A Prospective Study of Azilsartan Medoxomil in the Treatment of Patients with Essential Hypertension and Type 2 Diabetes in Asia

This phase 4 study evaluated the efficacy and safety of azilsartan medoxomil (AZL-M) in patients with essential hypertension and type 2 diabetes mellitus (T2DM) in Hong Kong, Taiwan, and Thailand. This was a prospective, multicenter, single-arm, open-label study with patients aged 18–75 years with T2DM and essential hypertension and on stable treatment for T2DM. Patients with uncontrolled hypertension were treated with AZL-M 40 mg daily, with the option to uptitrate to 80 mg at 6 weeks. In all, 380 of the 478 patients screened in Hong Kong, Taiwan, and Thailand were enrolled. At week 6, 97 patients (25.5%) were titrated up to AZL-M 80 mg based on BP readings. At 12 weeks, 54.8% of patients reached the blood pressure (BP) goal of <140/85 mm Hg by trough sitting clinic BP (primary endpoint), and 62.8% and 27.0% achieved a BP of <140/90 mm Hg and <130/80 mm Hg, respectively. The efficacy of AZL-M over 12 weeks was also seen in different age and body mass index groups. The incidence of treatment emergent adverse events (TEAEs) was 12.9% before 6 weeks and 16.1% after 6 weeks, and they were mostly mild in severity. The most frequent TEAE was dizziness (4.7%). The incidence of TEAEs leading to study drug discontinuation (4.5%) and drug-related TEAEs (5.0% before 6 weeks; 3.9% after 6 weeks) was low. In patients with essential hypertension and T2DM in Asia, treatment with AZL-M indicated a favorable efficacy and safety profile in achieving target BP.

Efficacy and safety of azilsartan medoxomil in various doses in patients with metabolic disorders

Background. Obesity is an independent risk factor of the cardiovascular complications in patients with arterial hypertension (HTN). It can directly contribute to an increase in blood pressure (BP). Thus, the treatment of patients with HTN and obesity becomes a complex clinical problem, which requires new highly effective antihypertensive drugs. Aim. To assess the effectiveness and safety of novel angiotensin II receptor blocker azilsartan medoxomil (AZL-M) as monotherapy and in free combinations with diuretics and/or calcium antagonists in obese or overweight patients with HTN in real clinical practice. Materials and methods. An international multicenter observational non-interventional prospective study of the efficacy and safety of AZL-M in patients with hypertension and overweight or obesity was performed in the Russian Federation and the Republic of Kazakhstan. Patients took the drug for 6 months in accordance with the approved local instructions for use. All examinations were performed in accordance with routine clinical practice on the basis of a physicians decision. Results. In patients prescribed AZL-M as monotherapy (without dosage changes during the study) a significant decrease in systolic and diastolic blood pressure (systolic BP and diastolic BP, respectively) was observed (p0.001, compared to baseline); the average decrease in systolic BP and diastolic BP was 30.5012.67 and 14.478.65 mmHg, respectively (n=865). Target BP (140/90 mmHg or 140/85 mmHg in patients with diabetes mellitus) was achieved in 112 (94.12%), 547 (92.24%) and 135 (88.24%) of patients who were prescribed AZL-M at doses of 20, 40, or 80 mg/day, correspondingly. In patients receiving AZL-M in combination with a diuretic or calcium antagonist, the rate of achievement of ad blood pressure targets was 78.887.5% and 81.385.5%, respectively, and the frequency of response to therapy was 68.892.9% and 81.393.9%, respectively. During the entire observation period, 43 adverse events (AEs) were recorded, the most common of which were arterial hypotension (14 cases). All AEs associated with the study drug were of mild or moderate intensity. Conclusion. AEs administered as monotherapy and as part of combination therapy provided a statistically and clinically significant decrease in BP and a high frequency of target BP achievement in patients with HTN and metabolic disorders associated with overweight or obesity. Given the high efficacy and good tolerance of the drug, AEs can be considered as the drug of choice for the treatment of HTN in patients with overweight or obesity.

Azilsartan medoxomil: opportunities and prospects in diabetes mellitus

Current data on the prevalence of hypertension and diabetes mellitus (DM) are presented. Concomitant DM complicates the course of cardiac diseases, affecting the effectiveness of antihypertensive therapy. Along with high blood pressure, lipid and carbohydrate metabolism parameters should be corrected. Nephroprotection is also important in these patients. These goals are achievable due to the pleiotropic effects of some drugs. The analytical paper reviews the pleiotropic organoprotective effects of the antihypertensive drug azilsartan medoxomil. The data on its antihypertensive efficacy versus other angiotensin II receptor blockers are presented. In addition, the results of clinical trials in patients with various components of the metabolic syndrome (obesity, dyslipidemia, hyperglycemia) and DM are described.

Efficacy and safety of using a fixed-dose combination of azilsartan medoxomil and chlorthalidone in patients with diabetes mellitus

All resent international and national guidelines for the treatment of patients with arterial hypertension offer a unified approach to the prescription of antihypertensive therapy. The vast majority of patients, including those with diabetes mellitus, require combined drugs. Renin-angiotensin-aldosterone system blockers, calcium channel blockers or diuretics are recommended as first-line therapy. The requirements for diuretics which can be used in this category of patients are especially strong. If patients with diabetes mellitus need diuretics as part of their antihypertensive therapy, thiazide-like diuretics should be preferred. Edarbi Clo, which is a fixed-dose combination of angiotensin receptor blocker azilsartan medoxomil and thiazide-like diuretic chlorthalidone met all these requirements. Along with its strong antihypertensive effect, Edarbi Clo has a beneficial effect on metabolism parameters, inflammation parameters and prevents damage to target organs, which makes it possible to recommend it as a drug of choice in this category of patients.

Evaluating the Safety and Tolerability of Azilsartan Medoxomil alone or in combination with Chlorthalidone in the Management of Hypertension: A Systematic Review

Background and aim: 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 of 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 report ing 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. 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 is similar with the exception of 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 fixed-dose combination is an attractive treatment option for hypertension management.

Full spectrum and genetic algorithm-selected spectrum-based chemometric methods for simultaneous determination of azilsartan medoxomil, chlorthalidone, and azilsartan: Development, validation, and application on commercial dosage form

Five various chemometric methods were established for the simultaneous determination of azilsartan medoxomil (AZM) and chlorthalidone in the presence of azilsartan which is the core impurity of AZM. The full spectrum-based chemometric techniques, namely partial least squares (PLS), principal component regression, and artificial neural networks (ANN), were among the applied methods. Besides, the ANN and PLS were the other two methods that were extended by genetic algorithm procedure (GA-PLS and GA-ANN) as a wavelength selection procedure. The models were developed by applying a multilevel multifactor experimental design. The predictive power of the suggested models was evaluated through a validation set containing nine mixtures with different ratios of the three analytes. For the analysis of Edarbyclor® tablets, all the proposed procedures were applied and the best results were achieved in the case of ANN, GA-ANN, and GA-PLS methods. The findings of the three methods were revealed as the quantitative tool for the analysis of the three components without any intrusion from the co-formulated excipient and without prior separation procedures. Moreover, the GA impact on strengthening the predictive power of ANN- and PLS-based models was also highlighted.