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olmesartan + amlodipine (Sevikar / Normetec / Konverge)

✓ Approved

Merck & Co. · AGTR1 · Small Molecule

What is olmesartan + amlodipine?

olmesartan + amlodipine is a small molecule developed by Merck & Co.. It is approved for therapeutic indications via oral (po).

Drug Profile

Brand NamesSevikar, Normetec, Konverge
CompanyMerck & Co.
Drug ClassSmall Molecule
Molecular TargetAGTR1, CACNA1C
RouteOral (PO)
StatusApproved
Sources: ClinicalTrials.gov, Merck & Co.

Mechanism of Action

Molecular Targets

olmesartan + amlodipine acts on 2 molecular targets:

AGTR1angiotensin II receptor type 1 (HAT1R, AT1)
CACNA1Ccalcium voltage-gated channel subunit alpha1 C (CACNL1A1, CACNA1C-IT2)
Want deeper analysis?Noah AI can explain complex mechanisms and compare to similar drugs.

Therapeutic Indications

olmesartan + amlodipine is developed for 1 unique indication across 1 therapeutic area.

Therapeutic AreaConditionPhase
Vascular disordersHypertension✓ Approved

Related Research Articles

PubMedJournal of geriatric cardiology : JGC2026-09-19

Blood pressure lowering efficacy of sacubitril/allisartan versus olmesartan in elderly Chinese hypertensive patients.

Zhang Wei W, Yan Jie J, Zhang Jin J, Ge Qian Q et al.

Sacubitril/Allisartan, a novel angiotensin receptor-neprilysin inhibitor, has demonstrated antihypertensive efficacy in patients with hypertension. Its effects in the elderly patients, who often present with increased arterial stiffness and comorbidities, remain less understood. We performed analysis of data from a randomized clinical trial that compared the blood pressure-lowering effect at 12 weeks of treatment with sacubitril/allisartan (240 mg/d or 480 mg/d) and olmesartan (20 mg/d). Eligible patients with mild-to-moderate hypertension and aged 65-75 years were included in the analysis. The primary outcome was change in clinic and 24-hour ambulatory blood pressure from baseline to week 12. Of the 1197 randomized patients, 338 elderly patients (41.5%) (mean age: 67.9 ± 2.3 years, 49.9% male) were included in this analysis. Baseline characteristics were comparable among treatment groups. At 12 weeks, least square mean (± standard error) changes from baseline in clinic systolic/diastolic blood pressure in the sacubitril/allisartan (240 mg/d or 480 mg/d) group and the olmesartan (20 mg/d) group were -24.0 ± 1.6/-5.7 ± 0.9 mmHg, -26.2 ± 1.6/-6.5 ± 0.9 mmHg, and -21.5 ± 1.6/-6.3 ± 0.9 mmHg, respectively. Greater reductions were also observed with sacubitril/allisartan (480 mg) compared with olmesartan (20 mg) in 24-hour, daytime and nighttime systolic blood pressure (all P-values < 0.05). The reductions in ambulatory blood pressure were dose-dependent (P = 0.007), and significantly greater with sacubitril/allisartan (480 mg) compared with olmesartan (20 mg) for nighttime blood pressure [-17.5 ± 1.8/-8.1 ± 1.0 mmHg, with a difference of -10.9 mmHg (-16.1 to -5.8, P < 0.0001) for systolic blood pressure and -4.5 mmHg (-7.3 to -1.8, P = 0.002) for diastolic blood pressure]. In elderly patients with hypertension, sacubitril/allisartan provided dose-dependent greater blood pressure reductions compared with olmesartan.

PMID 42760954
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PubMedInternational journal of legal medicine2026-09-17

Postmortem amlodipine concentrations and postmortem redistribution: a retrospective study of 33 cases.

Matheux Alice A, Amadieu Cassandra C, Pasquet Agathe A, François-Purssell Irène I et al.

Amlodipine is a calcium channel blocker used to treat cardiac conditions. At toxic doses, amlodipine can cause death by cardiogenic shock, tissue hypoperfusion and target organ damage. Its pharmacokinetic properties suggest that post-mortem redistribution is possible, precluding interpretation based on living data (plasma concentrations range from 3 to 15 µg/L). Our objective was to determine potentially fatal and non-fatal postmortem amlodipine concentrations. Thirty-three autopsy cases involving postmortem jugular vein blood amlodipine quantification were retrospectively reviewed and classified into two groups based on autopsy findings, regardless of amlodipine dosage results: amlodipine-related or possibly related deaths (G1) and amlodipine-unrelated deaths (G2).Amlodipine concentrations were determined using a validated LC-HRMS method. Groups were compared using a two-tailed Student's t-test. Of the 33 cases, 16 were classified G1 (median amlodipine concentration 115 µg/L [1st quartile: 85.5; 3rd quartile: 255.5]) and 17 were classified G2 (median amlodipine concentration 41 µg/L [1st quartile: 31; 3rd quartile: 87]) with a statistically significant difference between groups (p = 0.01**). In post mortem whole blood, analyzed by LC-HRMS, concentrations below 90 µg/L (87 µg/L according to our results) appear compatible with non-toxic exposure, whereas concentrations above 250-300 µg/L (255.5 µg/L according to our results) may indicate toxicity contributing to death. In G2, the median amlodipine concentration was 41 µg/L, which is 2.73 times higher than therapeutic concentrations observed in living plasma. The blood/plasma ratio for amlodipine (described as 1.48 or 1.7 depending on the respective reference) does not fully explain the observed difference in concentration in whole blood. Autopsy results involving increased amlodipine concentrations have been described in the literature and may point to the phenomenon of post-mortem redistribution. Postmortem redistribution significantly increases blood amlodipine concentrations compared with therapeutic levels in living subjects, making direct extrapolation unreliable. The distinction between non-toxic and potentially toxic concentrations is essential for forensic interpretation. Further large-scale, multicenter studies are warranted to establish validated postmortem reference ranges for this medication.

PMID 42749756
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PubMedEnvironmental pollution (Barking, Essex : 1987)2026-09-17

Unexpected Synergy: Calcium Channel Blockers and Residual Chlorine Cooperatively Accelerate Antibiotic Resistance Dissemination in Water Systems.

Ye Chengsong C, Chen Yidan Y, Yu Xin X

The dissemination of antibiotic resistance driven by non-antibiotic pharmaceuticals is an emerging concern warranting further investigation. Calcium channel blockers (CCBs), frequently detected in aquatic environments, have rarely been studied for their role in the spread of antibiotic resistance genes (ARGs). This study examines the impact of two representative CCBs, amlodipine (AML) and verapamil (VER), on conjugative horizontal gene transfer (HGT) under low-level chlorine conditions. A bacterial conjugation system was established using Escherichia coli harboring the conjugative plasmid RP4, under simulated residual chlorine exposure typical of water distribution networks (0.3 mg/L). Conjugation assays revealed that, in the absence of residual chlorine, AML and VER at environmentally relevant concentrations (0.01-100 μg/L) exerted negligible effects on ARG conjugative transfer. Similarly, residual chlorine alone did not significantly enhance HGT. However, the co-occurrence of CCBs and residual chlorine synergistically promoted HGT, yielding a maximal 15.2-fold increase in conjugation frequency. This promotional effect was not mediated by increased cell membrane permeability but was driven by elevated reactive oxygen species production, upregulation of efflux pumps and outer membrane porins, and modulated transcription of conjugation-related genes. Notably, the oxidative stress response gene rpoS was upregulated by over 20-fold, while korA/korB (negative regulators) and kilA/kilB (repressors of vertical transfer) were both downregulated, collectively relieving the repression on conjugative transfer. These findings demonstrate that environmental non-antibiotic pharmaceuticals can synergistically promote ARG dissemination under residual chlorine in water supply systems. This study provides a scientific basis for refining risk assessment frameworks for pharmaceutical contaminants in water.

PMID 42754197
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PubMedEuropean heart journal. Cardiovascular pharmacotherapy2026-09-15

Real-world analysis of adherence, persistence, and outcomes in patients receiving four-drug antihypertensive therapy.

Mancia Giuseppe G, Brouwers Sofie S, Calabria Silvia S, Leogrande Melania M et al.

Describe real-world use, adherence, persistence, and risk of non-fatal cardiovascular events (CVE) and mortality among patients receiving four-drug antihypertensive therapy. This was a retrospective, longitudinal cohort study of Italian administrative healthcare databases (N=7,160,298). Eligible patients were ≥18 years and received four-drug therapy between 2018 and 2022. Class- and molecule-level subcohort analyses required data for ≥1 year either side of four-drug therapy identification. Adherence and persistence were based on prescription availability. A Cox proportional hazards model was used for risk assessment.Among 228,594 eligible patients, 113,755 received either an angiotensin-converting enzyme inhibitor (ACEi; n=57,473) or angiotensin II receptor blocker (n=56,282), thiazide/thiazide-like diuretic (DIU), calcium channel blocker (CCB), and a fourth class (mostly beta-blockers [BBs]; n=87,022).In the Class subcohort (ACEi+DIU+CCB+BB; n=41,903), high adherence was more frequent among patients receiving two (52.1%) versus three (40.2%) or four (25.0%) pills (global P<0.001); persistence was also improved (P<0.02 from 6 months). Adherence and persistence were significantly higher with two versus three pills in the Molecule subcohort (perindopril, indapamide, amlodipine, and bisoprolol; n=8007). For persistent versus non-persistent patients, there was a risk reduction for CVE (12.4%; P<0.001) and mortality (16.4%; P<0.001) in the Class subcohort, with similar findings in the Molecule subcohort (20.9% [P=0.003] and 20.9% [P=0.002], respectively). In patients receiving four-drug antihypertensive therapy, adherence and persistence were significantly improved with lower pill burden. Persistence was associated with lower risks of CVE and mortality.

PMID 42736626
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PubMedInternational journal of molecular sciences2026-09-15

Elevated Prorenin Induces Podocyte Injury and Glomerular Fibrosis in cyp1a1-Prorenin Transgenic Rats.

Gu Chunyan C, Liu Xia X, Wu Jie J, Huang Yufeng Y

Plasma prorenin is commonly elevated in patients with diabetes and has been associated with the development of albuminuria and progression of diabetic nephropathy. Because albuminuria often reflects podocyte injury, the pathogenic role of prorenin in podocyte dysfunction warrants further investigation. In this study, we examined the association between prorenin and podocyte injury, as well as glomerular fibrosis, using a transgenic rat model in which prorenin is inducibly expressed and secreted from the liver. cyp1a1-prorenin transgenic rats were randomized to receive diets containing increasing concentrations of the gene activator indole-3-carbinol (I3C; 0.05%, 0.15%, or 0.3%) for 4 weeks. Wild-type rats maintained on a normal diet served as controls. I3C administration resulted in a dose-dependent increase in plasma prorenin levels in transgenic rats. Elevated prorenin was associated with increased mean arterial pressure and urinary albumin excretion, accompanied by a dose-dependent reduction in podocyte number and slit diaphragm protein expression, as well as segmental foot process effacement and podocyte hypertrophy. In addition, increased prorenin stimulated renal expression of profibrotic factors and promoted glomerular fibrosis. Treatment with either amlodipine or enalapril for 6 weeks prevented the development of hypertension and partially attenuated podocyte injury, albuminuria, and renal fibrosis, without fully reversing these changes. These protective effects were associated with suppression of NF-κB- and Nox2-mediated inflammatory and oxidative stress pathways. Collectively, these findings demonstrate that prorenin promotes podocyte injury and glomerular fibrosis through mechanisms that are partially dependent on hypertension and angiotensin II but also involve angiotensin II-independent pathways.

PMID 42737785
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PubMedJournal of drug targeting2026-09-14

A Repurposed Olmesartan-Loaded Hyaluronic Acid-Functionalized Lecithin-Chitosan Nanoparticle Hydrogel for Enhanced Topical Delivery in Diabetic Wound Healing.

El-Dakroury Walaa A WA, Asaad Gihan F GF, M Sallam Al-Aliaa AA, Salah Elballal Mohammed M et al.

A novel topical nanocarrier-based hydrogel system incorporating olmesartan medoxomil (OLM) was designed to enhance diabetic wound healing through targeted skin delivery. OLM was efficiently encapsulated within lecithin-chitosan hybrid nanoparticles (LCNPs), which were subsequently functionalized with hyaluronic acid (HA) to improve dermal adhesion, biocompatibility, and sustained release. The optimized OLM-HA-LCNPs exhibited a nanoscale size of 324.28 ± 5.71 nm, a negative zeta potential (-39.64 ± 3.2 mV), and a high entrapment efficiency of 89.86 ± 3.15%. In vitro release studies demonstrated a controlled, biphasic OLM release pattern over 24 h following Weibull kinetics, confirming diffusion erosion-controlled release behavior. Incorporation into a hydrogel base preserved pseudoplastic rheology, optimal pH (6.3 ± 0.2), and superior spreadability (35.26 cm2). In streptozotocin-induced diabetic rats, the OLM-HA-LCNP hydrogel produced 93.5% wound closure after 14 days, compared with 87.6%, 77.1%, and 90.8% for the marketed reference, plain HA-LCNPs, and OLM-pure treatments, respectively. OLM-HA-LCNP hydrogel also increased CAT, SOD, and GSH levels by 2.7, 1.45, and 2.16 fold, respectively, and reduced MDA levels by 77% compared with diabetic controls. Histological and immunohistochemical findings further demonstrated improved epidermal regeneration, collagen deposition, and normalization of VEGF and MMP-9 expression. Collectively, these findings demonstrate that HA-functionalized lecithin-chitosan nanoparticles incorporated into a hydrogel provide an effective platform for sustained topical OLM delivery and enhanced therapeutic performance in diabetic wound healing.

PMID 42735074
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