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{{drugbox |
| IUPAC_name        = (2''S'',4''S'',5''S'',7''S'')-5-amino-''N''-(2-carbamoyl-2-methyl-<br>propyl)-4-hydroxy-7-{[4-methoxy-3-(3-methoxypropoxy)<br>phenyl]methyl}-8-methyl-2-propan-2-yl-nonanamide
| image            = Aliskiren_svg.png
| width            = 240px
| CAS_number        = 173334-57-1
| ATC_prefix        = C09
| ATC_suffix        = XA02
| ATC_supplemental  = {{ATC|C09|XA52}}
| PubChem          = 5493444
| DrugBank          =
| C = 30 | H = 53 | N = 3 | O = 6
| molecular_weight  = 551.758 g/mol
| bioavailability  = Low (approximately 2.5%)
| protein_bound    =
| metabolism        = [[Liver|Hepatic]], [[CYP3A4]]-mediated
| elimination_half-life = 24 hours
| excretion        = [[Kidney|Renal]]
| pregnancy_AU      =  <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_US      =  <!-- A / B            / C / D / X -->
| pregnancy_category=  C in first trimester<br>D in second and third trimesters
| legal_AU          =  <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 -->
| legal_CA          =  <!--            / Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_UK          =  <!-- GSL        / P      / POM / CD / Class A, B, C -->
| legal_US          =  Rx-only
| legal_status      =
| routes_of_administration = Oral
}}
__NOTOC__
__NOTOC__
{{CMG}}


{{Aliskiren}}


{{CMG}}; {{AE}} {{SS}}


'''''For patient information about Aliskiren, click [[Aliskiren (patient information)|here]].'''''
{{SB}} TEKTURNA<sup>®</sup>


==[[Aliskiren (patient information)|For patient information, click here]]==
==Overview==


==Overview==
'''Aliskiren''' ([[International Nonproprietary Name|INN]]) is a first in class [[renin]] [[enzyme inhibitor|inhibitor]] co-developed by the Swiss pharmaceutical companies [[Novartis]] and [[Speedel]].<ref>{{cite journal |author=Gradman A, Schmieder R, Lins R, Nussberger J, Chiang Y, Bedigian M|title=Aliskiren, a novel orally effective renin inhibitor, provides dose-dependent antihypertensive efficacy and placebo-like tolerability in hypertensive patients |journal=Circulation |volume=111 |issue=8 |pages=1012-8 |year=2005 |pmid=15723979}}</ref><!--
'''Aliskiren''' ([[International Nonproprietary Name|INN]]) is a first in class [[renin]] [[enzyme inhibitor|inhibitor]] co-developed by the Swiss pharmaceutical companies [[Novartis]] and [[Speedel]].<ref>{{cite journal |author=Gradman A, Schmieder R, Lins R, Nussberger J, Chiang Y, Bedigian M |title=Aliskiren, a novel orally effective renin inhibitor, provides dose-dependent antihypertensive efficacy and placebo-like tolerability in hypertensive patients |journal=Circulation |volume=111 |issue=8 |pages=1012-8 |year=2005 |pmid=15723979}}</ref><!--
--><ref>
--><ref>
{{cite journal  
{{cite journal  
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|url=http://linkinghub.elsevier.com/retrieve/pii/S0140673606694427}}
|url=http://linkinghub.elsevier.com/retrieve/pii/S0140673606694427}}
</ref>
</ref>
It was approved by the U.S. [[Food and Drug Administration]] in 2007 for the treatment of [[hypertension]].<ref>{{cite news | url = http://www.cbc.ca/cp/HealthScout/070306/6030611AU.html | title = First Hypertension Drug to Inhibit Kidney Enzyme Approved | date = March 6, 2007| publisher = CBC}}</ref> The trade name for aliskiren is '''Tekturna''' in the USA, and '''Rasilez''' in the UK.
It was approved by the U.S. [[Food and Drug Administration]] in 2007 for the treatment of [[hypertension]].<ref>{{cite news | url =http://www.cbc.ca/cp/HealthScout/070306/6030611AU.html | title = First Hypertension Drug to Inhibit Kidney Enzyme Approved | date = March 6, 2007|publisher = CBC}}</ref> The trade name for aliskiren is '''Tekturna''' in the USA, and '''Rasilez''' in the UK.
==Category==
 
Renin inhibitors;Phenol ethers;Cardiovascular Drugs
==FDA Package Insert==


==Adverse effects==
====TEKTURNA (aliskiren hemifumarate) tablet, film coated ====
*[[Angioedema]]
*[[Hyperkalemia]] (particularly when used with ACE inhibitors in diabetic patients)
*[[Hypotension]] (particularly in volume-depleted patients)
*Diarrhea and other GI symptoms
*Rash, elevated [[uric acid]], [[gout]], and renal stones.


A rare adverse event was allergic swelling of the face, lips or tongue and difficulty breathing, side effects that are common with other drugs for hypertension that act directly on the renin-angiotensin system. <ref name=rxdrug>{{cite web | title =FDA approves renin inhibitor aliskiren for hypertension | publisher=RxDrug News | url=http://www.rxdrugnews.com/site/more/fda-approves-renin-inhibitor-aliskiren-for-hypertension/ | year = 2007}}</ref>
'''  [[Aliskiren indications and usage|Indications and Usage]]'''
'''| [[Aliskiren dosage and administration|Dosage and Administration]]'''
'''| [[Aliskiren dosage forms and strengths|Dosage Forms and Strengths]]'''
'''| [[Aliskiren contraindications|Contraindications]]'''
'''| [[Aliskiren warnings and precautions|Warnings and Precautions]]'''
'''| [[Aliskiren adverse reactions|Adverse Reactions]]'''
'''| [[Aliskiren drug interactions|Drug Interactions]]'''
'''| [[Aliskiren use in specific populations|Use in Specific Populations]]'''
'''| [[Aliskiren overdosage|Overdosage]]'''
'''| [[Aliskiren description|Description]]'''
'''| [[Aliskiren clinical pharmacology|Clinical Pharmacology]]'''
'''| [[Aliskiren nonclinical toxicology|Nonclinical Toxicology]]'''
'''| [[Aliskiren clinical studies|Clinical Studies]]'''
'''| [[Aliskiren how supplied storage and handling|How Supplied/Storage and Handling]]'''
'''| [[Aliskiren patient counseling information|Patient Counseling Information]]'''
'''| [[Aliskiren labels and packages|Labels and Packages]]'''


==Contraindications==
==Mechanism of Action==
As with [[ACE inhibitors]], renin inhibitors should not be used in pregnancy, specifically the second and third trimesters, during which they will interfere with fetal kidney development and lead to [[oligohydramnios]].


Aliskiren has not yet been evaluated in patients with significantly impaired renal function.
[[Renin]]is secreted by the kidney in response to decreases in blood volume and renal perfusion. [[Renin]]cleaves angiotensinogen to form the inactive decapeptide angiotensin I (Ang I). Ang I is converted to the active octapeptide angiotensin II (Ang II) by angiotensin-converting enzyme (ACE) and non-ACE pathways. Ang II is a powerful vasoconstrictor and leads to the release of catecholamines from the adrenal medulla and prejunctional nerve endings. It also promotes aldosterone secretion and sodium reabsorption. Together, these effects increase blood pressure. Ang II also inhibits [[Renin]]release, thus providing a negative feedback to the system. This cycle, from [[Renin]]through angiotensin to aldosterone and its associated negative feedback loop, is known as the renin-angiotensin-aldosterone system ([[RAAS]]). Aliskiren is a direct [[Renin]]inhibitor, decreasing plasma [[Renin]]activity (PRA) and inhibiting the conversion of angiotensinogen to Ang I. Whether aliskiren affects other [[RAAS]] components, e.g., [[ACE]] or non-[[ACE]] pathways, is not known.


==Drug Interactions==
All agents that inhibit the RAAS, including [[Renin]]inhibitors, suppress the negative feedback loop, leading to a compensatory rise in plasma [[Renin]]concentration. When this rise occurs during treatment with ACE inhibitors and ARBs, the result is increased levels of PRA. During treatment with aliskiren, however, the effect of increased [[Renin]]levels is blocked so that PRA, Ang I and Ang II are all reduced, whether aliskiren is used as monotherapy or in combination with other antihypertensive agents.


Minor substrate of [[CYP3A4]]:
*Reduces [[furosemide]] blood concentration.
*[[Atorvastatin]] or [[ketoconazole]] may increase blood concentration.


==References==
==References==
<references/>
{{reflist|2}}
 
==External links==
* {{PDFlink|[http://www.fda.gov/cder/foi/label/2007/021985lbl.pdf Tekturna U.S. prescribing information]|143&nbsp;KiB<!-- application/pdf, 147266 bytes -->}} at the U.S. [[Food and Drug Administration]] website
* [http://www.genome.jp/dbget-bin/www_bget?dr:D03208 Aliskiren] at [[KEGG PATHWAY Database|KEGG Ligand Database]]
* {{MeshName|aliskiren}}
* Speedel [http://www.speedel.com/]
 


{{Agents acting on the renin-angiotensin system}}
{{Agents acting on the renin-angiotensin system}}


[[Category:Antihypertensive agents]]
[[Category:Renin inhibitors]]
[[Category:Renin inhibitors]]
[[Category:Phenol ethers]]
[[Category:Cardiovascular Drugs]]
[[Category:Drugs]]
[[Category:Drugs]]
[[de:Aliskiren]]
{{WikiDoc Help Menu}}
{{WikiDoc Sources}}

Revision as of 03:03, 25 February 2014


Aliskiren
TEKTURNA® FDA Package Insert
Indications and Usage
Dosage and Administration
Dosage Forms and Strengths
Contraindications
Warnings and Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Overdosage
Description
Clinical Pharmacology
Nonclinical Toxicology
Clinical Studies
How Supplied/Storage and Handling
Labels and Packages
Clinical Trials on Aliskiren
ClinicalTrials.gov

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sheng Shi, M.D. [2]

For patient information about Aliskiren, click here. Synonyms / Brand Names: TEKTURNA®

Overview

Aliskiren (INN) is a first in class renin inhibitor co-developed by the Swiss pharmaceutical companies Novartis and Speedel.[1][2] It was approved by the U.S. Food and Drug Administration in 2007 for the treatment of hypertension.[3] The trade name for aliskiren is Tekturna in the USA, and Rasilez in the UK.

Category

Renin inhibitors;Phenol ethers;Cardiovascular Drugs

FDA Package Insert

TEKTURNA (aliskiren hemifumarate) tablet, film coated

Indications and Usage | Dosage and Administration | Dosage Forms and Strengths | Contraindications | Warnings and Precautions | Adverse Reactions | Drug Interactions | Use in Specific Populations | Overdosage | Description | Clinical Pharmacology | Nonclinical Toxicology | Clinical Studies | How Supplied/Storage and Handling | Patient Counseling Information | Labels and Packages

Mechanism of Action

Reninis secreted by the kidney in response to decreases in blood volume and renal perfusion. Renincleaves angiotensinogen to form the inactive decapeptide angiotensin I (Ang I). Ang I is converted to the active octapeptide angiotensin II (Ang II) by angiotensin-converting enzyme (ACE) and non-ACE pathways. Ang II is a powerful vasoconstrictor and leads to the release of catecholamines from the adrenal medulla and prejunctional nerve endings. It also promotes aldosterone secretion and sodium reabsorption. Together, these effects increase blood pressure. Ang II also inhibits Reninrelease, thus providing a negative feedback to the system. This cycle, from Reninthrough angiotensin to aldosterone and its associated negative feedback loop, is known as the renin-angiotensin-aldosterone system (RAAS). Aliskiren is a direct Renininhibitor, decreasing plasma Reninactivity (PRA) and inhibiting the conversion of angiotensinogen to Ang I. Whether aliskiren affects other RAAS components, e.g., ACE or non-ACE pathways, is not known.

All agents that inhibit the RAAS, including Renininhibitors, suppress the negative feedback loop, leading to a compensatory rise in plasma Reninconcentration. When this rise occurs during treatment with ACE inhibitors and ARBs, the result is increased levels of PRA. During treatment with aliskiren, however, the effect of increased Reninlevels is blocked so that PRA, Ang I and Ang II are all reduced, whether aliskiren is used as monotherapy or in combination with other antihypertensive agents.


References

  1. ↑ Gradman A, Schmieder R, Lins R, Nussberger J, Chiang Y, Bedigian M (2005). "Aliskiren, a novel orally effective renin inhibitor, provides dose-dependent antihypertensive efficacy and placebo-like tolerability in hypertensive patients". Circulation. 111 (8): 1012–8. PMID 15723979.
  2. ↑ Straessen JA, Li Y, and Richart T (2006). "Oral Renin Inhibitors". Lancet. 368 (9545): 1449–56. PMID 17055947.
  3. ↑ "First Hypertension Drug to Inhibit Kidney Enzyme Approved". CBC. March 6, 2007.

Template:Agents acting on the renin-angiotensin system

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