CASE REPORT
A 60-year-old Caucasian male, weighing 59 kg, liver transplanted 2
months ago. In the outpatient clinic he was asymptomatic, had normal
biochemistry, and tacrolimus trough concentrations within the
therapeutic range (7.2 ng/mL and an estimated area under the curve is
steady state (eAUC) of 245 ng·h/ml) (Table 1). He was on prophylactic
treatment with tacrolimus (extended-released capsules) 8 mg qd,
mycophenolate mofetil 1000 mg bid and prednisone 5 mg qd. His oral
medication at home included: magnesium 53 mg tid, hydropherol 0.266 mg,
furosemide 40 mg bid, cotrimoxazole 400/80 mg qd, nystatin and
pantoprazole 20 mg qd.
Fifteen days after the outpatient visit, he was admitted to hospital
with signs of respiratory infection and was diagnosed of empyema
secondary to Enterobacter cloacae infection. At admission, the
patient presented with significant renal impairment (creatinine
clearance (CrCl): 27.9 ml/min/1.72 m2) with a
tacrolimus trough concentration of 20.5 ng/ml and an eAUC 524 ng·h/ml,
consistent with the nephrotoxicity associated with supratherapeutic
exposure to tacrolimus (Table 1). Correct veno sampling were ensured and
no changes were made in the tacrolimus determination technique
(enzyme-linked immunosorbent assay (DimensionⓇ)), or to the commercial
presentation of the tacrolimus prescribed to the patient. No relevant
changes in the prescribed treatment were identified that could affect
the bioavailability or pharmacokinetics of tacrolimus.
After interviewing the patient, he reported a daily intake of an
over-the-counter (OTC) herbal laxative for several days taken
concomitant with tacrolimus first time in the morning. The OTC is
composed of 80% senna leaves (Cassia angustifolia vahl ),
hibiscus extract, liquorice (Glycyrrhiza glabra ) and peppermint
(Mentha piperita ). The herbal preparation and tacrolimus
treatment were discontinued until tacrolimus plasma concentrations
normalized.
A trough of 5 ng/ml was reached three days after drug withdrawal.
Tacrolimus treatment was then gradually reintroduced. The dose was
increased using individual pharmacokinetic parameters calculated by
Bayesian estimation (Graph 1). One week after tacrolimus intoxication
and after discontinuation of herbal medicine, the patient recovered
baseline renal function (ClCr 81.9 ml/min/1.72 m2) and
achieved tacrolimus target levels at a dose similar to that before the
episode (Table 1, Graph 1).