The effect of etoricoxib on the pharmacokinetics of oral contraceptives in healthy participants

• Published in: Journal of clinical pharmacology Vol. 49; no. 7; p. 807
• Main Authors: Schwartz, Jules, Hunt, Thomas, Smith, William B, Wong, Peggy, Larson, Patrick, Crumley, Tami, Mehta, Anish, Gottesdiener, Keith, Agrawal, Nancy
• Format: Journal Article
• Language: English
• Published: England 01.07.2009
• Subjects: Adolescent; Adult; Contraceptives, Oral, Combined - administration & dosage; Contraceptives, Oral, Combined - adverse effects; Contraceptives, Oral, Combined - pharmacokinetics; Cyclooxygenase Inhibitors - administration & dosage; Cyclooxygenase Inhibitors - adverse effects; Cyclooxygenase Inhibitors - pharmacology; Drug Interactions; Female; Headache - chemically induced; Humans; Mestranol - administration & dosage; Mestranol - adverse effects; Mestranol - pharmacokinetics; Middle Aged; Nausea - chemically induced; Norethindrone - administration & dosage; Norethindrone - adverse effects; Norethindrone - pharmacokinetics; Pyridines - administration & dosage; Pyridines - adverse effects; Pyridines - pharmacology; Serum Albumin - metabolism; Sex Hormone-Binding Globulin - metabolism; Sulfones - administration & dosage; Sulfones - adverse effects; Sulfones - pharmacology
• ISSN: 0091-2700
• DOI: 10.1177/0091270009337131

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.