Enhanced cyclosporine-itraconazole interaction with cola in lung transplant recipients

Background: Invasive aspergillosis is a major cause of morbidity and mortal ity in lung transplant recipients (LTR), occurring in up to 15% of patients post-transplant. The 14% aspergillus incidence at the Cleveland Clinic Fou ndation prompted institution of universal prophylaxis with oral itraconazol e (ICZ) in 1997. We report our experience with two protocols of ICZ adminis tration in non-cystic fibrosis LTR and the interaction with cyclosporine (C SA). Methods: Group 1 patients (n = 12) were administered ICZ capsules in a fast ing or fed state, with or without a histamine-2 (H-2) receptor antagonist o r proton pump inhibitor. Group 2 patients (n = 12) received the same protoc ol as group 1, but in a fed state with a carbonated beverage (cola) to incr ease acidity in the stomach to enhance absorption of ICZ, The ICZ dose was 200 mg/d, given as one daily dose. A historical control group (n = 10) did not receive chemoprophylaxis with ICZ. CSA daily doses, dose intervals, con centration, cost, and random ICZ levels were documented over a 1-month peri od of time and compared using generalized estimating equations. Results: The daily CSA mg/kg/d dose decreased over time in all three groups , but no differences were found between the three groups. The CSA dosing in terval over time was significantly prolonged in group 2 compared to group 1 or the control group (p less than or equal to 0.003). Over time, there was no difference in CSA concentration between all groups. There was no differ ence in cost over time between the three groups; however, the mean cost of CSA therapy was significantly lower in group 2 compared to the control grou p (p = 0.025). Group 2 administered ICZ with cola had greater random blood concentrations of ICZ (p = 0.019). Conclusions: ICZ capsules administered in a fed state with a cola resulted in greater random levels of ICZ, a decrease in cost/d of CSA, and a prolong ation of CSA dosing interval. Although daily CSA dosage trended lower in gr oup 2, it did not reach statistical significance. We believe these changes in CSA dosing over time reflect increased absorption of ICZ and recommend v erifying ICZ absorption with an itraconazole level. especially when CSA int ervals are not prolonged.