ADVERSE REACTIONS
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 and 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 Event1 | Percentage of Patients Reporting Events from BID Trials |
| STRATTERA
(N=340) | Placebo
(N=207) |
|
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.
|
| 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 |
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 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, impotence, urinary hesitation and/or urinary retention and/or difficulty in micturition, and dysmenorrhea (see Table 3).
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) |
|
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.
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2 Based on total number of males (STRATTERA, N=174; placebo, N=172).
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3 Based on total number of females (STRATTERA, N=95; placebo, N=91).
|
| 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 |
| Infections | | |
| 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 | | |
| Dysmenorrhea3 | 7 | 3 |
| Ejaculation failure2 and/or ejaculation disorder2 | 5 | 2 |
| Erectile disturbance2 | 7 | 1 |
| Impotence2 | 3 | 0 |
| Menses delayed3 | 2 | 1 |
| Menstrual disorder3 | 3 | 2 |
| Menstruation irregular3 | 2 | 0 |
| Orgasm abnormal | 2 | 1 |
| Prostatitis2 | 3 | 0 |
| Skin and Subcutaneous Tissue Disorders | | |
| Dermatitis | 2 | 1 |
| Sweating increased | 4 | 1 |
| Vascular Disorders | | |
| Hot flushes | 3 | 1 |
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 |
|
1 Males only.
|
| Erectile disturbance1 | 7% | 1% |
| Impotence1 | 3% | 0% |
| Orgasm abnormal | 2% | 1% |
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.
Postmarketing Spontaneous Reports
The following list of undesirable effects (adverse drug reactions) is based on post-marketing spontaneous reports, and corresponding reporting rates have been provided.
Vascular disorders — Very rare (<0.01%): Peripheral vascular instability and/or Raynaud's phenomenon (new onset and exacerbation of preexisting condition).
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