Ivabradine

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Structural formula
Structural formula of ivabradine
General
Non-proprietary name Ivabradine
other names

( 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-2 H -3-benzazepin-2-one ( IUPAC )

Molecular formula
  • C 27 H 36 N 2 O 5 (ivabradine)
  • C 27 H 36 N 2 O 5 HCl (ivabradine hydrochloride )
External identifiers / databases
CAS number
  • 155974-00-8 (ivabradine)
  • 148849-67-6 (ivabradine hydrochloride)
PubChem 132999
ChemSpider 117373
DrugBank DB09083
Wikidata Q425729
Drug information
ATC code

C01 EB17

Drug class

I f channel inhibitors

properties
Molar mass
  • 468.59 g mol −1
  • 505.05 g mol −1
Physical state

firmly

Melting point

135–140 ° C (ivabradine hydrochloride)

safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS hazard labeling
no classification available
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Ivabradine (trade name Procoralan ® ; manufacturer Servier ) is a medicinal substance with an exclusively heart rate lowering effect. It is the prototype of the new class of I f channel inhibitors or I f inhibitors, and leads to the heart to slow down the pulse without the conduction system , force of the heart muscle ( inotropy ) or blood pressure influence.

Ivabradine is used to treat chronic stable angina pectoris in adults with sinus rhythm who are contraindicated or intolerant to beta-blockers . It is also used in combination with beta-blockers in adult patients whose condition is not fully controlled with beta-blockers and who have an excessive heart rate of more than 60 beats per minute. In February 2012, ivabradine received an approval extension for the treatment of chronic heart failure (see indications).

Ivabradine received European approval in October 2005. On January 2, 2006, the manufacturer Servier brought it onto the market in Germany under the brand name Procoralan .

application areas

Ivabradine is used for the symptomatic treatment of chronic stable angina pectoris in adults with coronary artery disease and normal sinus rhythm. Ivabradine is indicated:

  • in adults who are intolerant to beta blockers or if beta blockers are contraindicated; or
  • in combination with beta-blockers in patients who are inadequately controlled with an optimal beta-blocker dose.

Ivabradine may be considered as a treatment option for chronic heart failure NYHA class II to IV with systolic dysfunction in patients with sinus rhythm with a heart rate ≥ 75 beats per minute (bpm) in combination with standard therapy including beta blockers, or when beta blockers are contraindicated or intolerant . This does not apply to patients with chronic atrial fibrillation.

Mode of action

Ivabradine selectively and specifically inhibits the I f ion flow, which, as an intrinsic pacemaker in the heart, controls the spontaneous diastolic depolarization in the sinus node and thus regulates the heart rate. The cardiac effects are specific to the sinus node and have no influence on intra-atrial, atrioventricular (PQ time) or intraventricular conduction times, nor on myocardial contractility (heart muscle strength) or ventricular repolarization (QTc time). The hemodynamics and thus the blood pressure also remain constant. Ivabradine works mainly by reducing the heart rate by a few beats per minute. This will reduce the heart's need for oxygen, especially in situations where angina attacks are likely to occur. In this way, ivabradine helps control and reduce the incidence of angina pectoris.

Dosage forms

Ivabradine is available in film-coated tablet form for oral use in strengths of 5 mg and 7.5 mg.

Side effects

The most common adverse drug reactions occurred in 2 to 14.5 percent of patients, dose-dependent and reversible, phosphenes (perception of light in the sense of isolated lightening in the visual field), which disappeared again during (in 77.5 percent of patients) or after treatment. They are caused by competitive inhibition of a variation of the I f channel in the retina. Caution should be exercised in patients with retinitis pigmentosa .

Contraindications

Ivabradine should not be used in

Pharmacokinetics

Ivabradine is rapidly and almost completely absorbed after oral administration. Maximum plasma levels are reached after about an hour on an empty stomach. The bioavailability is around 40 percent (first pass effect). Food delays absorption by about an hour. Ivabradine is approximately 70 percent bound to plasma protein.

Ivabradine is extensively metabolized ( metabolized ) in the liver and intestine via the cytochrome P450 3A4 ( CYP3A4 ) and broken down with an effective half-life of eleven hours. It is a weak inhibitor of the CYP3A4.

Trade names

Monopreparations

Corlentor (A), Procoralan (D, A, CH). The commercial products contain the hydrochloride of ivabradine. Since April 2018, the active ingredient ivabradine has also been available as a generic in Germany, e.g. B. under the brand names Ivabalan (company TAD Pharma), Ivabradin Hennig (company Hennig), Ivabradin Glenmark (company Glenmark) and some other companies.

Web links

Individual evidence

  1. ^ The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals , 14th Edition (Merck & Co., Inc.), Whitehouse Station, NJ, USA, 2006; P. 907, ISBN 978-0-911910-00-1 .
  2. ↑ This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.
  3. ↑ a b c d Procoralan ® specialist information : (PDF; 111 kB) on Fachinfo-Service.
  4. ↑ a b c d e Summary of the Product Characteristics, status: July 2010 (PDF; 130 kB) on the website of the European Medicines Agency .
  5. ↑ Summary of the European public assessment report (EPAR) for Procoralan Scientific discussion of the approval report of the European Medicines Agency.
  6. ↑ ROTE LISTE 2008 , Verlag Rote Liste Service GmbH, Frankfurt am Main, ISBN 978-3-939192-20-6 .
  7. ↑ Apotheke Adhoc: Procoralan - Clear the way for generics. Retrieved April 10, 2018 .