title: Direct renin inhibition: an evaluation of the safety and tolerability of aliskiren.
abstract: BACKGROUND
  Aliskiren, an antihypertensive drug approved in the United States and Europe, is the first in a new class known as direct renin inhibitors. Aliskiren has been evaluated for safety and tolerability in more than 6400 patients. It has demonstrated a favorable safety and tolerability profile alone or in combination with other drugs.
  
  
  OBJECTIVE
  This article reviews the currently available safety and tolerability data for aliskiren.
  
  
  METHODS
  Using the search term aliskiren, MEDLINE (no timeframe set) and major cardiovascular congresses (2005-2008) were searched. Articles and abstracts with safety and drug interaction data were included.
  
  
  RESULTS
  Aliskiren may share common adverse effects observed with angiotensin-converting enzyme (ACE)-inhibitor and angiotensin receptor blocker (ARB) therapy. In placebo-controlled trials, those commonly reported for aliskiren at the approved dosage were headache, diarrhea, for personal and fatigue, with incidences similar to those of placebo. Aliskiren has been well tolerated in black, geriatric, diabetic, or obese patients and patients with renal or hepatic impairment. Aliskiren neither inhibits nor induces the cytochrome P450 system; it does not inhibit P-glycoprotein, but is a substrate for this drug transporter. Adding a direct renin inhibitor to another renin-angiotensin-aldosterone system (RAAS) inhibitor may further improve cardiovascular outcomes, renal outcomes, or both, without increasing the incidence of adverse effects.
  
  
  CONCLUSIONS
  Aliskiren is well tolerated, has an adverse effect profile comparable to that of placebo, and has a low potential for drug interactions. Data from ongoing trials evaluating the effects of aliskiren on surrogate markers, morbidity, and mortality will further define the role of direct renin inhibition in the antihypertensive armamentarium.
authors.affiliation: Baylor College of Medicine, Texas Heart Institute, St Luke's Episcopal Hospital, Houston, TX 77030, USA. haroonur.rashid@kelsery-seybold.com
authors.forename: Haroonur
authors.initials: H
authors.lastname: Rashid
mesh_terms: D000577:Amides / Q000009:adverse effects / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D005650:Fumarates / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D010919:Placebos; D000092502:Renin Inhibitors
chemical_list: D000577:Amides; D000959:Antihypertensive Agents; D005650:Fumarates; D010919:Placebos; D000092502:Renin Inhibitors; C446481:aliskiren