Propafenone

Propafenone, sold under the brand name Rythmol among others, is a class 1C anti-arrhythmic medication, which treats illnesses associated with rapid heart beats such as atrial and ventricular arrhythmias.

Propafenone
Clinical data
Pronunciation/proʊˈpæfɪnoʊn/ proh-PAF-i-nohn
Trade namesRythmol, Rytmonorm, others
AHFS/Drugs.comMonograph
MedlinePlusa698002
License data
Pregnancy
category
  • US: N (Not classified yet) [1]
    Routes of
    administration    		By mouth
    ATC code
    Legal status
    Legal status
    Pharmacokinetic data
    Protein binding97%
    Elimination half-life2–10 hours
    Identifiers
    CAS Number
    PubChem CID
    IUPHAR/BPS
    DrugBank
    ChemSpider
    UNII
    KEGG
    ChEMBL
    CompTox Dashboard (EPA)
    ECHA InfoCard100.053.578
    Chemical and physical data
    FormulaC21H27NO3
    Molar mass341.451 g·mol−1
    3D model (JSmol)
      (verify)

    Mechanism of action

    Propafenone works by slowing the influx of sodium ions into the cardiac muscle cells, causing a decrease in excitability of the cells. Propafenone is more selective for cells with a high rate, but also blocks normal cells more than class Ia or Ib. Propafenone differs from the prototypical class Ic antiarrhythmic in that it has additional activity as a beta-adrenergic blocker which can cause bradycardia and bronchospasm.

    Metabolism

    Propafenone is metabolized primarily in the liver. Because of its short half-life, it requires dosing two or three times daily to maintain steady blood levels. The long-term safety of propafenone is unknown. Because it is structurally similar to another anti-arrhythmic medicine, flecainide, similar cautions should be exercised in its use. Flecainide and propafenone, like other antiarrhythmic drugs have been shown to increase the occurrence of arrhythmias (5.3% for propafenone, Teva physician prescribing information), primarily in patients with underlying heart disease. However, their use in structurally normal hearts is considered safe.

    Side effects

    Side effects attributed to propafenone include hypersensitivity reactions, lupus-like syndrome, agranulocytosis, CNS disturbances such as dizziness, lightheadedness, gastrointestinal upset, a metallic taste and bronchospasm. About 20% of patients discontinued the drug due to side effects.

    Initiation of therapy

    Propafenone generally needs to be started in a hospital setting to assure ECG monitoring of the patient. There are many different dosages of propafenone, depending on clinical presentation of the arrhythmia. The treatment is generally begun with relatively high dosages (450–900 mg/d) decreasing to near 300 mg/d. In most western countries the accepted maximal dosage is 900 mg/d.

    For economic and convenience reasons, some clinicians are starting certain antiarrhythmic agents in an outpatient setting for some patients. No consensus exists regarding the safety of this practice, and information is needed to determine which agents and which patients are appropriate for outpatient initiation of antiarrhythmic therapy. From a clinical point of view, this drug is used primarily in patients with relatively preserved myocardial function.[2]

    Contraindications and cautions

    Caution should be used in administrating propafenone in individuals with hepatic dysfunction, asthma, CHF, or bradycardia.

    Stereochemistry

    Propafenone contains a stereocenter and consists of two enantiomers. This is a racemate, ie a 1: 1 mixture of ( R ) – and the ( S ) – form:[3]

    Enantiomers of propafenone

    CAS-Nummer: 107381-31-7
    CAS-Nummer: 107381-32-8

    History

    Propafenone was approved for use in the United States in November 1989.[4][5]

    See also

    References
    1. "Propafenone Use During Pregnancy". Drugs.com. 13 November 2018. Retrieved 7 February 2020.
    2. "Clinical Guidelines and Recommendations". www.ahrq.gov. Retrieved 23 August 2019.
    3. F. v. Bruchhausen, G. Dannhardt, S. Ebel, A. W. Frahm, E. Hackenthal, U. Holzgrabe (Hrsg.): Hagers Handbuch der Pharmazeutischen Praxis: Band 9: Stoffe P–Z, Springer Verlag, Berlin, Aufl. 5, 2014, S. 387, ISBN 978-3-642-63389-8.
    4. "Drugs@FDA: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Retrieved 6 February 2020.
    5. "Drug Approval Package: Rythmol SR (Propafenone Hydrochloride) NDA #021416". U.S. Food and Drug Administration (FDA). 5 May 2004. Retrieved 6 February 2020.

    Further reading
    • "Propafenone". Drug Information Portal. U.S. National Library of Medicine.
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