Aliskiren 150mg 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.

Abstract licence: CC BY

Fruit juice-antihypertensive drug interactions can lead to subtherapeutic or supratherapeutic outcomes. This systematic review and meta-analysis assesses such interactions and their potential clinical relevance. PubMed, Scopus, and Science Direct databases were searched from their inception through June 2024. Eligible studies were those that investigated the effects of fruit juice on the pharmacokinetics of antihypertensive drugs. I 2 was used to determine heterogeneity among studies, and a random effect model was employed for meta-analysis. This review adhered to PRISMA guidelines and was registered in PROSPERO (CRD42022340159). Fifty-one studies were included. Most of them were open-label crossover trials. Grapefruit juice (GFJ), an inhibitor of organic-anion-transporting polypeptide (OATP) transporters and cytochrome P450 (CYP) 3A4, significantly decreased the AUC and C max of aliskiren and celiprolol by approximately 80–90 %. Conversely, the AUC and C max of calcium channel blockers decreased with variable degrees when co-administered with GFJ. Apple and orange juices have comparable effects on certain medications. Most studies had small sample sizes and were of moderate quality. Hemodynamic effects were not assessed in most studies; thus, the clinical significance of these interactions remains uncertain and should be further investigated. Co-administration of fruit juice with antihypertensive drugs can result in an increase or decrease in drugs’ bioavailability, depending on the drugs’ metabolism route and the involvement of transporters. Though further studies are needed to confirm clinical relevance in hypertensive patients, it is advised to avoid co-consumption of fruit juice with drugs showing significant changes in pharmacokinetic parameters to prevent subtherapeutic or supratherapeutic effects. • Grapefruit juice decreased AUC and C max of aliskiren, celiprolol, and calcium channel blockers. • Orange juice and apple juice also decreased C max and AUC of certain antihypertensive drugs such as aliskiren and atenolol. • The clinical relevance of fruit juice-antihypertensive drug interactions remains unexplored in hypertensive patients.

Abstract licence: CC BY-NC-ND

Renin Angiotensin System inhibitors (RASi) are widely used in cancer patients to treat high prevalence comorbidities such as hypertension, proteinuric nephropathies and cardiopathies. Emerging research has raised concerns about their potential role in oncogenesis, while uncovering promising anti-tumor properties. This systematic review investigates the effects of RASi, specifically angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARBs), and the direct renin inhibitor (DRI) Aliskiren, on cancer risk and progression. Emphasis is placed on underlying molecular pathways and potential impact of RASi on cancer development and growth. Evidence from the analyzed studies remains heterogeneous. ACEi and ARBs may contribute to oncogenic processes through bradykinin accumulation and renin activation, both of which are known to drive mechanisms associated with cancer development and progression, particularly in lung cancer. Conversely, Aliskiren may potentially exhibit a more favorable anticancer profile by interfering with neo-angiogenesis, oxidative stress, inflammatory signaling, tumor growth, and metastasis. Moreover, existing studies suggest that Aliskiren may help reduce cancer cachexia, further supporting its potential relevance in oncologic settings, although the available literature on Aliskiren remains limited. While the oncogenic effects of ACEi and ARBs on cancer remain inconclusive, Aliskiren emerges as an antihypertensive drug potentially able to interfere with pro-oncogenic signaling. Nonetheless, its limited evidence base underscores the urgent need for well-designed prospective studies to clarify the differential oncologic impact of various RASi classes across populations. Indeed, cancer patients undergoing long-term RASi deserve close monitoring and multidisciplinary approach for assessment of personalized therapy. • RAS dysregulation links hypertension to cancer through various oncogenic pathways, highlighting the differential effects of RASi on oncogenesis. • ACEi may increase lung cancer risk due to the accumulation of bradykinin and substance P. • Research on ARBs and cancer risk has yielded conflicting results; however some studies suggest an association with higher lung cancer rates. • Aliskiren, a direct renin inhibitor, suppresses renin activity and its downstream pro-oncogenic molecular pathways. Additionally, it may slow cancer cachexia progression.

Abstract licence: CC BY

Aliskiren has been proposed as an alternative for renin-angiotensin system blockage in chronic kidney disease (CKD); however, its efficacy and safety remain uncertain. The objective of this study was to evaluate the antihypertensive and antiproteinuric effects of aliskiren monotherapy in patients with CKD and hypertension. PRISMA 2020 guidelines were adopted for this systematic review and meta-analysis (PROSPERO: CRD420251024983). Relevant studies published (January 2001-February 2026) were identified in PubMed and Web of Science that compared aliskiren monotherapy with placebo or other antihypertensives in adults with CKD. Random-effects models were used to assess changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), and urinary protein excretion. Risk of bias was evaluated using the RoB 2 and ROBINS-I tools. Nine trials (eight for quantitative analysis) were included. Overall, aliskiren did not significantly reduce SBP (MD -2.91 mmHg; 95% CI -8.74 to 2.91; p = 0.33) or DBP (n = 300; MD -1.35 mmHg; 95% CI -4.72 to 2.02; p = 0.43). In subgroup analysis, short-term trials (<24 weeks) showed significant SBP reduction (MD -9.31 mmHg; 95% CI -17.72 to -0.89), whereas longer-term studies (≥24 weeks) did not. Five trials (n = 209) reported a 28% reduction in urinary protein excretion with aliskiren (log response ratio -0.33; 95% CI -0.57 to -0.09; p = 0.007). Aliskiren provides a transient decrease in blood pressure and sustained antiproteinuric effect in patients with CKD, although heterogeneous and estimation-dependent. It may be considered an option for individuals intolerant of ACE inhibitors or angiotensin receptor blockers, although evidence on long-term efficacy and safety remains limited.

Abstract licence: CC BY-NC

This systematic review evaluated the comparative efficacy of direct renin inhibitors, primarily aliskiren, versus angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) in the management of hypertension across varied patient populations. A total of 417 records were screened, with five studies meeting inclusion criteria, including four randomized controlled trials and one large prospective registry. Overall, clinic blood pressure reductions were similar between renin inhibitors and ACEi/ARB therapy. Subgroup analyses revealed nuanced differences: ARBs demonstrated superior effects on reducing urinary angiotensinogen and albuminuria in patients with high-normal albuminuria, while aliskiren provided greater reductions in microalbuminuria and systolic blood pressure when used as add-on therapy in type 2 diabetes with uncontrolled hypertension. In obese hypertensive men, aliskiren uniquely reduced filtration fraction and albuminuria, suggesting possible renal hemodynamic advantages. Real-world registry data further supported the effectiveness and tolerability of aliskiren, with comparable blood pressure reductions and safety outcomes to ACEi/ARB therapy, though limitations inherent to non-randomized designs persist. Risk of bias was judged as low to some concerns across studies, reflecting small sample sizes, limited blinding, and heterogeneous populations. Collectively, current evidence suggests that while renin inhibitors may serve as an alternative for patients intolerant to ACEi/ARB, they do not demonstrate clear superiority, and their role may be more relevant in specific subgroups such as obesity-related hypertension or advanced microalbuminuria. Larger, longer-term trials with hard cardiovascular and renal outcomes are warranted to define their optimal place in therapy.

Abstract licence: CC BY

We aimed to determine effects of aliskiren, a direct renin inhibitor, loaded onto polymeric nanoparticles on the (pro)renin receptor (Atp6ap2), angiotensin II type 1 receptor (Agtr1), and angiotensin-converting enzyme (ACE) gene expression in the heart of spontaneously hypertensive rats (SHR). Twelve-week-old male SHRs were divided into an untreated group and groups treated with powdered aliskiren or aliskiren-loaded nanoparticles (25 mg/kg/day). After three weeks, the accumulation of aliskiren, distribution of polymeric nanoparticles, gene expression of Atp6ap2 and Agtr1 receptors and ACE, and protein expression of NADPH oxidase along with the conjugated diene (CD) concentration were analyzed. The accumulation of aliskiren in the heart was higher in the aliskiren-loaded nanoparticle group than in the powdered group. The fluorescent signals of nanoparticles were visible in cardiomyocytes, vessel walls, and erythrocytes. Aliskiren-loaded nanoparticles decreased the gene expression of Atp6ap2 and ACE, while not affecting Agtr1. Both forms of aliskiren decreased the protein expression of NADPH oxidase, with a more pronounced effect observed in the aliskiren-loaded nanoparticle group. CD concentration was decreased only in the aliskiren-loaded nanoparticle group. We hypothesize that aliskiren-loaded nanoparticle-mediated downregulation of Atp6ap2 and ACE may contribute to a decrease in ROS generation with beneficial effects in the heart. Moreover, polymeric nanoparticles may represent a promising tool for targeted delivery of aliskiren.

Abstract licence: CC BY