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

Stem definitionDrug idCAS RN
1728 76-99-3

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • metadone
  • methadone
  • methadone hydrochloride
  • methadone HCl
A synthetic opioid that is used as the hydrochloride. It is an opioid analgesic that is primarily a mu-opioid agonist. It has actions and uses similar to those of MORPHINE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1082-3)
  • Molecular weight: 309.45
  • Formula: C21H27NO
  • CLOGP: 4.17
  • LIPINSKI: 0
  • HAC: 2
  • HDO: 0
  • TPSA: 20.31
  • ALOGS: -4.72
  • ROTB: 7

  • Status: OFP

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

Drug dosage:

DoseUnitRoute
25 mg O
25 mg P

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 120 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 24 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 1.62 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 92 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 4.40 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 1.70 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.21 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 31 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
Aug. 13, 1947 FDA ROXANE

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 abuse 3511.91 51.78 735 2883 11291 2343176
Toxicity to various agents 3489.72 51.78 877 2741 31877 2322590
Completed suicide 1842.72 51.78 488 3130 20546 2333921
Respiratory arrest 1528.97 51.78 333 3285 5845 2348622
Cardiac arrest 1400.31 51.78 367 3251 14563 2339904
Death 1106.69 51.78 463 3155 81005 2273462
Cardio-respiratory arrest 985.88 51.78 252 3366 8894 2345573
Poisoning 655.04 51.78 145 3473 2675 2351792
Overdose 641.05 51.78 215 3403 19692 2334775
Intentional product misuse 480.46 51.78 145 3473 9344 2345123
Accidental overdose 404.29 51.78 105 3513 3867 2350600
Exposure during pregnancy 403.20 51.78 163 3455 25056 2329411
Torsade de pointes 373.03 51.78 88 3530 2158 2352309
Electrocardiogram QT prolonged 359.29 51.78 111 3507 7703 2346764
Drug withdrawal syndrome neonatal 288.07 51.78 54 3564 403 2354064
Unresponsive to stimuli 210.09 51.78 66 3552 4810 2349657
Drug dependence 204.11 51.78 58 3560 2987 2351480
Exposure via ingestion 190.64 51.78 42 3576 746 2353721
Coma 177.24 51.78 68 3550 8988 2345479
Foetal exposure during pregnancy 176.94 51.78 59 3559 5193 2349274
Respiratory depression 171.31 51.78 47 3571 2123 2352344
Somnolence 162.23 51.78 85 3533 23400 2331067
Drug hypersensitivity 161.65 51.78 108 3510 46535 2307932
Hyperaesthesia 156.44 51.78 39 3579 1204 2353263
Intentional overdose 155.83 51.78 66 3552 11255 2343212
Drug withdrawal syndrome 132.60 51.78 51 3567 6770 2347697
Drug interaction 111.68 51.78 72 3546 29091 2325376
Accidental death 111.26 51.78 23 3595 296 2354171
Pulmonary oedema 94.86 51.78 41 3577 7322 2347145
Delirium 94.20 51.78 37 3581 5186 2349281
Depressed level of consciousness 90.35 51.78 40 3578 7564 2346903
Mental status changes 88.37 51.78 36 3582 5546 2348921
Drug diversion 83.40 51.78 17 3601 203 2354264
Brain oedema 81.91 51.78 27 3591 2283 2352184
Miosis 80.52 51.78 23 3595 1201 2353266
Sedation 79.36 51.78 29 3589 3333 2351134
Substance abuse 78.02 51.78 19 3599 530 2353937
Leukoencephalopathy 75.49 51.78 20 3598 787 2353680
Confusional state 73.69 51.78 52 3566 24292 2330175
Agitation 73.28 51.78 39 3579 11012 2343455
Drug screen positive 72.90 51.78 20 3598 900 2353567
Accidental poisoning 67.62 51.78 13 3605 112 2354355
Pneumonia aspiration 65.67 51.78 26 3592 3716 2350751
Maternal exposure during pregnancy 62.52 51.78 39 3579 14824 2339643
Cyanosis 62.50 51.78 24 3594 3161 2351306
Caesarean section 60.09 51.78 25 3593 4056 2350411
Pulmonary congestion 57.94 51.78 20 3598 1945 2352522
Hypoxic-ischaemic encephalopathy 57.55 51.78 16 3602 756 2353711
Ventricular tachycardia 56.63 51.78 22 3596 2989 2351478
Loss of consciousness 56.55 51.78 40 3578 18727 2335740
Accidental exposure to product by child 56.47 51.78 15 3603 596 2353871
Withdrawal syndrome 54.43 51.78 22 3596 3315 2351152
Drug abuser 54.09 51.78 16 3602 945 2353522
Hypoglycaemia 53.84 51.78 29 3589 8378 2346089
Respiratory acidosis 52.08 51.78 15 3603 806 2353661

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
Toxicity to various agents 5679.48 64.40 1504 3800 27637 1713840
Drug abuse 4530.20 64.40 1089 4215 12600 1728877
Respiratory arrest 1853.59 64.40 455 4849 5384 1736093
Cardiac arrest 1509.28 64.40 481 4823 15449 1726028
Overdose 1368.36 64.40 452 4852 16249 1725228
Completed suicide 1221.71 64.40 413 4891 15899 1725578
Death 1135.68 64.40 638 4666 86805 1654672
Cardio-respiratory arrest 1019.26 64.40 315 4989 8978 1732499
Poisoning 817.59 64.40 201 5103 2331 1739146
Electrocardiogram QT prolonged 757.25 64.40 223 5081 5322 1736155
Intentional product misuse 732.33 64.40 232 5072 7126 1734351
Accidental overdose 583.36 64.40 171 5133 3993 1737484
Torsade de pointes 503.00 64.40 120 5184 1204 1740273
Drug interaction 446.94 64.40 237 5067 27721 1713756
Substance abuse 417.90 64.40 98 5206 905 1740572
Coma 417.61 64.40 152 5152 7110 1734367
Respiratory depression 384.60 64.40 108 5196 2139 1739338
Unresponsive to stimuli 374.29 64.40 125 5179 4504 1736973
Somnolence 307.06 64.40 156 5148 16583 1724894
Drug withdrawal syndrome neonatal 274.81 64.40 65 5239 623 1740854
Pulmonary oedema 274.14 64.40 109 5195 6477 1735000
Prescription drug used without a prescription 246.78 64.40 49 5255 181 1741296
Drug-induced liver injury 240.07 64.40 82 5222 3155 1738322
Depressed level of consciousness 239.59 64.40 99 5205 6493 1734984
Drug dependence 233.98 64.40 81 5223 3246 1738231
Brain oedema 233.15 64.40 73 5231 2123 1739354
Miosis 229.97 64.40 66 5238 1412 1740065
Drug withdrawal syndrome 227.67 64.40 86 5218 4439 1737038
Hepatic fibrosis 218.23 64.40 53 5251 573 1740904
Serotonin syndrome 204.25 64.40 70 5234 2718 1738759
Exposure via ingestion 193.90 64.40 49 5255 631 1740846
Mental status changes 193.17 64.40 83 5221 5992 1735485
Rhabdomyolysis 178.94 64.40 95 5209 10995 1730482
Intentional overdose 177.70 64.40 84 5220 7586 1733891
Withdrawal syndrome 177.58 64.40 60 5244 2228 1739249
Loss of consciousness 176.22 64.40 104 5200 14771 1726706
Sedation 172.01 64.40 65 5239 3352 1738125
Foetal exposure during pregnancy 151.43 64.40 71 5233 6288 1735189
Delirium 151.39 64.40 71 5233 6291 1735186
Drug screen positive 132.74 64.40 40 5264 1017 1740460
Brain injury 129.41 64.40 39 5265 992 1740485
Hypoxic-ischaemic encephalopathy 126.13 64.40 37 5267 855 1740622
Poisoning deliberate 123.79 64.40 36 5268 806 1740671
Pneumonia aspiration 116.76 64.40 56 5248 5210 1736267
Confusional state 113.54 64.40 91 5213 21187 1720290
Accidental death 113.47 64.40 29 5275 391 1741086
Agitation 112.18 64.40 70 5234 10956 1730521
Hypotension 109.98 64.40 103 5201 29551 1711926
Drug diversion 102.63 64.40 24 5280 217 1741260
Hyperaesthesia 93.22 64.40 28 5276 703 1740774
Pulmonary congestion 89.55 64.40 34 5270 1771 1739706
Ventricular tachyarrhythmia 88.79 64.40 17 5287 49 1741428
Respiratory failure 88.05 64.40 67 5237 14438 1727039
Hypoglycaemia 86.86 64.40 54 5250 8384 1733093
Self-medication 86.44 64.40 26 5278 656 1740821
Suicide attempt 83.04 64.40 50 5254 7331 1734146
Compartment syndrome 83.03 64.40 24 5280 525 1740952
Hypoxia 81.94 64.40 46 5258 5917 1735560
Tachycardia 80.33 64.40 60 5244 12568 1728909
Bradypnoea 80.02 64.40 21 5283 316 1741161
Premature baby 79.83 64.40 36 5268 2906 1738571
Drug abuser 77.93 64.40 29 5275 1428 1740049
Ventricular tachycardia 74.00 64.40 37 5267 3761 1737716
Foetal growth restriction 73.61 64.40 23 5281 661 1740816
Apnoea 70.82 64.40 27 5277 1422 1740055
Arteriosclerosis coronary artery 70.57 64.40 29 5275 1863 1739614
Brachial plexopathy 69.10 64.40 13 5291 33 1741444
Cyanosis 67.12 64.40 31 5273 2643 1738834
Vomiting 67.09 64.40 90 5214 38225 1703252
Lethargy 66.49 64.40 43 5261 7141 1734336
Respiratory acidosis 65.21 64.40 21 5283 667 1740810
Pulse absent 64.95 64.40 23 5281 981 1740496

Pharmacologic Action:

SourceCodeDescription
ATC N02AC52 NERVOUS SYSTEM
ANALGESICS
OPIOIDS
Diphenylpropylamine derivatives
ATC N07BC02 NERVOUS SYSTEM
OTHER NERVOUS SYSTEM DRUGS
DRUGS USED IN ADDICTIVE DISORDERS
Drugs used in opioid dependence
MeSH PA D000700 Analgesics
MeSH PA D000701 Analgesics, Opioid
CHEBI has role CHEBI:35482 opioid analgesic
CHEBI has role CHEBI:55322 mu-opioid receptor agonist
MeSH PA D000996 Antitussive Agents
MeSH PA D002491 Central Nervous System Agents
MeSH PA D002492 Central Nervous System Depressants
MeSH PA D009294 Narcotics
MeSH PA D018373 Peripheral Nervous System Agents
MeSH PA D019141 Respiratory System Agents
MeSH PA D018689 Sensory System Agents
FDA MoA N0000175684 Full Opioid Agonists
FDA EPC N0000175690 Opioid Agonist

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Severe pain indication 76948002
Opioid withdrawal indication 87132004
Chronic disease of respiratory system contraindication 17097001
Mood swings contraindication 18963009
Inflammatory bowel disease contraindication 24526004 DOID:0050589
Hypercapnia contraindication 29596007
Torsades de pointes contraindication 31722008
Disorder of gallbladder contraindication 39621005 DOID:0060262
Hypothyroidism contraindication 40930008 DOID:1459
Conduction disorder of the heart contraindication 44808001
Low blood pressure contraindication 45007003
Bradycardia contraindication 48867003
Paralytic ileus contraindication 55525008 DOID:8442
Drug AND/OR toxin-induced diarrhea contraindication 65979008
Substance abuse contraindication 66214007
Benign intracranial hypertension contraindication 68267002 DOID:11459
Urethral stricture contraindication 76618002
Decreased respiratory function contraindication 80954004
Injury of head contraindication 82271004
Epilepsy contraindication 84757009 DOID:1826
Kidney disease contraindication 90708001 DOID:557
Prolonged QT interval contraindication 111975006
Acute abdominal pain contraindication 116290004
Procedure on urinary system contraindication 118677009
Disease of liver contraindication 235856003 DOID:409
Benign prostatic hyperplasia contraindication 266569009
Pseudomembranous enterocolitis contraindication 397683000
Congenital long QT syndrome contraindication 442917000
Acute exacerbation of asthma contraindication 708038006

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 8.55 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
Mu-type opioid receptor GPCR AGONIST Ki 8.78 WOMBAT-PK CHEMBL
Delta-type opioid receptor GPCR IC50 5.96 CHEMBL
Potassium voltage-gated channel subfamily H member 2 Ion channel IC50 5.01 CHEMBL
Kappa-type opioid receptor GPCR IC50 6.29 CHEMBL
Neuronal acetylcholine receptor subunit alpha-10 Ion channel WOMBAT-PK
Glutamate receptor ionotropic, NMDA 3A Ion channel WOMBAT-PK
Opioid receptor GPCR IC50 7.29 CHEMBL

External reference:

IDSource
4019820 VUID
N0000147909 NUI
C0025605 UMLSCUI
D02102 KEGG_DRUG
229809935B UNII
1095-90-5 SECONDARY_CAS_RN
51758009 SNOMEDCT_US
4019820 VANDF
6813 RXNORM
387286002 SNOMEDCT_US
d00050 MMSL
004628 NDDF
CHEMBL651 ChEMBL_ID
DB00333 DRUGBANK_ID
CHEMBL1200825 ChEMBL_ID
788 INN_ID
CHEBI:6807 CHEBI
4095 PUBCHEM_CID
D008691 MESH_DESCRIPTOR_UI
5458 IUPHAR_LIGAND_ID

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Methadone Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0054-0391 CONCENTRATE 10 mg ORAL ANDA 13 sections
Methadone Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0054-0392 CONCENTRATE 10 mg ORAL ANDA 13 sections
Methadone Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0054-3553 CONCENTRATE 10 mg ORAL ANDA 18 sections
Methadone Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0054-3555 SOLUTION 5 mg ORAL ANDA 19 sections
Methadone Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0054-3556 SOLUTION 10 mg ORAL ANDA 19 sections
DOLOPHINE HUMAN PRESCRIPTION DRUG LABEL 1 0054-4218 TABLET 5 mg ORAL NDA 19 sections
DOLOPHINE HUMAN PRESCRIPTION DRUG LABEL 1 0054-4219 TABLET 10 mg ORAL NDA 19 sections
DISKETS HUMAN PRESCRIPTION DRUG LABEL 1 0054-4538 TABLET 40 mg ORAL NDA 18 sections
METHADONE HYDROCHLORIDE HUMAN PRESCRIPTION DRUG LABEL 1 0054-4570 TABLET 5 mg ORAL NDA 19 sections
METHADONE HYDROCHLORIDE HUMAN PRESCRIPTION DRUG LABEL 1 0054-4571 TABLET 10 mg ORAL NDA 19 sections
METHADONE HYDROCHLORIDE HUMAN PRESCRIPTION DRUG LABEL 1 0054-8553 TABLET 5 mg ORAL NDA 19 sections
METHADONE HYDROCHLORIDE HUMAN PRESCRIPTION DRUG LABEL 1 0054-8554 TABLET 10 mg ORAL NDA 19 sections
METHADOSE HUMAN PRESCRIPTION DRUG LABEL 1 0406-0527 CONCENTRATE 10 mg ORAL NDA 13 sections
METHADOSE DISPERSIBLE HUMAN PRESCRIPTION DRUG LABEL 1 0406-0540 TABLET 40 mg ORAL ANDA 18 sections
Methadone Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0406-1510 POWDER 1 g ORAL NDA 13 sections
METHADONE HYDROCHLORIDE HUMAN PRESCRIPTION DRUG LABEL 1 0406-2540 TABLET 40 mg ORAL ANDA 18 sections
METHADONE HYDROCHLORIDE HUMAN PRESCRIPTION DRUG LABEL 1 0406-5755 TABLET 5 mg ORAL ANDA 19 sections
METHADONE HYDROCHLORIDE HUMAN PRESCRIPTION DRUG LABEL 1 0406-5771 TABLET 10 mg ORAL ANDA 19 sections
METHADOSE HUMAN PRESCRIPTION DRUG LABEL 1 0406-8725 CONCENTRATE 10 mg ORAL NDA 13 sections
Methadone Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0904-6530 TABLET 10 mg ORAL ANDA 19 sections
Methadone Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 13107-088 TABLET 5 mg ORAL ANDA 19 sections
Methadone Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 13107-089 TABLET 10 mg ORAL ANDA 19 sections
METHADONE HYDROCHLORIDE HUMAN PRESCRIPTION DRUG LABEL 1 16590-689 TABLET 5 mg ORAL NDA 15 sections
Methadone Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 17478-380 INJECTION, SOLUTION 10 mg INTRAMUSCULAR ANDA 13 sections
Methadone Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 17856-0392 CONCENTRATE 10 mg ORAL ANDA 13 sections
METHADOSE HUMAN PRESCRIPTION DRUG LABEL 1 17856-0526 CONCENTRATE 10 mg ORAL NDA 13 sections
METHADOSE HUMAN PRESCRIPTION DRUG LABEL 1 17856-0527 CONCENTRATE 10 mg ORAL NDA 13 sections
Methadone Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 17856-0694 CONCENTRATE 10 mg ORAL ANDA 14 sections
Methadone Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 17856-3553 CONCENTRATE 10 mg ORAL ANDA 18 sections
Methadone Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 17856-3554 SOLUTION 5 mg ORAL ANDA 19 sections