Effect of coadministered HIV-protease inhibitors on tacrolimus and sirolimus blood concentrations in a kidney transplant recipient.
A patient with human immunodeficiency virus infection and end-stage renal disease received a renal transplant. At the time of surgery, the patient was on quadruple antiretroviral therapy (lamivudine, zidovudine, and amprenavir/ritonavir). Immunosuppression was initiated with basiliximab, corticosteroid, mycophenolate mofetil, and a single 0.5 mg dose of tacrolimus. In the following days, an increase in tacrolimus concentration was observed with a peak of 37 ng/mL. Tacrolimus half-life was 6.5 days and tacrolimus maintenance dose was 0.5 mg every 4 days. Eleven months later, the patient had developed Kaposi sarcoma. Tacrolimus was replaced by sirolimus (first dose 1 mg), and the patient was stabilized with 1.5 mg of sirolimus once a week. Increased tacrolimus half-life and increased dose interval of sirolimus and tacrolimus were due to CYP3A4/5 and/or P-glycoprotein inhibition by protease inhibitors. Close monitoring is required in the management of tacrolimus and sirolimus dosing regimens when combined with ritonavir boosted HIV-1 protease inhibitors.
Barau
Caroline
C
Department of Clinical Pharmacy, Bicêtre Hospital, APHP, Le Kremlin Bicêtre, France.
Blouin
P
P
Creput
Caroline
C
Taburet
A M
AM
Durrbach
Antoine
A
Furlan
Valérie
V
D004347:Drug Interactions; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy; D017320:HIV Protease Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006207:Half-Life; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007676:Kidney Failure, Chronic / Q000628:therapy; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D012514:Sarcoma, Kaposi / Q000188:drug therapy / Q000209:etiology; D020123:Sirolimus / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016559:Tacrolimus / Q000493:pharmacokinetics* / Q000627:therapeutic use
D017320:HIV Protease Inhibitors; D007166:Immunosuppressive Agents; D020123:Sirolimus; D016559:Tacrolimus