Drug interaction between sevelamer and cyclosporin

Sir,

We read with interest the original report made by Miguel-Angel Guillen-Anaya and Michel Jadoul [1] of a drug interaction between sevelamer and cyclosporin (CsA) occurring in a liver transplant patient treated also by chronic haemodialysis. After sevelamer was started, the CsA trough levels reached values as low as 35 ng/ml and they dropped again after rechallenge. As potential explanation, the authors suggest that CsA absorption, which is bile-dependent [2], could be hampered by the fact that sevelamer binds bile acids in the gastrointestinal (GI) tract. Interestingly, in the clinical study performed by Jensen et al. [3], the bile acid sequestrant cholestyramine (4 g given at noon) did not interfere with CsA absorption.

We would like to mention that sevelamer is a poly(allylaminehydrochloride) polymer that may bind not only phosphate and bile acids, as the authors point out, but also cholesterol, vitamins D, E and K and folic acid [4]. A direct binding of a lipophilic substance such as CsA – and by extension also tacrolimus – appears, therefore, as an additional and more likely explanation.

This observation points to the distinction to be made between the two types of phosphate binding in the GI tract: (i) a specific one achieved by aluminium hydroxide and calcium salts and (ii) a non-specific binding attained by polymers such as sevelamer. This absence of specificity might be of less importance for vitamins or folic acid absorption, but may put the patient at risk when lipophilic agents such as immunosuppressive and/or other drugs (lipophilic statins?) are prescribed. Under those circumstances, it appears that sevelamer should be used with caution, i.e. at sufficient time lag to potentially interfering drugs and only when specific (and less expensive) phosphate binders are contraindicated.

Conflict of interest statement. None declared.

Jean-Pierre Wauters, Dominik Uehlinger and Hans-Peter Marti

Division of Nephrology – Hypertension University Hospital Bern Switzerland Email: jean-pierre.wauters{at}insel.ch

References

  1. Guillen-Anaya MA, Jadoul M. Drug interaction between sevelamer and cyclosporin. Nephrol Dial Transplant 2004; 19: 515[Free Full Text]
  2. Trull AK, Tan KKC, Tan L et al. Absorption of cyclosporin from conventional and new micro-emulsion oral formulations in liver transplant recipients with external bile diversion. Br J Clin Pharmacol 1995; 39: 627–631[ISI][Medline]
  3. Jensen RA, Lal SM, Diaz-Arias A et al. Does cholestyramine interfere with cyclosporine absorption? Prospective study in renal transplant patients. ASAIO J 1995; 41: 704–706.
  4. Product Information Brochure USA and Summary of Product Characteristics of the EMEA.