(British Approved Name Modified, rINNM)
INNs in main languages (French, Latin, and Spanish): Difenoksilaattihydrokloridi; Difenoksilat Hidroklorur; Difenoksilato hidrochloridas; Difenoxilat-hidroklorid; Difenoxilathydroklorid; Difenoxylat-hydrochlorid; Diphenoxylate, chlorhydrate de; Diphenoxylati hydrochloridum; Hidrocloruro de difenoxilato; R-II32.
Note. Compounded preparations of diphenoxylate hydrochloride may be represented by the following names:
• Co-phenotrope (BAN) — diphenoxylate hydrochloride 100 parts and atropine sulfate 1 part (w/w).
Pharmacopoeias. In China, Europe, International, and US. European Pharmacopoeia, 6th ed. (Diphenoxylate Hydrochloride). A white or almost white, crystalline powder. Very slightly soluble in water sparingly soluble in alcohol freely soluble in dichloromethane. Protect from light.
The United States Pharmacopeia 31, 2008 (Diphenoxylate Hydrochloride). A white odourless crystalline powder. Slightly soluble in water and in isopropyl alcohol sparingly soluble in alcohol and in acetone freely soluble in chloroform practically insoluble in ether and in petroleum spirit soluble in methyl alcohol. A saturated solution in water has a pH of about 3.3.
Dependence and Withdrawal
Preparations of diphenoxylate usually contain subclin-ical amounts of atropine sulfate in an attempt to discourage abuse. Short-term use of diphenoxylate with atropine in the recommended dosage carries a negligible risk of dependence, although prolonged use or use of high doses may produce dependence of the morphine type.
Adverse Effects and Treatment
Diphenoxylate is related to the opioid analgesics, and its adverse effects and their treatment are similar, particularly in overdosage. Reported adverse effects include: gastrointestinal effects such as anorexia, nausea and vomiting, abdominal distension or discomfort, paralytic ileus, toxic megacolon, and pancreatitis nervous system effects such as headache, drowsiness, dizziness, restlessness, euphoria, depression, numbness of the extremities and hypersensitivity reactions including angioedema, urticaria, pruritus, and swelling of the gums. Signs of overdosage may be delayed and patients should be observed for at least 48 hours. Young children are particularly susceptible to the effects of overdosage.
The presence of subclinical doses of atropine sulfate in preparations containing diphenoxylate may give rise to the adverse effects of atropine in susceptible individuals or in overdosage — see Atropine Sulfate.
Diphenoxylate hydrochloride should be avoided in patients with jaundice, intestinal obstruction, antibiotic-associated colitis, or diarrhoea associated with enterotoxin-producing bacteria, and should be used with caution in patients with hepatic impairment. It should also be used with caution in young children, in whom response is more variable, and is not generally recommended for use in infants. Patients with inflammatory bowel disease receiving diphenoxylate should be carefully observed for signs of toxic megacolon and diphenoxylate stopped promptly should abdominal distension
Because of the structural relationship of diphenoxylate to pethidine there is a theoretical risk of hypertensive crisis if diphenoxylate is used with MAOIs. Diphenoxylate may potentiate the effects of other CNS depressants such as alcohol, barbiturates, and some anxiolytics.
Diphenoxylate hydrochloride is well absorbed from the gastrointestinal tract. It is rapidly and extensively metabolised in the liver, mainly to diphenoxylic acid (difenoxin), which has antidiarrhoeal activity other metabolites include hydroxydiphenoxylic acid. It is excreted mainly as metabolites and their conjugates in the faeces lesser amounts are excreted in urine. It may be distributed into breast milk.
Uses and Administration
Diphenoxylate hydrochloride is a synthetic derivative of pethidine with little or no analgesic activity it reduces intestinal motility and is used in the symptomatic treatment of acute and chronic diarrhoea. It may also be used to reduce the frequency and fluidity of the stools in patients with colostomies or ileostomies.
Preparations of diphenoxylate usually contain subclinical amounts of atropine sulfate in an attempt to discourage abuse UK preparations are all in the form of co-phenotrope (see above).
In acute diarrhoea the usual initial dose for adults is 10 mg orally, followed by 5 mg every six hours, later reduced as the diarrhoea is controlled. In the UK, diphenoxylate hydrochloride is not licensed for children under 4 years of age. Suggested initial doses for children are: 4 to 8 years, 2.5 mg three times daily 9 to 12 years, 2.5 mg four times daily over 12 years, 5 mg three times daily. While emphasising that antimotility drugs are not recommended for acute diarrhoea in children under 12 years of age, the BNFC allows for a dose of 1.25 mg three times daily for children aged 2 to 4 years. In the USA, diphenoxylate is not recommended for children under the age of 2 years and an initial dose of 0.3 to 0.4 mg/kg (up to an effective maximum of 10 mg) daily in 4 divided doses is suggested for children aged 2 to 12 years. (For the view that antidiarrhoeal drugs should not be used at all in children)
Similar initial doses are used for chronic diarrhoea, and subsequently reduced as necessary. If clinical improvement is not seen after 10 days of treatment with the maximum daily dose of 20 mg (in adults) further use is unlikely to result in any benefit.
Diarrhoea. Co-phenotrope (see above) may be considered as an alternative to loperamide in the management of faecal incontinence in adults, see Diarrhoea, under Loperamide.
Substance dependence. Diphenoxylate may be useful in the symptomatic management of diarrhoea associated with opioid withdrawal syndromes.
The United States Pharmacopeia 31, 2008: Diphenoxylate Hydrochloride and Atropine Sulfate Oral Solution Diphenoxylate Hydrochloride and Atropine Sulfate Tablets.
Australia: Lofenoxal Lomotil
Czech Republic: Reasec
Hong Kong: Dhamotil Dimotil Lomotil
Malaysia: Atrotil Beamotil Dhamotil Lomotil Setmotil
New Zealand: Diastop Lomotil
South Africa: Lomotil
Singapore: Beamotil Dhamotil Lomotil Remodil
Thailand: DilomiHy Lomotil
United Kingdom: Dymotil Lomotil
USA: Logen Lomotil Lonox
The symbol denotes a preparation no longer actively marketed.