Pos0889 co Prescription of Anti-Acid Therapy Reduces the Bio Availability of Mycophenolate Mofetil in Systemic Sclerosis Patients

Abstract

Background:Mycophenolate mofetil (MMF) is an effective treatment option for systemic sclerosis (SSC). However, many patients require co administration of proton pump inhibitors (PPI) or H2 receptor blockers (HRB) because of significant gastrointestinal manifestations in SSC. Co-treatment with PPI or HRB have shown to be associated with reduced drug exposure in post-transplant patients.1, 2 There is scarcity of data among patients with SSC. We evaluated the drug concentration of MMF over 12 hours of exposure and assessed the impact of ranitidine and PPI in twenty patients with SSC.Objectives:To assess the effect of esomeprazole or ranitidine on the bioavailability of MMF in SSC patients who are on a stable dose of MMF.Methods:Twenty SSC patients, who were on a stable dose of MMF (1.5-3 g) for the past 3 months were selected for the study after obtaining informed written consent. All patients were given either MMF (without PPI or HRB), MMF + esomeprazole, MMF + ranitidine for one month each. At the end of each month, EDTA plasma samples were collected at various time points including 0, 1/2, 1, 1½, 2, 2½, 3, 4, 5, 6, 8 and 12 hours following drug administration to determine the 12-hour area under curve (AUC) of mycophenolic acid (MPA) levels. Estimation of MPA levels was carried out using reverse phase high performance liquid chromatography (HPLC). Total gastrointestinal score was calculated at the end of each month using UCLA Scleroderma Clinical Trial Consortium GIT 2.0 scoring. To compare the mean AUC, linear mixed effect model was fit by considering treatment as the fixed effect and subject as the random effect. MMF was set as the reference treatment for the other three treatments and these were analysed together using Linear mixed effect model.Results:All patients were females with mean age of 45 years. Addition of either ranitidine or esomeprazole significantly reduced the mean AUC and C max of the MMF over 12-hour time period. On the other hand, PPI or HRB helped in reduction of the total GI score at the end of 1 month. Details of pharmacokinetics are depicted in the table 1.Table 1.Pharmacokinetics and GI score with MMF in combination with PPI / HRBMMFMMF+ RMMF + EpAUCmean (95% CI)67.97 (62.73, 73.20)53.04 (44.80, 61.27)45.69 (41.10, 50.28)<0.001*T- MAXmean (95% CI)42.00 (33.60, 50.40)46.50 (32.48, 60.52)79.50 (58.99, 100.01)<0.001*C-MAXmean (95% CI)29.61(26.74, 32.48)15.14 (11.32, 18.97)12.62 (10.58, 14.66)<0.001*Mean GI scoremean (95% CI)0.28 (0.15,0.40)0.19 (0.09, 0.30)0.14 (0.06,0.23)0.009AUC, area under curve Mycophenolic acid; C-MAX, maximum concentration of MPA in 12 hours following MMF; CI confidence interval;Mean GI score, UCLA Scleroderma Clinical Trial Consortium GIT 2.0 scoring; MMF, mycophenolate mofetil; MMF+E, mycophenolate mofetil + esomeprazole; MMF+R, mycophenolate mofetil+ ranitidine;*p value < 0.05 considered as significantConclusion:As co administration of PPI or HRB can significantly reduce the bioavailability of MMF in patients with systemic sclerosis. To avoid therapeutic failure of MMF drug level monitoring is essential when these agents re prescribed with MMF.References:[1]Schaier M, Scholl C, Scharpf D, Hug F, Bönisch-Schmidt S, Dikow R, et al. Proton pump inhibitors interfere with the immunosuppressive potency of mycophenolate mofetil. Rheumatology (Oxford, England). 2010;49:2061–7.[2]Rissling O, Glander P, Hambach P, Mai M, Brakemeier S, Klonower D, et al. No relevant pharmacokinetic interaction between pantoprazole and mycophenolate in renal transplant patients: a randomized crossover study. British Journal of Clinical Pharmacology. 2015;80:1086–96.Disclosure of Interests:None declared

Pharmacology of drugs used in autoimmune dermatopathies in cats and dogs: A narrative review

“…omeprazole) and certain antibiotics (e.g. ciprofloxacin and amoxicillin/clavulanic acid) with MMF reduces the oral bioavailability of MMF, 145–147 yet this has not been recognised in animals.…”