Syncope associated with concurrent amitriptyline and fluconazole therapy

To report on a 12-year-old white male with prostatic rhabdomyosarcoma who experienced episodes of syncope attributed to concurrent amitriptyline and fluconazole therapy, confirmed by readministration.

The patient began experiencing syncopal episodes periodically over a seven-month period. These repeated episodes occurred when fluconazole was administered for periodic mucositis secondary to chemotherapy. The patient had received fluconazole in the past with no difficulty and had been receiving a stable dose of amitriptyline for neuropathic pain. On discontinuation of amitriptyline, no further episodes were noted.

Concurrent administration of fluconazole with amitriptyline likely resulted in the decreased metabolism of amitriptytine. Three case reports presented in the literature of adults receiving concurrent amitriptyline and fluconazole have shown an increase in serum amitriptyline concentrations with concurrent administration of fluconazole; however, none of these patients were rechallenged. Literature available on amitriptyline overdose confirms that syncope and the adverse events noted in the case studies may result from elevated amitriptyline plasma concentrations.

The consistent presentation of syncope in our patient during readministration of amitriptytine and fluconazole strongly suggests a drug-drug interaction.