Can a patient with Rheumatoid Arthritis (RA) or Systemic Lupus Erythematosus (SLE) on hydroxychloroquine (HCQ) hold the medication for 5 days while taking azithromycin (Z-pack) for pneumonia?

Hydroxychloroquine Should NOT Be Held During Azithromycin Treatment for Pneumonia

For patients with RA or SLE on hydroxychloroquine who require azithromycin for pneumonia, hydroxychloroquine should be continued rather than held for 5 days. The critical importance of maintaining hydroxychloroquine therapy in these conditions outweighs the theoretical cardiac interaction risk, which can be managed through appropriate monitoring.

Rationale for Continuing Hydroxychloroquine

Critical Role in Disease Control

• Hydroxychloroquine discontinuation significantly increases flare risk in both RA and SLE, with patients who stop treatment having a 2.5-fold higher risk of disease flares 1
• The American College of Rheumatology recommends indefinite (lifelong) continuation of hydroxychloroquine in SLE patients due to its profound beneficial effects 1
• Even brief interruptions can trigger disease exacerbations, particularly concerning in SLE where flares can involve major organ systems 2, 3
• Hydroxychloroquine reduces renal flares, cardiovascular events, thrombotic complications, organ damage accumulation, and overall mortality in SLE 1, 3

Perioperative Guidelines Support Continuation

• The 2022 ACR/AAHKS guideline for perioperative management conditionally recommends continuing hydroxychloroquine through surgery for patients with RA and SLE undergoing total joint arthroplasty 4
• If hydroxychloroquine can be safely continued through major orthopedic surgery, it should certainly be continued during a 5-day course of antibiotics for pneumonia 4

COVID-19 Pandemic Experience

• During the COVID-19 pandemic, the ACR task force endorsed continued use of hydroxychloroquine in SLE patients even in the setting of active SARS-CoV-2 infection, recognizing its favorable risk/benefit profile 4
• This recommendation was made despite concerns about potential cardiotoxicity when combined with other QT-prolonging agents 4

Managing the Drug Interaction

The Actual Risk

• The primary concern with hydroxychloroquine plus azithromycin is QT interval prolongation, which can predispose to ventricular arrhythmias 4, 5
• However, short-term hydroxychloroquine use (30 days) showed no excess risk of severe adverse events in large multinational studies of RA patients 5
• The combination of hydroxychloroquine plus azithromycin was associated with increased cardiovascular risk primarily in long-term use scenarios, not 5-day courses 5

Practical Monitoring Strategy

Instead of holding hydroxychloroquine, implement cardiac monitoring:

• Obtain baseline ECG before starting azithromycin if feasible, particularly in patients with pre-existing cardiac disease, electrolyte abnormalities, or those on other QT-prolonging medications 4
• Check and correct electrolytes (potassium, magnesium) before initiating azithromycin 4
• Avoid other QT-prolonging medications during the 5-day azithromycin course when possible 4
• Consider telemetry or repeat ECG if the patient is hospitalized or has risk factors for arrhythmia 4
• If QTc exceeds 500 msec or increases >60 msec from baseline, consider alternative antibiotic therapy 4

Alternative Antibiotic Consideration

If cardiac risk factors are substantial, consider using an alternative antibiotic that does not prolong QT interval rather than holding hydroxychloroquine:

• Amoxicillin-clavulanate, doxycycline, or fluoroquinolones (though fluoroquinolones also have QT concerns) may be appropriate alternatives depending on the pneumonia severity and local resistance patterns 5
• This approach maintains disease control while eliminating the drug interaction 5

Common Pitfalls to Avoid

• Do not assume a 5-day hold is "safe" - hydroxychloroquine has a very long half-life (40-50 days), so stopping for 5 days provides minimal reduction in drug exposure anyway 6
• Do not underestimate flare risk - patients in apparent remission can experience rapid disease exacerbation when hydroxychloroquine is interrupted 2, 3
• Do not forget that rescue corticosteroids for disease flares carry their own infection risks, potentially worsening the pneumonia 4
• Recognize that hydroxychloroquine blood levels vary by only 27% (median) over a 12-hour dosing interval at steady state, so the drug maintains relatively stable concentrations 6

The evidence strongly supports continuing hydroxychloroquine with appropriate cardiac monitoring rather than risking a potentially serious disease flare by holding this critical medication for a short antibiotic course.