STRATTERA SIDE EFFECTS
- Generic Name: atomoxetine hcl
- Brand Name: Strattera
SIDE EFFECTS
Clinical Trials Experience
STRATTERA was administered to 5382 children or adolescent patients with ADHD and 1007 adults with ADHD in clinical studies. During the ADHD clinical trials, 1625 children and adolescent patients were treated for longer than 1 year and 2529 children and adolescent patients were treated for over 6 months.
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Child And Adolescent Clinical Trials
Reasons For Discontinuation Of Treatment Due To Adverse Reactions In Child And Adolescent Clinical Trials
In acute child and adolescent placebo-controlled trials, 3.0% (48/1613) of atomoxetine subjects and 1.4% (13/945) placebo subjects discontinued for adverse reactions. For all studies, (including open-label and long-term studies), 6.3% of extensive metabolizer (EM) patients and 11.2% of poor metabolizer (PM) patients discontinued because of an adverse reaction. Among 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 1 patient.
Seizures
STRATTERA has not been systematically evaluated in pediatric patients with seizure disorder as these patients were excluded from clinical studies during the product’s premarket testing. In the clinical development program, seizures were reported in 0.2% (12/5073) of children whose average age was 10 years (range 6 to 16 years). In these clinical trials, the seizure risk among poor metabolizers was 0.3% (1/293) compared to 0.2% (11/4741) for extensive metabolizers.
Commonly Observed Adverse Reactions In Acute Child And Adolescent, Placebo-Controlled Trials
Commonly observed adverse reactions associated with the use of 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. Results were similar in the BID and the QD trial except as shown in Table 3, which shows both BID and QD results for selected adverse reactions based on statistically significant Breslow-Day tests. The most commonly observed adverse reactions in patients treated with STRATTERA (incidence of 5% or greater and at least twice the incidence in placebo patients, for either BID or QD dosing) were: nausea, vomiting, fatigue, decreased appetite, abdominal pain, and somnolence.
Additional data from ADHD clinical trials (controlled and uncontrolled) has shown that approximately 5 to 10% of pediatric patients experienced potentially clinically important changes in heart rate (≥20 beats per min) or blood pressure (≥15 to 20 mm Hg).
Table 1: Common Treatment–Emergent Adverse Reactions Associated with the Use of STRATTERA in Acute (up to 18 weeks) Child and Adolescent Trials
| Adverse Reactiona | Percentage of Patients Reporting Reaction | |
| System Organ Class/ Adverse Reaction | STRATTERA (N=1597) |
Placebo (N=934) |
| Gastrointestinal Disorders | ||
| Abdominal painb | 18 | 10 |
| Vomiting | 11 | 6 |
| Nausea | 10 | 5 |
| General Disorders and Administration Site Conditions | ||
| Fatigue | 8 | 3 |
| Irritability | 6 | 3 |
| Therapeutic response unexpected | 2 | 1 |
| Investigations | ||
| Weight decreased | 3 | 0 |
| Metabolism and Nutritional Disorders | ||
| Decreased appetite | 16 | 4 |
| Anorexia | 3 | 1 |
| Nervous System Disorders | ||
| Headache | 19 | 15 |
| Somnolencec | 11 | 4 |
| Dizziness | 5 | 2 |
| Skin and Subcutaneous Tissue Disorders | ||
| Rash | 2 | 1 |
| a Reactions reported by at least 2% of patients treated with atomoxetine, and greater than placebo. The following reactions did not meet this criterion but were reported by more atomoxetine-treated patients than placebo-treated patients and are possibly related to atomoxetine 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 atomoxetine, 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 a statistically significant dose relationship: pruritus. b Abdominal pain includes the terms: abdominal pain upper, abdominal pain, stomach discomfort, abdominal discomfort, epigastric discomfort. c Somnolence includes the terms: sedation, somnolence. |
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Table 2: Common Treatment-Emergent Adverse Reactions Associated with the Use of STRATTERA in Acute (up to 18 weeks) Child and Adolescent Trials
| Adverse Reaction | Percentage of Patients Reporting Reaction from BID Trials | Percentage of Patients Reporting Reaction from QD Trials | ||
| STRATTERA (N=715) |
Placebo (N=434) |
STRATTERA (N=882) |
Placebo (N=500) |
|
| Gastrointestinal Disorders | ||||
| Abdominal paina | 17 | 13 | 18 | 7 |
| Vomiting | 11 | 8 | 11 | 4 |
| Nausea | 7 | 6 | 13 | 4 |
| Constipationb | 2 | 1 | 1 | 0 |
| General Disorders | ||||
| Fatigue | 6 | 4 | 9 | 2 |
| Psychiatric Disorders | ||||
| Mood swingsc | 2 | 0 | 1 | 1 |
| a Abdominal pain includes the terms: abdominal pain upper, abdominal pain, stomach discomfort, abdominal discomfort, epigastric discomfort. b Constipation didn’t meet the statistical significance on Breslow-Day test but is included in the table because of pharmacologic plausibility. c Mood swings didn’t meet the statistical significance on Breslow-Day test at 0.05 level but p-value was <0.1 (trend). |
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The following adverse reactions occurred in at least 2% of child and adolescent CYP2D6 PM patients and were statistically significantly more frequent in PM patients compared with CYP2D6 EM patients: insomnia (11% of PMs, 6% of EMs); weight decreased (7% of PMs, 4% of EMs); constipation (7% of PMs, 4% of EMs); depression1 (7% of PMs, 4% of EMs); tremor (5% of PMs, 1% of EMs); excoriation (4% of PMs, 2% of EMs); middle insomnia (3% of PMs, 1% of EMs); conjunctivitis (3% of PMs, 1% of EMs); syncope (3% of PMs, 1% of EMs); early morning awakening (2% of PMs, 1% of EMs); mydriasis (2% of PMs, 1% of EMs); sedation (4% of PMs, 2% of EMs).
1Depression includes the following terms: depression, major depression, depressive symptoms, depressed mood, dysphoria.
Adult Clinical Trials
Reasons For Discontinuation Of Treatment Due To Adverse Reactions In Acute Adult Placebo-Controlled Trials
In the acute adult placebo-controlled trials, 11.3% (61/541) atomoxetine subjects and 3.0% (12/405) placebo subjects 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 1 patient.
Seizures
STRATTERA has not been systematically evaluated in adult patients with a seizure disorder as these patients were excluded from clinical studies during the product’s premarket testing. In the clinical development program, seizures were reported on 0.1% (1/748) of adult patients. In these clinical trials, no poor metabolizers (0/43) reported seizures compared to 0.1% (1/705) for extensive metabolizers.
Commonly Observed Adverse Reactions In Acute Adult Placebo-Controlled Trials
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 4. 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 4). Additional data from ADHD clinical trials (controlled and uncontrolled) has shown that approximately 5 to 10% of adult patients experienced potentially clinically important changes in heart rate (≥20 beats per min) or blood pressure (≥15 to 20 mm Hg).
Table 3: Common Treatment-Emergent Adverse Reactions Associated with the Use of STRATTERA in Acute (up to 25 weeks) Adult Trials
| Adverse Reactiona | Percentage of Patients Reporting Reaction | |
| System Organ Class/ Adverse Reaction | STRATTERA (N=1697) |
Placebo (N=1560) |
| Cardiac Disorders | ||
| Palpitations | 3 | 1 |
| Gastrointestinal Disorders | ||
| Dry mouth | 20 | 5 |
| Nausea | 26 | 6 |
| Constipation | 8 | 3 |
| Abdominal painb | 7 | 4 |
| Dyspepsia | 4 | 2 |
| Vomiting | 4 | 2 |
| General Disorders and Administration Site Conditions | ||
| Fatigue | 10 | 6 |
| Chills | 3 | 0 |
| Feeling jittery | 2 | 1 |
| Irritability | 5 | 3 |
| Thirst | 2 | 1 |
| Investigations | ||
| Weight decreased | 2 | 1 |
| Metabolism and Nutritional Disorders | ||
| Decreased appetite | 16 | 3 |
| Nervous System Disorders | ||
| Dizziness | 8 | 3 |
| Somnolencec | 8 | 5 |
| Paraesthesia | 3 | 0 |
| Psychiatric Disorders | ||
| Abnormal dreams | 4 | 3 |
| Insomniad | 15 | 8 |
| Libido decreased | 3 | 1 |
| Sleep disorder | 3 | 1 |
| Renal and Urinary Disorders | ||
| Urinary hesitatione | 6 | 1 |
| Dysuria | 2 | 0 |
| Reproductive System and Breast Disorders | ||
| Erectile dysfunctionf | 8 | 1 |
| Dysmenorrheag | 3 | 2 |
| Ejaculation delayedf and/or ejaculation disorderf | 4 | 1 |
| Skin and Subcutaneous Tissue Disorders | ||
| Hyperhidrosis | 4 | 1 |
| Vascular Disorders | ||
| Hot flush | 3 | 0 |
| a Reactions reported by at least 2% of patients treated with atomoxetine, and greater than placebo. The following reactions did not meet this criterion but were reported by more atomoxetine-treated patients than placebo-treated patients and are possibly related to atomoxetine 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. The following reactions were reported by at least 2% of patients treated with atomoxetine, and equal to or less than placebo: anxiety, diarrhea, back pain, headache, and oropharyngeal pain. bAbdominal pain includes the terms: abdominal pain upper, abdominal pain, stomach discomfort, abdominal discomfort,epigastric discomfort. cSomnolence includes the terms: sedation, somnolence. d Insomnia includes the terms: insomnia, initial insomnia, middle insomnia, and terminal insomnia. eUrinary hesitation includes the terms: urinary hesitation, urine flow decreased. fBased on total number of males (STRATTERA, N=943; placebo, N=869). gBased on total number of females (STRATTERA, N=754; placebo, N=691). |
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The following adverse events occurred in at least 2% of adult CYP2D6 poor metaboliser (PM) patients and were statistically significantly more frequent in PM patients compared to CYP2D6 extensive metaboliser (EM) patients: vision blurred (4% of PMs, 1% of EMs); dry mouth (35% of PMs, 17% of EMs); constipation (11% of PMs, 7% of EMs); feeling jittery (5% of PMs, 2% of EMs); decreased appetite (23% of PMs, 15% of EMs); tremor (5% of PMs, 1% of EMs); insomnia (19% of PMs, 11% of EMs); sleep disorder (7% of PMs, 3% of EMs); middle insomnia (5% of PMs, 3% of EMs); terminal insomnia (3% of PMs, 1% of EMs); urinary retention (6% of PMs, 1% of EMs); erectile dysfunction (21% of PMs, 9% of EMs); ejaculation disorder (6% of PMs, 2% of EMs); hyperhidrosis (15% of PMs, 7% of EMs); peripheral coldness (3% of PMs, 1% of EMs).
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. Table 4 above displays the incidence of sexual side effects reported by at least 2% of adult patients taking STRATTERA in placebo-controlled trials.
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 adverse reactions have been identified during post approval use of STRATTERA. Unless otherwise specified, these adverse reactions have occurred in adults and children and adolescents. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Cardiovascular system – QT prolongation, syncope.
Peripheral vascular effects – Raynaud’s phenomenon.
General disorders and administration site conditions – Lethargy.
Musculoskeletal system – Rhabdomyolysis.
Nervous system disorders – Hypoaesthesia; paraesthesia in children and adolescents; sensory disturbances; tics.
Psychiatric disorders – Depression and depressed mood; anxiety, libido changes.
Seizures – Seizures have been reported in the postmarketing period. The postmarketing seizure cases include patients with pre-existing seizure disorders and those with identified risk factors for seizures, as well as patients with neither a 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 children and adolescents; urinary retention in children and adolescents.
SRC: NLM .