Medications to Avoid in Patients with G6PD Deficiency During IVF Stimulation
Patients with Glucose-6-phosphate dehydrogenase (G6PD) deficiency undergoing IVF stimulation should strictly avoid methylene blue, primaquine, nitrofurantoin, phenazopyridine, dapsone, rasburicase, and tolonium chloride as these medications can cause severe hemolytic anemia. 1
Understanding G6PD Deficiency and Medication Risks
G6PD deficiency is the most common enzymatic disorder of red blood cells worldwide, affecting approximately 400 million people. Patients with this condition lack the ability to protect their red blood cells against oxidative stress, which can lead to hemolysis when exposed to certain medications, foods, or infections 2.
Medications with Strong Evidence to Avoid:
- Methylene blue: Can cause significant hemolytic anemia in G6PD-deficient patients. It may be ineffective and can worsen G6PD deficiency-related hemolysis 3
- Primaquine: Causes hemolytic anemia in G6PD deficiency and should be strictly avoided 3
- Nitrofurantoin: Has strong evidence for causing hemolysis in G6PD-deficient patients 1, 4
- Phenazopyridine: Should be avoided due to risk of hemolysis 1, 5
- Dapsone: Associated with hemolytic reactions in G6PD deficiency 3
- Rasburicase: Contraindicated in G6PD deficiency 1
- Tolonium chloride (toluidine blue): Should be avoided in G6PD-deficient patients 1
Additional Medications to Use with Caution:
- Local anesthetics: Benzocaine, prilocaine, lidocaine, and tetracaine have been reported to precipitate methemoglobinemia and should be used with caution 3
- Sulfonamides: Including sulfamethoxazole/cotrimoxazole may pose risk, though recent real-world data suggests they may be safer than previously thought 3, 5
- Nitroglycerin: Listed among substances that can precipitate methemoglobinemia 3
Clinical Management During IVF Stimulation
Screening Recommendations:
- Qualitative screening for G6PD deficiency is recommended before starting therapy with any oxidant drug in patients with predisposing racial or ethnic backgrounds (particularly those from Africa, southern Europe, the Middle East, Southeast Asia, and the central/southern Pacific islands) 3, 2
Safe Alternatives During IVF:
- Most standard IVF medications (gonadotropins, GnRH agonists/antagonists) have not been reported to cause hemolysis in G6PD-deficient patients 2
- For pain management and anxiety during procedures, medications considered safe include:
- Benzodiazepines
- Codeine and codeine derivatives
- Propofol
- Fentanyl
- Ketamine 2
Management of Hemolytic Crisis:
If hemolysis occurs during IVF treatment:
- Immediately discontinue the suspected medication 3
- Ascorbic acid (Vitamin C) is the treatment of choice for methemoglobinemia in G6PD-deficient patients when methylene blue is contraindicated 3
- Dosing of ascorbic acid ranges from 0.2-1.0 g/day orally in divided doses 3
- In severe cases, exchange transfusion may be necessary 3
Important Considerations
- Recent real-world data suggests that some medications previously thought to be high-risk (such as ciprofloxacin, hydroxychloroquine, and sulfamethoxazole) may be safer than previously believed 5
- The severity of G6PD deficiency varies by genetic variant - the Mediterranean variant (B-) carries higher risk of severe hemolysis than the African variant (A-) 3
- Always check for G6PD deficiency before administering any potentially oxidative medication 3
- Patients should be educated about signs and symptoms of hemolytic crisis (pallor, dark red urine, jaundice) 4
By carefully avoiding these high-risk medications during IVF stimulation protocols, clinicians can minimize the risk of hemolytic complications in G6PD-deficient patients while still providing effective fertility treatment.