STRATTERA 18MG

Indications

• Attention deficit hyperactivity disorder (ADHD)

Dosage

Children: Child 6–17 years (body-weight 70 kg and above): Initially 40 mg daily for 7 days, dose is increased according to response; maintenance 80 mg daily, maximum 120 mg per day.

Adults: Initially 40 mg daily for 7 days, dose may be increased according to response; maintenance 80 mg daily, total daily dose may be given either as a single dose in the morning or in 2 divided doses with last dose no later than early evening, maximum 120 mg per day.

Mechanism of action

Atomoxetine selectively inhibits the reuptake of norepinephrine, leading to increased levels of norepinephrine in the synaptic cleft, which is thought to improve attention and reduce impulsivity and hyperactivity in patients with ADHD.

Pharmacodynamics

The pharmacodynamic effects of atomoxetine include enhanced norepinephrine activity in the prefrontal cortex, which is associated with improved executive function and attention regulation. It does not exhibit the stimulant properties of traditional ADHD medications.

Pharmacokinetics

Atomoxetine is well-absorbed after oral administration, with peak plasma concentrations occurring within 1 to 2 hours. It has a large volume of distribution and is primarily metabolized by the liver via cytochrome P450 2D6. The elimination half-life is approximately 5 to 24 hours, depending on individual metabolic rates.

Contra-indications

• Phaeochromocytoma
• Severe cardiovascular disease
• Severe cerebrovascular disease

Adverse effects

• Anxiety
• Decreased appetite
• Irritability
• Agitation
• Depression
• Suicidal thoughts and behavior

Interactions

• berotralstat: Moderate (increases exposure)
• bupropion: Moderate (increases exposure)
• cinacalcet: Moderate (increases exposure)
• dacomitinib: Moderate (increases exposure)
• eliglustat: Moderate (increases exposure)
• fedratinib: Moderate (increases exposure)
• givosiran: Moderate (increases exposure)
• panobinostat: Moderate (increases exposure)
• terbinafine: Moderate (increases exposure)
• amfetamines: Unknown (increases risk of adverse effects)

Precautions

• Monitor for signs of hepatic disorders
• Risk of suicidal ideation
• Use caution in patients with aggressive behavior

Pregnancy

Safety during pregnancy is not established; benefit-risk should be considered.

Breast-feeding

Use with caution; limited data available.

Storage

Store in a cool, dry place away from direct sunlight.

Formulations

• Oral capsules (Strattera)
• Oral solution (Strattera 4mg/1ml)

Mechanism of action

Atomoxetine is known to be a potent and selective inhibitor of the norepinephrine transporter (NET), which prevents cellular reuptake of norepinephrine throughout the brain, which is thought to improve the symptoms of ADHD. More recently, positron emission tomography (PET) imaging studies in rhesus monkeys have shown that atomoxetine also binds to the serotonin transporter (SERT), and blocks the N-methyl-d-aspartate (NMDA) receptor, indicating a role for the glutamatergic system in the pathophysiology of ADHD. The selective norepinephrine (NE) transporter inhibitor atomoxetine (formerly called tomoxetine or LY139603) has been shown to alleviate symptoms in Attention Deficit/Hyperactivity Disorder (ADHD). We investigated the mechanism of action of atomoxetine in ADHD by evaluating the interaction of atomoxetine with monoamine transporters, the effects on extracellular levels of monoamines, and the expression of the neuronal activity marker Fos in brain regions. Atomoxetine inhibited binding of radioligands to clonal cell lines transfected with human NE, serotonin (5-HT) and dopamine (DA) transporters with dissociation constants (K(i)) values of 5, 77 and 1451 nM, respectively, demonstrating selectivity for NE transporters. In microdialysis studies, atomoxetine increased extracellular (EX) levels of NE in prefrontal cortex (PFC) 3-fold, but did not alter 5-HT(EX) levels. Atomoxetine also increased DA(EX) concentrations in PFC 3-fold, but did not alter DA(EX) in striatum or nucleus accumbens. In contrast, the psychostimulant methylphenidate, which is used in ADHD therapy, increased NE(EX) and DA(EX) equally in PFC, but also increased DA(EX) in the striatum and nucleus accumbens to the same level. The expression of the neuronal activity marker Fos was increased 3.7-fold in PFC by atomoxetine administration, but was not increased in the striatum or nucleus accumbens, consistent with the regional distribution of increased DA(EX). We hypothesize that the atomoxetine-induced increase of catecholamines in PFC, a region involved in attention and memory, mediates the therapeutic effects of atomoxetine in ADHD. In contrast to methylphenidate, atomoxetine did not increase DA in striatum or nucleus accumbens, suggesting it would not have motoric or drug abuse liabilities.

Pharmacodynamics

Atomoxetine is a selective norepinephrine (NE) reuptake inhibitor used for the treatment of attention deficit hyperactivity disorder (ADHD). Atomoxetine has been shown to specifically increase norepinephrine and dopamine within the prefrontal cortex, which results in improved ADHD symptoms. Due to atomoxetine's noradrenergic activity, it also has effects on the cardiovascular system such as increased blood pressure and tachycardia. Sudden deaths, stroke, and myocardial infarction have been reported in patients taking atomoxetine at usual doses for ADHD. Atomoxetine should be used with caution in patients whose underlying medical conditions could be worsened by increases in blood pressure or heart rate such as certain patients with hypertension, tachycardia, or cardiovascular or cerebrovascular disease. It should not be used in patients with severe cardiac or vascular disorders whose condition would be expected to deteriorate if they experienced clinically important increases in blood pressure or heart rate. Although the role of atomoxetine in these cases is unknown, consideration should be given to not treating patients with clinically significant cardiac abnormalities. Patients who develop symptoms such as exertional chest pain, unexplained syncope, or other symptoms suggestive of cardiac disease during atomoxetine treatment should undergo a prompt cardiac evaluation. In general, particular care should be taken in treating ADHD in patients with comorbid bipolar disorder because of concern for possible induction of a mixed/manic episode in patients at risk for bipolar disorder. Treatment emergent psychotic or manic symptoms, e.g., hallucinations, delusional thinking, or mania in children and adolescents without a prior history of psychotic illness or mania can be caused by atomoxetine at usual doses. If such symptoms occur, consideration should be given to a possible causal role of atomoxetine, and discontinuation of treatment should be considered. Atomoxetine capsules increased the risk of suicidal ideation in short-term studies in children and adolescents with Attention-Deficit/Hyperactivity Disorder (ADHD). All pediatric patients being treated with atomoxetine should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. Postmarketing reports indicate that atomoxetine can cause severe liver injury. Although no evidence of liver injury was detected in clinical trials of about 6000 patients, there have been rare cases of clinically significant liver injury that were considered probably or possibly related to atomoxetine use in postmarketing experience. Rare cases of liver failure have also been reported, including a case that resulted in a liver transplant. Atomoxetine should be discontinued in patients with jaundice or laboratory evidence of liver injury, and should not be restarted. Laboratory testing to determine liver enzyme levels should be done upon the first symptom or sign of liver dysfunction (e.g., pruritus, dark urine, jaundice, right upper quadrant tenderness, or unexplained “flu like” symptoms).