I have melena after a recent influenza diagnosis and starting oseltamivir (Tamiflu); could this be a side effect and what urgent management is needed?

Melena After Starting Tamiflu: Urgent Evaluation Required

Black stool (melena) after starting oseltamivir is NOT a recognized side effect of the medication and should be treated as gastrointestinal bleeding requiring urgent evaluation until proven otherwise. 1, 2

Why This Is Not Likely Tamiflu-Related

The most common adverse effects of oseltamivir are nausea (≈10%) and vomiting (≈9%), which are mild, transient, and markedly reduced when taken with food. 3, 1 Gastrointestinal bleeding and melena are not listed among the recognized adverse effects in FDA labeling, major guidelines, or clinical trial data involving thousands of patients. 1, 2

While there is one published case report from 2007 describing acute hemorrhagic colitis in a 61-year-old man after oseltamivir, 4 this represents an extraordinarily rare event that has not been reproduced in large-scale safety surveillance or clinical trials. 2, 5 The temporal association in that single case does not establish causation, and such isolated reports must be weighed against the extensive safety data showing gastrointestinal bleeding is not a characteristic oseltamivir toxicity.

What Melena Actually Indicates

Melena strongly suggests upper gastrointestinal bleeding (UGIB) with a likelihood ratio of 5.1–5.9 for patient-reported melena and 25 (95% CI 4–174) for melena confirmed on examination. 6 The black, tarry appearance results from blood that has been digested by gastric acid and intestinal bacteria—indicating the source is proximal to the ligament of Treitz (esophagus, stomach, or duodenum). 6

Urgent Management Steps

1. Immediate Risk Stratification

• Check vital signs: Tachycardia (heart rate >100 bpm) increases the likelihood of severe bleeding requiring urgent intervention (LR 4.9,95% CI 3.2–7.6). 6
• Obtain hemoglobin: A level <8 g/dL significantly increases the likelihood of severe UGIB (LR 4.5–6.2). 6
• Calculate Blatchford score: A score of 0 effectively rules out the need for urgent intervention (LR 0.02,95% CI 0–0.05), while higher scores mandate immediate gastroenterology consultation. 6

2. Do Not Delay Evaluation

• Stop oseltamivir temporarily until gastrointestinal bleeding is excluded or the source is identified and managed.
• Arrange urgent endoscopy if the patient has hemodynamic instability, ongoing bleeding, hemoglobin <8 g/dL, or a Blatchford score >0. 6
• Consider nasogastric lavage if the diagnosis is uncertain: blood or coffee-ground material increases the likelihood of UGIB (LR 9.6,95% CI 4.0–23.0). 6

3. Rule Out Alternative Causes

Common causes of melena include:

• Peptic ulcer disease (most common)
• Gastritis or esophagitis
• Variceal bleeding (in patients with liver disease)
• Mallory-Weiss tear (especially if there was preceding vomiting from influenza or oseltamivir)
• Medications: NSAIDs, aspirin, anticoagulants, or corticosteroids 6

Ask specifically about recent NSAID use, aspirin, or other medications that could cause gastric mucosal injury—these are far more likely culprits than oseltamivir.

Can Oseltamivir Be Resumed?

If endoscopy identifies and treats a bleeding source unrelated to oseltamivir (e.g., peptic ulcer, gastritis), the medication can be resumed to complete the 5-day course, provided the patient is hemodynamically stable and the bleeding has stopped. 3, 1 Taking oseltamivir with food reduces gastrointestinal side effects and should be emphasized if therapy is restarted. 3, 1

If no source is found and bleeding resolves spontaneously, oseltamivir may be cautiously resumed with close monitoring, though the influenza treatment window (optimal benefit within 48 hours of symptom onset) may have passed. 3

Key Clinical Pitfalls to Avoid

• Do not attribute melena to oseltamivir without excluding true gastrointestinal bleeding. This is a potentially life-threatening condition that requires urgent evaluation. 6
• Do not continue oseltamivir if active bleeding is suspected. Stabilize the patient first.
• Do not assume the black stool is from dietary causes (e.g., iron supplements, bismuth, black licorice) without confirming the absence of blood. A fecal occult blood test or visual inspection can help differentiate. 6
• Do not delay endoscopy in high-risk patients (tachycardia, hemoglobin <8 g/dL, Blatchford score >0). 6