What Is Diphenoxylate Hydrochloride?
Diphenoxylate hydrochloride is a medication primarily used to treat diarrhea. It belongs to the class of medications known as antidiarrheals.
Diphenoxylate is an opioid agonist that acts on the smooth muscle lining of the intestine, slowing down the movement of the intestines. This effect helps to reduce the frequency and urgency of bowel movements.
Diphenoxylate is often combined with atropine sulfate to discourage misuse and abuse. Atropine, in higher doses, can cause unpleasant side effects if the medication is taken in excessive amounts.
Diphenoxylate is primarily used for the symptomatic treatment of acute nonspecific diarrhea and chronic diarrhea associated with inflammatory bowel disease. It is not typically used to treat infectious diarrhea. The dosage of diphenoxylate/atropine combination is usually based on the severity of symptoms and individual response. It’s essential to follow the prescribed dosage and not to exceed it. This medication is usually taken orally.
Common side effects may include constipation, dizziness, drowsiness, and nausea. If you experience severe constipation or symptoms of opioid overdose (such as slow or difficult breathing), seek medical attention immediately.
Diphenoxylate is contraindicated in individuals with severe hepatic impairment and those with known hypersensitivity to opioids.
Caution is advised when using diphenoxylate in the elderly and individuals with conditions that may exacerbate anticholinergic effects, such as glaucoma or prostate enlargement.
It’s important to note that while diphenoxylate can effectively manage diarrhea, it does not address the underlying cause, and the cause should be identified and treated appropriately. As with any medication, it should be used under the guidance of a healthcare professional, and the prescribed dosage should be followed.
Diphenoxylate hydrochloride is well absorbed from the gastrointestinal tract. It is rapidly and extensively metabolized 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 feces 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 diarrhea. It may also reduce the frequency and fluidity of the stools in patients with colostomies or ileostomies.
Preparations of diphenoxylate usually contain subclinical amounts of atropine sulfate to discourage abuse. UK preparations are all in the form of co-phenotrope (see above).
In acute diarrhea, the usual initial dose for adults is 10 mg orally, followed by 5 mg every six hours, later reduced as the diarrhea 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, and 5 mg three times daily. While emphasizing that antimotility drugs are not recommended for acute diarrhea in children under 12, the BNFC allows 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 diarrhea 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.
Co-phenotrope may be an alternative to loperamide in managing fecal incontinence in adults.
Diphenoxylate may be helpful in the symptomatic management of diarrhea associated with opioid withdrawal syndromes.
Dependence and Withdrawal
Preparations of diphenoxylate usually contain subclinical amounts of atropine sulfate to discourage abuse. Short-term use of diphenoxylate with atropine in the recommended dosage carries a negligible risk of dependence. However, prolonged use or use of high doses may produce dependence on the morphine type.
Adverse Effects and Treatment
Diphenoxylate is related to 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.
Subclinical doses of atropine sulfate in preparations containing diphenoxylate may give rise to the adverse effects of atropine in susceptible individuals or overdosage.
Diphenoxylate hydrochloride should be avoided in patients with jaundice, intestinal obstruction, antibiotic-associated colitis, or diarrhea associated with enterotoxin-producing bacteria. It should be used with caution in patients with hepatic impairment. It should also be used cautiously in young children, in whom response is more variable and is not generally recommended for infants. Patients with inflammatory bowel disease receiving diphenoxylate should be carefully observed for signs of toxic megacolon, and diphenoxylate should be stopped promptly in 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.
(British Approved Name Modified, rINNM)
INNs in main languages (French, Latin, and Spanish): Difenoksilaattihydrokloridi; Difenoksilat Hidroklorur; Difenoksilato hydrochloride; 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 the US. European Pharmacopoeia, 6th ed. (Diphenoxylate Hydrochloride). A white or almost white crystalline powder. Very slightly soluble in water, sparingly soluble in alcohol, and freely soluble in dichloromethane. Protect from light.
The United States Pharmacopeia 31, 2008 (Diphenoxylate Hydrochloride). A white, odorless crystalline powder. Slightly soluble in water and isopropyl alcohol, sparingly soluble in alcohol and acetone, freely soluble in chloroform, practically insoluble in ether, and petroleum spirit soluble in methyl alcohol. A saturated solution in water has a pH of about 3.3.
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