atomoxetine 40 MG Oral Capsule [Strattera]

INDICATIONS AND USAGE Atomoxetine capsules are a selective norepinephrine reuptake inhibitor indicated for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD). ( 1.1 ) 1.1 Attention-Deficit/Hyperactivity Disorder (ADHD) Atomoxetine capsules are indicated for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD). The efficacy of atomoxetine capsules was established in seven clinical trials in outpatients with ADHD: four 6 to 9-week trials in pediatric patients (ages 6 to 18), two 10-week trial in adults, and one maintenance trial in pediatrics (ages 6 to 15) [ see Clinical Studies ( 14 ) ]. 1.2 Diagnostic Considerations A diagnosis of ADHD (DSM-IV) implies the presence of hyperactive-impulsive or inattentive symptoms that cause impairment and that were present before age 7 years. The symptoms must be persistent, must be more severe than is typically observed in individuals at a comparable level of development, must cause clinically significant impairment, e.g., in social, academic, or occupational functioning, and must be present in 2 or more settings, e.g., school (or work) and at home. The symptoms must not be better accounted for by another mental disorder. The specific etiology of ADHD is unknown, and there is no single diagnostic test. Adequate diagnosis requires the use not only of medical but also of special psychological, educational, and social resources. Learning may or may not be impaired. The diagnosis must be based upon a complete history and evaluation of the patient and not solely on the presence of the required number of DSM-IV characteristics. For the Inattentive Type, at least 6 of the following symptoms must have persisted for at least 6 months: lack of attention to details/careless mistakes, lack of sustained attention, poor listener, failure to follow through on tasks, poor organization, avoids tasks requiring sustained mental effort, loses things, easily distracted, forgetful. For the Hyperactive-Impulsive Type, at least 6 of the following symptoms must have persisted for at least 6 months: fidgeting/squirming, leaving seat, inappropriate running/climbing, difficulty with quiet activities, “on the go,” excessive talking, blurting answers, can’t wait turn, intrusive. For a Combined Type diagnosis, both inattentive and hyperactive-impulsive criteria must be met. 1.3 Need for Comprehensive Treatment Program Atomoxetine capsules are indicated as an integral part of a total treatment program for ADHD that may include other measures (psychological, educational, social) for patients with this syndrome. Drug treatment may not be indicated for all patients with this syndrome. Drug treatment is not intended for use in the patient who exhibits symptoms secondary to environmental factors and/or other primary psychiatric disorders, including psychosis. Appropriate educational placement is essential in children and adolescents with this diagnosis and psychosocial intervention is often helpful. When remedial measures alone are insufficient, the decision to prescribe drug treatment medication will depend upon the physician’s assessment of the chronicity and severity of the patient’s symptoms.

DOSAGE AND ADMINISTRATION Prior to initiating treatment with atomoxetine oral solution: Screen patients for a personal or family history of bipolar disorder, mania, or hypomania. ( 2.1 , 5.6 ) Consider genetic testing to determine the patient’s CYP2D6 metabolizer status prior to dosing. ( 2.1 , 2.5 ) See table below for the recommended atomoxetine oral solution dosage. ( 2.3 ) Age and Body Weight Starting Dosage Target Dosage 1 Maximum Total Daily Dose 1 Pediatrics who weigh less than 70 kg 0.5 mg/kg/day 1.2 mg/kg/day 1.4 mg/kg/day or 100 mg/day (whichever is less) Pediatrics who weigh 70 kg or more and adults 40 mg/day 80 mg/day 100 mg/day 1 Administer either as once daily dosage in the morning or as evenly divided twice daily dosage in the morning and late afternoon/early evening For the recommended dosage in patients with hepatic impairment, see Full Prescribing Information. ( 2.4 ) For the recommended dosage with concomitant use of a strong CYP2D6 inhibitor or in CYP2D6 poor metabolizers, see Full Prescribing Information. ( 2.5 ) 2.1 Recommendations Prior to Initiating Atomoxetine Oral Solution Treatment Prior to initiating treatment with atomoxetine oral solution: Screen patients for a personal or family history of bipolar disorder, mania, or hypomania [see Warnings and Precautions (5.6) ] . Consider genetic testing to determine the patient’s CYP2D6 metabolizer status [see Dosage and Administration (2.5) ] . 2.2 Administration Instructions Atomoxetine oral solution may be taken with or without food. Instruct patients to only use the supplied syringe and bottle adapter to measure and take atomoxetine oral solution [see Instructions for Use ] . 2.3 Recommended Dosage Table 1 includes the recommended dosage of atomoxetine oral solution in adult patients and pediatric patients 6 years of age and older for treatment of ADHD. Table 1: Recommended Dosage of Atomoxetine Oral Solution for the Treatment of ADHD​​​​​​​ Age and Body Weight Starting Dosage Titration Interval Target Dosage Maximum Dosage Pediatric patients who weigh less than 70 kg 0.5 mg/kg/day Minimum of 3 days 1.2 mg/kg/day a,b 1.4 mg/kg/day or 100 mg/day, whichever is less a Pediatric patients who weigh 70 kg or more and adult patients 40 mg/day Minimum of 3 days 80 mg/day a 100 mg/day a,c a Administered either as a single daily dose in the morning or as evenly divided doses in the morning and late afternoon/early evening. b No additional benefit has been demonstrated with atomoxetine dosages higher than 1.2 mg/kg/day [see Clinical Studies (14) ] . c If a patient has not achieved an optimal response at 80 mg/day after 2 to 4 additional weeks, may increase dosage to a maximum of 100 mg/day. There are no data that support increased effectiveness at a dosage higher than 100 mg/day [see Clinical Studies (14) ] . The health care provider who elects to use atomoxetine oral solution for extended periods should periodically reevaluate the long-term usefulness of atomoxetine oral solution for the individual patient. 2.4 Recommended Dosage in Patients with Hepatic Impairment For patients 6 years of age or older with: Severe hepatic impairment (HI) (Child-Pugh Class C), the recommended initial and target dosage is 25% of recommended dosage in patients with normal hepatic function [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3) ] . Moderate HI (Child-Pugh Class B), the recommended initial and target dosage is 50% of the recommended dosage in patients with normal hepatic function [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3) ] . Mild HI (Child-Pugh Class A) the recommended initial and target dosage is the same as those with normal hepatic function. 2.5 Recommended Dosage with Concomitant Use of Strong CYP2D6 Inhibitors or in CYP2D6 Poor Metabolizers Table 2 includes the recommended atomoxetine oral solution dosage in adult patients and pediatric patients aged 6 years of age or older with concomitant use of a strong CYP2D6 inhibitor or in CYP2D6 poor metabolizers [see Drug Interactions (7) and Use in Specific Populations (8.7) ] . The recommended titration interval in these patients is every four weeks (if ADHD symptoms fail to improve and the initial dosage is well tolerated). For other CYP2D6 metabolizer types (ultrarapid, normal, and intermediate), follow the recommended dosage, including the recommended titration interval (minimum of 3 days), as outlined in Table 1 [see Dosage and Administration (2.3) ] . Table 2: Recommended Dosage of Atomoxetine Oral Solution with Concomitant Use of a Strong CYP2D6 Inhibitor or in CYP2D6 Poor Metabolizers​​​​​​​ Age and Body Weight Starting Dosage Titration Interval a Target Dosage d Pediatric patients who weigh less than 70 kg 0.5 mg/kg/day 4 weeks 1.2 mg/kg/day b,c Pediatric patients who weigh 70 kg or more and adult patients 40 mg/day 4 weeks 80 mg/day b a Titrate if ADHD symptoms fail to improve and the initial dosage is well tolerated. b Administered either as a single daily dose in the morning or as evenly divided doses in the morning and late afternoon/early evening. c No additional benefit has been demonstrated with atomoxetine dosages higher than 1.2 mg/kg/day [see Clinical Studies (14) ] . d Maximum dosage has not been established with concomitant use of a strong CYP2D6 inhibitor or in CYP2D6 poor metabolizers. 2.6 Switching to or from a Monoamine Oxidase Inhibitor Antidepressant At least 14 days must elapse between discontinuation of a monoamine oxidase inhibitor (MAOI) antidepressant and initiation of atomoxetine oral solution. In addition, at least 14 days must elapse after stopping atomoxetine oral solution before starting an MAOI antidepressant. 2.7 Recommendations for a Missed Dose If the atomoxetine oral solution dose is missed, take the dose as soon as possible, but do not take more than the prescribed total daily amount of atomoxetine oral solution in any 24-hour period. 2.8 Recommendations for Discontinuation When discontinuing atomoxetine, no taper is needed [see Drug Abuse and Dependence (9.3) ] .

WARNINGS AND PRECAUTIONS • Suicidal Ideation – Monitor for suicidality, clinical worsening, and unusual changes in behavior. ( 5.1 ) • Severe Liver Injury – Should be discontinued and not restarted in patients with jaundice or laboratory evidence of liver injury. ( 5.2 ) • Serious Cardiovascular Events – Sudden death, stroke and myocardial infarction have been reported in association with atomoxetine treatment. Patients should have a careful history and physical exam to assess for presence of cardiovascular disease. Atomoxetine generally should not be used in children or adolescents with known serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, or other serious cardiac problems that may place them at increased vulnerability to its noradrenergic effects. Consideration should be given to not using atomoxetine capsules in adults with clinically significant cardiac abnormalities. ( 5.3 ) • Emergent Cardiovascular Symptoms – Patients should undergo prompt cardiac evaluation. ( 5.3 ) • Effects on Blood Pressure and Heart Rate –Increase in blood pressure and heart rate; orthostasis and syncope may occur. Use with caution in patients with hypertension, tachycardia, or cardiovascular or cerebrovascular disease. ( 5.4 ) • Emergent Psychotic or Manic Symptoms – Consider discontinuing treatment if such new symptoms occur. ( 5.5 ) • Bipolar Disorder – Screen patients to avoid possible induction of a mixed/manic episode. ( 5.6 ) • Aggressive behavior or hostility should be monitored. ( 5.7 ) • Possible allergic reactions, including anaphylactic reactions, angioneurotic edema, urticaria, and rash. ( 5.8 ) • Effects on Urine Outflow – Urinary hesitancy and retention may occur. ( 5.9 ) • Priapism – Prompt medical attention is required in the event of suspected priapism. ( 5.10 , 17 ) • Growth – Height and weight should be monitored in pediatric patients. ( 5.11 ) • Concomitant Use of Potent CYP2D6 Inhibitors or Use in patients known to be CYP2D6 PMs – Dose adjustment of atomoxetine may be necessary. ( 5.13 ) 5.1 Suicidal Ideation Atomoxetine increased the risk of suicidal ideation in short-term studies in children and adolescents with Attention-Deficit/Hyperactivity Disorder (ADHD). Pooled analyses of short-term (6 to 18 weeks) placebo-controlled trials of atomoxetine in children and adolescents have revealed a greater risk of suicidal ideation early during treatment in those receiving atomoxetine. There were a total of 12 trials (11 in ADHD and 1 in enuresis) involving over 2200 patients (including 1357 patients receiving atomoxetine and 851 receiving placebo). The average risk of suicidal ideation in patients receiving atomoxetine was 0.4% (5/1357 patients), compared to none in placebo-treated patients. There was 1 suicide attempt among these approximately 2200 patients, occurring in a patient treated with atomoxetine. No suicides occurred in these trials . All reactions occurred in children 12 years of age or younger. All reactions occurred during the first month of treatment. It is unknown whether the risk of suicidal ideation in pediatric patients extends to longer-term use. A similar analysis in adult patients treated with atomoxetine for either ADHD or major depressive disorder (MDD) did not reveal an increased risk of suicidal ideation or behavior in association with the use of atomoxetine. 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. The following symptoms have been reported with atomoxetine: anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania and mania. Although a causal link between the emergence of such symptoms and the emergence of suicidal impulses has not been established, there is a concern that such symptoms may represent precursors to emerging suicidality. Thus, patients being treated with atomoxetine should be observed for the emergence of such symptoms. Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients who are experiencing emergent suicidality or symptoms that might be precursors to emerging suicidality, especially if these symptoms are severe or abrupt in onset, or were not part of the patient’s presenting symptoms. Families and caregivers of pediatric patients being treated with atomoxetine should be alerted about the need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior, and the other symptoms described above, as well as the emergence of suicidality, and to report such symptoms immediately to healthcare providers. Such monitoring should include daily observation by families and caregivers. 5.2 Severe Liver Injury 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 capsules use in postmarketing experience. Rare cases of liver failure have also been reported, including a case that resulted in a liver transplant. Because of probable underreporting, it is impossible to provide an accurate estimate of the true incidence of these reactions. Reported cases of liver injury occurred within 120 days of initiation of atomoxetine in the majority of cases and some patients presented with markedly elevated liver enzymes [>20 X upper limit of normal (ULN)], and jaundice with significantly elevated bilirubin levels (>2 X ULN), followed by recovery upon atomoxetine discontinuation. In one patient, liver injury, manifested by elevated hepatic enzymes up to 40 X ULN and jaundice with bilirubin up to 12 X ULN, recurred upon rechallenge, and was followed by recovery upon drug discontinuation, providing evidence that atomoxetine likely caused the liver injury. Such reactions may occur several months after therapy is started, but laboratory abnormalities may continue to worsen for several weeks after drug is stopped. The patient described above recovered from his liver injury, and did not require 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) [see Warnings and Precautions ( 5.12 ); Patient Counseling Information ( 17 )]. 5.3 Serious Cardiovascular Events Sudden Death and Pre-existing Structural Cardiac Abnormalities or Other Serious Heart Problems Children and Adolescents — Sudden death has been reported in association with atomoxetine treatment at usual doses in children and adolescents with structural cardiac abnormalities or other serious heart problems. Although some serious heart problems alone carry an increased risk of sudden death, atomoxetine generally should not be used in children or adolescents with known serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, or other serious cardiac problems that may place them at increased vulnerability to the noradrenergic effects of atomoxetine. Adults — Sudden deaths, stroke, and myocardial infarction have been reported in adults taking atomoxetine at usual doses for ADHD. Although the role of atomoxetine in these adult cases is also unknown, adults have a greater likelihood than children of having serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, co

CONTRAINDICATIONS • Hypersensitivity to atomoxetine or other constituents of product. ( 4.1 ) • Atomoxetine capsules use within 2 weeks after discontinuing MAOI or other drugs that affect brain monoamine concentrations. ( 4.2 , 7.1 ) • Narrow Angle Glaucoma. ( 4.3 ) • Pheochromocytoma or history of pheochromocytoma.( 4.4 ) • Severe Cardiovascular Disorders that might deteriorate with clinically important increases in HR and BP. ( 4.5 ) 4.1 Hypersensitivity Atomoxetine capsules are contraindicated in patients known to be hypersensitive to atomoxetine or other constituents of the product [see Warnings and Precautions ( 5.8 )]. 4.2 Monoamine Oxidase Inhibitors (MAOI) Atomoxetine capsules should not be taken with an MAOI, or within 2 weeks after discontinuing an MAOI. Treatment with an MAOI should not be initiated within 2 weeks after discontinuing atomoxetine capsules. With other drugs that affect brain monoamine concentrations, there have been reports of serious, sometimes fatal reactions (including hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs, and mental status changes that include extreme agitation progressing to delirium and coma) when taken in combination with an MAOI. Some cases presented with features resembling neuroleptic malignant syndrome. Such reactions may occur when these drugs are given concurrently or in close proximity [see Drug Interactions ( 7.1 )]. 4.3 Narrow Angle Glaucoma In clinical trials, atomoxetine capsules use was associated with an increased risk of mydriasis and therefore its use is not recommended in patients with narrow angle glaucoma. 4.4 Pheochromocytoma Serious reactions, including elevated blood pressure and tachyarrhythmia, have been reported in patients with pheochromocytoma or a history of pheochromocytoma who received atomoxetine capsules. Therefore, atomoxetine capsules should not be taken by patients with pheochromocytoma or a history of pheochromocytoma. 4.5 Severe Cardiovascular Disorders Atomoxetine capsules should not be used in patients with severe cardiac or vascular disorders whose condition would be expected to deteriorate if they experience increases in blood pressure or heart rate that could be clinically important (for example, 15 to 20 mm Hg in blood pressure or 20 beats per minute in heart rate). [see Warnings and Precautions ( 5.4 )].

CLINICAL PHARMACOLOGY 12.1 Mechanism of Action The precise mechanism by which atomoxetine oral solution produces its therapeutic effects in the treatment of ADHD in adults and pediatric patients 6 years of age and older is unknown, but is thought to be related to selective inhibition of the pre-synaptic norepinephrine transporter, as determined in ex vivo uptake and neurotransmitter depletion studies. 12.2 Pharmacodynamics An exposure-response analysis of atomoxetine (0.5, 1.2 or 1.8 mg/kg/day) or placebo demonstrated atomoxetine exposure correlates with the treatment of the signs and symptoms of ADHD as measured by the ADHD Rating Scale (ADHDRS)-IV-Parent Version (investigator administered and scored). At the observed median area under the plasma-concentration curve (AUC) after administration of atomoxetine 0.5 mg/kg/day, 1.2 mg/kg/day, and 1.8 mg/kg/day, 62%, 78% and 85%, respectively, of the maximum improvement over baseline for the ADHDRS scores are expected. Cardiac Electrophysiology The effect of atomoxetine on QTc interval prolongation was evaluated in a randomized, double-blinded, positive-(moxifloxacin 400 mg) and placebo-controlled, cross-over study in healthy male CYP2D6 poor metabolizers. A total of 120 healthy subjects were administered another atomoxetine product (i.e., atomoxetine capsules) (20 mg and 60 mg) twice daily for 7 days. No large changes in QTc interval (i.e., increases >60 msec from baseline, absolute QTc >480 msec) were observed in the study. However, small changes in QTc interval cannot be excluded from this study, because the study failed to demonstrate assay sensitivity. There was a slight increase in QTc interval with increased atomoxetine concentration. Pharmacodynamic Drug Interaction Studies Consumption of ethanol with the other atomoxetine product did not change the intoxicating effects of ethanol. Concomitant use of the other atomoxetine product with methylphenidate did not increase cardiovascular effects beyond those seen with methylphenidate alone. Albuterol 600 mcg given intravenously over 2 hours (albuterol is not approved for intravenous use) induced heart rate and blood pressure increases; these effects were potentiated when co-administered with the other atomoxetine product (60 mg twice daily for 5 days), particularly initially [see Drug Interactions (7) ]. 12.3 Pharmacokinetics No clinically significant differences in pharmacokinetics of atomoxetine were observed after administration of atomoxetine oral solution and immediate-release atomoxetine capsules under fasted conditions. Pharmacokinetic parameters for atomoxetine and its metabolites in CYP2D6 poor metabolizers and other CYP2D6 metabolizer types (ultrarapid, normal, and intermediate) from studies of another atomoxetine product (i.e., atomoxetine capsules) are presented in Table 11. Table 11: Atomoxetine and Metabolite Pharmacokinetics in Adult CYP2D6 Poor Metabolizers and Other CYP2D6 Metabolizer Types Parameter Other CYP2D6 Metabolizer Types a CYP2D6 Poor Metabolizers b Absorption Dose proportionality 10-120 mg Accumulation 1.1-fold 3.3-fold Absolute bioavailability 63% 94% T max 1 hour - Effect of Food AUC: Unchanged; C max : Decreased 21% T max : Delayed 1 hour Distribution Protein Binding 98% Volume of distribution 0.85 L/kg Elimination Atomoxetine half-life 5.2 hours 21.6 hours Atomoxetine apparent oral clearance 0.35 L/hr/kg 0.03 L/hr/kg 4-Hydroxyatomoxetine half-life 6 to 8 hours - N-Desmethylatomoxetine half-life 6 to 8 hours 34 to 40 hours Metabolism Primary metabolic pathways CYP2D6 Other CYP enzymes 4-Hydroxyatomoxetine c concentration 1% of atomoxetine 0.1% of atomoxetine d N-Desmethylatomoxetine e concentration 5% of atomoxetine 45% of atomoxetine Excretion Urine Greater than 80% of the administered dose excreted as 4- hydroxyatomoxetine-O-glucuronide; Less than 3% as unchanged drug Feces Less than 17% of the administered dose Values shown in the table are average values; T max is represented as median values. Abbreviations : C max,ss : maximum plasma concentration at steady state; T max : time to peak concentration a In this analysis, other CYP2D6 metabolizers were defined as individuals who are not CYP2D6 poor metabolizers and included CYP2D6 ultrarapid, normal, and intermediate metabolizers. b CYP2D6 poor metabolizers were defined as individuals with two nonfunctional alleles (e.g., CYP2D6*3/*4, CYP2D6*5/*5 ), and as a result no CYP2D6 enzyme activity. ​​​​​​​ c Primarily formed by CYP2D6.The major oxidative metabolite formed, regardless of CYP2D6 metabolizer status, which is glucuronidated. 4-Hydroxyatomoxetine is equipotent to atomoxetine as an inhibitor of the norepinephrine transporter. d 4-hydroxyatomoxetine is formed at a slower rate by several other cytochrome P450 enzymes. ​​​​​​​ e Formed by CYP2C19 and other cytochrome P450 enzymes but has substantially (20-fold) less pharmacological activity compared with atomoxetine. Specific Populations The pharmacokinetics of atomoxetine after administration of atomoxetine oral solution in specific populations is based on the pharmacokinetics of atomoxetine after administration of another atomoxetine product (i.e., atomoxetine capsules) and these results are presented below. Hepatic Impairment: Atomoxetine exposure (AUC) was increased by 2-fold in patients with moderate (Child-Pugh Class B) hepatic impairment and 4-fold in patients with severe (Child-Pugh Class C) hepatic impairment compared to patients with normal hepatic function in other CYP2D6 metabolizer types (ultrarapid, normal, and intermediate) [see Dosage and Administration (2.4) and Use in Specific Populations (8.6) ] . Renal Impairment: Patients with severe renal impairment (end stage renal disease) had higher systemic atomoxetine exposure (about a 65% increase) than patients with normal renal function (CrCl ≥ 90 ml/minute) in other CYP2D6 metabolizer types (ultrarapid, normal, and intermediate), but there was no difference when exposure was corrected for mg/kg dose. Thus, the differences in exposure were not clinically significant. Pediatric Patients: The pharmacokinetics of atomoxetine have been evaluated in more than 400 pediatric patients treated with another atomoxetine product (i.e., atomoxetine capsules) in clinical studies, primarily using population pharmacokinetic studies. Single-dose and steady-state individual pharmacokinetic data were also obtained in pediatric patients and adults. When atomoxetine doses were normalized to a mg/kg basis, similar half-life, C max , and AUC values were observed in pediatric patients and adults. Clearance and volume of distribution after adjustment for body weight were also similar. Sex: Sex did not influence atomoxetine disposition. Ethnic Origin: Ethnic origin did not influence atomoxetine disposition. Drug interaction Studies The pharmacokinetics of atomoxetine after administration of atomoxetine oral solution with concomitant drugs is based on the pharmacokinetics of atomoxetine after administration of another atomoxetine product (i.e., atomoxetine capsules) and these results are presented below. Clinical Studies Strong CYP2D6 Inhibitors: Concomitant use of another atomoxetine product (i.e., atomoxetine capsules) (20 mg twice daily for 5 days) with paroxetine (20 mg once daily for 17 days), a known inhibitor of CYP2D6, in subjects who were not CYP2D6 poor metabolizers resulted in a 6.5-fold higher plasma exposure (AUC) to atomoxetine at steady state. Concomitant use of the other atomoxetine product (at sequential dosing of 10, 45, and 75 mg twice daily for up to 5 days of each dosage) with fluoxetine (20 mg once daily for 36 days) a known inhibitor of CYP2D6, in subjects who were not CYP2D6 poor metabolizers resulted in 6- to 8-fold increases of plasma atomoxetine exposure (AUC) at steady state compared to taking the other atomoxetine product alone. After concomitant use of the other atomoxetine product with paroxetine or fluoxetine, the C ss, max of atomoxetine was about 3-t