Development and Introduction of Guidelines Regarding the Co-Administration of Azole Antifungal Agents and Vinca Alkaloids (#272)
The azole class of antifungal agents inhibits cytochrome P450 3A4 isoenzymes and vinca alkaloids (VA) (vinblastine, vincristine, vinorelbine and vinflunine) are metabolised via this pathway. Some azoles also act as PgP inhibitors. Therefore, concomitant administration of these drug classes may increase serum levels of VA and increase risk of toxicity. Currently, we are unaware of guidelines to inform how best to manage patients in this situation.
Following a comprehensive literature review, a multidisciplinary working group was convened to develop and implement a guideline for use within our specialist cancer centre guiding the management of medical oncology and haematology patients who require prophylaxis or treatment with an azole antifungal (AA) whilst being treated on a VA-containing chemotherapy protocol.
The preferred antifungal agent for patients on VA-containing protocols depends on risk of developing an invasive fungal infection (IFI) and the intended purpose. The following guidance is based on the available literature and expert opinion, with risk assessment according to the tool proposed by Prentice HG et al. Patients at low/low-intermediate risk for IFI require no routine antifungal prophylaxis. Any AA prescribed should be withheld for 48hrs both pre and post-VA. Patients at high/intermediate-high risk (including patients receiving secondary prophylaxis) or those on AA treatment, should cease AA 48hrs pre-VA and the following day commence liposomal amphotericin B (100mg IV three times/week or 3-5mg/kg/day for patients requiring treatment for IFI) or caspofungin 70mg IV on day1 followed by 50mg IV daily thereafter with agent choice dependent on required anti-fungal spectrum. For treatment of fungi other than Aspergillus or Candida sp., Infectious Diseases advice is recommended. AA should be recommenced 48hrs post-VA administration and liposomal amphotericin B or caspofungin should continue for 72hrs post recommencement of AA.
These guidelines provide an evidence-based approach to these commonly encountered drug-class interactions.