title: Influence of alitretinoin on the pharmacokinetics of the oral contraceptive ethinyl estradiol/norgestimate.
abstract: BACKGROUND
  Alitretinoin (9-cis retinoic acid) is currently registered in many European countries and in Canada as the only licensed treatment for severe chronic hand eczema unresponsive to potent topical corticosteroids. Alitretinoin, like all retinoids, is teratogenic, and women of child-bearing potential must strictly adhere to pregnancy-prevention measures.
  
  
  OBJECTIVE
  To investigate the influence of alitretinoin on the pharmacokinetics (PK) of ethinyl estradiol/norgestimate (Ortho Tri-Cyclen 28(®)), a commonly prescribed combination oral contraceptive.
  
  
  METHODS
  In total, 16 healthy premenopausal women received three consecutive cycles of the triphasic contraceptive ethinyl estradiol/norgestimate together with concomitant oral alitretinoin 40 mg once daily during cycle 2. Steady-state PK (noncompartmental analysis) of ethinyl estradiol, 17-deacetyl norgestimate, alitretinoin and its main metabolite 4-oxo-alitretinoin were assessed alone and in combination.
  
  
  RESULTS
  The PK profiles of ethinyl estradiol and 17-deacetyl norgestimate were similar when contraceptives were given alone or with alitretinoin, and the area under the plasma concentration vs. time curve and the maximum concentration met the conventional criteria for PK equivalence. Similarly, the influence of ethinyl estradiol/norgestimate on systemic exposure to alitretinoin and 4-oxo-alitretinoin was not clinically relevant. Alitretinoin was well tolerated when given either alone or with ethinyl estradiol/norgestimate.
  
  
  CONCLUSIONS
  There was no clinically relevant influence of alitretinoin on the PK of ethinyl estradiol/norgestimate, and no influence of ethinyl estradiol/norgestimate on systemic exposure to alitretinoin and 4-oxo-alitretinoin. Consequently, oral contraception with ethinyl estradiol/norgestimate is an appropriate primary method of birth control during alitretinoin treatment for women of childbearing potential.
authors: Basilea Pharmaceutica International Ltd, Basel, Switzerland. anne.schmitt-hoffmann@basilea.com
authors: A H
authors: AH
authors: Schmitt-Hoffmann
authors: B
authors: B
authors: Roos
authors: J
authors: J
authors: Sauer
authors: M
authors: M
authors: Schleimer
authors: A
authors: A
authors: Schoetzau
authors: P T
authors: PT
authors: Leese
authors: E
authors: E
authors: Weidekamm
authors: J
authors: J
authors: Maares
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000077556:Alitretinoin; D002648:Child; D003277:Contraceptives, Oral, Combined / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood*; D003879:Dermatologic Agents / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D004334:Drug Administration Schedule; D004338:Drug Combinations; D004347:Drug Interactions; D004997:Ethinyl Estradiol / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009644:Norgestrel / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood; D011374:Progesterone / Q000097:blood; D014212:Tretinoin / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D003277:Contraceptives, Oral, Combined; D003879:Dermatologic Agents; D004338:Drug Combinations; C109079:norgestimate, ethinyl estradiol drug combination; D000077556:Alitretinoin; D009644:Norgestrel; D004997:Ethinyl Estradiol; D011374:Progesterone; D014212:Tretinoin