Basic Information
ID DDInter972 and DDInter46
Interaction In patients without diabetes, coadministration of aliskiren with ACE inhibitors or ARBs may also be associated with increased risk of symptomatic hypotension, hyperkalemia, and changes in renal function including acute renal failure. All drugs inhibiting the renin-angiotensin system (RAS) can have these effects, which may be additive during concomitant administration. The risk of symptomatic hypotension is increased in the presence of marked volume and/or salt depletion. In patients with type 2 diabetes and renal impairment, coadministration of aliskiren with ACE inhibitors or angiotensin receptor blockers (ARBs) has been associated with an increased risk of adverse events including renal complications, hyperkalemia, and hypotension.
Management The use of aliskiren with ACE inhibitors or ARBs is considered contraindicated in patients with diabetes and should be avoided in general, particularly in patients with moderate to severe renal impairment (i.e., creatinine clearance (CrCl) < 60 mL/min). Prescribers should not initiate aliskiren in diabetic patients who are taking an ACE inhibitor or an ARB, and should stop any aliskiren-containing treatment if these patients are already receiving the combination. Alternative antihypertensive treatment should be considered as necessary. Most patients do not obtain any additional benefit from combination therapy relative to monotherapy; therefore, the potential risks should be thoroughly assessed when aliskiren is prescribed with ACE inhibitors or ARBs for the treatment of essential hypertension in patients without diabetes. Volume or salt depletion should be corrected prior to initiation of treatment. Routine monitoring of blood pressure, electrolytes, and renal function are recommended, particularly in the elderly or patients with worsening heart failure or a risk for dehydration. Potassium supplementation should generally be avoided unless it is closely monitored, and patients should be advised to seek medical attention if they experience signs and symptoms of hyperkalemia such as weakness, listlessness, confusion, tingling of the extremities, and irregular heartbeat.
References [1] MHRA. Medicines and Healthcare Regulatory Agency "Combination use of medicines from different classes of renin-angiotensin system blocking agents: risk of hyperkalaemia, hypotension, and impaired renal function--new warnings. Available from: URL: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/" ([2014 June]): [2] National Kidney Foundation "KDOQI Clinical Practice Guideline for Diabetes and CKD: 2012 update." Am J Kidney Dis 60 (2012): 850-86 [3] Novartis International AG "Novartis announces termination of ALTITUDE study with Rasilez Tekturna in high-risk patients with diabetes and renal impairment. Available from: URL: http://cardiobrief.files.wordpress.com/2011/12/novartis-aliskiren-altitude-pr.pdf." ([2011 Dec 20]): [4] "Product Information. Tekturna (aliskiren)." Novartis Pharmaceuticals, East Hanover, NJ. [5] EMA. European Medicines Agency "PRAC recommends against combined use of medicines affecting the renin-angiotensin (RAS) system: recommendation will now be considered by CHMP for final opinion. Available from: URL: http://www.ema.europa.eu/docs/en_GB/document_library/Referrals_document/R" ([2014 Apr 11]): [6] Leclerc JM, Chief Scientific Officer and Senior Vice-President Clinical and Regulatory Affairs, Health Canada "Potential risks of cardiovascular and renal adverse events in patients with type 2 diabetes treated with aliskiren (RASILEZ) or aliskiren/hydrochlorothiazide (RASILEZ HCT). Available from: URL: http://www.hc-sc.gc.ca/dhp-mps/alt_formats/pdf/medeff/advisor" ([2012 Jan 18]): [7] "Product Information. Cozaar (losartan)." Merck & Co, Inc, West Point, PA. [8] "Product Information. Diovan (valsartan)." Novartis Pharmaceuticals, East Hanover, NJ. [9] Tapaninen T, Neuvonen PJ, Niemi M "Grapefruit juice greatly reduces the plasma concentrations of the OATP2B1 and CYP3A4 substrate aliskiren." Clin Pharmacol Ther 88 (2010): 339-42 [10] Vaidyanathan S, Jarugula V, Dieterich HA, Howard D, Dole WP "Clinical pharmacokinetics and pharmacodynamics of aliskiren." Clin Pharmacokinet 47 (2008): 515-31 [11] Tapaninen T, Neuvonen PJ, Niemi M "Orange and apple juices greatly reduce the plasma concentrations of the OATP2B1 substrate aliskiren." Br J Clin Pharmacol 71 (2010): 718-26 [12] "Product Information. Tekturna (aliskiren)." Novartis Pharmaceuticals, East Hanover, NJ.
Alternative for Irbesartan C09C

C09D
Sacubitril Aliskiren Nebivolol
Alternative for Aliskiren C09X

C09D
Sacubitril Azilsartan medoxomil Candesartan Eprosartan Irbesartan Nebivolol
Olmesartan
Potential Metabolism Interactions
Substrate-Substrate Interaction：If more than one drug is metabolized by the same CYP, it is possible that its metabolism is inhibited because of the competition between the drugs. That means, it can be useful to lower the dosage of the drugs in the drug-cocktail because they remain longer in the organism than in monotherapy.
Inhibitor-Inhibitor Interaction：Combining two or more inhibitors of one CYP, should be compensated by lowering the dosage of these drugs because the metabolism is reduced and the drugs remain longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.
Inhibitor-Substrate Interaction：Combining drugs that have inhibitory effect and are substrates of one particular CYP, should be compensated by lowering the dosage. They rest longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.