Can micafungin and Cresemba (isavuconazonium sulfate) be given together?

Micafungin and Cresemba (Isavuconazonium Sulfate) Combination Therapy

Micafungin and Cresemba (isavuconazonium sulfate) can be administered together and may be considered as a combination therapy in select cases of invasive fungal infections, particularly for aspergillosis.

Evidence for Combination Therapy

• Combination antifungal therapy with an azole (such as isavuconazole) and an echinocandin (such as micafungin) may be considered in select patients with documented invasive pulmonary aspergillosis (IPA) 1
• The 2023 Taiwan guidelines for COVID-19 associated pulmonary aspergillosis specifically list combination treatments including "Isavuconazole + Liposomal amphotericin B" as a potential option, demonstrating that isavuconazole can be used in combination regimens 1
• Combinations of azoles with echinocandins have shown additive or synergistic effects in some preclinical studies, although clinical evidence remains limited 1

In Vitro Evidence of Synergy

• In vitro studies have demonstrated that isavuconazole and micafungin are synergistically active against several fungal species including Aspergillus fumigatus, Aspergillus flavus, Aspergillus terreus, and Cunninghamella bertholletiae 2
• Bliss independence drug interaction analysis showed that the combination of isavuconazole and micafungin resulted in synergistic interactions against Candida albicans, Candida parapsilosis, and Candida krusei 3
• Time-kill assays confirmed concentration-dependent synergy between isavuconazole and micafungin against certain Candida species 3

Clinical Applications

• Combination therapy can be considered if drug-resistant fungal infection is a concern, such as when coinfections are present 1
• For invasive pulmonary aspergillosis, combination antifungal therapy with voriconazole (another azole) and an echinocandin may be considered in select patients with documented IPA, suggesting a similar approach could be taken with isavuconazole 1
• Micafungin has shown activity in the treatment of aspergillosis in patients refractory to or intolerant of other antifungal agents 1

Pharmacological Considerations

• Echinocandins like micafungin have relatively low toxicity profiles and limited drug-drug interactions 1
• Azoles like isavuconazole are CYP3A4 inhibitors, which can lead to toxicity when administered with several classes of drugs used in cancer therapy 1
• Clinicians should obtain serum trough drug levels for azole antifungal agents (including isavuconazole) and for potentially interacting drugs to optimize therapeutic efficacy and avoid potential toxicities 1

Potential Concerns

• Clinical evidence for combination therapy remains limited, with no randomized controlled trials specifically evaluating isavuconazole and micafungin together 4
• The combination of azoles with polyenes (like amphotericin B) may show antagonism in some cases, but this concern does not apply to the isavuconazole-micafungin combination 1
• The high cost of combination therapy and limited number of cases studied may lead to weak or sometimes contradictory results in the literature 4

Conclusion

While micafungin and isavuconazole can be administered together, this combination should be reserved for specific clinical scenarios such as severe or refractory invasive fungal infections, particularly aspergillosis. The decision to use combination therapy should involve consultation with infectious disease specialists and consider local epidemiology of fungal infections, including resistance patterns.