aliskiren
Sources réglementaires consultées
Indications approuvées
- Traitement de l’hypertension artérielle essentielle chez l’adulte ; l’étiquette américaine inclut également les patients âgés d’au moins 6 ans pesant 50 kg ou plus.
Contre-indications
Absolues
- Hypersensibilité, antécédent d’angio-œdème lié à l’aliskirène ou angio-œdème héréditaire ou idiopathique.
- Deuxième ou troisième trimestre de la grossesse.
- Utilisation avec un IEC ou un ARA II chez les patients diabétiques ou ayant un DFG inférieur à 60 ml/min/1,73 m².
- Enfants de moins de 2 ans.
Mises en garde cliniques
- Mise en garde encadrée · Toxicité fœtale : arrêter dès que la grossesse est détectée. — DailyMed aliskiren tablets set ID f3fd2503-25ef-4660-a29a-f62c491e28fb; openFDA Tekturna set ID 3dd61fa5-1620-4ebf-bbdb-ede29b92fce2
- Mise en garde majeure · Peut provoquer une hypotension, une hyperkaliémie et une altération rénale, y compris une insuffisance rénale aiguë ; surveiller la pression artérielle, la fonction rénale et les électrolytes. — CIMA registro 07405022
- Mise en garde majeure · Arrêter en cas de diarrhée sévère persistante ou de signes d’angio-œdème ou de réaction anaphylactique. — CIMA registro 07405022
Interactions médicamenteuses
- SévèreCiclosporine, itraconazole, quinidine et autres inhibiteurs puissants de la P-gp
Mécanisme: Ils augmentent fortement l’exposition à l’aliskirène.
Recommandation: Le RCP espagnol contre-indique cette association.
https://cima.aemps.es/cima/dochtml/ft/07405022/FT_07405022.html
- SévèreIEC ou ARA II
Mécanisme: Le double blocage augmente l’hypotension, l’hyperkaliémie et l’altération rénale.
Recommandation: Contre-indiqué en cas de diabète ou de DFG inférieur à 60 ; éviter en général et, si l’association est indispensable, surveiller étroitement.
https://cima.aemps.es/cima/dochtml/ft/07405022/FT_07405022.html
- ModéréeAINS
Mécanisme: Peuvent réduire l’effet antihypertenseur et altérer la fonction rénale.
Recommandation: Surveiller périodiquement la fonction rénale.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f3fd2503-25ef-4660-a29a-f62c491e28fb
- ModéréeFurosémide ou torasémide
Mécanisme: L’aliskirène peut réduire l’exposition au diurétique de l’anse.
Recommandation: Surveiller l’effet diurétique et l’état volémique.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f3fd2503-25ef-4660-a29a-f62c491e28fb
Effets indésirables
Communs (≥1%)
Diarrhée (2,3 % dans l’étiquette américaine) · Étourdissements · Arthralgie · Hyperkaliémie
Rares mais graves
Réaction anaphylactique · Angio-œdème · Réaction cutanée sévère · Insuffisance rénale aiguë
Grossesse et allaitement
Ne pas utiliser au premier trimestre ni lors d’un projet de grossesse ; le médicament est contre-indiqué aux deuxième et troisième trimestres et doit être arrêté si une grossesse est détectée. Il ne doit pas être utilisé pendant l’allaitement.
Bibliographie récente (PubMed)
Different first-line drug classes for patients with hypertension are often assumed to have similar effectiveness with respect to reducing mortality and morbidity outcomes, and lowering blood pressure. First-line low-dose thiazide diuretics have been previously shown to have the best mortality and morbidity evidence when compared with placebo or no treatment. Head-to-head comparisons of thiazides with other blood pressure-lowering drug classes would demonstrate whether there are important differences. To compare the effects of first-line diuretic drugs with other individual first-line classes of antihypertensive drugs on mortality, morbidity, and withdrawals due to adverse effects in patients with hypertension. Secondary objectives included assessments of the need for added drugs, drug switching, and blood pressure-lowering. Cochrane Hypertension's Information Specialist searched the Cochrane Hypertension Specialized Register, CENTRAL, MEDLINE, Embase, and trials registers to March 2021. We also checked references and contacted study authors to identify additional studies. A top-up search of the Specialized Register was carried out in June 2022. Randomized active comparator trials of at least one year's duration were included. Trials had a clearly defined intervention arm of a first-line diuretic (thiazide, thiazide-like, or loop diuretic) compared to another first-line drug class: beta-blockers, calcium channel blockers, alpha adrenergic blockers, angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor blockers, direct renin inhibitors, or other antihypertensive drug classes. Studies had to include clearly defined mortality and morbidity outcomes (serious adverse events, total cardiovascular events, stroke, coronary heart disease (CHD), congestive heart failure, and withdrawals due to adverse effects). We used standard Cochrane methodological procedures. We included 20 trials with 26 comparator arms randomizing over 90,000 participants. The findings
The role of chronic inflammatory process in the pathogenesis or exacerbation of hypertension has been already acknowledged. Therefore, one can speculate that hypotensive drugs may exert some of their therapeutic effects due to immunomodulatory properties. So far, this assumption has been tested in different studies, and the resulting knowledge is summarized in the current review article that is dedicated to different groups of antihypertensives, namely calcium channel blockers, beta blockers, as well as other less commonly used medications, such as hydralazine, alfa-2 receptor agonists, diazoxide, doxazosin, aliskiren, and sodium nitroprusside. Articles were found in the Pubmed by entering the name of a specific drug/group of drugs with the words: immunology, cellular response, humoral response, inflammation, interleukin. The 2000-2021 range was used to search for all drugs except propranolol (1980-2021) and calcium blockers (1990-2021). Observed decrease in serum/plasma concentration of proinflammatory cytokines, and CRP along with lower expression of adhesion molecules on immune cells strongly suggest that these drugs possess immunomodulatory properties, which seems to be crucial in the medical practice, especially in the therapy of hypertensive patients with other accompanying inflammatory-based diseases, such as type II diabetes, developed metabolic syndrome, allergies or autoimmunity.
The Renin-Angiotensin System (RAS) has attracted considerable interest beyond its traditional cardiovascular role due to emerging data indicating its potential involvement in neurodegenerative diseases, including Alzheimer's dementia (AD). This review investigates the therapeutic implications of RAS modulators, specifically focusing on angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), and renin inhibitors in AD. ACEIs, commonly used for hypertension, show promise in AD by reducing angiotensin (Ang) II levels. This reduction is significant as Ang II contributes to neuroinflammation, oxidative stress, and β-amyloid (Aβ) accumulation, all implicated in AD pathogenesis. ARBs, known for vasodilation, exhibit neuroprotection by blocking Ang II receptors, improving cerebral blood flow and cognitive decline in AD models. Renin inhibitors offer a novel approach by targeting the initial RAS step, displaying anti-inflammatory and antioxidant effects that mitigate AD degeneration. Preclinical studies demonstrate RAS regulation's favorable impact on neuroinflammation, neuronal damage, cognitive function, and Aβ metabolism. Clinical trials on RAS modulators in AD are limited, but with promising results, ARBs being more effective that ACEIs in reducing cognitive decline. The varied roles of ACEIs, ARBs, and renin inhibitors in RAS modulation present a promising avenue for AD therapeutic intervention, requiring further research to potentially transform AD treatment strategies.
To characterize and compare various medicines for chronic heart failure (CHF), changes in circulatory physiological parameter during pharmacotherapy were investigated by a model-based meta-analysis (MBMA) of circulatory physiology. The clinical data from 61 studies mostly in patients with heart failure with reduced ejection fraction (HFrEF), reporting changes in heart rate, blood pressure, or ventricular volumes after treatment with carvedilol, metoprolol, bisoprolol, bucindolol, enalapril, aliskiren, or felodipine, were analyzed. Seven cardiac and vasculature function indices were estimated without invasive measurements using models based on appropriate assumptions, and their correlations with the mortality were assessed. Estimated myocardial oxygen consumption, a cardiac load index, correlated excellently with the mortality at 3, 6, and 12 months after treatment initiation, and it explained differences in mortality across the different medications. The analysis based on the present models were reasonably consistent with the hypothesis that the treatment of HFrEF with various medications is due to effectively reducing the cardiac load. Assessment of circulatory physiological parameters by using MBMA would be insightful for quantitative understanding of CHF treatment.