of Other Drugs on Atomoxetine
should not be used with MAOIs.
inhibitors (SSRIs (e.g., fluoxetine, paroxetine), quinidine,
patients receiving these drugs, atomoxetine exposure may be 6-to
8-fold increased and Css
max 3 to 4 times
higher, because it is metabolised by the CYP2D6 pathway. Slower
titration and final lower dosage of atomoxetine may be necessary in
patients who are already taking CYP2D6 inhibitor drugs. If a CYP2D6
inhibitor is prescribed or discontinued after titration to the
appropriate atomoxetine dose has occurred, the clinical response and
tolerability should be re-evaluated for that patient to determine if
dose adjustment is
is advised when combining atomoxetine with potent inhibitors of
cytochrome P450 enzymes other than CYP2D6 in patients who are poor
CYP2D6 metabolisers as the risk of clinically relevant increases in
atomoxetine exposure in vivo is unknown.
(or other beta2
should be administered with caution to patients treated with high
dose nebulised or systemically administered salbutamol (or other
because cardiovascular effects can be potentiated.
findings regarding this interaction were found. Systemically
administered salbutamol (600 μg i.v. over 2 hrs) in combination
with atomoxetine (60 mg twice daily for 5 days) induced increases in
heart rate and blood pressure. This effect was most marked after the
initial coadministration of salbutamol and atomoxetine but returned
towards baseline at the end of 8 hours. However, in a separate study
the effects on blood pressure and heart rate of a standard inhaled
dose of salbutamol (200 μg) were not increased by the short-term
coadministration of atomoxetine (80 mg once daily for 5 days) in a
study of healthy Asian adults who were extensive atomoxetine
metabolisers. Similarly, heart rate after multiple inhalations of
salbutamol (800 μg) did not differ in the presence or absence of
should be paid to monitoring heart rate and blood pressure, and dose
adjustments may be justified for either atomoxetine or salbutamol (or
agonists) in the
event of significant increases in heart rate and blood pressure
during coadministration of these drugs.
is the potential for an increased risk of QT interval prolongation
when atomoxetine is administered with other QT prolonging drugs (such
as neuroleptics, class IA and III anti-arrhythmics, moxifloxacin,
erythromycin, methadone, mefloquine, tricyclic antidepressants,
lithium, or cisapride), drugs that cause electrolyte imbalance (such
as thiazide diuretics), and drugs that inhibit CYP2D6.
are a potential risk with atomoxetine. Caution is advised with
concomitant use of medicinal drugs which are known to lower the
seizure threshold (such as tricyclic antidepressants or SSRIs,
neuroleptics, phenothiazines or butyrophenone, mefloquine,
chloroquine, bupropion or tramadol). In addition, caution is advised
when stopping concomitant treatment with benzodiazepines due to
potential withdrawal seizures.
should be used cautiously with anti-hypertensive drugs. Because of a
possible increase in blood pressure, atomoxetine may decrease the
effectiveness of anti-hypertensive drugs / drugs used to treat
hypertension. Attention should be paid to monitoring of blood
pressure and review of treatment of atomoxetine or anti-hypertensive
drugs may be justified in the case of significant changes of blood
agents or drugs that increase blood pressure:
of possible increase in effects on blood pressure, atomoxetine should
be used cautiously with pressor agents or medications that may
increase blood pressure (such as salbutamol). Attention should be
paid to monitoring of blood pressure, and review of treatment for
either atomoxetine or pressor agents may be justified in the case of
significant change in blood pressure.
that affect noradrenaline:
that affect noradrenaline should be used cautiously when
co-administered with atomoxetine because of the potential for
additive or synergistic pharmacological effects. Examples include
antidepressants, such as imipramine, venlafaxine, and mirtazapine, or
the decongestants pseudoephedrine or phenylephrine.
that affect gastric pH:
that elevate gastric pH (magnesium hydroxide/aluminium hydroxide,
omeprazole) had no effect on atomoxetine bioavailability.
highly bound to plasma protein:
vitro drug-displacement studies were conducted with atomoxetine and
other highly-bound drugs at therapeutic concentrations. Warfarin,
acetylsalicylic acid, phenytoin, or diazepam did not affect the
binding of atomoxetine to human albumin. Similarly, atomoxetine did
not affect the binding of these compounds to human albumin.
Summary of Product Characteristics