Simeprevir versus Erythromycin
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Study Design
In a phase I, randomized, open-label, three-period crossover study with a washout period of at least 10 days, 24 healthy subjects (eight male) were administered simeprevir (150 mg once daily on days 1–7), erythromycin (500 mg three times daily on days 1–6; 500 mg single dose on day 7) or simeprevir (150 mg once daily on days 1–7) plus erythromycin (500 mg three times daily on days 1–7) under fed conditions.
Study Results
For simeprevir, coadministration with erythromycin increased the mean AUC24h, Cmax and Cmin by 7.47-, 4.53- and 12.74-fold, respectively, in comparison with simeprevir alone. For erythromycin, coadministration with simeprevir increased the mean AUC from 0 to 8 h (AUC8h) by 1.90-fold and increased the Cmax and Cmin by 1.59- and 3.08-fold, respectively, in comparison with administration of erythromycin alone.
Drug Effect on PK PK Parameters
Cmax AUC Cmin
Simeprevir Increase 4.53 (3.91 – 5.25) 7.47 (6.41 – 8.7) 12.74 (10.19 – 15.93)
Erythromycin Increase 1.59 (1.23 – 2.05) 1.9 (1.53 – 2.36) 3.08 (2.54 – 3.73)
Study Conclusions
Coadministration of erythromycin and simeprevir (SMV) is not recommended because concomitant use has resulted in significantly increased plasma concentrations of both drugs.
If concomitant use is clinically necessary, advise the patient to limit sun exposure and to use sunscreen to avoid photosensitivity rash associated increased simeprevir exposure, and consider monitoring for erythromycin toxicity.
References
Ouwerkerk Mahadevan S, Snoeys J, Peeters M, Beaumont Mauviel M, Simion A. Drug–drug interactions with the ns3/4a protease inhibitor simeprevir. Clinical Pharmacokinetics. 2016; 2: 197-208.
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