Aliskiren (Tekturna), a new antihypertensive and the first of a class called renin inhibitors, has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of mild-to-moderate hypertension.

In randomized, double-blind, placebo-controlled trials, aliskiren used alone once a day was effective within two weeks. Using it in combination with the diuretic hydrochlorothiazide was more effective than using either drug alone. When compared with drugs in the antihypertensive class of angiotensin-receptor blockers (ARBs), aliskiren was at least as effective. But whether blood pressure can be further reduced by using aliskiren in combination with angiotensin-converting enzyme (ACE) inhibitors or [beta]-blockers is not yet known. While aliskiren does lower blood pressure, there is no evidence yet that it lessens the morbidity or mortality associated with hypertension.

Blood pressure is regulated by the renin-angiotensin-aldosterone system. Renin, an enzyme produced in the kidneys, sets in motion processes that, by increasing vasoconstriction and circulating plasma volume, raise blood pressure by increasing peripheral resistance and cardiac output. Other classes of antihypertensives lower blood pressure by affecting the process of regulation at later stages, but aliskiren directly inhibits the production of renin. The long-term effects of reducing plasma levels of renin are not yet known.

Treatment with other drugs that alter the renin-angiotensin-aldosterone system is less effective in blacks than in whites and Asians, and the same is true for aliskiren. Like ACE inhibitors and ARBs, aliskiren is in FDA pregnancy category D and should not be used in the second or third trimester because "drugs that act directly on the renin-angiotensin system can cause fetal and neonatal morbidity and death," according to the FDA.

Aliskiren is metabolized through the cytochrome P-450 enzyme system, but it does not inhibit or induce any part of that system. Some drugs alter the serum level of aliskiren: irbesartan (Avapro), one of the ARBs, significantly reduces the peak serum level of aliskiren, and both atorvastatin (Lipitor), an antilipidemic, and ketoconazole (Nizoral), an antifungal agent, significantly increase that level. In addition, aliskiren significantly reduces the peak serum level of the loop diuretic furosemide (Lasix). Changes in the dosage of aliskiren might be indicated in patients taking any of those drugs.

Aliskiren is usually well tolerated and hypotension is unlikely, although volume depletion resulting from aggressive diuretic therapy should be corrected before initiating therapy with aliskiren. If hypotension does develop, an IV infusion of normal saline solution should be given. Hyperkalemia can occur when aliskiren is administered to diabetic patients who are also taking an ACE inhibitor (and rarely in other patients), and electrolytes and renal function should be routinely monitored in that population. There have been rare reports of angioedema of the head and neck, including respiratory distress, in patients taking aliskiren. This allergic reaction has been associated with other antihypertensive agents that act on the renin-angiotensin-aldosterone system. Aliskerin's adverse gastrointestinal effects, such as diarrhea, are mostly mild and more common at higher doses. Cough, comparable to that induced by ACE inhibitors but much less common, can also occur in patients taking aliskiren.