Hepatic Effects
Laboratory abnormalities in liver function tests have been seen in healthy volunteers
and patients treated with ERAXIS. In some patients with serious underlying medical
conditions who were receiving multiple concomitant medications along with ERAXIS,
clinically significant hepatic abnormalities have occurred. Isolated cases of significant
hepatic dysfunction, hepatitis, or worsening hepatic failure have been reported
in patients; a causal relationship to ERAXIS has not been established. Patients
who develop abnormal liver function tests during ERAXIS therapy should be monitored
for evidence of worsening hepatic function and evaluated for risk/benefit of continuing
ERAXIS therapy.
Drug Interactions
Pre-clinical in vitro and in vivo and clinical studies demonstrated
that anidulafungin is not a clinically relevant substrate, inducer, or inhibitor
of cytochrome P450 isoenzymes. Anidulafungin has negligible renal clearance. Minimal
interactions are expected from the concomitant medications (see CLINICAL PHARMACOLOGY
– Drug Interaction Studies).
Drug interaction studies were performed with anidulafungin and other drugs likely
to be co-administered. When used in therapeutic doses, no dosage adjustment of either
drug is recommended when anidulafungin is co-administered with voriconazole or tacrolimus,
and no dosage adjustment for anidulafungin is recommended when co-administered with
amphotericin B or rifampin (see CLINICAL PHARMACOLOGY – Drug Interaction Studies).
Co-administration with cyclosporine slightly increased the steady state AUC of anidulafungin
by 22%. A separate in vitro study showed that anidulafungin has no effect
on the metabolism of cyclosporine. Adverse events observed in the study were consistent
with adverse events observed from other studies with the administration of anidulafungin
alone. No dosage adjustment of either drug is warranted for patients on concomitant
cyclosporine (see CLINICAL PHARMACOLOGY – Drug Interaction Studies).
Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term animal carcinogenicity studies of anidulafungin have not been conducted.
Anidulafungin was not genotoxic in the following in vitro studies: bacterial reverse
mutation assays, a chromosome aberration assay with Chinese hamster ovary cells,
and a forward gene mutation assay with mouse lymphoma cells. Anidulafungin was not
genotoxic in mice using the in vivo micronucleus assay.
Anidulafungin produced no adverse effects on fertility in male or female rats at
intravenous doses of 20 mg/kg/day (equivalent to 2 times the proposed therapeutic
maintenance dose of 100 mg/day on the basis of relative body surface area).
Pregnancy
Pregnancy Category C
Embryo-fetal development studies were conducted with doses up to 20 mg/kg/day in
rats and rabbits (equivalent to 2 and 4 times, respectively, the proposed therapeutic
maintenance dose of 100 mg/day on the basis of relative body surface area). Anidulafungin
administration resulted in skeletal changes in rat fetuses including incomplete
ossification of various bones and wavy, misaligned or misshapen ribs. These changes
were not dose-related and were within the range of the laboratory's historical control
database. Developmental effects observed in rabbits (slightly reduced fetal weights)
occurred in the high dose group, a dose that also produced maternal toxicity. Anidulafungin
crossed the placental barrier in rats and was detected in fetal plasma.
There are no adequate and well-controlled studies in pregnant women. Because animal
reproduction studies are not always predictive of human response, ERAXIS should
be used during pregnancy only if the potential benefit justifies the risk to the
fetus.
Nursing Mothers
ERAXIS should be administered to nursing mothers only if the potential benefit justifies
the risk. Anidulafungin was found in the milk of lactating rats. It is not known
whether anidulafungin is excreted in human milk.
Pediatric Use
Safety and effectiveness of anidulafungin in pediatric patients has not been established
(see CLINICAL PHARMACOLOGY-Special Populations/Pediatric).