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TELMITRUST TABLETS
Telmisartan

COMPOSITION

PHARMACOLOGY
Pharmacodynamics
Telmisartan is a non-peptide Angiotensin II receptor (type AT1) antagonist. 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. Telmisartan 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 There is also an AT2 receptor found in many tissues, but AT2 is not known to be associated with cardiovascular homeostasis. Telmisartan has much greater affinity (>3,000 fold) for the AT1 receptor than for the AT2 receptor. Ace inhibitors block the renin-angiotensin system, thus inhibiting the biosynthesis of angiotensin II from angiotensin I. ACE inhibitors also inhibit the degradation of bradykinin. Because telmisartan does not inhibit ACE, it does not affect the response to bradykinin. Whether this difference has clinical relevance is not known. Telmisartan does not bind to or block other hormone receptors or ion channels known to be important in cardiovascular regulation. Blockade of the angiotensin II receptor inhibits the negative regulatory feedback of angiotensin II on renin secretion, but the resulting increased plasma renin activity and angiotensin II circulating levels do not overcome the effect of telmisartan on
Pharmacokinetics
Following oral administration, peak concentrations (Cmax) of telmisartan are reached in 0.5-1 hour. Food slightly reduces the bioavailability of telmisartan, with a reduction in the area under the plasma concentration-time curve (AUC) of about The absolute bioavailability of telmisartan is dose dependent. At 40 mg the bioavailability is approximately 42%. The pharmacokinetics of orally administered telmisartan are nonlinear over the dose range 20-160 mg, with greater than proportional increases of plasma concentrations (Cmax and AUC) with increasing doses. Telmisartan has a terminal elimination half life of approximately 24 hours. Trough plasma concentrations of telmisartan with once daily dosing are about 10- Metabolism & Elimination
Following oral administration, most of the administered dose (>97%) of telmisartan is eliminated unchanged in feces via biliary excretion; only minute amounts are Telmisartan is metabolized by conjugation to form a pharmacologically inactive acylglucuronide which is the only metabolite that has been identified in human plasma and urine. The cytochrome P450 isoenzymes are not involved in the Distribution
Telmisartan is highly bound to plasma proteins (>99.5%), mainly albumin and α1 - acid glycoprotein. The volume of distribution for telmisartan is approximately 500 liters indicating additional tissue binding.
INDICATION
Hypertension
TELMITRUST is indicated for the treatment of hypertension. It may be used alone
or in combination with other antihypertensive agents. Cardiovascular Risk Reduction
TELMITRUST is indicated for reduction of the risk of myocardial infarction, stroke,
or death from cardiovascular causes in patients 55 years of age or older at high risk of developing major cardiovascular events and who are unable to take ACE High risk for cardiovascular events can be evidenced by a history of coronary artery disease, peripheral arterial disease, stroke, transient ischemic attack, or high-risk diabetes (insulin-dependent or non-insulin dependent) with evidence of end-organ damage. TELMITRUST can be used in addition to other needed treatment (such as
antihypertensive, antiplatelet or lipid-lowering therapy).
DOSAGE & ADMINISTRATION
• Hypertension
Dosage must be individualized. The usual starting dose is TELMITRUST-20mg /
40mg once a day. Blood pressure response is dose-related over the range of 20-80
mg. Most of the antihypertensive effect is apparent within two weeks and maximal reduction is generally attained after four weeks. When additional blood pressure reduction beyond that achieved with 80 mg telmisartan is required, a diuretic may No initial dosing adjustment is necessary for elderly patients or patients with renal impairment, including those on hemodialysis. Patients on dialysis may develop orthostatic hypotension; their blood pressure should be closely monitored. TELMITRUST may be administered with other antihypertensive agents.
TELMITRUST may be administered with or without food.
• Cardiovascular Risk Reduction
The recommended dose of TELMITRUST is 80 mg once a day and can be
administered with or without food. It is not known whether doses lower than 80 mg of telmisartan are effective in reducing the risk of cardiovascular morbidity and mortality. When initiating TELMITRUST therapy for cardiovascular risk reduction,
monitoring of blood pressure is recommended, and adjustment of medications that
CONTRAINDICATION
TELMITRUST is contraindicated in patients who are hypersensitive to any

WARNINGS
Fetal/Neonatal Morbidity & Mortality
Drugs that act directly on the renin-angiotensin system can cause fetal and neonatal morbidity and death when administered to pregnant women. When pregnancy is detected, TELMITRUST (telmisartan) tablets should be discontinued
The use of drugs that act directly on the renin-angiotensin system during the second and third trimesters of pregnancy has been associated with fetal and neonatal injury, including hypotension, neonatal skull hypoplasia, anuria, reversible or irreversible renal failure, and death. Oligohydramnios has also been reported, presumably resulting from decreased fetal renal function; oligohydramnios in this setting has been associated with fetal limb contractures, craniofacial deformation, and hypoplastic lung development. Patients and physicians should be aware, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. These adverse effects do not appear to have resulted from intrauterine drug exposure that has been limited to the first trimester. Mothers whose embryos and fetuses are exposed to an angiotensin II receptor antagonist during the first trimester should be so informed that most reports of fetal toxicity have been associated with second and third trimester exposure. Nonetheless, when patients become pregnant, physicians should have the patient discontinue the use of TELMITRUST tablets as soon as possible.

Hypotension in Volume-Depleted Patients
In patients with an activated renin-angiotensin system, such as volume- and/or salt-depleted patients (e.g., those being treated with high doses of diuretics), symptomatic hypotension may occur after initiation of therapy with TELMITRUST
tablets. This condition should be corrected prior to administration of TELMITRUST
tablets, or treatment should start under close medical supervision with a reduced If hypotension does occur, the patient should be placed in the supine position and, if necessary, given an intravenous infusion of normal saline. A transient hypotensive response is not a contraindication to further treatment, which usually can be continued without difficulty once the blood pressure has stabilized.
Hyperkalemia
Hyperkalemia may occur in patients on ARBs, particularly in patients with advanced renal impairment, heart failure, on renal replacement therapy, or on potassium supplements, potassium-sparing diuretics, potassium-containing salt substitutes or other drugs that increase potassium levels. Consider periodic determinations of serum electrolytes to detect possible electrolyte imbalances,
Dual Blockade of the Renin-Angiotensin-Aldosterone System
As a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function (including acute renal failure) have been reported. Dual blockade of the renin-angiotensin-aldosterone system (e.g., by adding an ACE-inhibitor to an angiotensin II receptor antagonist) should include close monitoring of renal
PRECAUTIONS
Impaired Hepatic Function: As the majority of telmisartan is eliminated by biliary
excretion, patients with biliary obstructive disorders or hepatic insufficiency can be expected to have reduced clearance. Initiate TELMITRUST at low doses and titrate

Impaired Renal Function: As a consequence of inhibiting the renin-angiotensin-
aldosterone system, changes in renal function may be anticipated in susceptible individuals. In patients whose renal function may depend on the activity of the renin-angiotensin-aldosterone system (e.g., patients with severe congestive heart failure), treatment with angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists has been associated with oliguria and/or progressive azotemia and (rarely) with acute renal failure and/or death. Similar results may be anticipated in patients treated with TELMITRUST tablets.
In studies of ACE inhibitors in patients with unilateral or bilateral renal artery stenosis, increases in serum creatinine or blood urea nitrogen were observed. There has been no long term use of TELMITRUST tablets in patients with unilateral or
bilateral renal artery stenosis but an effect similar to that seen with ACE inhibitors
Pregnancy
Pregnancy Categories C (first trimester) and D (second & third trimesters)
See WARNINGS, Fetal/Neonatal Morbidity & Mortality.

Lactation
It is not known whether telmisartan is 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
Pediatric use
Safety and effectiveness in pediatric patients have not been established.
Geriatric Use
No overall differences in effectiveness and safety were observed in clinical studies, as compared to younger patients, but greater sensitivity of some older individuals
DRUG INTERACTIONS
Digoxin: Digoxin levels should be monitored when initiating, adjusting, and
discontinuing telmisartan to avoid possible over- or under-digitalization, as coadministration of telmisartan and digoxin increases the plasma levels of digoxin. Lithium: Reversible increases in serum lithium concentrations and toxicity have
been reported during concomitant administration of lithium with angiotensin II receptor antagonists including telmisartan. Therefore, monitor serum lithium levels Ramipril and Ramiprilat: When telmisartan and ramipril are coadministered, the
response may be greater because of the possibly additive pharmacodynamic effects of the combined drugs, and also because of the increased exposure to ramipril and ramiprilat in the presence of telmisartan. Concomitant use of telmisartan and Other Drugs: Co-administration of telmisartan does not result in a clinically
significant interaction with acetaminophen, amlodipine, glyburide, simvastatin, hydrochlorothiazide, warfarin or ibuprofen. Telmisartan is not metabolized by the UNDESIRABLE EFECTS
Telmisartan is usually well tolerated. The side effects have been mild and transient in nature and have only infrequently required discontinuation of therapy. The commonly observed side effects are back pain, sinusitis, diarrhea, pharyngitis, headache, dizziness, pain, fatigue, nausea, intermittent claudication and skin
OVERDOSAGE
Limited data are available with regard to overdosage in humans. The most likely manifestation of overdosage with telmisartan would be hypotension, dizziness and tachycardia; bradycardia could occur from parasympathetic (vagal) stimulation. If symptomatic hypotension should occur, supportive treatment should be instituted. Telmisartan is not removed by hemodialysis.
PRESENTATION
TELMITRUST 20mg/ 40mg Tablets are available in strips of 10

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