Tacrolimus and Chloramphenicol Injection: Interaction Details

a) The addition of chloramphenicol to a stable regimen of tacrolimus produced a substantial increase in tacrolimus blood concentrations in a renal/pancreatic transplant recipient. The patient, a 56-year-old man, had immunosuppression maintained for the prior 2 weeks with a stable dose regimen of oral tacrolimus 4 milligrams (mg) twice daily (blood concentrations maintained between 5 and 11 micrograms/liter (mcg/L)). Within 3 days of starting treatment for a vancomycin-resistant enterococcal infection with chloramphenicol 750 mg 4 times daily, the patient's tacrolimus blood concentrations had risen to above 30 mcg/L. This concentration level was maintained for seven days, after which tacrolimus dose was reduced to 1.5 mg orally twice daily. The tacrolimus blood concentration subsequently declined to between 18 and 25 mcg/L. Chloramphenicol was stopped, and the tacrolimus dose was doubled to 3 mg twice daily; however, tacrolimus blood concentrations declined to below 5 mcg/L, provoking an acute episode of cellular rejection which was successfully reversed with a course of pulsed methylPREDNISolone. Thereafter, tacrolimus blood concentrations slowly returned to within the therapeutic target range ².

b) Because of vancomycin-resistant enterococcus peritonitis, a 14-year-old living donor renal transplant patient was started on chloramphenicol 600 mg every six hours 16 days post-transplant. Other medications included mycophenolate mofetil, predniSONE, acyclovir, amLODIPine, cotrimoxazole, raNITIdine, insulin, phosphorus, and tacrolimus 6 mg twice daily. At the time of chloramphenicol initiation, the patient's serum creatinine was 0.6 mg/dL and her whole blood tacrolimus trough level was 12.6 ng/mL. Within four days, her tacrolimus trough level peaked at approximately 29 ng/mL while serum creatinine was 0.7 mg/dL. Following the completion of a 10-day course of chloramphenicol, the patient's tacrolimus dose was sequentially increased to 10 mg twice daily to maintain a therapeutic trough level ³.

c) Taber et al describes a case report of a 47-year-old white male with end-stage liver disease secondary to hepatitis B who received a liver transplant. The patient received tacrolimus (4 mg/day) and predniSONE as immunosuppressant therapy. The patient's post-transplant hospital course was uneventful. Tacrolimus 12-hour trough concentration was 8.3 ng/mL. Other medications after discharge included predniSONE , Vitamin D, calcium carbonate, omeprazole , aspirin, ganciclovir , lamiVUDine , atenolol, TMP/SMX, hepatitis B immune globulin. On post-op day 28 the tacrolimus dose was increased to 5 mg orally twice daily and remained at this dose until POD 84. The tacrolimus trough concentrations ranged between 9-11 ng/mL during this period. On POD 68 a urinalysis was performed on this patient after complaints of symptoms consistent with a urinary tract infection had surfaced. On POD 73 the culture was identified as vancomycin-resistant enterococcus (VRE) which is only sensitive to chloramphenicol and nitrofurantoin. Intravenous chloramphenicol was not received until POD 78 due to poor intravenous (IV) access. The patient was administered twice the maximum recommended daily dose of chloramphenicol (1850 mg IV every 6 hours). On POD 81 the 12-hour trough concentration was greater than 60 ng/mL. At this time the patient complained of lethargy, fatigue, headaches, and tremors. Chloramphenicol and tacrolimus were discontinued as a result. On POD 88, the tacrolimus concentration was 8.2 ng/mL and the patient's symptoms subsequently resolved. Tacrolimus was initiated again at 5 mg without the addition of chloramphenicol. The patient's tacrolimus concentrations returned to normal ⁴.