Micardis HCT (telmisartan and hydrochlorothiazide)
The following drug information is obtained from various newswires, published
medical journal articles, and medical conference presentations.
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
The antihypertensive effect was independent of age or
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
- flu-like symptoms
- upper respiratory tract infection
In clinical trials side effects have generally been mild and
have not required discontinuation of therapy.
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 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
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
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
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
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
The mechanism of the antihypertensive effect of thiazides is not
(From FDA Label)