What are the risks of combining azithromycin (Zithromax) and quetiapine (Seroquel)?

Risks of Combining Azithromycin (Zithromax) and Quetiapine (Seroquel)

The combination of azithromycin and quetiapine poses a significant risk of QT interval prolongation that could lead to potentially fatal cardiac arrhythmias, and this combination should be avoided whenever possible, especially in elderly patients and those with pre-existing cardiac conditions. 1

Cardiac Risks

• Azithromycin has been associated with QT interval prolongation and increased risk of cardiovascular death, particularly in patients with pre-existing cardiac risk factors 2, 3
• Quetiapine (Seroquel) is also known to prolong the QT interval, creating a potentially dangerous additive effect when combined with azithromycin 1
• The odds ratio for QT prolongation with azithromycin exposure alone is 1.40 (95% CI, 1.23-1.59), and for severe QT prolongation (QTc >500 ms) is 1.43 (95% CI, 1.13-1.82) 2
• The risk of QT prolongation is significantly higher in patients aged 60-79 years when exposed to azithromycin 2

Mechanism of Interaction

• Azithromycin metabolism is not affected by the cytochrome P450 (CYP450) system, unlike other macrolides, which makes some drug interactions less likely 4
• However, the primary concern with this combination is not metabolic interaction but rather the additive effect on cardiac repolarization (QT interval) 1
• Studies have documented highly probable drug interactions between antipsychotics and certain COVID-19 medications, including azithromycin, due to QT prolongation risk 1

Monitoring Recommendations

• If the combination cannot be avoided, ECG monitoring before and during treatment is essential 1, 5
• A baseline QTc greater than 377.5 ms may indicate increased risk of QTc prolongation above 430 ms when exposed to QT-prolonging medications 5
• Patients should be monitored for symptoms such as palpitations, dizziness, or syncope, which may indicate cardiac arrhythmias 3
• Electrolyte abnormalities (particularly hypokalemia, hypomagnesemia) should be corrected before initiating either medication, as they can exacerbate QT prolongation 4

Additional Risk Factors to Consider

• Elderly patients (60-79 years) have significantly higher risk of QT prolongation with azithromycin 2
• Patients with pre-existing cardiovascular disease are at higher risk for adverse events 3
• Concurrent use of other QT-prolonging medications further increases risk 1
• Hepatic or renal impairment may increase drug levels and associated risks 4
• Azithromycin has been rarely associated with rhabdomyolysis, which could potentially worsen with quetiapine 6

Alternative Options

• Consider amoxicillin instead of azithromycin when an antibiotic is needed, as it has not shown significant QT prolongation risk (OR 1.06,95% CI 0.97-1.15) 2
• If an antipsychotic is necessary, consider options with lower risk of QT prolongation than quetiapine 1
• When treating respiratory infections, evaluate whether antibiotic therapy is truly necessary, as guidelines recommend against routine use of azithromycin for conditions like COVID-19 4

Clinical Decision Algorithm

1. Assess baseline cardiac risk (age, cardiovascular history, electrolytes, baseline QTc if available)
2. If patient has pre-existing QTc prolongation or cardiovascular disease, absolutely avoid this combination 2, 1
3. If treatment with both medications is deemed necessary:
   • Obtain baseline ECG and electrolytes
   • Monitor QTc during treatment
   • Discontinue if QTc exceeds 500ms or increases by >60ms from baseline 2
   • Consider dose reduction of quetiapine
4. Evaluate for alternative treatments with lower risk profiles for either medication 2, 1