View source for Propafenone

{{Short description|Anti-arrhythmic medication}}
{{more citations needed|date=May 2019}}
{{Use dmy dates|date=February 2020}}
{{drugbox
| Watchedfields = changed
| verifiedrevid = 464215884
| IUPAC_name = 1-{2-[2-Hydroxy-3-(propylamino)propoxy]phenyl}-3-phenylpropan-1-one
| image = Propafenone Structure.svg
| image_class = skin-invert-image
| width = 200
| image2 = Propafenona ball-and-stick.png
| image_class2 = bg-transparent
| width2 = 200
<!--Clinical data-->
| pronounce = {{IPAc-en|p|r|oʊ|ˈ|p|æ|f|ᵻ|n|oʊ|n}} {{respell|proh|PAF|i-nohn}}
| tradename = Rythmol, Rytmonorm, others
| Drugs.com = {{drugs.com|monograph|propafenone-hydrochloride}}
| MedlinePlus = a698002
| DailyMedID = Propafenone
| pregnancy_AU      = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_AU_comment = 
| pregnancy_US      = N
| pregnancy_US_comment = <ref name="Drugs.com pregnancy">{{cite web | title=Propafenone Use During Pregnancy | website=Drugs.com | date=13 November 2018 | url=https://www.drugs.com/pregnancy/propafenone.html | access-date=7 February 2020}}</ref>
| pregnancy_category= 
| routes_of_administration = By mouth

<!-- Legal status -->
| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled-->
| legal_AU_comment = 
| legal_BR =  <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F-->
| legal_BR_comment = 
| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_CA_comment = 
| legal_DE = <!-- Anlage I, II, III or Unscheduled-->
| legal_DE_comment = 
| legal_NZ = <!-- Class A, B, C -->
| legal_NZ_comment = 
| legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM / Class A, B, C -->
| legal_UK_comment = 
| legal_US = Rx-only
| legal_US_comment = 
| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV-->
| legal_UN_comment = 
| legal_status      = <!--For countries not listed above-->

<!--Pharmacokinetic data-->
| bioavailability = 
| protein_bound = 97%
| metabolism = 
| elimination_half-life = 2–10 hours
<!--Identifiers-->
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 54063-53-5
| ATC_prefix = C01
| ATC_suffix = BC03
| ATC_supplemental = 
| PubChem = 4932
| IUPHAR_ligand = 2561
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB01182
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 4763
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 68IQX3T69U
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D08435
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 631
<!--Chemical data-->
| C=21 | H=27 | N=1 | O=3
| smiles = O=C(c1ccccc1OCC(O)CNCCC)CCc2ccccc2
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C21H27NO3/c1-2-14-22-15-18(23)16-25-21-11-7-6-10-19(21)20(24)13-12-17-8-4-3-5-9-17/h3-11,18,22-23H,2,12-16H2,1H3
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = JWHAUXFOSRPERK-UHFFFAOYSA-N
}}

'''Propafenone''', sold under the brand name '''Rythmol''' among others, is a class 1c [[antiarrhythmic agents|anti-arrhythmic medication]], which is used to treat illnesses associated with rapid heart beat such as [[atrium (anatomy)|atrial]] and [[ventricle (heart)|ventricular]] [[cardiac arrhythmias|arrhythmias]].

==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 anti-arrhythmic medications. 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.{{medcn|date=January 2021}} 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]], [[Central nervous system|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 a relatively high dose (450–900&nbsp;mg/d), decreasing to near 300&nbsp;mg/d. In most Western countries, the accepted maximal dose is 900&nbsp;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.<ref>{{cite web |title=Clinical Guidelines and Recommendations |url=http://www.ahrq.gov/clinic/epcsums/atrialsum.htm |website=www.ahrq.gov |access-date=23 August 2019 |language=en-us |archive-date=7 February 2012 |archive-url=https://web.archive.org/web/20120207171208/http://www.ahrq.gov/clinic/epcsums/atrialsum.htm |url-status=dead }}</ref>

==Contraindications and cautions==
Caution should be used in administering propafenone in individuals with hepatic dysfunction, asthma, congestive heart failure, or bradycardia.

==History==
Propafenone was approved for use in the United States in November 1989.<ref>{{cite web | title=Drugs@FDA: FDA-Approved Drugs | website=U.S. [[Food and Drug Administration]] (FDA) | url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=019151 | archive-url=https://web.archive.org/web/20170430174728/https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=019151 | url-status=dead | archive-date=30 April 2017 | access-date=6 February 2020}}</ref><ref>{{cite web | title=Drug Approval Package: Rythmol SR (Propafenone Hydrochloride) NDA #021416 | website=U.S. [[Food and Drug Administration]] (FDA) | date=2004-05-05 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-416_Rythmol.cfm | archive-url=https://web.archive.org/web/20150630232237/http://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-416_Rythmol.cfm | url-status=dead | archive-date=30 June 2015 | access-date=6 February 2020}}</ref>

==Stereochemistry==
Propafenone contains a stereocenter and consists of two enantiomers. This is a [[racemate]], a 1:1 mixture of (''R'')– and (''S'')–forms:<ref name="Hager">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}}.</ref>
{| class="wikitable" style="text-align:center"
|- class="hintergrundfarbe6"
! colspan="2"| Enantiomers of propafenone
|-
| [[File:(R)-Propafenon Structural Formula V1.svg|class=skin-invert-image|200 px]]<br />(''R'')-propafenone<br><small> CAS number: 107381-31-7</small>
| [[File:(S)-Propafenon Structural Formula V1.svg|class=skin-invert-image|200 px]]<br />(''S'')-propafenone<br><small> CAS number: 107381-32-8</small>
|}

==See also==
* [[List of cardiac pharmaceutical agents]]

==References==
{{reflist}}

==Further reading==
* {{cite book | title=Medical Genetics Summaries | chapter=Propafenone Therapy and CYP2D6 Genotype | chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK425391/ | veditors=Pratt VM, McLeod HL, Rubinstein WS, Scott SA, Dean LC, Kattman BL, Malheiro AJ | display-editors=3 | publisher=[[National Center for Biotechnology Information]] (NCBI) | year=2017 | pmid=28520383 | id=Bookshelf ID: NBK425391 | vauthors=Dean L | url=https://www.ncbi.nlm.nih.gov/books/NBK61999/ }}

==External links==
* {{cite web| url = https://druginfo.nlm.nih.gov/drugportal/name/propafenone | archive-url = https://web.archive.org/web/20190628224313/https://druginfo.nlm.nih.gov/drugportal/name/propafenone | url-status = dead | archive-date = 28 June 2019 | publisher = U.S. National Library of Medicine| work = Drug Information Portal | title = Propafenone }}

{{Antiarrhythmic agents}}
{{GlaxoSmithKline}}
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[[Category:Secondary amines]]
[[Category:Antiarrhythmic agents]]
[[Category:CYP2D6 inhibitors]]
[[Category:Drugs developed by GSK plc]]
[[Category:Ketones]]
[[Category:Phenol ethers]]
[[Category:Secondary alcohols]]
[[Category:Sodium channel blockers]]