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

Stem definition	Drug id	CAS RN
	2286	60-87-7

Description:

Molecule	Description
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

Molecule

Description

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:

Dose	Unit	Route
25	mg	O
25	mg	P
25	mg	R

ADMET properties:

Property	Value	Reference
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 µM/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:

Date	Agency	Company	Orphan
March 29, 1951	FDA	DELCOR ASSET CORP

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients 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 term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients 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:

Source	Code	Description
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)

Disease	Relation	SNOMED_ID	DOID
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 level	Dissociation constant	Type (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:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
Histamine H1 receptor	GPCR	P35367	HRH1_HUMAN	ANTAGONIST	Ki	9.62	WOMBAT-PK	CHEMBL
D(1A) dopamine receptor	GPCR	P21728	DRD1_HUMAN		Ki	5.86	DRUG MATRIX
Alpha-2A adrenergic receptor	GPCR	P08913	ADA2A_HUMAN		Ki	6.59	DRUG MATRIX
Sigma non-opioid intracellular receptor 1	Membrane receptor	Q99720	SGMR1_HUMAN		Ki	6.92	DRUG MATRIX
Sodium-dependent noradrenaline transporter	Transporter	P23975	SC6A2_HUMAN		Ki	5.38	DRUG MATRIX
5-hydroxytryptamine receptor 1A	GPCR	P08908	5HT1A_HUMAN		Ki	5.83	DRUG MATRIX
5-hydroxytryptamine receptor 2B	GPCR	P41595	5HT2B_HUMAN		Ki	7.37	DRUG MATRIX
5-hydroxytryptamine receptor 2C	GPCR	P28335	5HT2C_HUMAN		Ki	8.19	DRUG MATRIX
5-hydroxytryptamine receptor 6	GPCR	P50406	5HT6R_HUMAN		Ki	5.95	DRUG MATRIX
Alpha-2B adrenergic receptor	GPCR	P18089	ADA2B_HUMAN		Ki	7.62	DRUG MATRIX
D(3) dopamine receptor	GPCR	P35462	DRD3_HUMAN		Ki	6.72	DRUG MATRIX
Histamine H2 receptor	GPCR	P25021	HRH2_HUMAN		Ki	5.94	DRUG MATRIX
Muscarinic acetylcholine receptor M1	GPCR	P11229	ACM1_HUMAN		Ki	8.48	DRUG MATRIX
Muscarinic acetylcholine receptor M2	GPCR	P08172	ACM2_HUMAN		Ki	7.92	DRUG MATRIX
Muscarinic acetylcholine receptor M3	GPCR	P20309	ACM3_HUMAN		Ki	8.38	DRUG MATRIX
Muscarinic acetylcholine receptor M4	GPCR	P08173	ACM4_HUMAN		Ki	8.97	DRUG MATRIX
Muscarinic acetylcholine receptor M5	GPCR	P08912	ACM5_HUMAN		Ki	8.48	DRUG MATRIX
Alpha-2C adrenergic receptor	GPCR	P18825	ADA2C_HUMAN		Ki	6.45	DRUG MATRIX
Alpha-1D adrenergic receptor	GPCR	P25100	ADA1D_HUMAN		Ki	7.49	DRUG MATRIX
Solute carrier family 22 member 1	Transporter	O15245	S22A1_HUMAN		IC50	4.45	CHEMBL
Sodium channel alpha subunits; brain (Types I, II, III)	Ion channel	P35498 Q99250 Q9NY46	SCN1A_HUMAN SCN2A_HUMAN SCN3A_HUMAN		IC50	5.16	CHEMBL
Major prion protein	Surface antigen	P04156	PRIO_HUMAN		EC50	5.10	CHEMBL
Sodium-dependent serotonin transporter	Transporter	P31645	SC6A4_HUMAN		IC50	5.12	CHEMBL
Cholinesterase	Enzyme	P06276	CHLE_HUMAN		Ki	7.10	WOMBAT-PK
Alpha-1A adrenergic receptor	GPCR	P35348	ADA1A_HUMAN				WOMBAT-PK
5-hydroxytryptamine receptor 2A	GPCR	P28223	5HT2A_HUMAN		Ki	6.77	WOMBAT-PK
Aldehyde oxidase	Enzyme	Q06278	AOXA_HUMAN		IC50	6.29	WOMBAT-PK
Histamine H4 receptor	GPCR	Q9H3N8	HRH4_HUMAN		Ki	6.82	WOMBAT-PK
D(2) dopamine receptor	GPCR	P14416	DRD2_HUMAN		Ki	6.61	WOMBAT-PK
Cytochrome P450 2D6	Enzyme	P10635	CP2D6_HUMAN		Ki	5.42	WOMBAT-PK
FAD-linked sulfhydryl oxidase ALR	Enzyme	P55789	ALR_HUMAN		AC50	6.44	CHEMBL
Alpha-1B adrenergic receptor	GPCR		ADA1B_RAT		Ki	7.68	DRUG MATRIX
Chloroquine resistance transporter	Unclassified		CRT_PLAFA		IC50	4.07	CHEMBL
Pleiotropic ABC efflux transporter of multiple drugs	Transporter		PDR5_YEAST		IC50	4.75	CHEMBL
5-hydroxytryptamine receptor 1A	GPCR		5HT1A_RAT		IC50	5.59	CHEMBL
Alpha-1A adrenergic receptor	GPCR		ADA1A_RAT		IC50	7.10	CHEMBL

External reference:

ID	Source
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:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
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