General Information

MicardisPlus is a combination of hydrochlorothiazide and telmisartan. Hydrochlorothiazide is a diuretic and telmisartan is an orally active angiotensin II antagonist acting on the AT1 receptor subtype. 

MicardisPlus is specifically indicated for the treatment of hypertension, to lower blood pressure. It may be used alone or with other hypertensive treatments.

MicardisPlus is supplied as tablets for oral administration. Initiate a patient whose blood pressure is not adequately controlled with telmisartan (Micardis) monotherapy 80 mg on MicardisPlus 80 mg/12.5 mg once daily. Dose can be titrated up to 160 mg/25 mg after 2 to 4 weeks, if necessary. Initiate a patient whose blood pressure is not adequately controlled by 25 mg once daily of hydrochlorothiazide, or is controlled but who experiences hypokalemia with this regimen on MicardisPlus 80 mg/12.5 mg once daily. Dose can be titrated up to 160 mg/25 mg after 2 to 4 weeks, if necessary. Patients titrated to the individual components (telmisartan and hydrochlorothiazide) may instead receive the corresponding dose of MicardisPlus.

Mechanism of Action

MicardisPlus is a combination of two drugs with antihypertensive properties: a thiazide diuretic, hydrochlorothiazide, and an angiotensin II receptor blocker (ARB), telmisartan.

Telmisartan:

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 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. Telmisartan does not inhibit ACE (kininase II) nor does it 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:

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 in serum potassium. The renin-aldosterone link is mediated by angiotensin II, so co-administration of an ARB tends to reverse the potassium loss associated with these diuretics. The mechanism of the antihypertensive effect of thiazides is not fully understood.

Side Effects

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

• upper respiratory tract infection
• dizziness
• sinusitis
• diarrhea
• fatigue
• influenza-like symptoms
• nausea

The MicardisPlus drug label comes with the following Black Box Warning: When pregnancy is detected, discontinue MicardisPlus as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus.

Clinical Trial Results

Clinical trials involving more than 2,500 patients were conducted to test the effects of telmisartan and hydrochlorothiazide in combination for the treatment of hypertension. 1,017 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.