Atomoxetine: DOSING

It is supplied as capsules, in strengths of 10, 18, 25, 40, and 60 mg. For children and adolescents weighing up to 70 kg, the recommended initial dose is 0.5 mg/kg. After a minimum of three days, the dose should be increased to a targeted daily dose of 1.2 mg/kg. The targeted daily dose may be given once in the morning or in evenly divided doses in the morning and evening or late afternoon. No clinical benefits from doses higher than 1.2 mg/kg have been observed in clinical trials.

For children and adolescents who weigh more than 70 kg, the recommended initial dose is 40 mg. After a minimum of three days, it may be increased to 80 mg, administered as a single dose or as evenly divided doses in the morning and evening. After two to four weeks, this amount may be increased to a maximum of 100 mg daily in patients who are not experiencing the optimal effect.

In patients with hepatic failure, dosage adjustments are required. For patients with moderate hepatic impairment, the initial and targeted doses should be decreased to 50% of the normal amount; for patients with severe hepatic impairment, they should be reduced to 25% of the normal dose.

Because atomoxetine is metabolized by CYP2D6, dosage adjustments are required for strong CYP2D6 inhibitors. With the co-administration of atomoxe-tine and strong CYP2D6 inhibitors, the initial dosage of atomoxetine must remain the same in both groups. The maintenance dose should be increased only if no clinical benefit is observed after four weeks of therapy.

DRUG INTERACTIONS

Atomoxetine is metabolized primarily by the CYP2D6 pathway to 4-hydroxy-atomoxetine. Therefore, dosage adjustments may be necessary when the drug is co-administered with CYP2D6 inhibitors such as paroxetine canadian (Glaxo-SmithKline), fluoxetine (Prozac®, Eli Lilly), and quinidine (e.g., Quinidine Glu-conate or Sulfate, Watson). Patients should not take atomoxetine at the same time as, or within two weeks of, their taking a monoamine oxidase (MAO) inhibitor. Patients with narrow-angle glaucoma should not take atomoxetine.

Co-administration of atomoxetine and other agents has shown varying results:

  • (e.g., Scher-ing; GlaxoSmithKline): Alterations in heart rate and blood pressure were potentiated.
  • Desipramine (Norpramin®, Aven-tis; Desipramine, Geneva, Watson): No dose adjustments were required, and no pharmacokinetic parameters were altered.
  • Methylphenidate: Co-administration did not add to the cardiovascular effects that were already seen with methylphenidate alone.
  • Midazolam (e.g., Versed®, Roche): A 15% increase in the area-under-the-curve (AUC) concentration of midazolam was observed.
  • (DuPont), acetylsalicylic acid (aspirin), (Pfizer), and diazepam (Valium®, Roche): Atom-oxetine did not show any effect on the binding of these drugs to human albumin.
  • Aluminum hydroxide (e.g., Maa-lox®, Novartis; Mylanta®, Merck), magnesium hydroxide (e.g., Maa-lox®; Mylanta®; Pepcid®, Merck), omeprazole canadian (e.g., Prilosec tablet, Astra-Zeneca): These drugs, which elevate gastric pH, had no effect on the bioavailability of atomoxetine tablet.