Abstract
Duloxetine is a potent and selective inhibitor of serotonin and norepinephrine reuptake
with weak activity on dopamine reuptake. Enzymes involved in duloxetine metabolism
are cytochrome P450 isoenzymes (CYP) CYP1A2 and to a lesser extent CYP2D6 whereas
the selective serotonin reuptake inhibitor Fluvoxamine is known to be a potent inhibitor
of CYP1A2. Changes in plasma levels of duloxetine revealing pharmacokinetic interactions
with fluvoxamine, clinical effects and adverse effects of adding fluvoxamine in thirteen
patients with a steady-state duloxetine treatment by intraindividual comparisons were
analyzed in this retrospective survey. Patients had been treated with duloxetine under
steady-state conditions until fluvoxamine was added. Plasma duloxetine levels were
measured at steady state of different daily doses due to lacking experience with the
combination of DLX and FLX. Adding 25 mg of fluvoxamine (FLX) per day to a steady-state
treatment with 30 mg of duloxetine (DLX) in 8 patients led to an average increase
of duloxetine plasma levels that was 3-fold with a magnitude of 50–506%. Our findings
indicate that duloxetine plasma levels can be enhanced by a potent CYP1A2 inhibition
by FLX and that DLX, even in higher plasma levels, seems to be well tolerated. The
use of combined treatments, however, underscores the importance of understanding pharmacokinetic
interactions.
Key words
duloxetine - fluvoxamine - plasma level - interaction - CYP1A2 - TDM - depression
