Evaluating the Safety and Tolerability of Azilsartan Medoxomil Alone or in Combination With Chlorthalidone in the Management of Hypertension: A Systematic Review

Background: Azilsartan medoxomil (AZM) is the newest representative in the class of angiotensin receptor blockers. Azilsartan medoxomil in combination with the older diuretic chlorthalidone (CLD) in fixed-doses of AZM/CLD 40/12.5 mg and 40/25 mg has been approved by the FDA for use in patients with essential hypertension. We sought to evaluate the safety and tolerability of AZL-M alone and in combination with CLD. Methods: We conducted a search in PubMed using the keywords ‘azilsartan’, ‘azilsartan medoxomil’, ‘chlorthalidone, ‘safety’, ‘tolerability’ in order to find scientific studies evaluating the safety of these drugs. We included studies reporting side effects of these drugs, alone or in combination, in comparison to placebo or other antihypertensive medications. For our systematic review, we followed the PRISMA guidelines. Results: Azilsartan medoxomil is a potent antihypertensive medicine with an acceptable safety profile. The most commonly reported adverse events are dizziness, headache, fatigue, upper respiratory tract infection and urinary tract infection. Chlorthalidone is more potent and has a considerably longer duration of action than the most commonly prescribed diuretic hydrochlorothiazide. Safety and tolerability between these two drugs are similar except higher serum uric acid and lower potassium levels with chlorthalidone. Conclusions: The combination of azilsartan medoxomil with chlorthalidone has been shown to be effective in lowering blood pressure with an acceptable safety and tolerability profile. This fixeddose combination is an attractive treatment option for hypertension management.