Approved March 2007
Tekturna is an orally active, nonpeptide, potent renin inhibitor. Renin is the enzyme at the beginning of the Renin Angiotensin System (RAS), one of the key regulators of blood pressure. Suppression of the RAS has been shown to treat hypertension and reduce cardiovascular events.
Tekturna is specifically indicated for the treatment of hypertension. It may be used alone or in combination with other antihypertensive agents. The use of Tekturna with maximal doses of ACE inhibitors has not been adequately studied.
Tekturna is supplied as a 150 mg or 300 mg tablet designed for oral administration. The recommended initial dose of the drug is 150 mg once daily. In patients who do not have adequately controlled blood pressure, the daily dose may be increased to 300 mg.
FDA approval of Tekturna was based on the results of six clinical trials of aliskiren monotherapy, one trial of aliskiren alone and in combination with hydrochlorothiazide and one trial of aliskiren alone and in combination with valsartan. The six randomized, double-blind, placebo-controlled trials enrolled 2,730 subjects who received aliskiren in doses of 75-600 mg or placebo for eight weeks. Increase in response was observed for all doses studied, with reasonable effects seen at 150-300 mg, and no clear further increase at 600 mg. A substantial proportion (85%-90%) of the blood pressure lowering effect was observed within 2 weeks of treatment. Subjects in the placebo controlled trials continued in an open label trial for an additional year. A blood pressure lowering effect was demonstrated by a randomized withdrawal study, which showed a statistically significant difference between subjects kept on aliskiren and those randomized to placebo. When treatment ceased, blood pressure returned to baseline levels over a period of a couple of weeks.
Aliskiren and hydrochlorothiazide were studied alone and in combination with each-other. This randomized, double-blind, placebo-controlled, parallelgroup, 15-arm factorial study enrolled 2,776 subjects. Aliskiren was administered in doses of 75, 150, and 300 mg and hydrochlorothiazide in doses of 6.25, 12.5, and 25 mg, for eight weeks. Blood pressure reductions with the combinations were greater than the reductions with the monotherapies.
Aliskiren and valsartan were studied alone and in combination with each-other. This randomized, double-blind, placebo-controlled, parallel-group, 4-arm, dose escalation study enrolled 1,797 subjects. The dosages of aliskiren and valsartan were started at 150 and 160 mg, respectively, and increased at four weeks to 300 mg and 320 mg, respectively. Seated trough cuff blood pressure was measured at baseline, 4, and 8 weeks. Blood pressure reductions with the combinations were greater than the reductions with the monotherapies.
Ongoing Study Commitments
Adverse events associated with the use of Tekturna may include, but are not limited to, the following
Tekturna is a renin inhibitor. Renin is secreted by the kidney in response to decreases in blood volume and renal perfusion. Renin cleaves angiotensinogen, a peptide in the blood that causes vasoconstriction and increased blood pressure, to form the inactive decapeptide angiotensin I (Ang I). Ang I is converted to the active octapeptide angiotensin II (Ang II) by angiotensin-converting enzyme (ACE) and non-ACE pathways. Ang II is a vasoconstrictor and leads to the release of catecholamines from the adrenal medulla and prejunctional nerve endings. It also promotes aldosterone secretion and sodium reabsorption, which increases blood pressure and it inhibits renin release, providing a negative feedback to the system. This cycle is known as the renin-angiotensin-aldosterone system (RAAS). Thus, as a direct renin inhibitor, Tekturna disrupts the RAAS process by decreasing plasma renin activity (PRA) and inhibiting the conversion of angiotensinogen to Ang I.
For additional information regarding Tekturna or hypertension, please visit the Tekturna web page.
The Tekturna (aliskiren) drug information shown above is licensed from Thomson CenterWatch. The information provided here is for general educational purposes only and does not constitute medical or pharmaceutical advice which should be sought from qualified medical and pharmaceutical advisers.