 | |
 | |
| Clinical data | |
|---|---|
| Other names | R-1132, NIH-756 |
| AHFS/Drugs.com | Monograph |
| Routes of administration | Oral |
| Drug class | Opioid Antidiarrheal |
| ATC code | |
| Legal status | |
| Legal status |
|
| Pharmacokinetic data | |
| Protein binding | 74–95% |
| Eliminationhalf-life | 12–14 hours |
| Identifiers | |
| |
| CAS Number |
|
| PubChemCID | |
| IUPHAR/BPS | |
| DrugBank |
|
| ChemSpider |
|
| UNII | |
| KEGG |
|
| ChEBI | |
| ChEMBL | |
| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.011.837 |
| Chemical and physical data | |
| Formula | C30H32N2O2 |
| Molar mass | 452.598 g·mol−1 |
| 3D model (JSmol) | |
| |
| |
 N Y (what is this?) (verify) | |
Diphenoxylate is a centrally activeopioiddrug of thephenylpiperidine series that is used as acombination drug withatropine for the treatment ofdiarrhea. Diphenoxylate is anopioid and acts by slowingintestinal contractions; the atropine is present to preventdrug abuse and overdose. It should not be given to children due to the risk that they will stop breathing and should not be used in people withClostridioides difficile infection.
Diphenoxylate is used to treatdiarrhea in adults; it is only available as acombination drug with a subtherapeutic dose ofatropine to prevent abuse.[2]
It should not be used in children due to the risk ofrespiratory depression.[2] It does not appear harmful to a fetus but the risks have not been fully explored.[2]
It should not be taken with other centraldepressants like alcohol, as they can increase its risks.[2]
It should not be used for people with diarrhea caused by an infection, for example withClostridioides difficile infection, since the slowing of peristalsis can prevent clearing of the infectious organism.[2]
The drug label (in some jurisdictions) has warnings with regard to the risk ofrespiratory depression,anticholinergic toxicity andopioid overdose, the risk of dehydration and electrolyte imbalance that people with severe diarrhea always run, andtoxic megacolon in people withulcerative colitis.[2]
Other adverse effects include numbness in the hands and feet, euphoria, depression, lethargy, confusion, drowsiness, dizziness, restlessness, headache, hallucinations, edema, hives, swollen gums, itchiness, vomiting, nausea, loss of appetite, and stomach pain.[2]
Diphenoxylate is rapidly metabolized todifenoxin; it is eliminated mostly in feces but also in urine.[2]
Like otheropioids, diphenoxylate acts by slowingintestinal contractions, allowing the body to consolidate intestinal contents and prolong transit time, thus allowing the intestines to draw moisture out of them at a normal or higher rate and therefore stop the formation of loose and liquid stools; the atropine is ananticholinergic and is present to preventdrug abuse and overdose.[3]
Diphenoxylate was first synthesized byPaul Janssen atJanssen Pharmaceutica in 1956 as part of a medicinal chemistry investigation of opioids.[4]
Diphenoxylate is made by combining a precursor ofnormethadone withnorpethidine.Loperamide (Imodium) andbezitramide are analogs.[5] Like loperamide, it has amethadone-like structure and apiperidine moiety.[6]
In 2017Hikma Pharmaceuticals raised the price of its liquid formulation of generic diphenoxylate-atropine in the US by 430%, from $16 to $84.00.[7]
In the United States, drugs containing diphenoxylate combined withatropine salts are classified asSchedule V controlled substances.[8][2] (Diphenoxlate by itself is aSchedule II controlled substance.)
It is on Schedule III of theSingle Convention on Narcotic Drugs, only in forms that contain, according to the Yellow List: "not more than 2.5 milligrams of diphenoxylate calculated as base and a quantity of atropine sulfate equivalent to at least 1 per cent of the dose of diphenoxylate".[9]
Diphenoxylate and atropine have been studied in small trials as a treatment forfecal incontinence; it appears to be less efficacious and have more adverse effects when compared with loperamide or codeine.[10]
