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

Stem definitionDrug idCAS RN
local anaesthetics 432 38396-39-3

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • bupivacaine hydrochloride anhydrous
  • bupivacaine
  • (+/-)-Bupivacaine
  • bucain
  • bupivan
  • carbostesin
  • DL-Bupivacaine
  • bupivacaine hydrochloride
  • bupivacaine HCl
A widely used local anesthetic agent.
  • Molecular weight: 288.44
  • Formula: C18H28N2O
  • CLOGP: 3.69
  • LIPINSKI: 0
  • HAC: 3
  • HDO: 1
  • TPSA: 32.34
  • ALOGS: -3.47
  • ROTB: 5

  • Status: OFP

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

Drug dosage:

None

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 0.17 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 2 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 13.00 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 0 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 0.84 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 4.30 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.06 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 3.10 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
Oct. 3, 1972 FDA HOSPIRA

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
Drug ineffective 1295.03 44.31 481 1827 101143 2254634
Hypotension 762.63 44.31 246 2062 32190 2323587
Anaesthetic complication 686.63 44.31 106 2202 349 2355428
Exposure during pregnancy 685.55 44.31 214 2094 25005 2330772
Maternal exposure during delivery 279.74 44.31 43 2265 134 2355643
Chondrolysis 278.91 44.31 42 2266 109 2355668
Pain 272.71 44.31 142 2166 61715 2294062
Hypoaesthesia 236.15 44.31 92 2216 20123 2335654
Maternal exposure during pregnancy 196.14 44.31 74 2234 14789 2340988
Drug withdrawal syndrome 188.12 44.31 59 2249 6762 2349015
Cardiac arrest 170.72 44.31 67 2241 14863 2340914
Cauda equina syndrome 168.75 44.31 27 2281 116 2355661
Horner's syndrome 156.47 44.31 24 2284 73 2355704
Procedural hypotension 155.01 44.31 27 2281 211 2355566
Bradycardia 154.74 44.31 56 2252 9925 2345852
Incorrect route of product administration 138.08 44.31 44 2264 5292 2350485
Unresponsive to stimuli 137.78 44.31 43 2265 4833 2350944
Overdose 123.54 44.31 58 2250 19849 2335928
Seizure 115.08 44.31 59 2249 24407 2331370
Implant site extravasation 108.77 44.31 19 2289 151 2355626
Wrong product administered 102.70 44.31 26 2282 1356 2354421
Muscular weakness 100.43 44.31 46 2262 14851 2340926
Medical device site pain 100.07 44.31 15 2293 37 2355740
Caesarean section 98.76 44.31 32 2276 4049 2351728
Post procedural complication 95.90 44.31 29 2279 2925 2352852
Blood pressure decreased 93.40 44.31 38 2270 9198 2346579
Sensory loss 92.36 44.31 23 2285 1121 2354656
Paraplegia 87.72 44.31 19 2289 497 2355280
Therapeutic product effect decreased 87.70 44.31 38 2270 10751 2345026
Adverse drug reaction 86.91 44.31 35 2273 8248 2347529
Respiratory depression 86.60 44.31 25 2283 2145 2353632
Loss of consciousness 84.52 44.31 44 2264 18723 2337054
Sedation 83.93 44.31 27 2281 3335 2352442
Myoclonus 78.97 44.31 24 2284 2459 2353318
Parophthalmia 78.94 44.31 13 2295 69 2355708
Inadequate analgesia 78.52 44.31 18 2290 613 2355164
Conjunctival oedema 78.39 44.31 15 2293 206 2355571
Musculoskeletal pain 77.86 44.31 35 2273 10795 2344982
Procedural complication 77.68 44.31 20 2288 1115 2354662
Toxicity to various agents 71.32 44.31 48 2260 32706 2323071
Product quality issue 68.43 44.31 32 2276 10797 2344980
Exophthalmos 67.65 44.31 14 2294 292 2355485
Complication associated with device 65.91 44.31 22 2286 3047 2352730
Nausea 65.88 44.31 78 2230 112111 2243666
Pulseless electrical activity 65.16 44.31 17 2291 998 2354779
Procedural pain 64.87 44.31 19 2289 1713 2354064
Paraesthesia 64.55 44.31 39 2269 22049 2333728
Lagophthalmos 64.18 44.31 11 2297 77 2355700
Apnoea 64.14 44.31 18 2290 1393 2354384
Post lumbar puncture syndrome 62.89 44.31 12 2296 162 2355615
Hyperaesthesia 61.74 44.31 17 2291 1226 2354551
Therapy non-responder 60.81 44.31 27 2281 8077 2347700
Therapeutic product effect delayed 60.55 44.31 14 2294 495 2355282
Radiculopathy 60.49 44.31 15 2293 717 2355060
Arachnoiditis 60.41 44.31 11 2297 113 2355664
Mental status changes 59.94 44.31 24 2284 5558 2350219
Discomfort 58.25 44.31 23 2285 5136 2350641
Generalised tonic-clonic seizure 57.35 44.31 23 2285 5349 2350428
Premature delivery 57.22 44.31 20 2288 3180 2352597
Hypertensive encephalopathy 56.63 44.31 11 2297 164 2355613
Anaphylactic reaction 56.16 44.31 27 2281 9678 2346099
Anaphylactic shock 55.10 44.31 21 2287 4265 2351512
Device infusion issue 55.00 44.31 11 2297 192 2355585
Therapeutic product effect prolonged 54.98 44.31 10 2298 102 2355675
Tachycardia 53.20 44.31 31 2277 16378 2339399
Muscle spasticity 52.64 44.31 16 2292 1637 2354140
Asthenia 51.89 44.31 46 2262 46880 2308897
Therapeutic product effect incomplete 51.12 44.31 26 2282 10505 2345272
Paralysis 50.92 44.31 16 2292 1828 2353949
Heart rate decreased 50.83 44.31 19 2289 3657 2352120
Neurotoxicity 48.65 44.31 16 2292 2114 2353663
Cerebrospinal fluid leakage 48.48 44.31 10 2298 205 2355572
Device alarm issue 47.38 44.31 10 2298 230 2355547
Agitation 47.09 44.31 25 2283 11026 2344751
Rotator cuff syndrome 46.93 44.31 15 2293 1810 2353967
Neuromuscular blockade 46.80 44.31 8 2300 55 2355722
Joint range of motion decreased 46.68 44.31 15 2293 1841 2353936
Oxygen saturation decreased 46.61 44.31 22 2286 7564 2348213
Depressed level of consciousness 46.56 44.31 22 2286 7582 2348195
Nerve block 45.62 44.31 8 2300 65 2355712
Diplegia 45.60 44.31 10 2298 277 2355500
Respiratory distress 44.70 44.31 19 2289 5110 2350667

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
Anaesthetic complication 335.12 42.65 52 1148 216 1745365
Pain 298.23 42.65 112 1088 26545 1719036
Chondrolysis 296.96 42.65 40 1160 37 1745544
Drug ineffective 221.43 42.65 118 1082 63683 1681898
Drug withdrawal syndrome 156.66 42.65 45 1155 4480 1741101
Hypoaesthesia 148.84 42.65 52 1148 9783 1735798
Hypotension 107.68 42.65 57 1143 29597 1715984
Muscular weakness 106.02 42.65 41 1159 10208 1735373
Bradycardia 97.88 42.65 39 1161 10495 1735086
Cauda equina syndrome 90.48 42.65 15 1185 100 1745481
Musculoskeletal pain 88.89 42.65 30 1170 5044 1740537
Incorrect route of product administration 87.29 42.65 27 1173 3438 1742143
Therapy non-responder 82.69 42.65 30 1170 6236 1739345
Cardiac arrest 82.36 42.65 39 1161 15891 1729690
Paralysis 77.29 42.65 20 1180 1332 1744249
Loss of consciousness 72.53 42.65 35 1165 14840 1730741
Medical device site pain 69.68 42.65 10 1190 20 1745561
Device infusion issue 67.60 42.65 12 1188 125 1745456
Toxicity to various agents 65.29 42.65 41 1159 29100 1716481
Overdose 62.90 42.65 33 1167 16668 1728913
Mental status changes 61.60 42.65 24 1176 6051 1739530
Anal incontinence 60.61 42.65 16 1184 1150 1744431
Seizure 59.33 42.65 34 1166 20407 1725174
Paraplegia 56.42 42.65 13 1187 530 1745051
Muscle spasms 55.55 42.65 27 1173 11594 1733987
Back pain 54.61 42.65 30 1170 16583 1728998
Autonomic nervous system imbalance 53.99 42.65 12 1188 415 1745166
Blood pressure decreased 52.97 42.65 23 1177 7623 1737958
Arachnoiditis 51.88 42.65 9 1191 81 1745500
Device failure 51.85 42.65 13 1187 760 1744821
Urinary incontinence 51.11 42.65 17 1183 2719 1742862
Lagophthalmos 50.89 42.65 8 1192 36 1745545
Hyperhidrosis 50.77 42.65 26 1174 12462 1733119
Infusion site mass 50.71 42.65 8 1192 37 1745544
Foetal exposure during pregnancy 50.23 42.65 21 1179 6338 1739243
Therapeutic product effect decreased 47.08 42.65 20 1180 6277 1739304
Sensory loss 46.16 42.65 12 1188 811 1744770
Respiratory depression 46.14 42.65 15 1185 2232 1743349
Oculocardiac reflex 45.95 42.65 6 1194 3 1745578
Implant site extravasation 45.70 42.65 9 1191 170 1745411
Post procedural complication 45.29 42.65 15 1185 2365 1743216
Sinus arrest 44.76 42.65 10 1190 354 1745227
Device issue 44.67 42.65 15 1185 2467 1743114
Nausea 44.67 42.65 41 1159 51155 1694426
Coma 44.34 42.65 20 1180 7242 1738339
Apnoea 43.76 42.65 13 1187 1436 1744145
Dizziness 43.24 42.65 34 1166 34327 1711254
Paraesthesia 43.16 42.65 22 1178 10429 1735152
Myopathy toxic 42.94 42.65 8 1192 111 1745470

Pharmacologic Action:

SourceCodeDescription
ATC N01BB01 NERVOUS SYSTEM
ANESTHETICS
ANESTHETICS, LOCAL
Amides
ATC N01BB51 NERVOUS SYSTEM
ANESTHETICS
ANESTHETICS, LOCAL
Amides
FDA EPC N0000175682 Amide Local Anesthetic
FDA Chemical/Ingredient N0000007681 Amides
FDA PE N0000175976 Local Anesthesia
MeSH PA D000777 Anesthetics
CHEBI has role CHEBI:37887 adrenergic antagonist
CHEBI has role CHEBI:88188 drug allergen
CHEBI has role CHEBI:36333 local anaesthetic
MeSH PA D000779 Anesthetics, Local
MeSH PA D002491 Central Nervous System Agents
MeSH PA D002492 Central Nervous System Depressants
MeSH PA D018373 Peripheral Nervous System Agents
MeSH PA D018689 Sensory System Agents

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Anesthesia for cesarean section indication 4847005
Local anesthetic intrathecal block indication 231249005
Skin irritation indication 367466007
Local anesthesia indication 386761002
Itching of skin indication 418363000
Minor Skin Wound Pain indication
Major Nerve Block for Surgery indication
Regional Anesthesia for Surgery indication
Regional Anesthesia for Labor Pain indication
Regional Anesthesia for Ophthalmologic Surgery indication
Regional Anesthesia for Postoperative Pain indication
Local Anesthesia for Ophthalmologic Procedure indication
Suicidal thoughts contraindication 6471006
Dependent drug abuse contraindication 6525002
Alcoholism contraindication 7200002
Alcohol withdrawal delirium contraindication 8635005
Sinus tachycardia contraindication 11092001
Chronic obstructive lung disease contraindication 13645005 DOID:3083
Asthenia contraindication 13791008
Constipation contraindication 14760008 DOID:2089
Chronic disease of respiratory system contraindication 17097001
Mood swings contraindication 18963009
Myocardial infarction contraindication 22298006 DOID:5844
Inflammatory bowel disease contraindication 24526004 DOID:0050589
Alcohol intoxication contraindication 25702006
Complete atrioventricular block contraindication 27885002
Shock contraindication 27942005
Hypovolemia contraindication 28560003
Hypercapnia contraindication 29596007
Parkinsonism contraindication 32798002
Dehydration contraindication 34095006
Hyperthyroidism contraindication 34486009 DOID:7998
Hypertensive disorder contraindication 38341003 DOID:10763
Disorder of gallbladder contraindication 39621005 DOID:0060262
Hypothyroidism contraindication 40930008 DOID:1459
Hypokalemia contraindication 43339004
Decreased cardiac function contraindication 43650005
Conduction disorder of the heart contraindication 44808001
Low blood pressure contraindication 45007003
Stokes-Adams syndrome contraindication 46935006
Chronic heart failure contraindication 48447003
Bradycardia contraindication 48867003
Atrial fibrillation contraindication 49436004 DOID:0060224
Disorder of cardiovascular system contraindication 49601007 DOID:1287
Sinus bradycardia contraindication 49710005
Bleeding hemorrhoids contraindication 51551000
Paralytic ileus contraindication 55525008 DOID:8442
Acute nephropathy contraindication 58574008
Hepatic failure contraindication 59927004
Ulcerative colitis contraindication 64766004 DOID:8577
Cerebral arteriosclerosis contraindication 65312002
Drug AND/OR toxin-induced diarrhea contraindication 65979008
Substance abuse contraindication 66214007
Benign intracranial hypertension contraindication 68267002 DOID:11459
Diabetes mellitus contraindication 73211009 DOID:9351
Wolff-Parkinson-White pattern contraindication 74390002 DOID:384
Urethral stricture contraindication 76618002
Decreased respiratory function contraindication 80954004
Injury of head contraindication 82271004
Cor pulmonale contraindication 83291003 DOID:8515
Pulmonary emphysema contraindication 87433001
Cardiogenic shock contraindication 89138009
Kidney disease contraindication 90708001 DOID:557
Myasthenia gravis contraindication 91637004 DOID:437
Disorder of mucous membrane contraindication 95351003
Disorder of biliary tract contraindication 105997008 DOID:9741
Acute abdominal pain contraindication 116290004
Procedure on urinary system contraindication 118677009
Open wound contraindication 125643001
Neoplasm of brain contraindication 126952004 DOID:1319
Seizure disorder contraindication 128613002
Bleeding contraindication 131148009
Drug-induced psychosis contraindication 191483003 DOID:1742
Angina pectoris contraindication 194828000
Primary dilated cardiomyopathy contraindication 195021004
Partial atrioventricular block contraindication 195039008
Disease of liver contraindication 235856003 DOID:409
Morbid obesity contraindication 238136002 DOID:11981
Sepsis syndrome contraindication 238150007
Benign prostatic hyperplasia contraindication 266569009
Retention of urine contraindication 267064002
Exacerbation of asthma contraindication 281239006
Lesion of brain contraindication 301766008
Deficiency of cholinesterase contraindication 360607009
Coma contraindication 371632003
Primary adrenocortical insufficiency contraindication 373662000
Operation on gastrointestinal tract contraindication 386621005
Hypoxia contraindication 389086002
Angle-closure glaucoma contraindication 392291006 DOID:13550
Disorder of coronary artery contraindication 414024009
Central nervous system depression contraindication 418072004
Denuded skin contraindication 418242004
Dysfunction of sphincter of Oddi contraindication 430887001
Acute exacerbation of asthma contraindication 708038006
Reduced Hepatic Blood Flow contraindication
Lidocaine Toxicity contraindication

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 13.24 acidic
pKa2 7.92 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
133MG/10ML (13.3MG/ML) EXPAREL PACIRA PHARMS INC N022496 Oct. 28, 2011 RX INJECTABLE, LIPOSOMAL INJECTION April 6, 2021 REVISION OF THE INDICATION SECTION OF THE PACKAGE INSERT REGARDING AN INTERSCALENE BRACHIAL PLEXUS NERVE BLOCK TO PRODUCE POSTSURGICAL REGIONAL ANALGESIA
266MG/20ML (13.3MG/ML) EXPAREL PACIRA PHARMS INC N022496 Oct. 28, 2011 RX INJECTABLE, LIPOSOMAL INJECTION April 6, 2021 REVISION OF THE INDICATION SECTION OF THE PACKAGE INSERT REGARDING AN INTERSCALENE BRACHIAL PLEXUS NERVE BLOCK TO PRODUCE POSTSURGICAL REGIONAL ANALGESIA

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Sodium channel protein type 4 subunit alpha Ion channel BLOCKER IC50 6 WOMBAT-PK CHEMBL
Potassium voltage-gated channel subfamily A member 5 Ion channel BLOCKER Kd 5.40 IUPHAR
Cytochrome P450 2D6 Enzyme IC50 6.40 DRUG MATRIX
Potassium voltage-gated channel subfamily H member 2 Ion channel IC50 4.66 CHEMBL
Potassium voltage-gated channel subfamily D member 3 Ion channel IC50 4.50 WOMBAT-PK
Prostaglandin E2 receptor EP1 subtype GPCR IC50 5.51 WOMBAT-PK
5-hydroxytryptamine receptor 3A Ion channel IC50 4.23 WOMBAT-PK
Sodium channel protein type 1 subunit alpha Ion channel IC50 5.29 WOMBAT-PK
Sodium channel protein type 5 subunit alpha Ion channel BLOCKER IC50 5.66 IUPHAR
Potassium voltage-gated channel subfamily D member 3 Unclassified BLOCKER IC50 4.50 IUPHAR

External reference:

IDSource
D002045 MESH_DESCRIPTOR_UI
4019643 VUID
N0000147736 NUI
C0006400 UMLSCUI
D07552 KEGG_DRUG
27196008 SNOMEDCT_US
4019643 VANDF
005054 NDDF
1815 RXNORM
387150008 SNOMEDCT_US
d00180 MMSL
7TQO7W3VT8 UNII
73360-54-0 SECONDARY_CAS_RN
CHEBI:3215 CHEBI
CHEMBL1098 ChEMBL_ID
C472824 MESH_SUPPLEMENTAL_RECORD_UI
DB00297 DRUGBANK_ID
CHEMBL1200396 ChEMBL_ID
2279 INN_ID
2397 IUPHAR_LIGAND_ID
2474 PUBCHEM_CID

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Marcaine HUMAN PRESCRIPTION DRUG LABEL 2 0362-0557 INJECTION, SOLUTION 5 mg SUBCUTANEOUS ANDA 11 sections
Vivacaine HUMAN PRESCRIPTION DRUG LABEL 2 0362-9011 INJECTION, SOLUTION 5 mg SUBCUTANEOUS ANDA 11 sections
Marcaine HUMAN PRESCRIPTION DRUG LABEL 2 31382-557 INJECTION, SOLUTION 5 mg SUBCUTANEOUS ANDA 11 sections
Marcaine HUMAN PRESCRIPTION DRUG LABEL 1 52584-560 INJECTION, SOLUTION 5 mg EPIDURAL NDA 11 sections
Marcaine HUMAN PRESCRIPTION DRUG LABEL 1 54868-3134 INJECTION, SOLUTION 5 mg INFILTRATION NDA 11 sections
Marcaine HUMAN PRESCRIPTION DRUG LABEL 1 54868-3437 INJECTION, SOLUTION 2.50 mg INFILTRATION NDA 11 sections
Marcaine with Epinephrine HUMAN PRESCRIPTION DRUG LABEL 2 54868-3438 INJECTION, SOLUTION 2.50 mg INFILTRATION NDA 11 sections
Marcaine with Epinephrine HUMAN PRESCRIPTION DRUG LABEL 2 54868-3439 INJECTION, SOLUTION 5 mg INFILTRATION NDA 11 sections
Bupivacaine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 59923-717 INJECTION 2.50 mg EPIDURAL Unapproved drug for use in drug shortage 3 sections
Bupivacaine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 59923-718 INJECTION 5 mg EPIDURAL Unapproved drug for use in drug shortage 3 sections
Bupivacaine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 59923-719 INJECTION 2.50 mg EPIDURAL Unapproved drug for use in drug shortage 3 sections
Bupivacaine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 59923-720 INJECTION 5 mg EPIDURAL Unapproved drug for use in drug shortage 3 sections
EXPAREL HUMAN PRESCRIPTION DRUG LABEL 1 65250-133 INJECTION, SUSPENSION, LIPOSOMAL 13.30 mg INFILTRATION NDA 17 sections
EXPAREL HUMAN PRESCRIPTION DRUG LABEL 1 65250-266 INJECTION, SUSPENSION, LIPOSOMAL 13.30 mg INFILTRATION NDA 17 sections