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

Stem definitionDrug idCAS RN
2286 60-87-7

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • promethazine
  • diphergan
  • proazamine
  • prometazin
  • protazine
  • promethazine hydrochloride
  • promethazine HCl
A phenothiazine derivative with histamine H1-blocking, antimuscarinic, and sedative properties. It is used as an antiallergic, in pruritus, for motion sickness and sedation, and also in animals.
  • Molecular weight: 284.42
  • Formula: C17H20N2S
  • CLOGP: 4.60
  • LIPINSKI: 0
  • HAC: 2
  • HDO: 0
  • TPSA: 6.48
  • ALOGS: -4.07
  • ROTB: 3

  • Status: OFP

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

Drug dosage:

DoseUnitRoute
25 mg O
25 mg P
25 mg R

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 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) 5.03 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 25 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 14 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 14 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.09 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 14 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
March 29, 1951 FDA DELCOR ASSET CORP

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
Toxicity to various agents 1613.97 34.67 437 1892 32317 2323439
Completed suicide 1352.18 34.67 348 1981 20686 2335070
Drug hypersensitivity 1119.81 34.67 358 1971 46285 2309471
Drug abuse 1068.88 34.67 259 2070 11767 2343989
Poisoning 475.63 34.67 103 2226 2717 2353039
Intentional overdose 385.24 34.67 115 2214 11206 2344550
Cardiac arrest 374.42 34.67 120 2209 14810 2340946
Respiratory arrest 347.29 34.67 93 2236 6085 2349671
Cardio-respiratory arrest 306.84 34.67 92 2237 9054 2346702
Overdose 302.57 34.67 110 2219 19797 2335959
Death 219.37 34.67 136 2193 81332 2274424
Somnolence 201.78 34.67 86 2243 23399 2332357
Suicide attempt 199.89 34.67 70 2259 11212 2344544
Intentional product misuse 187.91 34.67 64 2265 9425 2346331
Intentional self-injury 153.22 34.67 45 2284 4082 2351674
Accidental overdose 150.49 34.67 44 2285 3928 2351828
Exposure via ingestion 144.96 34.67 31 2298 757 2354999
Nausea 124.39 34.67 110 2219 112079 2243677
Anxiety 123.89 34.67 66 2263 29293 2326463
Depressed level of consciousness 107.52 34.67 40 2289 7564 2348192
Serotonin syndrome 102.95 34.67 32 2297 3508 2352248
Accidental death 102.77 34.67 20 2309 299 2355457
Vomiting 99.20 34.67 80 2249 71522 2284234
Anticholinergic syndrome 98.07 34.67 19 2310 277 2355479
Confusional state 84.04 34.67 48 2281 24296 2331460
Medication error 82.08 34.67 31 2298 6100 2349656
Agitation 76.88 34.67 35 2294 11016 2344740
Drug interaction 76.01 34.67 48 2281 29115 2326641
Suicidal ideation 70.51 34.67 33 2296 11054 2344702
Mental status changes 70.30 34.67 27 2302 5555 2350201
Unresponsive to stimuli 70.16 34.67 26 2303 4850 2350906
Akathisia 69.80 34.67 20 2309 1654 2354102
Depression 65.14 34.67 43 2286 28089 2327667
Electrocardiogram QT prolonged 64.78 34.67 28 2301 7786 2347970
Sedation 63.75 34.67 22 2307 3340 2352416
Exposure during pregnancy 61.93 34.67 40 2289 25179 2330577
Lethargy 61.80 34.67 28 2301 8702 2347054
Tremor 61.39 34.67 37 2292 20624 2335132
Restlessness 60.79 34.67 23 2306 4540 2351216
Sinus tachycardia 60.12 34.67 21 2308 3304 2352452
Delirium 57.77 34.67 23 2306 5200 2350556
Incorrect route of product administration 57.29 34.67 23 2306 5313 2350443
Mydriasis 55.94 34.67 18 2311 2201 2353555
Hyperhidrosis 54.73 34.67 31 2298 15391 2340365
Coma 54.63 34.67 26 2303 9030 2346726
Dysarthria 53.60 34.67 23 2306 6279 2349477
Pain 53.33 34.67 53 2276 61804 2293952
Ureteric stenosis 52.59 34.67 10 2319 131 2355625
Respiratory depression 52.24 34.67 17 2312 2153 2353603
Dystonia 52.06 34.67 17 2312 2177 2353579
Extrapyramidal disorder 50.93 34.67 17 2312 2330 2353426
Helplessness 49.97 34.67 8 2321 34 2355722
Aggression 49.21 34.67 20 2309 4766 2350990
Product counterfeit 48.62 34.67 9 2320 101 2355655
Syncope 46.97 34.67 29 2300 16846 2338910
Dyskinesia 45.79 34.67 19 2310 4770 2350986
Hallucination 44.92 34.67 22 2307 8126 2347630
Poor feeding infant 44.52 34.67 8 2321 75 2355681
Coma blister 44.47 34.67 7 2322 26 2355730
Disorientation 43.70 34.67 20 2309 6352 2349404
Drug dependence 42.91 34.67 16 2313 3029 2352727
Respiratory rate increased 41.06 34.67 13 2316 1507 2354249
Neuroleptic malignant syndrome 40.93 34.67 14 2315 2066 2353690
Finger amputation 40.82 34.67 8 2321 124 2355632
Hypotension 40.00 34.67 34 2295 32402 2323354
Illness anxiety disorder 39.52 34.67 7 2322 60 2355696
Disturbance in attention 39.47 34.67 18 2311 5667 2350089
Product administration error 38.90 34.67 16 2313 3927 2351829
Drug screen positive 38.38 34.67 11 2318 909 2354847
Tachycardia 37.72 34.67 25 2304 16384 2339372
Pain in extremity 37.61 34.67 37 2292 42503 2313253
Hemiparesis 37.47 34.67 15 2314 3435 2352321
Gangrene 37.40 34.67 10 2319 639 2355117
Dehydration 37.38 34.67 28 2301 22267 2333489
Small for dates baby 37.13 34.67 10 2319 657 2355099
Skin discolouration 37.12 34.67 17 2312 5403 2350353
Respiratory failure 37.00 34.67 23 2306 13505 2342251
Hypopnoea 36.47 34.67 9 2320 417 2355339
Poisoning deliberate 35.57 34.67 11 2318 1180 2354576
Cardiogenic shock 34.77 34.67 13 2316 2478 2353278

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 658.88 48.12 203 946 28938 1716694
Drug abuse 461.86 48.12 131 1018 13558 1732074
Completed suicide 461.26 48.12 136 1013 16176 1729456
Respiratory arrest 289.21 48.12 76 1073 5763 1739869
Cardiac arrest 260.88 48.12 88 1061 15842 1729790
Overdose 248.95 48.12 86 1063 16615 1729017
Poisoning 231.46 48.12 54 1095 2478 1743154
Cardio-respiratory arrest 207.12 48.12 65 1084 9228 1736404
Drug hypersensitivity 194.78 48.12 70 1079 15065 1730567
Neuroleptic malignant syndrome 165.06 48.12 43 1106 3105 1742527
Agitation 149.09 48.12 53 1096 10973 1734659
Suicide attempt 132.88 48.12 44 1105 7337 1738295
Confusional state 115.33 48.12 53 1096 21225 1724407
Somnolence 110.84 48.12 48 1101 16691 1728941
Intentional product misuse 94.06 48.12 34 1115 7324 1738308
Intentional overdose 92.68 48.12 34 1115 7636 1737996
Vomiting 91.14 48.12 55 1094 38260 1707372
Death 89.92 48.12 75 1074 87368 1658264
Foetal exposure during pregnancy 87.34 48.12 31 1118 6328 1739304
Exposure via ingestion 80.74 48.12 18 1131 662 1744970
Dystonia 79.38 48.12 22 1127 1992 1743640
Unresponsive to stimuli 76.80 48.12 26 1123 4603 1741029
Lethargy 76.34 48.12 29 1120 7155 1738477
Product counterfeit 70.53 48.12 12 1137 100 1745532
Shock 67.55 48.12 23 1126 4138 1741494
Coma 65.38 48.12 26 1123 7236 1738396
Mental status changes 62.63 48.12 24 1125 6051 1739581
Serotonin syndrome 59.68 48.12 19 1130 2769 1742863
Respiratory depression 59.40 48.12 18 1131 2229 1743403
Foetal alcohol syndrome 56.42 48.12 8 1141 15 1745617
Drug interaction 55.79 48.12 36 1113 27922 1717710
Conduction disorder 55.35 48.12 12 1137 386 1745246
Dysarthria 54.99 48.12 21 1128 5238 1740394
Dextrocardia 53.30 48.12 8 1141 26 1745606
Hepatic ischaemia 48.24 48.12 8 1141 56 1745576

Pharmacologic Action:

SourceCodeDescription
ATC D04AA10 DERMATOLOGICALS
ANTIPRURITICS, INCL. ANTIHISTAMINES, ANESTHETICS, ETC.
ANTIPRURITICS, INCL. ANTIHISTAMINES, ANESTHETICS, ETC.
Antihistamines for topical use
ATC R06AD02 RESPIRATORY SYSTEM
ANTIHISTAMINES FOR SYSTEMIC USE
ANTIHISTAMINES FOR SYSTEMIC USE
Phenothiazine derivatives
ATC R06AD52 RESPIRATORY SYSTEM
ANTIHISTAMINES FOR SYSTEMIC USE
ANTIHISTAMINES FOR SYSTEMIC USE
Phenothiazine derivatives
ATC V03AB05 VARIOUS
ALL OTHER THERAPEUTIC PRODUCTS
ALL OTHER THERAPEUTIC PRODUCTS
Antidotes
FDA EPC N0000175746 Phenothiazine
FDA CS M0016525 Phenothiazines
CHEBI has role CHEBI:35717 sedative
CHEBI has role CHEBI:50919 antiemetic
CHEBI has role CHEBI:36333 local anaesthetic
CHEBI has role CHEBI:59683 antipruritic drug
CHEBI has role CHEBI:50857 anti-allergic agent
CHEBI has role CHEBI:37955 H1-receptor antagonist
MeSH PA D018926 Anti-Allergic Agents
MeSH PA D000982 Antipruritics
MeSH PA D003879 Dermatologic Agents
MeSH PA D018494 Histamine Agents
MeSH PA D006633 Histamine Antagonists
MeSH PA D006634 Histamine H1 Antagonists
MeSH PA D018377 Neurotransmitter Agents

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Vasomotor rhinitis indication 8229003 DOID:4730
Nausea and vomiting indication 16932000
General anesthesia indication 50697003
Sedation indication 72641008
Urticaria indication 126485001
Seasonal allergic rhinitis indication 367498001
Allergic conjunctivitis indication 473460002 DOID:11204

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 9.19 Basic
pKa2 3.55 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
Histamine H1 receptor GPCR ANTAGONIST Ki 9.62 WOMBAT-PK CHEMBL
D(1A) dopamine receptor GPCR Ki 5.86 DRUG MATRIX
Alpha-2A adrenergic receptor GPCR Ki 6.59 DRUG MATRIX
Sigma non-opioid intracellular receptor 1 Membrane receptor Ki 6.92 DRUG MATRIX
Sodium-dependent noradrenaline transporter Transporter Ki 5.38 DRUG MATRIX
5-hydroxytryptamine receptor 1A GPCR Ki 5.83 DRUG MATRIX
5-hydroxytryptamine receptor 2B GPCR Ki 7.37 DRUG MATRIX
5-hydroxytryptamine receptor 2C GPCR Ki 8.19 DRUG MATRIX
5-hydroxytryptamine receptor 6 GPCR Ki 5.95 DRUG MATRIX
Alpha-2B adrenergic receptor GPCR Ki 7.62 DRUG MATRIX
D(3) dopamine receptor GPCR Ki 6.72 DRUG MATRIX
Histamine H2 receptor GPCR Ki 5.94 DRUG MATRIX
Muscarinic acetylcholine receptor M1 GPCR Ki 8.48 DRUG MATRIX
Muscarinic acetylcholine receptor M2 GPCR Ki 7.92 DRUG MATRIX
Muscarinic acetylcholine receptor M3 GPCR Ki 8.38 DRUG MATRIX
Muscarinic acetylcholine receptor M4 GPCR Ki 8.97 DRUG MATRIX
Muscarinic acetylcholine receptor M5 GPCR Ki 8.48 DRUG MATRIX
Alpha-2C adrenergic receptor GPCR Ki 6.45 DRUG MATRIX
Alpha-1D adrenergic receptor GPCR Ki 7.49 DRUG MATRIX
Solute carrier family 22 member 1 Transporter IC50 4.45 CHEMBL
Sodium channel alpha subunits; brain (Types I, II, III) Ion channel IC50 5.16 CHEMBL
Major prion protein Surface antigen EC50 5.10 CHEMBL
Sodium-dependent serotonin transporter Transporter IC50 5.12 CHEMBL
Cholinesterase Enzyme Ki 7.10 WOMBAT-PK
Alpha-1A adrenergic receptor GPCR WOMBAT-PK
5-hydroxytryptamine receptor 2A GPCR Ki 6.77 WOMBAT-PK
Aldehyde oxidase Enzyme IC50 6.29 WOMBAT-PK
Histamine H4 receptor GPCR Ki 6.82 WOMBAT-PK
D(2) dopamine receptor GPCR Ki 6.61 WOMBAT-PK
Cytochrome P450 2D6 Enzyme Ki 5.42 WOMBAT-PK
FAD-linked sulfhydryl oxidase ALR Enzyme AC50 6.44 CHEMBL
Alpha-1B adrenergic receptor GPCR Ki 7.68 DRUG MATRIX
Chloroquine resistance transporter Unclassified IC50 4.07 CHEMBL
Pleiotropic ABC efflux transporter of multiple drugs Transporter IC50 4.75 CHEMBL
5-hydroxytryptamine receptor 1A GPCR IC50 5.59 CHEMBL
Alpha-1A adrenergic receptor GPCR IC50 7.10 CHEMBL

External reference:

IDSource
4019910 VUID
N0000147995 NUI
C0033405 UMLSCUI
D00480 KEGG_DRUG
8372007 SNOMEDCT_US
4019910 VANDF
8745 RXNORM
372871004 SNOMEDCT_US
d00787 MMSL
004459 NDDF
CHEBI:8461 CHEBI
CHEMBL643 ChEMBL_ID
CHEMBL251904 ChEMBL_ID
DB01069 DRUGBANK_ID
CHEMBL1200750 ChEMBL_ID
FF28EJQ494 UNII
516 INN_ID
58-33-3 SECONDARY_CAS_RN
4927 PUBCHEM_CID
D011398 MESH_DESCRIPTOR_UI
7282 IUPHAR_LIGAND_ID

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
PROMETHAZINE HYDROCHLORIDE AND CODEINE PHOSPHATE HUMAN PRESCRIPTION DRUG LABEL 2 0121-0547 SYRUP 6.25 mg ORAL ANDA 15 sections
Promethazine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0409-2312 INJECTION, SOLUTION 25 mg INTRAMUSCULAR ANDA 13 sections
Promethazine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0440-5195 TABLET 25 mg ORAL ANDA 11 sections
Promethazine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0440-8195 TABLET 25 mg ORAL ANDA 11 sections
PHENADOZ HUMAN PRESCRIPTION DRUG LABEL 1 0591-2985 SUPPOSITORY 12.50 mg RECTAL ANDA 12 sections
PHENADOZ HUMAN PRESCRIPTION DRUG LABEL 1 0591-2992 SUPPOSITORY 25 mg RECTAL ANDA 12 sections
Promethazine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0591-5307 TABLET 25 mg ORAL ANDA 11 sections
Promethazine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0591-5319 TABLET 50 mg ORAL ANDA 11 sections
Promethazine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0603-1584 SOLUTION 6.25 mg ORAL ANDA 12 sections
Promethazine with Codeine HUMAN PRESCRIPTION DRUG LABEL 2 0603-1585 SOLUTION 6.25 mg ORAL ANDA 18 sections
PROMETHAZINE DM HUMAN PRESCRIPTION DRUG LABEL 2 0603-1586 SOLUTION 6.25 mg ORAL ANDA 13 sections
Promethazine HUMAN PRESCRIPTION DRUG LABEL 1 0615-1539 TABLET 12.50 mg ORAL ANDA 12 sections
promethazine hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0615-7668 TABLET 25 mg ORAL ANDA 12 sections
Promethazine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0615-8154 TABLET 25 mg ORAL ANDA 13 sections
Promethazine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0641-0928 INJECTION 25 mg INTRAMUSCULAR ANDA 13 sections
Promethazine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0641-0929 INJECTION 50 mg INTRAMUSCULAR ANDA 13 sections
Promethazine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0641-0948 INJECTION 25 mg INTRAMUSCULAR ANDA 13 sections
Promethazine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0641-0949 INJECTION 50 mg INTRAMUSCULAR ANDA 13 sections
Promethazine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0641-0955 INJECTION 25 mg INTRAMUSCULAR ANDA 12 sections
Promethazine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0641-0956 INJECTION 50 mg INTRAMUSCULAR ANDA 12 sections
Promethazine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0641-1495 INJECTION 25 mg INTRAMUSCULAR ANDA 13 sections
Promethazine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0641-1496 INJECTION 50 mg INTRAMUSCULAR ANDA 13 sections
PHENERGAN HUMAN PRESCRIPTION DRUG LABEL 1 0641-6082 INJECTION 25 mg INTRAMUSCULAR ANDA 13 sections
PHENERGAN HUMAN PRESCRIPTION DRUG LABEL 1 0641-6083 INJECTION 50 mg INTRAMUSCULAR ANDA 13 sections
PHENERGAN HUMAN PRESCRIPTION DRUG LABEL 1 0641-6084 INJECTION 25 mg INTRAMUSCULAR ANDA 12 sections
PHENERGAN HUMAN PRESCRIPTION DRUG LABEL 1 0641-6085 INJECTION 50 mg INTRAMUSCULAR ANDA 12 sections
Promethazine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0641-6099 INJECTION 25 mg INTRAMUSCULAR ANDA 12 sections
Promethazine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0641-6208 INJECTION 25 mg INTRAMUSCULAR ANDA 13 sections
PROMETHEGAN HUMAN PRESCRIPTION DRUG LABEL 1 0713-0132 SUPPOSITORY 50 mg RECTAL ANDA 21 sections
PROMETHEGAN HUMAN PRESCRIPTION DRUG LABEL 1 0713-0526 SUPPOSITORY 25 mg RECTAL ANDA 21 sections