Managing Influenza in Patients with G6PD Deficiency
Patients with G6PD deficiency can be safely treated for influenza with standard antivirals (oseltamivir, zanamivir, peramivir, baloxavir), acetaminophen or ibuprofen for fever, and influenza vaccines, but must strictly avoid dapsone, methylene blue, nitrofurantoin, and phenazopyridine if bacterial complications arise. 1, 2, 3
Antiviral Therapy: Safe and Recommended
Oseltamivir (Tamiflu) 75 mg orally twice daily for 5 days is the first-line antiviral and is safe in G6PD deficiency—no evidence exists contraindicating neuraminidase inhibitors in G6PD-deficient patients. 2, 3
Alternative antivirals including zanamivir (10 mg inhaled twice daily), peramivir (600 mg IV single dose), and baloxavir (40-80 mg single oral dose) are equally safe options when oseltamivir is not tolerated or appropriate. 2, 3
Start antiviral treatment immediately upon suspicion of influenza, particularly in high-risk patients (age <2 years, ≥65 years, pregnant/postpartum women, chronic medical conditions, immunocompromised), regardless of symptom duration. 2
For otherwise healthy patients not at high risk, antivirals provide maximal benefit when started within 48 hours of symptom onset but can still be considered beyond this window. 2
Antipyretic Therapy: Safe Options
Acetaminophen and ibuprofen are both safe for fever management in G6PD-deficient patients—neither medication has evidence of causing hemolysis in this population. 2, 3
Provide adequate hydration alongside symptomatic fever treatment and encourage rest with isolation to prevent transmission. 2
Influenza Vaccination: Safe and Strongly Recommended
Influenza vaccines (both inactivated and live-attenuated formulations) are safe in G6PD deficiency—no contraindication exists, and vaccination remains the cornerstone of prevention. 3
Consider antiviral chemoprophylaxis during the 2-week period after vaccination before optimal immunity develops in high-risk G6PD-deficient patients. 2
Antibiotic Selection for Bacterial Complications: Critical Considerations
When to Suspect Bacterial Superinfection
- Investigate and empirically treat bacterial coinfection when any of the following occur: 2
- Clinical deterioration after initial improvement
- Failure to improve after 3-5 days of antiviral therapy
- Severe initial presentation with extensive pneumonia or respiratory failure
- Re-emergence of fever with increased dyspnea or new chest pain
Safe First-Line Antibiotics
Co-amoxiclav (amoxicillin-clavulanate) 625 mg orally three times daily for 7 days is the preferred first-line antibiotic, providing coverage against Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus—the major post-influenza pathogens. 4, 2
For penicillin-allergic patients, doxycycline (200 mg loading dose, then 100 mg once daily) is safe and effective in G6PD deficiency. 4, 2, 3
Clarithromycin (500 mg twice daily) or cefuroxime are acceptable alternatives for penicillin-allergic patients, particularly children under 12 years. 4
Respiratory fluoroquinolones (levofloxacin, moxifloxacin) and ciprofloxacin have been prescribed safely to thousands of G6PD-deficient patients in real-world studies. 5
Absolutely Contraindicated Antibiotics
Dapsone is absolutely contraindicated—it is a potent oxidant that causes methemoglobinemia and severe hemolysis by overwhelming the reductive capacity of G6PD-deficient red blood cells. 1, 3, 6
Nitrofurantoin must be avoided—solid evidence confirms it causes hemolysis in G6PD deficiency, though real-world data show it has been prescribed to 1,366 G6PD-deficient patients without major hemolysis in one large cohort. 3, 5
Phenazopyridine is contraindicated based on established evidence, though one real-world study reported safe use in hundreds of patients. 3, 5
Antibiotics Previously Suspected but Now Considered Safe
Sulfamethoxazole/trimethoprim (cotrimoxazole), sulfasalazine, and sulfacetamide have been prescribed safely to hundreds or thousands of G6PD-deficient patients in real-world practice, contradicting older warnings. 5
The confusion regarding sulfonamides likely arose because many patients receiving these drugs were simultaneously experiencing infection-related hemolytic episodes, wrongly attributing hemolysis to the medication. 3
Monitoring for Treatment Response and Complications
Expect clinical improvement within 48 hours of starting antiviral therapy; failure to improve warrants reassessment for bacterial superinfection or alternative diagnoses. 2
Red-flag signs requiring urgent evaluation include: 2
- Temperature >37.8°C with worsening respiratory symptoms
- Respiratory rate >24 breaths/min
- New confusion or altered mental status
- Systolic blood pressure <90 mmHg
- New focal chest findings on examination
Educate G6PD-deficient patients to recognize early signs of hemolysis: dark urine, sudden fatigue or pallor, jaundice, and abdominal or back pain. 1
Critical Pitfalls to Avoid
Never withhold antiviral therapy in elderly patients (≥65 years) who present beyond 48 hours—age ≥65 is an absolute indication for treatment regardless of timing due to markedly increased risk of severe complications. 2
Never use methylene blue for methemoglobinemia in G6PD-deficient patients—it can precipitate severe hemolytic anemia and paradoxically worsen methemoglobinemia; use high-dose ascorbic acid (0.5-10 g) or exchange transfusion instead. 1, 7, 3
Do not administer systemic corticosteroids for influenza treatment unless independently indicated for conditions like COPD or asthma exacerbation. 2
Screen for G6PD deficiency before prescribing any oxidant drug in patients of Mediterranean, African, Indian, or Southeast Asian descent to prevent inadvertent hemolytic crises. 1, 7
Special Populations
Children Under 12 Years
Co-amoxiclav remains the antibiotic of choice for bacterial complications in children with G6PD deficiency. 4
Clarithromycin or cefuroxime should be used in penicillin-allergic children. 4
Doxycycline is contraindicated in children under 8 years of age. 1