STRATTERA is indicated for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD). The effectiveness of STRATTERA in the treatment of ADHD was established in 2 placebo-controlled trials in children, 2 placebo-controlled trials in children and adolescents, and 2 placebo-controlled trials in adults who met DSM-IV criteria for ADHD (see CLINICAL STUDIES). 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, eg, in social, academic, or occupational functioning, and must be present in 2 or more settings, eg, 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.
Special Diagnostic Considerations
The specific etiology of ADHD is unknown, and there is no single diagnostic test. Adequate diagnosis requires the use not only of medical but 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.
Need for Comprehensive Treatment Program
STRATTERA is indicated as an integral part of a total treatment program for ADHD that may include other measures (psychological, educational, social) for patients with this syndrome. Drug treatment may not be indicated for all patients with this syndrome. Drug treatment is not intended for use in the patient who exhibits symptoms secondary to environmental factors and/or other primary psychiatric disorders, including psychosis. Appropriate educational placement is essential in children and adolescents with this diagnosis and psychosocial intervention is often helpful. When remedial measures alone are insufficient, the decision to prescribe drug treatment medication will depend upon the physician's assessment of the chronicity and severity of the patient's symptoms.
Long-Term Use
The effectiveness of STRATTERA for long-term use, ie, for more than 9 weeks in child and adolescent patients and 10 weeks in adult patients, has not been systematically evaluated in controlled trials. Therefore, the physician who elects to use STRATTERA for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient (see DOSAGE AND ADMINISTRATION).
Hypersensitivity
STRATTERA is contraindicated in patients known to be hypersensitive to atomoxetine or other constituents of the product (see WARNINGS).
Monoamine Oxidase Inhibitors (MAOI)
STRATTERA should not be taken with an MAOI, or within 2 weeks after discontinuing an MAOI. Treatment with an MAOI should not be initiated within 2 weeks after discontinuing 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 an MAOI. Some cases presented with features resembling neuroleptic malignant syndrome. Such reactions may occur when these drugs are given concurrently or in close proximity.
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.
Allergic Events
Although uncommon, allergic reactions, including angioneurotic edema, urticaria, and rash, have been reported in patients taking STRATTERA.
Growth
Growth should be monitored during treatment with STRATTERA. During acute treatment studies (up to 9 weeks), STRATTERA-treated patients lost an average of 0.4 kg, while placebo patients gained an average of 1.5 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 0.9 cm, while placebo-treated patients grew an average of 1.1 cm. There are no long-term, placebo-controlled data to evaluate the effect of STRATTERA on growth. Weight and height were assessed during open-label studies of 12 and 18 months, and mean rates of growth were compared to normal growth curves. Patients treated with STRATTERA for at least 18 months gained an average of 6.5kg while mean weight percentile decreased slightly from 68 to 60. For this same group of patients, the average gain in height was 9.3cm with a slight decrease in mean height percentile from 54 to 50. Among patients treated for at least 6 months, mean weight gain was lower for poor metabolizer (PM) patients compared with extensive metabolizer (EM) patients (+0.7 kg compared with +3.0 kg), while mean growth for PM patients was 4.3 cm and mean growth for EM patients was 4.4 cm. Whether final adult height or weight is affected by treatment with STRATTERA is unknown. Patients requiring long-term therapy should be monitored and consideration should be given to interrupting therapy in patients who are not growing or gaining weight satisfactorily.
General
PRECAUTIONS
Effects on blood pressure and heart rate
STRATTERA should be used with caution in patients with hypertension, tachycardia, 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, 3.6% (12/335) 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 0.5% (1/204) of placebo subjects. No pediatric subject had a heart rate increase of at least 25 beats/minute and a heart rate of at least 110 beats/minute on more than one occasion. Tachycardia was identified as an adverse event for 1.5% (5/340) of these pediatric subjects compared with 0.5% (1/207) of placebo subjects. The mean heart rate increase in extensive metabolizer (EM) patients was 6.7 beats/minute, and in poor metabolizer (PM) patients 10.4 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, 6.8% (22/324) of STRATTERA-treated pediatric subjects had high systolic blood pressure measurements compared with 3.0% (6/197) of placebo subjects. High systolic blood pressures were measured on 2 or more occasions in 8.6% (28/324) of STRATTERA- treated subjects and 3.6% (7/197) of placebo subjects. At the final study visit before drug discontinuation, 2.8% (9/326) of STRATTERA-treated pediatric subjects had high diastolic blood pressure measurements compared with 0.5% (1/200) of placebo subjects. High diastolic blood pressures were measured on 2 or more occasions in 5.2% (17/326) of STRATTERA- treated subjects and 1.5% (3/200) 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 3150 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 3100 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, 1.8% (6/340) of STRATTERA-treated subjects experienced symptoms of postural hypotension compared with 0.5% (1/207) of placebo-treated subjects. STRATTERA should be used with caution in any condition that may predispose patients to hypotension.
Effects on urine outflow from the bladder
In adult ADHD controlled trials, the rates of urinary retention (3%, 7/269) and urinary hesitation (3%, 7/269) were increased among atomoxetine subjects compared with placebo subjects (0%, 0/263). Two adult atomoxetine subjects and no placebo subjects discontinued from controlled clinical trials because of urinary retention. A complaint of urinary retention or urinary hesitancy should be considered potentially related to atomoxetine.
Information for Patients
Patients should consult a physician if they are taking or plan to take any prescription or over-the- counter medicines, dietary supplements, or herbal remedies. Patients should consult a physician if they are nursing, pregnant, or thinking of becoming pregnant while taking STRATTERA. Patients may take STRATTERA with or without food. If patients miss a dose, they should take it as soon as possible, but should not take more than the prescribed total daily amount of STRATTERA in any 24-hour period. Patients should use caution when driving a car or operating hazardous machinery until they are reasonably certain that their performance is not affected by atomoxetine.
Laboratory Tests
Routine laboratory tests are not required. CYP2D6 metabolism 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).
Drug-Drug Interactions
Albuterol -- STRATTERA should be administered with caution to patients being treated with albuterol (or other beta2 agonists) because the action of albuterol on the cardiovascular system can be potentiated.
CYP2D6 inhibitors
-- Atomoxetine is primarily metabolized by the CYP2D6 pathway to
4-hydroxyatomoxetine. In EMs, selective inhibitors of CYP2D6 increase atomoxetine steady- state plasma concentrations to exposures similar to those observed in PMs. Dosage adjustment of STRATTERA may be necessary when coadministered with CYP2D6 inhibitors, eg, paroxetine, fluoxetine, and quinidine. (see DOSAGE AND ADMINISTRATION) In EM individuals treated with paroxetine or fluoxetine, the AUC of atomoxetine is approximately 6- to 8-fold and Css,max is about 3- to 4-fold greater than atomoxetine alone. In vitro studies suggest that coadministration of cytochrome P450 inhibitors to PMs will not increase the plasma concentrations of atomoxetine.
Monoamine oxidase inhibitors
-- See CONTRAINDICATIONS.
Pressor agents
-- Because of possible effects on blood pressure, STRATTERA should be used cautiously with pressor agents.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenesis -- 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.
Mutagenesis
-- 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. 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 6 times the maximum human dose on a mg/m2 basis.
Pregnancy--Pregnancy Category C
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 resorption 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 (females) or 10 (males) weeks 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 (females) or 10 (males) weeks prior to mating throughout the period of organogenesis, a decrease in fetal (female only) weight 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.
Labor and Delivery
Parturition in rats was not affected by atomoxetine. The effect of STRATTERA on labor and delivery in humans is unknown.
Nursing Mothers
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.
Pediatric Use
The safety and efficacy of STRATTERA in pediatric patients less than 6 years of age have not been established. The efficacy of STRATTERA beyond 9 weeks and safety of STRATTERA beyond 1 year of treatment have not been systematically evaluated. 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 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.
Geriatric Use
The safety and efficacy of STRATTERA in geriatric patients have not been established.
STRATTERA was administered to 2067 children or adolescent patients with ADHD and 270 adults with ADHD in clinical studies. During the ADHD clinical trials, 169 patients were treated for longer than 1 year and 526 patients 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.
Child and Adolescent Clinical Trials
Reasons for discontinuation of treatment due to adverse events in child and adolescent clinical trials -- In acute child and adolescent placebo-controlled trials, 3.5% (15/427) of atomoxetine subjects and 1.4% (4/294) placebo subjects discontinued for adverse events. For all studies, (including open-label and long-term studies), 5% of extensive metabolizer (EM) patients and 7% of poor metabolizer (PM) patients discontinued because of an adverse event. Among STRATTERA-treated patients, aggression (0.5%, n=2); irritability (0.5%, n=2); somnolence (0.5%, n=2); and vomiting (0.5%, n=2) were the reasons for discontinuation reported by more than 1 patient. Commonly observed adverse events in acute child and adolescent, placebo-controlled trials -- 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 the BID trials. Results were similar in the QD trial 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: dyspepsia, nausea, vomiting, fatigue, appetite decreased, dizziness, and mood swings (see Tables 1 & 2).
| Table 1:Common Treatment-Emergent Adverse Events Associated with the Use of STRATTERA in Acute (up to 9 weeks) Child and Adolescent Trials | ||
| Adverse Event 1 | Percentage of Patients Reporting Events from BID Trials | |
| STRATTERA (N=340) | Placebo (N=207) | |
| Gastrointestinal Disorders | ||
| Abdominal pain upper | 20 | 16 |
| Constipation | 3 | 1 |
| Dyspepsia | 4 | 2 |
| Vomiting | 11 | 9 |
| Infections | ||
| Ear infection | 3 | 1 |
| Influenza | 3 | 1 |
| Investigations | ||
| Weight decreased | 2 | 0 |
| Metabolism and Nutritional Disorders | ||
| Appetite decreased | 14 | 6 |
| Nervous System Disorders | ||
| Dizziness (exc vertigo) | 6 | 3 |
| Headache | 27 | 25 |
| Somnolence | 7 | 5 |
| Psychiatric Disorders | ||
| Crying | 2 | 1 |
| Irritability | 8 | 5 |
| Mood swings | 2 | 0 |
| Respiratory, Thoracic, and Mediastinal Disorders | ||
| Cough | 11 | 7 |
| Rhinorrhea | 4 | 3 |
| Skin and Subcutaneous Tissue Disorders | ||
| Dermatitis | 4 | 1 |
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: anorexia, blood pressure increased, early morning awakening, flushing, mydriasis, sinus tachycardia, tearfulness. The following events were reported by at least 2% of patients treated with atomoxetine, and equal to or less than placebo: arthralgia, gastroenteritis viral, insomnia, sore throat, nasal congestion, nasopharyngitis, pruritus, sinus congestion, upper respiratory tract infection.
| Table 2:Common Treatment-Emergent Adverse Events Associated with the Use of STRATTERA In Acute (up to 9 weeks) Child and Adolescent Trials | ||||
| Adverse Event | Percentage of Patients Reporting Events from BID Trials | Percentage of Patients Reporting Events from QD Trials | ||
| STRATTERA (N=340) | Placebo (N=207) | STRATTERA (N=85) | Placebo (N=85) | |
| Gastrointestinal Disorders | ||||
| Abdominal pain upper | 20 | 16 | 16 | 9 |
| Constipation | 3 | 1 | 0 | 0 |
| Diarrhea | 3 | 6 | 4 | 1 |
| Dry mouth | 1 | 2 | 4 | 1 |
| Dyspepsia | 4 | 2 | 8 | 0 |
| Nausea | 7 | 8 | 12 | 2 |
| Vomiting | 11 | 9 | 15 | 1 |
| General Disorders | ||||
| Fatigue | 4 | 5 | 9 | 1 |
| Psychiatric Disorders | ||||
| Mood swings | 2 | 0 | 5 | 2 |
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: decreased appetite (23% of PMs, 16% of EMs); insomnia (13% of PMs, 7% of EMs); sedation (4% of PMs, 2% of EMs); depression (6% of PMs, 2% of EMs); tremor (4% of PMs, 1% of EMs); early morning awakening (3% of PMs, 1% of EMs); pruritus (2% of PMs, 1% of EMs); mydriasis (2% of PMs, 1% of EMs).
Adult Clinical Trials
Reasons for discontinuation of treatment due to adverse events in acute adult placebo-controlled trials -- 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 in acute adult placebo-controlled trials -- 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 2. 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, impotence, urinary hesitation and/or urinary retention and/or difficulty in micturition, and dysmenorrhea (see Table 2).
| Table 3:Common Treatment-Emergent Adverse Events Associated with the Use of STRATTERA in Acute (up to 10 weeks) Adult Trials | ||
| Adverse Event 1 | Percentage of Patients Reporting Event | |
| System Organ Class/Adverse Event | STRATTERA (n=269) | Placebo (n=263) |
| Cardiac Disorders | ||
| Palpitations | 4 | 1 |
| Gastrointestinal Disorders | ||
| Constipation | 10 | 4 |
| Dry mouth | 21 | 6 |
| Dyspepsia | 6 | 4 |
| Flatulence | 2 | 1 |
| Nausea | 12 | 5 |
| General Disorders and Administration Site Conditions | ||
| Fatigue and/or lethargy | 7 | 4 |
| Pyrexia | 3 | 2 |
| Rigors | 3 | 1 |
| Investigations and Infestations | ||
| Sinusitis | 6 | 4 |
| Investigations | ||
| Weight decreased | 2 | 1 |
| Metabolism and Nutritional Disorders | ||
| Appetite decreased | 10 | 3 |
| Musculoskeletal, Connective Tissue, and Bone Disorders | ||
| Myalgia | 3 | 2 |
| Nervous System Disorders | ||
| Dizziness | 6 | 2 |
| Headache | 17 | 17 |
| Insomnia and/or middle insomnia | 16 | 8 |
| Paraesthesia | 4 | 2 |
| Sinus headache | 3 | 1 |
| Psychiatric Disorders | ||
| Abnormal dreams | 4 | 3 |
| Libido decreased | 6 | 2 |
| Sleep disorder | 4 | 2 |
| Renal and Urinary Disorders | ||
| Urinary hesitation and/or urinary retention and/or difficulty in micturition | 8 | 0 |
| Reproductive System and Breast Disorders | ||
| Dysmenorrhoea 3 | 7 | 3 |
| Ejaculation failure 2 and/or ejaculation disorder 2 | 5 | 2 |
| Erectile disturbance 2 | 7 | 1 |
| Impotence 2 | 3 | 0 |
| Menses delayed 3 | 2 | 1 |
| Menstrual disorder 3 | 3 | 2 |
| Menstruation irregular 3 | 2 | 0 |
| Orgasm abnormal | 2 | 1 |
| Prostatitis 2 | 3 | 0 |
| Skin and Subcutaneous Tissue Disorders | ||
| Dermatitis | 2 | 1 |
| Sweating increased | 4 | 1 |
| Vascular Disorders | ||
| Hot flushes | 3 | 1 |
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.
Based on total number of males (STRATTERA, n=174; placebo, n=172).
Based on total number of females (STRATTERA, n=95; placebo, n=91).
Male and female sexual dysfunction
-- 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 labeling are likely to underestimate the actual incidence. The table below displays the incidence of sexual side effects reported by at least 2% of adult patients taking STRATTERA in placebo-controlled trials.
Table 4
| STRATTERA | Placebo | |
| Erectile disturbance 1 | 7% | 1% |
| Impotence 1 | 3% | 0% |
| Orgasm abnormal | 2% | 1% |
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.
Controlled Substance Class STRATTERA is not a controlled substance. Physical and Psychological Dependence In a randomized, double-blind, placebo-controlled, abuse-potential study in adults comparing effects of STRATTERA and placebo, STRATTERA was not associated with a pattern of response that suggested stimulant or euphoriant properties. Clinical study data in over 2000 children, adolescents, and adults with ADHD and over 1200 adults with depression showed only isolated incidents of drug diversion or inappropriate self- administration associated with STRATTERA. There was no evidence of symptom rebound or adverse events suggesting a drug-discontinuation or withdrawal syndrome.
Animal Experience
Drug discrimination studies in rats and monkeys showed inconsistent stimulus generalization between atomoxetine and cocaine.
The effects of overdose greater than twice the maximum recommended daily dose in humans are unknown. No specific information is available on the treatment of overdose with atomoxetine. Patients who overdose with atomoxetine should be monitored carefully and receive supportive care. Gastric emptying and repeated activated charcoal (with/without cathartics) may prevent systemic absorption.
Initial Treatment
DOSAGE AND ADMINISTRATION
Dosing of children and adolescents up to 70 kg body weight--STRATTERA should be initiated at a total daily dose of approximately 0.5 mg/kg and increased after a minimum of 3 days to a target total daily dose of approximately 1.2 mg/kg administered either as a single daily dose in the morning or as evenly divided doses in the morning and late afternoon/early evening. No additional benefit has been demonstrated for doses higher than 1.2 mg/kg/day (see CLINICAL STUDIES). The total daily dose in children and adolescents should not exceed 1.4 mg/kg or 100 mg, whichever is less. Dosing of children and adolescents over 70 kg body weight and adults--STRATTERA should be initiated at a total daily dose of 40 mg and increased after a minimum of 3 days to a target total daily dose of approximately 80 mg administered either as a single daily dose in the morning or as evenly divided doses in the morning and late afternoon/early evening. After 2 to 4 additional weeks, the dose may be increased to a maximum of 100 mg in patients who have not achieved an optimal response. There are no data that support increased effectiveness at higher doses (see CLINICAL STUDIES). The maximum recommended total daily dose in children and adolescents over 70 kg and adults is 100 mg.
Maintenance/Extended Treatment
There is no evidence available from controlled trials to indicate how long the patient with ADHD should be treated with STRATTERA. It is generally agreed, however, that pharmacological treatment of ADHD may be needed for extended periods. Nevertheless, the physician who elects to use STRATTERA for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient.
General Dosing Information
STRATTERA may be taken with or without food. The safety of single doses over 120 mg and total daily doses above 150 mg have not been systematically evaluated.
Dosing adjustment for hepatically impaired patients
For those ADHD patients who have hepatic insufficiency (HI), dosage adjustment is recommended as follows: For patients with moderate HI (Child-Pugh Class B), initial and target doses should be reduced to 50% of the normal dose (for patients without HI). For patients with severe HI (Child-Pugh Class C), initial dose and target doses should be reduced to 25% of normal (see Special Populations under CLINICAL PHARMACOLOGY).
Dosing adjustment for use with a strong CYP2D6 Inhibitor
In children and adolescents up to 70 kg body weight administered strong CYP2D6 inhibitors, eg, paroxetine, fluoxetine, quinidine, STRATTERA should be initiated at 0.5 mg/kg/day and only increased to the usual target dose of 1.2 mg/kg/day if symptoms fail to improve after 4 weeks and initial dose is well tolerated. In children and adolescents over 70 kg body weight and adults administered strong CYP2D6 inhibitors, eg, paroxetine, fluoxetine, quinidine, STRATTERA should be initiated at 40 mg/day and only increased to the usual target dose of 80 mg/day if symptoms fail to improve after 4 weeks and the initial dose is well tolerated. Atomoxetine can be discontinued without being tapered.
STRATTERA capsules are supplied in 5, 10, 18, 25, 40, and 60-mg strengths.
| STRATTER A TM Capsules | 5 mg * | 10 mg * | 18 mg * | 25 mg * | 40 mg * | 60 mg * |
| Color | Gold, Gold | Opaque White, Opaque White | Gold, Opaque White | Opaque Blue, Opaque White | Opaque Blue, Opaque Blue | Opaque Blue, Gold |
| Identification | LILLY 3226 5 mg | LILLY 3227 10 mg | LILLY 3238 18 mg | LILLY 3228 25 mg | LILLY 3229 40 mg | LILLY 3239 60 mg |
| NDC Codes: | ||||||
| Bottles of 30 | 0002-3226- | 0002-3227- | 0002-3238- | 0002-3228- | 0002-3229- | 0002-3239- |
| 30 | 30 | 30 | 30 | 30 | 30 | |
| Bottles of | 0002-3226- | 0002-3227- | 0002-3238- | 0002-3228- | 0002-3229- | 0002-3239- |
| 2000 | 07 | 07 | 07 | 07 | 07 | 07 |
* Atomoxetine base equivalent. Store at 25oC (77oF); excursions permitted to 15o to 30oC (59o to 86oF) [see USP Controlled Room Temperature].
Literature issued Month dd, yyyy
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