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| {{drugbox |
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| | IUPAC_name = (''S'')-3-(3-(((3,4-dimethoxybicyclo(4.2.0)<br/>octa-1,3,5-trien-7-yl)methyl)methylamino)<br/>propyl)-1,3,4,5-tetrahydro-<br/>7,8-dimethoxy-2''H''-3-benzazepin-2-one
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| | image = 170px-Ivabradine structure.svg.png
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| | width = 158
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| | CAS_number = 155974-00-8
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| | ATC_prefix = C01
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| | ATC_suffix = EB17
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| | PubChem = 132999
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| | DrugBank =
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| | C = 27 | H = 36 | N = 2 | O = 5
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| | molecular_weight = 468.585 g/mol
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| | bioavailability = 40%
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| | metabolism = Hepatic (first-pass) >50%, [[CYP3A4]]-mediated
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| | protein_bound = 70%
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| | elimination_half-life = 2 hours
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| | excretion = [[Kidney|Renal]] and fecal
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| | licence_EU = Procoralan
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| | pregnancy_AU = D
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| | legal_UK = POM
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| | routes_of_administration = Oral
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| }}
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| __NOTOC__
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| {{SI}}
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| {{CMG}}
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| ==Overview==
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| '''Ivabradine''' ([[International Nonproprietary Name|INN]]) ({{pronEng|ɪˈvæbrədin}}) is a novel [[medication]] used for the symptomatic management of stable [[angina pectoris]]. It is marketed under the trade name '''Procoralan''' (Servier Laboratories), and was also known as '''S-16257''' during its development. Ivabradine acts by reducing the [[heart rate]] in a mechanism different from [[beta blocker]]s and [[calcium channel blocker]]s, two commonly prescribed [[antianginal]] drugs. It is classified as a ''cardiotonic agent''. A study on the mortality and morbidity study regarding Ivabradine, named BEAUTIFUL has been conducted in 33 countries on 11.000 Coronary Artery Disease patients. [http://www.wikidoc.org/index.php/BEAUTIFUL_study_fails_to_meet_primary_endpoint_but_demonstrates_that_heart_rates_can_safely_be_reduced_with_Ivabradine The results] have been announced in the European Society of Cardiology meeting in August 2008.
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| ==Mode of action==
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| Ivabradine acts on the I<sub>''f''</sub> (''f'' is for "[[Funny current|funny]]", so called because it had unusual properties compared with other current systems known at the time of its discovery) ion current, which is highly expressed in the [[sinoatrial node]]. I<sub>''f''</sub> is a mixed Na<sup>+</sup>–K<sup>+</sup> inward current activated by hyperpolarization and modulated by the autonomic nervous system. It is one of the most important ionic currents for regulating pacemaker activity in the sinoatrial (SA) node. Ivabradine selectively inhibits the pacemaker I<sub>''f''</sub> current in a dose-dependent manner. Blocking this channel reduces [[cardiac pacemaker]] activity, slowing the [[heart rate]] and allowing more time for blood to flow to the myocardium.<ref>{{cite journal |author=Thollon C, Cambarrat C, Vian J, Prost JF, Peglion JL, Vilaine JP |title=Electrophysiological effects of S 16257, a novel sino-atrial node modulator, on rabbit and guinea-pig cardiac preparations: comparison with UL-FS 49 |journal=Br. J. Pharmacol. |volume=112 |issue=1 |pages=37–42 |year=1994 |pmid=8032660 |doi=}}</ref><ref>{{cite journal |author=Sulfi S, Timmis AD |title=Ivabradine -- the first selective sinus node I(f) channel inhibitor in the treatment of stable angina |journal=Int. J. Clin. Pract. |volume=60 |issue=2 |pages=222–8 |year=2006 |pmid=16451297 |doi=10.1111/j.1742-1241.2006.00817.x | url=http://www.pubmedcentral.gov/articlerender.fcgi?pubmedid=16451297}}</ref>
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| ==Uses==
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| Ivabradine was approved by the [[European Medicines Agency]] in 2005. It is indicated for the symptomatic treatment of stable [[angina pectoris]] in patients with normal [[sinus rhythm]], who have a contraindication to or intolerance to [[beta blocker]]s. It has been shown to be non-inferior to the beta-blocker [[atenolol]] for this indication<ref name=Tardif>{{cite journal |author=Tardif JC, Ford I, Tendera M, Bourassa MG, Fox K |title=Efficacy of ivabradine, a new selective I(f) inhibitor, compared with atenolol in patients with chronic stable angina |journal=Eur. Heart J. |volume=26 |issue=23 |pages=2529–36 |year=2005 |pmid=16214830 |doi=10.1093/eurheartj/ehi586}}</ref> and amlodipine.
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| Apart from angina, it is also being used off-label in the treatment of [[inappropriate sinus tachycardia]].<ref>{{cite journal |author=Yusuf S, Camm AJ |title=Sinus tachyarrhythmias and the specific bradycardic agents: a marriage made in heaven? |journal=J. Cardiovasc. Pharmacol. Ther. |volume=8 |issue=2 |pages=89–105 |year=2003 |pmid=12808482 |doi=}}</ref>
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| ==Dosage==
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| A dose of 5 mg twice daily is recommended initially; after 1 month, it is recommended to increase to 7.5 mg twice daily to get the optimal efficacy linked to heart rate reduction. Given limited experience in the elderly, the manufacturer recommends a starting dose of 2.5 mg<ref name=Servier>{{cite web |url=http://www.servier.com/pro/cardiologie/procoralan/procoralan.asp |title=Servier, procolaran product description for healthcare professionals |accessdate=2007-10-14 |format= |work=}}</ref>.
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| ==Adverse effects==
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| 14.5% of all patients taking ivabradine experience [[phosphene|luminous phenomena]] (by patients described as sensations of enhanced brightness in a fully maintained visual field). This is probably due to blockage of I <sub>''h''</sub> ion channels in the [[retina]] which are very similar to cardiac I<sub>''f''</sub>. These symptoms are mild, transient, fully reversible and non-severe. In clinical studies about 1% of all patients had to discontinue the drug because of these sensations, which occurred on average 40 days after commencement of the drug.<ref name=Tardif/>
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| [[Bradycardia]] (unusually slow heart rate) occurs at 2% and 5% for doses of 7.5 and 10 mg respectively (compared to 4.3% in atenonol)<ref name=Tardif/>. 2.6-4.8% reported [[headache]]s<ref name=Tardif/>. Other common [[adverse drug reaction]]s (1–10% of patients) include first-degree [[heart block|AV block]], [[Premature ventricular contraction|ventricular extrasystoles]], dizziness and/or blurred vision.<ref>{{cite journal | author = Anonymous | title = New medicines: Procoralan | url = http://www.pjonline.com/Editorial/20060204/products/p131products.html | journal = Pharmaceutical Journal | year = 2006 | volume = 276 | issue = 7386 | pages=131 }}}</ref>
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| ==Contraindications==
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| Ivabradine is contraindicated in [[sick sinus syndrome]], and cannot be used concominantly with inhibitors of [[CYP3A4]] such as [[antifungal drug|azole antifungals]] (such as [[ketoconazole]]), [[macrolide]] antibiotics, [[nefazodone]] and the anti-HIV drugs [[nelfinavir]] and [[ritonavir]]<ref name=Servier/>.
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| ==References==
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| {{reflist|2}}
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| ==External links==
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| * [http://www.procoralan.com/ Official site]
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| * [http://www.servier.com/ Manufacturer´s web site]
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| * [http://www.procoralan.co.uk/ Procoralan UK]
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| * Źródło: "http://pl.wikipedia.org/wiki/Iwabradyna"
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| *Regarding the BEAUTIFUL Study: "http://www.medical-tribune.com.tr/node/262"
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| {{Electrocardiography}}
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| {{Circulatory system pathology}}
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| [[Category:Antianginals]]
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| [[Category:Cardiovascular Drugs]]
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| [[Category:Drug]]
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