propafenone Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
antiarrhythmics, propafenone derivatives 2291 54063-53-5

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • propafenone
  • propafenone hydrochloride
  • polfenon
  • (RS)-Propafenone
  • propafenone HCl
An antiarrhythmia agent that is particularly effective in ventricular arrhythmias. It also has weak beta-blocking activity.
  • Molecular weight: 341.45
  • Formula: C21H27NO3
  • CLOGP: 3.64
  • LIPINSKI: 0
  • HAC: 4
  • HDO: 2
  • TPSA: 58.56
  • ALOGS: -4.65
  • ROTB: 11

  • Status: OFP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
0.30 g O
0.30 g P

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 0.09 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 0.50 % Benet LZ, Broccatelli F, Oprea TI
BA (Bioavailability) 12 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 2.20 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 16 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.04 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 2.10 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
Nov. 27, 1989 FDA GLAXOSMITHKLINE LLC

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Atrial fibrillation 290.05 17.17 189 7261 103401 46575211
Electrocardiogram QRS complex prolonged 149.58 17.17 49 7401 5400 46673212
Bradycardia 120.19 17.17 93 7357 66205 46612407
Drug interaction 108.56 17.17 147 7303 202947 46475665
Sinus bradycardia 96.19 17.17 46 7404 13736 46664876
Arrhythmia 67.73 17.17 51 7399 34790 46643822
Cardiac arrest 53.62 17.17 69 7381 90330 46588282
Enzyme induction 52.63 17.17 9 7441 51 46678561
Intentional overdose 48.98 17.17 56 7394 64888 46613724
Syncope 44.28 17.17 68 7382 104735 46573877
Completed suicide 41.00 17.17 79 7371 145841 46532771
Toxicity to various agents 40.41 17.17 98 7352 211668 46466944
Atrial flutter 39.17 17.17 22 7428 9126 46669486
Hypotension 37.50 17.17 101 7349 232488 46446124
Atrioventricular block complete 37.23 17.17 20 7430 7607 46671005
Systolic dysfunction 36.78 17.17 12 7438 1302 46677310
Palpitations 36.34 17.17 59 7391 95200 46583412
International normalised ratio increased 34.61 17.17 40 7410 46843 46631769
Ventricular tachycardia 33.31 17.17 25 7425 16942 46661670
Nodal arrhythmia 33.04 17.17 11 7439 1272 46677340
Asthenia 32.40 17.17 116 7334 310959 46367653
Cardiogenic shock 31.85 17.17 24 7426 16360 46662252
Suicide attempt 29.49 17.17 40 7410 54996 46623616
Generalised tonic-clonic seizure 28.64 17.17 28 7422 27094 46651518
Bradyarrhythmia 28.24 17.17 11 7439 1995 46676617
Dizziness 28.14 17.17 118 7332 340296 46338316
Tension 27.57 17.17 12 7438 2880 46675732
Bradykinesia 26.94 17.17 13 7437 3953 46674659
Atrioventricular block first degree 26.82 17.17 15 7435 6171 46672441
Coagulation test abnormal 26.55 17.17 8 7442 669 46677943
Labelled drug-drug interaction medication error 26.36 17.17 17 7433 9044 46669568
Bundle branch block left 26.34 17.17 15 7435 6384 46672228
Haemodynamic instability 26.26 17.17 16 7434 7709 46670903
Granulocytopenia 26.22 17.17 14 7436 5259 46673353
Loss of consciousness 26.07 17.17 55 7395 108183 46570429
Cardiac assistance device user 25.83 17.17 5 7445 61 46678551
Flat affect 25.16 17.17 9 7441 1289 46677323
Conduction disorder 24.51 17.17 9 7441 1389 46677223
Brugada syndrome 24.37 17.17 6 7444 234 46678378
Psychomotor retardation 23.18 17.17 11 7439 3222 46675390
Defect conduction intraventricular 22.89 17.17 5 7445 114 46678498
Electrocardiogram abnormal 22.50 17.17 14 7436 6998 46671614
Product measured potency issue 22.33 17.17 5 7445 128 46678484
N-terminal prohormone brain natriuretic peptide 21.39 17.17 4 7446 40 46678572
Periorbital haematoma 21.22 17.17 7 7443 786 46677826
Rhythm idioventricular 21.20 17.17 5 7445 162 46678450
Ischaemic hepatitis 21.15 17.17 9 7441 2044 46676568
Diastolic dysfunction 20.70 17.17 12 7438 5280 46673332
Overweight 20.53 17.17 10 7440 3103 46675509
Metabolic acidosis 20.49 17.17 28 7422 38752 46639860
Tachycardia 19.91 17.17 47 7403 99575 46579037
Brain oedema 19.35 17.17 16 7434 12462 46666150
pH body fluid abnormal 19.00 17.17 4 7446 76 46678536
Angina pectoris 18.35 17.17 22 7428 26753 46651859
Atrioventricular block 17.91 17.17 12 7438 6799 46671813
Pain 17.40 17.17 31 7419 476917 46201695
Sleep deficit 17.36 17.17 5 7445 357 46678255

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Electrocardiogram QRS complex prolonged 239.00 17.59 66 4561 4211 29943640
Atrial fibrillation 142.55 17.59 124 4503 108000 29839851
Bradycardia 117.47 17.59 90 4537 65436 29882415
Electrocardiogram PR prolongation 109.51 17.59 25 4602 726 29947125
Ventricular tachycardia 56.82 17.59 39 4588 23823 29924028
Drug interaction 55.11 17.59 105 4522 199463 29748388
Facial asymmetry 54.78 17.59 12 4615 287 29947564
Palpitations 49.10 17.59 41 4586 33532 29914319
Accidental exposure to product by child 39.08 17.59 13 4614 1550 29946301
Atrioventricular block first degree 37.27 17.59 18 4609 5670 29942181
Dry mouth 33.58 17.59 28 4599 22822 29925029
Brugada syndrome 32.17 17.59 9 4618 599 29947252
Arrhythmia 31.82 17.59 32 4595 33137 29914714
Atrial flutter 30.84 17.59 22 4605 14259 29933592
Dizziness 29.55 17.59 81 4546 194828 29753023
Heart rate irregular 26.74 17.59 19 4608 12240 29935611
Electrocardiogram QT prolonged 26.30 17.59 30 4597 35805 29912046
Accidental overdose 26.03 17.59 22 4605 18253 29929598
Drug level increased 25.95 17.59 22 4605 18332 29929519
Bundle branch block right 25.47 17.59 15 4612 7027 29940824
Nodal arrhythmia 24.95 17.59 8 4619 849 29947002
Speech disorder 24.15 17.59 24 4603 24488 29923363
Syncope 23.71 17.59 45 4582 84858 29862993
Cholestatic liver injury 23.60 17.59 9 4618 1592 29946259
Completed suicide 23.31 17.59 49 4578 99443 29848408
Trifascicular block 22.79 17.59 4 4623 28 29947823
Generalised tonic-clonic seizure 22.78 17.59 21 4606 19530 29928321
Sinus bradycardia 20.73 17.59 16 4611 11679 29936172
Ventricular arrhythmia 20.58 17.59 11 4616 4277 29943574
Cardiac flutter 19.95 17.59 8 4619 1618 29946233
Loss of consciousness 19.64 17.59 40 4587 79335 29868516
Transient ischaemic attack 18.32 17.59 21 4606 25179 29922672
Presyncope 18.23 17.59 17 4610 16039 29931812
Supraventricular tachycardia 18.09 17.59 14 4613 10258 29937593

Pharmacologic Action:

SourceCodeDescription
ATC C01BC03 CARDIOVASCULAR SYSTEM
CARDIAC THERAPY
ANTIARRHYTHMICS, CLASS I AND III
Antiarrhythmics, class Ic
FDA EPC N0000175426 Antiarrhythmic
MeSH PA D000889 Anti-Arrhythmia Agents
MeSH PA D002317 Cardiovascular Agents
MeSH PA D049990 Membrane Transport Modulators
MeSH PA D026941 Sodium Channel Blockers
MeSH PA D061567 Voltage-Gated Sodium Channel Blockers
CHEBI has role CHEBI:38070 antiarrhythmic agent

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Atrial fibrillation indication 49436004 DOID:0060224
Paroxysmal supraventricular tachycardia indication 67198005
Paroxysmal atrial fibrillation indication 282825002
Paroxysmal atrial flutter indication 427665004
Life-Threatening Ventricular Tachycardia indication
Cardioversion of Atrial Fibrillation off-label use
Bronchospasm contraindication 4386001
Bundle branch block contraindication 6374002
Hyperkalemia contraindication 14140009
Agranulocytosis contraindication 17182001 DOID:12987
Myocardial infarction contraindication 22298006 DOID:5844
Torsades de pointes contraindication 31722008
Sick sinus syndrome contraindication 36083008 DOID:13884
Hypokalemia contraindication 43339004
Low blood pressure contraindication 45007003
Chronic heart failure contraindication 48447003
Bradycardia contraindication 48867003
Coronary arteriosclerosis contraindication 53741008 DOID:3393
Cardiogenic shock contraindication 89138009
Kidney disease contraindication 90708001 DOID:557
Myasthenia gravis contraindication 91637004 DOID:437
Prolonged QT interval contraindication 111975006
Structural disorder of heart contraindication 128599005
Atrioventricular block contraindication 233917008 DOID:0050820
Disease of liver contraindication 235856003 DOID:409
Severe chronic obstructive pulmonary disease contraindication 313299006
Myocardial infarction in recovery phase contraindication 418044006
Congenital long QT syndrome contraindication 442917000

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 9.15 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Beta-1 adrenergic receptor GPCR ANTAGONIST Ki 6.69 DRUG MATRIX CHEMBL
Sodium channel protein type 5 subunit alpha Ion channel BLOCKER IC50 5.48 CHEMBL CHEMBL
Sigma non-opioid intracellular receptor 1 Membrane receptor Ki 5.96 DRUG MATRIX
Sodium-dependent noradrenaline transporter Transporter Ki 5.52 DRUG MATRIX
5-hydroxytryptamine receptor 1A GPCR Ki 6.03 DRUG MATRIX
5-hydroxytryptamine receptor 2A GPCR Ki 6.73 DRUG MATRIX
5-hydroxytryptamine receptor 2B GPCR Ki 7.24 DRUG MATRIX
5-hydroxytryptamine receptor 2C GPCR Ki 6.70 DRUG MATRIX
5-hydroxytryptamine receptor 6 GPCR Ki 6.06 DRUG MATRIX
Beta-3 adrenergic receptor GPCR Ki 6.50 DRUG MATRIX
Sodium-dependent dopamine transporter Transporter Ki 5.83 DRUG MATRIX
Cytochrome P450 2D6 Enzyme IC50 5.34 DRUG MATRIX
Alpha-1D adrenergic receptor GPCR Ki 5.60 DRUG MATRIX
Cytochrome P450 1A2 Enzyme IC50 5.48 DRUG MATRIX
Solute carrier family 22 member 2 Transporter IC50 4.60 WOMBAT-PK
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4 Ion channel IC50 4.84 WOMBAT-PK
Aldehyde oxidase Enzyme IC50 5.60 WOMBAT-PK
Multidrug resistance protein 1 Transporter ED50 7.06 WOMBAT-PK
Potassium voltage-gated channel subfamily H member 2 Ion channel IC50 6.10 WOMBAT-PK
Sodium channel subunit beta-4 Ion channel WOMBAT-PK
Sodium channel subunit beta-3 Ion channel WOMBAT-PK
Sodium channel subunit beta-1 Ion channel WOMBAT-PK
Solute carrier family 22 member 1 Transporter IC50 4.95 CHEMBL
Sulfonylurea receptor 2, Kir6.2 Ion channel IC50 5.66 CHEMBL
Sodium channel subunit beta-2 Ion channel WOMBAT-PK
Potassium voltage-gated channel subfamily A member 5 Ion channel BLOCKER IC50 4.40 IUPHAR
Beta-2 adrenergic receptor GPCR ANTAGONIST Ki 7.44 DRUG MATRIX
Alpha-1B adrenergic receptor GPCR Ki 5.85 DRUG MATRIX
5-hydroxytryptamine receptor 1A GPCR IC50 5.79 CHEMBL
Alpha-1A adrenergic receptor GPCR IC50 5.21 CHEMBL

External reference:

IDSource
4019911 VUID
N0000147996 NUI
D00640 KEGG_DRUG
34183-22-7 SECONDARY_CAS_RN
4019487 VANDF
4019911 VANDF
C0033429 UMLSCUI
CHEBI:63619 CHEBI
CHEMBL631 ChEMBL_ID
CHEMBL1201063 ChEMBL_ID
D011405 MESH_DESCRIPTOR_UI
DB01182 DRUGBANK_ID
2561 IUPHAR_LIGAND_ID
3312 INN_ID
68IQX3T69U UNII
4932 PUBCHEM_CID
203135 RXNORM
40681 MMSL
40682 MMSL
5368 MMSL
d00358 MMSL
003525 NDDF
004487 NDDF
108501006 SNOMEDCT_US
372910007 SNOMEDCT_US
96300001 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
RYTHMOLSR HUMAN PRESCRIPTION DRUG LABEL 1 0173-0823 CAPSULE, EXTENDED RELEASE 225 mg ORAL NDA 29 sections
RYTHMOLSR HUMAN PRESCRIPTION DRUG LABEL 1 0173-0824 CAPSULE, EXTENDED RELEASE 325 mg ORAL NDA 29 sections
RYTHMOLSR HUMAN PRESCRIPTION DRUG LABEL 1 0173-0826 CAPSULE, EXTENDED RELEASE 425 mg ORAL NDA 29 sections
Propafenone HCl HUMAN PRESCRIPTION DRUG LABEL 1 0591-0582 TABLET, FILM COATED 150 mg ORAL ANDA 29 sections
Propafenone HCl HUMAN PRESCRIPTION DRUG LABEL 1 0591-0583 TABLET, FILM COATED 225 mg ORAL ANDA 29 sections
Propafenone Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0591-2285 CAPSULE, EXTENDED RELEASE 225 mg ORAL ANDA 29 sections
Propafenone Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0591-2286 CAPSULE, EXTENDED RELEASE 325 mg ORAL ANDA 29 sections
Propafenone Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0591-2287 CAPSULE, EXTENDED RELEASE 425 mg ORAL ANDA 29 sections
Propafenone Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0603-5448 TABLET, FILM COATED 150 mg ORAL ANDA 29 sections
Propafenone Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0603-5449 TABLET, FILM COATED 225 mg ORAL ANDA 29 sections
Propafenone Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0603-5450 TABLET, FILM COATED 300 mg ORAL ANDA 29 sections
Propafenone Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0832-0740 CAPSULE, EXTENDED RELEASE 225 mg ORAL ANDA 30 sections
Propafenone Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0832-0741 CAPSULE, EXTENDED RELEASE 325 mg ORAL ANDA 30 sections
Propafenone Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0832-0742 CAPSULE, EXTENDED RELEASE 425 mg ORAL ANDA 30 sections
PROPAFENONE HYDROCHLORIDE Human Prescription Drug Label 1 16571-736 CAPSULE, EXTENDED RELEASE 225 mg ORAL ANDA 30 sections
PROPAFENONE HYDROCHLORIDE Human Prescription Drug Label 1 16571-737 CAPSULE, EXTENDED RELEASE 325 mg ORAL ANDA 30 sections
PROPAFENONE HYDROCHLORIDE Human Prescription Drug Label 1 16571-738 CAPSULE, EXTENDED RELEASE 425 mg ORAL ANDA 30 sections
propafenone hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 16714-825 CAPSULE, EXTENDED RELEASE 225 mg ORAL ANDA 29 sections
propafenone hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 16714-826 CAPSULE, EXTENDED RELEASE 325 mg ORAL ANDA 29 sections
propafenone hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 16714-827 CAPSULE, EXTENDED RELEASE 425 mg ORAL ANDA 29 sections
Propafenone HUMAN PRESCRIPTION DRUG LABEL 1 21695-814 CAPSULE, EXTENDED RELEASE 325 mg ORAL ANDA 21 sections
Propafenone Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 24979-085 CAPSULE, EXTENDED RELEASE 225 mg ORAL ANDA 29 sections
Propafenone Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 24979-086 CAPSULE, EXTENDED RELEASE 325 mg ORAL ANDA 29 sections
Propafenone Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 24979-087 CAPSULE, EXTENDED RELEASE 425 mg ORAL ANDA 29 sections
Propafenone Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 42291-545 CAPSULE, EXTENDED RELEASE 225 mg ORAL ANDA 29 sections
Propafenone Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 42291-546 CAPSULE, EXTENDED RELEASE 325 mg ORAL ANDA 29 sections
Propafenone Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 42291-547 CAPSULE, EXTENDED RELEASE 425 mg ORAL ANDA 29 sections
Propafenone Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 49884-113 CAPSULE, EXTENDED RELEASE 225 mg ORAL ANDA 29 sections
Propafenone Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 49884-210 CAPSULE, EXTENDED RELEASE 325 mg ORAL ANDA 29 sections
Propafenone Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 49884-211 CAPSULE, EXTENDED RELEASE 425 mg ORAL ANDA 29 sections