To the Editor:
Strattera®, atomoxetine HCl, is a norepinephrine reuptake inhibitor approved by the U.S. Food and Drug Administration for the treatment of attention deficit hyperactivity disorder (ADHD). It has a maximum recommended daily dose of 1.4 mg/kg in children and is administered once or twice daily Citation1. Currently, there is no published data regarding overdose with this medication. We report the acute ingestion of 5.3 mg/kg in an adolescent.
A 12-yr-old, 34 kg male was mistakenly given three tablets of Strattera® 60 mg instead of three tablets of his dextroamphetamine. Upon realizing the mistake, the patient's mother brought him to the emergency department (ED) 90 min after the ingestion occurred. His vital signs revealed blood pressure 118/74 mm Hg, pulse 106 bpm, respirations 19 rpm, normal oral temperature. His initial physical examination was normal. Activated charcoal was not given because of delayed presentation to the ED. Because peak plasma concentrations of atomoxetine occur within 1 to 2 h of oral administration Citation2, a 4–6 h observation period from the time of ingestion was deemed sufficient to detect any clinical changes. The patient's pulse returned to within the normal range soon after arrival, and he was discharged home following a symptom-free observation period of 3 h. A telephone follow-up performed 6.5 h post-ingestion revealed no ill effects from the overdose.
Atomoxetine is a methylphenoxy-benzene propanamine derivative that inhibits presynaptic norepinephrine reuptake with little or no affinity for other neurotransmitter receptors Citation3. Because of its reported nonaddictive properties, it is an attractive alternative to stimulant therapy for ADHD. Adverse effects reported during use include dizziness, fatigue, decreased appetite, gastrointestinal symptoms, rash, and statistically significant increases in blood pressure and pulse Citation3&4.
With a lack of published overdose data, it is difficult to estimate a threshold dose at which acute toxicity will occur. Pharmacokinetic factors that may influence the risk of toxicity include a 31% increase in bioavailability in poor metabolizers and drug interactions with medications also metabolized by cytochrome P450 isoenzyme 2D6 that could result in increased concentrations of both the parent compound and the active metabolite 4-hydroxyatomoxetine Citation1. Anticipated symptoms occurring in the overdose setting would be amplified forms of reported adverse effects. In our patient, an accidental overdose with almost four times the maximum recommended daily dose of atomoxetine resulted in a benign clinical course without intervention. Future experience involving supratherapeutic doses with this medication may assist in determining the relative safety of this medication in the overdose setting.
F. Lee Cantrell, Pharm.D.
California Poison Control System, San Diego Division
San Diego, California
University of California San Francisco School of Pharmacy
San Francisco, California
Mike Nestor, M.D.
Department of Emergency Medicine
Kaiser Permanente Medical Center
Anaheim, California
References
- Product Information: Strattera(TM), Atomoxetine. Eli Lilly & Co.: Indianapolis, IN, 2002.
- Witcher J W, Long A, Smith B, Sauer J M, Heilgenstein J, Wilens T, Spencer T, Biederman J. Atomoxetine pharmacokinetics in children and adolescents with attention deficit hyperactivity disorder. J Child Adolesc Psychopharmacol Spring, 2003; 13(1):53–63.
- Caballero J, Nahata M C. Atomoxetine hydrochloride for the treatment of attention-deficit/hyperactivity disorder. Clin Ther Dec, 2003; 25(12):3065–3083.
- Eiland L S, Guest A L. Atomoxetine treatment of attention-deficit/hyperactivity disorder. Ann Pharmacother Jan, 2004; 38(1):86–90.