Aliskiren

Administration

• Type: Antihypertensive
• Dosage Forms: 150mg, 300mg
• Routes of Administration: Oral
• Common Trade Names: Tekturna, Rasilez

Adult Dosing

Hypertension

• 150-300 mg PO qd

Pediatric Dosing

Safety/efficacy not established in pediatric patients

Special Populations

• Pregnancy Rating: X
• Lactation risk: Consider alternative

Renal Dosing

• Adult:
  • CrCl > 30: No adjustment
  • CrCl < 30: Not Definied
  • HD/PD: No Supplement
• Pediatric: Safety/efficacy not established in pediatric patients

Hepatic Dosing

• Adult: No adjustment
• Pediatric: Safety/efficacy not established in pediatric patients

Contraindications

• Allergy to class/drug
• Pregnancy

Adverse Reactions

Serious

• Anaphylaxis, angioedema
• Stevens-Johnson syndrome, Toxic epidermal necrolysis
• Hypotension
• Hyperkalemia
• Renal failure, Nephrolithiasis

Common

• Diarrhea
• Hyperkalemia
• BUN, Cr elevation

Pharmacology

• Half-life: 24h
• Metabolism: Liver partially; 3A4 substrate
• Excretion: Urine (25% unchanged)

Mechanism of Action

• Decreases plasma renin activity via direct inhibition
• Interferes with conversion of angiotensinogen to angiotensin I

References

• Funder JW, Carey RM, Mantero F, et al. The management of primary aldosteronism: case detection, diagnosis, and treatment: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016;101(5):1889-1916. doi: 10.1210/jc.2015-4061. [PubMed 26934393]
• Go AS, Bauman M, King SM, et al. An effective approach to high blood pressure control: a science advisory from the American Heart Association, the American College of Cardiology, and the Centers for Disease Control and Prevention [published online November 15, 2013]. Hypertension. [PubMed 24243703]
• Khadzhynov D, Slowinski T, Lieker I, et al, "Pharmacokinetics of Aliskiren in Patients With End-Stage Renal Disease Undergoing Haemodialysis," Clin Pharmacokinet, 2012, 51(10):661-9. [PubMed 23018529]
• Parving HH, Persson F, Lewis JB, et al, “Aliskiren Combined With Losartan in Type 2 Diabetes and Nephropathy,” N Engl J Med, 2008, 358(23):2433-46. [PubMed 18525041]
• Rasilez (aliskiren) [product monograph]. Dorval, Quebec, Canada: Novartis Pharmaceuticals Canada Inc; January 2018.
• Straessen JA, Li Y, and Richart T, “Oral Renin Inhibitors,” Lancet, 2006, 368(9545):1449-56. [PubMed 17055947]
• Tekturna (aliskiren) [prescribing information]. Boston, MA: Noden Pharma USA Inc; November 2017.
• Vaidyanathan S, Bigler H, Yeh C, et al, “Pharmacokinetics of the Oral Direct Renin Inhibitor Aliskiren Alone and in Combination with Irbesartan in Renal Impairment,” Clin Pharmacokinet, 2007, 46(8):661-75. [PubMed 17655373]
• Vaidyanathan S, Warren V, Yeh C, et al, “Pharmacokinetics, Safety, and Tolerability of the Oral Renin Inhibitor Aliskiren in Patients With Hepatic Impairment,” J Clin Pharmacol, 2007, 47(2):192-200. [PubMed 17244770]
• Weber MA, Schiffrin EL, White WB, et al. Clinical Practice Guidelines for the Management of Hypertension in the community: a statement by the American Society of Hypertension and the International Society of Hypertension. J Clin Hyperten (Greenwich). 2014;16(1):14-26. [PubMed 24341872]
• Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines [published online ahead of print on November 13, 2017.]. Hypertension. 2017. doi: 10.1161/HYP.0000000000000065. [PubMed 29133356]