General Information

Micardis (telmisartan) is a nonpeptide angiotensin II receptor (type AT1 10 ) antagonist.

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

Micardis is supplied as tablets for oral administration. The tablets can be administered with or without food. Dosage must be individualized. The usual starting dose of Micardis tablets is 40 mg 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 Micardis is required, a diuretic may be added.

Mechanism of Action

Micardis (telmisartan) is a nonpeptide angiotensin II receptor (type AT1 10 ) 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 AT 1 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 AT 2 receptor found in many tissues, but AT 2 is not known to be associated with cardiovascular homeostasis. Telmisartan has much greater affinity (>3,000 fold) for the AT 1 receptor than for the AT 2 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.

Side Effects

Adverse effects associated with the use of Micardis may include, but are not limited to, the following:

upper respiratory tract infection

back pain

sinusitis

diarrhea

pharyngitis

influenza-like symptoms

dyspepsia

myalgia

urinary tract infection

abdominal pain

headache

dizziness

pain

fatigue

coughing

hypertension

chest pain

nausea

peripheral edema

Clinical Trial Results

Micardis was evaluated in five principal placebo-controlled clinical trials, studying a range of 20-160 mg. The studies involved a total of 1,773 patients with mild to moderate hypertension (diastolic blood pressure of 95-114 mmHg), 1,031 of whom were treated with telmisartan. Following once daily administration of telmisartan, the magnitude of blood pressure reduction from baseline after placebo subtraction was approximately (SBP/DBP) 6-8 / 6 mmHg for 20 mg, 9-13 / 6-8 mmHg for 40 mg, and 12-13 / 7-8 mmHg for 80 mg. Larger doses (up to 160 mg) did not appear to cause a further decrease in blood pressure. Upon initiation of antihypertensive treatment with telmisartan, blood pressure was reduced after the first dose, with a maximal reduction by about 4 weeks. With cessation of treatment with Micardis, blood pressure gradually returned to baseline values over a period of several days to one week. During long term studies (without placebo control) the effect of telmisartan appeared to be maintained for up to at least one year.