Can clarithromycin be used as a substitute for azithromycin (Zithromax)?

Can Clarithromycin Be Used Instead of Azithromycin?

Yes, clarithromycin can be substituted for azithromycin as both macrolides demonstrate equivalent microbiological efficacy and clinical outcomes, but azithromycin is generally preferred due to better tolerability, fewer drug interactions, once-daily dosing, and lower pill burden. 1

When Clarithromycin Is an Acceptable Alternative

Clarithromycin is specifically recommended as a substitute when azithromycin is not tolerated or when drug interactions preclude azithromycin use. 1 The evidence shows:

• No clinically significant differences exist between the two drugs in sputum culture conversion rates at 6 months, end of therapy, sustained conversion after treatment, or acquisition of macrolide resistance 1
• Both drugs demonstrate similar bacteriological eradication rates (94-95%) and clinical success rates (95-97%) in respiratory tract infections 2
• Studies document successful switching between agents when intolerance occurs in either direction 1

Why Azithromycin Is Generally Preferred

Drug Interaction Profile

• Azithromycin has substantially fewer cytochrome P450-mediated drug interactions compared to clarithromycin 1
• When rifamycins (rifampicin or rifabutin) are used concurrently, clarithromycin creates bidirectional interactions with rifabutin, increasing rifabutin concentrations and causing uveitis risk 1
• Azithromycin serum concentrations are affected less by concurrent rifamycin administration 1

Tolerability Differences

• Expert panels consistently identify better tolerability as the primary reason for preferring azithromycin 1
• Clarithromycin at higher doses (1000 mg twice daily) associates with bitter taste, nausea, and elevated hepatic enzymes 1
• Azithromycin at higher doses (600 mg daily) in older patients associates with hearing loss and gastrointestinal symptoms 1
• Both drugs carry similar rates of gastrointestinal side effects (7.4-8.4%), which are lower than erythromycin 2

Practical Advantages

• Once-daily dosing with azithromycin versus twice-daily with clarithromycin improves compliance 1
• Lower pill burden with azithromycin 1
• Possibly lower costs 1

Context-Specific Recommendations

For MAC (Mycobacterium Avium Complex) Disease

• In HIV-infected patients with disseminated MAC, clarithromycin is actually the preferred first agent due to more extensive study and more rapid clearance of MAC from blood 1
• However, azithromycin can be substituted when drug interactions or clarithromycin intolerance occur 1

For Nontuberculous Mycobacterial Pulmonary Disease

• Azithromycin is preferred over clarithromycin for the same reasons as general use 1
• In places where azithromycin is unavailable, clarithromycin is an acceptable alternative, though more drug interactions are possible 1

Important Safety Considerations

QTc Prolongation Risk

• Both macrolides carry risk of sudden death from QTc prolongation, though systematic reviews show no increased cardiac mortality versus placebo 1
• Consider electrocardiographic monitoring when concurrent QTc-prolonging medications are used 1

Common Pitfalls to Avoid

• Do not assume equivalent drug interaction profiles—clarithromycin requires careful review of concurrent medications, particularly rifamycins, due to CYP450 interactions 1
• Monitor for rifabutin-induced uveitis if clarithromycin and rifabutin are used together 1
• Consider dose adjustments for clarithromycin in renal dysfunction when used with ritonavir or lopinavir-ritonavir 1

Practical Algorithm for Substitution

1. If azithromycin causes intolerance (GI symptoms, hearing loss): Switch to clarithromycin 1
2. If patient is on rifamycins or multiple CYP450-metabolized drugs: Prefer azithromycin 1
3. If azithromycin is unavailable: Use clarithromycin with careful drug interaction screening 1
4. If treating disseminated MAC in HIV patients: Consider clarithromycin as first-line option 1