Atomoxetine

RECENT MAJOR CHANGES Dosage and Administration, Screen for Bipolar Disorder Prior to Starting Atomoxetine Capsules (2.4) 1/2022 Warnings and Precautions, Emergence of New Psychotic or Manic Symptoms (5.5) 1/2022 Warnings and Precautions, Screening Patients for Bipolar Disorder (5.6) 1/2022 Warnings and Precautions, Aggressive Behavior or Hostility (5.7) 1/2022 Dosage and Administration, Screen for Bipolar Disorder Prior to Starting Atomoxetine Capsules ( 2.4 ) 1/2022 Warnings and Precautions, Emergence of New Psychotic or Manic Symptoms ( 5.5 ) 1/2022 Warnings and Precautions, Screening Patients for Bipolar Disorder ( 5.6 ) 1/2022 Warnings and Precautions, Aggressive Behavior or Hostility ( 5.7 ) 1/2022

1 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.

2 DOSAGE AND ADMINISTRATION Prior to initiating treatment with atomoxetine capsules, screen patients for a personal or family history of bipolar disorder, mania, or hypomania. ( 2.1 , 5.6 ) See table below for the recommended atomoxetine capsules dosage. ( 2.3 ) 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. 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 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 Capsules Treatment Prior to initiating treatment with atomoxetine capsules, screen patients for a personal or family history of bipolar disorder, mania, or hypomania [see Warnings and Precautions ( 5.6 )] 2.2 Administration Instructions Atomoxetine capsules may be taken with or without food. Take atomoxetine capsules whole; do not open the capsules. 2.3 Recommended Dosage Table 1 includes the recommended atomoxetine capsules dosage in adult patients and pediatric patients 6 years of age and older for acute treatment of ADHD. Table 1: Recommended Dosage of Atomoxetine Capsules for Acute Treatment of ADHD a Administer either as once daily dosage in the morning or as evenly divided twice daily dosage 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 the dosage to a maximum of 100 mg/day. There is no data that supports increased effectiveness at a dosage higher than 100 mg/day [see Clinical Studies ( 14 )] . Age and Body Weight Starting Dosage Titration Interval Target Dosage Maximum Dosage Pediatrics 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 Pediatrics patients who weigh 70 kg or more and adults patients 40 mg/day Minimum of 3 days 80 mg/day a 100 mg/day a,c The health care provider who elects to use atomoxetine capsules for extended periods should periodically reevaluate the long-term usefulness of atomoxetine capsules for the individual patient. 2.4 Recommended Dosage in Patients with Hepatic Impairment For patients aged 6 years of age or older with: Severe hepatic impairment (HI) (Child-Pugh Class C), the recommended initial and target atomoxetine capsules dosage are 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 atomoxetine capsules 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 atomoxetine capsules dosage are the same as those with normal hepatic function. 2.5 Recommended Dosage with Concomitant Use of Strong CYP2D6 Inhibitors or in CYP2D6 Poor Metabolizers Consider genetic testing to determine the patient's CYP2D6 metabolizer status. In patients taking a concomitant strong CYP2D6 inhibitor or who are CYP2D6 poor metabolizers, a longer titration interval of 4 weeks is recommended, if ADHD symptoms fail to improve and the initial atomoxetine capsules dosage are well tolerated. The recommended starting, target, and maximum atomoxetine capsules dosages are the same as outlined in Table 1 [ see Dosage …

3 DOSAGE FORMS AND STRENGTHS Atomoxetine Capsules, USP are available containing atomoxetine hydrochloride, USP equivalent to 10 mg, 18 mg, 25 mg, 40 mg, 60 mg, 80 mg or 100 mg of atomoxetine. A size "3", red opaque cap and light yellow opaque body, hard gelatin capsule filled with white to off-white powder. The cap imprinted with "Strides logo" and body imprinted with "010" axially in black ink. A size "3", orange opaque cap and light yellow opaque body, hard gelatin capsule filled with white to off-white powder. The cap imprinted with "Strides logo" and body imprinted with "018" axially in black ink. A size "3", light blue opaque cap and white opaque body, hard gelatin capsule filled with white to off-white powder. The cap imprinted with "Strides logo" and body imprinted with "025" axially in black ink. A size "2", blue opaque cap and light blue opaque body, hard gelatin capsule filled with white to off-white powder. The cap imprinted with "Strides logo" and body imprinted with "040" axially in black ink. A size "1", violet opaque cap and light yellow opaque body, hard gelatin capsule filled with white to off-white powder. The cap imprinted with "Strides logo" and body imprinted with "060" axially in black ink. A size "0", light orange opaque cap and light yellow opaque body, hard gelatin capsule filled with white to off-white powder. The cap imprinted with "Strides logo" and body imprinted with "080" axially in black ink. A size "0EL", light pink opaque cap and light yellow opaque body, hard gelatin capsule filled with white to off-white powder. The cap imprinted with "Strides logo" and body imprinted with "100" axially in black ink. Each capsule contains atomoxetine hydrochloride equivalent to 10, 18, 25, 40, 60, 80, or 100 mg of atomoxetine. (3, 11, 16)

4 CONTRAINDICATIONS • Hypersensitivity to atomoxetine or other constituents of product. (4.1) • Atomoxetine hydrochloride 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 hydrochloride use was associated with an increased risk of mydriasis and therefore its use is not recommended in patients with narro w 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 hydrochloride. 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 )].

6 ADVERSE REACTIONS Most common adverse reactions (≥5% and at least twice the incidence of placebo patients) Child and Adolescent Clinical Trials - Nausea, vomiting, fatigue, decreased appetite, abdominal pain, and somnolence. ( 6.1 ) Adult Clinical Trials - Constipation, dry mouth, nausea, decreased appetite, dizziness, erectile dysfunction, and urinary hesitation. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Teva at 1-888-838-2872 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Atomoxetine hydrochloride was administered to 5382 children or adolescent patients with ADHD and 1007 adults with ADHD in clinical studies. During the ADHD clinical trials, 1625 children and adolescent patients were treated for longer than 1 year and 2529 children and adolescent patients were treated for over 6 months. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Child and Adolescent Clinical Trials Reasons for discontinuation of treatment due to adverse reactions in child and adolescent clinical trials — In acute child and adolescent placebo-controlled trials, 3.0% (48/1613) of atomoxetine subjects and 1.4% (13/945) placebo subjects discontinued for adverse reactions. For all studies, (including open-label and long-term studies), 6.3% of extensive metabolizer (EM) patients and 11.2% of poor metabolizer (PM) patients discontinued because of an adverse reaction. Among atomoxetine-treated patients, irritability (0.3%, N = 5); somnolence (0.3%, N = 5); aggression (0.2%, N = 4); nausea (0.2%, N = 4); vomiting (0.2%, N = 4); abdominal pain (0.2%, N = 4); constipation (0.1%, N = 2); fatigue (0.1%, N = 2); feeling abnormal (0.1%, N = 2); and headache (0.1%, N = 2) were the reasons for discontinuation reported by more than 1 patient. Seizures — Atomoxetine has not been systematically evaluated in pediatric patients with seizure disorder as these patients were excluded from clinical studies during the product’s premarket testing. In the clinical development program, seizures were reported in 0.2% (12/5073) of children whose average age was 10 years (range 6 to 16 years). In these clinical trials, the seizure risk among poor metabolizers was 0.3% (1/293) compared to 0.2% (11/4741) for extensive metabolizers. Commonly observed adverse reactions in acute child and adolescent, placebo-controlled trials — Commonly observed adverse reactions associated with the use of atomoxetine (incidence of 2% or greater) and not observed at an equivalent incidence among placebo-treated patients (atomoxetine incidence greater than placebo) are listed in Table 2 . Results were similar in the BID and the QD trial except as shown in Table 3 , which shows both BID and QD results for selected adverse reactions based on statistically significant Breslow-Day tests. The most commonly observed adverse reactions in patients treated with atomoxetine (incidence of 5% or greater and at least twice the incidence in placebo patients, for either BID or QD dosing) were: nausea, vomiting, fatigue, decreased appetite, abdominal pain, and somnolence ( see Tables 2 and 3 ). Additional data from ADHD clinical trials (controlled and uncontrolled) has shown that approximately 5 to 10% of pediatric patients experienced potentially clinically important changes in heart rate (≥20 beats per min) or blood pressure (≥15 to 20 mm Hg) [ see Contraindications ( 4 ) and Warnings and Precautions ( 5 ) ]. Table 2: Common Treatment-Emergent Adverse Reactions Associated with the Use of Atomoxetine in Acute (up to 18 weeks) Child and Adolescent Trials Adverse Reaction a Percentage of Patients Reporting Reaction Atomoxetine (N = 1597) Placebo (N = 934) Gastrointestinal Disorders Abdominal pain b 18 10 Vomiting 11 6 Nausea 10 5 General Disorders and Administratio …

7 DRUG INTERACTIONS • Monoamine Oxidase Inhibitors. ( 4.2 , 7.1 ) • CYP2D6 Inhibitors - Concomitant use may increase atomoxetinesteady-state plasma concentrations in EMs. (7.2) • Antihypertensive Drugs and Pressor Agents - Possible effects on blood pressure. (7.3) • Albuterol (or other beta 2 agonists) - Action of albuterol on cardiovascular system can be potentiated. (7.4) 7.1 Monoamine Oxidase Inhibitors 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 Contraindications (4.2) ] . 7.2 Effect of CYP2D6 Inhibitors on Atomoxetine In extensive metabolizers (EMs), inhibitors of CYP2D6 (e.g., paroxetine, fluoxetine, and quinidine) increase atomoxetine steady-state plasma concentrations to exposures similar to those observed in poor metabolizers (PMs). In EM individuals treated with paroxetine or fluoxetine, the AUC of atomoxetine is approximately 6- to 8-fold and C ss, max is about 3- to 4-fold greater than atomoxetine alone. In vitro studies suggest that coadministration of cytochrome P450 inhibitors to PMs will not increase the plasma concentrations of atomoxetine. 7.3 Antihypertensive Drugs and Pressor Agents Because of possible effects on blood pressure, atomoxetine hydrochloride should be used cautiously with antihypertensive drugs and pressor agents (e.g., dopamine, dobutamine) or other drugs that increase blood pressure. 7.4 Albuterol Atomoxetine hydrochloride should be administered with caution to patients being treated with systemically-administered (oral or intravenous) albuterol (or other beta 2 agonists) because the action of albuterol on the cardiovascular system can be potentiated resulting in increases in heart rate and blood pressure. Albuterol (600 mcg iv over 2 hours) induced increases in heart rate and blood pressure. These effects were potentiated by atomoxetine (60 mg BID for 5 days) and were most marked after the initial coadministration of albuterol and atomoxetine. However, these effects on heart rate and blood pressure were not seen in another study after the coadministration with inhaled dose of albuterol (200 to 800 mcg) and atomoxetine (80 mg QD for 5 days) in 21 healthy Asian subjects who were excluded for poor metabolizer status. 7.5 Effect of Atomoxetine on P450 Enzymes Atomoxetine did not cause clinically important inhibition or induction of cytochrome P450 enzymes, including CYP1A2, CYP3A, CYP2D6, and CYP2C9. CYP3A Substrate (e.g., Midazolam ) - Coadministration of atomoxetine hydrochloride (60 mg BID for 12 days) with midazolam, a model compound for CYP3A4 metabolized drugs (single dose of 5 mg), resulted in 15% increase in AUC of midazolam. No dose adjustment is recommended for drugs metabolized by CYP3A. CYP2D6 Substrate (e.g., Desipramine) - Coadministration of atomoxetine hydrochloride (40 or 60 mg BID for 13 days) with desipramine, a model compound for CYP2D6 metabolized drugs (single dose of 50 mg), did not alter the pharmacokinetics of desipramine. No dose adjustment is recommended for drugs metabolized by CYP2D6. 7.6 Alcohol Consumption of ethanol with atomoxetine hydrochloride did not change the intoxicating effects of ethanol. 7.7 Methylphenidate Coadministration of methylphenidate with atomoxetine hydrochloride did not increase cardiovascular effects beyond those seen with methylphenidate alone. 7.8 Drugs Highly Bound to Plasma Protein In vitro drug-displacement studies were conducted with atomoxetine and other highly-bound drugs at therapeutic concentrations. Atomoxetine did not affect the binding of war …

8 USE IN SPECIFIC POPULATIONS Hepatic Insufficiency - Increased exposure (AUC) to atomoxetine than with normal subjects in EM subjects with moderate (Child-Pugh Class B) (2 fold increase) and severe (Child-Pugh Class C) (4 fold increase). ( 8.6 ) Renal Insufficiency - Higher systemic exposure to atomoxetine than healthy subjects for EM subjects with end stage renal disease - no difference when exposure corrected for mg/kg dose. ( 8.7 ) Patients with Concomitant Illness - Does not worsen tics in patients with ADHD and comorbid Tourette’s Disorder. ( 8.10 ) Patients with Concomitant Illness – Does not worsen anxiety in patients with ADHD and comorbid Anxiety Disorders. ( 8.10 ) 8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ADHD medications, including atomoxetine hydrochloride during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for ADHD Medications at 1-866-961-2388 or visiting https://womensmentalhealth.org/adhd-medications/. Risk Summary Available published studies with atomoxetine use in pregnant women are insufficient to establish a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Some animal reproduction studies of atomoxetine had adverse developmental outcomes. One of 3 studies in pregnant rabbits dosed during organogenesis resulted in decreased live fetuses and an increase in early resorptions, as well as slight increases in the incidences of atypical origin of carotid artery and absent subclavian artery. These effects were observed at plasma levels (AUC) 3 times and 0.4 times the human plasma levels in extensive and poor metabolizers receiving the maximum recommended human dose (MRHD), respectively. In rats dosed prior to mating and during organogenesis a decrease in fetal weight (female only) and an increase in the incidence of incomplete ossification of the vertebral arch in fetuses were observed at a dose approximately 5 times the MRHD on a mg/m 2 basis. In one of 2 studies in which rats were dosed prior to mating through the periods of organogenesis and lactation, decreased pup weight and decreased pup survival were observed at doses corresponding to 5 to 6 times the MRHD on a mg/m 2 basis. No adverse fetal effects were seen in pregnant rats dosed during the organogenesis period (see Data) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data Pregnant rabbits were treated with up to 100 mg/kg/day of atomoxetine by gavage throughout the period of organogenesis. At this dose, in 1 of 3 studies, a decrease in live fetuses and an increase in early resorptions was observed. Slight increases in the incidences of atypical origin of carotid artery and absent subclavian artery were observed. These findings were observed at doses that caused slight maternal toxicity. The no-effect dose for these findings was 30 mg/kg/day. The 100 mg/kg dose is approximately 23 times the MRHD on a mg/m 2 basis; plasma levels (AUC) of atomoxetine at this dose in rabbits are estimated to be 3.3 times (extensive metabolizers) or 0.4 times (poor metabolizers) those in humans receiving the MRHD. Rats were treated with up to approximately 50 mg/kg/day of atomoxetine (approximately 6 times the MRHD on a mg/m 2 basis) in the diet from 2 weeks (females) or 10 weeks (males) prior to mating through the periods of organogenesis and lactation. In 1 of 2 studies, decreases in pup weight and pup survival were observed. The decreased pup survival was also seen at 25 mg/kg (but not at 13 mg/kg). In a study in which rats were trea …

12.1 Mechanism of Action The precise mechanism by which atomoxetine produces its therapeutic effects in Attention-Deficit/Hyperactivity Disorder (ADHD) 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.

11 DESCRIPTION Atomoxetine is a selective norepinephrine reuptake inhibitor. Atomoxetine hydrochloride, USP is the R (-) isomer as determined by x-ray diffraction. and its chemical designation is (-)- N -Methyl-3-phenyl-3-(o- tolyloxy )-propylamine hydrochloride and its molecular formula is C17H21NO•HCl, which corresponds to a molecular weight of 291.82. The chemical structure is: Atomoxetine hydrochloride, USP is a white to off-white crystalline powder; sparingly soluble in water. Atomoxetine Capsules, USP are for oral administration only. Each capsule contains atomoxetine hydrochloride USP equivalent to 10 mg, 18 mg, 25 mg, 40 mg, 60 mg, 80 mg, or 100 mg of atomoxetine. The capsules also contain pregelatinized starch. The capsule shell for Atomoxetine Capsules, USP 10 mg contains gelatin, and titanium dioxide. The capsule shell for Atomoxetine Capsules, USP 18 mg contains D&C Yellow No. 10, FD&C Yellow No. 6, gelatin, sodium lauryl sulfate, and titanium dioxide. The capsule shell for Atomoxetine Capsules, USP 25 mg and 40 mg contains D&C Red No. 28, FD&C Blue No.1, gelatin, and titanium dioxide. The capsule shell for Atomoxetine Capsules, USP 60 mg contains D&C Yellow No. 10, FD&C Blue No. 1, FD&C Red No. 3, FD&C Yellow No. 6, gelatin, sodium lauryl sulfate, and titanium dioxide. The capsule shell for Atomoxetine Capsules, USP 80 mg and 100 mg contains D&C Red No. 28, D&C Yellow No. 10, FD&C Blue No. 1, gelatin, and titanium dioxide. The imprinting ink for Atomoxetine Capsules, USP 10 mg, 25 mg, 40 mg, 80 mg and 100 mg has the following components: black iron oxide, D&C Yellow No. 10, FD&C Blue No. 2, FD&C Blue No. 1, FD&C Red No. 40, propylene glycol, and shellac. The imprinting ink for Atomoxetine Capsules, USP 18 mg and 60 mg has the following components: black iron oxide, propylene glycol, potassium hydroxide, strong ammonia solution, and shellac. Structure

10 OVERDOSAGE 10.1 Human Experience There is limited clinical trial experience with atomoxetine hydrochloride overdose. During postmarketing, there have been fatalities reported involving a mixed ingestion overdose of atomoxetine hydrochloride and at least one other drug. There have been no reports of death involving overdose of atomoxetine hydrochloride alone, including intentional overdoses at amounts up to 1400 mg. In some cases of overdose involving atomoxetine hydrochloride, seizures have been reported. The most commonly reported symptoms accompanying acute and chronic overdoses of atomoxetine hydrochloride were gastrointestinal symptoms, somnolence, dizziness, tremor, and abnormal behavior. Hyperactivity and agitation have also been reported. Signs and symptoms consistent with mild to moderate sympathetic nervous system activation (e.g., tachycardia, blood pressure increased, mydriasis, dry mouth) have also been observed. Most events were mild to moderate. Less commonly, there have been reports of QT prolongation and mental changes, including disorientation and hallucinations [ see Clinical Pharmacology ( 12.2 ) ]. 10.2 Management of Overdose Consult with a Certified Poison Control Center for up to date guidance and advice. Because atomoxetine is highly protein-bound, dialysis is not likely to be useful in the treatment of overdose.

16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied Atomoxetine Capsules, USP are available containing atomoxetine hydrochloride, USP equivalent to 10 mg, 18 mg, 25 mg, 40 mg, 60 mg, 80 mg or 100 of atomoxetine. A size "3", red opaque cap and light yellow opaque body, hard gelatin capsule filled with white to off-white powder. The cap imprinted with "Strides logo" and body imprinted with "010" axially in black ink. They are available as follows: NDC 64380-472-01 bottles of 30 capsules NDC 64380-472-02 bottles of 500 capsules A size "3", orange opaque cap and light yellow opaque body, hard gelatin capsule filled with white to off-white powder. The cap imprinted with "Strides logo" and body imprinted with "018" axially in black ink. They are available as follows: NDC 64380-473-01 bottles of 30 capsules NDC 64380-473-02 bottles of 500 capsules A size "3", light blue opaque cap and white opaque body, hard gelatin capsule filled with white to off-white powder. The cap imprinted with "Strides logo" and body imprinted with "025" axially in black ink. They are available as follows: NDC 64380-474-01 bottles of 30 capsules NDC 64380-474-02 bottles of 500 capsules A size "2", blue opaque cap and light blue opaque body, hard gelatin capsule filled with white to off-white powder. The cap imprinted with "Strides logo" and body imprinted with "040" axially in black ink. They are available as follows: NDC 64380-475-01 bottles of 30 capsules NDC 64380-475-02 bottles of 500 capsules A size "1", violet opaque cap and light yellow opaque body, hard gelatin capsule filled with white to off-white powder. The cap imprinted with "Strides logo" and body imprinted with "060" axially in black ink. They are available as follows: NDC 64380-476-01 bottles of 30 capsules NDC 64380-476-02 bottles of 500 capsules A size "0", light orange opaque cap and light yellow opaque body, hard gelatin capsule filled with white to off-white powder. The cap imprinted with "Strides logo" and body imprinted with "080" axially in black ink. They are available as follows: NDC 64380-477-01 bottles of 30 capsules NDC 64380-477-02 bottles of 500 capsules A size "0EL", light pink opaque cap and light yellow opaque body, hard gelatin capsule filled with white to off-white powder. The cap imprinted with "Strides logo" and body imprinted with "100" axially in black ink. They are available as follows: NDC 64380-478-01 bottles of 30 capsules NDC 64380-478-02 bottles of 500 capsules 16.2 Storage and Handling Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (59° to 86°F) [See USP Controlled Room Temperature]. Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.

16.1 How Supplied Atomoxetine Capsules, USP are available containing atomoxetine hydrochloride, USP equivalent to 10 mg, 18 mg, 25 mg, 40 mg, 60 mg, 80 mg or 100 of atomoxetine. A size "3", red opaque cap and light yellow opaque body, hard gelatin capsule filled with white to off-white powder. The cap imprinted with "Strides logo" and body imprinted with "010" axially in black ink. They are available as follows: NDC 64380-472-01 bottles of 30 capsules NDC 64380-472-02 bottles of 500 capsules A size "3", orange opaque cap and light yellow opaque body, hard gelatin capsule filled with white to off-white powder. The cap imprinted with "Strides logo" and body imprinted with "018" axially in black ink. They are available as follows: NDC 64380-473-01 bottles of 30 capsules NDC 64380-473-02 bottles of 500 capsules A size "3", light blue opaque cap and white opaque body, hard gelatin capsule filled with white to off-white powder. The cap imprinted with "Strides logo" and body imprinted with "025" axially in black ink. They are available as follows: NDC 64380-474-01 bottles of 30 capsules NDC 64380-474-02 bottles of 500 capsules A size "2", blue opaque cap and light blue opaque body, hard gelatin capsule filled with white to off-white powder. The cap impr …