Brands, Medical Use, Clinical Data
- Angiotensin II Type 1 Receptor Blockers
- Angiotensin-Converting Enzyme Inhibitors
Brands / Synonyms
BIBR 277; BIBR 277SE; Micardis; Micardis HCT; Telmisartan [INN]
For the treatment of hypertension.
Telmisartan is an orally active nonpeptide angiotensin II antagonist that acts on the AT1 receptor subtype. New studies suggest that telmisartan may also have PPARγ agonistic properties that could potentially confer beneficial metabolic effects. This observation is currently being explored in clinical trials. 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 works by blocking the vasoconstrictor and aldosterone secretory effects of angiotensin II.
Mechanism of Action
Telmisartan interferes with the binding of angiotensin II to the angiotensin II AT1-receptor by binding reversibly and selectively to the receptors in vascular smooth muscle and the adrenal gland. As angiotensin II is a vasoconstrictor, which also stimulates the synthesis and release of aldosterone, blockage of its effects results in decreases in systemic vascular resistance. Telmisartan does not inhibit the angiotensin converting enzyme, other hormone receptors, or ion channels.
Absolute bioavailability depends on dosage. Food slightly decreases the bioavailability (a decrease of about 6% is seen when the 40-mg dose is administered with food).
Intravenous LD50 in rats is 150-200 mg/kg in males and 200 to 250 mg/kg in females. Acute oral toxicity is low: no deaths and no changes occurred in rats or dogs at 2000 mg/kg, the highest dose tested. Limited data are available with regard to overdosage in humans. The most likely manifestations of overdosage with telmisartan would be hypotension, dizziness and tachycardia; bradycardia could occur from parasympathetic (vagal) stimulation.
Biotrnasformation / Drug Metabolism
Minimally metabolized by conjugation to form a pharmacologically inactive acylglucuronide; the glucuronide of the parent compound is the only metabolite that has been identified in human plasma and urine. The cytochrome P450 isoenzymes are not involved in the metabolism of telmisartan.
MICARDIS HCT (telmisartan/hydrochlorothiazide) is contraindicated in patients who are hypersensitive
to any component of this product.
Because of the hydrochlorothiazide component, this product is contraindicated in patients with anuria
or hypersensitivity to other sulfonamide-derived drugs.
Digoxin: When telmisartan was coadministered 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
Warfarin: Telmisartan administered for 10 days slightly decreased the mean warfarin
trough plasma concentration; this decrease did not result in a change in International Normalized Ratio (INR).
Other Drugs: Coadministration 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.
Hydrochlorothiazide: When administered concurrently, the following drugs may interact
with thiazide diuretics: Alcohol, barbiturates, or narcotics: Potentiation of orthostatic hypotension may occur.
Antidiabetic drugs (oral agents and insulin): Dosage adjustment of the antidiabetic drug may be
Other antihypertensive drugs: Additive effect or potentiation.
Cholestyramine and colestipol resins: Absorption of hydrochlorothiazide is impaired in the presence
of anionic exchange resins. Single doses of either cholestyramine or colestipol resins bind the hydrochlorothiazide
and reduce its absorption from the gastrointestinal tract by up to 85% and 43%, respectively.
Corticosteroids, ACTH: Intensified electrolyte depletion, particularly hypokalemia.
Pressor amines (e.g., norepinephrine): Possible decreased response to pressure amines
but not sufficient to preclude their use.
Skeletal muscle relaxants, nondepolarizing (e.g., tubocurarine): Possible increased
responsiveness to the muscle relaxant.
Lithium: Should not generally be given with diuretics. Diuretic agents reduce the renal
clearance of lithium and add a high risk of lithium toxicity. Refer to the package insert for lithium preparations
before use of such preparations with MICARDIS HCT.
Non-steroidal anti-inflammatory drugs: In some patients, the administration of a
non-steroidal antiinflammatory agent can reduce the diuretic, natriuretic, and antihypertensive effects of loop,
potassium-sparing and thiazide diuretics. Therefore, when MICARDIS HCT and non-steroidal anti-inflammatory agents are
used concomitantly, the patient should be observed closely to determine if the desired effect of the diuretic is