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. AIM: To investigate the influence of alitretinoin on the pharmacokinetics (PK) of ethinyl estradiol/norgestimate (Ortho Tri-Cyclen 28((R))) 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. (c) 2011 The Author(s). Clinical and Experimental Dermatology (c) 2011 British Association of Dermatologists.