How to manage epigastric pain in a patient with Glucose-6-phosphate dehydrogenase (G6PD) deficiency?

Managing Epigastric Pain in G6PD Deficiency

Treat epigastric pain in G6PD-deficient patients with proton pump inhibitors (PPIs) like omeprazole, which are safe and effective for acid-related causes, while strictly avoiding NSAIDs and other oxidant medications that can trigger hemolysis. 1, 2

Initial Diagnostic Approach

When a G6PD-deficient patient presents with epigastric pain, focus on identifying the underlying cause while avoiding hemolytic triggers:

• Consider common etiologies: gastroesophageal reflux disease (GERD), peptic ulcer disease (PUD), gastritis, or duodenal ulcer—these account for the majority of epigastric pain cases 3
• Look for red flag symptoms: hematemesis, severe pain radiating to the back, or pain with exertion that might suggest more serious conditions like myocardial infarction or pancreatitis 3
• Note that 63-75% of patients with heartburn also have coexisting epigastric pain, making differentiation challenging 3

Safe Medication Options

First-Line Treatment: Proton Pump Inhibitors

PPIs are the safest and most effective option for acid-related epigastric pain in G6PD deficiency:

• Omeprazole 20 mg once daily for symptomatic GERD or 40 mg once daily for gastric ulcer, taken before meals 1
• Treatment duration: 4-8 weeks for most conditions 1
• No evidence exists contraindicating PPI use in G6PD deficiency 2
• Antacids may be used concomitantly if needed 1

Absolutely Contraindicated Medications

Never use these medications in G6PD-deficient patients with epigastric pain:

• Aspirin is explicitly contraindicated as it overwhelms the reduced antioxidant capacity in G6PD-deficient red blood cells 4
• NSAIDs (including ibuprofen and diclofenac) present moderate-to-high risk for hemolysis 4, 5
• Dapsone, methylene blue, primaquine, rasburicase, nitrofurantoin, phenazopyridine, and tolonium chloride are the seven definitively contraindicated medications 6, 2

A case report documented severe hemolysis triggered by diclofenac sodium suppository (50 mg) in a G6PD-deficient patient, resulting in hemoglobinuria, jaundice, and markedly elevated serum ferritin 5. This underscores the real danger of NSAID use in this population.

Safe Alternatives for Pain Management

If additional analgesia is needed beyond PPIs:

• Acetaminophen (paracetamol) in normal therapeutic doses can be used safely 2
• Codeine and codeine derivatives have not been shown to cause hemolytic crises 7
• Opioids including fentanyl are safe options 7

Clinical Monitoring

Watch for signs of hemolysis if any new medication is introduced:

• Jaundice (common presentation of acute hemolysis) 4
• Dark urine (hemoglobinuria) 5
• Severe fatigue and lumbar back pain 5
• Laboratory findings: elevated indirect bilirubin, decreased hemoglobin, elevated serum ferritin 5

If hemolysis occurs:

• Immediately discontinue the offending agent 8
• Monitor hemoglobin levels closely 4
• Consider transfusion if hemoglobin drops below 7-8 g/dL with symptoms 4
• Admit for close observation in severe cases 7

Diagnostic Workup Considerations

If symptoms persist despite PPI therapy or red flags are present:

• Upper endoscopy is the standard test for diagnosing GERD, esophagitis, PUD, and gastritis 3
• CT abdomen/pelvis may be performed if symptoms are nonspecific, though it's not first-line for suspected acid-related disease 3
• Distal esophageal wall thickening ≥5 mm on CT has 56% sensitivity and 88% specificity for reflux esophagitis 3

Critical Pitfalls to Avoid

• Never assume "just give an NSAID" for epigastric pain—this reflexive approach can be catastrophic in G6PD deficiency 4, 5
• Avoid testing G6PD levels during acute hemolysis, as reticulocytes may show falsely normal enzyme activity 8, 4
• Don't overlook infection as a hemolytic trigger—many drugs wrongly blamed for hemolysis were actually given during infection-related episodes 2
• Remember that penicillins (like amoxicillin) are safe and can be used for H. pylori eradication if needed 4, 1

Patient Education

Counsel G6PD-deficient patients to:

• Avoid all NSAIDs and aspirin permanently 4
• Inform all healthcare providers of their G6PD status before receiving any medication 7
• Recognize early signs of hemolysis (dark urine, yellowing of eyes, severe fatigue) and seek immediate care 4, 7
• Consider folic acid supplementation (1 mg daily) for chronic management 4