LACTATION SECTION.

8.2 Lactation. Risk SummaryThere are no data on the presence of atomoxetine or its metabolite in human milk, the effects on the breastfed child, or the effects on milk production. Atomoxetine is present in animal milk. When drug is present in animal milk, it is likely that the drug will be present in human milk.The developmental and health benefits of breastfeeding should be considered along with the mothers clinical need for STRATTERA and any potential adverse effects on the breastfed child from STRATTERA or from the underlying maternal condition.

MECHANISM OF ACTION SECTION.

12.1 Mechanism of Action. The precise mechanism by which STRATTERA produces its therapeutic effects in 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.

BOXED WARNING SECTION.

WARNING: SUICIDAL THOUGHTS AND BEHAVIORS IN PEDIATRIC PATIENTS YEARS OF AGE AND OLDER. All STRATTERA-treated pediatric patients years of age or older should be monitored and observed closely for suicidal thoughts and behavior, clinical worsening, or unusual changes in behavior, especially during the initial months of therapy or at times of dosage changes. Families and caregivers should be advised of the need for close observation and communication with the health care provider. Consider stopping STRATTERA in patients who experience emergent suicidal thoughts and behavior[see Warnings and Precautions (5.1)].STRATTERA increased the risk of suicidal ideation in pediatric patients aged years of age and older with attention-deficit/hyperactivity disorder (ADHD) in short-term studies.. WARNING: SUICIDAL THOUGHTS AND BEHAVIORS IN PEDIATRIC PATIENTS YEARS OF AGE AND OLDERSee full prescribing information for complete boxed warning.All STRATTERA-treated pediatric patients years of age or older should be monitored and observed closely for suicidal thoughts and behavior, clinical worsening, or unusual changes in behavior, especially during the initial months of therapy or at times of dosage changes (5.1)Consider stopping STRATTERA in patients who experience emergent suicidal thoughts and behavior (5.1)STRATTERA increased the risk of suicidal ideation in pediatric patients aged years of age and older with attention-deficit/hyperactivity disorder (ADHD) in short-term studies (5.1). All STRATTERA-treated pediatric patients years of age or older should be monitored and observed closely for suicidal thoughts and behavior, clinical worsening, or unusual changes in behavior, especially during the initial months of therapy or at times of dosage changes (5.1). Consider stopping STRATTERA in patients who experience emergent suicidal thoughts and behavior (5.1). STRATTERA increased the risk of suicidal ideation in pediatric patients aged years of age and older with attention-deficit/hyperactivity disorder (ADHD) in short-term studies (5.1).

GERIATRIC USE SECTION.

8.5 Geriatric Use. The safety, efficacy and pharmacokinetics of STRATTERA in geriatric patients have not been evaluated. Clinical studies of STRATTERA did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently from younger adult patients.

HEPATIC IMPAIRMENT SUBSECTION.

8.6 Patients with Hepatic Impairment. Compared with patients with normal hepatic function atomoxetine exposure (AUC) was increased in patients with moderate (Child- Pugh Class B) (2-fold increase) and in patients with severe hepatic impairment (Child-Pugh Class C) (4-fold increase). The recommended dosage in patients with moderate or severe hepatic impairment is lower than in patients with normal hepatic function [see Dosage and Administration (2.4) and Clinical Pharmacology (12.3)].

HOW SUPPLIED SECTION.

16 HOW SUPPLIED/STORAGE AND HANDLING. 16.1 How Supplied. Table 10 displays the available STRATTERA (atomoxetine) capsules strengths.Table 10: STRATTERA (atomoxetine) Capsules Strengthsa Strength is based on the base (atomoxetine).StrengthaColorIdentificationNDC10 mgopaque white, opaque whiteLILLY 32270002-3227-3018 mggold, opaque whiteLILLY 32380002-3238-3025 mgopaque blue, opaque whiteLILLY 32280002-3228-3040 mgopaque blue, opaque blueLILLY 32290002-3229-3060 mgopaque blue, goldLILLY 32390002-3239-3080 mgopaque brown, opaque whiteLILLY 32500002-3250-30100 mgopaque brown, opaque brownLILLY 32510002-3251-30. 16.2 Storage and Handling. Store at 25C (77F); excursions permitted to 15 to 30C (59 to 86F) [see USP Controlled Room Temperature].

INDICATIONS & USAGE SECTION.

1 INDICATIONS AND USAGE. STRATTERA is indicated for the treatment of attention-deficit/hyperactivity disorder (ADHD) in adults and pediatric patients years of age and older.STRATTERA is indicated as an integral part of total treatment program for ADHD that may include other measures (psychological, educational, social) for patients with ADHD.. STRATTERA(R) is selective norepinephrine reuptake inhibitor (SNRI) indicated for the treatment of ADHD in adults and pediatric patients years of age and older. (1).

INFORMATION FOR PATIENTS SECTION.

17 PATIENT COUNSELING INFORMATION. Advise the patient to read the FDA-approved patient labeling (Medication Guide).. Suicide RiskPatients, their families, and their caregivers should be alerted about the need to monitor patients daily for the emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, mania, other unusual changes in behavior, depression, and suicidal ideation, especially early during STRATTERA treatment and when the dosage is adjusted. Such symptoms should be reported to the patients health care provider immediately [see Warnings and Precautions (5.1)].. Severe Liver InjuryPatients initiating STRATTERA should be cautioned that severe liver injury may develop. Patients should be instructed to contact their healthcare provider immediately should they develop pruritus, dark urine, jaundice, right upper quadrant tenderness, or unexplained flu-like symptoms [see Warnings and Precautions (5.2)].. Serious Cardiovascular ReactionsPatients who develop symptoms such as exertional chest pain, unexplained syncope, or other symptoms suggestive of cardiac disease during STRATTERA treatment should stop STRATTERA and contact health care provider [see Warnings and Precautions (5.3)].. Increased Blood Pressure or Heart RateSTRATTERA can increase blood pressure and heart rate [see Warnings and Precautions (5.4)]. Emergence of New Psychotic or Manic Symptoms and Activation of ManiaInstruct patients and their caregivers to look for signs of activation of mania/hypomania and psychosis [see Warnings and Precautions (5.5)].. Aggression or HostilityInstruct patients and their caregivers to contact their healthcare provider as soon as possible should they notice an increase in aggression or hostility [see Warnings and Precautions (5.7)].. PriapismThe parents or guardians of pediatric patients taking STRATTERA and adult patients taking STRATTERA should be instructed that priapism requires prompt medical attention [see Warnings and Precautions (5.10)].. Ocular IrritantSTRATTERA is an ocular irritant. STRATTERA capsules are not intended to be opened. In the event of capsule content coming in contact with the eye, the affected eye should be flushed immediately with water, and medical advice obtained. Hands and any potentially contaminated surfaces should be washed as soon as possible.. Drug-Drug InteractionsPatients should be instructed to consult healthcare provider if they are taking or plan to take any prescription or over-the-counter drugs, dietary supplements, or herbal remedies [see Drug Interactions (7)].. Sexual DysfunctionAdvise patients that STRATTERA may impair sexual function. Advise patients if they experience sexual dysfunction, they should contact their health care provider [see Adverse Reactions (6.1)]. Pregnancy RegistryAdvise patients that there is pregnancy registry that monitors pregnancy outcomes in women exposed to atomoxetine during pregnancy [see Use in Specific Populations (8.1)]. FoodPatients may take STRATTERA with or without food.. Missed DoseIf patients miss dose, they should be instructed to take it as soon as possible but should not take more than the prescribed total daily amount of STRATTERA in any 24-hour period.. SomnolenceThe incidence of somnolence was higher in STRATTERA-treated patients than placebo-treated patients [see Adverse Reactions (6.1)]. Patients should be instructed to use caution when driving car or operating hazardous machinery until they are reasonably certain that their performance is not affected by STRATTERA.Marketed by: Lilly USA, LLC, Indianapolis, IN 46285, USACopyright (C) 2002, 2026, Eli Lilly and Company. All rights reserved.STR-0006-USPI-20260629.

ABUSE SECTION.

9.2 Abuse. In randomized, double-blind, placebo-controlled, abuse-potential study in adults that compared effects of STRATTERA and placebo, STRATTERA was not associated with stimulant or euphoriant properties. Clinical study data in over 2,000 adults and pediatric patients with ADHD and over 1,200 adults with depression (STRATTERA is not indicated for the treatment of depression) showed only isolated incidents of inappropriate STRATTERA self-administration.Drug discrimination studies in rats and monkeys showed inconsistent stimulus generalization between atomoxetine and cocaine.

ADVERSE REACTIONS SECTION.

6 ADVERSE REACTIONS. Most common adverse reactions (>=5% and at least twice the incidence of placebo patients):Pediatric Clinical Studies: Nausea, vomiting, fatigue, decreased appetite, abdominal pain, and somnolence. (6.1)Adult Clinical Studies: Constipation, dry mouth, nausea, decreased appetite, dizziness, erectile dysfunction, and urinary hesitation. (6.1)Patients should be instructed to use caution when driving car or operating hazardous machinery (because of somnolence) until they are reasonably certain that their performance is not affected by STRATTERA. (6.1)To report SUSPECTED ADVERSE REACTIONS, contact Eli Lilly and Company at 1-800-LillyRx (1-800-545-5979) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.. Pediatric Clinical Studies: Nausea, vomiting, fatigue, decreased appetite, abdominal pain, and somnolence. (6.1). Adult Clinical Studies: Constipation, dry mouth, nausea, decreased appetite, dizziness, erectile dysfunction, and urinary hesitation. (6.1). 6.1 Clinical Trials Experience. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.STRATTERA was administered to 5,382 pediatric patients years of age and older in clinical ADHD studies (Studies 1, 2, 3, 4, and 5) [see Clinical Studies (14.1)] and 1,007 adults in clinical ADHD studies (Studies and 7) [see Clinical Studies (14.2)]. In the ADHD clinical trials, 2,529 pediatric patients were treated for over months which included 1,625 pediatric patients who were treated for longer than year.. Adverse Reactions in the Clinical Trials of Pediatric Patients Years of Age and Older with ADHD. Discontinuation of Treatment Due to Adverse Reactions in the Clinical Studies of Pediatric Patients Years of Age and Older:In the acute placebo-controlled studies of pediatric patients years of age and older with ADHD, 3% (48/1,613) of STRATTERA-treated pediatric patients and 1.4% (13/945) of placebo-treated pediatric patients discontinued due to an adverse reaction. Among STRATTERA-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 one patient.For all studies, (including open-label and long-term studies), 6% of STRATTERA-treated pediatric patients who were other CYP2D6 metabolizer types (ultrarapid, normal, and intermediate) and 11% of those who were CYP2D6 poor metabolizers discontinued due to an adverse reaction.. Common Adverse Reactions in the Clinical Studies of Pediatric Patients Years of Age and Older: Common adverse reactions (incidence of 2% or greater in STRATTERA-treated patients and with higher incidence in STRATTERA-treated patients compared to placebo-treated patients) in pediatric patients years of age and older with ADHD are listed in Table 2. The most commonly observed adverse reactions in STRATTERA-treated patients (incidence of >=5% and >= twice the incidence in placebo-treated patients), for either twice daily or once daily dosing were: nausea, vomiting, fatigue, decreased appetite, abdominal pain, and somnolence (see Tables and 3).Table 2: Common Adverse Reactionsa in Acute Studies (up to 18 weeks) in Pediatric Patients Years and Older with ADHDa Adverse reactions reported by at least 2% of STRATTERA-treated patients and greater than placebo-treated patients.b Abdominal pain includes the terms: upper abdominal pain, and epigastric discomfort.c Somnolence includes the term sedation.Adverse ReactionSTRATTERA(N=1,597)Placebo(N=934)Headache19%15%Abdominal painb 18%10%Decreased appetite16%4%Somnolencec 11%4%Vomiting11%6%Nausea10%5%Fatigue8%3%Irritability6%3%Dizziness5%2%Decreased weight3%0%Anorexia3%1%Rash2%1%Adverse reaction in the STRATTERA-treated patients who received twice daily, and once daily dosing are shown in Table (adverse reactions based on statistically significant Breslow-Day tests).Table 3: Common Adverse Reactions in Acute Studies (up to 18 weeks) in Pediatric Patients Years and Older with ADHDa Abdominal pain included the terms: upper abdominal pain, and epigastric discomfort.b Mood swings didnt meet the statistical significance on Breslow-Day test at 0.05 level, but p-value was <0.1 (trend).c Constipation didnt meet the statistical significance on Breslow-Day test but is included in the table because of pharmacologic plausibility.Adverse ReactionADHD Studies with Twice Daily DosingADHD Studies with Once Daily DosingSTRATTERA(N=715)Placebo(N=434)STRATTERA(N=882)Placebo(N=500)Abdominal paina 17%13%18%7%Vomiting11%8%11%4%Nausea7%6%13%4%Fatigue6%4%9%2%Mood swingsb 2%0%1%1%Constipationc 2%1%1%0%. Common Adverse Reactions by CYP2D6 Metabolizer Status in the Clinical Studies of Pediatric Patients Years of Age and Older:Table displays adverse reactions that occurred in at least 2% of STRATTERA-treated pediatric patients who were CYP2D6 poor metabolizers and were statistically significantly more frequent in CYP2D6 poor metabolizers compared with other CYP2D6 metabolizer types (ultrarapid, normal, and intermediate).Table 4: Common Adverse Reactionsa in STRATTERA-treated Pediatric Patients Years and Older with ADHD by CYP2D6 Metabolizer Typesa Adverse reactions that occurred in at least 2% of STRATTERA-treated pediatric patients who were CYP2D6 poor metabolizers and were statistically significantly more frequent in poor metabolizers compared with other CYP2D6 metabolizer types (ultrarapid, normal, and intermediate).b Depression included the following terms: major depression, depressive symptoms, depressed mood, dysphoria.Adverse ReactionSTRATTERACYP2D6 Poor Metabolizers (N=355)STRATTERAOther CYP2D6 Metabolizer Types (N=5,019)Insomnia11%6%Decreased weight7%4%Constipation7%4%Depressionb 7%4%Tremor5%1%Excoriation4%2%Sedation4%2%Middle insomnia3%1%Conjunctivitis3%1%Syncope3%1%Early morning awakening2%1%Mydriasis2%1%. Less Common Adverse Reactions in the Clinical Studies of Pediatric Patients Years of Age and Older: The following reactions did not meet this criterion but were reported by more STRATTERA-treated patients than placebo-treated patients and are possibly related to STRATTERA treatment: blood pressure increased, early morning awakening (terminal insomnia), flushing, mydriasis, sinus tachycardia, asthenia, palpitations, mood swings, constipation, and dyspepsia.The following reactions were reported by at least 2% of patients treated with STRATTERA, and equal to or less than placebo: pharyngolaryngeal pain, insomnia (insomnia includes the terms, insomnia, initial insomnia, middle insomnia). The following reaction did not meet this criterion but shows statistically significant dose relationship: pruritus.. Seizures in the Clinical Studies of Pediatric Patients Years of Age and Older: STRATTERA has not been systematically evaluated in pediatric patients with seizure disorder as these patients were excluded from STRATTERA studies. In the clinical development program, seizures were reported in 0.2% (12/5,073) of STRATTERA-treated pediatric patients whose average age was 10 years old (range to 16 years of age). In these clinical trials, the seizure incidence among CYP2D6 poor metabolizers was 0.3% (1/293) compared to 0.2% (11/4,741) for other CYP2D6 metabolizer types.. Heart Rate and Blood Pressure Increases in the Clinical Studies of Pediatric Patients Years of Age and Older: Additional data from ADHD clinical trials (controlled and uncontrolled) has shown that approximately to 10% of pediatric patients experienced potentially clinically important changes in heart rate (>=20 beats per minute) or blood pressure (>=15 to 20 mm Hg) [see Contraindications (4) and Warnings and Precautions (5.4)].. Adverse Reactions in the Clinical Trials of Adults with ADHD. Discontinuation of Treatment Due to Adverse Reactions in the Clinical Studies of Adults: In the acute adult placebo-controlled trials, 11.3% (61/541) STRATTERA-treated patients and 3% (12/405) placebo-treated patients discontinued for adverse reactions. Among STRATTERA-treated patients, insomnia (0.9%, N=5); nausea (0.9%, N=5); chest pain (0.6%, N=3); fatigue (0.6%, N=3); anxiety (0.4%, N=2); erectile dysfunction (0.4%, N=2); mood swings (0.4%, N=2); nervousness (0.4%, N=2); palpitations (0.4%, N=2); and urinary retention (0.4%, N=2) were the reasons for discontinuation reported by more than patient.. Common Adverse Reactions in the Clinical Studies of Adults: Commonly observed adverse reactions associated with the use of STRATTERA (incidence of 2% or greater) and not observed at an equivalent incidence among placebo-treated patients (STRATTERA incidence greater than placebo) are listed in Table 5. The most commonly observed adverse reactions in patients treated with STRATTERA (incidence of 5% or greater and at least twice the incidence in placebo patients) were: constipation, dry mouth, nausea, decreased appetite, dizziness, erectile dysfunction, and urinary hesitation (see Table 5).Table 5: Common Adverse Reactionsa Associated in Acute Studies (up to 25 weeks) of Adult Patients with ADHDa Reactions reported by at least 2% of patients treated with STRATTERA, and greater than placebo. The following reactions did not meet this criterion but were reported by more STRATTERA-treated patients than placebo-treated patients and are possibly related to STRATTERAtreatment: peripheral coldness, tachycardia, prostatitis, testicular pain, orgasm abnormal, flatulence, asthenia, feeling cold, muscle spasm, dysgeusia, agitation, restlessness, micturition urgency, pollakiuria, pruritus, urticaria, flushing, tremor, menstruation irregular, rash, and urinary retention.b Insomnia includes the terms initial insomnia, middle insomnia, terminal insomnia and other related terms.c Based on total number of males (STRATTERA group, N=943; placebo group, N=869).d Somnolence includes related terms.e Abdominal pain includes the terms: upper abdominal pain and other related terms.f Urinary hesitation includes the term decreased urine flow.g Based on total number of females (STRATTERA, N=754; placebo, N=691).Adverse ReactionSTRATTERA (N=1,697)Placebo (N=1,560)Nausea26%6%Dry mouth20%5%Decreased appetite16%3%Insomniab 15%8%Fatigue10%6%Erectile dysfunctionc 8%1%Constipation8%3%Dizziness8%3%Somnolenced 8%5%Abdominal paine 7%4%Urinary hesitationf 6%1%Irritability5%3%Ejaculation delayedc and/or ejaculation disorderc 4%1%Hyperhidrosis4%1%Dyspepsia4%2%Vomiting4%2%Abnormal dreams4%3%Chills3%0%Paraesthesia3%0%Hot flush3%0%Palpitations3%1%Libido decreased3%1%Sleep disorder3%1%Dysmenorrheag 3%2%Dysuria2%0%Thirst2%1%Weight decreased2%1%Feeling jittery2%1%. Common Adverse Reactions by CYP2D6 Metabolizer Status in the Clinical Studies of Adults:Table displays adverse reactions that occurred in at least 2% of STRATTERA-treated adult patients who were CYP2D6 poor metabolizers and were statistically significantly more frequent compared to other CYP2D6 metabolizer types (ultrarapid, normal, and intermediate).Table 6: Common Adverse Reactionsa in STRATTERA-treated Adult Patients with ADHD by CYP2D6 Metabolizer Typesa Adverse reactions that occurred in at least 2% of STRATTERA-treated adult patients who were CYP2D6 poor metabolizers and were statistically significantly more frequent in CYP2D6 poor metabolizers compared with other CYP2D6 metabolizer types (ultrarapid, normal, and intermediate).Adverse ReactionSTRATTERACYP2D6 Poor Metabolizers (N=203)STRATTERAOther CYP2D6 Metabolizer Types (N=3,599)Dry mouth35%17%Decreased appetite23%15%Erectile dysfunction21%9%Insomnia19%11%Hyperhidrosis15%7%Constipation11%7%Sleep disorder7%3%Urinary retention6%1%Ejaculation disorder6%2%Tremor5%1%Feeling jittery5%2%Middle insomnia5%3%Blurred vision4%1%Terminal insomnia3%1%Peripheral coldness3%1%. Less Common Adverse Reactions in the Clinical Studies of Adults: The following reactions did not meet this criterion but were reported by more STRATTERA-treated patients than placebo-treated patients and are possibly related to STRATTERA treatment: peripheral coldness, tachycardia, prostatitis, testicular pain, orgasm abnormal, flatulence, asthenia, feeling cold, muscle spasm, dysgeusia, agitation, restlessness, micturition urgency, pollakiuria, pruritus, urticaria, flushing, tremor, menstruation irregular, rash, and urinary retention.. Seizures in the Clinical Studies of Adults: STRATTERA has not been systematically evaluated in adult patients with seizure disorder as these patients were excluded from clinical studies during the products premarket testing. In the clinical development program, seizures were reported on 0.1% (1/748) of adult patients. In these clinical trials, no CYP2D6 poor metabolizers (0/43) reported seizures compared to 0.1% (1/705) for other CYP2D6 metabolizer types.. Heart Rate and Blood Pressure Increases in the Clinical Studies of Adults:Table displays the proportion of STRATTERA-treated and placebo-treated patients who had an increase in diastolic blood pressure (DBP) >=15 mm Hg, systolic blood pressure (SBP) >=20 mm Hg, or heart rate >= 20 bpm in short-term, placebo-controlled clinical studies in pediatric and adult patients with ADHD [see Warnings and Precautions (5.4)]. Table 7: Proportion of ADHD Patients With an Increase of >= 15 mm Hg in DBP, >=20 mm Hg in SBP, or >= 20 bpm in Heart Ratea Abbreviations: bpm=beats per minute; DBP=diastolic blood pressure; HR=heart rate; mm Hg=millimeters mercury; SBP=systolic blood pressure.b Proportion of patients meeting threshold at any one time during the clinical studies.Pediatric Acute ADHD StudiesAdult Acute ADHD StudiesMaximumbEndpointMaximumbEndpointSTRATTERAPlaceboSTRATTERAPlaceboSTRATTERAPlaceboSTRATTERAPlaceboDBP (>=15 mm Hg)22%14%9%5%13%9%5%4%SBP (>=20 mm Hg)13%9%5%3%12%8%4%3%HR (>=20 bpm)23%12%12%4%22%8%10%2%Additional data from ADHD clinical trials (controlled and uncontrolled) showed that approximately to 10% of adult patients had potentially clinically important changes in heart rate (>=20 beats per minute) or blood pressure (>=15 to 20 mm Hg) [see Contraindications (4) and Warnings and Precautions (5.4)].. Male and Female Sexual Dysfunction in the Clinical Studies of Adults: STRATTERA impaired sexual function in some patients. Estimates of the incidence of untoward sexual experience and performance in these studies are likely to underestimate their actual incidence because patients and health care providers may be reluctant to discuss them. Table displays the incidence of sexual adverse reactions (reported by at least 2% of STRATTERA-treated adult patients in the placebo-controlled studies of adults with ADHD (i.e., erectile dysfunction, dysmenorrhea, and ejaculation delayed and/or ejaculation disorder).There are no adequate and well-controlled studies examining sexual dysfunction with STRATTERA treatment. While it is difficult to know the precise risk of sexual dysfunction associated with the use of STRATTERA, health care providers should routinely inquire about sexual dysfunction.. 6.2 Postmarketing Experience. The following adverse reactions have been identified during post approval use of STRATTERA. Unless otherwise specified, these adverse reactions have occurred in adults and pediatric patients. Because these reactions are reported voluntarily from population of uncertain size, it is not always possible to reliably estimate their frequency or establish causal relationship to drug exposure.Cardiovascular system: QT prolongation, syncope.Peripheral vascular effects: Raynauds phenomenon.General disorders and administration site conditions: Lethargy.Musculoskeletal system: Rhabdomyolysis.Nervous system disorders: Hypoaesthesia; paraesthesia in pediatric patients; sensory disturbances; tics.Psychiatric disorders: Depression and depressed mood; anxiety, libido changes.Seizures: Seizures have been reported and included patients with pre-existing seizure disorders, those with identified risk factors for seizures, and patients with neither history of nor identified risk factors for seizures. The exact relationship between STRATTERA and seizures is difficult to evaluate due to uncertainty about the background risk of seizures in ADHD patients.Skin and subcutaneous tissue disorders: Alopecia, hyperhidrosis.Urogenital system: Male pelvic pain; urinary hesitation in pediatric patients; urinary retention in pediatric patients.. Cardiovascular system: QT prolongation, syncope.. Peripheral vascular effects: Raynauds phenomenon.. General disorders and administration site conditions: Lethargy.. Musculoskeletal system: Rhabdomyolysis.. Nervous system disorders: Hypoaesthesia; paraesthesia in pediatric patients; sensory disturbances; tics.. Psychiatric disorders: Depression and depressed mood; anxiety, libido changes.. Seizures: Seizures have been reported and included patients with pre-existing seizure disorders, those with identified risk factors for seizures, and patients with neither history of nor identified risk factors for seizures. The exact relationship between STRATTERA and seizures is difficult to evaluate due to uncertainty about the background risk of seizures in ADHD patients.. Skin and subcutaneous tissue disorders: Alopecia, hyperhidrosis.. Urogenital system: Male pelvic pain; urinary hesitation in pediatric patients; urinary retention in pediatric patients.

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility. Carcinogenesis -- Atomoxetine HCl was not carcinogenic in rats and mice when given in the diet for years at time-weighted average doses up to 47 and 458 mg/kg/day, respectively. The highest dose used in rats is approximately and times the maximum recommended human dose (MRHD) in children and adults, respectively, on mg/m2 basis.Plasma levels (AUC) of atomoxetine at this dose in rats are estimated to be 1.8 times (other CYP2D6 metabolizer types) or 0.2 times (CYP2D6 poor metabolizers) those in humans receiving the maximum human dose. The highest dose used in mice is approximately 39 and 26 times the MRHD in children and adults, respectively, on mg/m2 basis.. Mutagenesis -- Atomoxetine HCl was negative in battery of genotoxicity studies that included reverse point mutation assay (Ames Test), an in vitro mouse lymphoma assay, chromosomal aberration test in Chinese hamster ovary cells, an unscheduled DNA synthesis test in rat hepatocytes, and an in vivo micronucleus test in mice. However, there was slight increase in the percentage of Chinese hamster ovary cells with diplochromosomes, suggesting endoreduplication (numerical aberration).The metabolite N-desmethylatomoxetine HCl was negative in the Ames Test, mouse lymphoma assay, and unscheduled DNA synthesis test.. Impairment of Fertility -- Atomoxetine HCl did not impair fertility in rats when given in the diet at doses of up to 57 mg/kg/day, which is approximately times the MRHD on mg/m2 basis.

CLINICAL PHARMACOLOGY SECTION.

12 CLINICAL PHARMACOLOGY. 12.1 Mechanism of Action. The precise mechanism by which STRATTERA produces its therapeutic effects in 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.. 12.2 Pharmacodynamics. An exposure-response analysis of STRATTERA (0.5, 1.2 or 1.8 mg/kg/day) or placebo demonstrated atomoxetine exposure correlates with efficacy as measured by the ADHD Rating Scale-IV-Parent Version: Investigator administered and scored. The exposure-efficacy relationship was similar to that observed between STRATTERA dosage and efficacy with median atomoxetine exposures at the two highest doses resulting in near maximal changes from baseline [see Clinical Studies (14.2)].. Cardiac ElectrophysiologyThe effect of STRATTERA on QTc interval prolongation was evaluated in randomized, double-blinded, positive-(moxifloxacin 400 mg) and placebo-controlled, cross-over study in healthy male CYP2D6 poor metabolizers. total of 120 healthy subjects were administered STRATTERA (20 mg and 60 mg) twice daily for 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 slight increase in QTc interval with increased atomoxetine concentration.. Pharmacodynamic Drug Interaction StudiesConsumption of ethanol with STRATTERA did not change the intoxicating effects of ethanol.Concomitant use of STRATTERA with methylphenidate did not increase cardiovascular effects beyond those seen with methylphenidate alone.Albuterol 600 mcg given intravenously over hours (albuterol is not approved for intravenous use) induced heart rate and blood pressure increases; these effects were potentiated when co-administered with STRATTERA (60 mg twice daily for days), particularly initially [see Drug Interactions (7)]. Consumption of ethanol with STRATTERA did not change the intoxicating effects of ethanol.. Concomitant use of STRATTERA with methylphenidate did not increase cardiovascular effects beyond those seen with methylphenidate alone.. Albuterol 600 mcg given intravenously over hours (albuterol is not approved for intravenous use) induced heart rate and blood pressure increases; these effects were potentiated when co-administered with STRATTERA (60 mg twice daily for days), particularly initially [see Drug Interactions (7)]. 12.3 Pharmacokinetics. Pharmacokinetic parameters for atomoxetine and its metabolites in CYP2D6 poor metabolizers and other CYP2D6 metabolizer types (ultrarapid, normal, and intermediate) are presented in Table 9.Table 9: Atomoxetine and Metabolite Pharmacokinetics in Adult CYP2D6 Poor Metabolizers and Other CYP2D6 Metabolizer TypesAbbreviations: Cmax,ss= maximum atomoxetine plasma concentration at steady state; Tmax time to peak concentrationa In this analysis, other CYP2D6 metabolizer types were defined as individuals who were 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., CYP2D63/4, CYP2D65/5), and as result no CYP2D6 enzyme activity.c Primarily formed by CYP2D6.The major oxidative metabolite formed, regardless of CYP2D6 metabolizer type, and is further glucuronidated. 4-Hydroxyatomoxetine is equipotent to atomoxetine as an inhibitor of the norepinephrine transporter.d 4-hydroxyatomoxetine is formed at 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.ParameterOther CYP2D6 Metabolizer TypesaCYP2D6 Poor MetabolizersbAbsorptionDose proportionality10-120 mgAccumulation1.1-fold3.3-foldAbsolute bioavailability63%94%Tmax median1 hour2.5 hourEffect of FoodAUC: Unchanged; Cmax: Decreased 37%; Tmax: Delayed hoursDistributionProtein Binding98%Volume of distribution0.85 L/kgEliminationAtomoxetine half-life5.2 hours21.6 hoursAtomoxetine apparent oral clearance0.35 L/hr/kg0.03 L/hr/kg4-Hydroxyatomoxetine half-life6 to hours--N-Desmethylatomoxetine half-life6 to hours34 to 40 hoursMetabolismPrimary metabolic pathwaysCYP2D6Other CYP enzymes4-Hydroxyatomoxetinec concentration1% of atomoxetine0.1% of atomoxetined N-Desmethylatomoxetinee concentration5% of atomoxetine45% of atomoxetineExcretionUrineGreater than 80% of the administered dose excreted as 4-hydroxyatomoxetine-O-glucuronide; Less than 3% as unchanged drugFecesLess than 17% of the administered dose. Specific Populations. Hepatic Impairment: Atomoxetine exposure (AUC) was increased in subjects with moderate (Child-Pugh Class B) (2-fold increase) and severe (Child-Pugh Class C) (4-fold increase) hepatic impairment compared to subjects 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 requiring hemodialysis) had higher systemic atomoxetine exposure (about 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 were evaluated in more than 400 pediatric patients in clinical studies, primarily using population pharmacokinetic modeling. Single-dose and steady-state individual pharmacokinetic data were also obtained in pediatric patients and adults. When STRATTERA doses were normalized to mg/kg basis, similar half- life, Cmax, 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. Clinical Studies:. Strong CYP2D6 Inhibitors: Concomitant use of STRATTERA (20 mg BID for days) with paroxetine (20 mg QD for 17 days), known inhibitor of CYP2D6, in subjects who were not CYP2D6 poor metabolizers resulted in 6.5-fold higher plasma exposure (AUC) to atomoxetine at steady state.Concomitant use of STRATTERA (at sequential dosing of 10, 45, and 75 mg BID for up to days of each dosage) with fluoxetine (20 mg QD for 36 days) 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 STRATTERA alone.After concomitant use of STRATTERA with paroxetine or fluoxetine, the Css, max of atomoxetine was about 3-to 4-fold greater than the use of STRATTERA alone [see Drug Interactions (7)]. CYP3A Substrates: Concomitant use of STRATTERA (60 mg twice daily for 12 days) with midazolam (CYP3A substrate) (single dose of mg), resulted in 15% increase in the midazolam AUC. This pharmacokinetic change is not clinically significant.. CYP2D6 Substrates: Concomitant use of STRATTERA (40 or 60 mg twice daily for 13 days) with desipramine, (CYP2D6 substrate) (single dose of 50 mg), did not alter the desipramine pharmacokinetics.. Drugs that Affect Gastric pH: Drugs that elevate gastric pH had no effect on atomoxetine bioavailability.. In Vitro Studies:. Drugs Highly Bound to Plasma Protein: In vitro drug-displacement studies were conducted with atomoxetine and other drugs highly bound to plasma protein at therapeutic atomoxetine concentrations. Atomoxetine did not affect the binding of warfarin, acetylsalicylic acid, phenytoin, or diazepam to human albumin. Similarly, warfarin, acetylsalicylic acid, phenytoin, or diazepam did not affect the binding of atomoxetine to human albumin.. CYP Inhibition/induction: Atomoxetine did not cause clinically important inhibition or induction of cytochrome P450 enzymes (including CYP1A2, CYP3A, CYP2D6, and CYP2C9).. 12.5 Pharmacogenomics. Atomoxetine is metabolized by CYP2D6 [see Clinical Pharmacology (12.3)]. The gene encoding CYP2D6 has variants that affect CYP2D6 metabolic function. CYP2D6 poor metabolizers are individuals with two nonfunctional alleles (e.g., CYP2D65/5), and as result have no CYP2D6 enzyme activity.Atomoxetine AUC was approximately 10-fold higher and atomoxetine Css, max was approximately 5-fold higher in CYP2D6 poor metabolizers compared to other CYP2D6 metabolizer types [see Dosage and Administration (2.5), Warnings and Precautions (5.4), Use in Specific Populations (8.7), and Clinical Pharmacology (12.3)]. In this analysis, other CYP2D6 metabolizer types were defined as individuals who were not CYP2D6 poor metabolizers and included CYP2D6 ultrarapid, normal, and intermediate metabolizers (e.g., CYP2D61/2xN, CYP2D61/1, CYP2D61/5, respectively).

CLINICAL STUDIES SECTION.

14 CLINICAL STUDIES. 14.1 ADHD Studies in Pediatric Patients Years of Age and Older. Acute Studies in Pediatric Patients Years of Age and Older with ADHD:The effectiveness of STRATTERA in the treatment of ADHD was established in four randomized, double-blind, placebo-controlled studies of pediatric patients to 18 years of age (Studies 1, 2, 3, and 4). In these studies, approximately one-third of the patients met DSM-IV criteria for inattentive subtype and two-thirds met criteria for both inattentive and hyperactive/impulsive subtypes.In these studies, signs and symptoms of ADHD were evaluated with the investigator administered and scored ADHD Rating Scale-IV-Parent Version (ADHDRS) total score including hyperactive/impulsive and inattentive subscales by comparing the mean change from baseline to endpoint in the STRATTERA and placebo groups using an intent-to-treat (ITT) analysis (the primary endpoint). Each text on the ADHDRS maps directly to one symptom criterion for ADHD in the DSM-IV.In Study 1, an 8-week randomized, double-blind, placebo-controlled, dose-response, acute treatment study, pediatric patients to 18 years of age (N=297) received either fixed dosage of STRATTERA (0.25, 0.6, or 0.9 mg/kg twice daily (in the early morning and late afternoon/early evening) or placebo. Improvements in ADHD symptoms were statistically significantly superior in patients treated with either of the two higher STRATTERA dosages compared with patients treated with placebo as measured on the ADHDRS scale. The 0.9 mg/kg twice daily STRATTERA dosage did not provide any additional benefit over that observed with the 0.6 mg/kg twice daily STRATTERA dosage. The 0.25 mg/kg twice daily STRATTERA dosage group was not superior to the placebo group.In Study 2, 6-week randomized, double-blind, placebo-controlled, acute treatment study, pediatric patients to 16 years of age (N=171) received either STRATTERA or placebo. STRATTERA was administered as once daily dose in the early morning and titrated on weight-adjusted basis according to clinical response, up to maximum dosage of 1.5 mg/kg once daily. The mean final dosage of STRATTERA was approximately 1.3 mg/kg once daily. ADHD symptoms were statistically significantly improved in the STRATTERA group compared to the placebo group, as measured on the ADHDRS scale. Study showed that STRATTERA was effective when administered once daily in the morning.In two identically designed, 9-week, acute, double-blind, placebo-controlled studies, pediatric patients to 13 years of age (Study 3, N=147; Study 4, N=144) were randomized to receive STRATTERA, methylphenidate, or placebo. In Studies and 4, STRATTERA was administered twice daily (in the early morning and late afternoon, after school) and titrated on weight-adjusted basis according to clinical response up to the maximum recommended STRATTERA dosage of mg/kg twice daily. The mean final dosage of STRATTERA in Studies and was approximately 0.8 mg/kg twice daily. In Studies and 4, ADHD symptoms statistically significantly improved more in the STRATTERA group than the placebo group, as measured on the ADHDRS scale.Examination of population subsets based on sex and age (<12 and 12 to 17 years of age) in these studies did not reveal any differences in response. There were not sufficient numbers of patients in racial or ethnic groups to determine if there were differences in responses in these subgroups.. Maintenance Study in Pediatric Patients Years of Age and Older with ADHDThe effectiveness of STRATTERA in the maintenance treatment of ADHD in pediatric patients years of age and older was established in an outpatient randomized withdrawal study of pediatric patients 6-15 years of age (Study 5). In this study, patients who met DSM-IV criteria for ADHD, and showed continuous response for about weeks during an initial 10-week open-label treatment phase with STRATTERA (1.2 to 1.8 mg/kg/day) were randomized to continue of their current STRATTERA dosage (N=292) or to placebo (N=124) under double-blind treatment for observation of relapse (first double-blind phase). Response during the open-label phase was defined as CGI-ADHD-S score <=2 and reduction of at least 25% from baseline in ADHDRS-IV-Parent: Investigator total score.Patients who were assigned to STRATTERA during the first double-blind phase who showed continuous response for approximately months during the first double-blind treatment phase were again randomized to continue their current STRATTERA dosage (N=81) or placebo (N=82) under double-blind treatment for observation of relapse (second double-blind phase). Relapse during each of the double-blind phases was defined as CGI-ADHD-S score increases of at least from the end of open-label phase and ADHDRS-IV-Parent: Investigator total score returns to >=90% of study entry score for consecutive visits.In both double-blind phases, patients who received STRATTERA treatment experienced significantly longer times to relapse than those who received placebo.. 14.2 ADHD Studies in Adults. The effectiveness of STRATTERA in the treatment of ADHD in adults was established in two 10-week, randomized, double-blind, placebo-controlled clinical studies of adult patients 18 years of age and older, who met DSM-IV criteria for ADHD (Study 6, N=280; Study 7, N=256).In Studies and 7, signs and symptoms of ADHD were evaluated using the 30-text investigator-administered Conners Adult ADHD Rating Scale Screening Version (CAARS). In these studies, the primary efficacy endpoint was the mean change from baseline to endpoint (using an ITT analysis) in the 18-text Total ADHD Symptom score (the sum of the inattentive and hyperactivity/impulsivity subscales from the CAARS).In Studies and 7, patients received either STRATTERA or placebo. Patients in the STRATTERA group received 30 mg to 60 mg twice day (in the early morning and late afternoon/early evening) of STRATTERA which was titrated according to clinical response. The mean final STRATTERA dosage in these studies was approximately 48 mg twice daily. In both studies, ADHD symptoms were statistically significantly improved in the STRATTERA group compared to the placebo group, as measured on the ADHD Symptom score from the CAARS scale.In Studies 6, and 7, examination of population subsets based on sex and age (<42 and >=42 years of age) did not reveal any differences in response. There was not sufficient number of patients in racial and ethnic groups to determine if there were differences in responses among these subgroups.. 14.3 Safety Studies in ADHD Patients with Tourettes Disorder or Chronic Motor Tic Disorder OR Anxiety Disorder. Tics in Patients with ADHD and Tourettes Disorder or Chronic Motor Tic DisorderIn randomized, double-blind, placebo-controlled 18-week trial in 148 pediatric patients to 17 years old with DSM-IV diagnosis of ADHD and concurrent Tourette syndrome or chronic motor tic disorder, STRATTERA affect on tic severity was assessed. Patients in the STRATTERA group received flexible dosage range of 0.5 to 1.5 mg/kg/day (mean dose of 1.3 mg/kg/day). In this study, 80% (n=116) of patients had Tourettes Disorder and 20% (n=29) of patients had chronic motor tic disorder. non-inferiority analysis revealed that STRATTERA did not worsen tics in these patients as determined by the Yale Global Tic Severity Scale Total Score (YGTSS). Out of 148 patients who entered the acute treatment phase, 103 (70%) patients discontinued the study. The primary reason for discontinuation in both the STRATTERA group (50% (38/76) and placebo group (63% (45/72) was identified lack of ADHD efficacy with most of the patients discontinuing at Week 12. There have been postmarketing reports of tics in STRATTERA-treated patients [see Adverse Reactions (6.2)].. Anxiety in Pediatric Patients with ADHD and Anxiety DisordersTwo post-marketing, double-blind, placebo-controlled trials demonstrated that treating patients with ADHD and comorbid anxiety disorders with STRATTERA does not worsen their anxiety.In 12-week double-blind, placebo-controlled trial, 176 pediatric patients 8-17 years of age, who met DSM-IV criteria for ADHD and at least one of the anxiety disorders of separation anxiety disorder, generalized anxiety disorder or social phobia were randomized to receive STRATTERA or placebo. In the STRATTERA group, following 2-week double-blind placebo lead-in, STRATTERA was initiated at 0.8 mg/kg/day with increase to target dose of 1.2 mg/kg/day (median dose 1.3 mg/kg/day +/- 0.29 mg/kg/day). STRATTERA did not worsen anxiety in these patients as determined by the Pediatric Anxiety Rating Scale (PARS). Of the 158 patients who completed the double-blind placebo lead-in, 26 (16%) patients discontinued the study.In separate 16-week, double-blind, placebo-controlled trial, 442 patients aged 18-65, who met DSM-IV criteria for adult ADHD and social anxiety disorder (23% of whom also had Generalized Anxiety Disorder) were randomized to receive STRATTERA or placebo. In the STRATTERA group, following 2-week double-blind placebo lead-in, STRATTERA was initiated at 40 mg/day to maximum dosage of 100 mg/day (mean daily dose 83 mg/day +/- 19.5 mg/day). STRATTERA did not worsen anxiety in these patients as determined by the Liebowitz Social Anxiety Scale (LSAS). Of the 413 patients who completed the double-blind placebo lead-in, 36% (n=149) patients discontinued the study. There have been postmarketing reports of anxiety [see Adverse Reactions (6.2)].

CLINICAL TRIALS EXPERIENCE SECTION.

6.1 Clinical Trials Experience. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.STRATTERA was administered to 5,382 pediatric patients years of age and older in clinical ADHD studies (Studies 1, 2, 3, 4, and 5) [see Clinical Studies (14.1)] and 1,007 adults in clinical ADHD studies (Studies and 7) [see Clinical Studies (14.2)]. In the ADHD clinical trials, 2,529 pediatric patients were treated for over months which included 1,625 pediatric patients who were treated for longer than year.. Adverse Reactions in the Clinical Trials of Pediatric Patients Years of Age and Older with ADHD. Discontinuation of Treatment Due to Adverse Reactions in the Clinical Studies of Pediatric Patients Years of Age and Older:In the acute placebo-controlled studies of pediatric patients years of age and older with ADHD, 3% (48/1,613) of STRATTERA-treated pediatric patients and 1.4% (13/945) of placebo-treated pediatric patients discontinued due to an adverse reaction. Among STRATTERA-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 one patient.For all studies, (including open-label and long-term studies), 6% of STRATTERA-treated pediatric patients who were other CYP2D6 metabolizer types (ultrarapid, normal, and intermediate) and 11% of those who were CYP2D6 poor metabolizers discontinued due to an adverse reaction.. Common Adverse Reactions in the Clinical Studies of Pediatric Patients Years of Age and Older: Common adverse reactions (incidence of 2% or greater in STRATTERA-treated patients and with higher incidence in STRATTERA-treated patients compared to placebo-treated patients) in pediatric patients years of age and older with ADHD are listed in Table 2. The most commonly observed adverse reactions in STRATTERA-treated patients (incidence of >=5% and >= twice the incidence in placebo-treated patients), for either twice daily or once daily dosing were: nausea, vomiting, fatigue, decreased appetite, abdominal pain, and somnolence (see Tables and 3).Table 2: Common Adverse Reactionsa in Acute Studies (up to 18 weeks) in Pediatric Patients Years and Older with ADHDa Adverse reactions reported by at least 2% of STRATTERA-treated patients and greater than placebo-treated patients.b Abdominal pain includes the terms: upper abdominal pain, and epigastric discomfort.c Somnolence includes the term sedation.Adverse ReactionSTRATTERA(N=1,597)Placebo(N=934)Headache19%15%Abdominal painb 18%10%Decreased appetite16%4%Somnolencec 11%4%Vomiting11%6%Nausea10%5%Fatigue8%3%Irritability6%3%Dizziness5%2%Decreased weight3%0%Anorexia3%1%Rash2%1%Adverse reaction in the STRATTERA-treated patients who received twice daily, and once daily dosing are shown in Table (adverse reactions based on statistically significant Breslow-Day tests).Table 3: Common Adverse Reactions in Acute Studies (up to 18 weeks) in Pediatric Patients Years and Older with ADHDa Abdominal pain included the terms: upper abdominal pain, and epigastric discomfort.b Mood swings didnt meet the statistical significance on Breslow-Day test at 0.05 level, but p-value was <0.1 (trend).c Constipation didnt meet the statistical significance on Breslow-Day test but is included in the table because of pharmacologic plausibility.Adverse ReactionADHD Studies with Twice Daily DosingADHD Studies with Once Daily DosingSTRATTERA(N=715)Placebo(N=434)STRATTERA(N=882)Placebo(N=500)Abdominal paina 17%13%18%7%Vomiting11%8%11%4%Nausea7%6%13%4%Fatigue6%4%9%2%Mood swingsb 2%0%1%1%Constipationc 2%1%1%0%. Common Adverse Reactions by CYP2D6 Metabolizer Status in the Clinical Studies of Pediatric Patients Years of Age and Older:Table displays adverse reactions that occurred in at least 2% of STRATTERA-treated pediatric patients who were CYP2D6 poor metabolizers and were statistically significantly more frequent in CYP2D6 poor metabolizers compared with other CYP2D6 metabolizer types (ultrarapid, normal, and intermediate).Table 4: Common Adverse Reactionsa in STRATTERA-treated Pediatric Patients Years and Older with ADHD by CYP2D6 Metabolizer Typesa Adverse reactions that occurred in at least 2% of STRATTERA-treated pediatric patients who were CYP2D6 poor metabolizers and were statistically significantly more frequent in poor metabolizers compared with other CYP2D6 metabolizer types (ultrarapid, normal, and intermediate).b Depression included the following terms: major depression, depressive symptoms, depressed mood, dysphoria.Adverse ReactionSTRATTERACYP2D6 Poor Metabolizers (N=355)STRATTERAOther CYP2D6 Metabolizer Types (N=5,019)Insomnia11%6%Decreased weight7%4%Constipation7%4%Depressionb 7%4%Tremor5%1%Excoriation4%2%Sedation4%2%Middle insomnia3%1%Conjunctivitis3%1%Syncope3%1%Early morning awakening2%1%Mydriasis2%1%. Less Common Adverse Reactions in the Clinical Studies of Pediatric Patients Years of Age and Older: The following reactions did not meet this criterion but were reported by more STRATTERA-treated patients than placebo-treated patients and are possibly related to STRATTERA treatment: blood pressure increased, early morning awakening (terminal insomnia), flushing, mydriasis, sinus tachycardia, asthenia, palpitations, mood swings, constipation, and dyspepsia.The following reactions were reported by at least 2% of patients treated with STRATTERA, and equal to or less than placebo: pharyngolaryngeal pain, insomnia (insomnia includes the terms, insomnia, initial insomnia, middle insomnia). The following reaction did not meet this criterion but shows statistically significant dose relationship: pruritus.. Seizures in the Clinical Studies of Pediatric Patients Years of Age and Older: STRATTERA has not been systematically evaluated in pediatric patients with seizure disorder as these patients were excluded from STRATTERA studies. In the clinical development program, seizures were reported in 0.2% (12/5,073) of STRATTERA-treated pediatric patients whose average age was 10 years old (range to 16 years of age). In these clinical trials, the seizure incidence among CYP2D6 poor metabolizers was 0.3% (1/293) compared to 0.2% (11/4,741) for other CYP2D6 metabolizer types.. Heart Rate and Blood Pressure Increases in the Clinical Studies of Pediatric Patients Years of Age and Older: Additional data from ADHD clinical trials (controlled and uncontrolled) has shown that approximately to 10% of pediatric patients experienced potentially clinically important changes in heart rate (>=20 beats per minute) or blood pressure (>=15 to 20 mm Hg) [see Contraindications (4) and Warnings and Precautions (5.4)].. Adverse Reactions in the Clinical Trials of Adults with ADHD. Discontinuation of Treatment Due to Adverse Reactions in the Clinical Studies of Adults: In the acute adult placebo-controlled trials, 11.3% (61/541) STRATTERA-treated patients and 3% (12/405) placebo-treated patients discontinued for adverse reactions. Among STRATTERA-treated patients, insomnia (0.9%, N=5); nausea (0.9%, N=5); chest pain (0.6%, N=3); fatigue (0.6%, N=3); anxiety (0.4%, N=2); erectile dysfunction (0.4%, N=2); mood swings (0.4%, N=2); nervousness (0.4%, N=2); palpitations (0.4%, N=2); and urinary retention (0.4%, N=2) were the reasons for discontinuation reported by more than patient.. Common Adverse Reactions in the Clinical Studies of Adults: Commonly observed adverse reactions associated with the use of STRATTERA (incidence of 2% or greater) and not observed at an equivalent incidence among placebo-treated patients (STRATTERA incidence greater than placebo) are listed in Table 5. The most commonly observed adverse reactions in patients treated with STRATTERA (incidence of 5% or greater and at least twice the incidence in placebo patients) were: constipation, dry mouth, nausea, decreased appetite, dizziness, erectile dysfunction, and urinary hesitation (see Table 5).Table 5: Common Adverse Reactionsa Associated in Acute Studies (up to 25 weeks) of Adult Patients with ADHDa Reactions reported by at least 2% of patients treated with STRATTERA, and greater than placebo. The following reactions did not meet this criterion but were reported by more STRATTERA-treated patients than placebo-treated patients and are possibly related to STRATTERAtreatment: peripheral coldness, tachycardia, prostatitis, testicular pain, orgasm abnormal, flatulence, asthenia, feeling cold, muscle spasm, dysgeusia, agitation, restlessness, micturition urgency, pollakiuria, pruritus, urticaria, flushing, tremor, menstruation irregular, rash, and urinary retention.b Insomnia includes the terms initial insomnia, middle insomnia, terminal insomnia and other related terms.c Based on total number of males (STRATTERA group, N=943; placebo group, N=869).d Somnolence includes related terms.e Abdominal pain includes the terms: upper abdominal pain and other related terms.f Urinary hesitation includes the term decreased urine flow.g Based on total number of females (STRATTERA, N=754; placebo, N=691).Adverse ReactionSTRATTERA (N=1,697)Placebo (N=1,560)Nausea26%6%Dry mouth20%5%Decreased appetite16%3%Insomniab 15%8%Fatigue10%6%Erectile dysfunctionc 8%1%Constipation8%3%Dizziness8%3%Somnolenced 8%5%Abdominal paine 7%4%Urinary hesitationf 6%1%Irritability5%3%Ejaculation delayedc and/or ejaculation disorderc 4%1%Hyperhidrosis4%1%Dyspepsia4%2%Vomiting4%2%Abnormal dreams4%3%Chills3%0%Paraesthesia3%0%Hot flush3%0%Palpitations3%1%Libido decreased3%1%Sleep disorder3%1%Dysmenorrheag 3%2%Dysuria2%0%Thirst2%1%Weight decreased2%1%Feeling jittery2%1%. Common Adverse Reactions by CYP2D6 Metabolizer Status in the Clinical Studies of Adults:Table displays adverse reactions that occurred in at least 2% of STRATTERA-treated adult patients who were CYP2D6 poor metabolizers and were statistically significantly more frequent compared to other CYP2D6 metabolizer types (ultrarapid, normal, and intermediate).Table 6: Common Adverse Reactionsa in STRATTERA-treated Adult Patients with ADHD by CYP2D6 Metabolizer Typesa Adverse reactions that occurred in at least 2% of STRATTERA-treated adult patients who were CYP2D6 poor metabolizers and were statistically significantly more frequent in CYP2D6 poor metabolizers compared with other CYP2D6 metabolizer types (ultrarapid, normal, and intermediate).Adverse ReactionSTRATTERACYP2D6 Poor Metabolizers (N=203)STRATTERAOther CYP2D6 Metabolizer Types (N=3,599)Dry mouth35%17%Decreased appetite23%15%Erectile dysfunction21%9%Insomnia19%11%Hyperhidrosis15%7%Constipation11%7%Sleep disorder7%3%Urinary retention6%1%Ejaculation disorder6%2%Tremor5%1%Feeling jittery5%2%Middle insomnia5%3%Blurred vision4%1%Terminal insomnia3%1%Peripheral coldness3%1%. Less Common Adverse Reactions in the Clinical Studies of Adults: The following reactions did not meet this criterion but were reported by more STRATTERA-treated patients than placebo-treated patients and are possibly related to STRATTERA treatment: peripheral coldness, tachycardia, prostatitis, testicular pain, orgasm abnormal, flatulence, asthenia, feeling cold, muscle spasm, dysgeusia, agitation, restlessness, micturition urgency, pollakiuria, pruritus, urticaria, flushing, tremor, menstruation irregular, rash, and urinary retention.. Seizures in the Clinical Studies of Adults: STRATTERA has not been systematically evaluated in adult patients with seizure disorder as these patients were excluded from clinical studies during the products premarket testing. In the clinical development program, seizures were reported on 0.1% (1/748) of adult patients. In these clinical trials, no CYP2D6 poor metabolizers (0/43) reported seizures compared to 0.1% (1/705) for other CYP2D6 metabolizer types.. Heart Rate and Blood Pressure Increases in the Clinical Studies of Adults:Table displays the proportion of STRATTERA-treated and placebo-treated patients who had an increase in diastolic blood pressure (DBP) >=15 mm Hg, systolic blood pressure (SBP) >=20 mm Hg, or heart rate >= 20 bpm in short-term, placebo-controlled clinical studies in pediatric and adult patients with ADHD [see Warnings and Precautions (5.4)]. Table 7: Proportion of ADHD Patients With an Increase of >= 15 mm Hg in DBP, >=20 mm Hg in SBP, or >= 20 bpm in Heart Ratea Abbreviations: bpm=beats per minute; DBP=diastolic blood pressure; HR=heart rate; mm Hg=millimeters mercury; SBP=systolic blood pressure.b Proportion of patients meeting threshold at any one time during the clinical studies.Pediatric Acute ADHD StudiesAdult Acute ADHD StudiesMaximumbEndpointMaximumbEndpointSTRATTERAPlaceboSTRATTERAPlaceboSTRATTERAPlaceboSTRATTERAPlaceboDBP (>=15 mm Hg)22%14%9%5%13%9%5%4%SBP (>=20 mm Hg)13%9%5%3%12%8%4%3%HR (>=20 bpm)23%12%12%4%22%8%10%2%Additional data from ADHD clinical trials (controlled and uncontrolled) showed that approximately to 10% of adult patients had potentially clinically important changes in heart rate (>=20 beats per minute) or blood pressure (>=15 to 20 mm Hg) [see Contraindications (4) and Warnings and Precautions (5.4)].. Male and Female Sexual Dysfunction in the Clinical Studies of Adults: STRATTERA impaired sexual function in some patients. Estimates of the incidence of untoward sexual experience and performance in these studies are likely to underestimate their actual incidence because patients and health care providers may be reluctant to discuss them. Table displays the incidence of sexual adverse reactions (reported by at least 2% of STRATTERA-treated adult patients in the placebo-controlled studies of adults with ADHD (i.e., erectile dysfunction, dysmenorrhea, and ejaculation delayed and/or ejaculation disorder).There are no adequate and well-controlled studies examining sexual dysfunction with STRATTERA treatment. While it is difficult to know the precise risk of sexual dysfunction associated with the use of STRATTERA, health care providers should routinely inquire about sexual dysfunction.

CONTRAINDICATIONS SECTION.

4 CONTRAINDICATIONS. STRATTERA is contraindicated in patients:With known hypersensitivity reaction to atomoxetine or other constituents of STRATTERA. Hypersensitivity reactions included anaphylaxis, angioneurotic edema, urticaria, and rash [see Warnings and Precautions (5.8)].Taking, or within 14 days of stopping, monoamine oxidase inhibitor (MAOI) [see Drug Interactions (7)].With narrow angle glaucoma. In clinical trials, STRATTERA use was associated with an increased risk of mydriasis.With pheochromocytoma or history of pheochromocytoma. Serious reactions, including elevated blood pressure and tachyarrhythmia, have been reported in patients with pheochromocytoma or history of pheochromocytoma who received STRATTERA.With severe cardiac or vascular disorders whose condition would be expected to deteriorate if they had clinically important increase in blood pressure or heart rate (e.g., 15 to 20 mm Hg in blood pressure or 20 beats per minute in heart rate) [see Warnings and Precautions (5.4)].. With known hypersensitivity reaction to atomoxetine or other constituents of STRATTERA. Hypersensitivity reactions included anaphylaxis, angioneurotic edema, urticaria, and rash [see Warnings and Precautions (5.8)].. Taking, or within 14 days of stopping, monoamine oxidase inhibitor (MAOI) [see Drug Interactions (7)].. With narrow angle glaucoma. In clinical trials, STRATTERA use was associated with an increased risk of mydriasis.. With pheochromocytoma or history of pheochromocytoma. Serious reactions, including elevated blood pressure and tachyarrhythmia, have been reported in patients with pheochromocytoma or history of pheochromocytoma who received STRATTERA.. With severe cardiac or vascular disorders whose condition would be expected to deteriorate if they had clinically important increase in blood pressure or heart rate (e.g., 15 to 20 mm Hg in blood pressure or 20 beats per minute in heart rate) [see Warnings and Precautions (5.4)].. Contraindicated in patients (4):With known hypersensitivity to atomoxetine or other constituents of STRATTERATaking or within 14 days of stopping, monoamine oxidase inhibitor (MAOI)With narrow angle glaucomaWith pheochromocytoma or history of pheochromocytomaWith severe cardiac or vascular disorders whose condition would be expected to deteriorate with clinically important increases in blood pressure or heart rate. With known hypersensitivity to atomoxetine or other constituents of STRATTERA. Taking or within 14 days of stopping, monoamine oxidase inhibitor (MAOI). With narrow angle glaucoma. With pheochromocytoma or history of pheochromocytoma. With severe cardiac or vascular disorders whose condition would be expected to deteriorate with clinically important increases in blood pressure or heart rate.

CONTROLLED SUBSTANCE SECTION.

9.1 Controlled Substance. STRATTERA contains atomoxetine which is not controlled substance.

DEPENDENCE SECTION.

9.3 Dependence. After STRATTERA discontinuation, there was no evidence of symptom rebound or adverse reactions suggesting STRATTERA-discontinuation or withdrawal syndrome.

DESCRIPTION SECTION.

11 DESCRIPTION. Atomoxetine is selective norepinephrine reuptake inhibitor. Atomoxetine hydrochloride 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 C17H21NOoHCl, which corresponds to molecular weight of 291.82. The chemical structure is:Atomoxetine hydrochloride is white to practically white solid, which has solubility of 27.8 mg/mL in water.STRATTERA (atomoxetine) capsules are for oral administration only.Each STRATTERA capsule contains 10 mg, 18 mg, 25 mg, 40 mg, 60 mg, 80 mg, or 100 mg of atomoxetine (equivalent to 11.4 mg, 20.6 mg, 28.6 mg, 45.7 mg, 68.6 mg, 91.4 mg and 114.3 mg of atomoxetine hydrochloride, respectively). The capsules also contain pregelatinized starch and dimethicone. The capsule shells contain gelatin, sodium lauryl sulfate, and one or more of the following inactive ingredients:FD&C Blue No. 2, synthetic yellow iron oxide, titanium dioxide, red iron oxide. The capsules are imprinted with edible black ink.. Chemical Structure.

DOSAGE & ADMINISTRATION SECTION.

2 DOSAGE AND ADMINISTRATION. Prior to initiating treatment with STRATTERA, screen patients for personal or family history of bipolar disorder, mania, or hypomania. (2.1, 5.6)See table below for the recommended STRATTERA 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 WeightStarting DosageTarget Dosage1Maximum Total Daily Dose1Pediatrics who weigh less than 70 kg0.5 mg/kg/day1.2 mg/kg/day1.4 mg/kg/day or 100 mg/day (whichever is less)Pediatrics who weigh 70 kg or more and adults40 mg/day80 mg/day100 mg/dayFor the recommended dosage in patients with hepatic impairment, see Full Prescribing Information. (2.4)For the recommended dosage with concomitant use of strong CYP2D6 inhibitor or in CYP2D6 poor metabolizers, see Full Prescribing Information. (2.5). Prior to initiating treatment with STRATTERA, screen patients for personal or family history of bipolar disorder, mania, or hypomania. (2.1, 5.6). See table below for the recommended STRATTERA dosage. (2.3). For the recommended dosage in patients with hepatic impairment, see Full Prescribing Information. (2.4). For the recommended dosage with concomitant use of strong CYP2D6 inhibitor or in CYP2D6 poor metabolizers, see Full Prescribing Information. (2.5). 2.1 Recommendations Prior to Initiating STRATTERA Treatment. Prior to initiating treatment with STRATTERA, screen patients for personal or family history of bipolar disorder, mania, or hypomania [see Warnings and Precautions (5.6)]. 2.2 Administration Instructions. STRATTERA may be taken with or without food. Take STRATTERA capsules whole; do not open the capsules.. 2.3 Recommended Dosage. Table includes the recommended STRATTERA dosage in adult patients and pediatric patients years of age and older for acute treatment of ADHD.Table 1: Recommended Dosage of STRATTERA for Acute Treatment of ADHDa 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 STRATTERA dosages higher than 1.2 mg/kg/day [see Clinical Studies (14)].c If patient has not achieved an optimal response at 80 mg/day after to additional weeks, may increase the dosage to maximum of 100 mg/day. There is no data that supports increased effectiveness at dosage higher than 100 mg/day [see Clinical Studies (14)].Age and Body WeightStarting DosageTitration IntervalTarget DosageMaximum DosagePediatric patients who weigh less than 70 kg0.5 mg/kg/dayMinimum of days1.2 mg/kg/daya,b 1.4 mg/kg/day or 100 mg/day, whichever is lessa Pediatric patients who weigh 70 kg or more and adult patients40 mg/dayMinimum of days80 mg/daya 100 mg/daya,c The health care provider who elects to use STRATTERA for extended periods should periodically reevaluate the long-term usefulness of STRATTERA for the individual patient.. 2.4 Recommended Dosage in Patients with Hepatic Impairment. For patients aged years of age or older with:Severe hepatic impairment (HI) (Child-Pugh Class C), the recommended initial and target STRATTERA 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 STRATTERA 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 STRATTERA dosage is the same as those with normal hepatic function.. Severe hepatic impairment (HI) (Child-Pugh Class C), the recommended initial and target STRATTERA 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 STRATTERA 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 STRATTERA 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. Consider genetic testing to determine the patients CYP2D6 metabolizer status.In patients taking concomitant strong CYP2D6 inhibitor or who are CYP2D6 poor metabolizers, longer titration interval of weeks is recommended, if ADHD symptoms fail to improve and the initial STRATTERA dosage is well tolerated. The recommended starting, target, and maximum STRATTERA dosages are the same as outlined in Table [see Dosage and Administration (2.3)].For other CYP2D6 metabolizer types (ultrarapid, normal, and intermediate), follow the recommended dosage, including the recommended titration interval (minimum of days), as outlined in Table [see Dosage and Administration (2.3)]. 2.6 Switching to or from Monoamine Oxidase Inhibitor Antidepressant. At least 14 days must elapse between discontinuation of monoamine oxidase inhibitor (MAOI) antidepressant and initiation of STRATTERA. In addition, at least 14 days must elapse after stopping STRATTERA before starting an MAOI antidepressant.. 2.7 Recommendations for Missed Dose. If STRATTERA dose is missed, take the dose as soon as possible, but do not take more than the prescribed total daily amount of STRATTERA in any 24-hour period.. 2.8 Recommendations for Discontinuation. When discontinuing STRATTERA, no taper is needed [see Drug Abuse and Dependence (9.2, 9.3)].

DOSAGE FORMS & STRENGTHS SECTION.

3 DOSAGE FORMS AND STRENGTHS. Capsules:10 mg of atomoxetine (opaque white, opaque white)18 mg of atomoxetine (gold, opaque white)25 mg of atomoxetine (opaque blue, opaque white)40 mg of atomoxetine (opaque blue, opaque blue)60 mg of atomoxetine (opaque blue, gold)80 mg of atomoxetine (opaque brown, opaque white)100 mg of atomoxetine (opaque brown, opaque brown). 10 mg of atomoxetine (opaque white, opaque white). 18 mg of atomoxetine (gold, opaque white). 25 mg of atomoxetine (opaque blue, opaque white). 40 mg of atomoxetine (opaque blue, opaque blue). 60 mg of atomoxetine (opaque blue, gold). 80 mg of atomoxetine (opaque brown, opaque white). 100 mg of atomoxetine (opaque brown, opaque brown). Capsules: contain 10 mg, 18 mg, 25 mg, 40 mg, 60 mg, 80 mg, or 100 mg of atomoxetine. (3, 11, 16).

DRUG ABUSE AND DEPENDENCE SECTION.

9 DRUG ABUSE AND DEPENDENCE. 9.1 Controlled Substance. STRATTERA contains atomoxetine which is not controlled substance.. 9.2 Abuse. In randomized, double-blind, placebo-controlled, abuse-potential study in adults that compared effects of STRATTERA and placebo, STRATTERA was not associated with stimulant or euphoriant properties. Clinical study data in over 2,000 adults and pediatric patients with ADHD and over 1,200 adults with depression (STRATTERA is not indicated for the treatment of depression) showed only isolated incidents of inappropriate STRATTERA self-administration.Drug discrimination studies in rats and monkeys showed inconsistent stimulus generalization between atomoxetine and cocaine.. 9.3 Dependence. After STRATTERA discontinuation, there was no evidence of symptom rebound or adverse reactions suggesting STRATTERA-discontinuation or withdrawal syndrome.

DRUG INTERACTIONS SECTION.

7 DRUG INTERACTIONS. SeeTable for clinically significant drug interactions with STRATTERA and other drugs.Table 8: Clinically Significant Drug Interactions with STRATTERA and Other DrugsMonoamine Oxidase Inhibitors (MAOIs)Prevention or ManagementSTRATTERA is contraindicated in patients taking MAOIs, including MAOIs such as linezolid or intravenous methylene blue, or in patients who stopped an MAOI within 14 days.Mechanism and Clinical Effect(s)As with other drugs affecting brain monoamine concentrations, there have been reports of serious, sometimes fatal reactions (hyperthermia, rigidity, myoclonus, autonomic instability with fluctuations of vital signs, extreme agitation progressing to delirium/coma) with concomitant use of STRATTERA and an MAOI. Some cases presented with features resembling neuroleptic malignant syndrome.Strong CYP2D6 InhibitorsPrevention or ManagementWith concomitant use of STRATTERA and strong CYP2D6 inhibitor, increase the titration interval [see Dosage and Administration (2.5) and Clinical Pharmacology (12.3)]. Mechanism and Clinical Effect(s)Atomoxetine is CYP2D6 substrate. The concomitant use of STRATTERA and strong CYP2D6 inhibitor increases atomoxetine exposure [see Clinical Pharmacology (12.3)].Antihypertensive DrugsPrevention or ManagementIncrease the frequency of monitoring blood pressure and adjust STRATTERA dosage as clinically appropriate.Mechanism and Clinical Effect(s)Because of increased risk of increased blood pressure, STRATTERA should be used cautiously with antihypertensive drugs, other drugs that increase blood pressure or pressor drugs (e.g., dopamine, dobutamine).Albuterol or Other Beta2 AgonistsPrevention or ManagementIncrease the frequency of monitoring blood pressure and heart rate and adjust STRATTERA dosage as clinically appropriate.Mechanism and Clinical Effect(s)Systemically administered albuterol (e.g., oral) can be potentiated by atomoxetine, resulting in increases in heart rate and blood pressure. [see Clinical Pharmacology (12.3)]. Monoamine Oxidase Inhibitors: Concomitant use contraindicated. (4, 7)Strong CYP2D6 Inhibitors: With concomitant use of STRATTERA and strong CYP2D6 inhibitors, increase the titration intervals. (7)Antihypertensives: Increase the frequency of monitoring blood pressure and adjust STRATTERA dosage as clinically appropriate. (7)Albuterol (or other beta2 agonists): Increase the frequency of monitoring blood pressure and heart rate. (7). Monoamine Oxidase Inhibitors: Concomitant use contraindicated. (4, 7). Strong CYP2D6 Inhibitors: With concomitant use of STRATTERA and strong CYP2D6 inhibitors, increase the titration intervals. (7). Antihypertensives: Increase the frequency of monitoring blood pressure and adjust STRATTERA dosage as clinically appropriate. (7). Albuterol (or other beta2 agonists): Increase the frequency of monitoring blood pressure and heart rate. (7).

NONCLINICAL TOXICOLOGY SECTION.

13 NONCLINICAL TOXICOLOGY. 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility. Carcinogenesis -- Atomoxetine HCl was not carcinogenic in rats and mice when given in the diet for years at time-weighted average doses up to 47 and 458 mg/kg/day, respectively. The highest dose used in rats is approximately and times the maximum recommended human dose (MRHD) in children and adults, respectively, on mg/m2 basis.Plasma levels (AUC) of atomoxetine at this dose in rats are estimated to be 1.8 times (other CYP2D6 metabolizer types) or 0.2 times (CYP2D6 poor metabolizers) those in humans receiving the maximum human dose. The highest dose used in mice is approximately 39 and 26 times the MRHD in children and adults, respectively, on mg/m2 basis.. Mutagenesis -- Atomoxetine HCl was negative in battery of genotoxicity studies that included reverse point mutation assay (Ames Test), an in vitro mouse lymphoma assay, chromosomal aberration test in Chinese hamster ovary cells, an unscheduled DNA synthesis test in rat hepatocytes, and an in vivo micronucleus test in mice. However, there was slight increase in the percentage of Chinese hamster ovary cells with diplochromosomes, suggesting endoreduplication (numerical aberration).The metabolite N-desmethylatomoxetine HCl was negative in the Ames Test, mouse lymphoma assay, and unscheduled DNA synthesis test.. Impairment of Fertility -- Atomoxetine HCl did not impair fertility in rats when given in the diet at doses of up to 57 mg/kg/day, which is approximately times the MRHD on mg/m2 basis.

OVERDOSAGE SECTION.

10 OVERDOSAGE. During postmarketing use, there have been fatalities reported involving mixed ingestion overdose of STRATTERA and at least one other drug. There have been no reports of death involving overdose of STRATTERA alone, including intentional overdoses at amounts up to 1,400 mg (14 times the maximum recommended dosage). The most commonly reported symptoms with acute and chronic overdoses of STRATTERA 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. In some cases of overdose involving STRATTERA, seizures have been reported. Less commonly, there have been reports of QT prolongation and mental changes, including disorientation and hallucinations [see Clinical Pharmacology (12.2)].If an overdose occurs, consider contacting the Poison Help line (1-800-222-1222) or medical toxicologist for additional overdose management recommendations. Because atomoxetine is highly protein-bound, dialysis is not likely to be useful in the treatment of STRATTERA overdose.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

PACKAGE LABEL STRATTERA 10 mg bottle of 3030 CapsulesNDC 0002-3227-30PU 3227strattera(R) atomoxetine capsulesRx only10 mgEach capsule equivalent to 10 mg atomoxetineDo not use if Lilly inner seal is missing or broken.www.strattera.comLilly. PACKAGE LABEL STRATTERA 10 mg bottle of 30.

PEDIATRIC USE SECTION.

8.4 Pediatric Use. The safety and effectiveness of STRATTERA for the treatment of ADHD have been established in pediatric patients years of age and older. Anyone considering the use of STRATTERA in pediatric patient should balance the potential risks with the clinical need [see Boxed Warning and Warnings and Precautions (5.1, 5.3, 5.4, 5.10)].The atomoxetine pharmacokinetics in pediatric patients years of age and older were similar to those in adults.The safety and effectiveness of STRATTERA in pediatric patients less than years of age have not been established.. Juvenile Toxicity Animal DataA study was conducted in young rats to evaluate the effects of atomoxetine on growth and neurobehavioral and sexual development. Rats were treated with 1, 10, or 50 mg/kg/day (approximately 0.2, 2, and times, respectively, the maximum human dose on mg/m2 basis) of atomoxetine given by gavage from the early postnatal period (Day 10 of age) through adulthood. Slight delays in onset of vaginal patency (all doses) and preputial separation (10 and 50 mg/kg), slight decreases in epididymal weight and sperm number (10 and 50 mg/kg), and slight decrease in corpora lutea (50 mg/kg) were seen, but there were no effects on fertility or reproductive performance. slight delay in onset of incisor eruption was seen at 50 mg/kg. slight increase in motor activity was seen on Day 15 (males at 10 and 50 mg/kg and females at 50 mg/kg) and on Day 30 (females at 50 mg/kg) but not on Day 60 of age. There were no effects on learning and memory tests. The significance of these findings to humans is unknown.

PHARMACODYNAMICS SECTION.

12.2 Pharmacodynamics. An exposure-response analysis of STRATTERA (0.5, 1.2 or 1.8 mg/kg/day) or placebo demonstrated atomoxetine exposure correlates with efficacy as measured by the ADHD Rating Scale-IV-Parent Version: Investigator administered and scored. The exposure-efficacy relationship was similar to that observed between STRATTERA dosage and efficacy with median atomoxetine exposures at the two highest doses resulting in near maximal changes from baseline [see Clinical Studies (14.2)].. Cardiac ElectrophysiologyThe effect of STRATTERA on QTc interval prolongation was evaluated in randomized, double-blinded, positive-(moxifloxacin 400 mg) and placebo-controlled, cross-over study in healthy male CYP2D6 poor metabolizers. total of 120 healthy subjects were administered STRATTERA (20 mg and 60 mg) twice daily for 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 slight increase in QTc interval with increased atomoxetine concentration.. Pharmacodynamic Drug Interaction StudiesConsumption of ethanol with STRATTERA did not change the intoxicating effects of ethanol.Concomitant use of STRATTERA with methylphenidate did not increase cardiovascular effects beyond those seen with methylphenidate alone.Albuterol 600 mcg given intravenously over hours (albuterol is not approved for intravenous use) induced heart rate and blood pressure increases; these effects were potentiated when co-administered with STRATTERA (60 mg twice daily for days), particularly initially [see Drug Interactions (7)]. Consumption of ethanol with STRATTERA did not change the intoxicating effects of ethanol.. Concomitant use of STRATTERA with methylphenidate did not increase cardiovascular effects beyond those seen with methylphenidate alone.. Albuterol 600 mcg given intravenously over hours (albuterol is not approved for intravenous use) induced heart rate and blood pressure increases; these effects were potentiated when co-administered with STRATTERA (60 mg twice daily for days), particularly initially [see Drug Interactions (7)].

PHARMACOGENOMICS SECTION.

12.5 Pharmacogenomics. Atomoxetine is metabolized by CYP2D6 [see Clinical Pharmacology (12.3)]. The gene encoding CYP2D6 has variants that affect CYP2D6 metabolic function. CYP2D6 poor metabolizers are individuals with two nonfunctional alleles (e.g., CYP2D65/5), and as result have no CYP2D6 enzyme activity.Atomoxetine AUC was approximately 10-fold higher and atomoxetine Css, max was approximately 5-fold higher in CYP2D6 poor metabolizers compared to other CYP2D6 metabolizer types [see Dosage and Administration (2.5), Warnings and Precautions (5.4), Use in Specific Populations (8.7), and Clinical Pharmacology (12.3)]. In this analysis, other CYP2D6 metabolizer types were defined as individuals who were not CYP2D6 poor metabolizers and included CYP2D6 ultrarapid, normal, and intermediate metabolizers (e.g., CYP2D61/2xN, CYP2D61/1, CYP2D61/5, respectively).

PHARMACOKINETICS SECTION.

12.3 Pharmacokinetics. Pharmacokinetic parameters for atomoxetine and its metabolites in CYP2D6 poor metabolizers and other CYP2D6 metabolizer types (ultrarapid, normal, and intermediate) are presented in Table 9.Table 9: Atomoxetine and Metabolite Pharmacokinetics in Adult CYP2D6 Poor Metabolizers and Other CYP2D6 Metabolizer TypesAbbreviations: Cmax,ss= maximum atomoxetine plasma concentration at steady state; Tmax time to peak concentrationa In this analysis, other CYP2D6 metabolizer types were defined as individuals who were 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., CYP2D63/4, CYP2D65/5), and as result no CYP2D6 enzyme activity.c Primarily formed by CYP2D6.The major oxidative metabolite formed, regardless of CYP2D6 metabolizer type, and is further glucuronidated. 4-Hydroxyatomoxetine is equipotent to atomoxetine as an inhibitor of the norepinephrine transporter.d 4-hydroxyatomoxetine is formed at 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.ParameterOther CYP2D6 Metabolizer TypesaCYP2D6 Poor MetabolizersbAbsorptionDose proportionality10-120 mgAccumulation1.1-fold3.3-foldAbsolute bioavailability63%94%Tmax median1 hour2.5 hourEffect of FoodAUC: Unchanged; Cmax: Decreased 37%; Tmax: Delayed hoursDistributionProtein Binding98%Volume of distribution0.85 L/kgEliminationAtomoxetine half-life5.2 hours21.6 hoursAtomoxetine apparent oral clearance0.35 L/hr/kg0.03 L/hr/kg4-Hydroxyatomoxetine half-life6 to hours--N-Desmethylatomoxetine half-life6 to hours34 to 40 hoursMetabolismPrimary metabolic pathwaysCYP2D6Other CYP enzymes4-Hydroxyatomoxetinec concentration1% of atomoxetine0.1% of atomoxetined N-Desmethylatomoxetinee concentration5% of atomoxetine45% of atomoxetineExcretionUrineGreater than 80% of the administered dose excreted as 4-hydroxyatomoxetine-O-glucuronide; Less than 3% as unchanged drugFecesLess than 17% of the administered dose. Specific Populations. Hepatic Impairment: Atomoxetine exposure (AUC) was increased in subjects with moderate (Child-Pugh Class B) (2-fold increase) and severe (Child-Pugh Class C) (4-fold increase) hepatic impairment compared to subjects 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 requiring hemodialysis) had higher systemic atomoxetine exposure (about 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 were evaluated in more than 400 pediatric patients in clinical studies, primarily using population pharmacokinetic modeling. Single-dose and steady-state individual pharmacokinetic data were also obtained in pediatric patients and adults. When STRATTERA doses were normalized to mg/kg basis, similar half- life, Cmax, 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. Clinical Studies:. Strong CYP2D6 Inhibitors: Concomitant use of STRATTERA (20 mg BID for days) with paroxetine (20 mg QD for 17 days), known inhibitor of CYP2D6, in subjects who were not CYP2D6 poor metabolizers resulted in 6.5-fold higher plasma exposure (AUC) to atomoxetine at steady state.Concomitant use of STRATTERA (at sequential dosing of 10, 45, and 75 mg BID for up to days of each dosage) with fluoxetine (20 mg QD for 36 days) 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 STRATTERA alone.After concomitant use of STRATTERA with paroxetine or fluoxetine, the Css, max of atomoxetine was about 3-to 4-fold greater than the use of STRATTERA alone [see Drug Interactions (7)]. CYP3A Substrates: Concomitant use of STRATTERA (60 mg twice daily for 12 days) with midazolam (CYP3A substrate) (single dose of mg), resulted in 15% increase in the midazolam AUC. This pharmacokinetic change is not clinically significant.. CYP2D6 Substrates: Concomitant use of STRATTERA (40 or 60 mg twice daily for 13 days) with desipramine, (CYP2D6 substrate) (single dose of 50 mg), did not alter the desipramine pharmacokinetics.. Drugs that Affect Gastric pH: Drugs that elevate gastric pH had no effect on atomoxetine bioavailability.. In Vitro Studies:. Drugs Highly Bound to Plasma Protein: In vitro drug-displacement studies were conducted with atomoxetine and other drugs highly bound to plasma protein at therapeutic atomoxetine concentrations. Atomoxetine did not affect the binding of warfarin, acetylsalicylic acid, phenytoin, or diazepam to human albumin. Similarly, warfarin, acetylsalicylic acid, phenytoin, or diazepam did not affect the binding of atomoxetine to human albumin.. CYP Inhibition/induction: Atomoxetine did not cause clinically important inhibition or induction of cytochrome P450 enzymes (including CYP1A2, CYP3A, CYP2D6, and CYP2C9).

POSTMARKETING EXPERIENCE SECTION.

6.2 Postmarketing Experience. The following adverse reactions have been identified during post approval use of STRATTERA. Unless otherwise specified, these adverse reactions have occurred in adults and pediatric patients. Because these reactions are reported voluntarily from population of uncertain size, it is not always possible to reliably estimate their frequency or establish causal relationship to drug exposure.Cardiovascular system: QT prolongation, syncope.Peripheral vascular effects: Raynauds phenomenon.General disorders and administration site conditions: Lethargy.Musculoskeletal system: Rhabdomyolysis.Nervous system disorders: Hypoaesthesia; paraesthesia in pediatric patients; sensory disturbances; tics.Psychiatric disorders: Depression and depressed mood; anxiety, libido changes.Seizures: Seizures have been reported and included patients with pre-existing seizure disorders, those with identified risk factors for seizures, and patients with neither history of nor identified risk factors for seizures. The exact relationship between STRATTERA and seizures is difficult to evaluate due to uncertainty about the background risk of seizures in ADHD patients.Skin and subcutaneous tissue disorders: Alopecia, hyperhidrosis.Urogenital system: Male pelvic pain; urinary hesitation in pediatric patients; urinary retention in pediatric patients.. Cardiovascular system: QT prolongation, syncope.. Peripheral vascular effects: Raynauds phenomenon.. General disorders and administration site conditions: Lethargy.. Musculoskeletal system: Rhabdomyolysis.. Nervous system disorders: Hypoaesthesia; paraesthesia in pediatric patients; sensory disturbances; tics.. Psychiatric disorders: Depression and depressed mood; anxiety, libido changes.. Seizures: Seizures have been reported and included patients with pre-existing seizure disorders, those with identified risk factors for seizures, and patients with neither history of nor identified risk factors for seizures. The exact relationship between STRATTERA and seizures is difficult to evaluate due to uncertainty about the background risk of seizures in ADHD patients.. Skin and subcutaneous tissue disorders: Alopecia, hyperhidrosis.. Urogenital system: Male pelvic pain; urinary hesitation in pediatric patients; urinary retention in pediatric patients.

PREGNANCY SECTION.

8.1 Pregnancy. Pregnancy Exposure RegistryThere is pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ADHD drugs, including STRATTERA, 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 SummaryAvailable published studies with STRATTERA use in pregnant women are insufficient to establish 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 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) times and 0.4 times the human plasma levels in other CYP2D6 metabolizer types (ultrarapid, normal, and intermediate) and poor metabolizers receiving the maximum recommended human dose (MRHD), respectively. In rats dosed prior to mating and during organogenesis decrease in fetal weight (female only) and an increase in the incidence of incomplete ossification of the vertebral arch in fetuses were observed at dose approximately times the MRHD on mg/m2 basis. In one of 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 5-6 times the MRHD on mg/m2 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 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 2-4% and 15-20%, 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 of studies, 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 mg/m2 basis; plasma levels (AUC) of atomoxetine at this dose in rabbits are estimated to be 3.3 times (other CYP2D6 metabolizer types) or 0.4 times (CYP2D6 poor metabolizers) those in humans receiving the MRHD.Rats were treated with up to approximately 50 mg/kg/day of atomoxetine (approximately times the MRHD on mg/m2 basis) in the diet from weeks (females) or 10 weeks (males) prior to mating through the periods of organogenesis and lactation. In of 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 study in which rats were treated with atomoxetine in the diet from weeks (females) or 10 weeks (males) prior to mating throughout the period of organogenesis, decrease in fetal weight (female only) and an increase in the incidence of incomplete ossification of the vertebral arch in fetuses were observed at 40 mg/kg/day (approximately times the MRHD on mg/m2 basis) but not at 20 mg/kg/day.No adverse fetal effects were seen when pregnant rats were treated with up to 150 mg/kg/day (approximately 17 times the MRHD on mg/m2 basis) by gavage throughout the period of organogenesis.

SPL MEDGUIDE SECTION.

This Medication Guide has been approved by the U.S. Food and Drug Administration.Revised: 06/2026STR-0002-MG-20260629MEDICATION GUIDESTRATTERA(R) (Stra-TAIR-a)(atomoxetine) capsulesfor oral useWhat is the most important information should know about STRATTERASTRATTERA can cause serious side effects, including:Suicidal thoughts and actions in children years of age and older. STRATTERA can increase the risk of suicidal thoughts and actions in children ages and older with attention deficit hyperactivity disorder (ADHD), especially within the first few months of treatment or when the dose is changed.How can watch for and try to prevent suicidal thoughts and actions Pay close attention to, and tell your healthcare provider right away about, any changes, especially sudden changes, in mood, behavior, actions, thoughts, or feelings, or suicidal thoughts or actions. This is very important when STRATTERA is started or when the dose is changed.Keep all follow-up visits with the healthcare provider as scheduled. Tell your healthcare provider about symptoms between visits as needed, especially if you have concerns. Tell your healthcare provider right away if any of the following symptoms develop during treatment, especially if they are new, worse, or worry you: anxietytrouble sleepingacting aggressiveextreme increase in activity or talking (mania)unusual decrease in activity (hypomania)feeling agitated or restlessirritabilityimpulsivitydepressionpanic attacksrestlessness or feeling like you have to movepanic attackshostility or being angry or violentsuicide attemptsthoughts about suicide or dyingother unusual changes in mood or behavior See What are the possible side effects of STRATTERA for more information about side effects.What is STRATTERASTRATTERA is prescription medicine used to treat ADHD in adults and children years of age and older. STRATTERA may help increase attention and decrease impulsiveness and hyperactivity in people with ADHD.STRATTERA should be used as part of total treatment program for ADHD that may include counseling or other therapies.It is not known if STRATTERA is safe and effective in children less than years old.Who should not take STRATTERADo not take STRATTERA if you or your child:are allergic to atomoxetine or any of the ingredients in STRATTERA. See the end of this Medication Guide for complete list of ingredients in STRATTERA.are taking or have stopped taking within the past 14 days medicine called monoamine oxidase inhibitor (MAOI).have an eye problem called narrow angle glaucoma.have or had rare tumor called pheochromocytoma.have severe heart or blood vessel problems that could get worse if your blood pressure or heart rate increases.Before taking STRATTERA, tell your healthcare provider about all medical conditions, including if you or your child:have, or have family history of, suicide thoughts or attempts, bipolar disorder, depression, mania, or hypomania.have liver problems.have, or have family history of, heart problems, heart defects, irregular heartbeat, or sudden death.have high blood pressure or low blood pressure.have problems urinating such as trouble starting urination, weak stream, or not fully emptying the bladder.have glaucoma.are pregnant or plan to become pregnant. It is not known if STRATTERA will harm the unborn baby.Tell your healthcare provider right away if you or your child become pregnant or plan to become pregnant during treatment with STRATTERA.There is pregnancy exposure registry for women who are exposed to ADHD medicines, including STRATTERA, during pregnancy. The purpose of the registry is to collect information about the health of women exposed to STRATTERA and their baby. If you or your child become pregnant during treatment with STRATTERA, talk to your healthcare provider about registering with the National Pregnancy Registry of ADHD Medications at 1-866-961-2388 or visit online at https://womensmentalhealth.org/adhdmedications/. are breastfeeding or plan to breastfeed. It is not known if STRATTERA passes into the breast milk. Talk to your healthcare provider about the best way to feed the baby during treatment with STRATTERA.Tell your healthcare provider about all the medicines that you or your child take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. STRATTERA and some medicines may interact with each other and cause serious side effects. Your healthcare provider will decide whether STRATTERA can be taken with other medicines. Especially tell your healthcare provider if you or your child take: MAOI, including linezolid and intravenous methylene bluemedicines that increase or decrease blood pressureasthma medicines Know the medicines you or your child take. Keep list of your medicines to show your healthcare provider and pharmacist. Do not start any new medicines during treatment with STRATTERA without talking to your healthcare provider first. How should take STRATTERATake STRATTERA exactly as your healthcare provider tells you. Your healthcare provider may adjust the dose until it is right for you or your child.Take STRATTERA with or without food.Swallow STRATTERA capsules whole. Do not open the capsules.STRATTERA is usually taken time day in the morning, or times day, in the morning and in the late afternoon or early evening.If you miss dose of STRATTERA, take the dose as soon as possible. Do not take more STRATTERA than your healthcare provider prescribes in 24-hour period.If you take too much STRATTERA, call your healthcare provider or Poison Help line at 1-800-222-1222 or go to the nearest emergency room right away.What should avoid while taking STRATTERADo not drive or operate heavy machinery until you know how STRATTERA affects you. STRATTERA can cause sleepiness.Do not get STRATTERA in or near the eyes. STRATTERA can irritate the eyes. If STRATTERA gets into the eyes, rinse them with water right away and tell your healthcare provider. If capsule breaks, avoid touching the contents and wash your hands and any surfaces that they come in contact with as soon as possible.What are possible side effects of STRATTERASTRATTERA can cause serious side effects, including:See What is the most important information should know about STRATTERASevere liver damage. Your healthcare provider will check the blood levels of liver enzymes if symptoms of liver damage develop. Tell your healthcare provider right away if any of the following symptoms develop at any time during treatment:itchingthe skin or the white part of the eyes turns yellowright upper stomach painunexplained flu-like symptomsdark urine Serious heart-related side effects. STRATTERA may increase the risk of serious heart problems including sudden death, heart attack, and stroke in adults and children who have serious heart problems or heart defects. Your healthcare provider should check for heart problems before starting treatment with STRATTERA. Stop taking STRATTERA and tell your healthcare provider or get medical help right away if any of the following symptoms develop during treatment: chest painloss of consciousness (fainting)shortness of breathheart palpitations or fast heart ratenumbness of weakness, especially on one side of the bodyslurred speechvision changessevere headache Increases in blood pressure and heart rate. Your healthcare provider should check blood pressure and heart rate before starting treatment, if the dose is increased, and as needed during treatment.New psychotic problems, manic symptoms, or mania episodes. People with bipolar disorder, or who have higher risk of developing bipolar disorder, have an increased risk of developing mania. Tell your healthcare provider if any of the following symptoms develop during treatment: greatly increased energyracing thoughtsunusually grand ideastalking more or faster than usualunusual decrease in activitysevere trouble sleepingreckless behaviorexcessive happiness or irritabilityseeing or hearing things that are not real (hallucinations)depression Aggressive behavior or hostility. New or worsening aggressive behavior or hostility can happen during treatment.Allergic reactions. Tell your healthcare provider right away if trouble breathing, hives, rash, or swelling of the face, eyes, lips, or throat develop during treatment.Problems with urination. STRATTERA may cause problems with urination including decreased urine flow or trouble starting urination (urinary hesitation) or being unable to pass any urine (urinary retention). Tell your healthcare provider if any problems with urination develop during treatment.Painful and prolonged erections (priapism). Priapism has happened in male children and adults who take STRATTERA. Priapism is serious problem that can cause lasting damage to the penis and may require surgery. Tell your healthcare provider and get medical help right away if you or your child develop priapism during treatment.Effect on growth (height and weight) in children. Children should have their height and weight checked often during treatment.The most common side effects of STRATTERA in children include:nauseavomitingtirednessdecreased appetitestomach (abdominal) painsleepinessThe most common side effects of STRATTERA in adults include:constipationdry mouthnauseadecreased appetitedizzinesserectile dysfunctionurinary hesitationSTRATTERA may cause sexual problems (dysfunction). Talk to your healthcare provider if any of the following symptoms develop:Symptoms in males may include:delayed ejaculation or inability to have an ejaculationdecreased sex driveproblems getting or keeping an erectionSymptoms in females may include:decreased sex drivedelayed orgasm or inability to have an orgasmYour healthcare provider may stop STRATTERA treatment if serious side effects develop during treatment.These are not all of the possible side effects STRATTERA. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.How should store STRATTERAStore STRATTERA at room temperature between 59 to 86F (15 to 30C).Keep STRATTERA and all medicines out of the reach of children.General information about safe and effective use of STRATTERA.Medicines are sometimes prescribed for purposes other than those listed in Medication Guide. Do not use STRATTERA for condition for which it was not prescribed. Do not give STRATTERA to other people, even if they have the same condition. It may harm them. You can ask your pharmacist or healthcare provider for information about STRATTERA that is written for health professionals.What are the ingredients in STRATTERAActive ingredient: atomoxetine hydrochloride. Inactive ingredients: Capsules contain pregelatinized starch and dimethicone. Capsule shells contain gelatin, sodium lauryl sulfate, and or more of the following inactive ingredients: FD&C Blue No. 2, synthetic yellow iron oxide, titanium dioxide, and red iron oxide. Capsules are imprinted with edible black ink.Marketed by: Lilly USA, LLCIndianapolis, IN 46285, USACopyright (C) 2003, 2026, Eli Lilly and Company. All rights reserved.For more information about Strattera, go to www.strattera.com or call 1-800-545-5979.. Suicidal thoughts and actions in children years of age and older. STRATTERA can increase the risk of suicidal thoughts and actions in children ages and older with attention deficit hyperactivity disorder (ADHD), especially within the first few months of treatment or when the dose is changed.How can watch for and try to prevent suicidal thoughts and actions Pay close attention to, and tell your healthcare provider right away about, any changes, especially sudden changes, in mood, behavior, actions, thoughts, or feelings, or suicidal thoughts or actions. This is very important when STRATTERA is started or when the dose is changed.Keep all follow-up visits with the healthcare provider as scheduled. Tell your healthcare provider about symptoms between visits as needed, especially if you have concerns. Tell your healthcare provider right away if any of the following symptoms develop during treatment, especially if they are new, worse, or worry you: anxietytrouble sleepingacting aggressiveextreme increase in activity or talking (mania)unusual decrease in activity (hypomania)feeling agitated or restlessirritabilityimpulsivitydepressionpanic attacksrestlessness or feeling like you have to movepanic attackshostility or being angry or violentsuicide attemptsthoughts about suicide or dyingother unusual changes in mood or behavior Pay close attention to, and tell your healthcare provider right away about, any changes, especially sudden changes, in mood, behavior, actions, thoughts, or feelings, or suicidal thoughts or actions. This is very important when STRATTERA is started or when the dose is changed.. Keep all follow-up visits with the healthcare provider as scheduled. Tell your healthcare provider about symptoms between visits as needed, especially if you have concerns.. anxiety. trouble sleeping. acting aggressive. extreme increase in activity or talking (mania). unusual decrease in activity (hypomania). feeling agitated or restless. irritability. impulsivity. depression. panic attacks. restlessness or feeling like you have to move. panic attacks. hostility or being angry or violent. suicide attempts. thoughts about suicide or dying. other unusual changes in mood or behavior. are allergic to atomoxetine or any of the ingredients in STRATTERA. See the end of this Medication Guide for complete list of ingredients in STRATTERA.. are taking or have stopped taking within the past 14 days medicine called monoamine oxidase inhibitor (MAOI).. have an eye problem called narrow angle glaucoma.. have or had rare tumor called pheochromocytoma.. have severe heart or blood vessel problems that could get worse if your blood pressure or heart rate increases.. have, or have family history of, suicide thoughts or attempts, bipolar disorder, depression, mania, or hypomania.. have liver problems.. have, or have family history of, heart problems, heart defects, irregular heartbeat, or sudden death.. have high blood pressure or low blood pressure.. have problems urinating such as trouble starting urination, weak stream, or not fully emptying the bladder.. have glaucoma.. are pregnant or plan to become pregnant. It is not known if STRATTERA will harm the unborn baby.Tell your healthcare provider right away if you or your child become pregnant or plan to become pregnant during treatment with STRATTERA.There is pregnancy exposure registry for women who are exposed to ADHD medicines, including STRATTERA, during pregnancy. The purpose of the registry is to collect information about the health of women exposed to STRATTERA and their baby. If you or your child become pregnant during treatment with STRATTERA, talk to your healthcare provider about registering with the National Pregnancy Registry of ADHD Medications at 1-866-961-2388 or visit online at https://womensmentalhealth.org/adhdmedications/. Tell your healthcare provider right away if you or your child become pregnant or plan to become pregnant during treatment with STRATTERA.. There is pregnancy exposure registry for women who are exposed to ADHD medicines, including STRATTERA, during pregnancy. The purpose of the registry is to collect information about the health of women exposed to STRATTERA and their baby. If you or your child become pregnant during treatment with STRATTERA, talk to your healthcare provider about registering with the National Pregnancy Registry of ADHD Medications at 1-866-961-2388 or visit online at https://womensmentalhealth.org/adhdmedications/.. are breastfeeding or plan to breastfeed. It is not known if STRATTERA passes into the breast milk. Talk to your healthcare provider about the best way to feed the baby during treatment with STRATTERA.. MAOI, including linezolid and intravenous methylene blue. medicines that increase or decrease blood pressure. asthma medicines. Take STRATTERA exactly as your healthcare provider tells you. Your healthcare provider may adjust the dose until it is right for you or your child.. Take STRATTERA with or without food.. Swallow STRATTERA capsules whole. Do not open the capsules.. STRATTERA is usually taken time day in the morning, or times day, in the morning and in the late afternoon or early evening.. If you miss dose of STRATTERA, take the dose as soon as possible. Do not take more STRATTERA than your healthcare provider prescribes in 24-hour period.. If you take too much STRATTERA, call your healthcare provider or Poison Help line at 1-800-222-1222 or go to the nearest emergency room right away.. Do not drive or operate heavy machinery until you know how STRATTERA affects you. STRATTERA can cause sleepiness.. Do not get STRATTERA in or near the eyes. STRATTERA can irritate the eyes. If STRATTERA gets into the eyes, rinse them with water right away and tell your healthcare provider. If capsule breaks, avoid touching the contents and wash your hands and any surfaces that they come in contact with as soon as possible.. See What is the most important information should know about STRATTERA. Severe liver damage. Your healthcare provider will check the blood levels of liver enzymes if symptoms of liver damage develop. Tell your healthcare provider right away if any of the following symptoms develop at any time during treatment:itchingthe skin or the white part of the eyes turns yellowright upper stomach painunexplained flu-like symptomsdark urine itching. the skin or the white part of the eyes turns yellow. right upper stomach pain. unexplained flu-like symptoms. dark urine. Serious heart-related side effects. STRATTERA may increase the risk of serious heart problems including sudden death, heart attack, and stroke in adults and children who have serious heart problems or heart defects. Your healthcare provider should check for heart problems before starting treatment with STRATTERA. Stop taking STRATTERA and tell your healthcare provider or get medical help right away if any of the following symptoms develop during treatment: chest painloss of consciousness (fainting)shortness of breathheart palpitations or fast heart ratenumbness of weakness, especially on one side of the bodyslurred speechvision changessevere headache chest pain. loss of consciousness (fainting). shortness of breath. heart palpitations or fast heart rate. numbness of weakness, especially on one side of the body. slurred speech. vision changes. severe headache. Increases in blood pressure and heart rate. Your healthcare provider should check blood pressure and heart rate before starting treatment, if the dose is increased, and as needed during treatment.. New psychotic problems, manic symptoms, or mania episodes. People with bipolar disorder, or who have higher risk of developing bipolar disorder, have an increased risk of developing mania. Tell your healthcare provider if any of the following symptoms develop during treatment: greatly increased energyracing thoughtsunusually grand ideastalking more or faster than usualunusual decrease in activitysevere trouble sleepingreckless behaviorexcessive happiness or irritabilityseeing or hearing things that are not real (hallucinations)depression greatly increased energy. racing thoughts. unusually grand ideas. talking more or faster than usual. unusual decrease in activity. severe trouble sleeping. reckless behavior. excessive happiness or irritability. seeing or hearing things that are not real (hallucinations). depression. Aggressive behavior or hostility. New or worsening aggressive behavior or hostility can happen during treatment.. Allergic reactions. Tell your healthcare provider right away if trouble breathing, hives, rash, or swelling of the face, eyes, lips, or throat develop during treatment.. Problems with urination. STRATTERA may cause problems with urination including decreased urine flow or trouble starting urination (urinary hesitation) or being unable to pass any urine (urinary retention). Tell your healthcare provider if any problems with urination develop during treatment.. Painful and prolonged erections (priapism). Priapism has happened in male children and adults who take STRATTERA. Priapism is serious problem that can cause lasting damage to the penis and may require surgery. Tell your healthcare provider and get medical help right away if you or your child develop priapism during treatment.. Effect on growth (height and weight) in children. Children should have their height and weight checked often during treatment.. nausea. vomiting. tiredness. decreased appetite. stomach (abdominal) pain. sleepiness. constipation. dry mouth. nausea. decreased appetite. dizziness. erectile dysfunction. urinary hesitation. delayed ejaculation or inability to have an ejaculation. decreased sex drive. problems getting or keeping an erection. decreased sex drive. delayed orgasm or inability to have an orgasm. Store STRATTERA at room temperature between 59 to 86F (15 to 30C).. Keep STRATTERA and all medicines out of the reach of children.

SPL UNCLASSIFIED SECTION.

2.1 Recommendations Prior to Initiating STRATTERA Treatment. Prior to initiating treatment with STRATTERA, screen patients for personal or family history of bipolar disorder, mania, or hypomania [see Warnings and Precautions (5.6)].

STORAGE AND HANDLING SECTION.

16.2 Storage and Handling. Store at 25C (77F); excursions permitted to 15 to 30C (59 to 86F) [see USP Controlled Room Temperature].

USE IN SPECIFIC POPULATIONS SECTION.

8 USE IN SPECIFIC POPULATIONS. Hepatic Impairment: Increased exposure (AUC) to atomoxetine in subjects with moderate (Child-Pugh Class B) (2-fold increase) and severe (Child-Pugh Class C) (4-fold increase) compared to subjects with normal liver function. (8.6 and 12.3)Use in Genomic Subgroups: CYP2D6 poor metabolizers have higher systemic exposures which may increase the risks of STRATTERA-related adverse reactions compared to other CYP2D6 metabolizer types (ultrarapid, normal, and intermediate) (8.7). Hepatic Impairment: Increased exposure (AUC) to atomoxetine in subjects with moderate (Child-Pugh Class B) (2-fold increase) and severe (Child-Pugh Class C) (4-fold increase) compared to subjects with normal liver function. (8.6 and 12.3). Use in Genomic Subgroups: CYP2D6 poor metabolizers have higher systemic exposures which may increase the risks of STRATTERA-related adverse reactions compared to other CYP2D6 metabolizer types (ultrarapid, normal, and intermediate) (8.7). 8.1 Pregnancy. Pregnancy Exposure RegistryThere is pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ADHD drugs, including STRATTERA, 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 SummaryAvailable published studies with STRATTERA use in pregnant women are insufficient to establish 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 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) times and 0.4 times the human plasma levels in other CYP2D6 metabolizer types (ultrarapid, normal, and intermediate) and poor metabolizers receiving the maximum recommended human dose (MRHD), respectively. In rats dosed prior to mating and during organogenesis decrease in fetal weight (female only) and an increase in the incidence of incomplete ossification of the vertebral arch in fetuses were observed at dose approximately times the MRHD on mg/m2 basis. In one of 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 5-6 times the MRHD on mg/m2 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 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 2-4% and 15-20%, 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 of studies, 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 mg/m2 basis; plasma levels (AUC) of atomoxetine at this dose in rabbits are estimated to be 3.3 times (other CYP2D6 metabolizer types) or 0.4 times (CYP2D6 poor metabolizers) those in humans receiving the MRHD.Rats were treated with up to approximately 50 mg/kg/day of atomoxetine (approximately times the MRHD on mg/m2 basis) in the diet from weeks (females) or 10 weeks (males) prior to mating through the periods of organogenesis and lactation. In of 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 study in which rats were treated with atomoxetine in the diet from weeks (females) or 10 weeks (males) prior to mating throughout the period of organogenesis, decrease in fetal weight (female only) and an increase in the incidence of incomplete ossification of the vertebral arch in fetuses were observed at 40 mg/kg/day (approximately times the MRHD on mg/m2 basis) but not at 20 mg/kg/day.No adverse fetal effects were seen when pregnant rats were treated with up to 150 mg/kg/day (approximately 17 times the MRHD on mg/m2 basis) by gavage throughout the period of organogenesis.. 8.2 Lactation. Risk SummaryThere are no data on the presence of atomoxetine or its metabolite in human milk, the effects on the breastfed child, or the effects on milk production. Atomoxetine is present in animal milk. When drug is present in animal milk, it is likely that the drug will be present in human milk.The developmental and health benefits of breastfeeding should be considered along with the mothers clinical need for STRATTERA and any potential adverse effects on the breastfed child from STRATTERA or from the underlying maternal condition.. 8.4 Pediatric Use. The safety and effectiveness of STRATTERA for the treatment of ADHD have been established in pediatric patients years of age and older. Anyone considering the use of STRATTERA in pediatric patient should balance the potential risks with the clinical need [see Boxed Warning and Warnings and Precautions (5.1, 5.3, 5.4, 5.10)].The atomoxetine pharmacokinetics in pediatric patients years of age and older were similar to those in adults.The safety and effectiveness of STRATTERA in pediatric patients less than years of age have not been established.. Juvenile Toxicity Animal DataA study was conducted in young rats to evaluate the effects of atomoxetine on growth and neurobehavioral and sexual development. Rats were treated with 1, 10, or 50 mg/kg/day (approximately 0.2, 2, and times, respectively, the maximum human dose on mg/m2 basis) of atomoxetine given by gavage from the early postnatal period (Day 10 of age) through adulthood. Slight delays in onset of vaginal patency (all doses) and preputial separation (10 and 50 mg/kg), slight decreases in epididymal weight and sperm number (10 and 50 mg/kg), and slight decrease in corpora lutea (50 mg/kg) were seen, but there were no effects on fertility or reproductive performance. slight delay in onset of incisor eruption was seen at 50 mg/kg. slight increase in motor activity was seen on Day 15 (males at 10 and 50 mg/kg and females at 50 mg/kg) and on Day 30 (females at 50 mg/kg) but not on Day 60 of age. There were no effects on learning and memory tests. The significance of these findings to humans is unknown.. 8.5 Geriatric Use. The safety, efficacy and pharmacokinetics of STRATTERA in geriatric patients have not been evaluated. Clinical studies of STRATTERA did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently from younger adult patients.. 8.6 Patients with Hepatic Impairment. Compared with patients with normal hepatic function atomoxetine exposure (AUC) was increased in patients with moderate (Child- Pugh Class B) (2-fold increase) and in patients with severe hepatic impairment (Child-Pugh Class C) (4-fold increase). The recommended dosage in patients with moderate or severe hepatic impairment is lower than in patients with normal hepatic function [see Dosage and Administration (2.4) and Clinical Pharmacology (12.3)].. 8.7 Use in Genomic Subgroups. The recommended titration interval (before increasing the STRATTERA dosage) is longer in CYP2D6 poor metabolizers than other CYP2D6 metabolizer types (ultrarapid, normal, and intermediate) [see Dosage and Administration (2.5)].Atomoxetine plasma concentrations were higher in CYP2D6 poor metabolizers which may increase the risk of STRATTERA-related adverse reactions. In pediatric and adult patients, the mean heart rate was higher in CYP2D6 poor metabolizers compared to other CYP2D6 metabolizer types. In adult patients, the mean change from baseline in diastolic and systolic blood pressure was higher in CYP2D6 poor metabolizers compared to other CYP2D6 metabolizer types [see Warnings and Precautions (5.4), Clinical Pharmacology (12.3, 12.5)].The prevalence of CYP2D6 poor metabolizers is approximately 7% in White populations, 2% in Asian populations, and 2% in Black or African American populations.

WARNINGS AND PRECAUTIONS SECTION.

5 WARNINGS AND PRECAUTIONS. Severe Liver Injury: STRATTERA should be discontinued and not restarted in patients with jaundice or laboratory evidence of liver injury. (5.2)Serious Cardiovascular Reactions: Prior to STRATTERA treatment, patients should have careful history and physical exam to assess for presence of cardiovascular (CV) disease. STRATTERA generally should not be used in pediatric patients with known serious cardiac abnormalities, cardiomyopathy, serious arrhythmias. Consideration should be given to not using STRATTERA in adults with clinically significant cardiac abnormalities. Patients who develop symptoms suggestive of cardiac disease during STRATTERA treatment should stop STRATTERA and undergo prompt cardiac evaluation. (5.3)Increase in Blood Pressure and Heart Rate: Heart rate and blood pressure should be measured at baseline, following STRATTERA dosage increase, and periodically while on therapy. (5.4)New Psychotic or Manic Symptoms and Activation of Mania: If psychotic or manic symptoms occur, consider discontinuing STRATTERA. (5.5)Aggressive Behavior or Hostility: Monitor for the appearance or worsening of aggressive behavior or hostility. (5.7)Effects on Urine Outflow: Urinary retention or hesitancy may occur. (5.9)Priapism: Prompt medical attention is required in the event of suspected priapism. (5.10)Effect on Growth in Pediatric Patients: Closely monitor growth (e.g., weight, height) in pediatric patients. (5.11). Severe Liver Injury: STRATTERA should be discontinued and not restarted in patients with jaundice or laboratory evidence of liver injury. (5.2). Serious Cardiovascular Reactions: Prior to STRATTERA treatment, patients should have careful history and physical exam to assess for presence of cardiovascular (CV) disease. STRATTERA generally should not be used in pediatric patients with known serious cardiac abnormalities, cardiomyopathy, serious arrhythmias. Consideration should be given to not using STRATTERA in adults with clinically significant cardiac abnormalities. Patients who develop symptoms suggestive of cardiac disease during STRATTERA treatment should stop STRATTERA and undergo prompt cardiac evaluation. (5.3). Increase in Blood Pressure and Heart Rate: Heart rate and blood pressure should be measured at baseline, following STRATTERA dosage increase, and periodically while on therapy. (5.4). New Psychotic or Manic Symptoms and Activation of Mania: If psychotic or manic symptoms occur, consider discontinuing STRATTERA. (5.5). Aggressive Behavior or Hostility: Monitor for the appearance or worsening of aggressive behavior or hostility. (5.7). Effects on Urine Outflow: Urinary retention or hesitancy may occur. (5.9). Priapism: Prompt medical attention is required in the event of suspected priapism. (5.10). Effect on Growth in Pediatric Patients: Closely monitor growth (e.g., weight, height) in pediatric patients. (5.11). 5.1 Suicidal Thoughts and Behaviors in Pediatric Patients Years of Age and Older. All STRATTERA-treated pediatric patients should be monitored and observed closely for clinical worsening, suicidal thoughts and behavior, and unusual changes in behavior, especially during the initial few months of STRATTERA therapy, or at times of dosage changes, either increases or decreases.Families and caregivers of STRATTERA-treated pediatric patients should be alerted about the need to monitor patients daily for the emergence of agitation, irritability, unusual changes in behavior, and mental health-related symptoms, as well as the emergence of suicidal thoughts and behavior, and to report such symptoms immediately to health care provider.Consider changing the therapeutic regimen, including stopping STRATTERA, in patients who experience emergent suicidality or symptoms that might be precursors to emerging suicidal thoughts and behavior, especially if these symptoms are severe or abrupt in onset, or were not part of the patients presenting symptoms.STRATTERA increased the risk of suicidal ideation in pediatric patients years and older with ADHD in pooled placebo-controlled short-term studies (6 to 18 weeks). In 12 studies (11 studies in patients with ADHD and study in another population) with over 2,200 pediatric patients, the mean incidence of suicidal ideation in STRATTERA-treated pediatric patients was 0.4% (5/1,357) (including one patient with suicide attempt) compared to 0% (0/851) in placebo-treated pediatric patients. No suicides occurred in these studies. All the suicidal ideations occurred in pediatric patients to 12 years of age, and all occurred during the first month of STRATTERA treatment. It is unknown whether the risk of suicidal ideation in pediatric patients extends to longer-term use. similar analysis in adult patients treated with STRATTERA for ADHD did not reveal an increased risk of suicidal ideation or behavior.The following psychiatric symptoms have been reported with STRATTERA: anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania and mania. Although causal link between the emergence of such symptoms and the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality.. All STRATTERA-treated pediatric patients should be monitored and observed closely for clinical worsening, suicidal thoughts and behavior, and unusual changes in behavior, especially during the initial few months of STRATTERA therapy, or at times of dosage changes, either increases or decreases.. Families and caregivers of STRATTERA-treated pediatric patients should be alerted about the need to monitor patients daily for the emergence of agitation, irritability, unusual changes in behavior, and mental health-related symptoms, as well as the emergence of suicidal thoughts and behavior, and to report such symptoms immediately to health care provider.. Consider changing the therapeutic regimen, including stopping STRATTERA, in patients who experience emergent suicidality or symptoms that might be precursors to emerging suicidal thoughts and behavior, especially if these symptoms are severe or abrupt in onset, or were not part of the patients presenting symptoms.. 5.2 Severe Liver Injury. STRATTERA should be discontinued and not restarted in patients with jaundice or laboratory evidence of liver injury. Liver enzyme and function tests should be obtained upon the first symptom or sign of liver dysfunction (e.g., pruritus, dark urine, jaundice, right upper quadrant tenderness, or unexplained flu like symptoms).Postmarketing reports indicate that STRATTERA can cause severe liver injury.Although no evidence of liver injury was detected in clinical trials of about 6,000 patients, there have been rare cases of clinically significant liver injury that were considered probably or possibly related to STRATTERA use during postmarketing use:Rare cases of liver failure have been reported during postmarketing use, including case that resulted in liver transplant.Reported cases of liver injury occurred within 120 days of initiation of STRATTERA in most cases and some patients presented with markedly elevated liver enzymes (>20 times upper limit of normal (ULN)), and jaundice with significantly elevated bilirubin levels (>2 times ULN), followed by recovery upon STRATTERA discontinuation. In one patient, liver injury, manifested by elevated hepatic enzymes up to 40 times ULN and jaundice with bilirubin up to 12 times ULN, recurred upon rechallenge, and was followed by recovery upon STRATTERA discontinuation, providing evidence that STRATTERA likely caused the liver injury. Such reactions may occur several months after STRATTERA is started, but laboratory abnormalities may continue to worsen for several weeks after STRATTERA is stopped.. Rare cases of liver failure have been reported during postmarketing use, including case that resulted in liver transplant.. Reported cases of liver injury occurred within 120 days of initiation of STRATTERA in most cases and some patients presented with markedly elevated liver enzymes (>20 times upper limit of normal (ULN)), and jaundice with significantly elevated bilirubin levels (>2 times ULN), followed by recovery upon STRATTERA discontinuation. In one patient, liver injury, manifested by elevated hepatic enzymes up to 40 times ULN and jaundice with bilirubin up to 12 times ULN, recurred upon rechallenge, and was followed by recovery upon STRATTERA discontinuation, providing evidence that STRATTERA likely caused the liver injury. Such reactions may occur several months after STRATTERA is started, but laboratory abnormalities may continue to worsen for several weeks after STRATTERA is stopped.. 5.3 Serious Cardiovascular Reactions. Risk Management Recommendations for Serious Cardiovascular ReactionsPrior to STRATTERA treatment, adults or pediatric patients years of age or older should have careful history (including assessment for family history of sudden death or ventricular arrhythmia) and physical exam to assess for the presence of cardiovascular disease, and should receive further cardiac evaluation if findings suggest such disease (e.g., electrocardiogram, echocardiogram).Although some serious heart problems alone carry an increased risk of sudden death, STRATTERA generally should not be used in pediatric patients with known serious structural cardiac abnormalities, cardiomyopathy, serious arrhythmias, or other serious cardiac problems.Consideration should be given to not treating adults with STRATTERA with clinically significant cardiac abnormalities.Patients who develop symptoms such as exertional chest pain, unexplained syncope, or other symptoms suggestive of cardiac disease during STRATTERA treatment should stop STRATTERA and undergo prompt cardiac evaluation.. Although some serious heart problems alone carry an increased risk of sudden death, STRATTERA generally should not be used in pediatric patients with known serious structural cardiac abnormalities, cardiomyopathy, serious arrhythmias, or other serious cardiac problems.. Consideration should be given to not treating adults with STRATTERA with clinically significant cardiac abnormalities.. Sudden Death and Pre-existing Structural Cardiac Abnormalities or Other Serious Heart Problems. Pediatric Patients Years of Age and Older: Sudden death has been reported in association with STRATTERA treatment at the recommended dosage in pediatric patients years of age and older with structural cardiac abnormalities or other serious heart problems.. Adults: Sudden deaths, stroke, and myocardial infarction have been reported in STRATTERA-treated adults at the recommended ADHD dosage. Although the role of STRATTERA in these adult cases is also unknown, adults have greater likelihood than pediatric patients of having serious structural cardiac abnormalities, cardiomyopathy, serious arrhythmias, coronary artery disease, or other serious cardiac problems.. 5.4 Increase in Blood Pressure and Heart Rate. STRATTERA is contraindicated in patients with severe cardiac or vascular disorders whose condition would be expected to deteriorate if they had clinically important increase in blood pressure or heart rate. STRATTERA should be used with caution in any condition that may predispose patients to hypotension, or conditions associated with abrupt heart rate or blood pressure changes. STRATTERA 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. Heart rate and blood pressure should be measured at baseline, following STRATTERA dosage increases, and periodically while on therapy to detect possible clinically important increases in heart rate and blood pressure.In the pediatric and adult patients in short-term, placebo-controlled clinical studies of ADHD, there were greater proportion of STRATTERA-treated patients, compared to placebo-treated patients, who had an increase in diastolic blood pressure (DBP) >=15 mm Hg, systolic blood pressure (SBP) >=20 mm Hg and heart rate >=20 bpm [see Adverse Reactions (6.1)]. Increase in Blood Pressure and Heart RateIn placebo-controlled studies of pediatric patients years of age and older with ADHD, tachycardia was identified as an adverse reaction in 0.3% (5/1,597) of STRATTERA-treated patients compared with 0% (0/934) of placebo-treated patients.In placebo-controlled adult ADHD studies, tachycardia was identified as an adverse reaction in 1.5% (8/540) of STRATTERA-treated patients compared with 0.5% (2/402) of placebo-treated patients.Orthostatic hypotension and syncope have been reported in STRATTERA-treated patients. In ADHD studies in pediatric patients years of age and older, 0.2% (12/5,596) of STRATTERA-treated patients had orthostatic hypotension and 0.8% (46/5,596) had syncope. In short-term ADHD studies in pediatric patients years of age and older, 1.8% (6/340) of STRATTERA- treated patients had orthostatic hypotension compared with 0.5% (1/207) of placebo-treated patients. Syncope was not reported during these studies.. In placebo-controlled studies of pediatric patients years of age and older with ADHD, tachycardia was identified as an adverse reaction in 0.3% (5/1,597) of STRATTERA-treated patients compared with 0% (0/934) of placebo-treated patients.. In placebo-controlled adult ADHD studies, tachycardia was identified as an adverse reaction in 1.5% (8/540) of STRATTERA-treated patients compared with 0.5% (2/402) of placebo-treated patients.. Orthostatic hypotension and syncope have been reported in STRATTERA-treated patients. In ADHD studies in pediatric patients years of age and older, 0.2% (12/5,596) of STRATTERA-treated patients had orthostatic hypotension and 0.8% (46/5,596) had syncope. In short-term ADHD studies in pediatric patients years of age and older, 1.8% (6/340) of STRATTERA- treated patients had orthostatic hypotension compared with 0.5% (1/207) of placebo-treated patients. Syncope was not reported during these studies.. Increase in Blood Pressure and Heart Rate in CYP2D6 Poor MetabolizersIn placebo-controlled studies of pediatric patients years of age and older with ADHD, the mean heart rate increase was 9.4 beats/minute in CYP2D6 poor metabolizers and was beats/minute in other CYP2D6 metabolizer types (ultrarapid, normal, and intermediate).In adult clinical trials where CYP2D6 metabolizer status was available, the mean heart rate increase in CYP2D6 poor metabolizers was significantly higher than in other CYP2D6 metabolizer types (11 beats/minute versus 7.5 beats/minute, respectively). In adult clinical trials where CYP2D6 metabolizer status was available, the mean change from baseline in DBP in CYP2D6 poor metabolizers was higher than in other CYP2D6 metabolizer types (4.2 versus 2.1 mm Hg) as was the mean change from baseline in SBP (CYP2D6 poor metabolizers: 2.8 versus other CYP2D6 metabolizer types: 2.4 mm Hg).. In placebo-controlled studies of pediatric patients years of age and older with ADHD, the mean heart rate increase was 9.4 beats/minute in CYP2D6 poor metabolizers and was beats/minute in other CYP2D6 metabolizer types (ultrarapid, normal, and intermediate).. In adult clinical trials where CYP2D6 metabolizer status was available, the mean heart rate increase in CYP2D6 poor metabolizers was significantly higher than in other CYP2D6 metabolizer types (11 beats/minute versus 7.5 beats/minute, respectively). In adult clinical trials where CYP2D6 metabolizer status was available, the mean change from baseline in DBP in CYP2D6 poor metabolizers was higher than in other CYP2D6 metabolizer types (4.2 versus 2.1 mm Hg) as was the mean change from baseline in SBP (CYP2D6 poor metabolizers: 2.8 versus other CYP2D6 metabolizer types: 2.4 mm Hg).. 5.5 New Psychotic or Manic Symptoms and Activation of Mania. If psychotic or manic symptoms occur, consider discontinuing STRATTERA.Psychotic symptoms (e.g., hallucinations, delusional thinking) manic symptoms (e.g., mania) in patients without prior history of psychotic illness or mania can be caused by STRATTERA at the recommended dosage.. 5.6 Screening Patients for Bipolar Disorder. Before initiating treatment with STRATTERA, patients should be adequately screened for risk factors for bipolar disorder such as personal or family history of mania and depression.Patients with bipolar disorder or risk factors for bipolar disorder may be at increased risk of developing mania or mixed episodes during treatment with STRATTERA. It may not be possible to determine whether manic or mixed episode that appears during treatment with STRATTERA is due to an adverse reaction to STRATTERA or patients underlying bipolar disorder.. 5.7 Aggressive Behavior or Hostility. Patients beginning treatment with STRATTERA should be monitored for the appearance or worsening of aggressive behavior or hostility.There is evidence that STRATTERA may cause the emergence or worsening of aggressive behavior or hostility. ADHD and other mental illnesses can be associated with irritability, which can make it difficult to determine if STRATTERA or the underlying psychiatric condition is causing the emergence or worsening of aggressive behavior or hostility in specific patients. If such symptoms occur during treatment, consider possible causal role of STRATTERA.. 5.8 Hypersensitivity Reactions. STRATTERA is contraindicated in patients with known hypersensitivity reaction to atomoxetine or other constituents of STRATTERA.Although uncommon, hypersensitivity reactions, including anaphylaxis, angioneurotic edema, urticaria, and rash, have been reported in STRATTERA-treated patients.. 5.9 Effects on Urine Outflow. complaint of urinary retention or urinary hesitancy should be considered potentially related to STRATTERA.In adult ADHD controlled studies, the incidence of urinary retention (1.7%, 9/540) and urinary hesitation (5.6%, 30/540) were increased among STRATTERA-treated patients compared with placebo-treated patients (0%, 0/402; 0.5%, 2/402, respectively). Two STRATTERA-treated adult patients and no placebo-treated patients discontinued from controlled clinical studies because of urinary retention.. 5.10 Priapism. Prompt medical attention is required in the event of suspected priapism in STRATTERA-treated patients.Rare postmarketing cases of priapism, defined as painful and nonpainful penile erection lasting more than hours, have been reported for pediatric and adult patients treated with STRATTERA. The erections resolved in cases in which follow-up information was available, some following discontinuation of STRATTERA.. 5.11 Effect on Growth in Pediatric Patients. Closely monitor growth (e.g., weight, height) in pediatric patients during STRATTERA treatment.. Weight and Height in Long-Term Open-Label Studies in Pediatric PatientsData on the long-term effects of STRATTERA on growth in pediatric patients from open-label studies in which weight and height changes were compared to normative pediatric population data. In general, the weight and height gain of STRATTERA-treated pediatric patients lagged behind that predicted by normative population data for about the first 9-12 months of treatment and subsequently (see Figure below):Weight gain rebounded. At about years of STRATTERA treatment, patients gained mean of 17.9 kg, which was 0.5 kg more than predicted by their baseline data.Height gain stabilized. At years of STRATTERA treatment, patients gained mean of 19.4 cm, which was 0.4 cm less than predicted by their baseline dataFigure 1: Mean Weight and Height Percentiles Over Time for STRATTERA -Treated Pediatric Patients in Comparison to Normative Pediatric Population ValuesAfter three years of STRATTERA treatment in the long-term open-label studies, patients who were:Pre-pubertal at the start of treatment (girls <=8 years old, boys <=9 years old) gained weight and height; however, the mean weight gain was 2.1 kg less than predicted and the mean height gain was 1.2 cm less than predicted.Pubertal (girls >8 to <=13 years old, boys >9 to <=14 years old) or late pubertal (girls >13 years old, boys >14 years old), the mean weight and height gains were close to or exceeded predicted weight and height gains.CYP2D6 poor metabolizers and other CYP2D6 metabolizer types (ultrarapid, normal, and intermediate) treated with STRATTERA for at least two years gained weight and height. However, in:CYP2D6 poor metabolizers the mean weight gain was 2.4 kg less than predicted and the mean height gain was 1.1 cm less than predictedOther CYP2D6 metabolizer types the mean weight gain was 0.2 kg less than predicted and the mean height gain was 0.4 cm less than predicted.In the long-term open-label studies, the growth pattern was generally similar regardless of pubertal status at the time ofSTRATTERA treatment initiation.. Weight gain rebounded. At about years of STRATTERA treatment, patients gained mean of 17.9 kg, which was 0.5 kg more than predicted by their baseline data.. Height gain stabilized. At years of STRATTERA treatment, patients gained mean of 19.4 cm, which was 0.4 cm less than predicted by their baseline data. Pre-pubertal at the start of treatment (girls <=8 years old, boys <=9 years old) gained weight and height; however, the mean weight gain was 2.1 kg less than predicted and the mean height gain was 1.2 cm less than predicted.. Pubertal (girls >8 to <=13 years old, boys >9 to <=14 years old) or late pubertal (girls >13 years old, boys >14 years old), the mean weight and height gains were close to or exceeded predicted weight and height gains.. CYP2D6 poor metabolizers the mean weight gain was 2.4 kg less than predicted and the mean height gain was 1.1 cm less than predicted. Other CYP2D6 metabolizer types the mean weight gain was 0.2 kg less than predicted and the mean height gain was 0.4 cm less than predicted.. Figure 1. Weight and Height in Short-Term, Placebo-Controlled Studies in Pediatric PatientsIn short-term, placebo-controlled studies (up to weeks), STRATTERA-treated patients lost an average of 0.4 kg in weight and gained an average of 0.9 cm in height, compared to gain of 1.5 kg in weight and 1.1 cm in height in the placebo-treated patients.In fixed-dose controlled trial, 1.3%, 7.1%, 19.3%, and 29.1% of patients in the placebo, 0.5, 1.2, and 1.8 mg/kg/day STRATTERA groups, respectively, lost at least 3.5% of their body weight.