diphenoxylate
Regulatory sources consulted
Approved indications
- Adjunctive treatment of diarrhea in patients aged 13 years or older.
Contraindications
Absolute
- Hypersensitivity to diphenoxylate or atropine; obstructive jaundice; diarrhea associated with Clostridioides difficile or other enterotoxin-producing or invasive bacteria; and children under 6 years of age.
Clinical warnings
- Major warning · It can cause respiratory or central nervous system depression; it is contraindicated in children under 6 and should not be given in severe dehydration before correction. — DailyMed/FDA label
- Major warning · Stop and assess if abdominal distension or symptoms compatible with toxic megacolon occur in acute ulcerative colitis. Correct dehydration or electrolyte imbalance first. — DailyMed/FDA label
- Major warning · Use with extreme caution in advanced hepatorenal disease or abnormal liver function because of risk of hepatic coma. — DailyMed/FDA label
Drug interactions
- ModerateAlcohol and central nervous system depressants
Mechanism: Potentiation of sedation and central nervous system or respiratory depression.
Recommendation: Avoid alcohol; if another central nervous system depressant cannot be avoided, consider an alternative and monitor closely.
DailyMed/FDA label
- ModerateMonoamine oxidase inhibitors
Mechanism: It may precipitate a hypertensive crisis.
Recommendation: Avoid concomitant use and monitor for signs of hypertensive crisis if exposure occurs.
DailyMed/FDA label
Adverse events
Common (≥1%)
Drowsiness · dizziness · nausea · vomiting · abdominal discomfort · dry mouth
Rare but serious
Respiratory depression · coma · paralytic ileus · toxic megacolon · anaphylaxis
Recent literature (PubMed)
Following extended colon resections, it may not always be possible to perform colorectal anastomosis. The Deloyers procedure, which involves the transposition of the right colon, has been identified as a viable solution. This report aims to discuss the circumstances under which the Deloyers procedure was performed, as well as to evaluate the early and late postoperative outcomes, by reviewing cases conducted between 2010 and 2023. In a 22-year-old female patient who suffered major organ and tissue loss (with injuries to the sigmoid colon, descending colon, transverse colon, and mesentery) due to a firearm injury, the Deloyers procedure was applied during restorative surgery following initial damage control surgery. The procedure involved mobilizing the cecum and right colon, performing a cranio-caudal rotation over the ileocolic artery pedicle, followed by an appendectomy, and creating a colorectal anastomosis using circular staplers. There were no complications during the postoperative follow-ups. By the 14th postoperative day, the patient was discharged and experienced bowel movements four times a day, managed with 2.5 mg of diphenoxylate hydrochloride and 0.025 mg of atropine sulfate. At the 6-month follow-up, the frequency of bowel movements had decreased to twice daily without the need for medical treatment. Given the functional outcomes in patients after extended left colectomies, the Deloyers procedure, with its low associated morbidity, stands out as a viable option.
The financial toxicity of anticancer drugs is well-documented, but little is known about the costs of drugs used to manage cancer-associated symptoms. We reviewed relevant guidelines and compiled drugs used to manage seven cancer-associated symptoms (anorexia and cachexia, chemotherapy-induced peripheral neuropathy, constipation, diarrhea, exocrine pancreatic insufficiency, cancer-associated fatigue, and chemotherapy-induced nausea and vomiting). Using GoodRx website, we identified the retail price (cash price at retail pharmacies) and lowest price (discounted, best-case scenario of out-of-pocket costs) for patients without insurance for each drug or formulation for a typical fill. We describe lowest prices here. For anorexia and cachexia, costs ranged from $5 US dollars (USD; generic olanzapine or mirtazapine tablets) to $1,156 USD (brand-name dronabinol solution) and varied widely by formulation of the same drug or dosage: for olanzapine 5 mg, $5 USD (generic tablet) to $239 USD (brand-name orally disintegrating tablet). For chemotherapy-induced peripheral neuropathy, costs of duloxetine varied from $12 USD (generic) to $529 USD (brand-name). For constipation, the cost of sennosides or polyethylene glycol was <$15 USD, whereas newer agents such as methylnaltrexone were expensive ($1,001 USD). For diarrhea, the cost of generic loperamide or diphenoxylate-atropine tablets was <$15 USD. For exocrine pancreatic insufficiency, only brand-name formulations were available, range of cost, $1,072 USD-$1,514 USD. For cancer-associated fatigue, the cost of generic dexamethasone or dexmethylphenidate was <$15 USD, whereas brand-name modafinil was more costly ($1,284 USD). For a 4-drug nausea and vomiting prophylaxis regimen, costs ranged from $181 USD to $1,430 USD. We highlight the high costs of many symptom control drugs and the wide variation in the costs of these drugs. These findings can guide patient-clinician discussions about cost-effectively managing symptoms, while
Chronic diarrhea is a common disorder that interferes with normal daily activities and results in poor quality of life. Fecal urgency and incontinence often necessitate clinical consultation, but the pathophysiological mechanisms are difficult to differentiate in a clinical setting. Therefore, drugs targeting the opioid receptors, such as diphenoxylate and loperamide, are typically used, as they reduce both gut motility and secretion. For severe diarrhea, morphine-containing extemporaneous opium tincture drops have recently been reprofiled to a pharmaceutical. The drug is indicated for severe diarrhea in adults when other antidiarrheals do not give sufficient fecal emptying control. The pronounced effect is due to the liquid formulation with rapid onset as a drug dissolution step is avoided. A recent prospective, noninterventional study (CLARIFY) of patients treated with opioid drops demonstrates a rapid and sustained therapeutic effect. Tolerance does not develop for the antidiarrheal effect and no dependence was observed after discontinuation. This mini-review discusses the use of opium derivates for treatment of diarrhea, with an emphasis on opium drops as a new medicinal grade opium for the use as additional treatment of severe diarrhea, emphasizing its mechanism of action and evaluation of the risk-benefit ratio in the clinical setting.
In patients with chronic idiopathic diarrhea resistant to standard treatment, opioids are often used as rescue therapy. This systematic review investigated opioid effects on gut function in chronic diarrhea. PubMed and Embase were searched regarding effects of opioid agonists on the gastrointestinal tract in humans with chronic or experimentally induced diarrhea. A total of 1472 relevant articles were identified and, after thorough evaluation, 11 clinical trials were included. Generally, studies reported a reduction in stool frequency and an increase in transit time during treatment with the opioid receptor agonists loperamide, asimadoline, casokefamide, and codeine compared with placebo. Loperamide and diphenoxylate significantly improved stool consistency compared with placebo, whereas asimadoline showed no such effects. Compared with placebo, loperamide treatment caused less abdominal pain and urgency. Asimadoline showed no significant subjective improvements, but fedotozine was superior to placebo in reducing abdominal pain and bloating in selected patients. Only two relevant studies were published within the last 20 years, and standardized endpoint measures are lacking. Most trials included few participants, and further evidence is needed from larger, prospective studies. Likewise, consensus is needed to standardize endpoints for stool frequency, transit time, and consistency to conduct future meta-analyses on opioids in management of chronic idiopathic diarrhea.