| Systematic (IUPAC) name | |
|---|---|
| 3-[3-({[(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]methyl}(methyl)amino)propyl]-7,8-dimethoxy-2,3,4,5-tetrahydro-1H-3-benzazepin-2-one | |
| Clinical data | |
| AHFS/Drugs.com | International Drug Names |
| Licence data | EMA:Link |
| Pregnancy cat. | D(AU) |
| Legal status | POM (UK) |
| Routes | Oral |
| Pharmacokinetic data | |
| Bioavailability | 40% |
| Protein binding | 70% |
| Metabolism | Hepatic (first-pass) >50%, CYP3A4-mediated |
| Half-life | 2 hours |
| Excretion | Renal and fecal |
| Identifiers | |
| CAS number | 155974-00-8 |
| ATC code | C01EB17 |
| PubChem | CID 132999 |
| IUPHAR ligand | 2357 |
| ChemSpider | 117373 |
| UNII | 3H48L0LPZQ |
| KEGG | D07165 |
| ChEMBL | CHEMBL471737 |
| Chemical data | |
| Formula | C27H36N2O5 |
| Mol. mass | 468.585 g/mol |
| SMILES | eMolecules & PubChem |
|
|
| (what is this?) (verify) |
|
Ivabradine (INN) ( /ɪˈvæbrədiːn/) is a novel medication used for the symptomatic management of stable angina pectoris. It is marketed under the trade name Procoralan (Servier), Coralan in India (Servier), Australia or such as in Italy Corlentor (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.
Contents |
Ivabradine was approved by the European Medicines Agency in 2005. It is indicated for the symptomatic treatment of chronic stable angina pectoris in patients with normalsinus rhythm, who have a contraindication to or intolerance to beta blockers. It is also indicated in combination with beta-blockers in patients inadequately controlled with an optimal beta-blocker dose and whose heart rate is superior to 60 bpm.
It has been shown to be non-inferior to the beta-blocker atenolol for this indication[1] and amlodipine.
Apart from angina, it is also being used off-label in the treatment of inappropriate sinus tachycardia.[2]
Adding ivabradine to heart-failure medication decreases cardiovascular death or heart-failure hospitalization.[3]
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]
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.[1]
Bradycardia (unusually slow heart rate) occurs at 2% and 5% for doses of 7.5 and 10 mg respectively (compared to 4.3% in atenolol).[1] 2.6-4.8% reported headaches.[1] Other common adverse drug reactions (1–10% of patients) include first-degree AV block, ventricular extrasystoles, dizziness and/or blurred vision.[5]
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.[6][7]
The BEAUTIFUL study has shown that in coronary patients with a heart rate more than 70 bpm, ivabradine significantly reduces the risk of[8]
In the SHIFT study, ivabradine significantly reduced the risk of the primary composite endpoint of hospitalization for worsening heart failure or cardiovascular death by 18% (P<0.0001) compared with placebo on top of optimal therapy.[3] These benefits were observed after 3 months of treatment. SHIFT also showed that administration of ivabradine to heart failure patients significantly reduced the risk of death from heart failure by 26% (P=0.014) and hospitalization for heart failure by 26% (P<0.0001). The improvements in outcomes were observed throughout all prespecified subgroups: female and male, with or without beta-blockers at randomization, patients below and over 65 years of age, with heart failure of ischemic or non-ischemic etiology, NYHA class II or class III, IV, with or without diabetes, and with or without hypertension.[9]