Aliskiren and amlodipine (Tekamlo): A new combination renin inhibitor and dihydropyridine calcium channel blocker for the treatment of hypertension

Combination aliskiren and amlodipine 150 mg/5 mg-, 150 mg/10 mg-, 300 mg/5 mg-, and 300 mg/10 mg-tablets have been recently approved by FDA as an initial therapy to treat hypertension in patients likely to need multiple drugs to achieve their blood pressure goals, in hypertensive patients not adequately controlled with monotherapy, or as a substitute for its individual components. The effects of combined treatment of aliskiren and amlodipine arise from the actions of 2 antihypertensive agents on different, but complementary mechanisms of action.

Efficacy. Aliskiren and amlodipine has been studied in a total of 5,549 patients with mild to moderate hypertension (diastolic blood pressure between 90 mmHg and 109 mmHg). In an 8-week, randomized, double-blind, placebo-controlled, multifactorial trial comparing the combinations 150 mg/5 mg, 150 mg/10 mg, 300 mg/5 mg, and 300 mg/10 mg of aliskiren and amlodipine with their individual components and placebo, the combination of aliskiren and amlodipine resulted in a statistically significant placebo-adjusted decreases in systolic/diastolic blood pressure at trough of 14-17/9-11 mmHg compared to 4-9/3-5 mmHg for aliskiren alone and 9-14/6-8 mmHg for amlodipine alone. Moreover, 2 additional double-blind, active controlled trials were conducted in which aliskiren and amlodipine was administered as initial therapy in patients with moderate to severe hypertension (systolic blood pressure between 160 and 200 mmHg). In one of these trials, which enrolled 443 black patients, at the primary end point of 8 weeks, the treatment difference between aliskiren/amlodipine and amlodipine was 5.2/3.8 mmHg. In the other trial of 484 patients, at the primary end point of 8 weeks, the treatment difference between aliskiren/amlodipine and amlodipine was 7.1/3.8 mmHg.

Safety. Aliskiren and amlodipine has been evaluated for safety in more than 2,800 patients during clinical trials, including 372 patients for 1 year or longer. Overall, the incidence of adverse events on therapy with aliskiren and amlodipine appears to be similar to that of taking the individual components. During clinical trials of aliskiren and amlodipine, discontinuation of therapy due to a clinical adverse event occurred in 1.7% of patients. The most common adverse event (incidence ≥2% and more common than with placebo) seen with aliskiren and amlodipine is peripheral edema. As aliskiren and amlodipine contains a drug that acts directly on the RAAS, it can cause injury or death to a developing fetus.