Is Metoclopramide Safe in G6PD Deficiency?
Yes, metoclopramide can be used safely in patients with G6PD deficiency—there is no evidence contraindicating its use, and it does not appear on any authoritative list of medications that cause hemolysis in G6PD-deficient patients.
Evidence-Based Safety Profile
The FDA drug label for metoclopramide specifically addresses G6PD deficiency only in the context of methemoglobinemia treatment, stating that "in patients with G6PD deficiency who experience metoclopramide-induced methemoglobinemia, methylene blue treatment is not recommended" 1. This warning pertains to the treatment of a rare adverse effect (methemoglobinemia), not to the use of metoclopramide itself in G6PD-deficient patients 1.
Comprehensive Medication Safety Review
Multiple systematic evidence reviews have examined medications and G6PD deficiency:
A 2010 evidence-based review found solid evidence to prohibit only seven medications: dapsone, methylene blue, nitrofurantoin, phenazopyridine, primaquine, rasburicase, and tolonium chloride 2. Metoclopramide was not among these contraindicated drugs 2.
A 2024 real-world study of 31,962 G6PD-deficient patients identified only 71 cases (0.2%) of major hemolysis requiring hospitalization, with 71.8% caused by fava beans, 8.5% by infections, and only 4.2% possibly associated with medications (nitrofurantoin, phenazopyridine, and an unspecified "pain killer"—not metoclopramide) 3.
Current guidelines consistently list dapsone, primaquine, rasburicase, methylene blue, and sulfonamides as the primary medications to avoid 4, 5, 6, but metoclopramide does not appear on these lists.
Clinical Practice Implications
Metoclopramide can be prescribed at standard doses for nausea, gastroparesis, or as adjunctive migraine therapy in G6PD-deficient patients without special precautions beyond those recommended for the general population 4. The medication's use as adjunctive therapy (10 mg IV or orally 20-30 minutes before analgesics) is well-established 4.
Important Caveats
While metoclopramide itself is safe, clinicians should:
- Avoid methylene blue if metoclopramide-induced methemoglobinemia occurs (though this is an exceedingly rare complication) 1
- Be aware that neonates with G6PD deficiency have reduced NADH-cytochrome b5 reductase, making them more susceptible to methemoglobinemia from any cause, so metoclopramide should be used cautiously in this population for pharmacokinetic reasons unrelated to G6PD status 1
- Monitor for standard metoclopramide adverse effects (extrapyramidal symptoms, tardive dyskinesia) which are unrelated to G6PD deficiency 4, 1
Medications That Actually Require Avoidance
For context, the medications that G6PD-deficient patients must avoid include:
- Absolutely contraindicated: dapsone, methylene blue, rasburicase, primaquine (in severe deficiency), and tafenoquine (if G6PD activity <70%) 4, 5, 2
- Use with extreme caution: nitrofurantoin, phenazopyridine, sulfonamides 5, 6, 2
- Generally safe despite historical concerns: chloroquine/hydroxychloroquine at standard doses, artemisinin-based therapies 5, 3
The evidence overwhelmingly supports that metoclopramide does not cause hemolysis in G6PD-deficient patients and can be used without restriction based on G6PD status alone.