BACKGROUND AND OBJECTIVE: The anti-oestrogen @entity440 requires metabolic activation to endoxifen by cytochrome P450 (CYP) enzymes, predominantly @entity5320 . Potent @entity5320 -inhibiting antidepressants can seriously disrupt @entity440 metabolism, probably influencing the efficacy of @entity440 . For this reason, @entity903 and @entity905 are recommended not to be used with @entity440 in @entity0 @entity1 . We investigated the effects of switching potent @entity5320 -inhibiting antidepressants to weak @entity5320 -inhibiting antidepressants on the plasma pharmacokinetics of @entity440 . METHODS: Ten @entity0 @entity1 who were treated with @entity440 in combination with a potent @entity5320 -inhibiting antidepressant ( @entity903 or @entity905 ) for at least 4  weeks were enrolled. Under close supervision by a psychiatrist, @entity1 were switched to treatment with @entity837 or @entity906 (weak @entity5320 -inhibiting antidepressants). Before and after the switch, pharmacokinetic blood sampling was performed over 24  h. Pharmacokinetic parameters were estimated using noncompartmental analysis. Adverse effects were recorded during the study. RESULTS: @entity34833 exposure was ~3-fold higher during @entity837 co-administration than during @entity903 or @entity905 co-administration (median 387  nM  h [range 159-637  nM  h] versus 99.2  nM  h [range 70.0-210  nM  h]; P  =  0.012; Wilcoxon signed-rank test). The ratio of @entity34833 to @entity28003 and the ratio of @entity25608 to @entity440 increased by 3.3- and ~1.5-fold, reflecting increased @entity5320 activity. Antidepressant switching did not result in @entity146 problems or antidepressant-related adverse effects. CONCLUSION: In this study, switching to the weak @entity5320 inhibitor @entity837 was safe and feasible and resulted in clinically relevant rises in endoxifen concentrations. We therefore advise switching @entity903 and @entity905 to @entity837 in @entity1 using @entity440 . However, switching should always be weighed in individual @entity1 .

Augmentation of Endoxifen Exposure in XXXX -Treated @entity1 Following SSRI Switch.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity0 :: ('MESH:D001943', 'Disease') :: ['breast cancer'] @entity905 :: ('MESH:D005473', 'Chemical') :: ['fluoxetine'] @entity440 :: ('MESH:D013629', 'Chemical') :: ['tamoxifen'] @entity5320 :: ('1565', 'Gene') :: ['CYP2D6'] @entity34833 :: ('MESH:C055492', 'Chemical') :: ['Endoxifen', 'endoxifen'] @entity146 :: ('MESH:D001523', 'Disease') :: ['psychiatric'] @entity903 :: ('MESH:D017374', 'Chemical') :: ['paroxetine'] @entity25608 :: ('MESH:C016601', 'Chemical') :: ['4-hydroxytamoxifen'] @entity837 :: ('MESH:D015283', 'Chemical') :: ['escitalopram'] @entity28003 :: ('MESH:C028787', 'Chemical') :: ['N-desmethyltamoxifen'] @entity906 :: ('MESH:C047426', 'Chemical') :: ['venlafaxine']
@entity440 :: (MESH:D013629,Chemical) :: ['Tamoxifen']
