The effect of etoricoxib on the pharmacokinetics of oral contraceptives in healthy participants.
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.
Schwartz
Jules
J
Merck Research Laboratories, Rahway, NJ, USA.
Hunt
Thomas
T
Smith
William B
WB
Wong
Peggy
P
Larson
Patrick
P
Crumley
Tami
T
Mehta
Anish
A
Gottesdiener
Keith
K
Agrawal
Nancy
N
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*
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