + Valsartan) is available for oral administration t herapeutic eff ect , and vals artan can theref ore be given with or Valsart an is highly bound t o s erum prot eins (94–97%), mainly Met abolismVals artan is not metabolized to a high ex tent as only about 20% of dose is rec overed as metabolites. A hy drox yl metabolit e has been identified in plasma at low concentrat ion (less t han 10% of t he valsartan AUC). This metabolite is pharmacologically inact ive.
(as Amlodipine Besylat e BP)Valsartan USP.160mg ExcretionValsart an is primarily eliminated in feces (about 83% of dose) and urine (about 13% of dose), mainly as unchanged drug. The terminal elimination half -life is about 5 to 9 hours.
Amlodipine. .10mg(as Amlodipine Besylat e BP) Speci al population
ElderlyTime to peak plasma amlodipine concentrations is similar in young CLINICAL PHARMACOLOGY
and elderly patient s. In elderly patients, amlodipine clearance tends Mechanism of Action
t o decline, caus ing increas es in AUC and elimination half-life.
Amlodipine and Valsartan are antihypertensive compounds wit h Systemic exposure t o valsartan is slightly elevated in t he elderly complementary mechanisms t o control blood pressure in patients as compared to the y oung, but t his is of no clinical significance.
with essential hypertension. The combination of t hese substanceshas an additive antihypertensive effect, reducing blood pressure t o a greater degree than either component alone.
The pharmacokinet ics of amlodipine is not significant ly influencedby renal insuff icienc y. There is no apparent correlat ion bet ween renal function (measured by creatinine c learance) and exposure Amlodipine inhibits the transmembrane influx of calcium ions int o (measured by AUC) to valsartan in pat ient s wit h diff erent degrees cardiac and vascular smooth muscle. The ant ihypert ensive action of amlodipine is due to a direct relaxant effect on vascular smoot hmuscle, causing reductions in peripheral v ascular resistance and Pat ient s with hepatic insuf ficiency hav e decreased clearance ofamlodipine with result ing increase in AUC of approximately 40% ValsartanValsartan block s t he vasoconst rict or and aldosterone-sec reting 60% in AUC. O n average, patients administered with Valsartan for eff ec ts of angiotensin II by select ively blocking t he binding of the treatment of mild to moderate chronic liver disease, AUC valueswere found to be doubled.
angiotensin II to the AT1 receptor in many tissues, such as vasculars mooth muscle and the adrenal gland. I ts act ion is t hereforei ndependent of the pat hways f or angiotensin I I s ynthesis .
THERAPEUTI C INDI CATI ONS
AMSTAN (Amlodipine + Valsartan) is indicated for the treatment of:
Pharmacokinetics
Combinat ion of amlodipine and valsartan Pat ient s whos e blood pr ess ur e i s not adequat el y Following oral administration of amlodipine and valsartan, peak plasma concentrations of amlodipine and valsart an are reached in Pat ient s who are likely t o need multiple drugs to achieve their 3 and 6 to 8 hours, respectively. The rate and extent of absorption DOSAGE & ADMI NI STRATION
antic onvulsant agents (e. g. , carbamazepine, phenobarbit al, A patient whose blood pressure is not adequat ely control ed on pheny toin, f os phenyt oin, primidone), rifampicin, Hy pericum monotherapy may be switched to combination therapy with AMSTAN perforatum may lead t o reduc ed plasma conc ent rations of AMSTAN (Amlodipine + Valsartan) can be taken with or withoutf ood and is recommended to take it with water.
LithiumConc urrent use of ACE inhibitors with lithium c auses reversible The recommended dose of AMSTAN (Amlodipine + Valsartan) is increases in serum lithium concentrations and toxicity.
one tablet per day for the f ollowing strengths:- Concomitant use of valsart an with pot as sium s upplements , potassium sparing diuretics, salt substitutes containing pot assium, The major antihypertensive effect is attained within 2 weeks af ter or other medicinal product s that may increase pot assium levels initiation of therapy or a change in dos e. The dosage c an be (heparin, et c.) should be undertaken with f requent monit oring of increased aft er 1 to 2 weeks of therapy as needed to control blood Non-steroidal anti-inflammatory medicines (NSAIDs) Concomitant administrat ion of NSAIDs including selective COX-2 Since both components of the combination are equally well tolerated inhibit ors, acetylsalicylic acid (>3 g/day), and non-selective NSAIDs when used at similar doses in elderly or younger patients, normal wi th angiotensin I I ant agoni st s may c ause att enuat ion of antihypert ensive effect. Furt hermore, it may lead to an increasedrisk of wors ening of renal func tion and an increase in serum No init ial dosage adjustment is required f or pat ients with mild ormoderate renal and liver insuff iciency. Titrat e slowly in pat ients Commonly used antihypertensive agents (e.g., alpha blockers, ADVERSE REACTIONS
diuretics) and other medicinal products which may cause hypotensive adverse effect s (e.g., tricyclic antidepressants, alpha blockers for Headache, nasopharyngitis, influenza, edema (pitting edema, facial t reat ment of benign prost at e hyperplasia) may i ncrease t he edema, edema peripheral), fat igue, flushing, asthenia, hot flush.
antihypertensive effect of the combination.
O VERDOSAGE
Tachycardia, palpitations, dizziness, somnolence, dizziness postural, T he major s ympt om of overdos e wi th val sart an i s pos si bly paraesthesia, vert igo, cough, phary ngolaryngeal pain, diarrhoea, pronounced hypotension with dizziness. Overdose with amlodipine nausea, abdominal pain, constipation, dry mouth, rash, erythema, may result in excessive peripheral vasodilation and, possibly, reflex joint swelling, back pain, art hralgia, orthostatic hypot ension.
tachycardia. Marked and potential y prolonged systemic hypotensionup t o and including shock with fatal out come may occur.
RareSyncope, visual dist urbance, tinnitus, pollak isuria, polyuria, hyperhidrosis, exanthema, pruritus, musc le spasm, sensation of I f ingestion is recent , induction of vomit ing or gast ric lavage may heaviness, hypot ension, hypersensit ivity, erect ile dysf unct ion, be considered. Administrat ion of activated charcoal immediat ely or up to two hours aft er ingestion of amlodipine can significantly The most common reasons for discontinuation of therapy wit h decrease amlodipine absorption. Clinically significant hypotension t he combination of Amlodipine and Valsartan are peripheral edema due to the combination of Amlodipine and Valsartan overdose calls f or active cardiovascular support, including frequent monitoring ofcardiac and respiratory func tion, elevation of extremities, and CONTRAINDI CATIONS
attention to circulating fluid volume and urine output. A vasoconstrictor The combination of Amlodipine and Valsart an is contraindicated; may be helpful in res toring v ascular t one and blood pres sure, In patients who are hypersensitive to any component s of t his provided that there is no contraindication to its use. I nt ravenous calcium gluconate may be beneficial in reversing the effects of I n pat ient s wit h sev ere hepat ic i nsuf f ici ency, bili ary calcium c hannel blockade. Bot h valsart an and amlodipine are cirrhosis, or c holestatis and s evere renal insufficiency (GFR unlikely to be removed by haemodialysis.
STO RAGE
Store at 25oC (Excursions permitt ed between 15oC to 30o C).
The combinat ion of amlodipine and valsartan is contraindicated in The expirat ion dat e refers t o the product correctly stored at the s econd and third trimesters of pregnancy. When pregnancy is det ected it should be discontinued as soon as possible becaus eit c an c ause injury and even death to t he developing f et us.
HOW SUPPLIED
AMSTAN (Amlodipine + Valsartan) Tablets 5mg+ 80mg are available
The combination of amlodipine and valsartan is not recommended AMSTAN (Amlodipine + Valsart an) Tablet s 5mg+ 160mg are during breast feeding and alt ernativ e treatment s with bett er available in blist er pack of 14’s.
established safety prof iles during breast -f eeding are preferable.
AMSTAN (Amlodipine + Valsart an) Tablet s 10mg+ 160mg are PRECAUTIO NS
available in blist er pack of 14’s.
In pat ient s with an act iv at ed reni n- angiot ens in sys tem(such as volume- and/or salt-deplet ed patients receiv ing high Keep out of reach of chil dren.
doses of diuretics) who are rec eiving angiotensin recept orblockers, sympt omat ic hypotension may occur. Correct ion of To be sold on prescription of a registered medical pr actitioner
this condit ion prior to administration of the combinat ion of only.
amlodipine and valsart an or close medical supervision at the Plea se re ad the c onte nts carefully be fore use .
This pa cka ge ins ert is continua l y update d from time to time .
Particular caution should be exercised when administering thecombinat ion of amlodipine and valsartan t o patients with mildto moderate hepat ic impairment or biliary obstructive disorders.
In case of moderate renal impairment , monitoring of potassiumlevels and creat inine is advised.
The combinat ion of am lodipine and vals art an s houl dbe used with caution in patients with severe heart f ailure.
As with all other vasodilators, special caut ion is indicat ed inpatients suffering from aortic or mit ral stenosis, or obstruct iv ehypertrophic cardiomyopathy.
Drug I nteractions
CYP3A4 inhibitorsCo-administration of amlodipine with CYP3A4 inhibitors like diltiazem inhibits the metabolism of amlodipine, thereby increasing the plasma concent ration of amlodipine by approximately 50% and the effectis also increased. The more pot ent inhibitors of CYP3A4 (i.e.
k etoconazole, itrac onazole, ritonavir) may increase t he plasmac oncentration of amlodipine t o a great er ext ent than dilt iazem.
Co-adminis tration of amlodipine wit h CYP3A4 induc ers lik e

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