Ivabradine
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Ivabradine
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| 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 |
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| Identifiers | |
| CAS number | |
| ATC code | C01 |
| PubChem | |
| 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 |
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| Pregnancy cat. |
D(AU) |
| Legal status | |
| Routes | Oral |
Ivabradine (INN) (IPA: [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.
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[edit] 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]
[edit] 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].
[edit] 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[4].
[edit] 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.[5]
Data about long-term safety are in progress but are promising.
[edit] 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[4].
[edit] Reference
- ^ Thollon C, Cambarrat C, Vian J, Prost JF, Peglion JL, Vilaine JP. 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 1994;112:37-42. PMID 8032660.
- ^ Sulfi S, Timmis AD. Ivabradine - the first selective sinus node I(f) channel inhibitor in the treatment of stable angina. Int J Clin Pract 2006;60:222-8. PMID 16451297. Full text
- ^ a b c d Tardif JC, Ford I, Tendera M, Bourassa MG, Fox K; INITIATIVE Investigators. Efficacy of ivabradine, a new selective I(f) inhibitor, compared with atenolol in patients with chronic stable angina. Eur Heart J 2005;26:2529-36. PMID 16214830.
- ^ a b Product description, servier.com (intended for healthcare professionals).
- ^ New medicines: Procoralan. Pharmaceutical Journal 2006;276(7386):131
