What is the mechanism by which isotretinoin (13-cis-retinoic acid) causes gastrointestinal symptoms, specifically diarrhea and vomiting?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: April 25, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

From the Guidelines

Isotretinoin causes diarrhea and vomiting primarily through its irritant effect on the gastrointestinal mucosa and by altering intestinal motility, as supported by the most recent evidence 1. The exact mechanism by which isotretinoin causes gastrointestinal side effects such as diarrhea and vomiting is multifaceted.

  • As a vitamin A derivative, isotretinoin can directly irritate the lining of the stomach and intestines, leading to inflammation that triggers nausea, vomiting, and diarrhea.
  • Additionally, isotretinoin affects the secretion of mucus in the intestinal tract, potentially disrupting the protective barrier of the gut and increasing susceptibility to irritation.
  • The medication may also influence gut motility by affecting smooth muscle function in the intestinal walls, leading to altered transit time of intestinal contents.
  • Some patients experience these side effects due to isotretinoin's impact on bile acid metabolism, which can cause malabsorption of fats and subsequent diarrhea. These gastrointestinal side effects typically occur in about 10-20% of patients taking standard isotretinoin doses (0.5-1 mg/kg/day) and are usually dose-dependent, meaning higher doses tend to cause more pronounced symptoms, as noted in earlier studies 1. However, the most recent guidelines suggest that the risk of inflammatory bowel disease and other severe gastrointestinal side effects is not significantly increased with isotretinoin use 1. Patients can minimize these effects by taking isotretinoin with food and maintaining adequate hydration throughout treatment, as recommended in the guidelines 1. It is essential to monitor patients for these side effects and adjust treatment accordingly, while also considering the potential benefits of isotretinoin in the management of acne vulgaris, as outlined in the most recent guidelines 1.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Mechanism of Isotretinoin-Induced Diarrhea and Vomiting

  • The mechanism by which isotretinoin causes diarrhea and vomiting is related to its effect on the intestinal mucosae, causing damage and leading to adverse effects such as bloody and mucousy diarrhea, colitis, and ileitis 2.
  • Isotretinoin can affect all mucous membranes, causing multiple disorders of varying severity, including gastrointestinal tract disorders such as colitis 2.
  • The exact mechanism of isotretinoin-induced diarrhea and vomiting is not fully understood, but it is thought to be related to the drug's ability to cause inflammation and damage to the intestinal lining 2.
  • There is no direct evidence to suggest that isotretinoin causes diarrhea and vomiting through a specific mechanism, but rather it is a result of the drug's overall effect on the body's mucous membranes 2.

Management of Isotretinoin-Induced Diarrhea and Vomiting

  • Loperamide, an antidiarrheal medication, may be effective in managing diarrhea caused by isotretinoin, but its effectiveness has not been specifically studied in this context 3, 4.
  • Octreotide, a somatostatin analogue, has been shown to be effective in managing chemotherapy-induced diarrhea, but its use in isotretinoin-induced diarrhea has not been studied 5.
  • Patients taking isotretinoin should be informed of the risk of mucosal damage and intestinal disorders, and should be monitored closely for signs of diarrhea and vomiting 2.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Isotretinoin and intestinal damage.

Prescrire international, 2008

Research

The role of loperamide in gastrointestinal disorders.

Reviews in gastroenterological disorders, 2008

Research

Loperamide: a pharmacological review.

Reviews in gastroenterological disorders, 2007

Research

Control of irinotecan-induced diarrhea by octreotide after loperamide failure.

Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer, 2001

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.