Aliskiren Tablets (Tekturna®)
Pharmacology Update
Aliskiren Tablets (Tekturna®)
By William T. Elliott, MD, FACP, and James Chan, PhD, PharmD, Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; Assistant Clinical Professor of Medicine, University of California, San Francisco; Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Drs. Chan and Elliott report no financial relationship to this field of study.
Introduction
The FDA has approved aliskiren, the first of a new class of antihypertensive drugs, the oral renin inhibitors. Aliskiren, which is approved for the treatment of hypertension, will be marketed by Novartis pharmaceuticals as Tekturna.
Indications
Aliskiren is indicated for the treatment of hypertension either as monotherapy or in combination with other antihypertensive agents.1
Dosage
The recommended starting dose is 150 mg once daily. The dose may be increased to 300 mg daily. Dosage adjustment is not needed for the elderly or patients with mild-to-severe renal or hepatic insufficiency. Patients should be consistent in taking the drug with regard to meals.1
Potential Advantages
Aliskiren provides a new site of action on the renin-angiotensin system (RAS). Unlike angiotensin converting enzyme inhibitors (ACEIs) aliskiren does not inhibit the inactivation of bradykinin that may be responsible for its side effects including cough. In contrast to ACEIs and ARBs, angiotensin I, angiotensin II, and plasma renin activity are reduced with aliskiren.2
Potential Disadvantages
Aliskiren produces dose-related gastrointestinal side effects that are more frequent in women or the elderly (65 years).1 It is poorly absorbed (bioavailability about 2.5%) and a high fat meal significantly reduces bioavailability. Long term safety and effectiveness have not been established. Aliskiren is metabolized by CYP3A4 and atorvastatin increases and irbesartan reduces its bioavailability by about 50%.1
Comments
Renin, produced by the juxtaglomerular apparatus of the kidneys, converts angiotensinogen to angiotensin I. Angiotensin I, in turn, is activated to angiotension II by angiotensin converting enzyme. Angiotensin II exerts its action by binding to the angiotensin II receptors resulting in increase sympathetic tone and aldosterone release.2 The efficacy of aliskiren was shown in 6 randomized, double-blind, placebo-controlled, 8-week trials in patients with mild-to-moderate hypertension.1,3 In 5 studies at 150 mg per day, the placebo-subtracted DBP/SBP reductions were 5.9/4.5, 6.1/2.9, 2.1/1.7, 4.8/2.0, and 9.3/5.4. At 300 mg per day in 6 studies reductions were 11.2/7.5, 10.5/5.4, 5.1/3.7,8.3/3.3, 10.9/6.2, and 8.4/4.9. At 150 mg, effectiveness was similar to irbesartan 150 mg and 300 mg was more effective.3 The combination of aliskiren with hydrochlorothiazide or ramipril provided additional blood pressure reduction but the combination with valsartan or irbesartan was less conclusive.1,4,5,6 As with ACEIs and ARBs, it is less effective in black patients and should not be used during pregnancy.1 Aliskiren is well tolerated; diarrhea is the most common side effect (2% vs 1% with placebo). The frequency of cough is slightly greater than with placebo (1% vs 0.6%) and angioedema has been reported.1 The wholesale cost for a 30-day supply is $56 (150 mg) and $74 (300 mg). The cost for a generic lisinopril (10 mg to 40 mg) ranges from $4 to $8 for 30 days.
Clinical Implications
The RAS plays a key role in the pathogenesis of hypertension, cardiovascular, and renal disease. Aliskiren, the first renin inhibitor to be approved, offers a new mechanism of action. However, ACEIs and ARBs should continue to be the mainstay of therapy due to their vast clinic experience. Renin inhibitors may be suitable for patients with high renin activity (eg, young whites) or in patients using drugs that elevate renin activity.2
References
1. Tekturna Product Information. Novartis Pharmaceuticals Corporation. February 2007.
2. Stessen JA, et al. Lancet. 2006;368:1449-1456.
3. Gradman AH, et al. Circulation. 2005;111(8):1012-1018.
4. Pool JL, et al. Am J Hypertens. 2007;20(1):11-20.
5. O'Brien E, et al. Hypertension. 2007;49(2):276-284.
6. Villamil A, et al. J Hypertens. 2007;25(1):217-226.
The FDA has approved aliskiren, the first of a new class of antihypertensive drugs, the oral renin inhibitors.Subscribe Now for Access
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