Micardis is a pill containing 2 drugs composed of hydrochlorothiazide and telmisartan. Hydrochlorothiazide is a diuretic and telmisartan is an orally active angiotensin II antagonist acting on the AT1 receptor subtype. Micardis is available by prescription only.
Clinical trials involving more than 2500 patients were conducted to test the effects of telmisartan and hydrochlorothiazide in combination for the treatment of hypertension. 1017 patients were given telmisartan (20 to 160 mg) and concomitant hydrochlorothiazide (6.25 to 25 mg). One factorial trial was included where patients were given combinations of telmisartan (20, 40, 80, 160mg or placebo) and hydrochlorothiazide (6.25, 12.5, 25mg and placebo). For patients who did not experience adequate control of their condition with the randomized monotherapy dose or had not achieved adequate response after completing the up-titration of telmisartan, four other studies were held of at least six months duration which allowed the add-on of hydrochlorothiazide.
The combination of telmisartan and hydrochlorothiazide resulted in additive placebo-adjusted decreases in systolic and diastolic blood pressure at trough of 16-21/9-11 mmHg at 40/12.5 mg and 80/12.5 mg, compared to 9-13/7-8 mmHg for telmisartan 40 mg to 80 mg and 4/4 mmHg for hydrochlorothiazide 12.5 mg alone.
In active controlled studies, the addition of 12.5 mg hydrochlorothiazide to titrated doses of telmisartan in patients who did not achieve or maintain adequate response with telmisartan monotherapy further reduced systolic and diastolic blood pressure.
The antihypertensive effect was independent of age or gender.
There was essentially no change in heart rate in patients treated with the combination of telmisartan and hydrochlorothiazide in the placebo controlled trial. (From FDA Label)
Micardis has been found to cause fetal and neonatal morbidity and death when taken by pregnant women. Numerous birth defects have been reported associated with angiotensin II receptor antagonists. Pregnant mothers should discontinue use of Micardis as soon as possible and physicians should warn them of all the risks to their fetus if the decision is made to continue treatment.
Possible side effects of Micardis include, but are not limited to:
In clinical trials side effects have generally been mild and have not required discontinuation of therapy.
Angiotensin II is formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme (ACE, kininase II). Angiotensin II is the principle 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.
Hydrochlorothiazide is a thiazide diuretic. Thiazides affect the renal tubular mechanisms of electrolyte reabsorption, directly increasing excretion of sodium salt and chloride in approximately equivalent amounts. Indirectly, the diuretic action of hydrochlorothiazide reduces plasma volume, with consequent increases in plasma renin activity, increases in aldosterone secretion, increases in urinary potassium loss, and decreases n serum potassium. The renin-aldosterone link is mediated by angiotensin II, so coadministration of an angiotensin II receptor antagonist tends to reverse the potassium loss associated with these diuretics.
The mechanism of the antihypertensive effect of thiazides is not
(From FDA Label)