ABSTRACT
Cassia angustifolia is a species of plant from the Senna family that has traditionally been used as a laxative in different herbal products and commercial medicines. Even though there are few documented drug-plant interactions, the use of C. angustifolia with different drugs may have additive effects, such as with other laxatives or potassium-depleting diuretics. Its use also increases peristalsis which, may reduce drug absorption. The combination with digoxin has been associated with an increased risk of digoxin toxicity, probably due to an increase in plasma digoxin concentrations and hypokalaemia. We present a case with supratherapeutic trough concentration of tacrolimus, an immunosuppressive agent, and a herbal product in a liver transplant patient after concomitant intake of tacrolimus and a herbal product based on C. angustifolia, suggesting a possible drug-lant interaction through by P-glycoprotein. We observed an increase in the patient's blood concentration 2.8-fold and the area under the curve at steady state 2.1-fold. This interaction could be of clinical relevance, given the dose-dependent side effects of tacrolimus, such as nephrotoxicity, neurotoxicity, hypertension, hyperglycaemia, or electrolyte alterations.
Subject(s)
Herb-Drug Interactions , Immunosuppressive Agents , Liver Transplantation , Tacrolimus , Humans , Tacrolimus/adverse effects , Tacrolimus/administration & dosage , Tacrolimus/pharmacokinetics , Tacrolimus/blood , Liver Transplantation/adverse effects , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/pharmacokinetics , Immunosuppressive Agents/administration & dosage , Male , Middle Aged , Senna Plant , Cassia , Drug InteractionsABSTRACT
INTRODUCTION: Enhanced recovery after surgery (ERAS) has been shown to facilitate discharge, decrease length of stay, improve outcomes and reduce costs. We used this concept to design a comprehensive fast-track pathway (OR-to-discharge) before starting our liver transplant activity and then applied this protocol prospectively to every patient undergoing liver transplantation at our institution, monitoring the results periodically. We now report our first six years results. PATIENTS AND METHODS: Prospective cohort study of all the liver transplants performed at our institution for the first six years. Balanced general anesthesia, fluid restriction, thromboelastometry, inferior vena cava preservation and temporary portocaval shunt were strategies common to all cases. Standard immunosuppression administered included steroids, tacrolimus (delayed in the setting of renal impairment, with basiliximab induction added) and mycophenolate mofetil. Tacrolimus dosing was adjusted using a Bayesian estimation methodology. Oral intake and ambulation were started early. RESULTS: A total of 240 transplants were performed in 236 patients (191â/45â) over 74 months, mean age 56.3±9.6 years, raw MELD score 15.5±7.7. Predominant etiologies were alcohol (n = 136) and HCV (n = 82), with hepatocellular carcinoma present in 129 (54.7%). Nine patients received combined liver and kidney transplants. The mean operating time was 315±64 min with cold ischemia times of 279±88 min. Thirty-one patients (13.1%) were transfused in the OR (2.4±1.2 units of PRBC). Extubation was immediate (< 30 min) in all but four patients. Median ICU length of stay was 12.7 hours, and median post-transplant hospital stay was 4 days (2-76) with 30 patients (13.8%) going home by day 2, 87 (39.9%) by day 3, and 133 (61%) by day 4, defining our fast-track group. Thirty-day-readmission rate (34.9%) was significantly lower (28.6% vs. 44.7% p=0.015) in the fast-track group. Patient survival was 86.8% at 1 year and 78.6% at five years. CONCLUSION: Fast-Tracking of Liver Transplant patients is feasible and can be applied as the standard of care.
