Eraxis Drug Interactions

Preclinical in vitro and in vivo studies and clinical studies have demonstrated that anidulafungin is not a clinically relevant substrate, inducer, or inhibitor of cytochrome P450 isoenzymes. Interaction studies have only been performed in adults. Anidulafungin has negligible renal clearance (<1%). Minimal interactions are expected with the concomitant medications (see Pharmacology: Pharmacokinetics under Actions).
In vitro studies showed that anidulafungin is not metabolized by human cytochrome P450 or by isolated human hepatocytes, and anidulafungin does not significantly inhibit the activities of human CYP isoforms (1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 3A) at clinically relevant concentrations. Of note, in vitro studies do not fully exclude possible in vivo interactions.
No clinically relevant drug-drug interactions were observed with the following drugs likely to be co-administered with anidulafungin.
Cyclosporin (CYP3A4 substrate): In a study of 12 healthy adult subjects who received 100 mg/day anidulafungin following a 200 mg loading dose alone and in combination with 1.25 mg/kg oral cyclosporin twice daily, the steady-state plasma peak concentration (C_max) of anidulafungin was not significantly altered by cyclosporin; however, the steady-state area under the concentration-time curve (AUC) was increased by 22%. An in vitro study has shown that anidulafungin has no effect on the metabolism of cyclosporine. Adverse events observed in this study were consistent with those observed in other studies where anidulafungin only was administered. No dosage adjustment of either drug is required when they are co-administered.
Voriconazole (CYP2C19, CYP2C9, CYP3A4 inhibitor and substrate): In a study of 17 healthy subjects who received 100 mg/day anidulafungin alone following a 200 mg loading dose, 200 mg twice daily oral voriconazole alone following 400 mg twice on the first day as loading doses, and both in combination, the steady-state C_max and AUC of anidulafungin and voriconazole were not significantly altered by co-administration. No dosage adjustment of either drug is required when co-administered.
Tacrolimus (CYP3A4 substrate): In a study of 35 healthy subjects who received a single oral dose of 5 mg tacrolimus alone, 100 mg/day anidulafungin alone following a 200 mg loading dose and both in combination, the steady-state C_max and AUC of anidulafungin and tacrolimus were not significantly altered by co-administration. No dosage adjustment of either drug is required when co-administered.
Liposomal amphotericin B: The pharmacokinetics of anidulafungin were examined in 27 patients (100 mg/day anidulafungin) who were co-administered with liposomal amphotericin B (doses up to 5 mg/kg/day). The population pharmacokinetic analysis showed that the pharmacokinetics of anidulafungin were not significantly altered by co-administration with amphotericin B when compared to data from patients who did not receive amphotericin B. No dosage adjustment of anidulafungin is required.
Rifampicin (potent CYP450 inducer): The pharmacokinetics of anidulafungin were examined in 27 patients (50 or 75 mg/day anidulafungin) who were co-administered with rifampicin (doses up to 600 mg/day). The population pharmacokinetic analysis showed that when compared to data from patients that did not receive rifampicin, the pharmacokinetics of anidulafungin were not significantly altered by co-administration with rifampicin. No dosage adjustment of anidulafungin is required.
Paediatric population: Interaction studies have only been performed in adults.