title: No clinically meaningful pharmacokinetic interaction between the hepatitis C virus inhibitors elbasvir and grazoprevir and the oral contraceptives ethinyl estradiol and levonorgestrel.
abstract: OBJECTIVE
  Oral contraceptive pills (OCPs) are an important element of hepatitis C virus (HCV) treatment in women of childbearing potential. These studies evaluated the safety and pharmacokinetic interactions between elbasvir (EBR) and grazoprevir (GZR) and ethinyl estradiol/levonorgestrel (EE/LNG).
  
  
  METHODS
  Both studies were open-label, single-site, two-period, fixed-sequence, one-way interaction studies. In period 1, subjects received one tablet of EE/LNG (0.03 mg/0.15 mg). In period 2, subjects received EBR (50 mg once daily) for 13 days or GZR (200 mg once daily) for 10 days, with one tablet of EE/LNG on day 7 (GZR group) or 10 (EBR group). Each study enrolled 20 healthy, nonsmoking adult females.
  
  
  RESULTS
  There was no clinically meaningful effect of multiple doses of EBR or GZR on the pharmacokinetics of EE or LNG. Geometric mean ratios (GMRs) for AUC0-∞and Cmaxin the presence and absence of EBR were 1.01 and 1.10 for EE and 1.14 and 1.02 for LNG, with 90% confidence intervals (CIs) that were contained in the interval [0.80, 1.25]. Similarly, the AUC0-∞and CmaxGMRs in the presence and absence of GZR were 1.10 and 1.05 for EE and 1.23 and 0.93 for LNG, respectively. The 90% CIs for EE AUC0-∞and for EE and LNG Cmaxwere contained in the interval [0.80, 1.25]; however, the 90% CI for the LNG AUC0-∞[1.15, 1.32] slightly exceeded the upper bound.
  
  
  CONCLUSIONS
  These results suggest that EBR/GZR can be co-administered to female patients with HCV of childbearing potential who are on OCPs to prevent pregnancy.
authors.affiliation: Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA.
authors.forename: William L
authors.initials: WL
authors.lastname: Marshall
authors.affiliation: Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA.
authors.forename: Hwa-Ping
authors.initials: HP
authors.lastname: Feng
authors.affiliation: Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA.
authors.forename: Luzelena
authors.initials: L
authors.lastname: Caro
authors.affiliation: Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Talaty
authors.affiliation: Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA.
authors.forename: Zifang
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA.
authors.forename: Xiaobi
authors.initials: X
authors.lastname: Huang
authors.affiliation: Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA.
authors.forename: Deborah
authors.initials: D
authors.lastname: Panebianco
authors.affiliation: Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA.
authors.forename: Joanne
authors.initials: J
authors.lastname: Ma
authors.affiliation: Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Mangin
authors.affiliation: Celerion, 2420 West Baseline Road, Tempe, AZ, 85283, USA.
authors.forename: Terry E
authors.initials: TE
authors.lastname: O'Reilly
authors.affiliation: Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA.
authors.forename: Joan R
authors.initials: JR
authors.lastname: Butterton
authors.affiliation: Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA. wendy.yeh@merck.com.|Merck Research Laboratories, Merck & Co., Inc., BMB3-423, 33 Avenue Louis Pasteur, Boston, MA, 02115, USA. wendy.yeh@merck.com.
authors.forename: Wendy W
authors.initials: WW
authors.lastname: Yeh
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000577:Amides; D000998:Antiviral Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D001572:Benzofurans / Q000493:pharmacokinetics* / Q000494:pharmacology; D002219:Carbamates; D003277:Contraceptives, Oral, Combined / Q000493:pharmacokinetics*; D003521:Cyclopropanes; D004347:Drug Interactions; D004997:Ethinyl Estradiol / Q000008:administration & dosage*; D005260:Female; D016174:Hepacivirus / Q000187:drug effects*; D006801:Humans; D007093:Imidazoles / Q000493:pharmacokinetics* / Q000494:pharmacology; D016912:Levonorgestrel / Q000008:administration & dosage*; D008875:Middle Aged; D011810:Quinoxalines / Q000493:pharmacokinetics* / Q000494:pharmacology; D013449:Sulfonamides; D055815:Young Adult; D047029:Lactams, Macrocyclic
chemical_list: D000577:Amides; D000998:Antiviral Agents; D001572:Benzofurans; D002219:Carbamates; D003277:Contraceptives, Oral, Combined; D003521:Cyclopropanes; D004997:Ethinyl Estradiol; D007093:Imidazoles; D016912:Levonorgestrel; D011810:Quinoxalines; D013449:Sulfonamides; C578009:grazoprevir; D047029:Lactams, Macrocyclic; C000589335:elbasvir
keywords: Clinical trial; Ethinyl estradiol; Hepatitis; Levonorgestrel; Oral contraceptive