4 research outputs found

    Red blood cell exchange as an approach for treating a case of severe tacrolimus overexposure

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    Immunosuppressive medication dosing errors are not unfrequent and may present a number of challenges to transplant clinicians. Tacrolimus (TAC) is a widely used immunosuppressant with a narrow therapeutic index and potential severe side effects, including neurotoxicity and kidney injury. We herein report a case of 60-year-old woman who underwent deceased-donor liver transplantation at our center and due to inadvertent TAC overexposure was admitted to the Intensive Care Unit because of severe neurologic impairment, kidney injury and arterial hypotension. This case was challenging because TAC is largely bound to erythrocytes, has a high molecular weight, is highly lipophilic, has a high distribution volume and cannot be removed by hemodialysis or plasmapheresis. Based on these considerations, we decided to replace TAC-saturated erythrocytes with blood-bank red cells with the aim to accelerate its clearance. The treatment was effective in decreasing TAC whole blood trough levels within the therapeutic ranges with a significant improvement of the patient's clinical status. Red-blood cell exchange is a potentially safe and effective means of managing severe and symptomatic TAC toxicity

    Switch to everolimus in maintenance liver transplant patients: preliminary results of a prospective, single-center trial

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    Renal function is often impaired after liver transplantation (LT). We present the preliminary results of a prospective trial on efficacy and safety of switching from calcineurin inhibitors (CNI) to everolimus (EVER) in maintenance LT recipients. Adult, consenting deceased donor LT recipients with a minimum follow-up of 12 months were included. EVER was introduced at 0.75 mg b.i.d. with overnight withdrawal of antimetabolites and a 50%-per-week reduction of CNI to a complete stop after 4 weeks. Steroids were kept at pre-switch levels. EVER target levels were 3-8ng/mL. Twenty-seven patients (mean age 56.4±9.6 years; M/F=18/9) on cyclosporine (21) or tacrolimus (6) were enrolled at a mean of 42.9±29.3 months post-LT. Native disease was HCV in 10 patients (37%). Indications were CrCl ≤80mL/min in 26 (96.3%) and CNI-related peripheral neuropathy in 1 (3.7%). At baseline, mean CrCl was 57.2±16.1mL/min (range 38.6/120.5). At a mean follow-up of 110.9±34.9 days, 17 (62.9%) patients had EVER-related complications: hypercholesterolemia/hypertriglyceridemia requiring medication in 5 (18.5%); oral ulcers in 4 (14.8%); acne in 2 (7.4%); eczema in 2 (7.4%); headache, urticaria, psoriasis, relapse of zoster infection in 1 patient each (3.7%). All cases were amenable to medication/EVER dose reduction. Two (7.4%) patients presented 1 episode of treated biopsy proven rejection each (1 RAI 6; 1 RAI 8), one of them (3.7%) dropped treatment. One further patient (3.7%) dropped treatment at 14 days for increase in HCV-RNA. Among the 17 patients (62.9%) with a minimum follow-up of 3 months, mean CrCl increased from 53.1±6.6mL/min (95% CI 49.6/56.5) to 58.7±12.3mL/min (95% CI 52.4/65.1). Preliminary data suggest that switching from CNI to EVER-based immunosuppression is feasible and associated with improvement in CrCl. Larger series and longer follow-ups are favored to tailor EVER on patients’ immunologic profile

    How to achieve optimal trough levels when switching calcineurin inhibitors (CNI) to everolimus (EVER): the 50%-per-week rule

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    Scanty data are available on the best schedule for switching calcineurin-inhibitors (CNI) to everolimus (EVER) in liver transplant (LT) patients. We explored prospectively introduction of EVER at a dosage of 0.75 mg b.i.d.with overnight withdrawal of antimetabolites and reduction of CNI by 50% per week to a complete stop after 4 weeks (the 50%-per-week rule). Adult, consenting recipients of LT from a deceased donor with a minimum follow-up of 12 months were included if they had a C0 ≤150ng/mL, and/or C2 ≤650ng/mL or a TAC trough level ≤8ng/mL. EVER trough levels were obtained 7, 14, 21, 28 days after switch and each month thereafte for 6 months. Target EVER trough levels were 3-8ng/mL. Twenty-seven patients were enrolled (mean age 56.4 ± 9.6 years; M/F=18/9) at a mean follow-up of 42.9 ± 29.3 months from LT. Twenty-one patients (77.8%) were on CsA; 6 patients (22.2%) were on TAC. At baseline, mean CsA dose was 131.6 ± 41.4mg/day and mean TAC dose was 2.8 ± 1.4 mg/day. Mean baseline C0 was 86.8 ± 70.9 ng/mL and mean baseline TAC trough level 6.7 ± 1 ng/mL. Seven days after switch, mean EVER trough level was 6.5 ± 3.2 ng/mL (2.2/14 ng/mL) and 21 patients (77.7%) were within the target range. In 2 patients (7.4%) EVER trough level was 8 ng/mL (3 CsA; 1 TAC). EVER at a dosage of 0.75 mg b.i.d. with 50% reduction of CNI allows to achieve trough levels between 3 and 8 ng/mL in 77.7% of cases, provided that patients have C0 ≤ 150ng/mL and/or C2 ≤ 650 ng/mL, or a TAC trough level ≤8 ng/mL at the time of switch
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