Safety of Candesartan, Amlodipine, and Atorvastatin in Combination: Interaction Study in Healthy Subjects

For efficient cardiovascular risk protection antihypertensive treatment is often combined with cholesterol-lowering treatment, although solid data of interaction and side effects are missing. This is a prospective, single-center interaction study conducted in a fixed sequence design at steady state of candesartan, amlodipine, and atorvastatin. Five-day monotherapy of candesartan 8 mg was followed by 5-day atorvastatin 40 mg monotherapy and subsequently 9-day amlodipine 5 mg monotherapy; each treatment separated by washout phases. Immediately after amlodipine monotherapy, all 3 drugs were administered concomitantly for 5 days. Pharmacokinetic parameters as well as safety were assessed. Eighteen healthy subjects enrolled and completed the study. No significant difference in the maximum concentration (C_max ) and the area the under plasma concentration-time curve (AUC) for amlodipine and AUC of atorvastatin was detected following combination versus monotherapy. C_max of atorvastatin decreased slightly but clinically not relevantly when given in combination. A statistically significant but not below 0.80-fold decrease between candesartan following combination vs monotherapy was detected for C_max and AUC. In general, all treatments were well tolerated. Concluding, systemic exposure of candesartan, amlodipine, and atorvastatin is not clinically significantly changed upon coadministration. These data support a fixed-dose combination of the 3 components for dual cardiovascular risk prevention.