Scientific Poster Session III - Case Reports

Abstract

Liver transplant recipients in chronic liver transplant rejection are expected to have decreased metabolism of any hepatically metabolized drug. This case report illustrates the use of pharmacokinetic monitoring and empiric dose adjustments for treatment of suspected fungal infection with voriconazole in a patient with limited hepatic function.

Case:

A 30 year old female liver transplant recipient presented 9.5 months post transplant with elevated liver enzymes and marked cholestasis with worsening chronic liver rejection. Voriconazole treatment initiated based on high suspicion of invasive fungal infection. Total bilirubin was elevated greater than 40 mg/dL during treatment course. After initial unadjusted voriconazole dosage of 6mg/kg every 12 hours for two doses, the dose was reduced to 2mg/kg every 12 hours on day 3. After two doses of this reduced regimen, serum voriconazole level was 3.5 mcg/mL. Due to level drawn prior to estimated steady state, the dose was reduced to 2mg/kg every 24 hours on day 4. Following three doses of this regimen, the serum voriconazole trough level was within goal range at 3.3 mcg/mL. The patient then transitioned to hospice care.

Discussion:

The adjustments in voriconazole dosage to maintain therapeutic concentrations were partially aligned with literature including the hepatic impairment population. Drug information references state to reduce maintenance dosing by 50% in mild to moderate hepatic impairment. The unique situation of this case gives rationale for early trough monitoring combined with both dose and frequency adjustments in patients with severe cholestasis.

Conclusion:

Empiric reduction of voriconazole is indicated to avoid toxicity in patients with severe cholestasis from chronic liver transplant rejection. Drawing an early in therapy trough level is useful to assess for accumulation. The results of this case suggest a reduction in weight based maintenance dosage to 2mg/kg every 24 hours with close monitoring of trough levels to confirm the dosing interval.

Presenting Author

Authors