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Atomoxetine is a brand name for Atomoxetine. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: 1 INDICATIONS AND USAGE Atomoxetine capsule is a selective norepinephrine reuptake inhibitor indicated for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD). ( 1.1 ) 1.1 Attention-Deficit/Hyperactivity Disorder (ADHD) Atomoxetine capsule is indicated for the treatment of Attention-Deficit/Hyperactivity…
Verbatim from this product's FDA label. Tap a section to expand.
4 mg/kg Children and adolescents over 70 kg and adults 40 mg 80 mg 100 mg Dosing adjustment — Hepatic Impairment, Strong CYP2D6 Inhibitor, and in patients known to be CYP2D6 poor metabolizers (PMs). 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.
2 mg/kg/day [see Clinical Studies ( 14 )]. 4 mg/kg or 100 mg, whichever is less. Dosing of children and adolescents over 70 kg body weight and adults - Atomoxetine capsules 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 ( 14 )].
The maximum recommended total daily dose in children and adolescents over 70 kg and adults is 100 mg. 2 Maintenance/Extended Treatment It is generally agreed that pharmacological treatment of ADHD may be needed for extended periods.
8 mg/kg/day was demonstrated in a controlled trial. Patients assigned to atomoxetine capsules in the maintenance phase were generally continued on the same dose used to achieve a response in the open label phase. 1 )]. 3 General Dosing Information Atomoxetine capsules may be taken with or without food.
Atomoxetine capsules can be discontinued without being tapered. Atomoxetine capsules are not intended to be opened, they should be taken whole [see Patient Counseling Information ( 17 )]. The safety of single doses over 120 mg and total daily doses above 150 mg have not been systematically evaluated.
4 Dosing in Specific Populations 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).
6 )]. 2 mg/kg/day if symptoms fail to improve after 4 weeks and the initial dose is well tolerated. , paroxetine, fluoxetine, and quinidine, atomoxetine capsule 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.
6 ADVERSE REACTIONS Most common adverse reactions (≥5% and at least twice the incidence of placebo patients) • Child and Adolescent Clinical Trials – Nausea, vomiting, fatigue, decreased appetite, abdominal pain, and somnolence. 1 ) • Adult Clinical Trials – Constipation, dry mouth, nausea, decreased appetite, dizziness, erectile dysfunction, and urinary hesitation.
gov/medwatch. 1 Clinical Trials Experience Atomoxetine 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.
4% (13/945) placebo subjects discontinued for adverse reactions. 2% of poor metabolizer (PM) patients discontinued because of an adverse reaction. 1%, N=2) were the reasons for discontinuation reported by more than 1 patient. Seizures — Atomoxetine 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.
2% (12/5073) of children whose average age was 10 years (range 6 to 16 years). 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 atomoxetine (incidence of 2% or greater) and not observed at an equivalent incidence among placebo-treated patients (atomoxetine incidence greater than placebo) are listed in Table 2.
5 WARNINGS AND PRECAUTIONS • Suicidal Ideation – Monitor for suicidality, clinical worsening, and unusual changes in behavior. 1 ) • Severe Liver Injury – Should be discontinued and not restarted in patients with jaundice or laboratory evidence of liver injury.
2 ) • Serious Cardiovascular Events – Sudden death, stroke and myocardial infarction have been reported in association with atomoxetine treatment. Patients should have a careful history and physical exam to assess for presence of cardiovascular disease.
Atomoxetine generally should not be used in children or adolescents with known serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, or other serious cardiac problems that may place them at increased vulnerability to its noradrenergic effects.
Consideration should be given to not using atomoxetine capsules in adults with clinically significant cardiac abnormalities. 3 ) • Emergent Cardiovascular Symptoms – Patients should undergo prompt cardiac evaluation. 3 ) • Effects on Blood Pressure and Heart Rate –Increase in blood pressure and heart rate; orthostasis and syncope may occur.
Use with caution in patients with hypertension, tachycardia, or cardiovascular or cerebrovascular disease. 4 ) • Emergent Psychotic or Manic Symptoms – Consider discontinuing treatment if such new symptoms occur. 5 ) • Bipolar Disorder – Screen patients to avoid possible induction of a mixed/manic episode.
6 ) • Aggressive behavior or hostility should be monitored. 7 ) • Possible allergic reactions, including anaphylactic reactions, angioneurotic edema, urticaria, and rash. 8 ) • Effects on Urine Outflow – Urinary hesitancy and retention may occur.
9 ) • Priapism – Prompt medical attention is required in the event of suspected priapism. 10 , 17 ) • Growth – Height and weight should be monitored in pediatric patients. 11 ) • Concomitant Use of Potent CYP2D6 Inhibitors or Use in patients known to be CYP2D6 PMs – Dose adjustment of atomoxetine may be necessary.
4 CONTRAINDICATIONS • Hypersensitivity to atomoxetine or other constituents of product. 1 ) • Atomoxetine capsules use within 2 weeks after discontinuing MAOI or other drugs that affect brain monoamine concentrations. 1 ) • Narrow Angle Glaucoma.
4 ) • Severe Cardiovascular Disorders that might deteriorate with clinically important increases in HR and BP. 8 )]. 2 Monoamine Oxidase Inhibitors (MAOI) Atomoxetine capsules 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 atomoxetine capsules. 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. 1 )]. 3 Narrow Angle Glaucoma In clinical trials, atomoxetine capsules use was associated with an increased risk of mydriasis and therefore its use is not recommended in patients with narrow angle glaucoma.
4 Pheochromocytoma Serious reactions, including elevated blood pressure and tachyarrhythmia, have been reported in patients with pheochromocytoma or a history of pheochromocytoma who received atomoxetine capsules. Therefore, atomoxetine capsules should not be taken by patients with pheochromocytoma or a history of pheochromocytoma.
5 Severe Cardiovascular Disorders Atomoxetine capsules should not be used in patients with severe cardiac or vascular disorders whose condition would be expected to deteriorate if they experience increases in blood pressure or heart rate that could be clinically important (for example, 15 to 20 mm Hg in blood pressure or 20 beats per minute in heart rate).
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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 atomoxetine (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 ( see Tables 2 and 3).
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) [see Contraindications ( 4 ) and Warnings and Precautions ( 5 )].
Table 2:
Common Treatment-Emergent Adverse Reactions Associated with the Use of Atomoxetine in Acute (up to 18 weeks) Child and Adolescent Trials Adverse Reaction a Percentage of Patients Reporting Reaction Atomoxetine (N=1597) Placebo (N=934) Gastrointestinal Disorders Abdominal Pain b 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 Somnolence c 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.
Table 3:
Common Treatment-Emergent Adverse Reactions Associated with the Use of Atomoxetine 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 Atomoxetine (N=715) Placebo (N=434) Atomoxetine (N=882) Placebo (N=500) Gastrointestinal Disorders Abdominal Pain a 17 13 18 7 Vomiting 11 8 11 4 Nausea 7 6 13 4 Constipation b 2 1 1 0 General Disorders Fatigue 6 4 9 2 Psychiatric Disorders Mood swings c 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. 1 (trend). 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. 3% (61/541) atomoxetine subjects and 3% (12/405) placebo subjects discontinued for adverse reactions. 4%, N=2) were the reasons for discontinuation reported by more than 1 patient.
Seizures — Atomoxetine 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. 1% (1/748) of adult patients. 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 atomoxetine (incidence of 2% or greater) and not observed at an equivalent incidence among placebo-treated patients (atomoxetine incidence greater than placebo) are listed in Table 4.
The most commonly observed adverse reactions in patients treated with atomoxetine (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) [see Contraindications ( 4 ) and Warnings and Precautions ( 5 )].
Table 4:
Common Treatment-Emergent Adverse Reactions Associated with the Use of Atomoxetine in Acute (up to 25 weeks) Adult Trials Adverse Reaction a Percentage of Patients Reporting Reaction Atomoxetine (N=1697) Placebo (N=1560) Cardiac Disorders Palpitations 3 1 Gastrointestinal Disorders Dry mouth 20 5 Nausea 26 6 Constipation 8 3 Abdominal pain b 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 Somnolence c 8 5 Paraesthesia 3 0 Psychiatric Disorders Abnormal dreams 4 3 Insomnia d 15 8 Libido decreased 3 1 Sleep disorder 3 1 Renal and Urinary Disorders Urinary hesitation e 6 1 Dysuria 2 0 Reproductive System and Breast Disorders Erectile dysfunction f 8 1 Dysmenorrhea g 3 2 Ejaculation delayed f and/or ejaculation disorder f 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. b Abdominal pain includes the terms: abdominal pain upper, abdominal pain, stomach discomfort, abdominal discomfort, epigastric discomfort.
c Somnolence includes the terms: sedation, somnolence. d Insomnia includes the terms: insomnia, initial insomnia, middle insomnia, and terminal insomnia. e Urinary hesitation includes the terms: urinary hesitation, urine flow decreased.
f Based on total number of males (atomoxetine, N=943; placebo, N=869). g Based on total number of females (atomoxetine, N=754; placebo, N=691). 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 atomoxetine in placebo-controlled trials.
There are no adequate and well-controlled studies examining sexual dysfunction with atomoxetine treatment. While it is difficult to know the precise risk of sexual dysfunction associated with the use of atomoxetine, physicians should routinely inquire about such possible side effects.
2 Postmarketing Spontaneous Reports The following adverse reactions have been identified during post approval use of atomoxetine. 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 atomoxetine 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.
1 Suicidal Ideation Atomoxetine increased the risk of suicidal ideation in short-term studies in children and adolescents with Attention-Deficit/Hyperactivity Disorder (ADHD). Pooled analyses of short-term (6 to 18 weeks) placebo-controlled trials of atomoxetine in children and adolescents have revealed a greater risk of suicidal ideation early during treatment in those receiving atomoxetine.
There were a total of 12 trials (11 in ADHD and 1 in enuresis) involving over 2200 patients (including 1357 patients receiving atomoxetine and 851 receiving placebo). 4% (5/1357 patients), compared to none in placebo-treated patients.
There was 1 suicide attempt among these approximately 2200 patients, occurring in a patient treated with atomoxetine. No suicides occurred in these trials . All reactions occurred in children 12 years of age or younger. All reactions occurred during the first month of treatment.
It is unknown whether the risk of suicidal ideation in pediatric patients extends to longer-term use. A similar analysis in adult patients treated with atomoxetine for either ADHD or major depressive disorder (MDD) did not reveal an increased risk of suicidal ideation or behavior in association with the use of atomoxetine.
All pediatric patients being treated with atomoxetine should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases.
The following symptoms have been reported with atomoxetine: anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania and mania. Although a causal link between the emergence of such symptoms and the emergence of suicidal impulses has not been established, there is a concern that such symptoms may represent precursors to emerging suicidality.
Thus, patients being treated with atomoxetine should be observed for the emergence of such symptoms. Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients who are experiencing emergent suicidality or symptoms that might be precursors to emerging suicidality, especially if these symptoms are severe or abrupt in onset, or were not part of the patient’s presenting symptoms.
Families and caregivers of pediatric patients being treated with atomoxetine should be alerted about the need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior, and the other symptoms described above, as well as the emergence of suicidality, and to report such symptoms immediately to healthcare providers.
Such monitoring should include daily observation by families and caregivers. 2 Severe Liver Injury Postmarketing reports indicate that atomoxetine can cause severe liver injury. Although no evidence of liver injury was detected in clinical trials of about 6000 patients, there have been rare cases of clinically significant liver injury that were considered probably or possibly related to atomoxetine capsules use in postmarketing experience.
Rare cases of liver failure have also been reported, including a case that resulted in a liver transplant. Because of probable underreporting, it is impossible to provide an accurate estimate of the true incidence of these reactions.
Reported cases of liver injury occurred within 120 days of initiation of atomoxetine in the majority of cases and some patients presented with markedly elevated liver enzymes [>20 X upper limit of normal (ULN)], and jaundice with significantly elevated bilirubin levels (>2 X ULN), followed by recovery upon atomoxetine discontinuation.
In one patient, liver injury, manifested by elevated hepatic enzymes up to 40 X ULN and jaundice with bilirubin up to 12 X ULN, recurred upon rechallenge, and was followed by recovery upon drug discontinuation, providing evidence that atomoxetine likely 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. The patient described above recovered from his liver injury, and did not require a liver transplant.
Atomoxetine should be discontinued in patients with jaundice or laboratory evidence of liver injury, and should not be restarted. 12 ); Patient Counseling Information ( 17 )]. 3 Serious Cardiovascular Events Sudden Death and Pre-existing Structural Cardiac Abnormalities or Other Serious Heart Problems Children and Adolescents — Sudden death has been reported in association with atomoxetine treatment at usual doses in children and adolescents with structural cardiac abnormalities or other serious heart problems.
Although some serious heart problems alone carry an increased risk of sudden death, atomoxetine generally should not be used in children or adolescents with known serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, or other serious cardiac problems that may place them at increased vulnerability to the noradrenergic effects of atomoxetine.
Adults — Sudden deaths, stroke, and myocardial infarction have been reported in adults taking atomoxetine at usual doses for ADHD. Although the role of atomoxetine in these adult cases is also unknown, adults have a greater likelihood than children of having serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, or other serious cardiac problems.
Consideration should be given to not treating adults with clinically significant cardiac abnormalities. , electrocardiogram and echocardiogram). Patients who develop symptoms such as exertional chest pain, unexplained syncope, or other symptoms suggestive of cardiac disease during atomoxetine treatment should undergo a prompt cardiac evaluation.
4 Effects on Blood Pressure and Heart Rate Atomoxetine 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.
5 )] . Pulse and blood pressure should be measured at baseline, following atomoxetine dose increases, and periodically while on therapy to detect possible clinically important increases. The following table provides short-term, placebo-controlled clinical trial data for the proportions of patients having an increase in: diastolic blood pressure ≥15 mm Hg; systolic blood pressure ≥20 mm Hg; heart rate greater than or equal to 20 bpm, in both the pediatric and adult populations ( see Table 1).
0 a 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 clinical trial. 3% (5/1597) of these atomoxetine patients compared with 0% (0/934) of placebo patients.
4 beats/minute. 5 beats/minute). The heart rate effects could be clinically important in some PM patients. 5% (2/402) of placebo patients. 40 mm Hg). The blood pressure effects could be clinically important in some PM patients. Orthostatic hypotension and syncope have been reported in patients taking atomoxetine.
8% (46/5596) experienced syncope. 5% (1/207) of placebo-treated patients. Syncope was not reported during short-term child and adolescent placebo-controlled ADHD registration studies. Atomoxetine 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.
, hallucinations, delusional thinking, or mania in children and adolescents without a prior history of psychotic illness or mania can be caused by atomoxetine at usual doses. If such symptoms occur, consideration should be given to a possible causal role of atomoxetine, and discontinuation of treatment should be considered.
2% (4 patients with reactions out of 1939 exposed to atomoxetine for several weeks at usual doses) of atomoxetine-treated patients compared to 0 out of 1056 placebo-treated patients. 6 Screening Patients for Bipolar Disorder In general, particular care should be taken in treating ADHD in patients with comorbid bipolar disorder because of concern for possible induction of a mixed/manic episode in patients at risk for bipolar disorder.
Whether any of the symptoms described above represent such a conversion is unknown. However, prior to initiating treatment with atomoxetine, patients with comorbid depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression.
7 Aggressive Behavior or Hostility Patients beginning treatment for ADHD should be monitored for the appearance or worsening of aggressive behavior or hostility. Aggressive behavior or hostility is often observed in children and adolescents with ADHD.
I. 64 – not statistically significant]). I. 88 – not statistically significant]). Although this is not conclusive evidence that atomoxetine capsules causes aggressive behavior or hostility, these behaviors were more frequently observed in clinical trials among children, adolescents, and adults treated with atomoxetine capsules compared to placebo.
8 Allergic Events Although uncommon, allergic reactions, including anaphylactic reactions, angioneurotic edema, urticaria, and rash, have been reported in patients taking atomoxetine. 5%, 2/402, respectively). 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. 10 Priapism Rare postmarketing cases of priapism, defined as painful and nonpainful penile erection lasting more than 4 hours, have been reported for pediatric and adult patients treated with atomoxetine.
The erections resolved in cases in which follow-up information was available, some following discontinuation of atomoxetine. Prompt medical attention is required in the event of suspected priapism. 11 Effects on Growth Data on the long-term effects of atomoxetine on growth come from open-label studies, and weight and height changes are compared to normative population data.
In general, the weight and height gain of pediatric patients treated with atomoxetine lags behind that predicted by normative population data for about the first 9 to 12 months of treatment. 5 kg more than predicted by their baseline data.
4 cm less than predicted by their baseline data ( see Figure 1 below).
Figure 1:
Mean Weight and Height Percentiles Over Time for Patients with Three Years of Atomoxetine Treatment This growth pattern was generally similar regardless of pubertal status at the time of treatment initiation. 2 cm less than predicted after three years.
Patients who were pubertal (girls >8 to ≤13 years old, boys >9 to ≤14 years old) or late pubertal (girls >13 years old, boys >14 years old) had average weight and height gains that were close to or exceeded those predicted after three years of treatment.
Growth followed a similar pattern in both extensive and poor metabolizers (EMs, PMs). 4 cm less than predicted. 1 cm in the placebo-treated patients. 8 mg/kg/day dose groups. Growth should be monitored during treatment with atomoxetine.
12 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 atomoxetine 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. 1 )]. 13 Concomitant Use of Potent CYP2D6 Inhibitors or Use in Patients who are known to be CYP2D6 PMs Atomoxetine is primarily metabolized by the CYP2D6 pathway to 4-hydroxyatomoxetine.
, paroxetine, fluoxetine, and quinidine) or when administered to CYP2D6 PMs. 2 )].
4 )].