Does clarithromycin (antibiotic) increase the serum concentration of acebrophylline (bronchodilator) in patients, particularly those with a history of respiratory issues, impaired renal function, or hepatic dysfunction?

Clarithromycin and Acebrophylline Drug Interaction

Direct Answer

Yes, clarithromycin significantly increases serum concentrations of theophylline-related compounds through CYP450 inhibition, and this interaction can lead to serious toxicity including rhabdomyolysis and acute renal failure, particularly in elderly patients or those with dehydration. While the evidence specifically addresses theophylline rather than acebrophylline (a theophylline derivative), the same metabolic pathway and mechanism of interaction applies 1, 2.

Mechanism of Interaction

Clarithromycin is a potent inhibitor of cytochrome P450 3A4 (CYP3A) isozymes, which are responsible for metabolizing theophylline and its derivatives 2. This inhibition results in:

• Decreased hepatic clearance of theophylline compounds 1
• Accumulation of drug in the bloodstream with repeated dosing 2
• Enhanced toxicity risk, especially with concurrent administration 1, 3

Clinical Significance and Risk Factors

The interaction between clarithromycin and theophylline compounds has resulted in documented cases of life-threatening complications 1. A case report demonstrated acute renal failure with rhabdomyolysis (CK elevation to 36,000 IU/L) in a 72-year-old patient receiving both medications concurrently 1.

High-Risk Patient Populations:

• Elderly patients (particularly those over 70 years) are at substantially increased risk 1
• Patients with dehydration have enhanced susceptibility to toxicity 1
• Those with pre-existing renal impairment face compounded risk, as both clarithromycin and its metabolites accumulate in renal dysfunction 2
• Patients with hepatic dysfunction may have further impaired drug metabolism 4

Monitoring and Management Recommendations

If concurrent use is unavoidable, implement intensive monitoring protocols:

• Monitor for early toxicity signs: generalized twitching, muscular weakness, tremor, high fever 1
• Check serum theophylline/acebrophylline levels within 2-3 days of starting clarithromycin 1, 3
• Assess renal function (BUN, creatinine) and muscle injury markers (CK) if symptoms develop 1
• Consider prophylactic dose reduction of acebrophylline by 25-50% when initiating clarithromycin, particularly in elderly or renally impaired patients 1

Alternative Antibiotic Considerations

Azithromycin represents a safer macrolide alternative as it does not undergo significant CYP450 metabolism and has minimal drug-drug interactions compared to clarithromycin 4. Azithromycin can be used safely without concerns of interactions with theophylline derivatives 4.

Common Pitfalls to Avoid

• Do not assume standard dosing is safe when combining these medications—proactive dose adjustment is necessary 1
• Do not overlook subtle early symptoms (mild tremor, nausea) as they may precede severe toxicity 1
• Do not delay discontinuation if toxicity signs appear—the interaction can rapidly progress to rhabdomyolysis and renal failure 1
• Do not forget that clarithromycin requires dose adjustment itself in patients with creatinine clearance <60 mL/min, which further complicates management 4

Contraindications Related to This Interaction

Clarithromycin should not be used in patients with severe hepatic failure combined with renal impairment, as this dramatically increases risk of drug accumulation and toxicity 4. In such patients requiring both a macrolide and bronchodilator therapy, azithromycin is the preferred macrolide 4.