Aliskiren
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| Clinical data | |
|---|---|
| Trade names | Tekturna, Rasilez |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a607039 |
| License data | |
| Pregnancy category |
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| Routes of administration | By mouth (tablets) |
| ATC code | |
| Legal status | |
| Legal status | |
| Pharmacokinetic data | |
| Bioavailability | Low (approximately 2.5%) |
| Metabolism | Hepatic, CYP3A4-mediated |
| Elimination half-life | 24 hours |
| Excretion | Renal |
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Aliskiren (brand names Tekturna and Rasilez) is the first in a class of drugs called direct renin inhibitors. It is used for essential (primary) hypertension.[2] While used for high blood pressure, other better studied medications are typically recommended due to concerns of higher side effects and less evidence of benefit.[3]
In December 2011, Novartis halted a trial of the drug after discovering increased nonfatal
As a result, in 2012:
- A new contraindication was added to the product label concerning the use of aliskiren with angiotensin-converting enzyme inhibitors (ACEIs) in patients with diabetes because of the risk of kidney impairment, low blood pressure, and high levels of potassium in the blood.[6]
- A warning to avoid use of aliskiren with ARBs or ACEIs was also added for patients with moderate to severe kidney impairment (i.e., where glomerular filtration rate is less than 60 ml/min).[6]
- Novartis decided to stop marketing Valturna (aliskiren/valsartan).[7]
Aliskiren was co-developed by the Swiss pharmaceutical companies Novartis and Speedel.[8][9]
Medical uses
While used for high blood pressure, other better-studied medications are typically recommended.[3] Prescrire has stated that aliskiren is potentially more harmful than beneficial and thus list it as a drug to avoid (as of 2014).[3]
Adverse effects
- Angioedema - The ADE of angioedema found in patients using Aliskiren is due to the inhibition of bradykinin degradation which occurs within the Renin-Angiotensin System (RAAS)
- High blood potassium level (particularly when used with ACE inhibitors in diabetic patients)
- Low blood pressure (particularly in volume-depleted patients)
- Diarrhea and other GI symptoms
- Headache
- Dizziness
- Cough
Contraindications
- Pregnancy: Other drugs such as ACE inhibitors, also acting on the renin–angiotensin system, have been associated with fetal malformations and neonatal death.[10] Angiotensin cannot be used in patients who are pregnant because it will result in disruption of normal fetal kidney development.
- Breastfeeding: During animal studies, the drug has been found present in milk.[10]
- Aliskiren has been shown to increase the likelihood of adverse cardiovascular outcomes in patients with diabetes and kidney or heart disease.[5]
Drug interactions
Aliskiren is a minor inhibitor of substrate CYP3A4 and, more importantly, P-glycoprotein:
- It reduces furosemide blood concentration.
- Atorvastatin may increase aliskiren's blood concentration, but no dose adjustment is needed.
- Due to possible interaction with ciclosporin, the use of ciclosporin and aliskiren at the same time is contraindicated.
- Caution should be exercised when aliskiren is administered with ketoconazole and other moderate P-glycoprotein inhibitors such asitraconazole, clarithromycin, telithromycin, erythromycin, or amiodarone.
- Recommendations have been made to stop prescribing aliskiren-containing medicines to patients with diabetes (type 1 or type 2) or with moderate to severe kidney impairment who are also taking an ACE inhibitor or ARB. Such patients should consider alternative antihypertensive treatment as necessary.[11]
Mechanism of action
Aliskiren is an antagonist to renin.
Chemistry
The chemical name for aliskiren is (2 S,4S,5S,7S)-5-amino-N-(2-carbamoyl-2-methylpropyl)-4-hydroxy-2-isopropyl-7-[ 4-methoxy-3-(3-methoxypropoxy)benzyl]-8-methylnonanamide.[14]
Rationale for design
Many drugs control blood pressure by interfering with angiotensin or aldosterone. However, when these drugs are used chronically, the body increases renin production, which drives blood pressure up again. Therefore, pharmacologists have been looking for a drug to inhibit renin directly. Aliskiren is the first drug to do so.[15][16]
References
- FDA. Retrieved 22 Oct 2023.
- ^ "First Hypertension Drug to Inhibit Kidney Enzyme Approved". CBC. 2007-03-06. Archived from the original on 2007-03-22. Retrieved 2007-03-14.
- ^ PMID 25121155.
- ^ Healthzone.ca: Blood-pressure drug reviewed amid dangerous side effects
- ^ PMID 23121378.
- ^ a b "FDA Drug Safety Communication: New Warning and Contraindication for blood pressure medicines containing aliskiren (Tekturna)". U.S. Food and Drug Administration (FDA). 19 January 2016. Retrieved 12 February 2020.
- ^ "Aliskiren Information". U.S. Food and Drug Administration. 8 July 2015. Retrieved 12 February 2020.
- PMID 15723979.
- S2CID 20729350.
- ^ a b Drugs.com: Tekturna
- ^ EMA (2018-09-17). "European Medicines Agency recommends new contraindications and warnings for aliskiren-containing medicines". European Medicines Agency. Retrieved 2023-11-05.
- ^ PMID 10903938.
- S2CID 26512682.
- ^ "Recommended INN List 45" (PDF). WHO Drug Information. 15 (1). 2001.
- PMID 18525047.
- ^ PharmaXChange: Direct Renin Inhibitors as Antihypertensive Drugs Archived 2010-12-07 at the Wayback Machine
External links
- "Aliskiren". Drug Information Portal. U.S. National Library of Medicine.
- Aliskiren at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
