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aliskiren (Tekturna, Rasilez)

Indications: - hypertension (FDA-approved use)* - heart failure* * as effective as enalopril in ATMOSPHERE trial * not shown to reduce cardiovascular events [9] (avoid) Contraindications: - pregnancy - coadministration of ACE inhibitor or ARB [4] Dosage: 150-600 mg QD Tabs: 150, 300 mg Storage: - store in orginal container - must be protected from moisture & heat [7] Pharmacokinetics: 1) eliminated unchanged through the biliary system 2) not metabolized by cytochrome P450 3) partially metabolized in the kidney [10] - insulin clearance may be reduced in patients with renal failure [10] No dosage adjustment necessary in the elderly or with mild to moderate hepatic insufficiency [2] Dosage adjustment with with renal failure: - if hypoglycemia develops in a patient with renal failure, reduce dose of insulin [10] - limited data on end-stage renal disease [2] Adverse effects: 1) diarrhea (2% with 300 mg QD) 2) abdominal pain, dyspepsia 3) headache 4) nasopharyngitis 5) cough (1%) 6) angioedema 7) hyperkalemia (0.3%) - but may potentiate effects of ACE inhibitor 8) animal studies showed inflammation of the colon Drug interactions: 1) may potentiate hyperkalemia in combination with ACE inhibitor 2) ketoconazole may increase levels of aliskiren (up to 80%) 3) aliskiren can diminish plasma levels of furosemide 4) no benefit when added to ACE inhibitor or ARB [5] Mechanism of action: - direct renin inhibitor - may diminish microalbuminuria in patients with diabetes [3] Clinical trials: - Altitude trial: - aliskiren in combination with ACE inhibitor or ARB in patients with type 2 diabetes & renal impairment - trial halted early due to higher than expected incidence of non fatal stroke, renal complications, hyperkalemia, & hypotension [4] - ASTRONAUT trial - did not improve cardiovascular mortality or hospital readmission in patients hospitalized with heart failure [6] - ATMOSPHERE trial [8] - aliskiren alone or addition of aliskiren to enalapril no better than enalapril alone for treatment of heart failure [8] Notes: Cost (2007) $2-3/day

Interactions

drug interactions drug adverse effects (more general classes)

General

renin inhibitor vasodilator agent

Properties

INHIBITS: renin

Database Correlations

PUBCHEM correlations

References

  1. Prescriber's Letter 14(3): 2007 Investigational Drug: Tekturna (Aliskiren) Detail-Document#: 230306 (subscription needed) http://www.prescribersletter.com
  2. Prescriber's Letter 14(4): 2007 New Drug: Tekturna (Aliskiren) Detail-Document#: 230402 (subscription needed) http://www.prescribersletter.com
  3. Parving HH et al Aliskiren combined with losartan in type 2 diabetes and nephropathy. N Engl J Med. 2008 Jun 5;358(23):2433-46 PMID: 18525041
  4. Media releases: December 20, 2011 Novartis announces termination of ALTITUDE study with Rasilez/ Tekturna in high-risk patients with diabetes and renal impairment http://www.novartis.com/newsroom/media-releases/en/2011/1572562.shtml - FDA MedWatch Aliskiren-containing Medications: Drug Safety Comunication - New Warning and Contraindication http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm301120.htm
  5. Parving H-H et al. Cardiorenal end points in a trial of aliskiren for type 2 diabetes. N Engl J Med 2012 Dec 6; 367:2204. PMID: 23121378 http://www.nejm.org/doi/full/10.1056/NEJMoa1208799
  6. Gheorghiade M et al. Effect of aliskiren on postdischarge mortality and heart failure readmissions among patients hospitalized for heart failure: The ASTRONAUT randomized trial. JAMA 2013 Mar 11 PMID: 23478743
  7. Prescriber's Letter 21(6): 2014 Oral Meds to Keep in Original Containers Detail-Document#: 300622 (subscription needed) http://www.prescribersletter.com
  8. McMurray JJ et al. Aliskiren, enalapril, or aliskiren and enalapril in heart failure. N Engl J Med 2016 Apr 4; PMID: 27043774
  9. Therapeutics Letter #108. Therapeutics Initiative Drugs to Avoid. http://www.ti.ubc.ca/2018/01/04/108-drugs-avoid/
  10. NEJM Knowledge+ Endocrinology
  11. Novartis Pharmaceuticals http://www.tekturna.com

Component-of

aliskiren/amlodipine (Tekamlo) aliskiren/amlodipine/hydrochlorothiazide (Amturnide) aliskiren/hydrochlorothiazide (Tekturna HCT) aliskiren/valsartan (Valturna)