aliskiren (Tekturna, Rasilez)
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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
- eliminated unchanged through the biliary system
- not metabolized by cytochrome P450
- 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
- diarrhea (2% with 300 mg QD)
- abdominal pain, dyspepsia
- headache
- nasopharyngitis
- cough (1%)
- angioedema
- hyperkalemia (0.3%)
- but may potentiate effects of ACE inhibitor
- animal studies showed inflammation of the colon
- drug adverse effects of renin-angiotensin-aldosterone system inhibitors (RAAS inhibitors)
- drug adverse effects of antihypertensive agents
Drug interactions
- may potentiate hyperkalemia in combination with ACE inhibitor
- ketoconazole may increase levels of aliskiren (up to 80%)
- aliskiren can diminish plasma levels of furosemide
- no benefit when added to ACE inhibitor or ARB[5]
- drug interaction(s) of fluticasone with HIV1 protease inhibitors
- drug interaction(s) of renin-angiotensin-aldosterone inhibitors with trimethoprim-sulfamethoxazole
- drug interaction(s) of angiotensin II receptor antagonists with aliskiren
- drug interaction(s) of ACE inhibitors with aliskiren
- drug interaction(s) of NSAIDs & antihypertensives
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
More general terms
Component of
- aliskiren/valsartan (Valturna)
- aliskiren/amlodipine/hydrochlorothiazide (Amturnide)
- aliskiren/hydrochlorothiazide (Tekturna HCT)
- aliskiren/amlodipine (Tekamlo)
References
- ↑ Prescriber's Letter 14(3): 2007 Investigational Drug: Tekturna (Aliskiren) Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=230306&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 2.0 2.1 2.2 Prescriber's Letter 14(4): 2007 New Drug: Tekturna (Aliskiren) Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=230402&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 3.0 3.1 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: https://www.ncbi.nlm.nih.gov/pubmed/18525041
- ↑ 4.0 4.1 4.2 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 - ↑ 5.0 5.1 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. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23121378 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1208799
- ↑ 6.0 6.1 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: https://www.ncbi.nlm.nih.gov/pubmed/23478743
- ↑ 7.0 7.1 Prescriber's Letter 21(6): 2014 Oral Meds to Keep in Original Containers Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=300622&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 8.0 8.1 8.2 McMurray JJ et al. Aliskiren, enalapril, or aliskiren and enalapril in heart failure. N Engl J Med 2016 Apr 4; PMID: https://www.ncbi.nlm.nih.gov/pubmed/27043774
- ↑ 9.0 9.1 Therapeutics Letter #108. Therapeutics Initiative Drugs to Avoid. http://www.ti.ubc.ca/2018/01/04/108-drugs-avoid/
- ↑ 10.0 10.1 10.2 10.3 NEJM Knowledge+ Endocrinology
- ↑ Novartis Pharmaceuticals http://www.tekturna.com