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High Blood Pressure & Cardiovascular... Sep 2017Recent epidemiological surveys have demonstrated that effective and sustained blood pressure (BP) control is achieved in a relatively small proportion of treated... (Review)
Review
Recent epidemiological surveys have demonstrated that effective and sustained blood pressure (BP) control is achieved in a relatively small proportion of treated hypertensive patients. Indeed, treatment of hypertension represents a key strategy for preventing coronary artery disease, stroke, congestive heart failure and cardiovascular death. Several interventions have been proposed by international guidelines for ameliorating hypertension management and control, mostly including integrated and multi-dimensional pharmacological and non-pharmacological strategies. In particular, numerous evidence demonstrated that a more extensive use of combination therapy may represent a valid therapeutic option for treating hypertensive patients at different risk profile. This strategy has been definitely strengthened by the availability of single pill fixed-dose combinations. Among potential combination therapies, those based on the association of renin-angiotensin system antagonists, thiazide diuretics and calcium channel blockers are very effective in lowering BP levels and well tolerated. We will provide here an overview of clinical evidence supporting the use of triple combination therapy, with a focus on that based on olmesartan medoxomil, a thiazide diuretic (hydrochlorothiazide) and a calcium channel blocker (amlodipine besylate), which is available in multiple dosages. Finally, in view of the recognised importance of single-pill combination therapy for treating hypertension, we will examine the potential benefits of dual (fixed) combination therapy based on olmesartan medoxomil with either thiazide diuretic hydrochlorothiazide or calcium channel blocker amlodipine in terms of efficacy, safety and tolerability profile.
Topics: Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Blood Pressure; Drug Therapy, Combination; Humans; Hypertension; Imidazoles; Olmesartan Medoxomil; Precision Medicine; Renin-Angiotensin System; Tetrazoles; Time Factors; Treatment Outcome
PubMed: 28608025
DOI: 10.1007/s40292-017-0217-0 -
High Blood Pressure & Cardiovascular... Sep 2017Olmesartan medoxomil is an antihypertensive drug of the class of angiotensin II type 1 (AT1) receptor antagonists (or blockers), characterized by tight and prolonged... (Review)
Review
Olmesartan medoxomil is an antihypertensive drug of the class of angiotensin II type 1 (AT1) receptor antagonists (or blockers), characterized by tight and prolonged binding to AT1 receptor compared to other molecules within the same class. These characteristics produce effective and sustained blood pressure reductions in hypertensive patients at different cardiovascular risk profile with a good tolerability profile. After a brief description of the pharmacological characteristics of olmesartan, we will provide a thorough overview of the clinical studies that investigated its efficacy and safety in the clinical management of hypertensive patients both in monotherapy and in dual combination therapies with either thiazide diuretics or calcium channel blockers. These studies demonstrated that olmesartan-based antihypertensive strategy may indeed provide sustained BP control over the 24-h period in a wide proportion of hypertensive patients, thus contributing to a substantial progress in hypertension management. Finally, since growing evidence suggest that olmesartan may also exert potential favourable effects at vascular level, thereby antagonizing the vascular inflammatory process involved in the development and progression of atherosclerosis, the main clinical studies addressing this issue will be also discussed.
Topics: Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Blood Pressure; Drug Therapy, Combination; Humans; Hypertension; Imidazoles; Olmesartan Medoxomil; Tetrazoles; Time Factors; Treatment Outcome
PubMed: 28608026
DOI: 10.1007/s40292-017-0216-1 -
The American Journal of Cardiology Nov 2018Two post hoc analyses in self-identified black and white patients with hypertension evaluated the angiotensin II receptor blocker azilsartan medoxomil (AZL-M) and the... (Randomized Controlled Trial)
Randomized Controlled Trial
Two post hoc analyses in self-identified black and white patients with hypertension evaluated the angiotensin II receptor blocker azilsartan medoxomil (AZL-M) and the fixed-dose combination of AZL-M with chlorthalidone (AZL-M/CLD) versus the ARB olmesartan (OLM) and the OLM fixed-dose combination with hydrochlorothiazide (OLM/HCTZ). One analysis pooled 1,610 patients from two 6-week randomized controlled trials to compare once daily AZL-M 40 mg, AZL-M 80 mg, OLM 40 mg, and placebo. The second analysis included 1,020 patients from a 12-week randomized controlled trial to compare once daily AZL-M/CLD 40/25 mg, AZL-M/CLD 80/25 mg, and OLM/HCTZ 40/25 mg. Efficacy end points were 24-hour mean ambulatory and clinic systolic and diastolic blood pressure (SPB/DBP) and the percentage of patients achieving clinic SBP/DBP targets. Treatment with AZL-M 80 mg lowered mean clinic SBP by 12.5 mm Hg (p <0.01 vs OLM), treatment with AZL-M/CLD 40 mg/25 mg lowered mean ambulatory SBP by 31.0 mm Hg and mean clinic SBP by 39.3 mm Hg (both p <0.05 vs OLM/HCTZ), and treatment with AZL-M/CLD 80 mg/25 mg lowered mean ambulatory SBP by 34.4 mm Hg (p <0.01 vs OLM/HCTZ) and mean clinic SBP by 39.2 mm Hg (p <0.05 vs OLM/HCTZ). Target BP goals were achieved more frequently with AZL-M versus OLM and with AZL-M/CLD versus OLM/HCTZ. In conclusion, in both black and white patients, BP was lowered more effectively with AZL-M versus OLM and with AZL-M/CLD versus OLM/HCTZ. The AZL-M/CLD 40 mg/25 mg combination resulted in a statistically significant reduction in BP in both black and white patients.
Topics: Black or African American; Aged; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Benzimidazoles; Chlorthalidone; Dose-Response Relationship, Drug; Drug Combinations; Female; Humans; Hydrochlorothiazide; Hypertension; Imidazoles; Male; Middle Aged; Oxadiazoles; Tetrazoles; United States; White People
PubMed: 30217371
DOI: 10.1016/j.amjcard.2018.07.022 -
Journal of Clinical Hypertension... May 2021Angiotensin-receptor blockers are often considered insufficiently efficacious in reducing blood pressure. However, newer angiotensin-receptor blockers may be more... (Meta-Analysis)
Meta-Analysis
Is the newest angiotensin-receptor blocker azilsartan medoxomil more efficacious in lowering blood pressure than the older ones? A systematic review and network meta-analysis.
Angiotensin-receptor blockers are often considered insufficiently efficacious in reducing blood pressure. However, newer angiotensin-receptor blockers may be more effective than the older ones. A network meta-analysis was performed to compare the efficacy of various angiotensin-receptor blockers in reducing office and ambulatory blood pressure in hypertensive patients. Relevant literature was searched from English and Chinese databases for randomized controlled trials involving angiotensin-receptor blockers in hypertension. Efficacy variables included systolic and diastolic blood pressure either in the office or on ambulatory blood pressure monitoring. Absolute blood pressure reductions at 6-12 weeks of treatment and their credible intervals were reported. A total of 34 publications provided adequate data for analysis (n = 14 859). In 28 studies on office systolic blood pressure (n = 12 731), against the common comparator valsartan 80 mg, the differences in systolic blood pressure were in favor of azilsartan medoxomil (20-80 mg), irbesartan (300 mg), olmesartan (20-40 mg), telmisartan (80 mg), and valsartan (160-320 mg), but not candesartan (8-16 mg), losartan (50-100 mg), irbesartan (150 mg), olmesartan (10 mg), and telmisartan (40 mg). The ranking plot shows that azilsartan medoxomil 80 mg had a possibility of 99% being the best in the class. Similar results were observed for office diastolic blood pressure and from 13 studies for 24-hour ambulatory systolic and diastolic blood pressure. In conclusion, angiotensin-receptor blockers had different blood pressure lowering efficacy. The newest angiotensin-receptor blocker azilsartan medoxomil at the dose of 80 mg seemed to be most efficacious in reducing both systolic and diastolic blood pressure in the office and on ambulatory measurement.
Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Angiotensins; Antihypertensive Agents; Benzimidazoles; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Humans; Hypertension; Network Meta-Analysis; Olmesartan Medoxomil; Oxadiazoles; Tetrazoles
PubMed: 33609077
DOI: 10.1111/jch.14227 -
Clinical Pharmacology in Drug... Jun 2022Combined antihypertensive drugs have become the basic method of treating hypertension. Olmesartan and amlodipine, as representative drugs of angiotensin receptor... (Randomized Controlled Trial)
Randomized Controlled Trial
Pharmacokinetics and Bioequivalence Evaluation of 2 Olmesartan Medoxomil and Amlodipine Besylate Fixed-Dose Combination Tablets in Healthy Chinese Volunteers Under Fasting and Fed Conditions.
Combined antihypertensive drugs have become the basic method of treating hypertension. Olmesartan and amlodipine, as representative drugs of angiotensin receptor blockers and calcium channel blockers, were developed as a compound formulation for antihypertensive treatment. The purpose of this study was to evaluate the bioequivalence of olmesartan medoxomil/amlodipine besylate tablet (20 mg/5 mg) under fasting and fed conditions in healthy Chinese volunteers. A phase 1 randomized, open-label, 2-period, single-dose crossover study (n = 56) was designed, with subjects under fasting (n = 28) or fed (n = 28) conditions. Of the 56 enrolled participants, 55 healthy volunteers completed the study. Blood samples for pharmacokinetic analysis were collected from 1.5 hours before dosing to 168 hours after dosing. The 90%CIs for the geometric mean ratios of maximum plasma drug concentration, area under the plasma concentration-time curve (AUC) from time 0 to the last measurable concentration and AUC from time 0 to infinity of the test/reference were all within the acceptance range for bioequivalence (80%-125%). The data showed that the absorption of amlodipine is not affected by food, but the exposure of olmesartan (both AUC from time 0 to the last measurable concentration and AUC from time 0 to infinity were P < .05) reduced significantly after consuming a high-fat meal, which indicates that the effects of food on olmesartan exposure in healthy Chinese were clinically relevant. During the study, there were no suspected serious adverse reactions or serious adverse events. All adverse events were determined to be mild after Common Terminology Criteria for Adverse Events 5.0 evaluation. These results indicated that both the test and reference formulations were bioequivalent with similar safety profiles.
Topics: Amlodipine; Antihypertensive Agents; China; Cross-Over Studies; Fasting; Healthy Volunteers; Humans; Olmesartan Medoxomil; Tablets; Therapeutic Equivalency
PubMed: 35289500
DOI: 10.1002/cpdd.1086 -
Journal of Clinical Hypertension... Apr 2018An open-label, long-term study evaluated safety and tolerability of azilsartan medoxomil/chlorthalidone (AZL-M/CLD) vs olmesartan/hydrochlorothiazide (OLM/HCTZ) in... (Comparative Study)
Comparative Study Randomized Controlled Trial
An open-label, long-term study evaluated safety and tolerability of azilsartan medoxomil/chlorthalidone (AZL-M/CLD) vs olmesartan/hydrochlorothiazide (OLM/HCTZ) in hypertensive participants with stage 3 chronic kidney disease. Initial therapy was AZL-M/CLD 20/12.5 mg (n = 77) or OLM/HCTZ 20/12.5 mg (n = 76), but could be up-titrated (AZL-M/CLD to 40/25 mg; OLM/HCTZ to 40/25 mg [US] or 20/25 mg [Europe]) with other agents added during weeks 4-52. Primary endpoint was proportion of participants with ≥ 1 adverse event (AE) through week 52. Baseline demographics were similar. AEs did not differ between groups (88.3%, AZL-M/CLD vs 76.3%, OLM/HCTZ; P = .058). AZL-M/CLD showed greater systolic BP reductions after initial dosing (P = .037) but not during long-term follow-up (P = .588). A greater proportion of participants up-titrated to the highest dose with OLM/HCTZ (48.7%) vs AZL-M/CLD (29.9%) (P = .021) and were taking additional antihypertensive medications (26.3% vs 16.9%). Both AZL-M/CLD and OLM/HCTZ showed similar efficacy and tolerability.
Topics: Aged; Benzimidazoles; Chlorthalidone; Drug Therapy, Combination; Female; Humans; Hydrochlorothiazide; Hypertension; Male; Middle Aged; Olmesartan Medoxomil; Oxadiazoles; Renal Insufficiency, Chronic; Treatment Outcome
PubMed: 29504252
DOI: 10.1111/jch.13230 -
Pakistan Journal of Pharmaceutical... Nov 2022This study aims to formulate Olmesartan medoxomil (OM) into oral fast-dissolving tablets (FDTs) to improve its solubility and bioavailability via two different...
This study aims to formulate Olmesartan medoxomil (OM) into oral fast-dissolving tablets (FDTs) to improve its solubility and bioavailability via two different techniques; The polymer-based surface solid dispersion (SSD) technique and the solidified surfactant (SS) technique. In the first technique, two polymers were used; polyvinylpyrrolidone (PVP K90) and Poloxamer 407 (Pluronic®F127), while in the second technique the liquid Tween 80 was solidified by adsorption onto Aeroperl®300. The pre-compression and post-compression parameters of the obtained formulations were assessed. The best formulations were subjected to a taste masking evaluation and a short-term stability study. The results demonstrated that, in comparison to the pure drug, the proportion of drug released from each of the prepared FDTs considerably increased. Results of the stability studies showed that the chosen drug formulations remained stable throughout the storage period.
Topics: Olmesartan Medoxomil; Surface-Active Agents; Solubility; Polymers; Poloxamer; Pulmonary Surfactants; Biological Availability; Tablets
PubMed: 36789807
DOI: No ID Found -
Molecules (Basel, Switzerland) May 2024Olmesartan medoxomil (OLM) is a selective angiotensin II receptor antagonist used in the treatment of hypertension. Its therapeutic potential is limited by its poor...
Olmesartan medoxomil (OLM) is a selective angiotensin II receptor antagonist used in the treatment of hypertension. Its therapeutic potential is limited by its poor water solubility, leading to poor bioavailability. Encapsulation of the drug substance by two methylated cyclodextrins, namely randomly methylated β-cyclodextrin (RM-β-CD) and heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin (TM-β-CD), was carried out to overcome the limitation related to OLM solubility, which, in turn, is expected to result in an improved biopharmaceutical profile. Supramolecular entities were evaluated by means of thermoanalytical techniques (TG-thermogravimetry; DTG-derivative thermogravimetry), spectroscopic methods including powder X-ray diffractometry (PXRD), universal-attenuated total reflectance Fourier-transform infrared (UATR-FTIR) and UV spectroscopy, saturation solubility studies, and by a theoretical approach using molecular modeling. The phase solubility method reveals an -type diagram for both inclusion complexes, indicating a stoichiometry ratio of 1:1. The values of the apparent stability constant indicate the higher stability of the host-guest system OLM/RM-β-CD. The physicochemical properties of the binary systems are different from those of the parent compounds, emphasizing the formation of inclusion complexes between the drug and CDs when the kneading method was used. The molecular encapsulation of OLM in RM-β-CD led to an increase in drug solubility, thus the supramolecular adduct can be the subject of further research to design a new pharmaceutical formulation containing OLM, with improved bioavailability.
Topics: beta-Cyclodextrins; Olmesartan Medoxomil; Solubility; Spectroscopy, Fourier Transform Infrared; X-Ray Diffraction; Thermogravimetry; Models, Molecular
PubMed: 38792072
DOI: 10.3390/molecules29102209 -
Journal of Clinical Pharmacology Apr 2016Two studies (ROADMAP and ORIENT) evaluating the renoprotective effects of olmesartan medoxomil (OM) in patients with type 2 diabetes suggested OM is associated with... (Randomized Controlled Trial)
Randomized Controlled Trial
Two studies (ROADMAP and ORIENT) evaluating the renoprotective effects of olmesartan medoxomil (OM) in patients with type 2 diabetes suggested OM is associated with increased cardiovascular mortality. We conducted a thorough QTc study to evaluate the effects of OM on cardiac repolarization. A randomized, double-blind, phase 1 study was conducted per E14 Guidance to assess the effects of single doses of OM therapeutic dose (40 mg), OM supratherapeutic dose (160 mg), placebo, or moxifloxacin (MOXI; 400 mg) on QTc in 56 healthy subjects. The primary endpoint was the baseline-adjusted, placebo-corrected QTc interval using Fridericia's formula (ΔΔQTcF) for OM and MOXI. Assay sensitivity was concluded if lower limit of 1-sided 95%CI > 5 milliseconds of ΔΔQTcF for MOXI. No threshold pharmacologic effect for OM was concluded if upper limit of 1-sided 95%CI <10 milliseconds for ΔΔQTcF at any timepoint. Pharmacokinetics, ECGs, and safety were assessed. Assay sensitivity was demonstrated. The largest upper limit of the 1-sided 95%CI for ΔΔQTcF was <5 milliseconds for OM. No clinically significant changes were observed in ECGs. Pharmacokinetics and safety profile were consistent with previous data. Therapeutic and supratherapeutic OM doses had no clinically significant effect on cardiac repolarization and were well tolerated.
Topics: Adolescent; Adult; Cross-Over Studies; Diabetes Mellitus, Type 2; Double-Blind Method; Electrocardiography; Female; Healthy Volunteers; Heart; Humans; Long QT Syndrome; Male; Middle Aged; Olmesartan Medoxomil; Young Adult
PubMed: 26239632
DOI: 10.1002/jcph.610 -
American Journal of Therapeutics 2014Health care providers managing hypertension (HTN) have a large selection of pharmacologic agents to choose from, including several different classes of drugs and many... (Review)
Review
Health care providers managing hypertension (HTN) have a large selection of pharmacologic agents to choose from, including several different classes of drugs and many similar drugs within each class. Antagonism of the renin-angiotensin-aldosterone system has been shown to be very effective for HTN, especially in patients with cardiovascular disease, diabetes, and heart failure. Within this group, there have been 2 new agents recently introduced to the US market and approved by the Food and Drug Administration. It is important for the HTN specialist to be familiar with the merits of these 2 drugs: the angiotensin receptor blocker Edarbi (azilsartan) and the renin inhibitor Tekturna (aliskiren). Additionally, there have been several new, fixed-dose combination antihypertensives introduced to the market since 2006 that use a renin-angiotensin-aldosterone antagonist. Seven of these combine 2 drugs together in a single pill: Edarbyclor (azilsartan/chlorthalidone), Exforge (amlodipine/valsartan), Azor (olmesartan/amlodipine), Twynsta (amlodipine/telmisartan), Tekturna HCT [aliskiren/hydrochlorothiazide (HCTZ)], Valturna (aliskiren/valsartan), Tekamlo (aliskiren/amlodipine). Three triple-drug combination medications have also been introduced recently: Exforge HCT (amlodipine/valsartan/HCTZ), Tribenzor (olmesartan/amlodipine/HCTZ), and Amturnide (aliskiren/amlodipine/hydrocholorothiazide). This review will summarize the trial data and important pharmacologic merits of these 2 new renin-angiotensin-aldosterone antagonists and the advantages of initiating treatment with one of the new fixed-dose, combination drugs approved over the last 5 years.
Topics: Amides; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Benzimidazoles; Calcium Channel Blockers; Diuretics; Drug Therapy, Combination; Fumarates; Humans; Hypertension; Oxadiazoles; Renin
PubMed: 22975662
DOI: 10.1097/MJT.0b013e31824a0ed7