Correspondence
Reduction in Blood Cyclosporine Concentrations by Orlistat
N Engl J Med 2000; 342:1141-1142April 13, 2000
- Article
To the Editor:
A 10 percent increase in body weight during the first year after organ transplantation is common, and many patients become obese (body-mass index [the weight in kilograms divided by the square of the height in meters], >30) within two years after the procedure.1,2
In April 1999, the Food and Drug Administration (FDA) approved orlistat for the treatment of obesity. Orlistat partially inhibits the absorption of dietary fat by binding to pancreatic lipase in the gastrointestinal tract. Since its approval, the FDA has received six reports of transplant recipients who had subtherapeutic blood cyclosporine concentrations soon after the initiation of orlistat therapy.
Cyclosporine is a highly lipid-soluble drug with variable and slow absorption from the upper small intestine.3 Dietary fat may increase its absorption.4 When taken as prescribed, orlistat increases fecal fat content. It is likely that the reported reductions in blood cyclosporine concentrations in patients concomitantly taking orlistat were due primarily to reduced absorption of cyclosporine. Until detailed data on drug–drug interactions become available, transplant recipients should take cyclosporine at least two hours before or after orlistat, and blood cyclosporine concentrations should be measured to minimize the risk of inadequate immunosuppression and organ rejection.
(The views expressed are those of the authors and do not necessarily represent those of the FDA.)
4 ReferencesEric Colman, M.D.
Michael Fossler, Pharm.D., Ph.D.
Food and Drug Administration, Rockville, MD 208571
Johnson CP ,Gallagher-Lepak S ,Zhu YR , et al. Factors influencing weight gain after renal transplantation. Transplantation 1993;56:822-827
CrossRef | Web of Science | Medline2
Everhart JE ,Lombardero M ,Lake JR ,Wiesner RH ,Zetterman RK ,Hoofnagle JH . Weight change and obesity after liver transplantation: incidence and risk factors. Liver Transpl Surg 1998;4:285-296
CrossRef | Medline3
McMillan MA . Clinical pharmacokinetics of cyclosporin. Pharmacol Ther 1989;42:135-156
CrossRef | Web of Science | Medline4
Evans WE, Schentag JJ, Jusko WJ. Applied pharmacokinetics. Vancouver, Wash.: Applied Therapeutics, 1992.
Author/Editor Response
The above letter was referred to Roche Laboratories, the manufacturer of orlistat, which offers the following reply:
To the Editor: Orlistat (Xenical) is a non-systemically acting gastrointestinal lipase inhibitor used for obesity management and for reducing the risk that weight will be regained after a previous weight loss. Orlistat has been studied in controlled clinical trials involving more than 10,000 patients, and post-marketing surveillance has now included more than 3 million patients worldwide. In this extensive clinical experience, Roche identified a decrease in cyclosporine levels in a few persons during concomitant administration of orlistat. Roche and the FDA agreed on appropriate revisions to the U.S. package insert in October 1999.
Russell H. Ellison, M.D.
Roche Laboratories, Nutley, NJ 07110-1199- Citing Articles (15)
Citing Articles
1
M. Hazzan. (2011) Obésité et transplantation rénale. Obésité 6:1, 11-15
CrossRef2
Aneta Novotna, Aneta Doricakova, Radim Vrzal, Patrick Maurel, Petr Pavek, Zdenek Dvorak. (2010) Investigation of Orlistat effects on PXR activation and CYP3A4 expression in primary human hepatocytes and human intestinal LS174T cells. European Journal of Pharmaceutical Sciences 41:2, 276-280
CrossRef3
Kavitha Potluri, Susan Hou. (2010) Obesity in Kidney Transplant Recipients and Candidates. American Journal of Kidney Diseases 56:1, 143-156
CrossRef4
Roberto Bogarin, Jean-Pierre Chanoine. (2009) Efficacy, safety and tolerability of orlistat, a lipase inhibitor, in the treatment of adolescent weight excess. Therapy 6:1, 23-30
CrossRef5
Michael J. Perrio, Lynda V. Wilton, Saad A. W. Shakir. (2007) The Safety Profiles of Orlistat and Sibutramine: Results of Prescription-Event Monitoring Studies in England. Obesity 15:11, 2712-2722
CrossRef6
Benoit Drolet, Chantale Simard, Paul Poirier. (2007) Impact of Weight-Loss Medications on the Cardiovascular System. American Journal of Cardiovascular Drugs 7:4, 273-288
CrossRef7
David Cassiman, Mieke Roelants, Gerda Vandenplas, Schalk W. Van der Merwe, Ann Mertens, Louis Libbrecht, Chris Verslype, Johan Fevery, Raymond Aerts, Jacques Pirenne, Erik Muls, Frederik Nevens. (2006) Orlistat treatment is safe in overweight and obese liver transplant recipients: a prospective, open label trial. Transplant International 19:12, 1000-1005
CrossRef8
2006. Ciclosporin. , 743-770.
CrossRef9
Wilson Y.S Leung, G Neil Thomas, Juliana C.N Chan, Brian Tomlinson. (2003) Weight management and current options in pharmacotherapy: Orlistat and sibutramine. Clinical Therapeutics 25:1, 58-80
CrossRef10
Ion Anghelescu, Christoph Klawe, Otto Benkert. (2000) Orlistat in the Treatment of Psychopharmacologically Induced Weight Gain. Journal of Clinical Psychopharmacology 20:6, 716-717
CrossRef11
Christine le Beller, Yvonnick Bezie, Claire Chabatte, Romain Guillemain, Catherine Amrein, Eliane M. Billaud. (2000) CO-ADMINISTRATION OF ORLISTAT AND CYCLOSPORINE IN A HEART TRANSPLANT RECIPIENT. Transplantation 70:10, 1541-1542
CrossRef12
Bruno Schnetzler, Mitsuko Kondo-Oestreicher, Dominique Vala, Gregory Khatchatourian, Bernard Faidutti. (2000) ORLISTAT DECREASES THE PLASMA LEVEL OF CYCLOSPORINE AND MAY BE RESPONSIBLE FOR THE DEVELOPMENT OF ACUTE REJECTION EPISODES. Transplantation 70:10, 1540-1541
CrossRef13
(2000) Current Awareness. Pharmacoepidemiology and Drug Safety 9:5, 441-456
CrossRef14
&NA;. (2000) Orlistat may reduce cyclosporin concentrations: concerns voiced. Reactions Weekly &NA;:798, 3
CrossRef15
&NA;. (2000) Orlistat may reduce cyclosporin concentrations: concerns voiced. Inpharma Weekly &NA;:1234, 3
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