STRATTERA (atomoxetine hydrochloride) is indicated for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in children 6 years of age and over, adolescents, and adults. ADHD was formerly known as Attention Deficit Disorder (ADD) with or without hyperactivity.

A diagnosis of ADHD (DSM-IV) implies the presence of hyperactive-impulsive or inattentive symptoms that cause impairment and that were present before age 7 years. The symptoms must be persistent, must be more severe than is typically observed in individuals at a comparable level of development, must cause clinically significant impairment, e.g., in social, academic, or occupational functioning, and must be present in 2 or more settings, e.g., school (or work) and at home. The symptoms must not be better accounted for by another mental disorder. For the Inattentive Type, at least 6 of the following symptoms must have persisted for at least 6 months: lack of attention to details/careless mistakes, lack of sustained attention, poor listener, failure to follow through on tasks, poor organization, avoids tasks requiring sustained mental effort, loses things, easily distracted, forgetful. For the Hyperactive-Impulsive Type, at least 6 of the following symptoms must have persisted for at least 6 months: fidgeting/squirming, leaving seat, inappropriate running/climbing, difficulty with quiet activities, “on the go,” excessive talking, blurting answers, can't wait turn, intrusive. For a Combined Type diagnosis, both inattentive and hyperactive-impulsive criteria must be met.

The specific etiology of ADHD is unknown, and there is no single diagnostic test. Adequate diagnosis requires the use not only of medical but also of special psychological, educational, and social resources. Learning may or may not be impaired. The diagnosis must be based upon a complete history and evaluation of the patient and not solely on the presence of the required number of DSM-IV characteristics.

STRATTERA is indicated as an integral part of a total treatment program for ADHD that may include other measures (psychological, educational, and social) for patients with this syndrome. Drug treatment may not be indicated for all patients with this syndrome. Drug treatment is not intended for use in the patient who exhibits symptoms secondary to environmental factors and/or other primary psychiatric disorders, including psychosis. Appropriate educational placement is essential in children and adolescents with this diagnosis and psychosocial intervention is often helpful. When remedial measures alone are insufficient, the decision to prescribe drug treatment medication will depend upon the physician's assessment of the chronicity and severity of the patient's symptoms.

The safety and efficacy of STRATTERA in pediatric patients less than 6 years of age have not been established.

• Hypersensitivity: STRATTERA (atomoxetine hydrochloride) is contraindicated in patients known to be hypersensitive to atomoxetine or other constituents of the product (see Warnings and Precautions).

  
  

• Monoamine Oxidase Inhibitors: STRATTERA should not be taken with monoamine oxidase inhibitors (MAOI), or within 2 weeks after discontinuing MAOI. Treatment with MAOI should not be initiated within 2 weeks after discontinuing STRATTERA. With other drugs that affect brain monoamine concentrations, there have been reports of serious, sometimes fatal, reactions (including hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs, and mental status changes that include extreme agitation progressing to delirium and coma) when taken in combination with MAOI. Some cases presented with features resembling neuroleptic malignant syndrome. Such reactions may occur when these drugs are given concurrently or in close proximity.

  
  

• Narrow Angle Glaucoma: In clinical trials, STRATTERA use was associated with an increased risk of mydriasis and therefore its use is not recommended in patients with narrow angle glaucoma.

  
  

• Symptomatic cardiovascular disease.

  
  

• Moderate to severe hypertension.

  
  

• Advanced arteriosclerosis.

  
  

• Uncontrolled hyperthyroidism.

  
  

An increased risk over placebo for suicide-related events in children and adolescents taking STRATTERA, was identified in a combined analysis of placebo-controlled trials of 6-8 weeks duration. Of 1357 patients who received STRATTERA, 5 (0.37%) had reports of suicidal ideation compared to 0% of 851 patients who received placebo. In addition, one suicide attempt (overdose) was identified, which occurred in a STRATTERA patient. No completed suicides occurred during these trials. (See also Warnings and Precautions, Special Populations, Pediatrics (6-18 years of age)).

There have been very rare reports of suicidal ideation, suicidal attempts, suicidal depression and completed suicides in children, adolescents and adults (see Adverse Reactions, Post-Market Adverse Drug Reactions, Table 5 and Table 6).

Rigorous clinical monitoring for suicidal ideation or other indicators of potential for suicidal behaviour is advised in patients of all ages. This includes monitoring for agitation-type of emotional and behavioural changes, and clinical worsening.

Post-marketing reports indicate that STRATTERA (atomoxetine hydrochloride) can cause severe liver injury in rare cases. Although no evidence of liver injury was detected in clinical trials, there have been 2 reported cases of markedly elevated hepatic enzymes and bilirubin, in the absence of other obvious explanatory factors, out of more than 2 million patients during the first 2 years of post-marketing experience. In one patient, liver injury, manifested by elevated hepatic enzymes (up to 40 × upper limit of normal [ULN]) and jaundice (bilirubin up to 12 × ULN), recurred upon rechallenge, and was followed by recovery upon drug discontinuation providing evidence that STRATTERA caused the liver injury. Such reactions may occur several months after therapy is started, but laboratory abnormalities may continue to worsen for several weeks after drug is stopped. Because of probable under-reporting, it is impossible to provide an accurate estimate of the true incidence of these events. The patients described above recovered from their liver injury, and did not require a liver transplant. However, in a small percentage of patients, severe drug-related liver injury may progress to acute liver failure resulting in death or the need for a liver transplant.

STRATTERA should be discontinued in patients with jaundice or laboratory evidence of liver injury, and should not be restarted. Laboratory testing to determine liver enzyme levels should be done upon the first symptom or sign of liver dysfunction (e.g., pruritus, dark urine, jaundice, right upper quadrant tenderness, or unexplained "flu-like" symptoms). (See also Information for the Patient.)

Although uncommon, allergic reactions, including rash, angioneurotic edema, and urticaria, have been reported in patients taking STRATTERA.

Chronic open-label treatment studies (up to 2 years) indicate minimal, if any, long-term effects of STRATTERA on weight and height compared with normal growth curves. Patients treated with STRATTERA for at least 2 years gained an average of 10.7 kg, an average of 0.9 kg less than expected according to normal growth curves. For this same group of patients, the average gain in height was 13.1 cm, an average of 0.5 cm below expected. Among patients treated for at least 1 year, mean weight and height gain were lower than expected according to normal growth curves for poor metabolizer (PM) patients (4.8 kg, an average of 3.7 kg below expected; 8.5 cm, an average of 1.5 cm below expected) compared with extensive metabolizer (EM) patients (7.4 kg, an average of 1.2 kg below expected; 9.5 cm, an average of 0.7 cm below expected). There are no long-term, placebo-controlled data to evaluate the effect of STRATTERA on growth. Minor, transient decreases in weight and height may occur during initial therapy. During acute treatment studies (up to 9 weeks), STRATTERA-treated patients lost an average of 0.6 kg, while placebo patients gained an average of 1.2 kg. In a controlled trial that randomized patients to placebo or 1 of 3 atomoxetine doses, 1.3%, 7.1%, 19.3%, and 29.1% of patients lost at least 3.5% of their body weight in the placebo, 0.5, 1.2, and 1.8 mg/kg/day STRATTERA dose groups, respectively. During acute treatment studies, STRATTERA-treated patients grew an average of 0.8 cm while placebo-treated patients grew an average of 1.0 cm. Whether final adult height or weight is affected by treatment with STRATTERA is unknown. Growth should be monitored during treatment with STRATTERA.

STRATTERA should be used with caution in patients with hypertension, tachycardia, congenital long QT syndrome, or cardiovascular or cerebrovascular disease because it can increase blood pressure and heart rate. Pulse and blood pressure should be measured at baseline, following STRATTERA dose increases, and periodically while on therapy.

In pediatric placebo-controlled trials, STRATTERA-treated subjects experienced a mean increase in heart rate of about 6 beats/minute compared with placebo subjects. At the final study visit before drug discontinuation, 3.1% (16/518) of STRATTERA-treated subjects had heart rate increases of at least 25 beats/minute and a heart rate of at least 110 beats/minute, compared with 0.3% (1/338) of placebo subjects. 1.9% (10/518) of STRATTERA-treated subjects and 0.3% (1/338) of placebo subjects had a heart rate increase of at least 25 beats/minute and a heart rate of at least 110 beats/minute on 2 or more occasions. Tachycardia was identified as an adverse event for 0.5% (3/657) of these pediatric subjects compared with 0.0% (0/408) of placebo subjects. The mean heart rate increase in extensive metabolizer (EM) patients was 5.8 beats/minute, and in poor metabolizer (PM) patients 9.7 beats/minute.

STRATTERA-treated pediatric subjects experienced mean increases of about 1.5 mm Hg in systolic and diastolic blood pressures compared with placebo. At the final study visit before drug discontinuation, 5.2% (26/496) of STRATTERA-treated pediatric subjects had high systolic blood pressure measurements compared with 2.4% (8/327) of placebo subjects. High systolic blood pressures were measured on 2 or more occasions in 6.0% (30/496) of STRATTERA-treated subjects and 2.4% (8/327) of placebo subjects. At the final study visit before drug discontinuation, 3.0% (15/506) of STRATTERA-treated pediatric subjects had high diastolic blood pressure measurements compared with 0.9% (3/330) of placebo subjects. High diastolic blood pressures were measured on 2 or more occasions in 4.2% (21/506) of STRATTERA-treated subjects and 0.9% (3/330) of placebo subjects. (High systolic and diastolic blood pressure measurements were defined as those exceeding the 95th percentile, stratified by age, gender, and height percentile—National High Blood Pressure Education Working Group on Hypertension Control in Children and Adolescents.)

In adult placebo-controlled trials, STRATTERA-treated subjects experienced a mean increase in heart rate of 5 beats/minute compared with placebo subjects. Tachycardia was identified as an adverse event for 3% (8/269) of these adult atomoxetine subjects compared with 0.8% (2/263) of placebo subjects.

STRATTERA-treated adult subjects experienced mean increases in systolic (about 3 mm Hg) and diastolic (about 1 mm Hg) blood pressures compared with placebo. At the final study visit before drug discontinuation, 1.9% (5/258) of STRATTERA-treated adult subjects had systolic blood pressure measurements 150 mm Hg compared with 1.2% (3/256) of placebo subjects. At the final study visit before drug discontinuation, 0.8% (2/257) of STRATTERA-treated adult subjects had diastolic blood pressure measurements 100 mm Hg compared with 0.4% (1/257) of placebo subjects. No adult subject had a high systolic or diastolic blood pressure detected on more than one occasion.

Orthostatic hypotension has been reported in subjects taking STRATTERA. In short-term child- and adolescent-controlled trials, 5.2% (34/657) of STRATTERA-treated subjects experienced symptoms of postural hypotension compared with 2.0% (8/408) of placebo-treated subjects. STRATTERA should be used with caution in any condition that may predispose patients to hypotension.

Sudden death has been reported in association with stimulant drugs used for ADHD treatment at usual doses in children with structural cardiac abnormalities. Although STRATTERA is not a stimulant drug, it should not generally be used in children, adolescents, or adults with known structural cardiac abnormalities.

Theoretically there exists a pharmacological potential for all ADHD drugs to increase the risk of sudden/cardiac death. Although confirmation of an incremental risk for adverse cardiac events arising from treatment with ADHD medications is lacking, prescribers should consider this potential risk.

All drugs with sympathomimetic effects prescribed in the management of ADHD should be used with caution in patients who: a) are involved in strenuous exercise or activities, b) use stimulants, or c) have a family history of sudden/cardiac death. Prior to the initiation of treatment, a personal and family history should be obtained. In patients with relevant risk factors and based on the clinician's judgment, further cardiovascular evaluation may be considered.

In adult ADHD controlled trials, the rates of urinary retention and urinary hesitation were increased among atomoxetine subjects compared with placebo subjects. A complaint of urinary retention or urinary hesitancy should be considered potentially related to atomoxetine.

Atomoxetine HCl was not carcinogenic in rats and mice when given in the diet for 2 years at time-weighted average doses up to 47 and 458 mg/kg/day, respectively. The highest dose used in rats is approximately 8 and 5 times the maximum human dose in children and adults, respectively, on a mg/m² basis. Plasma levels (AUC) of atomoxetine at this dose in rats are estimated to be 1.8 times (extensive metabolizers) or 0.2 times (poor metabolizers) those in humans receiving the maximum human dose. The highest dose used in mice is approximately 39 and 26 times the maximum human dose in children and adults, respectively, on a mg/m² basis.

Atomoxetine HCl was negative in a battery of genotoxicity studies that included a reverse point mutation assay (Ames Test), an in vitro mouse lymphoma assay, a 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 a 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.

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 6 times the maximum human dose on a mg/m² basis.

Pregnant rabbits were treated with up to 100 mg/kg/day of atomoxetine by gavage throughout the period of organogenesis. At this dose, in 1 of 3 studies, a decrease in live fetuses and an increase in early resorptions was observed. Slight increases in the incidences of atypical origin of carotid artery and absent subclavian artery were observed. These findings were observed at doses that caused slight maternal toxicity. The no-effect dose for these findings was 30 mg/kg/day. The 100-mg/kg dose is approximately 23 times the maximum human dose on a mg/m² basis; plasma levels (AUC) of atomoxetine at this dose in rabbits are estimated to be 3.3 times (extensive metabolizers) or 0.4 times (poor metabolizers) those in humans receiving the maximum human dose.

Rats were treated with up to approximately 50 mg/kg/day of atomoxetine (approximately 6 times the maximum human dose on a mg/m² basis) in the diet from 2 weeks (females) or 10 weeks (males) prior to mating through the periods of organogenesis and lactation. In 1 of 2 studies, decreases in pup weight and pup survival were observed. The decreased pup survival was also seen at 25 mg/kg (but not at 13 mg/kg). In a study in which rats were treated with atomoxetine in the diet from 2 weeks (females) or 10 weeks (males) prior to mating throughout the period of organogenesis, a decrease in fetal weight (female only) and an increase in the incidence of incomplete ossification of the vertebral arch in fetuses were observed at 40 mg/kg/day (approximately 5 times the maximum human dose on a 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 maximum human dose on a mg/m² basis) by gavage throughout the period of organogenesis.

No adequate and well-controlled studies have been conducted in pregnant women. STRATTERA should not be used during pregnancy unless the potential benefit justifies the potential risk to the fetus. The effect of STRATTERA on labour and delivery in humans is unknown.

The extent of exposure in pregnancy during clinical trials was very limited.

Atomoxetine and/or its metabolites were excreted in the milk of rats. It is not known if atomoxetine is excreted in human milk. Caution should be exercised if STRATTERA is administered to a nursing woman.

The safety and efficacy of STRATTERA in pediatric patients less than 6 years of age have not been established.

Risk of Suicide-Related Behaviours and Ideation in Children (see also Warnings and Precautions, Potential Association with the Occurrence of Behavioural and Emotional Changes, Including Self-Harm).

An increased risk over placebo, for suicide-related events in children and adolescents taking STRATTERA was identified in a combined analysis of 12 short-term (6-18 weeks) placebo-controlled trials (11 in ADHD and 1 in enuresis). Of 1357 patients who received STRATTERA, 5 (0.37%) had reports of suicidal ideation compared to 0% of 851 patients who received placebo. In addition, one suicide attempt (overdose) was identified which occurred in a STRATTERA patient. These 6 events occurred in STRATTERA patients 7 to 12 years of age who were male. There were no events in older adolescents, who comprised about 25 percent of the study population. Time to onset ranged from 9 to 32 days, and doses ranged from 0.48 to 1.40 mg/kg/day. A similar analysis in adult patients treated with STRATTERA for either ADHD or major depressive disorder (MDD) found no increased risk over placebo of suicidal ideation or behaviour with the use of STRATTERA.

Not included in these numerators were 6 cases (3 in the STRATTERA arms and 3 in the placebo arms) of non-fatal potentially self-injurious actions where the intent is unknown, including burns and taking more than one dose of medication at a time.

There have been very rare reports of suicidal ideation, suicidal attempts, suicidal depression and completed suicides in children and adolescents (see Adverse Reactions, Post-Market Adverse Drug Reactions, Table 5 and Table 6).

Rigorous clinical monitoring for suicidal ideation or other indicators of potential for suicidal behaviour is advised in patients of all ages. This includes monitoring for agitation-type of emotional and behavioural changes, and clinical worsening.

Clinical trial data in children and adolescents show higher rates than placebo for irritability, mood swings, aggression, crying and tearfulness (see Adverse Reactions, Table 1 and Table 2). The relationship, if any, between these events and suicide-related behaviours in children and adolescents with ADHD is unclear.

Aggressive behaviour or hostility has been observed in children and adolescents with ADHD, and has been reported with some medications indicated for the treatment of ADHD. Although there is no conclusive evidence that atomoxetine causes aggressive behaviour or hostility, this was observed more frequently in clinical trials among children and adolescents treated with atomoxetine compared to placebo (overall risk ratio of 1.33—not statistically significant). Patients beginning treatment for ADHD should be monitored for the appearance of, or worsening of, aggressive behaviour or hostility.

Caregivers/patients should be instructed to call their doctor as soon as possible should they notice an increase in aggression or hostility.

A 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 8 times, respectively, the maximum human dose on a 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 a slight decrease in corpora lutea (50 mg/kg) were seen, but there were no effects on fertility or reproductive performance. A slight delay in onset of incisor eruption was seen at 50 mg/kg. A 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.

The safety and efficacy of STRATTERA in geriatric patients have not been established.

Routine laboratory tests are not required.

Poor metabolizers (PMs) of CYP2D6 have a 10-fold higher AUC and a 5-fold higher peak concentration to a given dose of STRATTERA compared with extensive metabolizers (EMs). Approximately 7% of a Caucasian population are PMs. Laboratory tests are available to identify CYP2D6 PMs. The blood levels in PMs are similar to those attained by taking strong inhibitors of CYP2D6. The higher blood levels in PMs lead to a higher rate of some adverse effects of STRATTERA (see Adverse Reactions).

STRATTERA was administered to 3262 children or adolescent patients with ADHD and 471 adults with ADHD in clinical studies. During the ADHD clinical trials, 1409 patients (1236 pediatric and 173 adults) were treated for longer than 1 year and 1940 patients (1704 pediatric and 236 adults) were treated for over 6 months.

The data in the following tables and text cannot be used to predict the incidence of side effects in the course of usual medical practice where patient characteristics and other factors differ from those that prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with data obtained from other clinical investigations involving different treatments, uses, or investigators. The cited data provide the prescribing physician with some basis for estimating the relative contribution of drug and non-drug factors to the adverse event incidence in the population studied.

In acute child and adolescent placebo-controlled trials, 4.1% (27/661) of atomoxetine subjects and 1.2% (5/410) placebo subjects discontinued for adverse events. For all studies, (including open-label and long-term studies), 5.8% of extensive metabolizer (EM) patients and 8.9% of poor metabolizer (PM) patients discontinued because of an adverse event. Among STRATTERA-treated patients, somnolence (0.8%, N=5); aggression (0.5%, N=3); irritability (0.5%, N=3); vomiting (0.5%, N=3) and abdominal pain (0.3%, N=2) were the reasons for discontinuation reported by more than 1 patient.

Commonly observed adverse events 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 1 for all acute placebo-controlled trials. Results were similar in the BID trials and QD trials except as shown in Table 2, which shows both BID and QD results for selected adverse events. The most commonly observed adverse events in patients treated with STRATTERA (incidence of 5% or greater and at least twice the incidence in placebo patients, for either BID or QD dosing) were: appetite decreased, dizziness, dyspepsia, fatigue and/or lethargy, irritability, nausea, somnolence, and vomiting (see Table 2).

Table 1: STRATTERA

Common Treatment-Emergent Adverse Events Reported in STRATTERA Placebo-Controlled Clinical Trials in Children and Adolescents with ADHD<sup>a

a.</sup> Events reported by at least 2% of patients treated with atomoxetine, and greater than placebo. The following events did not meet this criterion but were reported by more atomoxetine-treated patients than placebo-treated patients and are possibly related to atomoxetine treatment: aggression, blood pressure increased, early morning awakening, flushing, mydriasis, sinus tachycardia, crying, tearfulness, suicidal ideation. The following events were reported by at least 2% of patients treated with atomoxetine, and equal to or less than placebo: cough, diarrhea, insomnia, nasal congestion, nasopharyngitis, pharyngitis, pyrexia, upper respiratory tract infection.



Table 2: STRATTERA

Common Treatment-Emergent Adverse Events Associated with the Use of STRATTERA in Acute (up to 9 weeks) Child and Adolescent Trials<sup>a

a.</sup> Events reported by at least 2% of patients treated with atomoxetine, and greater than placebo in either BID or QD trials.

The following adverse events occurred in at least 2% of PM patients and were either twice as frequent or statistically significantly more frequent in PM patients compared with EM patients: appetite decreased (24% of PMs, 17% of EMs); insomnia and middle insomnia (14% of PMs, 8% of EMs); sedation (4% of PMs, 2% of EMs); depression and/or depressed mood (5% of PMs, 3% of EMs); abrasion (5% of PMs, 2% of EMs); tremor (5% of PMs, 1% of EMs); early morning awakening (3% of PMs, 1% of EMs); enuresis (3% of PMs, 1% of EMs); pruritus (3% of PMs, 1% of EMs); mydriasis (3% of PMs, 1% of EMs); conjunctivitis (3% of PMs, 1% of EMs); syncope (2% of PMs, 1% of EMs); animal bite (2% of PMs, 1% of EMs).

In the acute adult placebo-controlled trials, 8.5% (23/270) atomoxetine subjects and 3.4% (9/266) placebo subjects discontinued for adverse events. Among STRATTERA-treated patients, insomnia (1.1%, N=3); chest pain (0.7%, N=2); palpitations (0.7%, N=2); and urinary retention (0.7%, N=2) were the reasons for discontinuation reported by more than 1 patient.

Commonly observed adverse events 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 3.

The most commonly observed adverse events in patients treated with STRATTERA (incidence of 5% or greater and at least twice the incidence in placebo patients) were: constipation, dry mouth, nausea, appetite decreased, dizziness, insomnia, decreased libido, ejaculatory problems, erectile disturbance, urinary hesitation and/or urinary retention and/or difficulty in micturition, and dysmenorrhea (see Table 3).

Table 3: STRATTERA

Common Treatment-Emergent Adverse Events Associated with the Use of STRATTERA in Acute (up to 10 weeks) Adult Trials

^a. Events reported by at least 2% of patients treated with atomoxetine, and greater than placebo. The following events did not meet this criterion but were reported by more atomoxetine-treated patients than placebo-treated patients and are possibly related to atomoxetine treatment: early morning awakening, peripheral coldness, tachycardia. The following events were reported by at least 2% of patients treated with atomoxetine, and equal to or less than placebo: abdominal pain upper, arthralgia, back pain, cough, diarrhea, influenza, irritability, nasopharyngitis, sore throat, upper respiratory tract infection, vomiting.
^b. Based on total number of males (STRATTERA, N=174; placebo, N=172).
^c. Based on total number of females (STRATTERA, N=95; placebo, N=91).

Atomoxetine appears to impair sexual function in some patients. Changes in sexual desire, sexual performance, and sexual satisfaction are not well assessed in most clinical trials because they need special attention and because patients and physicians may be reluctant to discuss them. Accordingly, estimates of the incidence of untoward sexual experience and performance cited in product labelling are likely to underestimate the actual incidence. Table 4 displays the incidence of sexual side effects reported by at least 2% of adult patients taking STRATTERA in placebo-controlled trials.

Table 4: STRATTERA

Incidence of Sexual Side Effects

	STRATTERA	Placebo
Erectile Disturbancea	7%	1%
Libido Decreased	6%	2%
Ejaculation Failurea and/or Ejaculation Disordera	5%	2%
Impotencea	3%	0%
Orgasm Abnormal	2%	1%

^a. Males only.

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, physicians should routinely inquire about such possible side effects.

During the first 24 months of post-market experience, it is estimated that over 2 million patients have been treated with STRATTERA, for 600 000 patient-years of therapy.

Table 5 and Table 6 are based on post-market spontaneous adverse event reports. The percentages shown are calculated by dividing the number of adverse events reported to the company by the estimated number of patients exposed to the drug during the same time period. The causal relationship between STRATTERA and the emergence of these events has not been established.

Table 5: STRATTERA

STRATTERA Post-Market Spontaneous Adverse Event Reports in Children and Adolescents with ADHD