diphenoxylate 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
analgesics, pethidine derivatives and other synthetic small molecule miu-opioid receptor agonists	918	915-30-0

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: diphenoxylate diphenoxylate hydrochloride diphenoxylate HCl	A MEPERIDINE congener used as an antidiarrheal, usually in combination with ATROPINE. At high doses, it acts like morphine. Its unesterified metabolite difenoxin has similar properties and is used similarly. It has little or no analgesic activity. Molecular weight: 452.60 Formula: C30H32N2O2 CLOGP: 5.33 LIPINSKI: 1 HAC: 4 HDO: 0 TPSA: 53.33 ALOGS: -5.49 ROTB: 9 Status: OFP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

diphenoxylate
diphenoxylate hydrochloride
diphenoxylate HCl

A MEPERIDINE congener used as an antidiarrheal, usually in combination with ATROPINE. At high doses, it acts like morphine. Its unesterified metabolite difenoxin has similar properties and is used similarly. It has little or no analgesic activity.

Molecular weight: 452.60
Formula: C30H32N2O2
CLOGP: 5.33
LIPINSKI: 1
HAC: 4
HDO: 0
TPSA: 53.33
ALOGS: -5.49
ROTB: 9

Status: OFP

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

Drug dosage:

Dose	Unit	Route
15	mg	O

ADMET properties:

Property	Value	Reference
MRTD (Maximum Recommended Therapeutic Daily Dose)	0.63 µM/kg/day	Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BDDCS (Biopharmaceutical Drug Disposition Classification System)	2	Bocci G, Oprea TI, Benet LZ

Approvals:

Date	Agency	Company	Orphan
Sept. 15, 1960	FDA	GD SEARLE LLC

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
Presbyacusis	142.32	16.89	38	7365	2827	63478792
Pleural fibrosis	135.09	16.89	38	7365	3434	63478185
Deafness neurosensory	126.74	16.89	39	7364	4816	63476803
Pleural thickening	118.77	16.89	33	7370	2850	63478769
Diarrhoea	109.74	16.89	250	7153	715116	62766503
Blood magnesium increased	108.04	16.89	31	7372	3007	63478612
Dehydration	104.01	16.89	114	7289	173240	63308379
Epigastric discomfort	94.75	16.89	34	7369	6746	63474873
Osteopenia	85.21	16.89	43	7360	19742	63461877
Macular degeneration	85.03	16.89	46	7357	24330	63457289
Osteosclerosis	75.74	16.89	25	7378	3863	63477756
Bone cyst	75.70	16.89	22	7381	2232	63479387
Cyst	73.76	16.89	35	7368	14064	63467555
Skin lesion	65.07	16.89	42	7361	30679	63450940
Blood potassium increased	62.31	16.89	34	7369	18275	63463344
Dry eye	52.19	16.89	41	7362	40720	63440899
Exostosis	44.30	16.89	27	7376	17835	63463784
Osteoarthritis	44.18	16.89	55	7348	95288	63386331
Deformity	40.59	16.89	22	7381	11662	63469957
Blood creatinine increased	33.42	16.89	46	7357	87798	63393821
Chronic sinusitis	33.36	16.89	20	7383	12823	63468796
Crohn's disease	31.33	16.89	14	7389	4899	63476720
Paraesthesia oral	28.22	16.89	21	7382	19235	63462384
Renal impairment	27.39	16.89	42	7361	88313	63393306
Abdominal pain	25.82	16.89	84	7319	293372	63188247
Procedural pain	24.01	16.89	20	7383	21549	63460070
Nausea	23.60	16.89	175	7228	854296	62627323
Myocardial infarction	23.58	16.89	42	7361	99851	63381768
Sleep disorder	22.83	16.89	37	7366	81529	63400090
Small intestinal obstruction	22.50	16.89	18	7385	18319	63463300
Hypokalaemia	21.18	16.89	41	7362	103763	63377856
Purpura senile	21.16	16.89	6	7397	557	63481062
Bone hypertrophy	18.13	16.89	5	7398	419	63481200
Gastroenteritis radiation	17.60	16.89	5	7398	467	63481152
Clostridial infection	17.32	16.89	9	7394	4383	63477236
Large intestinal stenosis	17.18	16.89	7	7396	1956	63479663

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
Dehydration	123.77	18.81	100	3181	129869	34823781
Diarrhoea	100.20	18.81	150	3131	389762	34563888
Small intestinal obstruction	24.46	18.81	16	3265	14850	34938800
Off label use	22.26	18.81	6	3275	419518	34534132

FDA Adverse Event Reporting System (Geriatric)

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
Presbyacusis	152.63	17.97	38	7582	2622	79734146
Pleural fibrosis	144.89	17.97	40	7580	4127	79732641
Diarrhoea	140.92	17.97	278	7342	880211	78856557
Dehydration	126.08	17.97	136	7484	248051	79488717
Deafness neurosensory	124.99	17.97	40	7580	6858	79729910
Pleural thickening	124.17	17.97	33	7587	2949	79733819
Blood magnesium increased	109.75	17.97	31	7589	3475	79733293
Epigastric discomfort	96.30	17.97	34	7586	7862	79728906
Osteopenia	90.06	17.97	41	7579	18323	79718445
Cyst	84.35	17.97	36	7584	13804	79722964
Osteosclerosis	71.82	17.97	23	7597	3948	79732820
Bone cyst	70.88	17.97	22	7598	3411	79733357
Dry eye	58.31	17.97	39	7581	36892	79699876
Blood potassium increased	56.30	17.97	35	7585	29240	79707528
Skin lesion	56.20	17.97	40	7580	41804	79694964
Osteoarthritis	53.47	17.97	53	7567	87256	79649512
Deformity	48.84	17.97	22	7598	9583	79727185
Exostosis	39.79	17.97	23	7597	16835	79719933
Chronic sinusitis	34.05	17.97	19	7601	13007	79723761
Macular degeneration	33.75	17.97	18	7602	11278	79725490
Blood creatinine increased	33.39	17.97	56	7564	155001	79581767
Nausea	32.48	17.97	178	7442	957018	78779750
Sleep disorder	30.13	17.97	39	7581	85638	79651130
Paraesthesia oral	28.47	17.97	20	7600	20451	79716317
Gastrointestinal disorder	24.80	17.97	43	7577	122162	79614606
Procedural pain	24.14	17.97	19	7601	23065	79713703
Small intestinal obstruction	23.38	17.97	20	7600	27252	79709516
Myocardial infarction	18.85	17.97	49	7571	184080	79552688
Crohn's disease	18.20	17.97	7	7613	2053	79734715
Vertigo positional	18.12	17.97	8	7612	3322	79733446
Purpura senile	18.01	17.97	5	7615	525	79736243

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

Source	Code	Description
ATC	A07DA01	ALIMENTARY TRACT AND METABOLISM ANTIDIARRHEALS, INTESTINAL ANTIINFLAMMATORY/ANTIINFECTIVE AGENTS ANTIPROPULSIVES Antipropulsives
CHEBI has role	CHEBI:55323	antidiarrheal drug
MeSH PA	D000700	Analgesics
MeSH PA	D000701	Analgesics, Opioid
MeSH PA	D000930	Antidiarrheals
MeSH PA	D002491	Central Nervous System Agents
MeSH PA	D002492	Central Nervous System Depressants
MeSH PA	D005765	Gastrointestinal Agents
MeSH PA	D009294	Narcotics
MeSH PA	D018373	Peripheral Nervous System Agents
MeSH PA	D018689	Sensory System Agents
FDA EPC	N0000178374	Antidiarrheal

Drug Use | Suggest Off label Use Form| |View source of the data|

Disease	Relation	SNOMED_ID	DOID
Diarrhea	indication	62315008
Chemotherapy-Induced Diarrhea	off-label use
Alcoholism	contraindication	7200002
Severe chronic ulcerative colitis	contraindication	14311001
Infectious diarrheal disease	contraindication	19213003	DOID:13250
Dehydration	contraindication	34095006
Shigellosis	contraindication	36188001
Hepatorenal syndrome	contraindication	51292008	DOID:11823
Obstructive hyperbilirubinemia	contraindication	59848001
Drug AND/OR toxin-induced diarrhea	contraindication	65979008
Kidney disease	contraindication	90708001	DOID:557
Disease of liver	contraindication	235856003	DOID:409
Angle-closure glaucoma	contraindication	392291006	DOID:13550
Pseudomembranous enterocolitis	contraindication	397683000
Gastroenteritis due to Salmonella	contraindication
Diarrhea due to E. Coli	contraindication

🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	6.82	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])	Mechanism action	Bioact source	MoA source
Mu-type opioid receptor	GPCR	P35372	OPRM_HUMAN	AGONIST	IC50	7.17		WOMBAT-PK	CHEMBL
Potassium voltage-gated channel subfamily A member 3	Ion channel	P22001	KCNA3_HUMAN		IC50	5.30		CHEMBL

External reference:

ID	Source
4019726	VUID
N0000147818	NUI
D03860	KEGG_DRUG
3810-80-8	SECONDARY_CAS_RN
3500	RXNORM
4017877	VANDF
4019726	VANDF
C0012525	UMLSCUI
CHEBI:4639	CHEBI
CHEMBL1201294	ChEMBL_ID
CHEMBL1200665	ChEMBL_ID
D004157	MESH_DESCRIPTOR_UI
DB01081	DRUGBANK_ID
7164	IUPHAR_LIGAND_ID
850	INN_ID
73312P173G	UNII
13505	PUBCHEM_CID
4613	MMSL
d03071	MMSL
001153	NDDF
004544	NDDF
15052009	SNOMEDCT_US
440585000	SNOMEDCT_US
71563009	SNOMEDCT_US

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Lomotil	HUMAN PRESCRIPTION DRUG LABEL	2	0025-0061	TABLET	2.50 mg	ORAL	NDA	23 sections
Lomotil	HUMAN PRESCRIPTION DRUG LABEL	2	0025-0061	TABLET	2.50 mg	ORAL	NDA	23 sections
Lomotil	HUMAN PRESCRIPTION DRUG LABEL	2	0025-0061	TABLET	2.50 mg	ORAL	NDA	23 sections
Diphenoxylate Hydrochloride and Atropine Sulfate	HUMAN PRESCRIPTION DRUG LABEL	2	0054-3194	SOLUTION	2.50 mg	ORAL	ANDA	21 sections
Diphenoxylate Hydrochloride and Atropine Sulfate	HUMAN PRESCRIPTION DRUG LABEL	2	0054-3194	SOLUTION	2.50 mg	ORAL	ANDA	21 sections
Diphenoxylate Hydrochloride and Atropine Sulfate	HUMAN PRESCRIPTION DRUG LABEL	2	0378-0415	TABLET	2.50 mg	ORAL	ANDA	20 sections
Diphenoxylate Hydrochloride and Atropine Sulfate	HUMAN PRESCRIPTION DRUG LABEL	2	0406-1236	TABLET	2.50 mg	ORAL	ANDA	23 sections
Diphenoxylate Hydrochloride and Atropine Sulfate	HUMAN PRESCRIPTION DRUG LABEL	2	0406-1236	TABLET	2.50 mg	ORAL	ANDA	23 sections
DIPHENOXYLATE HYDROCHLORIDE AND ATROPINE SULFATE	HUMAN PRESCRIPTION DRUG LABEL	2	0527-1170	TABLET	2.50 mg	ORAL	ANDA	12 sections
DIPHENOXYLATE HYDROCHLORIDE AND ATROPINE SULFATE	HUMAN PRESCRIPTION DRUG LABEL	2	0527-1170	TABLET	2.50 mg	ORAL	ANDA	12 sections
Diphenoxylate hydrochloride and atropine sulfate	HUMAN PRESCRIPTION DRUG LABEL	2	0832-0590	TABLET	2.50 mg	ORAL	ANDA	21 sections
Diphenoxylate hydrochloride and atropine sulfate	HUMAN PRESCRIPTION DRUG LABEL	2	0832-0590	TABLET	2.50 mg	ORAL	ANDA	21 sections
Diphenoxylate Hydrochloride and Atropine Sulfate	HUMAN PRESCRIPTION DRUG LABEL	2	12634-531	TABLET	2.50 mg	ORAL	ANDA	21 sections
Diphenoxylate Hcl and Atropine Sulfate	HUMAN PRESCRIPTION DRUG LABEL	2	16590-080	TABLET	2.50 mg	ORAL	ANDA	13 sections
Diphenoxylate Hydrochloride and Atropine Sulfate	HUMAN PRESCRIPTION DRUG LABEL	2	17856-1061	TABLET	2.50 mg	ORAL	NDA AUTHORIZED GENERIC	23 sections
Diphenoxylate Hydrochloride and Atropine Sulfate	HUMAN PRESCRIPTION DRUG LABEL	2	17856-3194	SOLUTION	2.50 mg	ORAL	ANDA	20 sections
Diphenoxylate Hydrochloride and Atropine Sulfate	HUMAN PRESCRIPTION DRUG LABEL	2	21695-688	TABLET	2.50 mg	ORAL	ANDA	21 sections
Diphenoxylate Hydrochloride and Atropine Sulfate	HUMAN PRESCRIPTION DRUG LABEL	2	33261-685	TABLET	2.50 mg	ORAL	ANDA	21 sections
Diphenoxylate Hydrochloride and Atropine Sulfate	HUMAN PRESCRIPTION DRUG LABEL	2	43063-089	TABLET	2.50 mg	ORAL	ANDA	20 sections
Diphenoxylate hydrochloride and atropine sulfate	HUMAN PRESCRIPTION DRUG LABEL	2	43063-957	TABLET	2.50 mg	ORAL	ANDA	21 sections
Diphenoxylate hydrochloride and atropine sulfate	HUMAN PRESCRIPTION DRUG LABEL	2	43063-957	TABLET	2.50 mg	ORAL	ANDA	21 sections
Diphenoxylate hydrochloride and atropine sulfate	HUMAN PRESCRIPTION DRUG LABEL	2	43063-957	TABLET	2.50 mg	ORAL	ANDA	21 sections
Diphenoxylate Hydrochloride and Atropine Sulfate	HUMAN PRESCRIPTION DRUG LABEL	2	43353-083	TABLET	2.50 mg	ORAL	NDA AUTHORIZED GENERIC	23 sections
Diphenoxylate Hydrochloride and Atropine Sulfate	HUMAN PRESCRIPTION DRUG LABEL	2	43353-594	TABLET	2.50 mg	ORAL	ANDA	21 sections
Diphenoxylate Hydrochloride and Atropine Sulfate	HUMAN PRESCRIPTION DRUG LABEL	2	49884-771	TABLET	2.50 mg	ORAL	ANDA	20 sections
Diphenoxylate Hydrochloride and Atropine Sulfate	HUMAN PRESCRIPTION DRUG LABEL	2	50090-0039	TABLET	2.50 mg	ORAL	ANDA	20 sections
Diphenoxylate Hydrochloride and Atropine Sulfate	HUMAN PRESCRIPTION DRUG LABEL	2	50090-0040	TABLET	2.50 mg	ORAL	ANDA	20 sections
Diphenoxylate Hydrochloride and Atropine Sulfate	HUMAN PRESCRIPTION DRUG LABEL	2	50090-2641	TABLET	2.50 mg	ORAL	NDA AUTHORIZED GENERIC	23 sections
Diphenoxylate Hydrochloride and Atropine Sulfate	HUMAN PRESCRIPTION DRUG LABEL	2	50090-2872	TABLET	2.50 mg	ORAL	NDA AUTHORIZED GENERIC	23 sections
Diphenoxylate Hydrochloride and Atropine Sulfate	HUMAN PRESCRIPTION DRUG LABEL	2	50090-3452	TABLET	2.50 mg	ORAL	ANDA	19 sections