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Ivabradine



Ivabradine
Systematic (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
Identifiers
CAS number 155974-00-8
ATC code C01EB17
PubChem 132999
Chemical data
Formula C27H36N2O5 
Mol. mass 468.585 g/mol
Pharmacokinetic data
Bioavailability 40%
Protein binding 70%
Metabolism Hepatic (first-pass) >50%, CYP3A4-mediated
Half life 2 hours
Excretion Renal and fecal
Therapeutic considerations
Licence data

EU 

Pregnancy cat.

D(AU)

Legal status

POM(UK)

Routes Oral

Ivabradine (INN) (pronounced /ɪˈvæbrədin/) is a novel medication used for the symptomatic management of stable angina pectoris. It is marketed under the trade name Procoralan (Servier), 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.

Additional recommended knowledge

Contents

Mode of action

Ivabradine acts on the If (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. If 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 If 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]. 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 If. 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]

Data about long-term safety are in progress but are promising.[citation needed]

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

  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.
  3. ^ a b c d 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.
  5. ^ a b Servier, procolaran product description for healthcare professionals. Retrieved on 2007-10-14.
  6. ^ (2006) "{{{title}}}". Pharmaceutical Journal 276 (7386): 131.}
 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Ivabradine". A list of authors is available in Wikipedia.
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