QHow can you mitigate the gastrointestinal side effects of oral apremilast?

Cynthia Trickett, PA-C, MPAS

Cynthia Trickett, PA-C, MPAS

Medically reviewed on 12.1.2022 by Mark Lebwohl, MD

Proactively discuss the potential for GI side effects when starting a patient on oral apremilast.

Use the percentages found in clinical trials:  diarrhea occurs in up to 17%, nausea occurs in up to 17%, and vomiting (in the psoriatic arthritis trials) seen in up to 3.2%.  This is likely related to the MOA of PDE 4 moleculary, as it is seen in another PDE 4 approved for COPD.  For most individuals, this is usually temporary, as the gut will adapt to the change.

1)  Nausea can be reduced by the following:  eating smaller, more frequent meals, eating small amounts of fresh ginger (in tea, in salads, on fresh fruits/vegetables), small amounts of oral liquid diphenhydramine.  I also offer that if nausea is more intense, to prescribe odansetron if needed.  Ensure there is at least 6 hours between the am and pm dose.

The first 10mg should be taken on day 1, then the next dose should be 24 hours after the first dose.

2)  Diarrhea, while usually not severe or long lasting, can be reduced by increasing soluble fiber (found in oats, peas, apples, citrus fruits, carrots, barley, beans/lentils, and psyllium husk, and increasing fluids and replacing electrolytes if needed.  Ingesting caffeine stimulates the gastrocolic reflex which controls the lower GI tract and leads to gastric motility and defecation.  Patients who use their morning coffee to stimulate their bowels may benefit by taking oral apremilast 1 hour before coffee, or 2 -3 hours after morning coffee.  If diarrhea persists despite these measures, patients may try bismuth salicylate or loperamide.  Lastly, crofelemer, an anti-diarrheal that was approved for HIV induced diarrhea, may be prescribed.

One last suggestion, which is off-label, is to start dosing even slower than what is in the starter dose.  On more than one occasion, I have given 3 or 4 starter packs and asked the patient to finish all ‘first day’ doses before moving on to completing the ‘second day’ doses.  It just may take a little longer to get to therapeutic range to see improvement in psoriasis.


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  2. Gooderham M, Papp K.  Apremilast in the treatment of psoriasis and psoriatic arthritis.  Skin Therapy Lett 2015 Sept-Oct:20(5):1-6 
  3. Wald A, Back C, Bayless TM.  Effect of caffeine on the human small intestine.  Gastroenterology. 1976 Nov;71(5):738-742 
  4. Patel T S et.al.  Crofelemer for the treatment of chronic diarrhea in patients living with HIV/AIDS.  HIV AIDS (Auckland). 2013: 5: 153-162