High-dose caspofungin as a component of combination antifungal therapy in 91 patients with neoplastic diseases and hematopoietic stem cell transplantation: a critical review of short-term and long-term adverse events.

Safdar A, Rodriguez G, Zuniga J, Al Akhrass F, Pande A.

J Pharm Pract. 2015 Apr;28(2):175-82.

The antifungal activity of echinocandins is concentration dependent. Previously,
we demonstrated that high-dose caspofungin (HD-CSP; 100 mg daily) was well
tolerated in 34 immunosuppressed patients with cancer and may have favorably
influenced outcomes. We retrospectively assessed all 91 patients in whom HD-CSP
was given for the treatment of invasive fungal disease (IFD). The median number
of doses was 18.5 ± 21.5, and in 8 (9%) patients more than 40 doses were given.
Most (62%) of the patients had leukemia. A total of 45 (49%) patients had
undergone stem cell transplantation; 80% received allogeneic grafts and 47% had
graft-versus-host disease. High-dose corticosteroids were given during antifungal
therapy in 26 (29%) patients. In all, 8 (9%) patients had new elevation in serum
bilirubin during HD-CSP therapy; normalization occurred after voriconazole and
HD-CSP were discontinued in 4 patients each. No other short-term or delayed
adverse events were observed. In all, 40 (44%) patients died of IFD. High-dose
corticosteroids during HD-CSP (odds ratio [OR] 8, 95% confidence interval [CI]
2.1-30.4; P < .002) and starting HD-CSP in the critical care unit (OR 67.5, 95%
CI 5.25-868.9; P < .001) were associated with death from fungal disease.
Prolonged HD-CSP therapy was well tolerated. Drug-induced hyperbilirubinemia may
pose a potential limitation for continued HD-CSP use in highly susceptible
patients with hematologic neoplasms and stem cell transplantation.