Can omeprazole cause fatigue?

Can Omeprazole Cause Fatigue?

Fatigue is a recognized adverse effect of omeprazole, documented in both FDA labeling and clinical case reports, though it occurs infrequently and is typically mild when it does occur.

Evidence from FDA Drug Labeling

The FDA-approved prescribing information for omeprazole explicitly lists fatigue as a postmarketing adverse reaction 1. This means fatigue has been reported by patients taking omeprazole in real-world clinical practice, though the exact frequency cannot be reliably determined from voluntary reporting systems 1.

Additional adverse effects documented in the FDA label that may contribute to or be confused with fatigue include:

• Malaise (general feeling of discomfort or weakness) 1
• Anemia (which commonly causes fatigue) 1
• Fever and pain (which can manifest as tiredness) 1

Clinical Trial Safety Data

In controlled clinical trials, the most common adverse reactions with omeprazole included diarrhea, nausea, upper respiratory infection, headache, and dizziness—but fatigue was not among the most frequently reported effects in the trial setting 1. This suggests that while fatigue can occur, it is relatively uncommon compared to gastrointestinal and neurological side effects 1.

Serious Adverse Reactions That May Present as Fatigue

Acute interstitial nephritis (AIN) is a serious but rare complication of omeprazole that characteristically presents with fatigue as a prominent symptom 2. In a case series of 18 patients who developed AIN from omeprazole:

• Fatigue was one of the most common presenting symptoms 2
• AIN developed after an average of 2.7 months of therapy with 20-40 mg daily 2
• Other symptoms included fever, anorexia, and nausea 2
• Laboratory findings included elevated serum creatinine, hematuria, proteinuria, and anemia 2

If a patient on omeprazole develops new-onset fatigue, particularly if accompanied by fever, decreased appetite, nausea, or weight loss, check renal function immediately to rule out AIN 2.

Overall Safety Profile

Long-term safety data from over 19,000 patients and 1.2 million patient treatments demonstrate that omeprazole is generally well tolerated 3. The overall incidence of adverse events is low and comparable to H2-receptor antagonists 3. Most adverse events are mild, transient, and do not require dose reduction or discontinuation 3.

Clinical Recommendations

When evaluating fatigue in a patient taking omeprazole:

1. Assess timing: Determine when fatigue began relative to omeprazole initiation 2
2. Check for red flags: Look for fever, rash, decreased urine output, nausea, or weight loss that might suggest AIN 2
3. Order laboratory tests: Obtain complete blood count (to assess for anemia), comprehensive metabolic panel (to assess renal function), and urinalysis 1, 2
4. Consider discontinuation: If fatigue is bothersome and no other cause is identified, discontinue omeprazole and observe for symptom resolution 2
5. Do not rechallenge: If AIN is diagnosed, omeprazole rechallenge universally causes recurrence and should be avoided 2

Important Caveats

• The absence of fatigue in the most common adverse events from clinical trials does not mean it cannot occur in individual patients 1, 3
• Fatigue is a non-specific symptom with many potential causes; omeprazole may be coincidental rather than causative 1
• Patients over 65 years have the same adverse event profile as younger patients, so age alone should not change clinical suspicion 3