Diphenoxylate

31 interactions 3 explained in plain English
About Diphenoxylate

Diphenoxylate is used along with other treatments such as fluid and electrolyte replacement for the treatment of diarrhea. Diphenoxylate should not be given to children younger than 2 years of age. Diphenoxylate is in a class of medications called antidiarrheal agents. It works by decreasing activity of the bowel. Read the full Diphenoxylate drug information page →

Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by Dr. Brian Staiger, PharmD, BCPS · Updated Jun 30, 2026 · Editorial policy · Data sources

Sources: FDA prescribing information (Structured Product Labeling), the published literature cited in each entry, DDInter 2.0 (a major open-access drug-interaction database), and legacy DrugBank interaction data distributed by the NIH's RxNav service (decommissioned in 2024) — analyzed and reviewed by our pharmacist team. How we build this library →

Most serious with: Palonosetron Injection Fentanyl Transdermal Patch Buprenorphine Morphine Injection Linezolid Injection Clopidogrel
29 Major 2 Moderate
All (31) Major (29) Moderate (2)

Major

Diphenoxylate Acetaminophen And Codeine Capital® & Codeine Explained Increased risk of respiratory and CNS depression and an increased risk of serotonin syndrome Details Diphenoxylate Sertraline Explained An increased risk of serotonin syndrome Details Diphenoxylate Buprenorphine Belbuca Explained An increased risk of serotonin syndrome and an increased risk of respiratory and CNS depression Details Diphenoxylate Butorphanol Injection Butorphic Increased risk of serotonin syndrome; increased risk of respiratory and CNS depression Details Diphenoxylate Butorphanol Nasal Spray Stadol® NS Increased risk of serotonin syndrome; increased risk of respiratory and CNS depression Details Diphenoxylate Cetirizine Injection Aller-Tec Increased risk of CNS depression Details Diphenoxylate Cetirizine Ophthalmic Zerviate Increased risk of CNS depression Details Diphenoxylate Clopidogrel Plavix Reduced efficacy of clopidogrel Details Diphenoxylate Diazepam Nasal Spray Valtoco Increased risk of profound sedation, respiratory and CNS depression, coma and death Details Diphenoxylate Diazepam Rectal Diastat Increased risk of profound sedation, respiratory and CNS depression, coma and death Details Diphenoxylate Digoxin Cardoxin® Increased digoxin exposure Details Diphenoxylate Esketamine Nasal Spray Spravato Increased risk of sedation Details Diphenoxylate Fentanyl Transdermal Patch Duragesic® Increased risk of respiratory and CNS depression and an increased risk of serotonin syndrome Details Diphenoxylate Granisetron Transdermal Patch Sancuso Increased risk of serotonin syndrome Details Diphenoxylate Granisetron Injection Granisol Increased risk of serotonin syndrome Details Diphenoxylate Hydromorphone Injection Dilaudid Increased risk of respiratory and CNS depression and an increased risk of serotonin syndrome Details Diphenoxylate Hydromorphone Rectal available generically Increased risk of respiratory and CNS depression and an increased risk of serotonin syndrome Details Diphenoxylate Hydroxychloroquine Plaquenil An increased risk of seizures Details Diphenoxylate Lacosamide Injection Motpoly An increased risk of CNS depression Details Diphenoxylate Levodopa Oral Inhalation Inbrija An increased risk of CNS depression Details Diphenoxylate Linezolid Injection Zyvox An increased risk of hypertensive crisis (headache, hyperpyrexia, hypertension) Details Diphenoxylate Lithium Carbonate Lithobid Increased risk of serotonin syndrome Details Diphenoxylate Metoclopramide Injection Gimoti Increased risk of CNS depression Details Diphenoxylate Metoclopramide Nasal Spray Gimoti Increased risk of CNS depression Details Diphenoxylate Midazolam Nasal Spray Nayzilam Increased risk of hypoventilation, airway obstruction, desaturation, or apnea Details Diphenoxylate Midazolam Injection Nayzilam Increased risk of hypoventilation, airway obstruction, desaturation, or apnea Details Diphenoxylate Morphine Injection Astramorph® PF Increased risk of respiratory and CNS depression and an increased risk of serotonin syndrome Details Diphenoxylate Nalbuphine Injection Nubain® Increased risk of serotonin syndrome; increased risk of respiratory and CNS depression Details Diphenoxylate Palonosetron Injection Aloxi® An increased risk of serotonin syndrome Details

Moderate

Diphenoxylate Clonidine Transdermal Patch Catapres An increased risk of sedation and somnolence Details Diphenoxylate Desmopressin Nasal Concentraid® Increased risk of water intoxication with hyponatremia Details

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Educational information only, not medical advice. Always confirm interactions with your pharmacist or prescriber before making any change to your medications.