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Journal of Hypertension Apr 2018Azilsartan medoxomil (AZL-M), an angiotensin II receptor blocker, has been developed in fixed-dose combinations (FDCs) with chlorthalidone (CTD). (Comparative Study)
Comparative Study Randomized Controlled Trial
A randomized titrate-to-target study comparing fixed-dose combinations of azilsartan medoxomil and chlorthalidone with olmesartan and hydrochlorothiazide in stage-2 systolic hypertension.
BACKGROUND
Azilsartan medoxomil (AZL-M), an angiotensin II receptor blocker, has been developed in fixed-dose combinations (FDCs) with chlorthalidone (CTD).
OBJECTIVE/METHODS
We compared FDCs of AZL-M/CTD 20/12.5 mg once daily titrated to 40/25 mg if needed or AZL-M/CTD 40/12.5 mg once daily titrated to 80/25 mg if needed with an olmesartan medoxomil (OLM)-hydrochlorothiazide (HCTZ) 20/12.5 mg FDC once daily titrated to 40/25 mg if needed in a randomized, double-blind, 8-week study of 1085 participants with clinic SBP 160-190 mmHg and DBP 119 mmHg or less. Titration to higher doses occurred at week 4 if BP was at least 140/90 mmHg (≥130/80 mmHg if diabetes or chronic kidney disease). The primary endpoint was change from baseline in clinic SBP; 24-h ambulatory BP monitoring was also measured.
RESULTS
Greater reductions in clinic SBP from a baseline of 165 mmHg were observed (P < 0.001) in both AZL-M/CTD arms (-37.6 and -38.2 mmHg) versus OLM/HCTZ (-31.5 mmHg), despite greater dose titration in the OLM/HCTZ group. At 8 weeks, both AZL-M/CTD FDCs reduced 24-h SBP more than OLM/HCTZ (-26.4 and -27.9 versus -20.7 mmHg; both P < 0.001), and higher proportions in both AZL-M/CTD groups achieved target BP compared with the OLM/HCTZ group (69.4 and 68.9 versus 54.7%, both P < 0.001). Adverse events leading to drug discontinuation occurred in 6.2, 9.5, and 3.1% with the AZL-M/CTD lower and higher doses, and OLM/HCTZ, respectively.
CONCLUSION
This large, titration-to-target BP study demonstrated AZL-M/CTD FDCs to have superior antihypertensive efficacy compared with the maximum approved dose of OLM/HCTZ.
Topics: Aged; Antihypertensive Agents; Benzimidazoles; Blood Pressure; Chlorthalidone; Diuretics; Double-Blind Method; Drug Combinations; Female; Humans; Hydrochlorothiazide; Hypertension; Imidazoles; Male; Middle Aged; Oxadiazoles; Tetrazoles
PubMed: 29334491
DOI: 10.1097/HJH.0000000000001647 -
Journal of Clinical Hypertension... Mar 2007This 12-week, randomized, double-blind, forced-titration study compared the efficacy of 3 angiotensin receptor blockers. Patients received olmesartan medoxomil 20 mg,... (Randomized Controlled Trial)
Randomized Controlled Trial
This 12-week, randomized, double-blind, forced-titration study compared the efficacy of 3 angiotensin receptor blockers. Patients received olmesartan medoxomil 20 mg, losartan potassium 50 mg, valsartan 80 mg, or placebo once daily. At week 4, doses were titrated to 40, 100, and 160 mg once daily for olmesartan, losartan, and valsartan, respectively. At week 8, losartan was increased to 50 mg twice daily and valsartan increased to 320 mg once daily (olmesartan remained at 40 mg once daily). The primary end point was mean change from baseline in seated diastolic blood pressure (SeDBP) at week 8. All 3 medications significantly reduced mean SeDBP from baseline compared with placebo at weeks 4, 8, and 12 (P<.001). At week 8, olmesartan reduced mean SeDBP more than losartan (P<.001); more patients in the olmesartan medoxomil group achieved a blood pressure goal of <140/90 mm Hg (P<.001). Olmesartan did not reduce mean SeDBP significantly compared with valsartan, although more patients attained blood pressure goal with olmesartan (P=.031). At week 12, all agents lowered blood pressure equivalently.
Topics: Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Blood Pressure; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Hypertension; Imidazoles; Losartan; Male; Middle Aged; Olmesartan Medoxomil; Severity of Illness Index; Single-Blind Method; Tetrazoles; Treatment Outcome; Valine; Valsartan
PubMed: 17341994
DOI: 10.1111/j.1524-6175.2007.06395.x -
Cureus Jul 2023Olmesartan is a commonly used antihypertensive medication belonging to the class of angiotensin II receptor blockers. Though generally well-tolerated, olmesartan can...
Olmesartan is a commonly used antihypertensive medication belonging to the class of angiotensin II receptor blockers. Though generally well-tolerated, olmesartan can rarely cause olmesartan-associated enteropathy (OAE) with non-bloody diarrhea, weight loss, abdominal pain, and vomiting. Patients may develop enteropathy months to years after drug initiation. In severe cases, patients may develop complications that require hospitalization. Diagnosis is often delayed due to unfamiliarity of OAE, nonspecific presenting symptoms, and normal-appearing gross endoscopic findings. Esophagogastroduodenoscopy (EGD) with biopsy is essential to the diagnosis, showing sprue-like enteropathy with intestinal villous atrophy and mucosal inflammation. This report describes a case of a 70-year-old man who presented with three months of profuse watery diarrhea and 40-pound unintentional weight loss. After an extensive workup, including EGD with duodenal biopsies, the patient was diagnosed with OAE. The biopsies showed findings consistent with acute and chronic duodenitis, mucosal desquamation and ulceration, blunting of villi, and a sprue-like pattern with neutrophils. Celiac serologies and anti-enterocyte antibodies were negative, further supporting the diagnosis of OAE. Complete resolution of symptoms was achieved by discontinuing olmesartan and administering a steroid taper. Considering the frequent use of olmesartan, the increasing occurrence of OAE, and the wide range of associated symptoms, it is crucial for providers to recognize OAE and consider early discontinuation of olmesartan. This approach can help prevent further intestinal damage, protracted symptoms, unnecessary diagnostic tests, and financial burdens on both patients and the healthcare system.
PubMed: 37559845
DOI: 10.7759/cureus.41604 -
Indian Journal of Pharmaceutical... Sep 2009Two methods for simultaneous estimation of hydrochlorothiazide and olmesartan medoxomil in combined tablet dosage form have been developed. The first method is the...
Two methods for simultaneous estimation of hydrochlorothiazide and olmesartan medoxomil in combined tablet dosage form have been developed. The first method is the application of Q-analysis method (absorbance ratio), which involves the formation of Q-absorbance equation at 264 nm (isobestic point) and at 271 nm, the maximum absorption of hydrochlorothiazide. The linearity ranges for hydrochlorothiazide and olmesartan medoxomil were 2.5-22.5 mug/ml and 4-36 mug/ml, respectively. The second method is based on the derivative spectrophotometric method at zero crossing wavelengths. The linearity ranges for hydrochlorothiazide and olmesartan medoxomil were 2.5-20 mug/ml and 4-32 mug/ml, respectively. The accuracy of the methods were assessed by recovery studies and was found to be 100.45% +/-0.4215 and 100.24% +/-0.3783 for absorbance ratio method and 99.39% +/-0.221 and 99.72% +/-0.11 for first derivative method, for hydrochlorothiazide and olmesartan medoxomil, respectively. These methods are simple, accurate and rapid, those require no preliminary separation and can therefore be used for routine analysis of both drugs in quality control laboratories.
PubMed: 20502567
DOI: 10.4103/0250-474X.58176 -
Journal of Pharmaceutics 2013Olmesartan medoxomil (OLM) is an angiotensin II receptor blocker (ARB) antihypertensive agent administered orally that has absolute bioavailability of only 26% due to...
Olmesartan medoxomil (OLM) is an angiotensin II receptor blocker (ARB) antihypertensive agent administered orally that has absolute bioavailability of only 26% due to the poor aqueous solubility (7.75 μg/ml). The aim of the present investigation was to develop a self-microemulsifying drug delivery system (SMEDDS) to enhance the oral absorption of OLM. The solubility of OLM in various oils, surfactants, and cosurfactants was determined. Pseudoternary phase diagrams were constructed using Acrysol EL 135, Tween 80, Transcutol P, and distilled water to identify the efficient self-microemulsification region. Prepared SMEDDS was further evaluated for its emulsification time, drug content, optical clarity, droplet size, zeta potential, in vitro dissolution, and in vitro and ex vivo drug diffusion study. The optimized formulation S2 contained OLM (20 mg), Tween 80 (33%v/v), Transcutol P (33%v/v), and Acrysol EL 135 (34%v/v) had shown the smallest particle size, maximum solubility, less emulsification time, good optical clarity, and in vitro release. The in vitro and ex vivo diffusion rate of the drug from the SMEDDS was significantly higher than that of the plain drug suspension. It was concluded that SMEDDS would be a promising drug delivery system for poorly water-soluble drugs by the oral route.
PubMed: 26555991
DOI: 10.1155/2013/728425 -
Journal of Clinical Hypertension... Oct 2004Most hypertensive patients require more than one drug for adequate blood pressure (BP) control. The seventh report of the Joint National Committee on Prevention,... (Review)
Review
Most hypertensive patients require more than one drug for adequate blood pressure (BP) control. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure recommends starting treatment with a thiazide diuretic or, when BP is >20/10 mm Hg above goal or in patients with diabetes, using two different antihypertensive agents. Searches of Medline, EMBASE, and BIOSIS databases identified four similarly designed, randomized, factorial studies comparing various doses of angiotensin II receptor blockers with hydrochlorothiazide as monotherapy and in combination. The methodology and results of these studies were compared. The primary efficacy end point in these studies was a decrease from baseline in mean diastolic BP after 8 weeks of therapy. All currently available angiotensin I receptor blocker/hydrochlorothiazide combinations evaluated (irbesartan, olmesartan medoxomil, telmisartan, and valsartan plus hydrochlorothiazide) produced significant systolic BP and diastolic BP reductions. Olmesartan medoxomil/hydrochlorothiazide 40 mg/25 mg provided the largest mean reduction in absolute and placebo-corrected systolic BP/diastolic BP. For all angiotensin II receptor blocker/hydrochlorothiazide combinations evaluated, > or =63% of patients achieved a diastolic BP response (diastolic BP <90 mm Hg or > or =10-mm Hg reduction). In conclusion, the combination of an angiotensin II receptor blocker and hydrochlorothiazide produces more substantial BP responses than monotherapy with either component.
Topics: Angiotensin-Converting Enzyme Inhibitors; Drug Therapy, Combination; Humans; Hydrochlorothiazide; Hypertension; Randomized Controlled Trials as Topic
PubMed: 15470286
DOI: 10.1111/j.1524-6175.2004.02632.x -
Congestive Heart Failure (Greenwich,... 2002Angiotensin II receptor blockers (ARBs) have been available in the United States since 1995. These agents have demonstrated antihypertensive efficacy at least similar to... (Review)
Review
Angiotensin II receptor blockers (ARBs) have been available in the United States since 1995. These agents have demonstrated antihypertensive efficacy at least similar to that of agents from other antihypertensive classes. Recent large-scale, randomized, controlled clinical trials have demonstrated that ARBs offer cardiovascular and renal protective benefits independent of their effects on systemic blood pressure (BP), which make them valuable as first-line antihypertensive agents, especially in high-risk patients. However, as is the case with other antihypertensive classes, monotherapy with the first-available ARBs (losartan potassium, valsartan, and irbesartan) may not provide sufficient BP reduction to achieve currently recommended BP goals in many patients. The diuretic hydrochlorothiazide is frequently added to enhance the ability of ARBs to lower BP. Several head-to-head comparison studies have shown differences in antihypertensive efficacy among the available ARBs. The newest ARB, olmesartan medoxomil, was recently compared with losartan potassium, irbesartan, and valsartan in a prospective, head-to-head, randomized trial. In this study, olmesartan medoxomil demonstrated a significantly greater reduction in diastolic BP, the primary end point, compared with the other three ARBs. Further, a review of the absolute reductions in diastolic BP achieved with olmesartan medoxomil monotherapy appears comparable to that of previously available ARBs when they are used in combination with hydrochlorothiazide. These comparisons may have important clinical implications regarding the optimal choice of first-line antihypertensive therapy.
Topics: Angiotensin Receptor Antagonists; Antihypertensive Agents; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Therapy, Combination; Humans; Hydrochlorothiazide; Hypertension; Imidazoles; Olmesartan Medoxomil; Randomized Controlled Trials as Topic; Receptors, Angiotensin; Tetrazoles; Treatment Outcome; United States
PubMed: 12461321
DOI: 10.1111/j.1527-5299.2002.02077.x -
Acta Pharmaceutica (Zagreb, Croatia) Mar 2010A simple, sensitive and precise RP-HPLC-DAD method was developed and validated for the determination of olmesartan medoxomil (AT-II receptor blocker) in the presence of... (Comparative Study)
Comparative Study
A simple, sensitive and precise RP-HPLC-DAD method was developed and validated for the determination of olmesartan medoxomil (AT-II receptor blocker) in the presence of its degradation products. Olmesartan medoxomil and all the degradation products were resolved on a C(18) column with the mobile phase composed of methanol, acetonitrile and water (60:15:25, V/V/V, pH 3.5 by orthophosphoric acid) at 260 nm using a photodiode array detector. The method was linear over the concentration range of 1-18 microg mL(-1) and precise with RSD < 1 % in intra- and inter-day study. Excellent recoveries of 99.3 +/- 0.9 to 100.8 +/- 1.2% proved the accuracy of the method. Developed method was specific, as indicated by chromatographic resolution > 2.0 for each peak and sensitive with LOD 0.03 microg mL(-1) and LOQ 0.1 microg mL(-1). The method was used to study the drug degradation behavior under forced conditions. Four degradation products (DP-I, II, III, IV) were formed during the degradation study in 0.1 mol L(-1) HCl whereas only DP-I, II and III were formed in water, 0.01 mol L(-1) NaOH and 3% H(2)O(2). No significant thermal or photolytic degradation was observed in solid drug. The method was applied successfully for the assay of olmesartan medoxomil in the tablet dosage form.
Topics: Chemistry, Pharmaceutical; Chromatography, High Pressure Liquid; Imidazoles; Olmesartan Medoxomil; Reproducibility of Results; Tablets; Tetrazoles
PubMed: 20228038
DOI: 10.2478/v10007-010-0010-2 -
Journal of Clinical Hypertension... Sep 2017This 52-week, randomized, open-label study evaluated long-term safety/tolerability of fixed-dose combination azilsartan medoxomil/chlorthalidone (AZL-M/CLD) vs... (Comparative Study)
Comparative Study Randomized Controlled Trial
This 52-week, randomized, open-label study evaluated long-term safety/tolerability of fixed-dose combination azilsartan medoxomil/chlorthalidone (AZL-M/CLD) vs fixed-dose combination olmesartan medoxomil/hydrochlorothiazide (OLM/HCTZ) in patients with essential hypertension (stage 2; clinic systolic blood pressure 160-190 mm Hg). Initial AZL-M/CLD 40/12.5 mg/d (n=418) or OLM/HCTZ 20/12.5 mg/d (n=419) could be uptitrated during weeks 4 to 52 (AZL-M/CLD to 80/25 mg; OLM/HCTZ to 40/25 mg [United States] or 20/25 mg [Europe]) to meet blood pressure targets. Treatment-emergent adverse events/serious adverse events occurred in 78.5%/5.7% of patients taking AZL-M/CLD vs 76.4%/6.2% taking OLM/HCTZ. The most frequent adverse events were dizziness (16.3% vs 12.6%), blood creatinine increase (21.5% vs 8.6%), headache (7.4% vs 11.0%), and nasopharyngitis (12.2% vs 11.5%). Hypokalemia was uncommon (1.0% vs 0.7%). Greater blood pressure reductions with AZL-M/CLD by week 2 were maintained throughout the study, despite less uptitration (32.3% vs 48.9% with OLM/HCTZ). Fixed-dose combination AZL-M/CLD showed an encouraging benefit-risk profile when used per standard clinical practice in a titrate-to-target strategy.
Topics: Aged; Aged, 80 and over; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Benzimidazoles; Blood Pressure; Chlorthalidone; Diuretics; Dose-Response Relationship, Drug; Drug Therapy, Combination; Essential Hypertension; Female; Humans; Hydrochlorothiazide; Male; Middle Aged; Olmesartan Medoxomil; Oxadiazoles; Treatment Outcome
PubMed: 28681550
DOI: 10.1111/jch.13009 -
American Journal of Cardiovascular... Apr 2016
Erratum to: Efficacy and Safety Study of Olmesartan Medoxomil, Amlodipine, and Hydrochlorothiazide Combination Therapy in Patients with Hypertension Not Controlled with Olmesartan Medoxomil and Hydrochlorothiazide Combination Therapy: Results of a Randomized, Double-Blind, Multicenter Trial.
PubMed: 26994003
DOI: 10.1007/s40256-016-0167-2