aliskiren
Regulatory sources consulted
Approved indications
- Treatment of essential hypertension in adults; the US label also includes patients at least 6 years old who weigh 50 kg or more.
Contraindications
Absolute
- Hypersensitivity, previous aliskiren-associated angioedema, or hereditary or idiopathic angioedema.
- Second or third trimester of pregnancy.
- Use with an ACE inhibitor or ARB in patients with diabetes or GFR below 60 mL/min/1.73 m².
- Children younger than 2 years.
Clinical warnings
- Boxed warning · Fetal toxicity: discontinue as soon as pregnancy is detected. — DailyMed aliskiren tablets set ID f3fd2503-25ef-4660-a29a-f62c491e28fb; openFDA Tekturna set ID 3dd61fa5-1620-4ebf-bbdb-ede29b92fce2
- Major warning · May cause hypotension, hyperkalemia, and renal impairment, including acute renal failure; monitor blood pressure, renal function, and electrolytes. — CIMA registro 07405022
- Major warning · Discontinue for severe persistent diarrhea or signs of angioedema or an anaphylactic reaction. — CIMA registro 07405022
Drug interactions
- HighCyclosporine, itraconazole, quinidine, and other strong P-gp inhibitors
Mechanism: They markedly increase aliskiren exposure.
Recommendation: The Spanish label contraindicates this combination.
https://cima.aemps.es/cima/dochtml/ft/07405022/FT_07405022.html
- HighACE inhibitor or ARB
Mechanism: Dual blockade increases hypotension, hyperkalemia, and renal impairment.
Recommendation: Contraindicated in diabetes or GFR below 60; generally avoid and, if essential, monitor closely.
https://cima.aemps.es/cima/dochtml/ft/07405022/FT_07405022.html
- ModerateNSAIDs
Mechanism: May reduce the antihypertensive effect and impair renal function.
Recommendation: Monitor renal function periodically.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f3fd2503-25ef-4660-a29a-f62c491e28fb
- ModerateFurosemide or torsemide
Mechanism: Aliskiren may reduce exposure to the loop diuretic.
Recommendation: Monitor the diuretic effect and volume status.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f3fd2503-25ef-4660-a29a-f62c491e28fb
Adverse events
Common (≥1%)
Diarrhea (2.3% in the US label) · Dizziness · Arthralgia · Hyperkalemia
Rare but serious
Anaphylactic reaction · Angioedema · Severe cutaneous adverse reaction · Acute renal failure
Pregnancy and lactation
Do not use in the first trimester or when planning pregnancy; it is contraindicated in the second and third trimesters and must be discontinued if pregnancy is detected. It should not be used during breastfeeding.
Recent literature (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.