STEPS

New Drug Reviews

Aliskiren (Tekturna) for the Treatment of Hypertension

Allison bernknopf, PharmD, Ferris State University, Kalamazoo, Michigan

Aliskiren (Tekturna) is the first direct renin inhibitor approved for the treatment of hypertension when used alone or in combination with other antihypertensive agents. Aliskiren causes a reduction in plasma renin activity, thereby inhibiting production of angiotensin-I and -II receptor antagonists.1

Name	Starting dosage	Dose form	Approximate monthly cost*
Aliskiren (Tekturna)	150 mg daily	150- or 300-mg tablets	$71
*-Average wholesale cost, based on Red Book, Montvale, N.J.: Medical Economics Data, 2007.

Safety

Aliskiren has a good short-term (eight weeks) safety profile. Angioedema occurs in less than one in 1,500 patients (0.06 percent). Hyperkalemia is rare when aliskiren is used alone, but when it is combined with an angiotensin-converting enzyme (ACE) inhibitor, rates are higher by approximately 5 percent. Compared with hydrochlorothiazide (Ezide) monotherapy, a combination of aliskiren and hydrochlorothiazide will increase uric acid levels, resulting in a slight increase in the incidence of gout (0.1 versus 0.2 percent, respectively) and kidney stones (0 versus 0.2 percent, respectively). Creatine kinase will be increased in a small number of patients. Aliskiren is U.S. Food and Drug Administration pregnancy category C during the first trimester and category D during the second and third trimesters.1

Tolerability

Aliskiren was generally well tolerated in clinical trials. The percentage of patients taking aliskiren who dropped out because of adverse events ranged from 0.5 to 4.4 percent compared with 3.4 to 3.6 percent of patients receiving placebo.2-8 Diarrhea and cough occurred more often with aliskiren than with placebo; however, these side effects occurred in less than 3 percent of patients.1

Effectiveness

When used alone, aliskiren in dosages of 150 to 300 mg per day will decrease systolic blood pressure by 8 to 15 mm Hg and diastolic blood pressure by 8 to 11 mm Hg. Dosages of aliskiren greater than 300 mg per day will not lower blood pressure further.2-5 When combined with hydrochlorothiazide, aliskiren will produce an additional 1 to 4 mm Hg decrease in systolic blood pressure and a 2 to 7 mm Hg decrease in diastolic blood pressure.6 Aliskiren alone produces results similar to those of the angiotensin-receptor blockers losartan (Cozaar) and irbesartan (Avapro), and it has an added effect when combined with valsartan (Diovan).2-5 Aliskiren has not been studied in combination with other antihypertensives such as calcium channel blockers, beta blockers, or alpha-adrenergic blockers. It also has not been studied in the long term, and no research has been performed to demonstrate its effect on morbidity or mortality.

Price

Aliskiren costs approximately $71 per month. In contrast, the ACE inhibitor lisinopril (Zestril) costs about $9 to $30 for the generic version and $32 to $40 for the brand per month, and hydrochlorothiazide costs about $0.30 to $4 per month.

Simplicity

The usual dosage of aliskiren is 150 mg or 300 mg given orally once a day in a routine manner with regard to meals.1 No initial dosage adjustments are required for older patients or patients with hepatic or renal impairment.1,9

Bottom Line

Aliskiren provides a new pharmacologic approach to treating hypertension; however, short-term studies have not identified a unique role. It is more expensive than commonly used first-line diuretics, and long-term safety has not been demonstrated. It is unknown if aliskiren will provide beneficial patient-orientated outcomes, such as renal protection and reduction in cardiovascular events. Aliskiren may only be valuable in patients with hypertension who are resistant to multiple-drug treatment; however, it has not yet been studied in this population.

Address correspondence to Allison Bernknopf, PharmD, at bernknopf@kcms.msu.edu. Reprints are not available from the author.

Author disclosure: Nothing to disclose.

REFERENCES

1. Tekturna (aliskiren) [Prescribing information]. East Hanover, N.J.: Novartis, 2007. Accessed August 3, 2007, at: http://www.pharma.us.novartis.com/product/pi/pdf/tekturna.pdf.

2. Oh BH, Mitchell J, Herron JR, Chung J, Khan M, Keefe DL. Aliskiren, an oral renin inhibitor, provides dose-dependent efficacy and sustained 24-hour blood pressure control in patients with hypertension. J Am Coll Cardiol 2007;49:1157-63.

3. Kushiro T, Itakura H, Abo Y, Gotou H, Terao S, Keefe DL. Aliskiren, a novel oral renin inhibitor, provides dose-dependent efficacy and placebo-like tolerability in Japanese patients with hypertension. Hypertens Res 2006;29:997-1005.

4. Gradman AH, Schmieder RE, Lins RL, Nussberger J, Chiang Y, Bedigian MP. Aliskiren, a novel orally effective renin inhibitor, provides dose-dependent antihypertensive efficacy and placebo-like tolerability in hypertensive patients. Circulation 2005;111:1012-8.

5. Stanton A, Jensen C, Nussberger J, O'Brien E. Blood pressure lowering in essential hypertension with oral renin inhibitor, aliskiren. Hypertension 2003;42:1137-43.

6. Jordan J, Engeli S, Boye SW, Brenton SL, Keefe DL. Direct renin inhibition with aliskiren in obese patients with arterial hypertension. Hypertension 2007;49:1047-55.

7. Villamil A, Chrysant SG, Calhoun D, Schober B, Hsu H, Matrisciano-Dimichino L, et al. Renin inhibition with aliskiren provides additive antihypertensive efficacy when used in combination with hydrochlorothiazide. J Hypertens 2007;25:217-26.

8. Pool JL, Schmieder RE, Azizi M, Aldigier JC, Januszewicz A, Zidek W, et al. Aliskiren, an orally effective renin inhibitor, provides antihypertensive efficacy alone and in combination with valsartan. Am J Hypertens 2007;20:11-20.

9. Vaidyanathan S, Warren V, Yeh CM, Bizot MN, Dieterich HA, Dole WP. Pharmacokinetics, safety, and tolerability of the oral renin inhibitor aliskiren in patients with hepatic impairment. J Clin Pharmacol 2007;47:192-200.

STEPS new drug reviews cover Safety, Tolerability, Effectiveness, Price, and Simplicity. Each independent review is provided by authors who have no financial association with the drug manufacturer.

The series coordinator for AFP is Allen F. Shaughnessy, PharmD, Tufts University Family Medicine Residency Program at Cambridge Health Alliance, Malden, Mass.

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