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Sertraline is a moderate inhibitor of CYP2D6 and CYP2B6 in vitro.
Accordingly, in human trials it caused an increased blood level
of such CYP2D6 substrates as metoprolol (Lopressor, Toprol XL),
desipramine (Norpramin), imipramine (Tofranil) and nortriptyline
(Pamelor) and CYP3A4/CYP2D6 substrate haloperidol (Haldol). This
effect was dose-dependent; for example, desipramine co-administration
with 50 mg of sertraline resulted in a 20% increase of exposure
and with 150 mg of sertraline—in a 70% increase of exposure. In
a placebo-controlled study, the concomitant administration of sertraline
caused a 40% increase of the blood level of methadone, which is
primarily metabolized by CYP2B6. Sertraline had a slight inhibitory
effect on the metabolism of diazepam (Valium), tolbutamide (Orinase)
and warfarin (Coumadin), which are CYP2C9 or CYP2C19 substrates;
this effect was not considered to be clinically relevant. As expected
from the in vitro data, sertraline did not alter the human metabolism
of CYP3A4 substrates erythromycin, alprazolam (Xanax), carbamazepine
(Tegretol), clonazepam (Klonopin), and terfenadine (Seldane) as
well as CYP1A2 substrate clozapine (Clozaril). Sertraline had no
effect on the actions of digoxin (Lanoxin) and atenolol (Tenormin),
which are not metabolized in the liver. Case reports suggest that
taking sertraline with phenytoin (Dilantin) or zolpidem (Ambien)
may induce sertraline metabolism and decrease its efficacy and taking
sertraline with lamotrigine (Lamictal) may increase the blood level
of lamotrigine via an unknown mechanism. Clinical reports indicate
that interaction between sertraline and MAOIs isocarboxazid (Marplan)
and tranylcypromine (Parnate) may cause serotonin syndrome. In a
placebo-controlled study of co-administration of sertraline with
lithium, 35% of the subjects experienced tremors versus 0% with
placebo. |
