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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

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)
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Therapeutic Indications

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

Therapeutic AreaConditionPhase
Vascular disordersHypertension✓ Approved

Related Research Articles

PubMedEuropean journal of case reports in internal medicine2026-11-11

Combined Calcium Channel Blocker And Angiotensin-Converting Enzyme Inhibitor Overdose.

Kahal Fares F, Guérard-Poirier Natasha N, Ji Cheng C, Gursahaney Ashvini A et al.

Combined overdoses of angiotensin-converting enzyme inhibitors and calcium channel blockers are rare but associated with more severe toxicity than either agent alone. A 48-year-old woman presented to the emergency department nine hours after intentionally ingesting 40 tablets of amlodipine (10 mg) and 40 tablets of ramipril (10 mg). On arrival, she was hypotensive and tachycardic. Initial management included fluids, intravenous calcium and insulin bolus followed by high-dose insulin euglycaemic therapy (HIET). Despite escalating vasopressor support, she developed mixed vasoplegic and cardiogenic shock complicated by acute kidney injury, fluid overload, respiratory failure and metabolic acidosis, necessitating intubation and continuous renal replacement therapy. Improvement in haemodynamics was only achieved by day 9. She was transferred from the intensive care unit (ICU) on day 20 with residual weakness from ICU-acquired myopathy and was ultimately discharged after 66 days, with a prolonged hospitalisation attributed to delirium and deconditioning. Severe combined angiotensin-converting enzyme inhibitors (ACEI) and calcium channel blockers (CCB) overdose may cause prolonged, refractory haemodynamic instability requiring extended high-dose insulin euglycaemic therapy (HIET), vasoactive support and fluid administration. Concentrated insulin, dextrose and vasopressor preparations may help mitigate fluid overload. Angiotensin II may be a potential treatment for refractory vasoplegia, although evidence and availability remain limited. Secondary complications can prolong recovery beyond the duration of drug toxicity. This case highlights the need for individualised, multidisciplinary management, early HIET, vasoactive support and fluid-sparing strategies in severe combined ACEI and CCB overdose. Management of severe combined calcium channel blocker and angiotensin-converting enzyme inhibitor overdose may require prolonged resuscitation with high-dose insulin euglycaemic therapy, vasoactive support and fluid administration. The cumulative fluid requirements of these therapies, combined with complications such as acute kidney injury, can contribute to severe fluid overload. The use of concentrated insulin, dextrose and vasopressor preparations may help limit the iatrogenic fluid accumulation.Clinicians should anticipate and proactively manage secondary complications, including acute kidney injury, volume overload, respiratory failure and infection, as these complications may independently prolong recovery beyond the expected duration of drug toxicity.Combined angiotensin-converting enzyme inhibitor and calcium channel blocker overdose lacks established management guidelines and requires individualised, multidisciplinary care based on clinical severity and response to therapy.

PubMedAdvanced pharmaceutical bulletin2026-11-10

Optimization, Ex-Vivo Penetration and In-Vivo Evaluation of Pegylated Nanostructured Lipid Carriers of Olmesartan Medoxomil to Enhance Transdermal Delivery.

Albash Rofida R, Abdelbary Aly A AA, Refai Hanan H, El-Nabarawi Mohamed A MA

Olmesartan medoxomil (OLM), a poorly water soluble hypertension medication with 26% oral bioavailability, was encapsulated in PEGylated nanostructured lipid carriers (PNLCs) for transdermal distribution. Tween 80 or sodium deoxycholate stabilized the PNLCs, which were made up of liquid lipid including a mixture of medium chain triglycerides (labrasol and labrafil) and solid lipid (compritol and tristearin). Hot melt emulsification, high-speed stirring, and ultrasonication were used to create PNLCs. To distinguish the effects of formulation independent variables on entrapment efficiency %, particle size, polydispersity index, zeta potential, and amount of drug released after 6 hours (Q6h), a 24 complete factorial design using Design Expert® software was created. For additional research, the formula (PNLC16) with the best requirements was chosen. When compared to OLM solution, PNLC16 showed higher permeation ex vivo permeation using both shed snake and rat skin. Histopathological analysis demonstrated that the topically administered PNLCs were safe. Pharmacodynamic research further demonstrated PNLC16's superiority over commercial oral pills in terms of long-lasting effects. Accordingly, the results showed that PNLC16 would be a viable vehicle for OLM transdermal delivery.

PubMedNeuroscience2026-11-10

Association of metoprolol with temporal changes in SIRT1, oxidative stress, and inflammatory biomarkers.

Gupta Sandeep Kumar SK, Kalita Jayantee J, Pandey Prakash C PC, Mahajan Roopali R et al.

There is a paucity of studies on the effect of beta-blocker on sirtuins (SIRT1)-mediated inflammation and oxidative stress in ischemic stroke. We report the effect of metoprolol on the temporal kinetics of SIRT1-mediated oxidative stress markers [catalase (CAT), glutathione peroxidase (GPx), malondialdehyde (MDA), and reactive oxygen species (ROS)], proinflammatory cytokines (TNFα and IL1β), and their association with outcomes. This was a sub-analysis of our earlier study on effect of beta-blocker in acute stroke. Forty-eight patients within 3-days of ischemic stroke were included. Their demographic characteristics, risk factors for stroke, GCS/NIHSS score, hematological and biochemical parameters, electrocardiogram, echocardiography, and cranial-MRI findings were noted. SIRT1, TNFα, and IL1β mRNA fold-changes were measured by using real-time PCR, and GPx, CAT, MDA, and ROS were measured by using a spectrophotometer. These biomarkers were also measured in 59 healthy-controls. The outcome was defined at 1 and 3-months using the modified Rankin Scale. Twenty-eight patients received metoprolol, and 20 received amlodipine. There is a gradual reduction in TNFα, IL1β, ROS, and MDA and an increase in CAT level in both groups; however, more marked in the metoprolol group. On day 15, the metoprolol group had a comparable level of SIRT1, TNFα, IL1β, and CAT to those with the healthy controls. Metoprolol in acute ischemic stroke helps in upregulating SIRT1 and CAT and downregulating TNFα and IL1β; however, the overall p-value for treatment-by-time interaction was insignificant. The patients in the metoprolol group had a better outcome at 3-months. A large study is needed to confirm these findings.

PubMedCureus2026-11-09

Celiac Crisis: An Unusual Case of Severe Diarrhea.

Chen Ellie E, Cusumano Vivy V

Celiac disease is an immune-mediated enteropathy triggered by dietary gluten. Celiac crisis is a severe manifestation characterized by profuse diarrhea, dehydration, hypotension, and severe metabolic derangements. We describe the case of an elderly patient with a remote childhood diagnosis of celiac disease who presented in celiac crisis. A 79-year-old man with hypertension managed on olmesartan presented with two weeks of severe watery diarrhea, weight loss, and edema that progressed to hypotension, acute kidney injury, and profound electrolyte abnormalities, necessitating multiple hospitalizations. Celiac serologies were markedly elevated, and he subsequently disclosed a childhood diagnosis of celiac disease that he had believed resolved. Duodenal biopsies demonstrated duodenitis with intraepithelial lymphocytosis and villous blunting. His symptoms persisted despite a gluten-free diet, withholding olmesartan, and supportive care but improved rapidly after initiation of budesonide. He was diagnosed with celiac crisis, with a possible contribution from olmesartan-associated enteropathy. Repeat endoscopy eight months later showed histologic remission. Celiac crisis should be considered in any patient presenting with severe diarrhea, dehydration, and metabolic abnormalities, especially when there is evidence of underlying celiac disease. In this patient, concurrent olmesartan use raised the possibility of a superimposed drug-induced enteropathy; although olmesartan was discontinued five days before budesonide was started, its contribution cannot be excluded and remains a confounding factor. Even so, this case highlights the importance of promptly recognizing celiac crisis and suggests a potential role for budesonide in patients whose symptoms persist despite gluten withdrawal and supportive care.

PubMedPediatric nephrology (Berlin, Germany)2026-11-09

Persistent systemic hypertension in a child with carbonic anhydrase II deficiency.

Arslan Bengü B, Polat Recep R, Çelakıl Mehtap M

Carbonic anhydrase II (CA II) deficiency is a rare autosomal recessive disorder classically characterized by osteopetrosis, renal tubular acidosis (RTA), and intracranial calcifications. We report a 10-year-old girl with genetically confirmed CA II deficiency who developed acute severe hypertension after previously documented normotension. Blood pressure reached 160/100 mmHg and was accompanied by headache, vomiting, and transient neurological symptoms requiring intravenous antihypertensive therapy. Hypertension persisted beyond the acute episode and was confirmed by ambulatory blood pressure monitoring (ABPM) despite treatment, requiring long-term antihypertensive therapy. Serial ABPM during follow-up subsequently demonstrated sustained blood pressure control, permitting stepwise dose reduction and eventual discontinuation of amlodipine approximately two years after presentation. Systemic hypertension has not previously been reported in CA II deficiency. This single-patient observation is hypothesis-generating and does not establish a causal relationship.

PubMedMolecular and cellular biochemistry2026-11-08

Angiotensin II type 1 receptor (AT1R) drives human Tenon's capsule fibroblast activation and myofibroblast transformation via the RhoA/ROCK signaling pathway.

Zhang Yuanyuan Y, Luo Xu X, Zuo Lei L, Cui Hongping H

Although the angiotensin II type 1 receptor (AT1R) participates in systemic tissue remodeling, its exact contribution to human subconjunctival fibrosis remains poorly understood. This study investigated the expression of AT1R in human clinical scar specimens, the downstream involvement of the RhoA/ROCK pathway, and the independent anti-fibrotic effects of receptor blockade. Primary human Tenon's capsule fibroblasts (HTCFs) were isolated from patient tissue biopsies and verified as a pure mesenchymal lineage using immunofluorescence and quantitative real-time PCR (qRT-PCR). To model the scar microenvironment, primary cells were stimulated with transforming growth factor-beta 1 (TGF-β1), either alone or in combination with Angiotensin II, the AT1R antagonist Olmesartan (OMS), or the selective ROCK inhibitor Y-27,632. Profibrotic and structural markers, including AT1R, alpha-smooth muscle actin (α-SMA), RhoA, ROCK1, fibronectin, and collagen I alpha (COL1A1), were quantified via Western blotting, qRT-PCR and immunofluorescence. Cellular proliferation and migration were evaluated using CCK-8 and Transwell migration assays. Our ex vivo tissue analyses revealed that AT1R expression was upregulated at gene and protein levels in human Tenon's capsule scars compared to normal controls. In vitro, stimulation with TGF-β1 induced a dose-dependent upregulation of AT1R alongside core profibrotic biomarkers, while accelerating HTCF proliferation and migration rates. Conversely, treatment with OMS or Y-27,632 counteracted this TGF-β1-induced activation, reversing cellular proliferation, cell motility, and the expression of extracellular matrix components. Together, these findings indicate that subconjunctival fibrosis is driven by AT1R-RhoA/ROCK1 axis which might provide a promising mechanistic pipeline to modulate tissue scarring and optimize outcomes in glaucoma management.

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