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Identification
NameDifenoxin
Accession NumberDB01501
TypeSmall Molecule
GroupsApproved, Illicit
DescriptionDifenoxin is a 4-phenylpiperidine which is closely related to the opioid analgesic meperidine. Difenoxin alone is a USA Schedule I controlled drug, as it may be habit forming. However, it is listed as a Schedule IV controlled drug if combined with atropine, which is added to decrease deliberate misuse. Motofen(R) is a brand mixture which combines atropine sulfate and difenoxin hydrochloride. It is approved by the FDA to treat acute and chronic diarrhea. Difenoxin is an active metabolite of the anti-diarrheal drug, diphenoxylate, which is also used in combination with atropine in the brand mixture Lomotil(R). It works mostly in the periphery and activates opioid receptors in the intestine rather than the central nervous system (CNS). [3] Difenoxin is also closely related to loperamide, but unlike loperamide it is still capable of crossing the blood brain barrier to produce weak sedative and analgesic effects. However, the antidiarrheal potency of difenoxin is much greater than its CNS effects, which makes it an attractive alternative to other opioids.
Structure
Thumb
Synonyms
1-(3-Cyano-3,3-diphenylpropyl)-4-phenylisonipecotic acid
Difenoxin
Difenoxina
Difenoxinum
Diphenoxilic acid
Diphenoxin
Diphenoxylic acid
External Identifiers
  • McN-JR 15403-11
  • R-15403
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
LyspafenJanssen
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Difenoxin hydrochloride
35607-36-4
Thumb
  • InChI Key: VMIZTXDGZPTKIK-UHFFFAOYSA-N
  • Monoisotopic Mass: 460.191755889
  • Average Mass: 460.995
DBSALT000047
Categories
UNII3ZZ5BJ9F2Q
CAS number28782-42-5
WeightAverage: 424.5341
Monoisotopic: 424.21507815
Chemical FormulaC28H28N2O2
InChI KeyInChIKey=UFIVBRCCIRTJTN-UHFFFAOYSA-N
InChI
InChI=1S/C28H28N2O2/c29-22-28(24-12-6-2-7-13-24,25-14-8-3-9-15-25)18-21-30-19-16-27(17-20-30,26(31)32)23-10-4-1-5-11-23/h1-15H,16-21H2,(H,31,32)
IUPAC Name
1-(3-cyano-3,3-diphenylpropyl)-4-phenylpiperidine-4-carboxylic acid
SMILES
OC(=O)C1(CCN(CCC(C#N)(C2=CC=CC=C2)C2=CC=CC=C2)CC1)C1=CC=CC=C1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as diphenylacetonitriles. These are cyclic aromatic compounds containing a diphenylacetonitrile moiety, which consists of a diphenylmethane linked to and acetonitrile to form 2,2-diphenylacetonitrile.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassDiphenylacetonitriles
Direct ParentDiphenylacetonitriles
Alternative Parents
Substituents
  • Diphenylacetonitrile
  • Diphenylmethane
  • Phenylpiperidine
  • Phenylpropylamine
  • Phenylacetate
  • Piperidinecarboxylic acid
  • Benzyl-cyanide
  • Aralkylamine
  • Piperidine
  • Tertiary aliphatic amine
  • Tertiary amine
  • Azacycle
  • Organoheterocyclic compound
  • Nitrile
  • Carbonitrile
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Pharmacology
IndicationMotofen(R) is a combination of atropine, an anticholinergic drug, and difenoxin, an antidiarrheal drug. It has been used in many countries for many years as a second line opioid-agonist antidiarrheal, which exists an intermediate between loperamide and paragoric. [2] Diarrhea which is a result of cyclic or diarrhea predominant Inflammatory Bowel Syndrome may not be treated effectively with difenoxin, diphenoxylate, or loperamide. As such, diarrhea and cramping which does not respond to non-centrally acting derivatives or belladonna derivatives such as atropine are often treated with conservative doses of codeine. In patients with acute ulcerative colitis, as induction of toxic megacolon is possible, and thus use of Motofen(R) is cautioned. Motofen(R) has been assigned pregnancy category C by the FDA, and is to be used only when the potential benefits outweigh the potential risk to the fetus. The safety of use during lactation is unknown and thus not recommended.
PharmacodynamicsDifenoxin acts as a potent antidiarrheal by slowing the movement of the intestines. It also crosses the blood brain barrier to a slight degree to exert weak sedative and analgesic effects. Adverse reactions thus include dizziness, drowsiness, lightheadedness and headache, in addition to gastrointestal side effects such as nausea, vomiting, dry mouth and epigastric distress. [Lexicomp, 2013]
Mechanism of actionDifenoxin acts as an antidiarrheal by activating peripheral opioid receptors in the small intestine and thereby inhibiting peristalsis. However, research has suggested that non-opioid receptor pathways exist. This would explain the potent antidiarrheal effects of difenoxin despite only limited opioid action [1].
Related Articles
AbsorptionA high percentage of Motofen(R) is absorbed, and absorption occurs rapidly. Peak plasma concentrations are achieved within 40-60 minutes. [Lexicomp, 2013]
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Metabolism occurs by hydroxylation to form an inactive metabolite. [Lexicomp, 2013]

Route of eliminationBoth the drug and its metabolites are excreted, mainly as conjugates, in urine and feces. [Lexicomp, 2012]
Half lifeThe elimination half life was calculated to be 7.24 hours. The appearance half life was calculated to be 0.82h. [3]
ClearanceNot Available
ToxicityNot Available
Affected organismsNot Available
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9182
Blood Brain Barrier+0.8984
Caco-2 permeable+0.507
P-glycoprotein substrateSubstrate0.6311
P-glycoprotein inhibitor INon-inhibitor0.7353
P-glycoprotein inhibitor IIInhibitor0.5519
Renal organic cation transporterInhibitor0.6229
CYP450 2C9 substrateNon-substrate0.8171
CYP450 2D6 substrateNon-substrate0.6612
CYP450 3A4 substrateNon-substrate0.6411
CYP450 1A2 substrateNon-inhibitor0.8832
CYP450 2C9 inhibitorNon-inhibitor0.8628
CYP450 2D6 inhibitorNon-inhibitor0.6599
CYP450 2C19 inhibitorNon-inhibitor0.8411
CYP450 3A4 inhibitorNon-inhibitor0.6724
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9199
Ames testNon AMES toxic0.8242
CarcinogenicityNon-carcinogens0.9211
BiodegradationNot ready biodegradable0.9849
Rat acute toxicity3.4236 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.827
hERG inhibition (predictor II)Non-inhibitor0.6311
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.00208 mg/mLALOGPS
logP4.39ALOGPS
logP2.65ChemAxon
logS-5.3ALOGPS
pKa (Strongest Acidic)3.38ChemAxon
pKa (Strongest Basic)9.41ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area64.33 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity137.24 m3·mol-1ChemAxon
Polarizability47.56 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Download (7.02 KB)
SpectraNot Available
References
Synthesis Reference

Soudyn, W. and van Wijngaarden, I.; US. Patent 3,646,207; February 29,1972; assigned to
Janssen Pharrnaceutica, N.V. (Belgium).

General References
  1. De Luca A, Coupar IM: Difenoxin and loperamide: studies on possible mechanisms of intestinal antisecretory action. Naunyn Schmiedebergs Arch Pharmacol. 1993 Feb;347(2):231-7. [PubMed:8386327 ]
  2. Innocenti P, Rossi L, Bombardieri G: [Clinical effectiveness of difenoxine in patients with acute and chronic diarrhea]. Boll Chim Farm. 1983 Dec;122(12):64S-68S. [PubMed:6675727 ]
  3. Jackson LS, Stafford JE: The evaluation and application of a radioimmunoassay for the measurement of diphenoxylic acid, the major metabolite of diphenoxylate hydrochloride (Lomotil), in human plasma. J Pharmacol Methods. 1987 Nov;18(3):189-97. [PubMed:3682841 ]
External Links
ATC CodesA07DA04
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
7-NitroindazoleThe risk or severity of adverse effects can be increased when 7-Nitroindazole is combined with Difenoxin.
AcepromazineThe risk or severity of adverse effects can be increased when Acepromazine is combined with Difenoxin.
AceprometazineThe risk or severity of adverse effects can be increased when Aceprometazine is combined with Difenoxin.
adipiplonThe risk or severity of adverse effects can be increased when adipiplon is combined with Difenoxin.
AgomelatineThe risk or severity of adverse effects can be increased when Agomelatine is combined with Difenoxin.
AlfaxaloneThe risk or severity of adverse effects can be increased when Alfaxalone is combined with Difenoxin.
AlfentanilThe risk or severity of adverse effects can be increased when Alfentanil is combined with Difenoxin.
AlphacetylmethadolThe risk or severity of adverse effects can be increased when Alphacetylmethadol is combined with Difenoxin.
AlprazolamThe risk or severity of adverse effects can be increased when Alprazolam is combined with Difenoxin.
AmisulprideThe risk or severity of adverse effects can be increased when Amisulpride is combined with Difenoxin.
AmitriptylineThe risk or severity of adverse effects can be increased when Amitriptyline is combined with Difenoxin.
AmobarbitalThe risk or severity of adverse effects can be increased when Amobarbital is combined with Difenoxin.
AmoxapineThe risk or severity of adverse effects can be increased when Difenoxin is combined with Amoxapine.
AmperozideThe risk or severity of adverse effects can be increased when Amperozide is combined with Difenoxin.
AripiprazoleThe risk or severity of adverse effects can be increased when Aripiprazole is combined with Difenoxin.
ArticaineThe risk or severity of adverse effects can be increased when Articaine is combined with Difenoxin.
AsenapineThe risk or severity of adverse effects can be increased when Asenapine is combined with Difenoxin.
AzaperoneThe risk or severity of adverse effects can be increased when Azaperone is combined with Difenoxin.
AzelastineDifenoxin may increase the central nervous system depressant (CNS depressant) activities of Azelastine.
AzelastineThe risk or severity of adverse effects can be increased when Azelastine is combined with Difenoxin.
BaclofenThe risk or severity of adverse effects can be increased when Baclofen is combined with Difenoxin.
BarbitalThe risk or severity of adverse effects can be increased when Barbital is combined with Difenoxin.
BenzocaineThe risk or severity of adverse effects can be increased when Benzocaine is combined with Difenoxin.
Benzyl alcoholThe risk or severity of adverse effects can be increased when Benzyl alcohol is combined with Difenoxin.
BrexpiprazoleThe risk or severity of adverse effects can be increased when Difenoxin is combined with Brexpiprazole.
BrimonidineBrimonidine may increase the central nervous system depressant (CNS depressant) activities of Difenoxin.
BrimonidineThe risk or severity of adverse effects can be increased when Difenoxin is combined with Brimonidine.
BromazepamThe risk or severity of adverse effects can be increased when Bromazepam is combined with Difenoxin.
BrompheniramineThe risk or severity of adverse effects can be increased when Brompheniramine is combined with Difenoxin.
BrotizolamThe risk or severity of adverse effects can be increased when Brotizolam is combined with Difenoxin.
BupivacaineThe risk or severity of adverse effects can be increased when Bupivacaine is combined with Difenoxin.
BuprenorphineThe risk or severity of adverse effects can be increased when Buprenorphine is combined with Difenoxin.
BuspironeThe risk or severity of adverse effects can be increased when Buspirone is combined with Difenoxin.
ButabarbitalThe risk or severity of adverse effects can be increased when Butabarbital is combined with Difenoxin.
ButacaineThe risk or severity of adverse effects can be increased when Butacaine is combined with Difenoxin.
ButalbitalThe risk or severity of adverse effects can be increased when Butalbital is combined with Difenoxin.
ButambenThe risk or severity of adverse effects can be increased when Butamben is combined with Difenoxin.
ButethalThe risk or severity of adverse effects can be increased when Butethal is combined with Difenoxin.
ButorphanolThe risk or severity of adverse effects can be increased when Butorphanol is combined with Difenoxin.
CarbamazepineThe risk or severity of adverse effects can be increased when Carbamazepine is combined with Difenoxin.
CarbinoxamineThe risk or severity of adverse effects can be increased when Carbinoxamine is combined with Difenoxin.
CarfentanilThe risk or severity of adverse effects can be increased when Carfentanil is combined with Difenoxin.
CarisoprodolThe risk or severity of adverse effects can be increased when Carisoprodol is combined with Difenoxin.
CetirizineThe risk or severity of adverse effects can be increased when Cetirizine is combined with Difenoxin.
Chloral hydrateThe risk or severity of adverse effects can be increased when Chloral hydrate is combined with Difenoxin.
ChlordiazepoxideThe risk or severity of adverse effects can be increased when Chlordiazepoxide is combined with Difenoxin.
ChlormezanoneThe risk or severity of adverse effects can be increased when Chlormezanone is combined with Difenoxin.
ChloroprocaineThe risk or severity of adverse effects can be increased when Chloroprocaine is combined with Difenoxin.
ChlorphenamineThe risk or severity of adverse effects can be increased when Chlorphenamine is combined with Difenoxin.
ChlorpromazineThe risk or severity of adverse effects can be increased when Chlorpromazine is combined with Difenoxin.
ChlorprothixeneThe risk or severity of adverse effects can be increased when Chlorprothixene is combined with Difenoxin.
ChlorzoxazoneThe risk or severity of adverse effects can be increased when Chlorzoxazone is combined with Difenoxin.
CinchocaineThe risk or severity of adverse effects can be increased when Cinchocaine is combined with Difenoxin.
CitalopramThe risk or severity of adverse effects can be increased when Difenoxin is combined with Citalopram.
ClemastineThe risk or severity of adverse effects can be increased when Clemastine is combined with Difenoxin.
ClidiniumThe risk or severity of adverse effects can be increased when Clidinium is combined with Difenoxin.
ClobazamThe risk or severity of adverse effects can be increased when Clobazam is combined with Difenoxin.
clomethiazoleThe risk or severity of adverse effects can be increased when clomethiazole is combined with Difenoxin.
ClomipramineThe risk or severity of adverse effects can be increased when Difenoxin is combined with Clomipramine.
ClonazepamThe risk or severity of adverse effects can be increased when Clonazepam is combined with Difenoxin.
ClonidineThe risk or severity of adverse effects can be increased when Clonidine is combined with Difenoxin.
ClorazepateThe risk or severity of adverse effects can be increased when Clorazepate is combined with Difenoxin.
ClozapineThe risk or severity of adverse effects can be increased when Clozapine is combined with Difenoxin.
CocaineThe risk or severity of adverse effects can be increased when Cocaine is combined with Difenoxin.
CodeineThe risk or severity of adverse effects can be increased when Codeine is combined with Difenoxin.
CyclizineThe risk or severity of adverse effects can be increased when Cyclizine is combined with Difenoxin.
CyclobenzaprineThe risk or severity of adverse effects can be increased when Cyclobenzaprine is combined with Difenoxin.
CyproheptadineThe risk or severity of adverse effects can be increased when Cyproheptadine is combined with Difenoxin.
DantroleneThe risk or severity of adverse effects can be increased when Dantrolene is combined with Difenoxin.
DapiprazoleThe risk or severity of adverse effects can be increased when Dapiprazole is combined with Difenoxin.
DapoxetineThe risk or severity of adverse effects can be increased when Difenoxin is combined with Dapoxetine.
deramciclaneThe risk or severity of adverse effects can be increased when deramciclane is combined with Difenoxin.
DesfluraneThe risk or severity of adverse effects can be increased when Desflurane is combined with Difenoxin.
DesipramineThe risk or severity of adverse effects can be increased when Desipramine is combined with Difenoxin.
DesloratadineThe risk or severity of adverse effects can be increased when Desloratadine is combined with Difenoxin.
DetomidineThe risk or severity of adverse effects can be increased when Detomidine is combined with Difenoxin.
DexbrompheniramineThe risk or severity of adverse effects can be increased when Dexbrompheniramine is combined with Difenoxin.
DexmedetomidineThe risk or severity of adverse effects can be increased when Dexmedetomidine is combined with Difenoxin.
DextromoramideThe risk or severity of adverse effects can be increased when Dextromoramide is combined with Difenoxin.
DextropropoxypheneThe risk or severity of adverse effects can be increased when Dextropropoxyphene is combined with Difenoxin.
DezocineThe risk or severity of adverse effects can be increased when Dezocine is combined with Difenoxin.
DiazepamThe risk or severity of adverse effects can be increased when Diazepam is combined with Difenoxin.
DihydrocodeineThe risk or severity of adverse effects can be increased when Dihydrocodeine is combined with Difenoxin.
DihydroetorphineThe risk or severity of adverse effects can be increased when Dihydroetorphine is combined with Difenoxin.
DihydromorphineThe risk or severity of adverse effects can be increased when Dihydromorphine is combined with Difenoxin.
DimenhydrinateThe risk or severity of adverse effects can be increased when Dimenhydrinate is combined with Difenoxin.
DiphenhydramineThe risk or severity of adverse effects can be increased when Diphenhydramine is combined with Difenoxin.
DiphenoxylateThe risk or severity of adverse effects can be increased when Diphenoxylate is combined with Difenoxin.
DoramectinThe risk or severity of adverse effects can be increased when Doramectin is combined with Difenoxin.
DoxepinThe risk or severity of adverse effects can be increased when Doxepin is combined with Difenoxin.
DoxylamineDoxylamine may increase the central nervous system depressant (CNS depressant) activities of Difenoxin.
DoxylamineThe risk or severity of adverse effects can be increased when Difenoxin is combined with Doxylamine.
DPDPEThe risk or severity of adverse effects can be increased when DPDPE is combined with Difenoxin.
DronabinolDronabinol may increase the central nervous system depressant (CNS depressant) activities of Difenoxin.
DroperidolThe risk or severity of adverse effects can be increased when Droperidol is combined with Difenoxin.
DrotebanolThe risk or severity of adverse effects can be increased when Drotebanol is combined with Difenoxin.
DyclonineThe risk or severity of adverse effects can be increased when Dyclonine is combined with Difenoxin.
EcgonineThe risk or severity of adverse effects can be increased when Ecgonine is combined with Difenoxin.
ECGONINE METHYL ESTERThe risk or severity of adverse effects can be increased when ECGONINE METHYL ESTER is combined with Difenoxin.
EfavirenzThe risk or severity of adverse effects can be increased when Efavirenz is combined with Difenoxin.
EnfluraneThe risk or severity of adverse effects can be increased when Enflurane is combined with Difenoxin.
EntacaponeThe risk or severity of adverse effects can be increased when Entacapone is combined with Difenoxin.
EscitalopramThe risk or severity of adverse effects can be increased when Difenoxin is combined with Escitalopram.
EstazolamThe risk or severity of adverse effects can be increased when Estazolam is combined with Difenoxin.
EszopicloneThe risk or severity of adverse effects can be increased when Eszopiclone is combined with Difenoxin.
EthanolDifenoxin may increase the central nervous system depressant (CNS depressant) activities of Ethanol.
EthanolThe risk or severity of adverse effects can be increased when Ethanol is combined with Difenoxin.
EthchlorvynolThe risk or severity of adverse effects can be increased when Ethchlorvynol is combined with Difenoxin.
EthosuximideThe risk or severity of adverse effects can be increased when Ethosuximide is combined with Difenoxin.
EthotoinThe risk or severity of adverse effects can be increased when Ethotoin is combined with Difenoxin.
Ethyl carbamateThe risk or severity of adverse effects can be increased when Ethyl carbamate is combined with Difenoxin.
Ethyl loflazepateThe risk or severity of adverse effects can be increased when Ethyl loflazepate is combined with Difenoxin.
EthylmorphineThe risk or severity of adverse effects can be increased when Ethylmorphine is combined with Difenoxin.
EtidocaineThe risk or severity of adverse effects can be increased when Etidocaine is combined with Difenoxin.
EtifoxineThe risk or severity of adverse effects can be increased when Etifoxine is combined with Difenoxin.
EtizolamThe risk or severity of adverse effects can be increased when Etizolam is combined with Difenoxin.
EtomidateThe risk or severity of adverse effects can be increased when Etomidate is combined with Difenoxin.
EtoperidoneThe risk or severity of adverse effects can be increased when Difenoxin is combined with Etoperidone.
EtorphineThe risk or severity of adverse effects can be increased when Etorphine is combined with Difenoxin.
EzogabineThe risk or severity of adverse effects can be increased when Difenoxin is combined with Ezogabine.
FelbamateThe risk or severity of adverse effects can be increased when Felbamate is combined with Difenoxin.
FencamfamineThe risk or severity of adverse effects can be increased when Fencamfamine is combined with Difenoxin.
FenfluramineThe risk or severity of adverse effects can be increased when Difenoxin is combined with Fenfluramine.
FentanylThe risk or severity of adverse effects can be increased when Fentanyl is combined with Difenoxin.
FexofenadineThe risk or severity of adverse effects can be increased when Fexofenadine is combined with Difenoxin.
FlibanserinThe risk or severity of adverse effects can be increased when Difenoxin is combined with Flibanserin.
FludiazepamThe risk or severity of adverse effects can be increased when Fludiazepam is combined with Difenoxin.
FlunarizineThe risk or severity of adverse effects can be increased when Difenoxin is combined with Flunarizine.
FlunitrazepamThe risk or severity of adverse effects can be increased when Flunitrazepam is combined with Difenoxin.
FluoxetineThe risk or severity of adverse effects can be increased when Difenoxin is combined with Fluoxetine.
FlupentixolThe risk or severity of adverse effects can be increased when Flupentixol is combined with Difenoxin.
FluphenazineThe risk or severity of adverse effects can be increased when Fluphenazine is combined with Difenoxin.
FlurazepamThe risk or severity of adverse effects can be increased when Flurazepam is combined with Difenoxin.
FluspirileneThe risk or severity of adverse effects can be increased when Fluspirilene is combined with Difenoxin.
Fluticasone PropionateThe risk or severity of adverse effects can be increased when Fluticasone Propionate is combined with Difenoxin.
FluvoxamineThe risk or severity of adverse effects can be increased when Difenoxin is combined with Fluvoxamine.
FosphenytoinThe risk or severity of adverse effects can be increased when Fosphenytoin is combined with Difenoxin.
FospropofolThe risk or severity of adverse effects can be increased when Fospropofol is combined with Difenoxin.
GabapentinThe risk or severity of adverse effects can be increased when Gabapentin is combined with Difenoxin.
gabapentin enacarbilThe risk or severity of adverse effects can be increased when Difenoxin is combined with gabapentin enacarbil.
Gamma Hydroxybutyric AcidThe risk or severity of adverse effects can be increased when Gamma Hydroxybutyric Acid is combined with Difenoxin.
GlutethimideThe risk or severity of adverse effects can be increased when Glutethimide is combined with Difenoxin.
GuanfacineThe risk or severity of adverse effects can be increased when Guanfacine is combined with Difenoxin.
HalazepamThe risk or severity of adverse effects can be increased when Halazepam is combined with Difenoxin.
HaloperidolThe risk or severity of adverse effects can be increased when Haloperidol is combined with Difenoxin.
HalothaneThe risk or severity of adverse effects can be increased when Halothane is combined with Difenoxin.
HeroinThe risk or severity of adverse effects can be increased when Heroin is combined with Difenoxin.
HexobarbitalThe risk or severity of adverse effects can be increased when Hexobarbital is combined with Difenoxin.
HydrocodoneThe risk or severity of adverse effects can be increased when Hydrocodone is combined with Difenoxin.
HydromorphoneThe risk or severity of adverse effects can be increased when Hydromorphone is combined with Difenoxin.
HydroxyzineHydroxyzine may increase the central nervous system depressant (CNS depressant) activities of Difenoxin.
HydroxyzineThe risk or severity of adverse effects can be increased when Difenoxin is combined with Hydroxyzine.
IloperidoneThe risk or severity of adverse effects can be increased when Difenoxin is combined with Iloperidone.
ImipramineThe risk or severity of adverse effects can be increased when Imipramine is combined with Difenoxin.
IndalpineThe risk or severity of adverse effects can be increased when Difenoxin is combined with Indalpine.
IsofluraneThe risk or severity of adverse effects can be increased when Isoflurane is combined with Difenoxin.
KetamineThe risk or severity of adverse effects can be increased when Ketamine is combined with Difenoxin.
KetazolamThe risk or severity of adverse effects can be increased when Ketazolam is combined with Difenoxin.
KetobemidoneThe risk or severity of adverse effects can be increased when Ketobemidone is combined with Difenoxin.
LamotrigineThe risk or severity of adverse effects can be increased when Lamotrigine is combined with Difenoxin.
LevetiracetamThe risk or severity of adverse effects can be increased when Levetiracetam is combined with Difenoxin.
LevobupivacaineThe risk or severity of adverse effects can be increased when Levobupivacaine is combined with Difenoxin.
LevocabastineThe risk or severity of adverse effects can be increased when Levocabastine is combined with Difenoxin.
LevocetirizineThe risk or severity of adverse effects can be increased when Difenoxin is combined with Levocetirizine.
LevodopaThe risk or severity of adverse effects can be increased when Levodopa is combined with Difenoxin.
Levomethadyl AcetateThe risk or severity of adverse effects can be increased when Levomethadyl Acetate is combined with Difenoxin.
LevomilnacipranThe risk or severity of adverse effects can be increased when Difenoxin is combined with Levomilnacipran.
LevorphanolThe risk or severity of adverse effects can be increased when Levorphanol is combined with Difenoxin.
LidocaineThe risk or severity of adverse effects can be increased when Lidocaine is combined with Difenoxin.
LithiumThe risk or severity of adverse effects can be increased when Lithium is combined with Difenoxin.
LofentanilThe risk or severity of adverse effects can be increased when Lofentanil is combined with Difenoxin.
LoratadineThe risk or severity of adverse effects can be increased when Loratadine is combined with Difenoxin.
LorazepamThe risk or severity of adverse effects can be increased when Lorazepam is combined with Difenoxin.
LoxapineThe risk or severity of adverse effects can be increased when Loxapine is combined with Difenoxin.
Lu AA21004The risk or severity of adverse effects can be increased when Difenoxin is combined with Lu AA21004.
LurasidoneThe risk or severity of adverse effects can be increased when Lurasidone is combined with Difenoxin.
Magnesium SulfateMagnesium Sulfate may increase the central nervous system depressant (CNS depressant) activities of Difenoxin.
Magnesium SulfateThe risk or severity of adverse effects can be increased when Difenoxin is combined with Magnesium Sulfate.
MaprotilineThe risk or severity of adverse effects can be increased when Maprotiline is combined with Difenoxin.
MeclizineThe risk or severity of adverse effects can be increased when Meclizine is combined with Difenoxin.
MedetomidineThe risk or severity of adverse effects can be increased when Medetomidine is combined with Difenoxin.
MelatoninThe risk or severity of adverse effects can be increased when Melatonin is combined with Difenoxin.
MelperoneThe risk or severity of adverse effects can be increased when Melperone is combined with Difenoxin.
MepivacaineThe risk or severity of adverse effects can be increased when Mepivacaine is combined with Difenoxin.
MeprobamateThe risk or severity of adverse effects can be increased when Meprobamate is combined with Difenoxin.
MesoridazineThe risk or severity of adverse effects can be increased when Mesoridazine is combined with Difenoxin.
MetaxaloneThe risk or severity of adverse effects can be increased when Metaxalone is combined with Difenoxin.
MethadoneThe risk or severity of adverse effects can be increased when Methadone is combined with Difenoxin.
Methadyl AcetateThe risk or severity of adverse effects can be increased when Methadyl Acetate is combined with Difenoxin.
MethapyrileneThe risk or severity of adverse effects can be increased when Methapyrilene is combined with Difenoxin.
MethaqualoneThe risk or severity of adverse effects can be increased when Methaqualone is combined with Difenoxin.
MethocarbamolThe risk or severity of adverse effects can be increased when Methocarbamol is combined with Difenoxin.
MethohexitalThe risk or severity of adverse effects can be increased when Methohexital is combined with Difenoxin.
MethotrimeprazineThe risk or severity of adverse effects can be increased when Methotrimeprazine is combined with Difenoxin.
MethoxyfluraneThe risk or severity of adverse effects can be increased when Methoxyflurane is combined with Difenoxin.
MethsuximideThe risk or severity of adverse effects can be increased when Difenoxin is combined with Methsuximide.
MethylphenobarbitalThe risk or severity of adverse effects can be increased when Methylphenobarbital is combined with Difenoxin.
MetyrosineDifenoxin may increase the sedative activities of Metyrosine.
MidazolamThe risk or severity of adverse effects can be increased when Midazolam is combined with Difenoxin.
MilnacipranThe risk or severity of adverse effects can be increased when Difenoxin is combined with Milnacipran.
MinocyclineMinocycline may increase the central nervous system depressant (CNS depressant) activities of Difenoxin.
MirtazapineDifenoxin may increase the central nervous system depressant (CNS depressant) activities of Mirtazapine.
MirtazapineThe risk or severity of adverse effects can be increased when Mirtazapine is combined with Difenoxin.
MolindoneThe risk or severity of adverse effects can be increased when Molindone is combined with Difenoxin.
MorphineThe risk or severity of adverse effects can be increased when Morphine is combined with Difenoxin.
NabiloneNabilone may increase the central nervous system depressant (CNS depressant) activities of Difenoxin.
NabiloneThe risk or severity of adverse effects can be increased when Difenoxin is combined with Nabilone.
NalbuphineThe risk or severity of adverse effects can be increased when Nalbuphine is combined with Difenoxin.
NitrazepamThe risk or severity of adverse effects can be increased when Nitrazepam is combined with Difenoxin.
Nitrous oxideThe risk or severity of adverse effects can be increased when Nitrous oxide is combined with Difenoxin.
NormethadoneThe risk or severity of adverse effects can be increased when Normethadone is combined with Difenoxin.
NortriptylineThe risk or severity of adverse effects can be increased when Nortriptyline is combined with Difenoxin.
OlanzapineThe risk or severity of adverse effects can be increased when Difenoxin is combined with Olanzapine.
OlopatadineThe risk or severity of adverse effects can be increased when Olopatadine is combined with Difenoxin.
OndansetronThe risk or severity of adverse effects can be increased when Ondansetron is combined with Difenoxin.
OpiumThe risk or severity of adverse effects can be increased when Opium is combined with Difenoxin.
OrphenadrineDifenoxin may increase the central nervous system depressant (CNS depressant) activities of Orphenadrine.
OrphenadrineThe risk or severity of adverse effects can be increased when Orphenadrine is combined with Difenoxin.
OsanetantThe risk or severity of adverse effects can be increased when Osanetant is combined with Difenoxin.
OxazepamThe risk or severity of adverse effects can be increased when Oxazepam is combined with Difenoxin.
OxprenololThe risk or severity of adverse effects can be increased when Oxprenolol is combined with Difenoxin.
OxybuprocaineThe risk or severity of adverse effects can be increased when Oxybuprocaine is combined with Difenoxin.
OxycodoneThe risk or severity of adverse effects can be increased when Oxycodone is combined with Difenoxin.
OxymorphoneThe risk or severity of adverse effects can be increased when Oxymorphone is combined with Difenoxin.
PaliperidoneThe risk or severity of adverse effects can be increased when Paliperidone is combined with Difenoxin.
ParaldehydeDifenoxin may increase the central nervous system depressant (CNS depressant) activities of Paraldehyde.
ParaldehydeThe risk or severity of adverse effects can be increased when Paraldehyde is combined with Difenoxin.
ParoxetineThe risk or severity of adverse effects can be increased when Difenoxin is combined with Paroxetine.
PentazocineThe risk or severity of adverse effects can be increased when Pentazocine is combined with Difenoxin.
PentobarbitalThe risk or severity of adverse effects can be increased when Pentobarbital is combined with Difenoxin.
PerampanelThe risk or severity of adverse effects can be increased when Difenoxin is combined with Perampanel.
PerospironeThe risk or severity of adverse effects can be increased when Perospirone is combined with Difenoxin.
PerphenazineThe risk or severity of adverse effects can be increased when Perphenazine is combined with Difenoxin.
PethidineThe risk or severity of adverse effects can be increased when Pethidine is combined with Difenoxin.
PhenobarbitalThe risk or severity of adverse effects can be increased when Phenobarbital is combined with Difenoxin.
PhenoxyethanolThe risk or severity of adverse effects can be increased when Phenoxyethanol is combined with Difenoxin.
PhenytoinThe risk or severity of adverse effects can be increased when Phenytoin is combined with Difenoxin.
PimozideThe risk or severity of adverse effects can be increased when Pimozide is combined with Difenoxin.
PipamperoneThe risk or severity of adverse effects can be increased when Pipamperone is combined with Difenoxin.
PipotiazineThe risk or severity of adverse effects can be increased when Difenoxin is combined with Pipotiazine.
PizotifenThe risk or severity of adverse effects can be increased when Difenoxin is combined with Pizotifen.
PomalidomideThe risk or severity of adverse effects can be increased when Difenoxin is combined with Pomalidomide.
PramipexoleDifenoxin may increase the sedative activities of Pramipexole.
PramocaineThe risk or severity of adverse effects can be increased when Pramocaine is combined with Difenoxin.
PrazepamThe risk or severity of adverse effects can be increased when Prazepam is combined with Difenoxin.
PregabalinThe risk or severity of adverse effects can be increased when Pregabalin is combined with Difenoxin.
PrilocaineThe risk or severity of adverse effects can be increased when Prilocaine is combined with Difenoxin.
PrimidoneThe risk or severity of adverse effects can be increased when Primidone is combined with Difenoxin.
ProcaineThe risk or severity of adverse effects can be increased when Procaine is combined with Difenoxin.
ProchlorperazineThe risk or severity of adverse effects can be increased when Prochlorperazine is combined with Difenoxin.
PromazineThe risk or severity of adverse effects can be increased when Promazine is combined with Difenoxin.
PromethazineThe risk or severity of adverse effects can be increased when Promethazine is combined with Difenoxin.
ProparacaineThe risk or severity of adverse effects can be increased when Proparacaine is combined with Difenoxin.
PropofolThe risk or severity of adverse effects can be increased when Propofol is combined with Difenoxin.
PropoxycaineThe risk or severity of adverse effects can be increased when Propoxycaine is combined with Difenoxin.
ProtriptylineThe risk or severity of adverse effects can be increased when Protriptyline is combined with Difenoxin.
PSD502The risk or severity of adverse effects can be increased when PSD502 is combined with Difenoxin.
QuazepamThe risk or severity of adverse effects can be increased when Quazepam is combined with Difenoxin.
QuetiapineThe risk or severity of adverse effects can be increased when Quetiapine is combined with Difenoxin.
RamelteonThe risk or severity of adverse effects can be increased when Ramelteon is combined with Difenoxin.
RemifentanilThe risk or severity of adverse effects can be increased when Remifentanil is combined with Difenoxin.
RemoxiprideThe risk or severity of adverse effects can be increased when Remoxipride is combined with Difenoxin.
ReserpineThe risk or severity of adverse effects can be increased when Reserpine is combined with Difenoxin.
RisperidoneThe risk or severity of adverse effects can be increased when Risperidone is combined with Difenoxin.
RomifidineThe risk or severity of adverse effects can be increased when Romifidine is combined with Difenoxin.
RopiniroleDifenoxin may increase the sedative activities of Ropinirole.
RopivacaineThe risk or severity of adverse effects can be increased when Ropivacaine is combined with Difenoxin.
RotigotineDifenoxin may increase the sedative activities of Rotigotine.
RufinamideThe risk or severity of adverse effects can be increased when Rufinamide is combined with Difenoxin.
S-EthylisothioureaThe risk or severity of adverse effects can be increased when S-Ethylisothiourea is combined with Difenoxin.
ScopolamineThe risk or severity of adverse effects can be increased when Scopolamine is combined with Difenoxin.
SecobarbitalThe risk or severity of adverse effects can be increased when Secobarbital is combined with Difenoxin.
SertindoleThe risk or severity of adverse effects can be increased when Sertindole is combined with Difenoxin.
SertralineThe risk or severity of adverse effects can be increased when Difenoxin is combined with Sertraline.
SevofluraneThe risk or severity of adverse effects can be increased when Sevoflurane is combined with Difenoxin.
Sodium oxybateThe risk or severity of adverse effects can be increased when Sodium oxybate is combined with Difenoxin.
StiripentolThe risk or severity of adverse effects can be increased when Difenoxin is combined with Stiripentol.
SufentanilThe risk or severity of adverse effects can be increased when Sufentanil is combined with Difenoxin.
SulpirideThe risk or severity of adverse effects can be increased when Sulpiride is combined with Difenoxin.
SuvorexantThe risk or severity of adverse effects can be increased when Difenoxin is combined with Suvorexant.
TapentadolThe risk or severity of adverse effects can be increased when Difenoxin is combined with Tapentadol.
TasimelteonThe risk or severity of adverse effects can be increased when Difenoxin is combined with Tasimelteon.
TemazepamThe risk or severity of adverse effects can be increased when Temazepam is combined with Difenoxin.
TetrabenazineThe risk or severity of adverse effects can be increased when Difenoxin is combined with Tetrabenazine.
TetracaineThe risk or severity of adverse effects can be increased when Tetracaine is combined with Difenoxin.
TetrodotoxinThe risk or severity of adverse effects can be increased when Tetrodotoxin is combined with Difenoxin.
ThalidomideDifenoxin may increase the central nervous system depressant (CNS depressant) activities of Thalidomide.
ThalidomideThe risk or severity of adverse effects can be increased when Thalidomide is combined with Difenoxin.
ThiamylalThe risk or severity of adverse effects can be increased when Thiamylal is combined with Difenoxin.
ThiopentalThe risk or severity of adverse effects can be increased when Thiopental is combined with Difenoxin.
ThioridazineThe risk or severity of adverse effects can be increased when Thioridazine is combined with Difenoxin.
ThiothixeneThe risk or severity of adverse effects can be increased when Thiothixene is combined with Difenoxin.
TiagabineThe risk or severity of adverse effects can be increased when Tiagabine is combined with Difenoxin.
TiletamineThe risk or severity of adverse effects can be increased when Tiletamine is combined with Difenoxin.
TizanidineThe risk or severity of adverse effects can be increased when Tizanidine is combined with Difenoxin.
TolcaponeThe risk or severity of adverse effects can be increased when Tolcapone is combined with Difenoxin.
TopiramateThe risk or severity of adverse effects can be increased when Topiramate is combined with Difenoxin.
TramadolThe risk or severity of adverse effects can be increased when Tramadol is combined with Difenoxin.
Trans-2-PhenylcyclopropylamineThe risk or severity of adverse effects can be increased when Trans-2-Phenylcyclopropylamine is combined with Difenoxin.
TranylcypromineThe risk or severity of adverse effects can be increased when Tranylcypromine is combined with Difenoxin.
TrazodoneThe risk or severity of adverse effects can be increased when Difenoxin is combined with Trazodone.
TriazolamThe risk or severity of adverse effects can be increased when Triazolam is combined with Difenoxin.
TrifluoperazineThe risk or severity of adverse effects can be increased when Trifluoperazine is combined with Difenoxin.
TriflupromazineThe risk or severity of adverse effects can be increased when Triflupromazine is combined with Difenoxin.
TrimipramineThe risk or severity of adverse effects can be increased when Trimipramine is combined with Difenoxin.
TriprolidineThe risk or severity of adverse effects can be increased when Triprolidine is combined with Difenoxin.
Valproic AcidThe risk or severity of adverse effects can be increased when Valproic Acid is combined with Difenoxin.
VigabatrinThe risk or severity of adverse effects can be increased when Vigabatrin is combined with Difenoxin.
VilazodoneThe risk or severity of adverse effects can be increased when Difenoxin is combined with Vilazodone.
VortioxetineThe risk or severity of adverse effects can be increased when Difenoxin is combined with Vortioxetine.
XylazineThe risk or severity of adverse effects can be increased when Xylazine is combined with Difenoxin.
ZaleplonThe risk or severity of adverse effects can be increased when Zaleplon is combined with Difenoxin.
ZiconotideThe risk or severity of adverse effects can be increased when Difenoxin is combined with Ziconotide.
ZimelidineThe risk or severity of adverse effects can be increased when Difenoxin is combined with Zimelidine.
ZiprasidoneThe risk or severity of adverse effects can be increased when Ziprasidone is combined with Difenoxin.
ZolazepamThe risk or severity of adverse effects can be increased when Zolazepam is combined with Difenoxin.
ZolpidemThe risk or severity of adverse effects can be increased when Zolpidem is combined with Difenoxin.
ZonisamideThe risk or severity of adverse effects can be increased when Zonisamide is combined with Difenoxin.
ZopicloneThe risk or severity of adverse effects can be increased when Zopiclone is combined with Difenoxin.
ZotepineThe risk or severity of adverse effects can be increased when Zotepine is combined with Difenoxin.
ZuclopenthixolThe risk or severity of adverse effects can be increased when Zuclopenthixol is combined with Difenoxin.
Food Interactions
  • Ethanol use may increase CNS depression.
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Drug created on July 31, 2007 07:10 / Updated on August 17, 2016 12:23