Retrospective study of the hepatic safety profile of patients concomitantly treated with caspofungin and cyclosporin A.
BACKGROUND
Mild, transient alanine aminotransferase (ALT) elevations were seen in Phase I studies of caspofungin and cyclosporin A (CsA).


METHODS
We conducted a retrospective chart review at four sites to characterize the hepatic safety in patients receiving > or =1 day of both drugs over a 20-month period. Investigators assessed reasons for discontinuing concomitant therapy and the presence/etiology of any hepatotoxicity.


RESULTS
Forty patients receiving concomitant therapy for 1-290 days (median 17.5 days) were identified. Although common, liver enzyme abnormalities were frequently attributed to other comorbidities or medications. ALT and/or aspartate aminotransferase (AST) elevations occurred in 14 patients (35%). Five had AST elevations at least possibly related to caspofungin/CsA, but none were >3.6 times the normal upper limit. No ALT elevations were related to caspofungin/CsA. Two of 4 patients had discontinuation of therapy because of hepatotoxicity possibly related to caspofungin/CsA. No serious adverse events occurred because of caspofungin.


CONCLUSIONS
These data do not suggest a significant risk of clinically relevant hepatotoxicity with concomitant caspofungin/CsA.
Marr
K A
KA
Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Hachem
R
R
Papanicolaou
G
G
Somani
J
J
Arduino
J M
JM
Lipka
C J
CJ
Ngai
A L
AL
Kartsonis
N
N
Chodakewitz
J
J
Sable
C
C
D000293:Adolescent; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001219:Aspartate Aminotransferases / Q000097:blood; D000077336:Caspofungin; D056486:Chemical and Drug Induced Liver Injury; D016572:Cyclosporine / Q000008:administration & dosage / Q000009:adverse effects*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D054714:Echinocandins; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D055666:Lipopeptides; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000009:adverse effects*; D012189:Retrospective Studies
D000935:Antifungal Agents; D054714:Echinocandins; D007166:Immunosuppressive Agents; D055666:Lipopeptides; D010456:Peptides, Cyclic; D016572:Cyclosporine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000077336:Caspofungin