Ivabradine

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Ivabradine
Clinical data
[[Regulation of therapeutic goods \|Template:Engvar data]]	EU EMA: by INN;
Pregnancy; category	AU: D ; ;
Routes of; administration	Oral
ATC code	C01EB17 (WHO) ;
Legal status
Legal status	UK: POM (Prescription only) ;
Pharmacokinetic data
Bioavailability	40%
Protein binding	70%
Metabolism	Hepatic (first-pass) >50%, CYP3A4-mediated
Elimination half-life	2 hours
Excretion	Renal and fecal
Identifiers
	IUPAC name (S)-3-(3-(((3,4-dimethoxybicyclo(4.2.0); octa-1,3,5-trien-7-yl)methyl)methylamino); propyl)-1,3,4,5-tetrahydro-; 7,8-dimethoxy-2H-3-benzazepin-2-one;
CAS Number	155974-00-8;
PubChem CID	132999;
E number	{{#property:P628}}
ECHA InfoCard	{{#property:P2566}}Lua error in Module:EditAtWikidata at line 36: attempt to index field 'wikibase' (a nil value).
Chemical and physical data
Formula	C27H36N2O5
Molar mass	468.585 g/mol

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Ivabradine (INN) (Template:PronEng) 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 blockers and calcium channel blockers, 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. The results have been announced in the European Society of Cardiology meeting in August 2008.

Mode of action

Ivabradine acts on the I_f (f is for "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_f is a mixed Na⁺–K⁺ 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_f 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.^[1]^[2]

Uses

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 blockers. It has been shown to be non-inferior to the beta-blocker atenolol for this indication^[3] and amlodipine.

Apart from angina, it is also being used off-label in the treatment of inappropriate sinus tachycardia.^[4]

Dosage

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^[5].

Adverse effects

14.5% of all patients taking ivabradine experience luminous phenomena (by patients described as sensations of enhanced brightness in a fully maintained visual field). This is probably due to blockage of I _h ion channels in the retina which are very similar to cardiac I_f. 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.^[3]

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)^[3]. 2.6-4.8% reported headaches^[3]. Other common adverse drug reactions (1–10% of patients) include first-degree AV block, ventricular extrasystoles, dizziness and/or blurred vision.^[6]

Contraindications

Ivabradine is contraindicated in sick sinus syndrome, and cannot be used concominantly with inhibitors of CYP3A4 such as azole antifungals (such as ketoconazole), macrolide antibiotics, nefazodone and the anti-HIV drugs nelfinavir and ritonavir^[5].

References

↑ Thollon C, Cambarrat C, Vian J, Prost JF, Peglion JL, Vilaine JP (1994). "Electrophysiological effects of S 16257, a novel sino-atrial node modulator, on rabbit and guinea-pig cardiac preparations: comparison with UL-FS 49". Br. J. Pharmacol. 112 (1): 37–42. PMID 8032660.
↑ Sulfi S, Timmis AD (2006). "Ivabradine -- the first selective sinus node I(f) channel inhibitor in the treatment of stable angina". Int. J. Clin. Pract. 60 (2): 222–8. doi:10.1111/j.1742-1241.2006.00817.x. PMID 16451297.
↑ ^3.0 ^3.1 ^3.2 ^3.3 Tardif JC, Ford I, Tendera M, Bourassa MG, Fox K (2005). "Efficacy of ivabradine, a new selective I(f) inhibitor, compared with atenolol in patients with chronic stable angina". Eur. Heart J. 26 (23): 2529–36. doi:10.1093/eurheartj/ehi586. PMID 16214830.
↑ Yusuf S, Camm AJ (2003). "Sinus tachyarrhythmias and the specific bradycardic agents: a marriage made in heaven?". J. Cardiovasc. Pharmacol. Ther. 8 (2): 89–105. PMID 12808482.
↑ ^5.0 ^5.1 "Servier, procolaran product description for healthcare professionals". Retrieved 2007-10-14.
↑ Anonymous (2006). "New medicines: Procoralan". Pharmaceutical Journal. 276 (7386): 131.}

External links

Official site
Manufacturer´s web site
Procoralan UK
Źródło: "http://pl.wikipedia.org/wiki/Iwabradyna"
Regarding the BEAUTIFUL Study: "http://www.medical-tribune.com.tr/node/262"

[1] Thollon C, Cambarrat C, Vian J, Prost JF, Peglion JL, Vilaine JP (1994). "Electrophysiological effects of S 16257, a novel sino-atrial node modulator, on rabbit and guinea-pig cardiac preparations: comparison with UL-FS 49". Br. J. Pharmacol. 112 (1): 37–42. PMID 8032660.

[2] Sulfi S, Timmis AD (2006). "Ivabradine -- the first selective sinus node I(f) channel inhibitor in the treatment of stable angina". Int. J. Clin. Pract. 60 (2): 222–8. doi:10.1111/j.1742-1241.2006.00817.x. PMID 16451297.

[Tardif-3] 3.0 ^3.1 ^3.2 ^3.3 Tardif JC, Ford I, Tendera M, Bourassa MG, Fox K (2005). "Efficacy of ivabradine, a new selective I(f) inhibitor, compared with atenolol in patients with chronic stable angina". Eur. Heart J. 26 (23): 2529–36. doi:10.1093/eurheartj/ehi586. PMID 16214830.

[4] Yusuf S, Camm AJ (2003). "Sinus tachyarrhythmias and the specific bradycardic agents: a marriage made in heaven?". J. Cardiovasc. Pharmacol. Ther. 8 (2): 89–105. PMID 12808482.

[Servier-5] 5.0 ^5.1 "Servier, procolaran product description for healthcare professionals". Retrieved 2007-10-14.

[6] Anonymous (2006). "New medicines: Procoralan". Pharmaceutical Journal. 276 (7386): 131.}

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v t e Electrocardiography
Overview	History of the EKG • EKG interpretation basics • Normal sinus rhythm
EKG Complexes	P wave • QRS complex • ST Segment • T wave • T wave alternans • Tombstone T wave • U wave Osborn wave • H wave • K wave • Delta wave NSSTW changes
EKG Intervals	PR Interval • QRS Interval • ST Interval • QT Interval
Conduction System & Bradycardia	Cardiac pacemaker • SA node • AV node• Bundle of His • Purkinje fibers • Sinus bradycardia • First Degree AV Block • Second Degree AV Block • Complete or Third-Degree AV Block • Concealed conduction • AV Junctional Rhythms • LBBB • LAHB • LPHB • RBBB • Trifascicular block
Atrial Arrhythmias	Sinus tachycardia • Premature Atrial Contractions (PACs) • Ectopic Atrial Rhythm • Paroxysmal Atrial Tachycardia (PAT) • Paroxysmal Atrial Tachycardia (PAT) with Block • Multifocal Atrial Tachycardia (MAT) • Atrial Flutter • Atrial Fibrillation • Wandering atrial pacemaker
Ventricular Arrhythmias	Differential Diagnosis of Tachycardia with a Wide QRS Complex • Accelerated Idioventricular Rhythm • Ventricular Parasystole • Premature Ventricular Contractions (PVCs) • Ventricular tachycardia • Ventricular Fibrillation • Sudden cardiac death
EKG Abnormalities in Disease States	Hypertrophy & Dilatation • Right atrial enlargement • Left atrial enlargement • Biatrial enlargement • Left Ventricular Hypertrophy • Right Ventricular Hypertrophy • Biventricular Hypertrophy • Acute myocardial infarction • NSTEMI • STEMI • Tombstone ST elevation • Right ventricular myocardial infarction • Atrial infarction Pre-excitation Syndromes • Wolff-Parkinson-White Syndrome • Lown Ganong Levine Syndrome • Mahaim Type Preexcitation Cardiomyopathies • Arrhythmogenic Right Ventricular Dysplasia • Dilated Cardiomyopathy • Hypertrophic Cardiomyopathy Drug Effects on the EKG • Adenosine • β-blockers • Digitalis • Quinidine • Procainamide • Disopyramide • Lidocaine • Tocainide and Mexiletine • Phenytoin • Encainide, Flecainide and Propafenone • Amiodarone • Bretylium • Ca Channel Blockers • Phenothiazines • Tricyclic Antidepressants • Lithium Congenital Heart Disease • Dextrocardia • Atrial Septal Defect • Ventricular Septal Defect • Tetralogy of Fallot • Conjoined Twins or Siamese Twins • Congenital heart block Electrolyte Disturbances • Hyperkalemia • Hypokalemia • Hypercalcemia • Hypocalcemia • Nonspecific Changes Other Heart Diseases • Pericarditis • Myocarditis • Tamponade • Heart Transplantation • Sick Sinus Syndrome • Long QT Syndrome Inherited Disease • Brugada Syndrome Systemic Diseases • CNS Disease • Cardiac Tumors Heart Transplantation • EKG Changes in patient with Heart Transplantation Exogenous Effects • Hypothermia • Chest Trauma • Insect Bites • Electric Injuries
Technical Issues and Potential Errors in Interpretation	Artifacts • Lead Placement Errors • The EKG in a Patient with a Pacemaker • EKG in athletes

Clinical data

[[Regulation of therapeutic goods \|Template:Engvar data]]	EU EMA: by INN
Pregnancy category	AU: D
Routes of administration	Oral
ATC code	C01EB17 (WHO)
Legal status
Legal status	UK: POM (Prescription only)
Pharmacokinetic data
Bioavailability	40%
Protein binding	70%
Metabolism	Hepatic (first-pass) >50%, CYP3A4-mediated
Elimination half-life	2 hours
Excretion	Renal and fecal
Identifiers
IUPAC name (S)-3-(3-(((3,4-dimethoxybicyclo(4.2.0) octa-1,3,5-trien-7-yl)methyl)methylamino) propyl)-1,3,4,5-tetrahydro- 7,8-dimethoxy-2H-3-benzazepin-2-one
CAS Number	155974-00-8
PubChem CID	132999
E number	{{#property:P628}}
ECHA InfoCard	{{#property:P2566}}Lua error in Module:EditAtWikidata at line 36: attempt to index field 'wikibase' (a nil value).
Chemical and physical data
Formula	C₂₇H₃₆N₂O₅
Molar mass	468.585 g/mol