Pharmacy Times – June 2018


Drug Interactions: Insights and Observations


Endothelin Receptor Antagonist Drug Interactions


John R. Horn, PharmD, FCCP and Philip D. Hansten, PharmD




1. Letairis [package insert]. Foster City, CA; Gilead Sciences, Inc, 2015.

2. Tracleer [package insert]. San Francisco, CA; Actelion Pharmaceuticals US, Inc, 2017.

3. Opsumit [package insert]. San Francisco, CA; Actelion Pharmaceuticals US, Inc, 2017.

4. Spence R, Mandagere A, Richards DB et al. Potential for pharmacokinetic interaction between ambrisentan and cyclosporine. Clin Pharmacol Ther. 2010;88:513-20.

5. Richards DB, Walker GA, Mandagere A et al. Effect of ketoconazole on the pharmacokinetic profile of ambrisentan. J Clin Pharmacol. 2009;49:19-24.

6. Harrison B, Magee MH, Mandagere A et al. Effects of rifampicin on the pharmacokinetics and safety of ambrisentan in healthy subjects: a single-sequence, open-label study. Clin Drug Investig. 2010;30:875-85.

7. Market C, Hellwig R, Burhenne J et al. Interaction of ambrisentan with clarithromycin and is modulation by polymorphic SLCO1B1. Eur J Clin Pharmacol. 2013;69:1785-93.

8. Binet I, Wallnofer A, Wealker GA et al. Renal hemodynamics and pharmacokinetics of bosentan with and without cyclosporine A. Kidney Int. 2000;57:224-31.

9. Van Giersbergen PL, Halabi A, Dingemanse J. Single- and multiple-dose pharmacokinetics of bosentan and its interaction with ketoconazole. Br J Clin Pharmacol. 2002;53:589-95.

10. Van Giersbergen PL, Trreiber A, Schneiter R, et al. Inhibitory and inductive effects of rifampin on the pharmacokinetics of bosentan in healthy subjects. Clin Pharmacol Ther. 2007;81:414-9.

11. Dingemanse J, Van Giersbergen PL, Patat A, et al. Mutual pharmacokinetic interactions between bosentan and lopinavir/ritonavir in healthy participants. Antivir Ther. 2010;15:157-63.

12. Atsmon J, Dingemanse J, Shaikevich D, et al. Investigation of the effects of ketoconazole on the pharmacokinetics of macitentan, a novel dual endothelin receptor antagonist, in healthy subjects. Clin Pharmacokinet. 2013;52:685-92.

13. Bruderer S, Aanismaa P, Homery M-C, et al. Effect of cyclosporine and rifampin on the pharmacokinetics of macitentan, a tissue-targeting dual endothelin receptor antagonist. AAPS Journal. 2012;14:68-78.