oxidase inhibitors (MAOIs): Due
to the risk of serotonin syndrome, duloxetine should not be used in
combination with non-selective irreversible monoamine oxidase
inhibitors (MAOIs), or within at least 14 days of discontinuing
treatment with an MAOI. Based on the half-life of duloxetine, at
least 5 days should be allowed after stopping Cymbalta before
starting an MAOI.
concomitant use of Cymbalta with selective, reversible MAOIs, like
moclobemide, is not recommended. The antibiotic linezolid is a
reversible non-selective MAOI and should not be given to patients
treated with Cymbalta.
of CYP1A2: Because
CYP1A2 is involved in duloxetine metabolism, concomitant use of
duloxetine with potent inhibitors of CYP1A2 is likely to result in
higher concentrations of duloxetine. Fluvoxamine (100 mg once daily),
a potent inhibitor of CYP1A2, decreased the apparent plasma clearance
of duloxetine by about 77% and increased AUCo-t
6-fold. Therefore Cymbalta should not be administered in combination
with potent inhibitors of CYP1A2 like fluvoxamine.
The risk of using duloxetine in combination with other CNS-active
medicinal products has not been systematically evaluated, except in
the cases described in this section. Consequently, caution is advised
when Cymbalta is taken in combination with other centrally acting
medicinal products or substances, including alcohol and sedative
medicinal products (e.g. benzodiazepines, morphinomimetics,
antipsychotics, phenobarbital, sedative
rare cases, serotonin syndrome has been reported in patients using
SSRIs/SNRIs concomitantly with serotonergic agents. Caution is
advisable if Cymbalta is used concomitantly with serotonergic agents
like SSRIs, SNRIs, tricyclic antidepressants like clomipramine or
amitriptyline, MAOIs like moclobemide or linezolid, St John’s
wort (Hypericum perforatum) or triptans, tramadol, pethidine and
of duloxetine on other medicinal products
products metabolised by CYP1A2: The
pharmacokinetics of theophylline, a CYP1A2 substrate, were not
significantly affected by co-administration with duloxetine (60 mg
products metabolised by CYP2D6: Duloxetine
is a moderate inhibitor of CYP2D6. When duloxetine was administered
at a dose of 60 mg twice daily with a single dose of desipramine, a
CYP2D6 substrate, the AUC of desipramine increased 3-fold. The
co-administration of duloxetine (40 mg twice daily) increases steady
state AUC of tolterodine (2 mg twice daily) by 71 %, but does not
affect the pharmacokinetics of its active 5-hydroxyl metabolite and
no dosage adjustment is recommended. Caution is advised if Cymbalta
is co-administered with medicinal products that are predominantly
metabolised by CYP2D6 (risperidone, tricyclic antidepressants [TCAs]
such as nortriptyline, amitriptyline, and imipramine) particularly if
they have a narrow therapeutic index (such as flecainide, propafenone
contraceptives and other steroidal agents: Results
demonstrate that duloxetine does not induce the catalytic activity of
CYP3A. Specific in
interaction studies have not been performed.
and antiplatelet agents: Caution
should be exercised when duloxetine is combined with oral
anticoagulants or antiplatelet agents due to a potential increased
risk of bleeding attributable to a pharmacodynamic interaction.
Furthermore, increases in INR values have been reported when
duloxetine was co-administered to patients treated with warfarin.
However, concomitant administration of duloxetine with warfarin under
steady state conditions, in healthy volunteers, as part of a clinical
pharmacology study, did not result in a clinically significant change
in INR from baseline or in the pharmacokinetics of R- or S-warfarin.
of other medicinal products on duloxetine
and H2 antagonists: Co-administration
of duloxetine with aluminium- and magnesium- containing antacids or
duloxetine with famotidine had no significant effect on the rate or
extent of duloxetine absorption after administration of a 40 mg oral
of CYP1A2: Population
pharmacokinetic analyses have shown that smokers have almost 50%
lower plasma concentrations of duloxetine compared with non-smokers.
[Summary of Product Characteristics]. Utrecht, The Netherlands: Eli
Lilly Nederland B.V..