Diphenoxylate

• Diphenoxylate hydrochloride and atropine sulfate tablets are indicated as adjunctive therapy in the management of diarrhea in patients 13 years of age and older.

• Diphenoxylate hydrochloride and atropine sulfate tablets are contraindicated in: Pediatric patients less than 6 years of age due to the risks of respiratory and central nervous system (CNS) depression (see WARNINGS ). Patients with diarrhea associated with pseudomembranous enterocolitis (Clostridium difficile) or other enterotoxin-producing bacteria due to the risk of gastrointestinal (GI) complications, including sepsis (see WARNINGS ).contraindicated

Management of Diarrhea in Patients 13 Years of Age and Older Diphenoxylate hydrochloride and atropine sulfate tablets are recommended as adjunctive therapy for the management of diarrhea in patients 13 years of age and older. Consider the nutritional status and degree of dehydration in patients prior to initiating therapy with diphenoxylate hydrochloride and atropine sulfate tablets. The use of diphenoxylate hydrochloride and atropine sulfate tablets should be accompanied by appropriate fluid and electrolyte therapy, when indicated. If severe dehydration or electrolyte imbalance is present, do not administer diphenoxylate hydrochloride and atropine sulfate tablets until appropriate corrective therapy has been indicated (see WARNINGS ). Initial and Maximum Recommended Dosage in Patients 13 Years of Age and Older The initial adult dosage is 2 diphenoxylate hydrochloride and atropine sulfate tablets four times daily (maximum total daily dose of 20 mg per day of diphenoxylate hydrochloride). Most patients will require this dosage until initial control of diarrhea has been achieved. Clinical improvement of acute diarrhea is usually observed within 48 hours. Dosage after Initial Control of Diarrhea After initial control has been achieved, the diphenoxylate hydrochloride and atropine sulfate tablet dosage may be reduced to meet individual requirements. Control may often be maintained with as little as two diphenoxylate hydrochloride and atropine sulfate tablets daily.

Respiratory and/or CNS Depression in Pediatric Patients Less Than 6 Years of Age Cases of severe respiratory depression and coma, leading to permanent brain damage or death have been reported in patients less than 6 years of age who received diphenoxylate hydrochloride and atropine sulfate tablets . Diphenoxylate hydrochloride and atropine sulfate tablets are contraindicated in patients less than 6 years of age due to these risks (see CONTRAINDICATIONS ). Anticholinergic and Opioid-Toxicities Toxicities associated with the atropine and diphenoxylate components of diphenoxylate hydrochloride and atropine sulfate tablets have been reported. The initial presenting symptoms may be delayed by up to 30 hours due to prolonged gastric emptying time induced by diphenoxylate hydrochloride. Clinical presentations vary in terms of which toxicity (anticholinergic vs. opioid) will present first or predominate; non-specific findings have been reported and include symptoms such as drowsiness (see OVERDOSAGE ). Dehydration and Electrolyte Imbalance The use of diphenoxylate hydrochloride and atropine sulfate tablets should be accompanied by appropriate fluid and electrolyte therapy, when indicated. If severe dehydration or electrolyte imbalance is present, diphenoxylate hydrochloride and atropine sulfate tablets should be withheld until appropriate corrective therapy has been initiated. Drug-induced inhibition of peristalsis may result in fluid retention in the intestine, which may further aggravate dehydration and electrolyte imbalance.

The following serious adverse reactions are described elsewhere in labeling: Respiratory and/or CNS depression (see WARNINGS ) Anticholinergic and opioid-toxicities, including atroponism (see WARNINGS and PRECAUTIONS ) Dehydration and electrolyte imbalance (see WARNINGS ) GI Complications in patients with infectious diarrhea (see WARNINGS ) Toxic megacolon in patients with acute ulcerative colitis (see WARNINGS ) At therapeutic doses of diphenoxylate hydrochloride and atropine sulfate tablets, the following other adverse reactions have been reported; they are listed in decreasing order of severity, but not of frequency: Nervous system: numbness of extremities, euphoria, depression, malaise/lethargy, confusion, sedation/drowsiness, dizziness, restlessness, headache, hallucination Allergic: anaphylaxis, angioneurotic edema, urticaria, swelling of the gums, pruritus Gastrointestinal system: megacolon, paralytic ileus, pancreatitis, vomiting, nausea, anorexia, abdominal discomfort The following adverse reactions related to atropine sulfate are listed in decreasing order of severity, but not of frequency: hyperthermia, tachycardia, urinary retention, flushing, dryness of the skin and mucous membranes. CALL YOUR DOCTOR FOR MEDICAL ADVICE ABOUT SIDE EFFECTS. YOU MAY REPORT SIDE EFFECTS TO THE FDA AT 1-800-FDA-1088 OR LEADING PHARMA, LLC AT 1-844-740-7500.

Pregnancy: Diphenoxylate hydrochloride has been shown to have an effect on fertility in rats when given in doses 50 times the human dose (see above discussion). Other findings in this study include a decrease in maternal weight gain of 30% at 20 mg/kg/day and of 10% at 4 mg/kg/day. At 10 times the human dose (4 mg/kg/day), average litter size was slightly reduced. Teratology studies were conducted in rats, rabbits, and mice with diphenoxylate hydrochloride at oral doses of 0.4 to 20 mg/kg/day. Due to experimental design and small numbers of litters, embryotoxic, fetotoxic, or teratogenic effects cannot be adequately assessed. However, examination of the available fetuses did not reveal any indication of teratogenicity. There are no adequate and well-controlled studies in pregnant women. Diphenoxylate hydrochloride and atropine sulfate tablets should be used during pregnancy only if the anticipated benefit justifies the potential risk to the fetus.

Diagnosis: Overdosage can be life-threatening. Symptoms of overdosage may include opioid and/or anticholinergic effects including respiratory depression, coma, delirium, lethargy, dryness of the skin and mucous membranes, mydriasis or miosis, flushing, hyperthermia, tachycardia, hypotonia, tachypnea, toxic encephalopathy, seizures and incoherent speech. Respiratory depression has been reported up to 30 hours after ingestion and may recur despite an initial response to narcotic antagonists. Treat all possible diphenoxylate hydrochloride and atropine sulfate overdosages as serious and maintain medical observation/hospitalization until patients become asymptomatic without naloxone use. Treatment: A pure narcotic antagonist (e.g., naloxone) should be used in the treatment of respiratory depression caused by diphenoxylate hydrochloride and atropine sulfate tablets. Refer to the prescribing information for naloxone. Consider diphenoxylate hydrochloride and atropine sulfate toxicity even in settings of negative toxicology tests. Following initial improvement of respiratory function, repeated doses of naloxone hydrochloride may be required to counteract recurrent respiratory depression.

• Sep 15, 1960NDANDA012462Pfizer
• Oct 29, 1979ANDAANDA086727Ani Pharms
• May 3, 1982ANDAANDA087708Hikma
• Nov 13, 2018ANDAANDA210819Unichem
• Feb 20, 2020ANDAANDA213413Leading
• Oct 6, 2020ANDAANDA213335Specgx Llc
• Oct 21, 2020ANDAANDA207128Chartwell Rx
• Jan 27, 2021ANDAANDA211362Winder Labs Llc

1. 1Diarrhoea2,69620%
2. 2Nausea1,59612%
3. 3Fatigue1,45111%
4. 4Drug Ineffective1,1198.3%
5. 5Vomiting9086.7%
6. 6Weight Decreased8686.4%
7. 7Pain7775.8%
8. 8Dehydration7625.7%
9. 9Off Label Use7405.5%
10. 10Abdominal Pain7335.4%
11. 11Asthenia7075.2%
12. 12Dyspnoea6634.9%
13. 13Headache6614.9%
14. 14Decreased Appetite6374.7%
15. 15Malaise5894.4%

Recent PubMed references pinned to Diphenoxylate as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

• Inhibitory Effect of Lactiplantibacillus plantarun HFY11 on Compound Diphenoxylate-Induced Constipation in Mice.
  Biomolecules · 2025 · Tan F, Kong CS
  PMID 40149894DOI 10.3390/biom15030358
• Ji-Chuan decoction ameliorates slow transit constipation via regulation of intestinal glial cell apoptosis.
  World journal of gastroenterology · 2022 · Wang XM, Lv LX, Qin YS, et al.
  PMID 36160643DOI 10.3748/wjg.v28.i34.5007
• Antimotility agents for the treatment of acute noninfectious diarrhea in critically ill patients: A practice management guideline from the Eastern Association for the Surgery of Trauma.
  The journal of trauma and acute care surgery · 2019 · Bugaev N, Bhattacharya B, Chiu WC, et al.
  PMID 31574060DOI 10.1097/TA.0000000000002449
• Polysaccharide from Spirulina platensis ameliorates diphenoxylate-induced constipation symptoms in mice.
  International journal of biological macromolecules · 2019 · Ma H, Xiong H, Zhu X, et al.
  PMID 31054300DOI 10.1016/j.ijbiomac.2019.04.209
• Protective effect of mulberry (Morus atropurpurea) fruit against diphenoxylate-induced constipation in mice through the modulation of gut microbiota.
  Food & function · 2019 · Hu TG, Wen P, Fu HZ, et al.
  PMID 30785176DOI 10.1039/c9fo00132h
• [Abuse of diphenoxylate and related factors of forced drug abstainer in Gansu province].
  Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi · 2018 · Huang JJ, Rong YM, Li RC, et al.
  PMID 30293314DOI 10.3760/cma.j.issn.0254-6450.2018.09.015
• Bacterial Cellulose Relieves Diphenoxylate-Induced Constipation in Rats.
  Journal of agricultural and food chemistry · 2018 · Zhai X, Lin D, Zhao Y, et al.
  PMID 29627986DOI 10.1021/acs.jafc.8b00385
• Sergio Henrique Ferreira (1934-2016).
  British journal of pharmacology · 2017 · Bakhle YS, Flower RJ
  PMID 28116748DOI 10.1111/bph.13683

The 10 most recently updated of 12 ClinicalTrials.gov registrations naming Diphenoxylate as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• E7 TCR T Cells for Human Papillomavirus-Associated Cancers
  Completed · Phase 1 · Phase 2 · Interventional · 224 enrolled · National Cancer Institute (NCI)
  NCT02858310updated 2026-03-09
• Sunitinib or Cediranib for Alveolar Soft Part Sarcoma
  Completed · Phase 2 · Interventional · 34 enrolled · National Cancer Institute (NCI)
  NCT01391962updated 2026-02-02
• Sacituzumab Govitecan for Relapsed Ovarian, Endometrial, and Cervical Carcinomas
  Terminated · Phase 2 · Interventional · 2 enrolled · National Cancer Institute (NCI)
  NCT06865677updated 2026-01-21
• Incidence and Severity of Diarrhea in Patients With HER2 Positive Breast Cancer Treated With Trastuzumab and Neratinib
  Completed · Phase 2 · Interventional · 11 enrolled · University of California, San Francisco
  NCT03094052updated 2025-06-26
• Immunochemotherapy ± Salvage Chemoradiation for Local Recurrence of Esophageal Squamous Cell Carcinoma After Definitive Chemoradiotherapy
  Enrolling by invitation · Phase 3 · Interventional · 79 enrolled · Ye jinjun
  NCT07016737updated 2025-06-12
• Indenoisoquinoline LMP744 in Adults With Relapsed Solid Tumors and Lymphomas
  Completed · Phase 1 · Interventional · 36 enrolled · National Cancer Institute (NCI)
  NCT03030417updated 2024-12-10
• TRC102 and Temozolomide for Relapsed Solid Tumors and Lymphomas
  Completed · Phase 1 · Phase 2 · Interventional · 93 enrolled · National Cancer Institute (NCI)
  NCT01851369updated 2024-05-08
• An Innovative Smartphone Application for Adverse Event Management During Breast Cancer Adjuvant Chemotherapy
  Unknown · Interventional · 108 enrolled · Peking Union Medical College Hospital
  NCT05258461updated 2022-02-28
• Sugammadex Versus Neostigmine for Postoperative Nausea and Vomiting After Laparoscopic Gynaecological Surgery
  Completed · Phase 3 · Interventional · 184 enrolled · KK Women's and Children's Hospital
  NCT02666014updated 2018-06-28
• A Phase III Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Investigational Product MP-101 in Subjects With Short Bowel Syndrome Who Have Had an Inadequate Response to Anti-Diarrheals
  Withdrawn · Phase 3 · Interventional · 0 enrolled · Marathon Pharmaceuticals, LLC
  NCT02242656updated 2015-02-18

Frequently asked questions

What is Diphenoxylate used for?

According to FDA labeling, Diphenoxylate carries indications including: Diphenoxylate hydrochloride and atropine sulfate tablets are indicated as adjunctive therapy in the management of diarrhea in patients 13 years of age and older.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Diphenoxylate?

Diphenoxylate is classified as Antipropulsives, Antidiarrheal, Decreased GI Motility.

What are the brand names for Diphenoxylate?

Diphenoxylate is marketed under brand names including Lomotil.

What are the contraindications for Diphenoxylate?

Diphenoxylate labeling lists contraindications including: Diphenoxylate hydrochloride and atropine sulfate tablets are contraindicated in: Pediatric patients less than 6 years of age due to the risks of respiratory and central nervous system (CNS) depression (see WARNINGS ). Patients with diarrhea associated with pseudomembranous enterocolitis (Clostridium difficile) or other enterotoxin-producing bacteria due to the risk of gastrointestinal (GI) complications, including sepsis (see WARNINGS ).. Always consult the full prescribing information and a clinician.