Aliskiren

Aliskiren
Clinical data
Trade namesTekturna, Rasilez
AHFS/Drugs.comMonograph
MedlinePlusa607039
License data
Pregnancy
category
  • C in first trimester
    D in second and third trimesters
Routes of
administration		By mouth (tablets)
ATC code
Legal status
Legal status
Pharmacokinetic data
BioavailabilityLow (approximately 2.5%)
MetabolismHepatic, CYP3A4-mediated
Elimination half-life24 hours
ExcretionRenal
Identifiers
  • (2S,4S,5S,7S)-5-amino-N-(2-carbamoyl-2,2-dimethylethyl)-4-hydroxy-7-{[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl}-8-methyl-2-(propan-2-yl)nonanamide
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
PDB ligand
CompTox Dashboard (EPA)
ECHA InfoCard100.127.451 Edit this at Wikidata
Chemical and physical data
FormulaC30H53N3O6
Molar mass551.769 g·mol−1
3D model (JSmol)
  • O=C(N)C(C)(C)CNC(=O)[C@H](C(C)C)C[C@H](O)[C@@H](N)C[C@@H](C(C)C)Cc1cc(OCCCOC)c(OC)cc1
  • InChI=1S/C30H53N3O6/c1-19(2)22(14-21-10-11-26(38-8)27(15-21)39-13-9-12-37-7)16-24(31)25(34)17-23(20(3)4)28(35)33-18-30(5,6)29(32)36/h10-11,15,19-20,22-25,34H,9,12-14,16-18,31H2,1-8H3,(H2,32,36)(H,33,35)/t22-,23-,24-,25-/m0/s1 ☒N
  • Key:UXOWGYHJODZGMF-QORCZRPOSA-N ☒N
 ☒NcheckY (what is this?)  (verify)

Aliskiren (brand names Tekturna and Rasilez) is the first in a class of drugs called direct renin inhibitors. It is used for essential (primary) hypertension.[2] 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.[3]

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.[4][5]

As a result, in 2012:

  • A new contraindication was added to the product label concerning the use of aliskiren with angiotensin receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors (ACEIs) in patients with diabetes because of the risk of kidney impairment, low blood pressure, and high levels of potassium in the blood.[6]
  • A warning to avoid use of aliskiren with ARBs or ACEIs was also added for patients with moderate to severe kidney impairment (i.e., where glomerular filtration rate is less than 60 ml/min).[6]
  • Novartis decided to stop marketing Valturna (aliskiren/valsartan).[7]

Aliskiren was co-developed by the Swiss pharmaceutical companies Novartis and Speedel.[8][9]

  1. ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 Oct 2023.
  2. ^ "First Hypertension Drug to Inhibit Kidney Enzyme Approved". CBC. 2007-03-06. Archived from the original on 2007-03-22. Retrieved 2007-03-14.
  3. ^ Cite error: The named reference Pres2014 was invoked but never defined (see the help page).
  4. ^ Healthzone.ca: Blood-pressure drug reviewed amid dangerous side effects
  5. ^ Parving HH, Brenner BM, McMurray JJ, de Zeeuw D, Haffner SM, Solomon SD, et al. (December 2012). "Cardiorenal end points in a trial of aliskiren for type 2 diabetes" (PDF). The New England Journal of Medicine. 367 (23): 2204–13. doi:10.1056/NEJMoa1208799. PMID 23121378.
  6. ^ a b "FDA Drug Safety Communication: New Warning and Contraindication for blood pressure medicines containing aliskiren (Tekturna)". U.S. Food and Drug Administration (FDA). 19 January 2016. Retrieved 12 February 2020.
  7. ^ "Aliskiren Information". U.S. Food and Drug Administration. 8 July 2015. Retrieved 12 February 2020.
  8. ^ Gradman AH, Schmieder RE, Lins RL, Nussberger J, Chiang Y, Bedigian MP (March 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.
  9. ^ Staessen JA, Li Y, Richart T (October 2006). "Oral renin inhibitors". Lancet. 368 (9545): 1449–56. doi:10.1016/S0140-6736(06)69442-7. PMID 17055947. S2CID 20729350.