Tolerability and efficacy of colestipol hydrochloride for accelerated elimination of teriflunomide

ABSTRACT

Background: Teriflunomide is an oral disease modifying therapy approved for the treatment of relapsing forms of multiple sclerosis. Teriflunomide’ s pharmacokinetics (PK) contribute to its slow elimination, on average taking 6–8 months, though it can take up to 2 years in some instances. This slow elimination can become problematic in certain clinical situations – such as during pregnancy, when teriflunomide has potential teratogenic effects. In such scenarios, an accelerated elimination procedure (AEP) is recommended. Currently, AEPs with oral cholestyramine or activated charcoal are available but are restricted by adverse effects, limited administration routes, and dosing frequencies.

Methods: A single-center, PK interaction study was performed in a total of 14 healthy volunteers, to investigate colestipol hydrochloride (HCl) as an alternative to cholestyramine for the elimination of teriflunomide. Participants received teriflunomide for 14 days, followed by an AEP with colestipol HCl for 15 days.

Results and conclusions: The administration of colestipol HCl for 15 days was sufficient to reduce plasma teriflunomide concentrations by greater than 96%. Although colestipol HCl did not completely eliminate teriflunomide with the same effectiveness as cholestyramine, it may offer an alternative method for accelerated elimination of teriflunomide with potentially improved tolerability and more favorable dosing and administration options.

KEYWORDS:

• Teriflunomide
• colestipol HCl
• accelerated elimination procedure
• pharmacokinetics
• multiple sclerosis

Declaration of interest

D Robertson has been a consultant for Biogen, EMD Serono, Genentech, Genzyme, Novartis, Pfizer, and Teva; has received honoraria or speaker’s fees from Acorda, Biogen, EMD Serono, Genentech, Genzyme, Mallinckrodt, Novartis, Pfizer, and Teva; and has received research grant support from Actelion, Biogen, EMD Serono, Genentech, Genzyme, Mallinckrodt, MedImmune, Novartis, and Sun Pharma. L Casady has received honoraria or speaker’s fees from Genzyme, Biogen and Genentech. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

Derrick Robertson contributed to the design of the study, analysis and interpretation of the data, and drafting the manuscript.

Angela Aungst contributed to the design of the study, analysis and interpretation of the data, and drafting the manuscript.

Crystal Dixon contributed to the analysis and interpretation of the data, and drafting the manuscript.

Bradlee McCoy contributed to data collection and drafting the manuscript.

Natalie Moreo contributed to drafting the manuscript.

Lise Casady contributed to data collection and drafting the manuscript.

Janice Maldonado contributed to drafting the manuscript.

Additional information

Funding

Study funded by Sanofi Genzyme.