Telmefixx

Each uncoated tablet contains: Telmisartan 40 mg.
White to off white, oblong, biconvex, break line on one side and other side plain uncoated tablet.

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 vasoconstriction 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: Following oral administration, peak concentrations (C_max) of Telmisartan are reached in 0.5-1 hour after dosing. Food slightly reduces the bioavailability of Telmisartan, with a reduction in the area under the plasma concentration-time curve (AUC) of about 6% with the 80 mg tablet and about 20% after a 160 mg dose. The absolute bioavailability of Telmisartan is dose dependent. At 40 and 160 mg, the bioavailability was 42% and 58%, respectively. The pharmacokinetics of orally administered Telmisartan is nonlinear over the dose range 20-160 mg, with greater than proportional increases of plasma concentrations (C_max and AUC) with increasing doses.
Telmisartan shows bi-exponential decay kinetics with a terminal elimination half-life of approximately 24 hours. Trough plasma concentrations of Telmisartan with once daily dosing are about 10-25% of peak plasma concentrations. Telmisartan has an accumulation index in plasma of 1.5 to 2.0 upon repeated once daily dosing.
Metabolism and Elimination: Following either intravenous or oral administration of ¹⁴C-labeled telmisartan, most of the administered dose (>97%) was eliminated unchanged in feces via biliary excretion; only minute amounts were found in the urine (0.91% and 0.49% of total radioactivity, respectively). Telmisartan is metabolized by conjugation to form a pharmacologically inactive acyglucuronide; the glucuronide of the parent compound is the only metabolite that has been identified in human plasma and urine. After a single dose, the glucuronide represents approximately 11% of the measured radioactivity in plasma. The cytochrome P450 isoenzymes are not involved in the metabolism of Telmisartan. Total plasma clearance of telmisartan is >800 mL/min. Terminal half-life and total clearance appear to be independent of dose.
Distribution: Telmisartan is highly bound to plasma proteins (>99.5%), mainly albumin and α₁-acid glycoprotein. Plasma protein binding is constant over the concentration range achieved with recommended doses. The volume of distribution for Telmisartan is approximately 500 liters indicating additional tissue binding.

It is indicated for the treatment of hypertension. It may be used alone or in combination with other antihypertensive agents.

Dosage must be individualized. The usual starting dose of Telmisartan tablets is 40 mg once a day. Blood pressure response is dose-related over the range of 20-80 mg, or as prescribed by the physician.

Limited data are available with regard to overdosage in humans. The most likely manifestation of overdosage with Telmisartan tablets 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.

It is contraindicated in patients who are hypersensitive to any component of this product.

Impaired Hepatic Function: As majority of Telmisartan is eliminated by biliary excretion, patients with biliary obstructive disorders or hepatic insufficiency can be expected to have reduced clearance. Telmisartan 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 Telmisartan 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.
Effects on Ability to Drive and Use Machines: When driving vehicles or operating machinery it should be taken into account that dizziness or drowsiness may occasionally occur when taking antihypertensive therapy such as Telmisartan.

Pregnancy: The use of angiotensin II receptor antagonists is not recommended during the first trimester of pregnancy. The use of angiotensin II receptor antagonists is contraindicated during the second and third trimesters of pregnancy.
There are no adequate data from the use of Telmisartan in pregnant women. Studies in animals have shown reproductive toxicity. Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE inhibitors during the first trimester of pregnancy has not been conclusive; however a small increase in risk cannot be excluded. While there is no controlled epidemiological data on the risk with angiotensin II receptor antagonists, similar risks may exist for this class of drugs. Unless continued angiotensin II receptor antagonist therapy is considered essential, patients planning pregnancy should be changed to alternative antihypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with angiotensin II receptor antagonists should be stopped immediately, and, if appropriate, alternative therapy should be started. Exposure to angiotensin II receptor antagonist therapy during the second and third trimesters is known to induce human fetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalaemia). Should exposure to angiotensin II receptor antagonists have occurred from the second trimester of pregnancy, ultrasound check of renal function and skull is recommended. Infants whose mothers have taken angiotensin II receptor antagonists should be closely observed for hypotension.
Breastfeeding: Because no information is available regarding the use of Telmisartan during breastfeeding, Telmisartan is not recommended and alternative treatments with better established safety profiles during breastfeeding are preferable, especially while nursing a newborn or preterm infant.
Fertility: In preclinical studies, no effects of Telmisartan on male and female fertility were observed.

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. 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%). In addition, it cannot be determined whether these events were causally related to Telmisartan tablets: Autonomic Nervous System: Impotence, increased sweating, flushing.
Body as a Whole: Allergy, fever, leg pain, malaise.
Cardiovascular: Palpitation, dependent edema, abnormal ECG.
CNS: Insomnia, somnolence, migraine, vertigo, paresthesia, involuntary muscle contractions, hypoesthesia.
Gastrointestinal: Flatulence, constipation, gastritis, vomiting, dry mouth, hemorrhoids, gastroenteritis, enteritis, gastroesophageal reflux, toothache, non-specific gastrointestinal disorders.
Metabolic: Gout, hypercholesterolemia, diabetes mellitus.
Musculoskeletal: Arthritis, arthralgia, leg cramps.
Psychiatric: Anxiety, depression, nervousness.
Resistance Mechanism: Infection, fungal infection, abscess, otitis media.
Respiratory: Asthma, bronchitis, rhinitis, dyspnea, epistaxis.
Skin: Dermatitis, rash, eczema, pruritus.
Urinary: Micturition frequency, cystitis.
Vascular: Cerebrovascular disorder.
Special Senses: Abnormal vision, conjunctivitis, tinnitus, earache.
During initial clinical studies, a single case of angioedema was reported (among a total of 3,781 patients treated).

Digoxin: When Telmisartan was co-administered with Digoxin, media 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.
Warfarin: Telmisartan administered for 10 days slightly decreased the mean warfarin trough plasma concentration; this decrease did not result in a chance 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.

Angiotensin II Antagonists

C09CA07 - telmisartan ; Belongs to the class of angiotensin II receptor blockers (ARBs). Used in the treatment of cardiovascular disease.

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