Figure 2 - available via license: Creative Commons Attribution-NonCommercial 4.0 International
Content may be subject to copyright.
Antihypertensive efficacy of olmesartan medoxomil/HCTZ 20/12.5 mg/ day (n=308) compared with losartan/HCTZ 50/12.5 mg/day (n=305) as initial therapy in patients with moderate to severe hypertension. Results of a randomized, double-blind trial of 12 weeks' treatment in 613 patients who had either newly diagnosed hypertension with mean seated DBP 100-120 mmHg and SBP ≥160 mmHg or inadequately controlled hypertension with DBP 90110 mmHg despite previous treatment (Rump et al 2006). (a) Reduction in mean trough BP (DBP = primary endpoint); (b) Proportion of patients achieving BP control (<140/90 mmHg) are shown for the intent-to-treat population. *p=0.002, **p≤0.0003. Abbreviations: DBP, diastolic BP; HCTZ, hydrochlorothiazide; LOS, losartan; OLM, olmesartan medoxomil; SBP, systolic BP.
Source publication
In most patients with hypertension, especially Stage 2 hypertension, adequate control of blood pressure (BP) is only achieved with combination drug therapy. When using combination therapy, antihypertensive agents with complementary mechanisms of action are recommended, for example, an angiotensin receptor blocker (ARB) in combination with hydrochlo...
Contexts in source publication
Context 1
... besylate/benazepril is a well-established, fixed-dose calcium channel blocker/ACE inhibitor combination antihypertensive therapy. A direct comparison between amlodipine besylate/benazepril and olmesartan medoxomil/HCTZ has not been performed; however, an indirect comparison of data from several factorial studies (Quan et al 2006) suggests that mean reductions in seated DBP may be quantitatively greater with olmesartan medoxomil/HCTZ 40/25 mg/day than with amlodipine besylate/benazepril 5/20 mg/day (approximately 22 vs 17 mmHg), whereas reductions in seated SBP appear similar between the combinations (approximately 27 vs 27 mmHg) (Quan et al 2006). The studies used similar designs and enrolled patients with a baseline DBP of 100-115 mmHg. ...
Context 2
... SBP is often more difficult to control than DBP (Swales 1999;Mancia et al 2002). Treatment algorithms based on olmesartan medoxomil/HCTZ have been shown to significantly reduce SBP, in addition to DBP, in patients with Stage 1 and Stage 2 hypertension, allowing the majority of patients in both groups to achieve the SBP goal of ≤140 mmHg (Neutel et al 2006). ...
Similar publications
Blood pressure (BP) is one of the most important and common vascular risk factors but it is often poorly controlled. Inhibition of the renin-angiotensin-aldosterone system (RAAS) provides beneficial effects in hypertensives. The association of low-dosed diuretics in combination with RAAS blocking agents allows maximum benefit from potassium depleti...
The aim of this study was to compare the effect of the beta-adrenergic blocker atenolol and the Angiotensin II type 1 (AT1) receptor antagonist losartan on cognitive function in very elderly hypertensive patients. A total of 120 mild to moderate essential hypertensive (DBP >90 and <105 mmHg) patients, aged 75-89 years, were studied. After a 4-week...
Blockade of the renin-angiotensin system is an important approach in managing high blood pressure, and has increasingly been shown to affect cardiovascular disease processes mediated by angiotensin II throughout the cardiovascular and renal continua. Telmisartan is an angiotensin II receptor blocker (ARB) displaying unique pharmacologic properties,...
To evaluate the importance of providing guidelines to patients via active telephone calls for blood pressure control and for preventing the discontinuation of treatment among hypertensive patients.
Many reasons exist for non-adherence to medical regimens, and one of the strategies employed to improve treatment compliance is the use of active teleph...
Citations
... Numerous phase III and phase IV studies have demonstrated the additional benefits of combining OM either with AML or with HCTZ in terms of BP control and target BP achievements [33][34][35][36][37]. The ability of OM to lower BP has been documented in patients poorly controlled on OM alone as well as in patients uncontrolled on AML or HCTZ alone. ...
Blood pressure control remains an unmet clinical need. Only about half of patients achieve their blood pressure (BP) targets and of these, the majority require combination and double or triple therapies. International guidelines recommend the association of drugs with complementary mechanisms of action and, in particular, the combination of renin-angiotensin system (RAS) inhibitors, calcium channel blockers (CCBs), and diuretics. Among the various angiotensin receptor blockers, olmesartan (OM) is available as a monotherapy and in dual and triple single-pill combinations (SPCs) with amlodipine (AML) and/or hydrochlorothiazide (HCTZ). Several phase III and IV studies, together with real-world studies, have demonstrated the additional benefits of combining OM either with AML or with HCTZ in terms of BP control and target BP achievements both in the general population and in special subgroups of hypertensive patients, such as the elderly, diabetic, chronic kidney disease or obese patients. Ambulatory BP monitoring studies assessing 24h BP have also demonstrated that dual, as well as triple, OM-based SPCs induce a more sustained and smoother BP reduction than placebo and monotherapy. Furthermore, triple OM-based SPC has been shown to improve therapeutic adherence in hypertensive patients compared to free combinations. The availability of OM combined with HCTZ, AML or both at different dosages makes it a valuable option to customize therapy based on the levels of BP and the clinical characteristics of hypertensive patients.
... In this regard, patients with Stage 2 hypertension (systolic BP ≥ 160 mmHg or diastolic ≥ 100 mmHg), have achieved adequate control of BP only by drug combination therapy. Consequently, the combination of antihypertensive agents with complementary mechanisms of action [3][4][5][6] is recommended. Studies have reported that the addition of hydrochlorothiazide (HCT) improves the BP lowering effects of angiotensin II receptor blockers (ARBs) and, angiotensin-converting enzyme (ACE) inhibitors. ...
... However, monotherapy [8,9] compared to other ACE inhibitors [10,11] or to different antihypertensive drug classes [12,13], the one containing olmesartan medoxomil (OLM) and HCT has been demonstrated in clinical trials to be the most effective in significant BP reductions and BP control in many patients while it is a well-tolerated therapy [3,14], hence, increasing the interest in developing formulations containing the OLM-HCT combination. ...
... Several fixed-dose combinations (FDCs) containing HCT with β-blockers, ACE inhibitors, ARB along with ACE inhibitors, and calcium channel blockers are now available. However, monotherapy [8,9] compared to other ACE inhibitors [10,11] or to different antihypertensive drug classes [12,13], the one containing olmesartan medoxomil (OLM) and HCT has been demonstrated in clinical trials to be the most effective in significant BP reductions and BP control in many patients while it is a well-tolerated therapy [3,14], hence, increasing the interest in developing formulations containing the OLM-HCT combination. ...
A drug–drug and drug–excipient interactions and compatibilities study was conducted for two fixed-dose combination (FDC) products containing olmesartan medoxomil (OLM)/hydrochlorothiazide (HCT) 20/12.5 mg and OLM/HCT 40/12.5 mg during their development including storage. The study consisted of the evaluation of samples retrieved during all stages of a real manufacturing process. Powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetry (TGA), Fourier transform infrared spectroscopy (FT-IR), and contact angle techniques were applied to the samples to determine interactions and incompatibilities. Dissolution tests and long-term stability studies were conducted to evaluate dosage form performance. Results showed weak solid–state interactions able to obtain a eutectic mixture of OLM and HCT while microcrystalline cellulose (MC) impacted the thermal stability of both drugs. Reliable dissolution and long-term stability tests confirmed that the interactions observed were not considered incompatibilities because they were not influenced by the performance of the final products.
... Combination of OLM and HCZ is an effective and highly tolerated antihypertensive combined therapy that decreases the systolic and diastolic blood pressure (SBP and DBP) to higher extent than other compound alone. This combined antihypertensive therapy was observed to compare favorably than other antihypertensive combined therapies [8,9] because FOS prevents the counter-regulatory increase in the level of angiotensin II produced as due to HCZ stimulant effect on reninangiotensin system [10]. Additionally, lower doses of the combined therapy is needed than mono-therapy lowering dose-related side effects [9]. ...
... The proposed RP-HPLC method linearity was assessed using different samples of several concentrations of each of the cited compounds. Linearity was obtained in the range of (0.5-15), (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15), , (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20), , and (10-100) µg /mL for SAL, CZ, HCZ, OL, OLM, and FOS, respectively. The regression parameters were calculated and shown in Table 2. Correlation coefficients values proved the linearity of the developed method within the studied ranges. ...
... The proposed RP-HPLC method linearity was assessed using different samples of several concentrations of each of the cited compounds. Linearity was obtained in the range of (0.5-15), (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15), , (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20), , and (10-100) µg /mL for SAL, CZ, HCZ, OL, OLM, and FOS, respectively. The regression parameters were calculated and shown in Table 2. Correlation coefficients values proved the linearity of the developed method within the studied ranges. ...
Hydrochlorothiazide is a widely used thiazide diuretic. Its combinations with either olmesartan medoxomil or fosinopril sodium are well known antihypertensive combinations that compare positively than other related combined therapies. A first RP-HPLC method was introduced for simultaneous estimation of two antihypertensive combinations containing hydrochlorothiazide with either olmesartan medoxomil or fosinopril sodium. The work was extended to quantify the drugs along with their degradation products; salamide as hydrochlorothiazide degradate and olmesartan as olmesartan medoxomil degradate. Also, it succeeded to determine the pharmacopoeial impurity of hydrochlorothiazide (chlorothiazide). The established RP-HPLC was performed on RP-C18 column utilizing gradient mixture of 0.05M KH2PO4 (pH 3 with aqueous O-phosphoric acid), acetonitrile, and methanol. Temperature was adjusted to 35 °C and UV detection was done at 205 nm for fosinopril sodium and at 225 nm for the rest of the cited components.
ICH guidelines were used to validate the method and all the results affirmed efficiency of the method. In addition, it was effectively used for measuring hydrochlorothiazide in binary mixtures with either olmesartan medoxomil or fosinopril sodium in their available pharmaceutical formulation. Also, the statistical comparison with published methods was executed and no noteworthy difference concerning accuracy and precision was detected.
... Olmesartan medoxomil and hydrochlorothiazide are reported as the two most preferred drugs of choice for combination therapy of hypertension (Chrysant et al., 2004;Greathouse, 2006;Bramlage et al., 2013). Olmesartan medoxomil has the better antihypertensive effect when treatment is combined with diuretics ( Zhang et al., 2017) and is described chemically as the (5-methyl-2-oxo-1,3-dioxol-4-yl) methyl ester of 4-(1hydroxy-1-methylethyl)-2-propyl-1-{ [20-(1H-tetrazol-5-yl) [1,10-biphenyl]-4-yl]methyl}-1H-imidazole-5-carboxylic acid. ...
... Olmesartan medoxomil and hydrochlorothiazide are reported as the two most preferred drugs of choice for combination therapy of hypertension (Chrysant et al., 2004;Greathouse, 2006;Bramlage et al., 2013). Olmesartan medoxomil has the better antihypertensive effect when treatment is combined with diuretics ( Zhang et al., 2017) and is described chemically as the (5-methyl-2-oxo-1,3-dioxol-4-yl) methyl ester of 4-(1hydroxy-1-methylethyl)-2-propyl-1-{ [20-(1H-tetrazol-5-yl) [1,10-biphenyl]-4-yl]methyl}-1H-imidazole-5-carboxylic acid. ...
A new, simple, sensitive, selective, rapid, and high-throughput liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for simultaneous quantification of Olmesartan and hydrochlorothiazide in human plasma. Simple liquid-liquid extraction procedure was applied for plasma sample pretreatment using a mixture of diethyl ether and dichloromethane, as an extraction solution. Analytes were separated on UNISOL C18 150*4.6 mm, 5 µm column using methanol, and 2 mM ammonium acetate pH 5.5 (80:20, v/v) as a mobile phase and detected by electrospray ionization in the multiple reaction monitoring (MRM) mode. The mass transition ion pairs were followed in negative ion mode as m/z 445.20 → 148.90 for Olmesartan; m/z 451.40 → 154.30 for Olmesartan D 6 and m/z 295.80 → 205.10 for hydrochlorothiazide; m/z 298.90 → 206.30 for hydrochlorothiazide 13 C D 2. The method showed excellent linearity (r 2 > 0.99) over the concentration range of 5.002-2,599.934 ng/ml for Olmesartan and from 3.005 to 499.994 ng/ml for hydrochlorothiazide. Precision (% CV) and accuracy (% bias) for Olmesartan were found in the range of 3.07-9.02% and −5.00-0.00%, respectively. Precision (% CV) and accuracy (% bias) for hydrochlorothiazide were found in the range of 3.32-8.21% and 1.99-3.80%, respectively. This as developed novel and high-throughput liquid-liquid extraction bioanalytical method has substantial innovative value with the benefits of cost effectiveness, good extraction efficiency, shorter analysis run time, low organic solvent consumption, and simpler procedure over the previously reported solid-phase extraction method. The application of this method in pharmacokinetic studies was further demonstrated successfully through a bioequivalence study conducted on healthy human subjects, following oral administration of combined formulation of Olmesartan medoxomil and hydrochlorothiazide in fixed-dose tablet.
... Olmesartan medoxomil and hydrochlorothiazide are reported as the two most preferred drugs of choice for combination therapy of hypertension (Chrysant et al., 2004;Greathouse, 2006;Bramlage et al., 2013). Olmesartan medoxomil has the better antihypertensive effect when treatment is combined with diuretics ( Zhang et al., 2017) and is described chemically as the (5-methyl-2-oxo-1,3-dioxol-4-yl) methyl ester of 4-(1hydroxy-1-methylethyl)-2-propyl-1-{ [20-(1H-tetrazol-5-yl) [1,10-biphenyl]-4-yl]methyl}-1H-imidazole-5-carboxylic acid. ...
... Olmesartan medoxomil and hydrochlorothiazide are reported as the two most preferred drugs of choice for combination therapy of hypertension (Chrysant et al., 2004;Greathouse, 2006;Bramlage et al., 2013). Olmesartan medoxomil has the better antihypertensive effect when treatment is combined with diuretics ( Zhang et al., 2017) and is described chemically as the (5-methyl-2-oxo-1,3-dioxol-4-yl) methyl ester of 4-(1hydroxy-1-methylethyl)-2-propyl-1-{ [20-(1H-tetrazol-5-yl) [1,10-biphenyl]-4-yl]methyl}-1H-imidazole-5-carboxylic acid. ...
... Olmesartan medoxomil and hydrochlorothiazide are reported as the two most preferred drugs of choice for combination therapy of hypertension (Chrysant et al., 2004;Greathouse, 2006;Bramlage et al., 2013). Olmesartan medoxomil has the better antihypertensive effect when treatment is combined with diuretics ( Zhang et al., 2017) and is described chemically as the (5-methyl-2-oxo-1,3-dioxol-4-yl) methyl ester of 4-(1hydroxy-1-methylethyl)-2-propyl-1-{ [20-(1H-tetrazol-5-yl) [1,10-biphenyl]-4-yl]methyl}-1H-imidazole-5-carboxylic acid. ...
A new, simple, sensitive, selective, rapid, and high-throughput liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for simultaneous quantification of Olmesartan and hydrochlorothiazide in human plasma. Simple liquid–liquid extraction procedure was applied for plasma sample pretreatment using a mixture of diethyl ether and dichloromethane, as an extraction solution. Analytes were separated on UNISOL C18 150*4.6 mm, 5 µm column using methanol, and 2 mM ammonium acetate pH 5.5 (80:20, v/v) as a mobile phase and detected by electrospray ionization in the multiple reaction monitoring (MRM) mode. The mass transition ion pairs were followed in negative ion mode as m/z 445.20 → 148.90 for Olmesartan; m/z 451.40 → 154.30 for Olmesartan D6 and m/z 295.80 → 205.10 for hydrochlorothiazide; m/z 298.90 → 206.30 for hydrochlorothiazide ¹³C D2. The method showed excellent linearity (r ² > 0.99) over the concentration range of 5.002–2,599.934 ng/ml for Olmesartan and from 3.005 to 499.994 ng/ml for hydrochlorothiazide. Precision (% CV) and accuracy (% bias) for Olmesartan were found in the range of 3.07–9.02% and −5.00–0.00%, respectively. Precision (% CV) and accuracy (% bias) for hydrochlorothiazide were found in the range of 3.32–8.21% and 1.99–3.80%, respectively. This as developed novel and high-throughput liquid–liquid extraction bioanalytical method has substantial innovative value with the benefits of cost effectiveness, good extraction efficiency, shorter analysis run time, low organic solvent consumption, and simpler procedure over the previously reported solid-phase extraction method. The application of this method in pharmacokinetic studies was further demonstrated successfully through a bioequivalence study conducted on healthy human subjects, following oral administration of combined formulation of Olmesartan medoxomil and hydrochlorothiazide in fixed-dose tablet.
... Olmesartan medoxomil and hydrochlorothiazide are reported as the two most preferred drugs of choice for combination therapy of hypertension (Chrysant et al., 2004;Greathouse, 2006;Bramlage et al., 2013). Olmesartan medoxomil has the better antihypertensive effect when treatment is combined with diuretics ( Zhang et al., 2017) and is described chemically as the (5-methyl-2-oxo-1,3-dioxol-4-yl) methyl ester of 4-(1hydroxy-1-methylethyl)-2-propyl-1-{ [20-(1H-tetrazol-5-yl) [1,10-biphenyl]-4-yl]methyl}-1H-imidazole-5-carboxylic acid. ...
A new, simple, sensitive, selective, rapid, and high-throughput liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for simultaneous quantification of Olmesartan and hydrochlorothiazide in human plasma. Simple liquid-liquid extraction procedure was applied for plasma sample pretreatment using a mixture of diethyl ether and dichloromethane, as an extraction solution. Analytes were separated on UNISOL C18 150*4.6 mm, 5 µm column using methanol, and 2 mM ammonium acetate pH 5.5 (80:20, v/v) as a mobile phase and detected by electrospray ionization in the multiple reaction monitoring (MRM) mode. The mass transition ion pairs were followed in negative ion mode as m/z 445.20 → 148.90 for Olmesartan; m/z 451.40 → 154.30 for Olmesartan D 6 and m/z 295.80 → 205.10 for hydrochlorothiazide; m/z 298.90 → 206.30 for hydrochlorothiazide 13 C D 2. The method showed excellent linearity (r 2 > 0.99) over the concentration range of 5.002-2,599.934 ng/ml for Olmesartan and from 3.005 to 499.994 ng/ml for hydrochlorothiazide. Precision (% CV) and accuracy (% bias) for Olmesartan were found in the range of 3.07-9.02% and −5.00-0.00%, respectively. Precision (% CV) and accuracy (% bias) for hydrochlorothiazide were found in the range of 3.32-8.21% and 1.99-3.80%, respectively. This as developed novel and high-throughput liquid-liquid extraction bioanalytical method has substantial innovative value with the benefits of cost effectiveness, good extraction efficiency, shorter analysis run time, low organic solvent consumption, and simpler procedure over the previously reported solid-phase extraction method. The application of this method in pharmacokinetic studies was further demonstrated successfully through a bioequivalence study conducted on healthy human subjects, following oral administration of combined formulation of Olmesartan medoxomil and hydrochlorothiazide in fixed-dose tablet.
... This FDC is available as tablet containing Olm/HCTZ in strengths of 20/12.5 and 40/25 mg. The bioavailability of the drugs in this combination depends on their individual specification (11). Unfortunately, HCTZ suffers from poor bioavailability which is attributed to slow dissolution and poor permeability (BCS class IV) (12). ...
Olmesartan medoxomil (Olm) and hydrochlorothiazide (HCTZ) are fixed dose combination (FDC) for treatment of hypertension. They have hydrogen bonding sites and may interact during co-processing. The consequences of such interaction are not clear. This study investigated the possibility of this interaction during co-processing. The research was extended to inhibit deleterious interactions. The drugs were co-evaporated from ethanolic solution to maximize the chance of interaction. This was performed in the absence and presence of hydroxypropyl methylcellulose (HPMC) and/or aerosil. The products were characterized using Fourier transform infrared spectroscopy (FTIR), differential thermal analysis, and powder X-ray diffraction (PXRD) in addition to dissolution studies. Co-evaporation of Olm with HCTZ in the absence of excipients produced crystalline material with FTIR spectrum showing intermolecular hydrogen bonding. This material showed thermal pattern of new crystalline species. This was identified as Olm/HCTZ co-crystal by PXRD. This co-crystallization reduced the dissolution rate of both drugs. This co-crystallization was inhibited in the presence of HPMC, but the dissolution rate was not significantly enhanced accordingly. Co-processing in the presence of both HPMC and aerosil eliminated the co-crystallization and minimized the intermolecular drug-drug interaction with subsequent dissolution enhancement. The study introduced a composition for fixed dose combination of Olm and HCTZ with enhanced dissolution.
