Atomoxetine

Usage

• Atomoxetine is primarily prescribed for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in children, adolescents, and adults as part of a comprehensive treatment program. It is a non-stimulant medication.
• Pharmacological Classification: Selective Norepinephrine Reuptake Inhibitor (SNRI).
• Mechanism of Action: Atomoxetine selectively inhibits the presynaptic norepinephrine transporter, increasing the availability of norepinephrine in the prefrontal cortex, which is believed to be the primary mechanism for its therapeutic effect in ADHD.

Alternate Names

• International Nonproprietary Name (INN): Atomoxetine
• Brand Name: Strattera

How It Works

• Pharmacodynamics: Atomoxetine primarily affects norepinephrine neurotransmission. By inhibiting its reuptake, it increases the concentration of norepinephrine in the synaptic cleft, particularly in the prefrontal cortex, an area of the brain involved in attention, executive function, and impulse control. It is believed to have minimal direct effects on dopamine, although indirect dopaminergic effects in the prefrontal cortex might be observed.
• Pharmacokinetics:
  • Absorption: Atomoxetine is well-absorbed after oral administration, reaching peak plasma concentrations within 1 to 2 hours. Food does not significantly affect its absorption.
  • Metabolism: Primarily metabolized in the liver, mainly by the cytochrome P450 2D6 (CYP2D6) enzyme.
  • Elimination: Excreted primarily in the urine as metabolites, with a small amount excreted unchanged. The elimination half-life is approximately 5 hours in extensive metabolizers and considerably longer in poor metabolizers of CYP2D6.

Dosage

Standard Dosage

Adults:

• Initial dose: 40 mg orally once daily.
• Maintenance dose: Increase to 80 mg/day orally after a minimum of 3 days. This can be given as a single dose or divided into two doses (morning and late afternoon/early evening).
• Maximum dose: After 2-4 weeks, the dose can be increased to 100 mg/day if an optimal response isn’t achieved.

Children (6 years and older):

• <70 kg:
  • Initial dose: 0.5 mg/kg orally once daily.
  • Maintenance dose: Increase to 1.2 mg/kg/day orally (single or divided doses) after a minimum of 3 days.
  • Maximum dose: 1.4 mg/kg/day or 100 mg/day (whichever is less).
• >70 kg: Follow adult dosing guidelines.

Special Cases:

• Elderly Patients: Start at a lower dose (40mg daily) and titrate cautiously, considering age-related changes in hepatic and renal function.
• Patients with Renal Impairment: No dosage adjustment is generally necessary. However, monitor for hypertension, especially in patients with end-stage renal disease.
• Patients with Hepatic Dysfunction:
  • Moderate (Child-Pugh Class B): Reduce initial and target dose by 50%.
  • Severe (Child-Pugh Class C): Reduce initial and target dose by 75%.
• Patients with Comorbid Conditions: Monitor closely for exacerbations of pre-existing conditions such as hypertension, tachycardia, cardiovascular disease, or cerebrovascular disease. Careful assessment and individualized dosing are crucial. Consider pre-screening for bipolar disorder.

Clinical Use Cases

Atomoxetine is not indicated for use in situations like intubation, surgical procedures, mechanical ventilation, intensive care unit (ICU) use, or emergency situations such as status epilepticus or cardiac arrest. Its primary indication is for the management of ADHD.

Dosage Adjustments

• CYP2D6 Poor Metabolizers: Initiate treatment with a lower dose (0.5 mg/kg/day for children ≤70 kg or 40 mg/day for adults/children >70 kg). Increase to 1.2 mg/kg/day (children ≤70 kg) or 80 mg/day (adults/children >70 kg) only if symptoms don’t improve after 4 weeks and the initial dose is well-tolerated.

Side Effects

Common Side Effects:

• Decreased appetite, weight loss
• Nausea, vomiting, constipation, dry mouth, dyspepsia
• Headache, dizziness, insomnia, fatigue
• Mood swings, irritability, anxiety

Rare but Serious Side Effects:

• Allergic reactions (angioedema, urticaria)
• Liver injury (jaundice, elevated liver enzymes)
• Suicidal ideation (particularly in children and adolescents)
• Cardiovascular effects (tachycardia, palpitations, hypertension)
• Priapism
• Seizures
• Severe skin reactions (Stevens-Johnson Syndrome)

Long-Term Effects:

Potential long-term effects are not fully characterized but may include growth suppression in children and adolescents with prolonged use. Regular monitoring of height and weight is recommended.

Adverse Drug Reactions (ADR):

Serious ADRs like angioedema, hepatotoxicity, suicidal ideation, severe cardiovascular effects, priapism, or seizures require immediate discontinuation of atomoxetine and prompt medical attention.

Contraindications

• Hypersensitivity to atomoxetine
• Concomitant or recent (within 14 days) use of MAOIs
• Narrow-angle glaucoma
• Pheochromocytoma
• Severe cardiovascular disorders (e.g., severe hypertension, tachyarrhythmias, advanced arteriosclerosis)

Drug Interactions

• MAOIs: Concomitant use contraindicated due to the risk of serious, potentially fatal reactions.
• CYP2D6 Inhibitors: May increase atomoxetine concentrations. Dose adjustment may be required.
• QT Prolonging Drugs: Use with caution as combined effects may increase the risk of QT prolongation and Torsades de Pointes.
• Albuterol: May increase cardiovascular effects. Monitor blood pressure and heart rate.
• Pressors/Hypertensive agents: May enhance the hypertensive effects of these agents. Careful monitoring is needed.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: C. Atomoxetine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
• Breastfeeding: Atomoxetine is excreted in breast milk. Limited data suggest a potential for adverse effects in nursing infants. Weigh the benefits of breastfeeding against the potential risks to the infant.

Drug Profile Summary

• Mechanism of Action: Selective Norepinephrine Reuptake Inhibitor (SNRI)
• Side Effects: Nausea, decreased appetite, insomnia, headache, dizziness, dry mouth. Serious but rare: suicidal ideation, liver injury, cardiovascular effects.
• Contraindications: Hypersensitivity, concurrent MAOI use, narrow-angle glaucoma, pheochromocytoma, severe cardiovascular disorders.
• Drug Interactions: MAOIs, CYP2D6 inhibitors, QT prolonging drugs, albuterol.
• Pregnancy & Breastfeeding: Category C; excreted in breast milk; potential risks to the infant.
• Dosage: Adults: 40-100 mg/day; Children: 0.5-1.4 mg/kg/day (or up to 100 mg/day). Adjust based on response, CYP2D6 metabolizer status, and hepatic impairment.
• Monitoring Parameters: Blood pressure, heart rate, liver function tests, growth in children and adolescents, and any emergence of suicidal thoughts or behaviors.

Popular Combinations

While atomoxetine is generally used as monotherapy, in some cases, it might be combined with behavioral therapy or other non-pharmacological interventions for managing ADHD. Combination with other medications for ADHD, like stimulants, would require careful consideration of potential drug interactions and additive side effects.

Precautions

• General Precautions: Careful patient evaluation including medical history, cardiovascular assessment, and screening for psychiatric comorbidities is essential. Monitor for suicidal ideation, especially at the beginning of treatment. Regular monitoring of blood pressure, heart rate, liver function, and growth (in children) is recommended.

• Specific Populations:

  • Pregnant Women: Use with caution.
  • Breastfeeding Mothers: Potential for adverse effects in infants.
  • Children & Elderly: Start with lower doses and titrate cautiously.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Atomoxetine?

A: Adults: Start at 40mg/day, increase to 80mg/day after 3 days, max 100mg/day. Children (6+ years): <70 kg: 0.5mg/kg/day initially, increasing to 1.2mg/kg/day after 3 days, max 1.4mg/kg/day or 100mg/day (whichever is less). >70 kg: follow adult dosing.

Q2: What are the common side effects of Atomoxetine?

A: Decreased appetite, nausea, vomiting, constipation, dry mouth, headache, insomnia, dizziness.

Q3: Is Atomoxetine a stimulant?

A: No, atomoxetine is a non-stimulant medication.

Q4: How long does it take for Atomoxetine to work?

A: Initial effects may be seen within 1-4 weeks, but full therapeutic benefits may take up to 8 weeks or longer.

Q5: Can Atomoxetine be used during pregnancy?

A: It’s a pregnancy category C drug. Use only if the potential benefit outweighs the potential risk to the fetus.

Q6: Does Atomoxetine interact with other medications?

A: Yes, it can interact with MAOIs, CYP2D6 inhibitors, and QT prolonging agents. Always review concomitant medications.

Q7: Are there any contraindications for using Atomoxetine?

A: Yes, contraindications include hypersensitivity, concurrent MAOI use, narrow-angle glaucoma, pheochromocytoma, and severe cardiovascular disorders.

Q8: What should I monitor in patients taking Atomoxetine?

A: Monitor blood pressure, heart rate, liver function, growth (in children), and for any signs of suicidal ideation.

Q9: Can Atomoxetine be used with other ADHD medications?

A: Combining with other ADHD medications, especially stimulants, requires careful monitoring due to potential drug interactions and additive side effects.

Q10: Can patients abruptly stop taking atomoxetine?

A: While not typically associated with severe withdrawal symptoms, it is generally recommended to gradually taper the dose under medical supervision, especially after prolonged use, to minimize the risk of any potential discontinuation effects.