Does Zyflo (zileuton) cause a drug interaction with Daliresp (roflumilast)?

Drug Interaction Between Zyflo (Zileuton) and Daliresp (Roflumilast)

There is no documented direct drug interaction between Zyflo (zileuton) and Daliresp (roflumilast), but caution is warranted due to their metabolic pathways and potential for additive side effects.

Mechanism of Action and Metabolism

Zyflo (Zileuton)

• Zileuton is a 5-lipoxygenase inhibitor used for asthma treatment 1
• Metabolized by the liver through cytochrome P450 enzymes 2
• Known to be a microsomal P450 enzyme inhibitor that can affect metabolism of other drugs like warfarin and theophylline 1

Daliresp (Roflumilast)

• Roflumilast is a phosphodiesterase-4 (PDE4) inhibitor used for severe COPD with chronic bronchitis and exacerbation history 1
• Metabolized in the liver by cytochrome P450 enzymes 3
• Strong CYP inducers (rifampin, phenobarbital, carbamazepine, phenytoin) can decrease roflumilast efficacy 1

Theoretical Concerns

While no direct interaction studies between zileuton and roflumilast have been published, there are several theoretical concerns:

1. Hepatic metabolism overlap: Both medications are metabolized by cytochrome P450 enzymes, creating potential for competitive inhibition 1, 3

2. Additive side effects: Both medications can cause:

   • Gastrointestinal disturbances (nausea, diarrhea)
   • Headache
   • Psychiatric effects (depression, anxiety)

3. Liver function: Both medications require liver function monitoring

   • Zileuton requires essential liver function monitoring 1
   • Roflumilast is metabolized in the liver and may have altered clearance in hepatic impairment 1

Clinical Recommendations

1. Monitor liver function: Regular liver enzyme testing is essential when using zileuton 1 and should be continued if using both medications

2. Watch for psychiatric symptoms: Both medications have been associated with psychiatric effects

   • Roflumilast may cause depression, anxiety, and sleep disturbances in up to 7.1% of patients 1
   • Zileuton has been included in FDA warnings about potential neuropsychiatric events 4

3. Monitor for gastrointestinal side effects: Both medications can cause GI disturbances, which may be additive

4. Consider alternative options: If both medications are needed, consider:

   • Using alternative treatments for either condition if possible
   • Spacing administration times to minimize potential interactions
   • Close monitoring for adverse effects

Conclusion

While there is no documented direct interaction between zileuton and roflumilast, their shared metabolic pathways and overlapping side effect profiles warrant caution. If both medications are deemed necessary, close monitoring of liver function and side effects is essential. Consider consulting with a clinical pharmacist for specific dosing recommendations if both medications must be used concurrently.