Can oral methylprednisolone (corticosteroid) cause diarrhea?

Can Oral Methylprednisolone Cause Diarrhea?

No, oral methylprednisolone does not typically cause diarrhea as a direct adverse effect; in fact, corticosteroids like methylprednisolone are used therapeutically to treat severe diarrhea and colitis. 1

Evidence from FDA Drug Labeling

The FDA-approved prescribing information for oral methylprednisolone lists extensive adverse effects but does not include diarrhea among the documented gastrointestinal side effects. 1 The gastrointestinal adverse reactions specifically listed are:

• Peptic ulcer with possible perforation and hemorrhage 1
• Pancreatitis 1
• Abdominal distention 1
• Ulcerative esophagitis 1

Notably absent from this comprehensive list is diarrhea, which would be expected to appear if it were a recognized adverse effect of the medication. 1

Therapeutic Use for Diarrhea

Methylprednisolone is actually prescribed to treat severe diarrhea in multiple clinical contexts:

Immune Checkpoint Inhibitor-Related Colitis

• For grade 2 immune-related colitis, guidelines recommend starting oral prednisone or methylprednisolone 1-2 mg/kg/day immediately. 2, 3
• For grade 3-4 colitis with severe diarrhea (≥7 bowel movements per day), intravenous methylprednisolone 1-2 mg/kg/day is the standard treatment. 2
• The NCCN specifically recommends methylprednisolone as first-line therapy for managing severe diarrhea associated with immunotherapy. 2

Inflammatory Bowel Disease

• Corticosteroids including methylprednisolone are potent anti-inflammatory agents used for moderate to severe relapses of ulcerative colitis and Crohn's disease, both of which present with diarrhea. 2
• Oral prednisolone (equivalent to methylprednisolone) induced remission in 77% of patients with active ulcerative colitis characterized by diarrhea. 2

Chemotherapy-Related Diarrhea

• A 2023 case report demonstrated that IV methylprednisolone successfully treated severe chemotherapy-related diarrhea that was refractory to all standard antidiarrheal therapies including loperamide, diphenoxylate-atropine, and octreotide. 4
• The patient experienced rapid symptom reduction after IV steroid initiation. 4

Important Clinical Caveat: Infection-Related Diarrhea

While methylprednisolone itself does not cause diarrhea, immunosuppression from corticosteroid therapy can increase susceptibility to infections that cause diarrhea:

• The FDA warns that corticosteroids suppress the immune system and increase risk of infection with viral, bacterial, fungal, and protozoal pathogens. 1
• Corticosteroids may activate latent amebiasis, and the FDA recommends ruling out latent or active amebiasis before initiating methylprednisolone in patients with unexplained diarrhea. 1
• Strongyloides infestation can lead to hyperinfection with severe enterocolitis when corticosteroid-induced immunosuppression occurs. 1

If a patient on methylprednisolone develops diarrhea, consider infectious causes rather than the medication itself as the primary etiology. 1

Mechanism of Action Supports Anti-Diarrheal Effect

Corticosteroids work through multiple anti-inflammatory pathways that would be expected to reduce, not cause, diarrhea:

• Induction of T cell apoptosis 2
• Suppression of interleukin transcription 2
• Suppression of arachidonic acid metabolism 2
• Stimulation of lymphocyte apoptosis within the gut lamina propria 2

These mechanisms explain why methylprednisolone is effective in treating inflammatory diarrhea rather than causing it. 2

Distinguishing from Other Medications

A comprehensive review of drug-induced diarrhea identified over 700 drugs that can cause diarrhea, with the most common culprits being antimicrobials, laxatives, magnesium-containing antacids, NSAIDs, prostaglandins, colchicine, and antineoplastics. 5 Corticosteroids were not listed among the drug classes commonly associated with diarrhea. 5, 6