Clinical data
Trade names Tekturna, Rasilez
AHFS/ Monograph
MedlinePlus a607039
License data
  • C in first trimester
    D in second and third trimesters
Routes of
By mouth (tablets)
ATC code C09XA02 (WHO)
C09XA52 (WHO) (with HCT)
Legal status
Legal status
Pharmacokinetic data
Bioavailability Low (approximately 2.5%)
Metabolism Hepatic, CYP3A4-mediated
Biological half-life 24 hours
Excretion Renal
CAS Number 173334-57-1 YesY
PubChem (CID) 5493444
DrugBank DB01258 YesY
ChemSpider 4591452 N
UNII 502FWN4Q32 YesY
KEGG D03208 YesY
ChEBI CHEBI:601027 N
Chemical and physical data
Formula C30H53N3O6
Molar mass 551.758 g/mol
3D model (Jmol) Interactive image
 NYesY (what is this?)  (verify)

Aliskiren (trade names Tekturna and Rasilez) is the first in a class of drugs called direct renin inhibitors. Its is used for essential (primary) hypertension.[1] While used for high blood pressure, other better studied medications are typically recommended due to concerns of higher side effects and less evidence of benefit.[2]

In December 2011, Novartis halted a trial of the drug after discovering increased nonfatal stroke, kidney complications, high blood potassium, and low blood pressure in people with diabetes and kidney problems.[3][4]

As a result, in April 20, 2012:

Aliskiren was co-developed by the Swiss pharmaceutical companies Novartis and Speedel.[5][6]

Medical uses

While used for high blood pressure, other better studied medications are typically recommended.[2] Prescrire has stated that aliskiren is potentially more harmful than beneficial and thus list it as of 2014 as a drug to avoid.[2]

Mechanism of action

Renin, the first enzyme in the renin–angiotensin–aldosterone system, plays a role in blood pressure control. It cleaves angiotensinogen to angiotensin I, which is in turn converted by angiotensin-converting enzyme (ACE) to angiotensin II. Angiotensin II has both direct and indirect effects on blood pressure. It directly causes arterial smooth muscle to contract, leading to vasoconstriction and increased blood pressure. Angiotensin II also stimulates the production of aldosterone from the adrenal cortex, which causes the tubules of the kidneys to increase reabsorption of sodium, with water following, thereby increasing plasma volume, and thus blood pressure. Aliskiren binds to the S3bp binding site of renin, essential for its activity.[7] Binding to this pocket prevents the conversion of angiotensinogen to angiotensin I. Aliskiren is also available as combination therapy with hydrochlorothiazide.[8]

Adverse effects


Drug interactions

Aliskiren is a minor inhibitor of substrate CYP3A4 and, more importantly, P-glycoprotein:

Rationale for design

Many drugs control blood pressure by interfering with angiotensin or aldosterone. However, when these drugs are used chronically, the body increases renin production, which drives blood pressure up again. Therefore, pharmacologists have been looking for a drug to inhibit renin directly. Aliskiren is the first drug to do so.[12][13]


  1. "First Hypertension Drug to Inhibit Kidney Enzyme Approved". CBC. 2007-03-06. Retrieved 2007-03-14.
  2. 1 2 3 "Towards better patient care: drugs to avoid in 2014". Prescrire International. 23 (150): 161–165. June 2014.
  3. Blood-pressure drug reviewed amid dangerous side effects
  4. Parving, Hans-Henrik; Brenner, Barry M.; McMurray, John J.V.; de Zeeuw, Dick; Haffner, Steven M.; Solomon, Scott D.; Chaturvedi, Nish; Persson, Frederik; Desai, Akshay S.; Nicolaides, Maria; Richard, Alexia; Xiang, Zhihua; Brunel, Patrick; Pfeffer, Marc A.; ALTITUDE Investigators (2012). "Cardiorenal End Points in a Trial of Aliskiren for Type 2 Diabetes". NEJM. 367 (23): 2204–13. doi:10.1056/NEJMoa1208799. PMID 23121378.
  5. Gradman A, Schmieder R, Lins R, Nussberger J, Chiang Y, Bedigian M (2005). "Aliskiren, a novel orally effective renin inhibitor, provides dose-dependent antihypertensive efficacy and placebo-like tolerability in hypertensive patients". Circulation. 111 (8): 1012–8. doi:10.1161/01.CIR.0000156466.02908.ED. PMID 15723979.
  6. Straessen JA, Li Y, Richart T (2006). "Oral Renin Inhibitors". Lancet. 368 (9545): 1449–56. doi:10.1016/S0140-6736(06)69442-7. PMID 17055947.
  7. "Chemistry & Biology : Structure-based drug design: the discovery of novel nonpeptide orally active inhibitors of human renin". ScienceDirect. Retrieved 2010-01-20.
  8. Baldwin CM, Plosker GL.. doi:10.2165/00003495-200969070-00004. Drugs 2009; 69(7):833-841.
  9. 1 2 Tekturna
  10. Cardiorenal end points in a trial of aliskiren for type 2 diabetes, N Engl J MED. 2012;367(23):2204-2213
  11. European Medicines Agency recommends new contraindications and warnings for aliskiren-containing medicines.
  12. Ingelfinger JR (June 2008). "Aliskiren and dual therapy in type 2 diabetes mellitus". N. Engl. J. Med. 358 (23): 2503–5. doi:10.1056/NEJMe0803375. PMID 18525047.
  13. PharmaXChange: Direct Renin Inhibitors as Antihypertensive Drugs

External links

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