title: The effect of etoricoxib on the pharmacokinetics of oral contraceptives in healthy participants.
abstract: The pharmacokinetics of oral contraceptive (OC) components, ethinyl estradiol (EE) and norethindrone (NET), were evaluated after coadministration with etoricoxib in 3 double-blind, randomized, 2-period crossover studies of healthy women. There were 16, 39, and 24 participants enrolled in studies 1 (part I, part II), and 2, respectively. Each participant received triphasic OC (EE 35 microg/NET 0.5 mgx7 days, 0.75 mgx7 days, 1.0 mgx7 days) throughout each 28-day period. OC was coadministered with 21 days of etoricoxib daily followed by placebo for 7 days; the alternate period followed the reverse regimen (placebo to etoricoxib). Study 1 (part I) examined concurrent (morning) administration of OC/etoricoxib 120 mg, study 1 (part II) examined staggered (morning/night) administration of OC/etoricoxib 120 mg, and study 2 examined concurrent (morning) administration of OC/etoricoxib 60 mg. Coadministration of OC and etoricoxib 120 mg once daily was associated with a approximately 50% to 60% increase in EE concentrations, whereas etoricoxib 60 mg once daily was associated with a approximately 37% increase in EE concentrations. Coadministration of OC and etoricoxib was generally well tolerated. A clinically important change in NET AUC0-24 h was not observed. Adverse events included dyspepsia, diarrhea, headache, nausea, fatigue, loss of appetite, and taste disturbance.
authors.affiliation: Merck Research Laboratories, Rahway, NJ, USA.
authors.forename: Jules
authors.initials: J
authors.lastname: Schwartz
authors.forename: Thomas
authors.initials: T
authors.lastname: Hunt
authors.forename: William B
authors.initials: WB
authors.lastname: Smith
authors.forename: Peggy
authors.initials: P
authors.lastname: Wong
authors.forename: Patrick
authors.initials: P
authors.lastname: Larson
authors.forename: Tami
authors.initials: T
authors.lastname: Crumley
authors.forename: Anish
authors.initials: A
authors.lastname: Mehta
authors.forename: Keith
authors.initials: K
authors.lastname: Gottesdiener
authors.forename: Nancy
authors.initials: N
authors.lastname: Agrawal
mesh_terms: D000293:Adolescent; D000328:Adult; D003277:Contraceptives, Oral, Combined / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D004338:Drug Combinations; D004347:Drug Interactions; D000077613:Etoricoxib; D005260:Female; D006261:Headache / Q000139:chemically induced; D006801:Humans; D008656:Mestranol / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009640:Norethindrone / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D011725:Pyridines / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*; D012709:Serum Albumin / Q000378:metabolism; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D013450:Sulfones / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D003277:Contraceptives, Oral, Combined; D016861:Cyclooxygenase Inhibitors; D004338:Drug Combinations; D011725:Pyridines; D012709:Serum Albumin; D012738:Sex Hormone-Binding Globulin; D013450:Sulfones; C014715:Norinyl; D008656:Mestranol; D009640:Norethindrone; D000077613:Etoricoxib