Olmesartan medoxomil 40mg / Amlodipine 10mg tablets

Background: Amlodipine has recently been incidentally reported with angioedema and is frequently prescribed with renin-angiotensin-aldosterone system inhibitors (RAAS-i) for hypertension management. While RAAS-i drugs are known to cause angioedema, the risk associated with amlodipine alone or in combination with RAAS-i drugs remains unclear. This study aimed to evaluate the association between amlodipine use and angioedema using pharmacovigilance data. Methods: We analyzed adverse event reports from the US FDA Adverse Event Reporting System using both frequentist and Bayesian approaches. Drug-drug interactions were assessed using multiplicative models. Additionally, we conducted a systematic review of published case reports of amlodipine-associated angioedema. Results: Among 29,661,136 reports, 2076 cases of angioedema were identified (1067 with amlodipine alone, 1009 with amlodipine-RAAS-i combinations). Significant safety signals were detected for amlodipine alone and in combination with aliskiren, specific ACE inhibitors (quinapril, benazepril, trandolapril, fosinopril, perindopril), and certain ARBs (candesartan, losartan). No significant interactions were observed between amlodipine and RAAS-i drugs except for the amlodipine-trandolapril combination. A review of published cases demonstrated definite causality in two cases and possible association in others, with most patients presenting with oropharyngeal/facial edema and achieving complete recovery following drug discontinuation and standard therapy. Conclusions: Our findings suggest a potentially increased risk of angioedema with amlodipine, both as monotherapy and in specific RAAS-i combinations. While these results should not discourage appropriate clinical use, they emphasize the importance of monitoring for angioedema, particularly during therapy initiation. The findings from this study need to be validated in prospective studies for further elucidation of the underlying mechanisms.

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BackgroundInsulin autoimmune syndrome (IAS) is a rare immune-mediated hypoglycemic disorder predominantly triggered by pharmacological agents. Despite the established links to thiol-containing drugs, emerging non-thiol triggers and significant geographical reporting biases limit comprehensive risk profiling. This study integrated pharmacovigilance data and published evidence to establish the first systematic epidemiological and pharmacological profile of drug-induced IAS.MethodsWe analysed 228 IAS cases from the FDA AE Reporting System (FAERS; 2004-Q2 2024) and a systematic review of 263 published cases (1980-2024). Multimodal disproportionality analysis-including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Multi-item Gamma Poisson Shrinker (MGPS), and Bayesian Confidence Propagation Neural Network (BCPNN)-identified drug-induced adverse event signals. Associations were stratified into a three-tier evidence framework (Levels 1-3) based on methodological concordance, case counts, and strength of the supporting literature.ResultsFifty-eight agents showed potential IAS associations, including 12 novel pharmacovigilance signals (e.g., bevacizumab, sitagliptin, amlodipine, and olmesartan). Thiol-containing drugs exhibit the strongest signals (PRR > 200; e.g., captopril, methimazole, and clopidogrel). Level 1 evidence (highest confidence) implicated the use of clopidogrel, captopril, omeprazole, and methimazole. IAS was predominantly affected in older patients (median age, 66 years; IQR, 58-77 years), with a male predominance (59.21%), reflecting sex-specific prescription patterns. Geographical disparities persisted, with 85.17% of the cases reported in the literature in Asia. Reports of hypoglycemia exceeded IAS cases for most agents, suggesting an underdiagnosis.ConclusionsThis study established the first evidence-based hierarchy for drug-induced IAS, identifying 58 agents warranting clinical vigilance. Thiol-containing drugs dominate the high-risk profile; however, novel associations (e.g., proton pump inhibitors (PPIs), dipeptidyl peptidase-4 (DPP-4) inhibitors) reveal broader immunological mechanisms. Clinicians should prioritize IAS in older patients with unexplained hypoglycemia exposed to antiplatelet agents or PPIs. Standardized diagnostic criteria and pharmacogenetic profiling (e.g., human leukocyte antigen DRB1 (HLA-DRB1) *04:06) are urgently required to improve detection.

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ObjectiveTo systematically evaluate the relative efficacy and impact on cardiac function of sacubitril/valsartan (Sac/Val) vs. active antihypertensive comparators represented in the eligible evidence base for reversing left ventricular hypertrophy (LVH) in patients with hypertension using network meta-analysis.MethodsPubMed, Embase, The Cochrane Library, CNKI, Wanfang Data, and SinoMed databases were searched from inception to December 2025 for randomized controlled trials (RCTs) evaluating sacubitril/valsartan vs. active antihypertensive comparators in patients with essential hypertension and cardiovascular remodeling. The primary outcome was the change in left ventricular mass index (LVMI). Network meta-analysis was performed using STATA 18.0 software based on the frequentist framework. Given the clinical heterogeneity in imaging assessment modalities, a random-effects model was employed to calculate the weighted mean difference (MD) and 95% confidence intervals (CI). The surface under the cumulative ranking curve (SUCRA) was used as a supportive ranking metric, whereas comparative interpretation primarily relied on effect estimates and their confidence intervals.ResultsEleven RCTs involving 851 patients were included. The network meta-analysis showed that Sac/Val achieved greater LVMI regression than Amlodipine (MD = -22.54 g/m2, 95% CI: -40.23, -4.86) and Valsartan (MD = -11.34 g/m2, 95% CI: -21.45, -1.23) in reversing LVMI. Compared with Enalapril and Olmesartan, Sac/Val also showed numerically greater LVMI regression, but these differences were not statistically significant. Sac/Val had the highest SUCRA value (96.4%); however, rankings were interpreted descriptively only, while comparative interpretation was primarily based on effect sizes and confidence intervals. Secondary outcome analysis indicated that while Sac/Val effectively reduced systolic and diastolic blood pressure, it had no significant impact on left ventricular ejection fraction (LVEF) (P > 0.05).ConclusionIn hypertensive patients with cardiovascular remodeling, sacubitril/valsartan was associated with greater LVMI regression than amlodipine and valsartan within the current network, whereas comparisons with enalapril and olmesartan remained inconclusive. Given the substantial heterogeneity, evidence of network incoherence, and low-to-very-low certainty of the main comparisons, these results should be regarded as tentative rather than definitive.Systematic review registrationPROSPERO CRD420261281426.

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BackgroundSome clinical guidelines recommend initiating combination antihypertensive therapy as first-line treatment rather than monotherapy. Evidence indicates that a substantial proportion of patients with hypertension require more than one antihypertensive agent to achieve recommended blood pressure targets. However, it remains unclear whether the benefits of initiating combination therapy outweigh the potential risks compared with antihypertensive monotherapy.ObjectiveThis systematic review and meta-analysis was conducted to assess the efficacy of blood pressure control and the risk of drug-related adverse events associated with amlodipine monotherapy compared against first-line combination therapy of amlodipine and an angiotensin receptor blocker (ARB) in patients with primary hypertension.MethodsA systematic literature search was conducted in PubMed, PubMed Central, and the Cochrane Library up to 15 November 2025, using the following search terms: "amlodipine" AND "angiotensin receptor blocker" AND "primary hypertension" AND "randomized controlled trial." Only randomized controlled trials comparing amlodipine monotherapy with first-line combination therapy of amlodipine and an ARB, administered for at least 8 weeks, were included. The primary outcomes were blood pressure control and drug-related adverse events. Meta-analysis was performed using Review Manager (RevMan), version 5.4.ResultsBased on six included studies, the analytical results showed that combination therapy with Calcium Channel Blocker (CCB) and an ARB was associated with 2.25 (odds ratio = 2.25: 95% CI: 1.78-2.83) times odds ratio with statistically significant overall effect (P P = 0.24) compared with CCB (amlodipine 5 mg) monotherapy.ConclusionsThe results of this study indicate that combination therapy with CCB and an ARB is associated with a 2.25-fold higher likelihood of achieving blood pressure control, with a significant correlation, and a lower risk of drug-related adverse events, without a significant correlation, compared with CCB monotherapy.

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ObjectivesThis study investigated the safety of azilsartan and amlodipine combination therapy versus other angiotensin receptor blockers (ARBs) and amlodipine in patients with hypertension.MethodsWe conducted a cohort study utilizing healthcare databases from Korea and Taiwan. Patients aged between 18 years and 75 years who were newly prescribed both an ARB and amlodipine within 6 months of hypertension diagnosis were included. Safety outcomes assessed were hypotension, angioedema, acute pancreatitis, hyperkalemia, hypokalemia, toxic liver disease, hepatic failure, nausea and vomiting, and fall-related injury. Hazard ratios (HRs) with 95% confidence intervals (CIs) for each safety outcome associated with azilsartan medoxomil and amlodipine versus other ARBs combined with amlodipine were calculated within a 1:1 propensity score (PS)-matched cohort. Summary HRs across databases were computed using random-effects meta-analysis.ResultsWe identified 2,472 eligible patients (1,521 from Korea, 951 from Taiwan) initiating treatment with azilsartan medoxomil and amlodipine, and 671,468 patients (312,322 from Korea, 355,409 from Taiwan) initiating other ARBs with amlodipine. After PS matching, baseline characteristics were well-balanced between treatment groups. During the 180-day follow-up, most adverse outcomes did not occur even once in either group, thus precluding the calculation of HRs. The risk of acute pancreatitis was not significantly different between the azilsartan medoxomil and amlodipine group and the other ARB and amlodipine groups (summary HR, 0.86; 95% CI, 0.14 to 5.37).ConclusionsIn this population-based cohort study, azilsartan medoxomil combined with amlodipine was not associated with an increased risk of adverse outcomes compared to other ARBs combined with amlodipine.

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ImportanceNocturnal blood pressure is difficult to manage in clinical practice. Antihypertensive chronotherapy may offer a potential approach for better control. However, the clinical evidence supporting this approach remains controversial.ObjectiveTo compare the effects of morning vs bedtime antihypertensive medication administration on nocturnal blood pressure reduction and circadian rhythm among patients with hypertension.Design, setting, and participantsThis randomized clinical trial was conducted at 15 hospitals in China from June 1, 2022, to April 30, 2024, with a 12-week follow-up. Patients with hypertension without prior antihypertensive treatment or who had discontinued antihypertensive agents for 2 weeks were randomized to the morning (6:00-10:00 am) or bedtime (6:00-10:00 pm) dosing group.InterventionsPatients received a single pill containing olmesartan, 20 mg, and amlodipine, 5 mg, daily for 12 weeks, with dosage adjustments based on ambulatory and office blood pressure measurements at week 4 and week 8.Main outcomes and measuresThe primary outcome was the change in nighttime systolic blood pressure from baseline to 12 weeks. Key secondary outcomes included changes in office and other ambulatory blood pressure indicators. The primary and secondary outcomes were analyzed in the intention-to-treat and the per-protocol populations.ResultsA total of 720 patients (mean [SD] age, 55.5 [10.6] years; 409 men [56.8%]) were randomized to morning (n = 352) or bedtime (n = 368) dosing groups. The mean (SD) baseline blood pressure values for morning vs bedtime dosing at 24 hours were 148.0 (11.1)/91.4 (9.0) mm Hg vs 147.6 (11.0)/91.6 (9.2) mm Hg, for daytime were 152.3 (11.0)/94.0 (9.2) mm Hg vs 151.5 (11.6)/94.0 (9.8) mm Hg, for nighttime were 138.4 (15.1)/85.4 (10.4) mm Hg vs 138.3 (13.0)/85.8 (9.4) mm Hg, and in the office were 154.4 (12.1)/94.6 (10.3) mm Hg vs 154.3 (12.5)/95.1 (11.1) mm Hg. Compared with patients in the morning dosing group, those in the bedtime dosing group showed significantly greater reductions in nighttime systolic blood pressure (between-group difference, -3.0 mm Hg [95% CI, -5.1 to -1.0 mm Hg]; P = .004), and nighttime diastolic blood pressure (between-group difference, -1.4 mm Hg [95% CI, -2.8 to -0.1 mm Hg]; P = .04), with better nocturnal systolic blood pressure control (79.0% [244 of 309] vs 69.8% [208 of 298]; P = .01) and improved circadian rhythm. The incidence of nocturnal hypotension did not differ.Conclusions and relevanceIn this randomized clinical trial of antihypertensive chronotherapy, bedtime dosing provided better control of nocturnal blood pressure and improved the circadian rhythm, without reducing the efficacy on mean daytime or 24-hour blood pressure, or increasing the risk of nocturnal hypotension. These findings support the potential advantages of bedtime administration and offer new evidence to guide future research on antihypertensive chronotherapy.Trial registrationChinese Clinical Trial Registry Identifier: ChiCTR2200059719.

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