Nifedipine interaction with tacrolimus in liver transplant recipients.
OBJECTIVE
To examine the possible drug interaction between nifedipine and tacrolimus in liver transplant recipients.


METHODS
A retrospective study was done comparing two groups of liver transplant recipients. The starting time for comparison was the same after transplant. One group (n = 22) consisted of hypertensive patients who were treated with nifedipine; the other group (n = 28) did not receive nifedipine. The two groups were compared over 1 year. The effect of nifedipine on tacrolimus was measured in terms of tacrolimus whole blood trough concentrations, daily tacrolimus dosages, and cumulative tacrolimus dosages at 1, 3, 6, and 12 months. All patient charts were reviewed with regard to concurrent medication that could affect the metabolism of tacrolimus and eventually affect tacrolimus concentrations and dosages.


METHODS
All required information was retrieved from medical records.


RESULTS
There was a statistically significant difference between daily dosage requirements of tacrolimus at 90 (p = 0.03), 180 (p = 0.004), and 365 (p = 0.0004) days between the nifedipine and no-nifedipine groups. The tacrolimus daily dosage in the nifedipine group was decreased by 26%, 29%, and 38% at 3, 6, and 12 months, respectively, compared with the dosage of the no-nifedipine group. Statistically significant differences in cumulative dosages of tacrolimus were observed at 180 (p = 0.02) and 365 (p = 0.003) days between the nifedipine and no-nifedipine groups, with cumulative dosage reduction of 25% and 31% by 6 and 12 months, respectively, in the nifedipine group compared with the no-nifedipine group.


CONCLUSIONS
Nifedipine decreased the daily and cumulative dosage requirement of tacrolimus. The interaction observed between nifedipine and tacrolimus is the first reported in humans and is clinically important. As a result of this drug interaction, it is recommended that blood concentrations of tacrolimus be monitored during coadministration of these drugs and that the tacrolimus dosage be adjusted accordingly.
Seifeldin
R A
RA
GD Searle & Co., Skokie, IL 60077, USA.
Marcos-Alvarez
A
A
Gordon
F D
FD
Lewis
W D
WD
Jenkins
R L
RL
D000328:Adult; D000368:Aged; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D003404:Creatinine / Q000097:blood; D004347:Drug Interactions; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008111:Liver Function Tests; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009543:Nifedipine / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D012189:Retrospective Studies; D016559:Tacrolimus / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use
D002121:Calcium Channel Blockers; D007166:Immunosuppressive Agents; D003404:Creatinine; D009543:Nifedipine; D016559:Tacrolimus