Safety profile of concomitant use of caspofungin and cyclosporine or tacrolimus in liver transplant patients.
BACKGROUND
Caspofungin is the first substance of a new class of antifungal agents, the echinocandins that interfere with fungal cell wall synthesis by inhibition of glucan synthesis. Alanine aminotransferase (ALT) elevations were seen in phase I studies of patients receiving caspofungin and cyclosporine A (CyA). Actually, there is no information regarding hepatotoxicity in liver transplant patients treated concomitantly with caspofungin and immunosuppressant agents like CyA or tacrolimus (TAC).


METHODS
We conducted a retrospective study in 12 liver transplant patients (9 patients Child C, 3 patients acute liver failure) to assess the hepatic safety of simultaneous administration of caspofungin with CyA or TAC. Caspofungin was administered as first-line agent to patients for a 2-week period with either proofed invasive fungal infection (IFI) (n = 4), IFI-probable (n = 4), and IFI-possible (n = 4). All patients received concomitantly CyA or TAC as immunosuppressant agent.


RESULTS
Two patients died within the first 10 days after start of treatment, caused by gram-negative rods. All other ten patients completed the 14-day treatment period. No liver enzyme elevation was recorded in these patients and administration of caspofungin with CyA or TAC was well tolerated without hepatotoxicity.


CONCLUSIONS
The concomitant use of caspofungin with CyA or TAC in liver transplant patients is safe and seemed to be without hepatotoxic effect.
Saner
F
F
Dept. of General Surgery and Transplantation, University Essen, Hufelandstr. 55, 45122, Essen, Germany. fuat.saner@uni-essen.de
Gensicke
J
J
Rath
P
P
Fruhauf
N
N
Gu
Y
Y
Paul
A
A
Radtke
A
A
Malagó
M
M
Broelsch
C
C
D000935:Antifungal Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000077336:Caspofungin; D016572:Cyclosporine / Q000009:adverse effects / Q000627:therapeutic use*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D054714:Echinocandins; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D055666:Lipopeptides; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000009:adverse effects / Q000627:therapeutic use*; D012189:Retrospective Studies; D016559:Tacrolimus / Q000009:adverse effects / Q000627:therapeutic use*
D000935:Antifungal Agents; D054714:Echinocandins; D007166:Immunosuppressive Agents; D055666:Lipopeptides; D010456:Peptides, Cyclic; D016572:Cyclosporine; D000077336:Caspofungin; D016559:Tacrolimus