How to manage chronic musculoskeletal pain in patients with Glucose-6-phosphate dehydrogenase (G6PD) deficiency?

Management of Chronic Musculoskeletal Pain in Patients with G6PD Deficiency

For patients with G6PD deficiency experiencing chronic musculoskeletal pain, the safest approach is to use non-oxidant analgesics such as acetaminophen as first-line therapy, followed by opioids like codeine or fentanyl if needed, while avoiding NSAIDs with oxidative potential.

Understanding G6PD Deficiency and Pain Management Risks

G6PD deficiency is the most common enzymatic disorder of red blood cells, affecting approximately 400 million people worldwide 1. This X-linked genetic condition reduces the body's ability to protect red blood cells against oxidative damage from certain medications, infections, and metabolic conditions.

When managing chronic musculoskeletal pain in these patients, the primary concern is avoiding medications that can trigger hemolytic anemia. The risk varies based on:

• The specific G6PD variant (GdA- found in 10-15% of Black individuals causes milder hemolysis, while Gdmed found in Mediterranean, Indian, and Southeast Asian populations can cause life-threatening hemolysis) 2
• The oxidative potential of the medication
• The patient's current health status

Safe Pain Management Algorithm for G6PD Deficiency

First-Line Options:

1. Non-pharmacological approaches

   • Physical activity and aerobic exercise (shown to reduce pain severity and improve physical function) 2
   • Physical therapy
   • Heat/cold therapy

2. Safe pharmacological options

   • Acetaminophen/paracetamol (first-line pharmacological choice)
   • Benzodiazepines for muscle spasms (safe in G6PD deficiency) 1

Second-Line Options (if first-line inadequate):

1. Opioid analgesics

   • Codeine and codeine derivatives (confirmed safe in G6PD deficiency) 1
   • Fentanyl (confirmed safe in G6PD deficiency) 1

2. Adjuvant medications

   • Gabapentin/pregabalin for neuropathic pain component 2
   • Ketamine (safe in G6PD deficiency) 1

Medications to Avoid:

1. High-risk medications (documented to cause hemolysis):

   • Dapsone 2, 3
   • Methylene blue 3
   • Nitrofurantoin 4
   • Rasburicase 4

2. Use with caution (conflicting evidence):

   • NSAIDs (especially at high doses)
   • Sulfonamides 4

Special Considerations

Monitoring

• Baseline G6PD enzyme activity testing is essential before starting any new medication 2
• Monitor for signs of hemolysis: fatigue, pallor, jaundice, dark urine
• Regular follow-up for medication efficacy and adverse effects

For Chronic Non-Inflammatory Pain

• Avoid repeated use of NSAIDs or glucocorticoids 2
• Consider antidepressants for chronic pain management 2
• Emphasize non-pharmacological management over medications 2

For Neuropathic Pain Components

• Gabapentin, pregabalin, or amitriptyline may be used (with attention to potential exacerbation of dryness symptoms) 2

Recent Evidence

Recent real-world data from a large cohort study (n=31,962 G6PD-deficient patients) found that many medications previously considered risky were actually prescribed safely to G6PD-deficient patients 5. Among 71 cases of major hemolysis requiring hospitalization (0.2% of the cohort), only 3 cases (4.2%) were potentially associated with medications 5.

This suggests that the risk of medication-induced hemolysis in G6PD-deficient patients may be lower than previously thought for many medications, but caution is still warranted with known high-risk medications.

Practical Approach

1. Start with acetaminophen at appropriate doses for pain control
2. Add non-pharmacological approaches (physical therapy, exercise)
3. If inadequate relief, consider safe opioids (codeine, fentanyl)
4. For neuropathic components, add gabapentin/pregabalin
5. Avoid high-risk oxidative medications
6. Educate patients about signs of hemolysis and when to seek medical attention

By following this approach, chronic musculoskeletal pain can be effectively managed in patients with G6PD deficiency while minimizing the risk of hemolytic complications.