aliskiren + losartan

The combination of aliskiren and losartan is a dual renin-angiotensin-aldosterone system (RAAS) blockade approach used primarily for treating hypertension and diabetic nephropathy. This combination pairs a direct renin inhibitor (aliskiren) with an angiotensin II receptor blocker (losartan). ## Mechanism and Clinical Effects Aliskiren works by directly inhibiting renin, the enzyme that converts angiotensinogen to angiotensin I, while losartan blocks the angiotensin II receptor (specifically AT1 receptors)[1][3]. When used together, they provide a more complete blockade of the RAAS system than either agent alone. Clinical studies, particularly the AVOID trial, demonstrated that adding aliskiren (300 mg) to losartan (100 mg) plus other antihypertensive therapy provided significant antiproteinuric effects in patients with type 2 diabetes and nephropathy[1][3]. This combination reduced the urinary albumin-to-creatinine ratio by 20% compared to losartan alone, with a reduction of 50% or more in 24.7% of patients receiving the combination versus 12.5% with losartan alone[3]. Importantly, these renoprotective effects appeared to be independent of blood pressure lowering, as the antiproteinuric benefits were consistent across different baseline blood pressure groups[1]. ## Safety Concerns and Contraindications In 2012, the FDA issued significant safety warnings regarding this combination therapy[2]. Based on data from the ALTITUDE trial, the FDA contraindicated the use of aliskiren with ARBs (including losartan) or ACE inhibitors in patients with diabetes due to increased risks of: - Kidney impairment - Hypotension (low blood pressure) - Hyperkalemia (high potassium levels) Additionally, the FDA recommended avoiding this combination in patients with kidney impairment where GFR < 60 mL/min[2]. The preliminary data from ALTITUDE also showed a slight increase in cardiovascular events (death or stroke) in the aliskiren group, though the FDA did not conclusively link these events to the drug combination at that time[2]. ## Current Status Following these safety concerns, the combination of aliskiren with ARBs like losartan is now classified as a major drug interaction that should generally be avoided[5]. The manufacturer of aliskiren-containing combination products (Novartis) discontinued marketing Valturna (a combination of aliskiren and valsartan, another ARB) after July 2012[2]. Currently, this combination would only be used in very specific clinical circumstances where the potential benefits might outweigh the established risks, and with careful monitoring of renal function and potassium levels.

Other names

aliskiren/losartanlosartan/aliskiren