Atomoxetine, a selective norepinephrine reuptake inhibitor with minimal affinity for other noradrenergic receptors, is used
to treat attention deficit hyperactivity disorder (ADHD) in children and adults.1 It is available by prescription under the brand name Strattera (Eli Lilly) in 10-, 18-, 25-, 40-, 60-, 80-, and 100-mg capsules.
This drug is not used in veterinary medicine. However, you should be aware of its toxic potential because of its availability
in households that have pets or animal visitors. Since the release of atomoxetine in 2003, the American Society for the Prevention
of Cruelty to Animals (ASPCA) Animal Poison Control Center (APCC) has received more than 700 calls involving a possible exposure
to atomoxetine (ASPCA APCC Database, Urbana, Ill: Unpublished data, 2003-2011).
MECHANISM OF ACTION AND PHARMACOKINETICS
The mechanism of action by which this medication improves clinical signs associated with ADHD is not yet known, but it is
thought to be due to the selective inhibition of the presynaptic norepinephrine transporter.1
In people, atomoxetine is well-absorbed orally with a peak plasma concentration occurring one or two hours after administration.2 It is highly protein bound in both dogs (97%) and people (98%).3 In people, atomoxetine is metabolized primarily through the cytochrome P-450 enzymatic pathway CYP2D6 to an oxidative metabolite
(4-hydroxyatomoxetine). There is a genetic polymorphism of CYP2D6 in people. Those that metabolize CYP2D6 poorly experience
plasma concentrations that are five times greater than the concentrations that extensive metabolizers experience. About 7%
of Caucasian populations are poor metabolizers. The reported elimination half-life in people is 5.3 hours in extensive metabolizers
and 24 hours in poor metabolizers.2
Dogs do not express CYP2D6; they metabolize the drug by aromatic ring hydroxylation and N-demethylation, but atomoxetine is
ultimately metabolized to the same primary oxidative metabolite as in humans, 4-hydroxyatomoxetine.3 In dogs, 48% of the drug is excreted through the kidneys and 42% in the feces. The terminal half-life in dogs after oral
administration of atomoxetine at a dose of 2 mg/kg is about 3.7 (+/- 0.5) hours.3
Clinical research involving acute atomoxetine toxicosis in dogs and cats is minimal, and there is no LD50 established for either species. Because atomoxetine selectively inhibits the presynaptic norepinephrine transporter while
having minimal affinity and effect on other neurotransmitter receptors, it may cause an increase in autonomic tone.4
As with the body's natural fight-or-flight response, a pharmacologically induced increase in norepinephrine may result in
clinical signs that are consistent with cardiovascular stimulation: vasoconstriction, hypertension, or tachycardia followed
by possible reflex bradycardia. Other noradrenergic effects such as urinary sphincter contractions, transient hyperglycemia,
and mydriasis may also be seen with excessive accumulation of norepinephrine.5
Additionally, since the drug's release, there have been some documented cases of severe hepatic injury in people receiving
this medication.2 This has not been noted in any ASPCA APCC cases.
In a study involving 8-week-old beagle puppies receiving oral doses of atomoxetine at 4, 8, or 16 mg/kg/day for four weeks,
dose-related clinical signs of vomiting, retching, tremors, mydriasis, and decreased pupillary light reflex were noted. With
the exception of repetitive head movements reported at 16 mg/kg/day, the abstract (the full study was not published) does
not provide doses at which specific clinical signs were seen.6
A rodent study showed that when 25 mg/kg of atomoxetine was fed to female rats for two weeks before conception and continued
throughout lactation, decreased pup survival rates were observed.2 A decrease in pup survival was also noted when male rats were fed the same dose starting 10 weeks before mating.