Each Telmisartan 40 mg tablet contains: Telmisartan USP 40 mg.
Each Telmisartan 80 mg tablet contains: Telmisartan USP 80 mg.
Telmisartan tablets is a non-peptide angiotensin II receptor (type At1) antagonist.
Telmisartan is chemically described as 4'-[(1,4'-dimethyl-2'-propyl [2,6'-bi-1H-benzimidazol]-1'-yl)methyl]-[1,1'-biphenyl]-2-carboxylic acid. Its empirical formula is C33H30N4O2, its molecular weight is 514.63.
Telmisartan is a white or slightly yellowish crystalline powder. It is practically insoluble in water; slightly soluble in methyl alcohol; sparingly soluble in dichloromethane. It dissolves in 1M sodium hydroxide. It exhibits polymorphism.
MISTEL tablets are available for oral administration, containing 40 or 80 mg of Telmisartan.
Excipients/Inactive Ingredients: The tablets contain the following inactive ingredients: calcium phosphate, maize starch, croscarmellose sodium, colloidal anhydrous silica, povidone K30, purified talc, magnesium stearate and sodium starch glycolate.
Pharmacology: Mechanism of Action: 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 synthesis.
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.
Blockade of the renin-angiotensin system with ACE inhibitors, which inhibit the biosynthesis of angiotensin II from angiotensin I, is widely used in the treatment of hypertension. ACE inhibitors also inhibit the degradation of bradykinin, a reaction also catalyzed by ACE. Because telmisartan does not inhibit ACE (kininase II), it does not affect the response to bradykinin. Whether this difference has clinical relevance is not yet 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 blood pressure.
Pharmacodynamics: In normal volunteers, a dose of Telmisartan 80 mg inhibited the pressor response to an intravenous infusion of angiotensin II by about 90% at peak plasma concentrations with approximately 40% inhibition persisting for 24 hours.
Plasma concentration of angiotensin II and plasma renin activity (PRA) increased in a dose-dependent manner after single administration of Telmisartan to healthy subjects and repeated administration to hypertensive patients. The once-daily administration of up to 80 mg Telmisartan to healthy subjects did not influence plasma aldosterone concentrations. In multiple dose studies with hypertensive patients, there were no clinically significant changes in electrolytes (serum potassium or sodium), or in metabolic function (including serum levels of cholesterol, triglycerides, HDL, LDL, glucose, or uric acid).
In 30 hypertensive patients with normal renal function treated for 8 weeks with Telmisartan 80 mg or Telmisartan 80 mg in combination with hydrochlorothiazide 12.5 mg, there were no clinically significant changes from baseline in renal blood flow, glomerular filtration rate, filtration fraction, renovascular resistance, or creatinine clearance.
Pharmacokinetics: Telmisartan is rapidly absorbed from the gastrointestinal tract; the absolute oral bioavailability is dose-dependent and is about 42% after a 40-mg dose and 58% after a 160-mg dose. Peak plasma concentrations of Telmisartan are reached about 0.5 to 1 hour after an oral dose. Telmisartan is over 99% bound to plasma proteins. It is excreted almost entirely in the faeces via bile, mainly as unchanged drug. The terminal elimination half-life of Telmisartan is about 24 hours.
Used in the management of hypertension.
Telmisartan is given orally. After a dose the hypotensive effect peaks within 3 hours and persists for at least 24 hours. The maximum hypotensive effect occurs within about 4 to 8 weeks after starting therapy.
In hypertension, Telmisartan is given in an initial dose of 40 mg once daily. Lower doses should be considered in patients with hepatic or renal impairment.
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.
Contraindicated in patients who are hypersensitive to any component of this product.
General: 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. Telmisartan (MISTEL) tablets should be used with caution in these patients.
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 MISTEL 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 Telmisartan tablets in patients with unilateral or bilateral renal artery stenosis but an effect similar to that seen with ACE inhibitors should be anticipated.
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 function.
Concomitant use of Telmisartan and Ramipril is not recommended.
Use in Children: Safety and effectiveness in pediatric patients have not been established.
Use in the Elderly: Of the total number of Patients receiving Telmisartan tablets in clinical studies, 551 (18.6%) were 65 to 74 years of age and 130 (4.4%) were 75 years or older. No overall differences in effectiveness and safety were observed in these patients compared to younger patients and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
Nursing Mothers: It is not known whether Telmisartan is excreted in human milk, but Telmisartan was shown to be present in the milk of lactating rats. 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.
Telmisartan have been evaluated for safety in more than 3700 patients, including 1900 treated for over six months and more than 1300 for over one year. Adverse experiences have generally been mild and transient in nature and have only infrequently required discontinuation of therapy.
In placebo-controlled trials involving 1041 patients treated with various doses of Telmisartan (20-160 mg) monotherapy for up to 12 weeks, an overall incidence of adverse events similar to that of placebo was observed.
Adverse events occurring at an incidence of 1% or more in patients treated with Telmisartan and at a greater rate than in patients treated with placebo, irrespective of their causal association, are presented in the following table. (See table.)
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In addition to the adverse events in the table, the following events occurred at rate of 1% but were at least as frequent in the placebo group: influenza-like symptoms, dyspepsia, myalgia, urinary tract infection, abdominal pain, headache, dizziness, pain, fatigue, coughing, hypertension, chest pain, nausea and peripheral edema. Discontinuation of therapy due to adverse events was required in 2.8% of 1455 patients treated with Telmisartan and 6.1% of 380 placebo patients in placebo-controlled clinical trials. The incidence of adverse events was not dose-related and did not correlate with gender, age, or race of patients. The incidence of cough occurring with Telmisartan in six placebo-controlled trials was identical to that noted for placebo-treated patients (1.6%).
Digoxin: When Telmisartan was co-administered with digoxin, median increases in digoxin peak plasma concentration (49%) and in trough concentration (20%) were observed. It is, therefore, recommended that digoxin levels be monitored when initiating, adjusting, and discontinuing Telmisartan to avoid possible over- or under-digitalization.
Lithium: Reversible increases in serum lithium concentrations and toxicity have been reported during concomitant administration of lithium with angiotensin converting enzyme inhibitors. Cases have also been reported with angiotensin II receptor antagonists including Telmisartan tablets. Therefore, serum lithium level monitoring is advisable during concomitant use.
Ramipril and Ramiprilat: Co-administration of Telmisartan 80 mg once daily and Ramipril 10 mg once daily to healthy subjects increases steady-state Cmax and AUC of Ramipril 2.3 and 2.1 fold, respectively, and Cmax and AUC of Ramiprilat 2.4 and 1.5 fold, respectively. In contrast, Cmax and AUC of Telmisartan decrease by 31% and 16%, respectively. When co-administering Telmisartan and Ramipril, 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.
Warfarin: Telmisartan administered for 10 days slightly decreased the mean warfarin trough plasma concentrations; this decrease did not result in a change in International Normalized Ratio (INR).
Other Drugs: Co-administration of Telmisartan did not result in a clinically significant interaction with acetaminophen, amlodipine, glibenclamide, simvastatin, hydrochlorothiazide or ibuprofen. Telmisartan is not metabolized by the cytochrome P450 system and had no effects in vitro on cytochrome P450 enzymes, except for some inhibition of CYP2C19. Telmisartan is not expected to interact with drugs that inhibit cytochrome P450 enzymes; it is also not expected to interact with drugs metabolized by cytochrome P450 enzymes, except for possible inhibition of the metabolism of drugs metabolized by CYP2C19.
Store at temperatures not exceeding 30°C.
C09CA07 - telmisartan ; Belongs to the class of angiotensin II receptor blockers (ARBs). Used in the treatment of cardiovascular disease.
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