Atomoxetine is a selective norepinephrine reuptake inhibitor (NRI) and was the first nonstimulant drug approved for attention-deficit hyperactivity disorder (ADHD). It is structurally similar to fluoxetine, does not have a potential for abuse, and is not classified as a controlled substance. Atomoxetine has been shown to be safe and effective in adults and pediatric patients 6 years and adults with ADHD per DSM-IV criteria (for inattentive subtype and both inattentive and hyperactive/impulsive subtypes). Well-controlled comparative data with stimulants are limited. However, when compared with stimulants (effect size = 1), atomoxetine has an effect size of 0.7. While atomoxetine is effective for the management of ADHD in many patients, the body of evidence supporting its use is smaller than traditional psychostimulants. Atomoxetine has a slower onset to action than the stimulants; the onset of effect may take 1 week; and full effect may not be seen for up to 4 weeks on a given target dose. Atomoxetine may be considered an alternate ADHD therapy in patients where psychostimulants are not an option or if initially preferred by parents and/or health care provider. Atomoxetine is a particularly attractive treatment option for patients in whom misuse or diversion is a concern due to its lack of abuse potential. In patients with co-morbid anxiety disorder, the drug has been noted to not increase anxiety symptoms in some studies. However, clinical guidelines generally recommend the use of the stimulants (e.g., methylphenidate, dextroamphetamine, or amphetamine salts), in combination with behavioral therapy, as first-line treatment in ADHD. As with other medications for ADHD, careful monitoring of patients during treatment is necessary. Although it is not a stimulant medication, atomoxetine has been reported to increase blood pressure and heart rate and has been associated with rare sudden death in children with structural cardiac abnormalities or other serious heart conditions. The American Heart Association (AHA) recommends careful screening of all children and adolescents prior to initiating pharmacologic therapy for ADHD. Rare reports of drug-induced liver injury have been reported. There have also been reports of suicidal thinking in children and adolescents being treated for ADHD with atomoxetine and a boxed warning in the product label notes the increased risk of suicidality in children and adolescents. Patients being treated with atomoxetine should be closely monitored for clinical worsening, as well as agitation, irritability, suicidal thinking or behaviors, and unusual changes in moods or behavior.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
-Administer as a single daily dose in the morning or in evenly divided doses in the morning and late afternoon/early evening. Patients who have insomnia due to the medication should take the last dose of the day before 6 PM.
Oral Solid Formulations
-Administer capsules whole; do not cut, crush, or chew. May give with or without food. If nausea occurs, it may be helpful to administer after a meal.
-Do not open the capsules. Atomoxetine is an ocular irritant. If contact with the eye occurs, immediately flush the affected eye with water and seek medical advice. Hands or contaminated surfaces should be washed promptly.
During clinical trials, atomoxetine was administered to 5382 children and adolescents with attention-deficit hyperactivity disorder (ADHD) and and 270 adults. Of the pediatric patients, 2529 patients were treated for longer than 6 months and 1625 patients were treated for longer than 1 year. The safety of single doses over 120 mg PO and total daily doses above 150 mg/day PO have not been systematically evaluated. The most commonly reported adverse events (>= 5% and twice the incidence vs. placebo) involved the central nervous system (CNS) and gastrointestinal tract (GI). In adults, genitourinary (GU) complaints were also commonly reported. Poor metabolizers (PMs) of CYP2D6 substrates have been shown to be at higher risk for adverse drug reactions. For all studies in children and adolescents, 6.3% of extensive metabolizers (EMs) and 11.2% of poor metabolizers (PMs) discontinued therapy due to an adverse event.
During clinical trials of atomoxetine in adults with Attention-Deficit/Hyperactivity Disorder (ADHD), the following centrally-mediated effects occurred more frequently with atomoxetine than placebo: dizziness (8% vs 3%), drowsiness (8% vs 5%), abnormal dreams (4% vs 3%), sleep disorder (3% vs 1%), feeling jittery (2% vs 1%), and insomnia (15% vs 8%). In placebo-controlled clinical trials in pediatric patients, the following CNS effects occurred: drowsiness (11% vs 4%) and dizziness (5% vs 2%). Insomnia (0.9%) and drowsiness (0.3%) were among the most common reasons for study discontinuation in adult and/or pediatric patients. Early morning awakenings occurred at an incidence < 2% but greater than placebo in children. Tremor occurred at an incidence < 2% but greater than placebo in adult patients. Asthenia occurred at an incidence < 2% but greater than placebo in both children and adult patients. Certain adverse events have been noted by the manufacturer to have a greater incidence in atomoxetine poor metabolizers (PM) vs. extensive metabolizers (EM). The following CNS adverse events 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), tremor (5% of PMs, 1% of EMs), middle insomnia (3% of PMs, 1% of EMs), sedation (4% of PMs, 2% of EMs), and early morning awakening (2% of PMs, 1% of EMs). The following CNS effects occurred in at least 2% of adult CYP2D6 PMs and were statistically significantly more frequent in PM patients than CYP2D6 EM patients: feeling jittery (5% of PMs, 2% 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), and terminal insomnia (3% of PMs, 1% of EMs).
During clinical trials of atomoxetine in adults with Attention-Deficit/Hyperactivity Disorder (ADHD), fatigue occurred more frequently with atomoxetine than placebo (10% vs 6%). In placebo-controlled clinical trials in pediatric patients, fatigue also occurred more frequently in atomoxetine-treated patients than placebo-treated patients (6-9% vs 2-4%). Fatigue resulted in treatment discontinuation in 0.1% of pediatric patients and 0.6% of adult patients during clinical trials. Lethargy has been reported during post-marketing use of atomoxetine; however, the frequency is unknown and causality to the drug has not been established.
During clinical trials of atomoxetine in children and adolescents with Attention-Deficit/Hyperactivity Disorder (ADHD), the following psychiatric effects occurred more frequently with atomoxetine than placebo: irritability (6% vs. 3%) and emotional lability (mood swings 1% to 2% vs 0% to 1%). Irritability (5% vs. 3%), agitation (less than 2%), and restlessness (less than 2%) were reported more frequently with atomoxetine than placebo in adult patients. Emergent hostility-related adverse events were reported in 1.6% of atomoxetine-treated pediatric patients versus 1.1% of placebo-treated patients and in 0.35% of atomoxetine-treated adult patients versus 0.26% of placebo-treated patients. Psychotic or manic symptoms (e.g., hallucinations, delusional thinking, or mania) were reported in 0.2% of pediatric patients without a prior history of a psychotic disorder or bipolar disorder receiving atomoxetine versus 0% of patients receiving placebo. Psychiatric adverse effects resulting in treatment discontinuation during clinical trials in pediatric patients included irritability (0.3%), aggression (0.2%), and feeling abnormal (0.1%). Adverse effects resulting in treatment discontinuation in adults included anxiety (0.4%), mood swings (0.4%), and nervousness (0.4%). Certain adverse events have been noted by the manufacturer to have a greater incidence in atomoxetine poor metabolizers (PM) vs. extensive metabolizers (EM). Depression was reported in 7% of child and adolescent CYP2D6 PM patients compared with 4% of CYP2D6 EM patients. Depression, depressed mood, and anxiety have been reported during postmarketing use of the drug; these may also be co-morbid disorders in ADD patients. Patients receiving atomoxetine, particularly children and adolescents, should be closely monitored for clinical worsening, as well as agitation, aggressiveness, akathisia, anxiety, hostility, hypomania, mania, impulsivity, irritability, insomnia, panic attacks, suicidal thinking or behaviors, and unusual changes in behavior, especially during the initial few months of therapy or when the dose is changed (either increased or decreased). While all of these adverse events have not been reported or associated with atomoxetine treatment, many of these symptoms may be precursors to suicidal behavior. Co-morbidities occurring with ADHD may increase the risk of suicidal ideation and/or behavior. Twelve clinical trials conducted in children with ADHD and 1 trial in children with enuresis identified an increased risk of suicidal ideation when taking atomoxetine. There was 1 suicide attempt by a patient who received atomoxetine among the approximately 2,200 patients in the trial. The database and clinical trials included more than 2,200 patients (1,357 patients receiving atomoxetine and 851 receiving a placebo). The analysis showed that 0.4% of children (5 cases) treated with atomoxetine reported suicidal thinking compared to no cases in children treated with the placebo. A similar analysis in adult patients treated with atomoxetine for either ADHD or depression found no increased risk of suicidal ideation or behavior. There were no completed suicides among children, adolescents, or adults. Health care providers should discuss with parents and/or caregivers the need to actively monitor pediatric patients for behavioral changes. In addition, atomoxetine should be prescribed in the smallest quantity consistent with good patient management in order to reduce the risk of overdose. According the Institute for Safe Medication Practices (ISMP), atomoxetine has been reported as a frequently suspected drug in serious adverse drug events in children. Of the serious events reported to the FDA during a 5-year time span (2008 to 2012), psychiatric (e.g., suicidal behaviors, aggression, psychosis or psychotic episodes) and cardiac events were predominant. Because reports submitted to the FDA likely represent only a portion of actual events and may be skewed, further investigation to determine frequency of occurrence and causality to the drug is warranted.
In pediatric clinical trials, headache was reported in 19% of those receiving active drug versus 15% of those on placebo and resulted in treatment discontinuation in 0.1% of pediatric patients. Headache was reported in >= 2% of adult patients receiving atomoxetine but was not reported more frequently than placebo. Paresthesias were reported in adult but not pediatric patients (3% vs 0% for placebo). Paresthesias have been reported in children and adolescents during post-marketing use of atomoxetine; however, the frequency is unknown and causality to the drug has not been established. Hypoesthesia, sensory disturbances, and tics have also occurred during post-marketing use, although frequency and causality are unknown.
Neurologic effects including seizures occurred in 0.1% and 0.2% of adults and pediatrics, respectively, in clinical trials that followed premarket testing of atomoxetine. Within these trials, the seizure risk among pediatrics was greater among poor metabolizers (0.3%) than extensive metabolizers (0.2%). Causality to the drug has not been established. Seizures have been reported in those with and without risk factors for seizures or preexisting seizure disorders during post-marketing use of the drug.
During clinical trials of atomoxetine in adults with Attention-Deficit/Hyperactivity Disorder (ADHD), the following gastrointestinal (GI) effects occurred more frequently with atomoxetine than placebo: xerostomia (20% vs 5%), nausea (26% vs 6%), constipation (8% vs 3%), abdominal pain (7% vs 4%), dyspepsia (4% vs 2%), and vomiting (4% vs 2%). In placebo-controlled clinical trials in pediatric patients, the following GI effects occurred: abdominal pain (17-18% vs 7-13%), vomiting (11% vs 4-8%), nausea (7-13% vs 4-6%), and constipation (1-2% vs 0-1%). Dysgeusia occurred at an incidence < 2% but greater than placebo in adult patients. Diarrhea was reported in >= 2% adults receiving atomoxetine but not more frequently than placebo. GI effects associated with treatment discontinuation in pediatrics or adults included nausea (0.2-0.9%), vomiting (0.2%), abdominal pain (0.2%), and constipation (0.1%). Certain GI adverse events have been noted by the manufacturer to have a greater incidence in atomoxetine poor metabolizers (PM) vs. extensive metabolizers (EM). Constipation has been reported in 7% of child and adolescent CYP2D6 PMs and 4% of CYP2D6 EMs. The following GI effects occurred in at least 2% of adult CYP2D6 PMs and were statistically significantly more frequent in PM patients than CYP2D6 EM patients: xerostomia (35% of PMs, 17% of EMs) and constipation (11% of PMs, 7% of EMs).
During clinical trials of atomoxetine in adults with Attention-Deficit/Hyperactivity Disorder (ADHD), the following genitourinary and reproductive system effects occurred more frequently with atomoxetine than placebo: urinary retention/hesitancy (6% vs 1%), dysuria (2% vs 0%), and dysmenorrhea (3% vs 2%). Menstrual irregularity, urinary urgency, and pollakiuria (increased urinary frequency) occurred at an incidence < 2% but greater than placebo in adult patients. Prostatitis and testicular pain were reported in less than 2% of patients but occurred in more patients receiving atomoxetine than placebo. In adult trials, urinary retention (0.4%) was among the most common reasons for study discontinuation. Certain adverse events have been noted by the manufacturer to have a greater incidence in atomoxetine poor metabolizers (PM) vs. extensive metabolizers (EM). Urinary retention occurred in at least 2% of adult CYP2D6 PMs and was statistically significantly more frequent in PM patients than CYP2D6 EM patients (6% of PMs, 1% of EMs). Urinary hesitation and urinary retention have been reported in children and adolescents during post-marketing use; however, the frequencies are unknown and causality to the drug has not been established. Male pelvic pain has been reported during post-marketing use of the drug although the frequency is unknown and causality has not been established.
Atomoxetine may cause hypertension. Results from clinical trial data indicate that the following increases in blood pressure occurred at any one time during clinical trial evaluation or at study endpoint in adult patients receiving atomoxetine versus placebo, respectively: increased diastolic blood pressure of >= 15 mmHg (4.8-12.6% vs 3.5-8.7%) and increased systolic blood pressure of >= 20 mmHg (4.2-12.4% vs 3.2-7.8%). In pediatric patients, the following increases in blood pressure occurred at any one time during clinical trial evaluation or at study endpoint in patients receiving atomoxetine versus placebo, respectively: increased diastolic blood pressure of >= 15 mmHg (9.3-21.5% vs 4.8-14.1%) and increased systolic blood pressure of >= 20 mm Hg (4.9-12.5% vs 3.3-8.7%). In trials with adults where patient metabolizer status was accessible, poor metabolizers of atomoxetine had higher average increases from baseline in both diastolic and systolic blood pressures compared to extensive metabolizers, with diastolic increases of 4.21 vs 2.13 mmHg and systolic increases of 2.75 vs 2.4 mmHg. These differences may be clinically significant in certain patients who are poor metabolizers. Atomoxetine is contraindicated in patients with severe cardiac conditions that would be expected to deteriorate from potentially significant increases in blood pressure (e.g., 15-20 mmHg); caution is recommended for less severe conditions (e.g., mild hypertension) that may be worsened by increased blood pressure. Blood pressure measurements should be obtained at baseline, following dose increases, and periodically throughout atomoxetine therapy.
During clinical trials, cardiovascular adverse reactions included orthostatic hypotension and syncope. Orthostatic hypotension (0.2-1.8%) and syncope (0.8%) were been reported during controlled trials in children. Syncope has also been reported in post-market use of atomoxetine in both adults and children. Atomoxetine should be used with caution in patients with a predisposition to hypotension or other conditions associated with abrupt heart rate or blood pressure changes. There appears to be a greater incidence in atomoxetine poor metabolizers (PM) vs. extensive metabolizers (EM) ; syncope was reported in 3% of child and adolescent CYP2D6 PMs and 1% of CYP2D6 EMs. According the Institute for Safe Medication Practices (ISMP), atomoxetine has been reported as a frequently suspected drug in serious adverse drug events in children. Of the serious events reported to the FDA during a 5-year time span (2008-2012), psychiatric and cardiac (e.g., syncope, chest pain, ECG changes) events were predominant. Because reports submitted to the FDA likely represent only a portion of actual events and may be skewed, further investigation to determine frequency of occurrence and causality to the drug is warranted. Monitor blood pressure and pulse regularly during treatment. Patients who develop symptoms such as unexplained syncope, or other symptoms suggestive of cardiac disease during atomoxetine treatment should undergo a prompt cardiac evaluation.
Results from clinical trial data indicate that 10.2-22.4% of adult patients receiving atomoxetine experienced an increase in heart rate of at least 20 beats/minute at any one time during clinical trial evaluation or at study endpoint compared to 2-8.3% of those receiving placebo. In pediatric patients receiving atomoxetine, 12.2-23.4% experienced increases in heart rate of at least 20 beats/minute compared to 3.8-11.5% of those receiving placebo. Sinus tachycardia was observed in 1.5% of adults receiving atomoxetine versus 0.5% of those on placebo. In pediatric patients, sinus tachycardia was observed in 0.3% of atomoxetine-treated patients and 0% of placebo-treated patients. Mean increases in heart rate were higher among pediatric patients who were poor metabolizers (PMs) than extensive metabolizers (EMs), reported as increases of 9.4 beats/minute and 5 beats/minute, respectively. In clinical trials with adults where patient metabolizer status was accessible, adult PMs of atomoxetine had significantly higher mean increases in heart rate compared to adult EMs (11 beats/minute compared to 7.5 beats/minute). These differences may be clinically significant in some patients who are poor metabolizers. Atomoxetine is contraindicated in patients with severe cardiac conditions that would be expected to deteriorate from potentially significant increases in heart rate (e.g., 20 beats/min); caution is recommended for less severe conditions that may be worsened by an increase in heart rate. Pulse and blood pressure measurements should be obtained at baseline, following dose increases, and periodically throughout atomoxetine therapy. Any unexplained cardiac symptoms should be promptly investigated.
During clinical trials of Attention-Deficit/Hyperactivity Disorder (ADHD) in adults, cardiovascular adverse reactions occurring more frequently with atomoxetine than placebo included palpitations (3% vs 1%). In adult trials, palpitations (0.4%) and chest pain (unspecified) (0.6%) were among the most common reasons for study discontinuation. Palpitations were reported in less than 2% of pediatric patients during clinical trials, but were reported by more pediatric patients receiving atomoxetine than placebo. Cardiovascular events, including sudden death, have been associated with atomoxetine use in pediatric patients with structural cardiac abnormalities or other serious heart problems. Cardiovascular effects associated with atomoxetine use in adults and children range in severity from mild to life-threatening and include sinus tachycardia (< 2%), hypertension, orthostasis, syncope, myocardial infarction (reported in adults), stroke (reported in adults), and a prolonged QT interval. Patients who develop symptoms such as exertional chest pain (unspecified), unexplained syncope, or other symptoms suggestive of cardiac disease during atomoxetine treatment should undergo a prompt cardiac evaluation. Minor manifestations of any of these symptoms may indicate a need for dosage reduction or discontinuation. Atomoxetine is contraindicated in patients with severe cardiac conditions that would be expected to deteriorate from potentially significant increases in heart rate (e.g., 20 beats/min) or blood pressure (e.g., 15-20 mmHg); caution is recommended for less severe conditions that may be worsened by an increase in heart rate or blood pressure. Blood pressure and pulse measurements should be obtained at baseline, after dosage increases, and periodically throughout atomoxetine therapy. According the Institute for Safe Medication Practices (ISMP), atomoxetine has been reported as a frequently suspected drug in serious adverse drug events in children. Of the serious events reported to the FDA during a 5-year time span (2008-2012), psychiatric events and cardiac events (e.g., chest pain, syncope or fainting, prolonged QT interval) were predominant for atomoxetine. Because reports submitted to the FDA likely represent only a portion of actual events, further investigation to determine frequency of occurrence and causality to the drug is warranted.
QT prolongation has been reported during post-marketing use of atomoxetine and the drug was listed in 2015 as a medication that may cause prolongation of the QT interval. A randomized, double-blind, crossover trial involving 120 healthy males who were poor metabolizers of CYP2D6 metabolized drugs assessed the effect of atomoxetine on QT prolongation. Positive (moxifloxacin 400 mg) and placebo controls were used. Subjects received atomoxetine twice daily (20 mg and 60 mg) for 1 week. No large QTc interval changes (> 60 msec from baseline, absolute QTc > 480 msec) were detected. Small QTc interval changes cannot be ruled out, as the trial failed to establish assay sensitivity. A slight increase in QTc interval was seen with increased atomoxetine concentration. An open-label, unpublished study noted a clinically insignificant decrease of 4.8 msec in mean Fridericia corrected QT interval from baseline in patients taking atomoxetine. One case report describes a QTc interval of 607 msec in a patient 15 years of age following ingestion of 1200 mg of atomoxetine; subsequently, the QTc interval decreased to 435 msec. According the Institute for Safe Medication Practices (ISMP), atomoxetine has been reported as a frequently suspected drug in serious adverse drug events in children. Of the serious events reported to the FDA during a 5-year time span (2008-2012), psychiatric events and cardiac events (e.g., chest pain, syncope or fainting, QT interval prolongation) were predominant for atomoxetine. Because reports submitted to the FDA likely represent only a portion of actual events, further investigation to determine frequency of occurrence and causality to the drug is warranted. Use atomoxetine cautiously in patients with known cardiac conduction defects (e.g., AV block, bundle-branch block, and cardiac arrhythmias) , structural heart disease, or congenital heart disease (e.g., congenital long QT syndrome). Pulse and blood pressure measurements should be obtained at baseline, following dose increases, and periodically throughout atomoxetine therapy. Any unexplained cardiac symptoms should be promptly investigated.
During clinical trials of atomoxetine in adults with Attention-Deficit/Hyperactivity Disorder (ADHD), chills occurred more frequently with atomoxetine than placebo (3% vs 0%). Peripheral coldness and feeling cold occurred at an incidence < 2% but greater than placebo in adult clinical trials. Certain adverse events have been noted by the manufacturer to have a greater incidence in atomoxetine poor metabolizers (PM) vs. extensive metabolizers (EM). Peripheral coldness occurred in at least 2% of adult CYP2D6 PMs and was statistically significantly more frequent in PM patients than CYP2D6 EM patients (3% of PMs, 1% of EMs). Raynaud's phenomenon (peripheral vasoconstriction of new onset and exacerbation of preexisting condition) has been reported during post-marketing use.
During clinical trials of atomoxetine in adults with Attention-Deficit/Hyperactivity Disorder (ADHD), the following dermatologic effects occurred more frequently with atomoxetine than placebo: hyperhidrosis (4% vs 1%) and hot flush (3% vs 0%). Flushing occurred in < 2% of pediatric patients but was reported in more atomoxetine-treated pediatric patients than placebo-treated patients. Certain adverse events have been noted by the manufacturer to have a greater incidence in atomoxetine poor metabolizers (PM) vs. extensive metabolizers (EM). Excoriation was reported in 4% of child and adolescent CYP2D6 PMs and 2% of CYP2D6 EMs. Hyperhidrosis occurred in at least 2% of adult CYP2D6 PMs and was statistically significantly more frequent in PM patients than CYP2D6 EM patients (15% of PMs, 7% of EMs). Hyperhidrosis has been reported during post-marketing use.
Atomoxetine may cause libido changes and impair sexual functioning in some patients. During clinical trials of atomoxetine in adults with Attention-Deficit/Hyperactivity Disorder (ADHD), the following effects occurred more frequently with atomoxetine than placebo: impotence (erectile dysfunction) (8% vs 1%), ejaculation dysfunction (4% vs 1%), and libido decrease (3% vs 1%). Orgasm dysfunction occurred at an incidence < 2% but greater than placebo in adult clinical trials. Erectile dysfunction resulted in treatment discontinuation in 0.4% of male adult patients during clinical trials. Incidences of sexual dysfunction are likely to be underreported in controlled clinical trials since these specific effects have not been systematically evaluated. Frequent or prolonged erections and priapism have been reported during post-marketing use of stimulant medications, as well as with atomoxetine. Reported cases of priapism have occurred after a period of time on stimulant therapy and often subsequent to a dose increase. Priapism has also been reported during periods of drug withdrawal (e.g., drug holidays or discontinuation). Priapism appears to occur more commonly during atomoxetine administration than methylphenidate administration; although the exact frequency for either product is unknown. Prolonged erections in male patients should be promptly reported, as immediate diagnosis and treatment are essential to avoid tissue damage. Certain adverse events have been noted by the manufacturer to have a greater incidence in atomoxetine poor metabolizers (PM) vs. extensive metabolizers (EM). The following effects occurred in at least 2% of adult CYP2D6 PMs and were statistically significantly more frequent in PM patients than CYP2D6 EM patients: erectile dysfunction (21% vs 9%) and ejaculation disorder (6% vs 2%).
Mydriasis was reported in less than 2% of pediatric patients during clinical trials but occurred in more atomoxetine-treated patients than placebo-treated patients. Mydriasis may occur in patients of any age, and the drug is not recommended for those with narrow-angle glaucoma. Certain adverse events have been noted by the manufacturer to have a greater incidence in atomoxetine poor metabolizers (PM) vs. extensive metabolizers (EM). The following ophthalmic adverse events 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: conjunctivitis (3% of PMs, 1% of EMs) and mydriasis (2% of PMs, 1% of EMs). Blurred vision was statistically significantly more frequent in adult CP2D6 PMs than in CYP2D6 EM patients (4% of PMs, 1% of EMs).
During clinical trials of atomoxetine in adults with Attention-Deficit/Hyperactivity Disorder (ADHD), decreased appetite (11% vs 2%) and weight loss (2% vs 1%) occurred more frequently with atomoxetine than placebo. In placebo-controlled clinical trials in pediatric patients, weight loss (3% vs 0%), decreased appetite (16% vs 3%), and anorexia (3% vs 1%) occurred more frequently with atomoxetine than placebo. Certain adverse events have been noted by the manufacturer to have a greater incidence in atomoxetine poor metabolizers (PM) vs. extensive metabolizers (EM). Weight loss occurred in at least 2% of child and adolescent CYP2D6 PM patients and was statistically significantly more frequent in PM patients than CYP2D6 EM patients (7% vs 4%). Decreased appetite occurred in at least 2% of adult CYP2D6 PMs and was statistically significantly more frequent in PM patients than CYP2D6 EM patients (23% vs 15%). The potential for growth inhibition should be monitored in children during continued therapy with atomoxetine. Monitor height and weight at atomoxetine initiation and periodically thereafter. Studies are not available to define the impact of atomoxetine on final adult height and weight, but short-term (9-week) studies have shown that up to 3.5% of body weight can be lost, and this loss may be dose-related. In a fixed-dose controlled trial, 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 dose groups, respectively. Data from open-label trials indicate that, in general, the weight and height gain of children treated with atomoxetine lags behind that predicted by normative population data for the first 9-12 months of treatment; subsequently, weight gain rebounds and at about 3 years of treatment, patients have gained slightly more weight (0.5 kg) than predicted by their baseline data. After about 12 months, gain in height stabilizes, and at 3 years, patients have gained only slightly less (0.4 cm) than predicted. Growth patterns are similar regardless of pubertal status; however, mean weight gain has been shown to be slower for poor vs. extensive metabolizers (2.4 kg less vs. 0.2 kg less than predicted, respectively), while height gain is similar between poor and extensive metabolizers (1.1 cm less vs. 0.4 cm less than predicted, respectively).
The risk for allergic reactions is possible with any drug, although allergic reactions were uncommon in clinical trials with atomoxetine. Angioedema, rash (unspecified), anaphylactoid reactions, and urticaria have been reported in patients taking atomoxetine. In pediatric studies, rash was reported in 2% of those receiving active drug versus 1% of those on placebo. Rash, pruritus (which may be dose related), and urticaria were reported in less than 2% of adult patients receiving active drug and more frequently than placebo. Alopecia was reported during postmarketing use.
Postmarketing reports have included rare cases of severe idiosyncratic liver injury (hepatotoxicity), including jaundice, hepatitis, hepatic fibrosis, and hepatic necrosis. Concurrent laboratory abnormalities have included prolonged bleeding time, as well as significantly elevated hepatic enzymes (e.g., more than 20 times the upper limit of normal [ULN]) and bilirubin (e.g., more than 2 times ULN). One patient experienced elevations in hepatic enzymes of up to 40 times ULN and jaundice with hyperbilirubinemia up to 12 times ULN with a recurrence upon re-challenge. In an FDA review of 6 postmarketing cases of severe liver injury, 5 occurred in pediatric patients. The onset of symptoms ranged from 21 to 730 days after treatment initiation, with a median onset of 62.5 days. Four of the patients recovered after atomoxetine discontinuation. One adult male patient died as a result of hepatic failure and renal failure; however, causality to atomoxetine could not be definitively established. During pre-approval clinical trials, severe hepatotoxicity was not reported; however, 41 postmarketing cases were identified as having hepatobiliary events requiring additional analysis. The mechanism of atomoxetine-induced hepatic injury is unknown, and the incidence is uncertain due to probable under-reporting of postmarketing adverse events. Symptoms that are indicative of liver injury include unexplained flu-like symptoms (musculoskeletal pain, chills), fatigue, loss of appetite, pain in the right upper quadrant of the stomach, pruritus, nausea/vomiting, jaundice of the sclera or skin, or dark-colored urine. Monitoring of liver function tests is not routinely recommended for those who take atomoxetine. However, patients should be informed of the signs and symptoms of liver toxicity and should be instructed to promptly report such effects to their health care provider. Discontinue atomoxetine in any patient who exhibits jaundice or laboratory evidence of liver injury: atomoxetine should not be restarted in these patients.
During clinical trials of atomoxetine in adults with Attention-Deficit/Hyperactivity Disorder (ADHD), muscle cramps occurred at an incidence < 2% but greater than placebo. Back pain occurred in >= 2% of adults receiving atomoxetine but not more frequently than placebo.
Rhabdomyolysis has been reported with post-marketing use of atomoxetine; however, frequency and causality have not been established.
Atomoxetine is contraindicated in any patient with a known hypersensitivity to atomoxetine (e.g., angioedema or urticaria due to the drug) or any inactive ingredients in the product. The risk for allergic reactions is possible with any drug, although allergic reactions were uncommon in clinical trials with atomoxetine. Anaphylaxis, angioedema, rash, and urticaria have been reported in patients taking atomoxetine.
Atomoxetine is contraindicated in patients with pheochromocytoma or history of pheochromocytoma, as serious reactions (including increased blood pressure and tachyarrhythmia) and the potential risk for prolonged QT interval have been reported during use.
Atomoxetine is contraindicated for concomitant use in patients receiving MAOI therapy.
Atomoxetine undergoes extensive hepatic metabolism resulting in an active metabolite and exposures to the drug are increased with moderate to severe hepatic disease. Reduce atomoxetine dosage in those with moderate to severe hepatic impairment. Rare cases of severe drug-induced liver injury (hepatotoxicity) causally associated with atomoxetine have been reported postmarketing; in these cases most patients recovered with normal liver function after stopping the medication. Routine liver function tests are not a standard recommendation during atomoxetine treatment; hepatotoxicity is unpredictable and rare. Patients should be informed of the signs and symptoms of liver toxicity and to notify their health care provider immediately if they notice such effects. Discontinue atomoxetine in patients who exhibit jaundice (yellowing of the skin or the whites of the eyes) or laboratory evidence of liver injury; do not restart atomoxetine. Perform laboratory testing to determine liver enzyme concentrations at the first symptom or sign of liver dysfunction (e.g., pruritus, dark urine, jaundice, right upper quadrant tenderness, or unexplained flu-like symptoms).
The use of atomoxetine is contraindicated in patients with closed-angle glaucoma. In clinical trials, atomoxetine use was associated with an increased risk for mydriasis.
Urinary retention and urinary hesitancy (roughly 3% each) have been reported in adult ADHD controlled trials with atomoxetine. Two adult patients withdrew from atomoxetine studies due to urinary retention. In the placebo groups, no patients withdrew and no urinary hesitancy was reported. Use atomoxetine with caution in patients with benign prostatic hypertrophy (BPH), and be aware that complaints of new or worsened urinary retention or hesitancy could be related to atomoxetine. Despite the low affinity of atomoxetine for cholinergic receptors, constipation and xerostomia have also been reported. Therefore, atomoxetine should also be used cautiously in patients with bladder obstruction, GI obstruction, or ileus.
Seizures occurred in 0.1% and 0.2% of adults and pediatrics, respectively, in clinical trials that followed premarket testing. Within these trials, the seizure risk among pediatrics was greater among poor metabolizers (0.3%) than extensive metabolizers (0.2%). Causality to the drug has not been established. In some instances, seizures have been reported in those with risk factors for seizures or with a preexisting seizure disorder; therefore, atomoxetine should be used cautiously under these conditions until further information becomes available.
Patients should exercise caution when driving or operating machinery until the full effects of atomoxetine are known. Atomoxetine may cause drowsiness, dizziness or fatigue. Patients should avoid taking atomoxetine with ethanol and avoid ethanol intoxication.
Before initiating treatment with atomoxetine, patients should be adequately screened for risk factors for bipolar disorder such as a personal or family history of mania and depression. Patients with bipolar disorder or risk factors for bipolar disorder may be at increased risk of developing mania or mixed episodes during treatment with atomoxetine. It may not be possible to determine whether a manic or mixed episode that appears during treatment with atomoxetine is due to an adverse reaction to atomoxetine or a patient's underlying bipolar disorder. Patients should also be monitored for the appearance or worsening of aggressive behavior or hostility as there is evidence that atomoxetine may cause these behaviors during treatment. ADHD and other mental illnesses can be associated with irritability, which can make it difficult to determine if the drug or the underlying psychiatric condition is causing these symptoms. If such symptoms occur during treatment, consider a possible causal role of atomoxetine. Psychotic or manic symptoms (e.g., hallucinations, delusional thinking, psychosis, or mania) in patients without a prior history of psychotic illness or mania may also be caused by atomoxetine at usual doses; if such symptoms occur, consider discontinuing atomoxetine.
Atomoxetine is contraindicated for use in patients who have severe cardiac or vascular conditions that could deteriorate with significant increases in blood pressure (15 to 20 mmHg) or heart rate (20 beats per minute), such as symptomatic or uncontrolled cardiac disease, advanced arteriosclerosis, symptomatic heart failure, cardiomyopathy, severe coronary artery disease, severe hypertension, serious cardiac arrhythmias (e.g., ventricular arrhythmias), structural cardiac abnormalities, or ventricular dysfunction. Use with caution in patients who have conditions that could be worsened by increased blood pressure or heart rate, such as controlled or mild hypertension, tachycardia, cardiac-related diseases, or cerebrovascular disease. There is a possible risk of torsade de pointes (TdP) with use. Use atomoxetine with caution in patients with conditions that may increase the risk of QT prolongation including congenital long QT syndrome, bradycardia, AV block, heart failure, stress-related cardiomyopathy, myocardial infarction, stroke, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to prolong the QT interval or cause electrolyte imbalances. Females, people 65 years and older, patients with sleep deprivation, pheochromocytoma, sickle cell disease, hypothyroidism, hyperparathyroidism, hypothermia, systemic inflammation (e.g., human immunodeficiency virus (HIV) infection, fever, and some autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus (SLE), and celiac disease) and patients undergoing apheresis procedures (e.g., plasmapheresis [plasma exchange], cytapheresis) may also be at increased risk for QT prolongation. Measure pulse and blood pressure at baseline, after dosage increases, and periodically throughout therapy. In patients receiving standard doses of atomoxetine, sudden death has occurred in adults and has been associated with use in pediatric and adolescent patients who have structural congenital heart disease or other serious heart conditions; myocardial infarction and stroke have also occurred in adults. However, a large retrospective cohort study including over 1.2 million pediatric patients and young adults aged 2 to 24 years did not find an increased risk of serious cardiovascular events in current users of ADHD medication compared to nonusers (adjusted hazard ratio 0.75; 95% CI 0.31 to 1.85). Similar results were seen when current users of ADHD drugs were compared to former users and when current users with severe underlying cardiovascular disease were included in the analysis. The authors concluded that although the absolute magnitude of risk appears to be low, a modest increase in risk could not be ruled out. The American Heart Association (AHA) states that it is reasonable to consider using ADHD medications in pediatric patients who congenital heart disease without current hemodynamic or arrhythmic concerns, or congenital heart disease that is considered stable by the patient's pediatric cardiologist, unless the cardiologist has specific concerns. Monitor closely and consider discontinuing treatment in patients who develop: heart condition associated with sudden cardiac death (SCD); arrhythmia requiring cardiopulmonary resuscitation; direct current cardioversion or defibrillation, or overdrive pacing; arrhythmia associated with SCD; any clinically significant arrhythmia that is not treated or controlled; QTc on electrocardiogram (ECG) longer than 0.46 sec; or heart rate or blood pressure more than 2 standard deviations above the mean for age. When considering ADHD medications, carefully evaluate the medical history (including family history of sudden death or ventricular arrhythmia) and perform a physical exam to assess for the presence of cardiac disease. In any patient with suspected cardiac disease, further evaluation including an ECG and echocardiogram is warranted. The AHA states that obtaining a baseline ECG as a part of the initial evaluation is reasonable for pediatric patients. Consult a pediatric cardiologist before initiating medication in a child or adolescent who has any significant findings on physical examination, ECG, or family history. Once the medication is started, a repeat ECG may be helpful if the original ECG was obtained before the child was 12 years old, if cardiac symptoms develop, or if there is a change in family history.
Atomoxetine is not approved for the treatment of major depressive disorder (MDD). Atomoxetine increased the risk of suicidal thoughts and behavior in children and adolescents in short-term studies; the risk appears to be the greatest early in treatment. Co-morbidities occurring with ADHD may increase the risk of suicidal ideation and/or behavior. Monitor all pediatric patients receiving atomoxetine closely for clinical worsening, suicidal ideation, and unusual behavioral changes, such as anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, and mania, especially during the first few months of therapy and after any dosage adjustment. Instruct caregivers and patients to immediately notify the prescriber of changes in behavior or suicidal ideation. Consider changing the therapeutic regimen or discontinuing the medication in patients with persistent or worrisome symptoms, especially if these symptoms are severe, abrupt in onset, or were not part of the patient's presenting symptoms. In clinical trials, all reactions occurred in children 12 years and younger and within the first month of therapy. No suicides occurred in these trials. It is unknown whether the risk of suicidal ideation in pediatric patients extends to longer-term use. In addition to suicide risk, monitor pediatric patients for the potential for growth inhibition during atomoxetine therapy. Monitor height and weight at treatment initiation and periodically thereafter. Short-term (9-week) studies have shown that up to 3.5% of body weight can be lost, and this loss may be dose-related. Data from open-label trials indicate that in general, the weight and height gain of children treated with atomoxetine lags behind that predicted by normative population data for the first 9 to 12 months of treatment; subsequently, weight gain rebounds and at about 3 years of treatment, patients have gained slightly more weight (0.5 kg) than predicted by their baseline data. After about 12 months, gain in height stabilizes, and at 3 years, patients have gained only slightly less (0.4 cm) than predicted. Growth patterns are similar regardless of pubertal status; however, mean weight gain has been shown to be slower for CYP2D6 poor metabolizers (PMs) compared to extensive metabolizers (EMs) (2.4 kg less vs. 0.2 kg less than predicted, respectively), while height gain is similar between PMs and EMs (1.1 cm less vs. 0.4 cm less than predicted, respectively).
Orthostatic hypotension and syncope have been reported in atomoxetine clinical studies. Use caution when administering atomoxetine to patients who have a history of orthostatic or postural hypotension, or any condition that may predispose a patient to postural hypotension, hypovolemia, low blood pressure, antihypertensive medications, dehydration, or abrupt heart rate or blood pressure changes.
Available published studies with atomoxetine use during pregnancy are insufficient to establish a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Atomoxetine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. In rabbit organogenesis studies, decreases in live fetuses, increases in early resorption and slight increases in the incidences of atypical origin of the carotid artery and absent subclavian artery. These effects were observed at plasma levels (AUC) 3 times and 0.4 times the human plasma levels in extensive and poor metabolizers receiving the maximum recommended human dose (MRHD), respectively. The no-effect dose for these findings was 30 mg/kg/day. In rats dosed prior to mating and during 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 a dose approximately 5 times the MRHD (mg/m2 basis). In one of 2 studies in which rats were dosed prior to mating through the periods of organogenesis and lactation, decreased pup weight and decreased pup survival were observed at doses corresponding to 5 to 6 times the MRHD (mg/m2 basis). No adverse fetal effects were seen in pregnant rats dosed during the organogenesis period. Rat studies have not shown impairment of fertility during use of atomoxetine doses 6 times the MHRD. According to one brief correspondence, 3 pregnancies have occurred during adult clinical trials of atomoxetine, with 2 pregnancies resulting in healthy newborns, and 1 unknown outcome because the patient was lost to follow-up. There is a pregnancy registry that monitors pregnancy outcomes in women exposed to ADHD medications, including atomoxetine, during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for ADHD Medications at 1-866-961-2388 or by visiting the worldwide web at https://womensmentalhealth.org/adhd-medications/. The effect of atomoxetine on labor and delivery is unknown.
There are no data on the presence of atomoxetine or its metabolite in human milk, the effects on the breastfed child, or the effects on milk production. Atomoxetine is present in animal milk. When a drug is present in animal milk, it is likely that the drug will be present in human milk. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. Limited data exist; reports from the manufacturer found no serious adverse effects in two breastfed infants. Consider if an alternate drug would be preferred, especially while the woman is nursing a newborn or preterm infant. If atomoxetine therapy cannot be avoided during breast-feeding, the nursing infant should be monitored for signs of potential toxicity, such as poor feeding, irritability, or changes in sleep patterns. Although methylphenidate may be considered as an alternative to other ADHD medications during lactation and breast-feeding due to low excretion into breastmilk, the medical use of stimulant medications during breast-feeding has not been formally evaluated.
The pharmacokinetics, safety and efficacy regarding the use of atomoxetine in the geriatric population has not been evaluated in controlled clinical trials. No prospective trials have been published which address the use of atomoxetine in sufficient numbers of adults 50 years and older, and thus atomoxetine is not considered a first-line therapy for the geriatric population.
For the treatment of attention-deficit hyperactivity disorder (ADHD):
Oral dosage:
Adults 18 to 64 years: 40 mg PO once daily in the morning or 20 mg PO twice daily, initially. After at least 3 days, increase the dose to 80 mg/day in 1 or 2 divided doses. May increase the dose to 100 mg/day if optimal response has not been achieved after an additional 2 to 4 weeks. Max: 100 mg/day. For poor CYP2D6 metabolizers, only increase the dose to 80 mg/day if symptoms fail to improve after 4 weeks and the initial dose is well tolerated. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
Children and Adolescents 6 to 17 years weighing more than 70 kg: 40 mg PO once daily in the morning or 20 mg PO twice daily, initially. After at least 3 days, increase the dose to 80 mg/day in 1 or 2 divided doses. May increase the dose to 100 mg/day if optimal response has not been achieved after an additional 2 to 4 weeks. Max: 100 mg/day. For poor CYP2D6 metabolizers, only increase the dose to 80 mg/day if symptoms fail to improve after 4 weeks and the initial dose is well tolerated. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
Children and Adolescents 6 to 17 years weighing 70 kg or less: 0.5 mg/kg/dose PO once daily in the morning or 0.25 mg/kg/dose PO twice daily, initially. After at least 3 days, may increase the dose to 1.2 mg/kg/day in 1 or 2 divided doses. Max: 1.4 mg/kg/day or 100 mg/day, whichever is less. For poor CYP2D6 metabolizers, only increase the dose to 1.2 mg/kg/day if symptoms fail to improve after 4 weeks and the initial dose is well tolerated. No additional benefit has been demonstrated for doses higher than 1.2 mg/kg/day. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
For the treatment of neurogenic orthostatic hypotension*:
Oral dosage:
Adults: 10 mg PO twice daily, initially. The dose may be increased up to 18 mg PO twice daily based on clinical response and tolerability. Atomoxetine is beneficial in neurogenic orthostatic hypotension with preserved peripheral sympathetic fiber function (multiple system atrophy).
Maximum Dosage Limits:
-Adults
100 mg/day PO for ADHD; 36 mg/day PO has been suggested for neurogenic orthostatic hypotension.
-Geriatric
36 mg/day PO has been suggested for neurogenic orthostatic hypotension. Safety and efficacy have not been established for ADHD.
-Adolescents
Weighing more than 70 kg: 100 mg/day PO.
Weighing 70 kg or less: 1.4 mg/kg/day PO (Max: 100 mg/day PO).
-Children
6 to 12 years weighing more than 70 kg: 100 mg/day PO.
6 to 12 years weighing 70 kg or less: 1.4 mg/kg/day PO (Max: 100 mg/day PO).
1 to 5 years: Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Moderate hepatic impairment (Child-Pugh Class B): Reduce initial and target dosage by 50% of normal.
Severe hepatic impairment (Child-Pugh Class C): Reduce initial and target dosage by 75% of normal.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed. Renal clearance is not an important predictor of atomoxetine clearance.
*non-FDA-approved indication
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Due to the potential for additive increases in blood pressure and heart rate, atomoxetine should be used cautiously with vasopressors such as phenylephrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if vasopressors are coadministered with atomoxetine.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Use atomoxetine with caution and monitor blood pressure in patients receiving concomitant pseudoephedrine due to potential effects on blood pressure.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Due to the potential for additive increases in blood pressure and heart rate, atomoxetine should be used cautiously with vasopressors such as phenylephrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if vasopressors are coadministered with atomoxetine.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Due to the potential for additive increases in blood pressure and heart rate, atomoxetine should be used cautiously with vasopressors such as phenylephrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if vasopressors are coadministered with atomoxetine.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Use atomoxetine with caution and monitor blood pressure in patients receiving concomitant pseudoephedrine due to potential effects on blood pressure.
Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Due to the potential for additive increases in blood pressure and heart rate, atomoxetine should be used cautiously with vasopressors such as phenylephrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if vasopressors are coadministered with atomoxetine.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) Use atomoxetine with caution and monitor blood pressure in patients receiving concomitant pseudoephedrine due to potential effects on blood pressure.
Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) Due to the potential for additive increases in blood pressure and heart rate, atomoxetine should be used cautiously with vasopressors such as phenylephrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if vasopressors are coadministered with atomoxetine.
Acetaminophen; Phenylephrine: (Moderate) Due to the potential for additive increases in blood pressure and heart rate, atomoxetine should be used cautiously with vasopressors such as phenylephrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if vasopressors are coadministered with atomoxetine.
Acetaminophen; Pseudoephedrine: (Moderate) Use atomoxetine with caution and monitor blood pressure in patients receiving concomitant pseudoephedrine due to potential effects on blood pressure.
Acrivastine; Pseudoephedrine: (Moderate) Use atomoxetine with caution and monitor blood pressure in patients receiving concomitant pseudoephedrine due to potential effects on blood pressure.
Adagrasib: (Major) Concomitant use of adagrasib and atomoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Alfuzosin: (Moderate) Concomitant use of atomoxetine and alfuzosin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Amiodarone: (Major) Concomitant use of amiodarone and atomoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after drug discontinuation.
Amisulpride: (Major) Monitor ECGs for QT prolongation when amisulpride is administered with atomoxetine. QT prolongation and torsade de pointes have been reported in patients receiving clofazimine in combination with QT prolonging medications. Amisulpride causes dose- and concentration- dependent QT prolongation.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Concomitant use of atomoxetine and clarithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Amphetamine: (Moderate) Monitor blood pressure during concomitant amphetamine; dextroamphetamine and atomoxetine use. Because of possible effects on blood pressure, atomoxetine should be used cautiously with other drugs that affect blood pressure, such as amphetamine; dextroamphetamine.
Amphetamine; Dextroamphetamine Salts: (Moderate) Monitor blood pressure during concomitant amphetamine; dextroamphetamine and atomoxetine use. Because of possible effects on blood pressure, atomoxetine should be used cautiously with other drugs that affect blood pressure, such as amphetamine; dextroamphetamine.
Amphetamine; Dextroamphetamine: (Moderate) Monitor blood pressure during concomitant amphetamine; dextroamphetamine and atomoxetine use. Because of possible effects on blood pressure, atomoxetine should be used cautiously with other drugs that affect blood pressure, such as amphetamine; dextroamphetamine.
Anagrelide: (Moderate) Concomitant use of atomoxetine and anagrelide may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Apomorphine: (Moderate) Concomitant use of atomoxetine and apomorphine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Aripiprazole: (Moderate) Concomitant use of aripiprazole and atomoxetine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Arsenic Trioxide: (Major) Concomitant use of atomoxetine and arsenic trioxide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Artemether; Lumefantrine: (Major) QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Both atomoxetine and artemether; lumefantrine are considered drugs with a possible risk of torsade de pointes (TdP); therefore, the combination should be used cautiously and with close monitoring. In addition, atomoxetine is primarily metabolized by CYP2D6 and lumefantrine is a strong CYP2D6 inhibitor. In children and adolescents up to 70 kg receiving a strong CYP2D6 inhibitor or who are known CYP2D6 poor metabolizers (PMs), atomoxetine 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 the initial dose is well tolerated. In children and adolescents over 70 kg and adults receiving a strong CYP2D6 inhibitor or who are known CYP2D6 poor metabolizers, atomoxetine 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. If concurrent use is necessary, monitor for adverse effects, such as dizziness, drowsiness, nervousness, insomnia, and cardiac effects (e.g., hypertension, increased pulse rate, QT prolongation).
Articaine; Epinephrine: (Moderate) Use atomoxetine with caution and monitor blood pressure in patients receiving concomitant epinephrine due to potential effects on blood pressure.
Asenapine: (Major) Concomitant use of asenapine and atomoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Atazanavir; Cobicistat: (Moderate) The plasma concentrations of atomoxetine may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as dizziness, drowsiness, hypertension, and other cardiac adverse events, is recommended during coadministration and dosage adjustments for atomoxetine may be warranted. Cobicistat is a CYP2D6 inhibitor and atomoxetine is a CYP2D6 substrate.
Atropine: (Major) Atropine and atomoxetine should be combined cautiously in patients with known cardiac disease. Atropine or scopolamine may alter the heart rate; the predominant clinical effect is sinus tachycardia. An additive effect on heart rate may occur as atomoxetine may elevate heart rate as well as blood pressure.
Atropine; Difenoxin: (Major) Atropine and atomoxetine should be combined cautiously in patients with known cardiac disease. Atropine or scopolamine may alter the heart rate; the predominant clinical effect is sinus tachycardia. An additive effect on heart rate may occur as atomoxetine may elevate heart rate as well as blood pressure.
Azithromycin: (Major) Concomitant use of azithromycin and atomoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Bedaquiline: (Major) QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Atomoxetine is considered a drug with a possible risk of torsade de pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with atomoxetine include bedaquiline.
Benzphetamine: (Moderate) Amphetamines increase both systolic and diastolic blood pressure; atomoxetine has been reported to also increase blood pressure and heart rate, probably via inhibition of norepinephrine reuptake. Due to an additive pharmacodynamic effect, amphetamines and atomoxetine should be used together cautiously, particularly in patients with a history of cardiac disease. Consider monitoring heart rate and blood pressure at baseline and regularly throughout treatment if these agents must be used together.
Betrixaban: (Major) Monitor patients closely and promptly evaluate any signs or symptoms of bleeding if betrixaban and selective norepinephrine reuptake inhibitors (SNRIs) are used concomitantly. Coadministration of betrixaban and SNRIs may increase the risk of bleeding.
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and atomoxetine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and atomoxetine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Due to the potential for additive increases in blood pressure and heart rate, atomoxetine should be used cautiously with vasopressors such as phenylephrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if vasopressors are coadministered with atomoxetine.
Brompheniramine; Phenylephrine: (Moderate) Due to the potential for additive increases in blood pressure and heart rate, atomoxetine should be used cautiously with vasopressors such as phenylephrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if vasopressors are coadministered with atomoxetine.
Brompheniramine; Pseudoephedrine: (Moderate) Use atomoxetine with caution and monitor blood pressure in patients receiving concomitant pseudoephedrine due to potential effects on blood pressure.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Use atomoxetine with caution and monitor blood pressure in patients receiving concomitant pseudoephedrine due to potential effects on blood pressure.
Bupivacaine; Epinephrine: (Moderate) Use atomoxetine with caution and monitor blood pressure in patients receiving concomitant epinephrine due to potential effects on blood pressure.
Buprenorphine: (Major) Concomitant use of atomoxetine and buprenorphine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Buprenorphine; Naloxone: (Major) Concomitant use of atomoxetine and buprenorphine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Bupropion: (Major) Dosage reduction of atomoxetine is recommended in patients receiving bupropion due to the potential for increased atomoxetine exposure and related adverse effects. In children and adolescents up to 70 kg receiving bupropion, atomoxetine 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 the initial dose is well-tolerated. In children and adolescents over 70 kg and adults receiving bupropion, atomoxetine 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. Bupropion is a strong CYP2D6 inhibitor; atomoxetine is a CYP2D6 substrate. Coadministration of a strong CYP2D6 inhibitor and atomoxetine in extensive metabolizers of CYP2D6, increased atomoxetine steady-state plasma concentrations by approximately 6 to 8-fold. This increase is similar to exposures observed in poor metabolizers. Concurrent use of a strong CYP2D6 inhibitor with atomoxetine in poor metabolizers is not expected to increase atomoxetine exposure.
Bupropion; Naltrexone: (Major) Dosage reduction of atomoxetine is recommended in patients receiving bupropion due to the potential for increased atomoxetine exposure and related adverse effects. In children and adolescents up to 70 kg receiving bupropion, atomoxetine 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 the initial dose is well-tolerated. In children and adolescents over 70 kg and adults receiving bupropion, atomoxetine 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. Bupropion is a strong CYP2D6 inhibitor; atomoxetine is a CYP2D6 substrate. Coadministration of a strong CYP2D6 inhibitor and atomoxetine in extensive metabolizers of CYP2D6, increased atomoxetine steady-state plasma concentrations by approximately 6 to 8-fold. This increase is similar to exposures observed in poor metabolizers. Concurrent use of a strong CYP2D6 inhibitor with atomoxetine in poor metabolizers is not expected to increase atomoxetine exposure.
Cabotegravir; Rilpivirine: (Moderate) Concomitant use of atomoxetine and rilpivirine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Ceritinib: (Major) Avoid coadministration of ceritinib with atomoxetine if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent QT prolongation. Prolongation of the QT interval has occurred during therapeutic use of atomoxetine as well as following overdose.
Cetirizine; Pseudoephedrine: (Moderate) Use atomoxetine with caution and monitor blood pressure in patients receiving concomitant pseudoephedrine due to potential effects on blood pressure.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Use atomoxetine with caution and monitor blood pressure in patients receiving concomitant pseudoephedrine due to potential effects on blood pressure.
Chloroquine: (Major) Avoid coadministration of chloroquine with atomoxetine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Chloroquine is associated with an increased risk of QT prolongation and torsade de pointes (TdP); the risk of QT prolongation is increased with higher chloroquine doses. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Due to the potential for additive increases in blood pressure and heart rate, atomoxetine should be used cautiously with vasopressors such as phenylephrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if vasopressors are coadministered with atomoxetine.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Use atomoxetine with caution and monitor blood pressure in patients receiving concomitant pseudoephedrine due to potential effects on blood pressure.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Use atomoxetine with caution and monitor blood pressure in patients receiving concomitant pseudoephedrine due to potential effects on blood pressure.
Chlorpheniramine; Phenylephrine: (Moderate) Due to the potential for additive increases in blood pressure and heart rate, atomoxetine should be used cautiously with vasopressors such as phenylephrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if vasopressors are coadministered with atomoxetine.
Chlorpheniramine; Pseudoephedrine: (Moderate) Use atomoxetine with caution and monitor blood pressure in patients receiving concomitant pseudoephedrine due to potential effects on blood pressure.
Chlorpromazine: (Major) Concomitant use of atomoxetine and chlorpromazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ciprofloxacin: (Moderate) Concomitant use of atomoxetine and ciprofloxacin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Cisapride: (Contraindicated) Avoid concomitant use of cisapride and atomoxetine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Citalopram: (Major) Concomitant use of atomoxetine and citalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Clarithromycin: (Major) Concomitant use of atomoxetine and clarithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Clofazimine: (Moderate) Concomitant use of clofazimine and atomoxetine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Clomipramine: (Minor) Atomoxetine should be used cautiously with tricyclic antidepressants (TCAs) such as clomipramine as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Tricyclic antidepressants share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
Clozapine: (Moderate) Concomitant use of atomoxetine and clozapine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Cobicistat: (Moderate) The plasma concentrations of atomoxetine may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as dizziness, drowsiness, hypertension, and other cardiac adverse events, is recommended during coadministration and dosage adjustments for atomoxetine may be warranted. Cobicistat is a CYP2D6 inhibitor and atomoxetine is a CYP2D6 substrate.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Use atomoxetine with caution and monitor blood pressure in patients receiving concomitant pseudoephedrine due to potential effects on blood pressure.
Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of atomoxetine and promethazine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. (Moderate) Due to the potential for additive increases in blood pressure and heart rate, atomoxetine should be used cautiously with vasopressors such as phenylephrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if vasopressors are coadministered with atomoxetine.
Codeine; Promethazine: (Moderate) Concomitant use of atomoxetine and promethazine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Crizotinib: (Major) Avoid coadministration of crizotinib with atomoxetine due to the risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib if QT prolongation occurs. Crizotinib has been associated with concentration-dependent QT prolongation. Prolongation of the QT interval has also occurred during therapeutic use of atomoxetine as well as following overdose.
Dacomitinib: (Major) A lower initial dose of atomoxetine is recommended in patients receiving dacomitinib due to the potential for increased atomoxetine exposure and related adverse effects. In children and adolescents up to 70 kg receiving dacomitinib, atomoxetine 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 the initial dose is well tolerated. In children and adolescents over 70 kg and adults receiving dacomitinib, atomoxetine 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. Monitor for adverse effects, such as dizziness, drowsiness, nervousness, insomnia, and cardiac effects (e.g., hypertension, increased pulse rate, QT prolongation). Dacomitinib is a strong CYP2D6 inhibitor; atomoxetine is a CYP2D6 substrate. Coadministration of a strong CYP2D6 inhibitor and atomoxetine in extensive metabolizers of CYP2D6, increased atomoxetine steady-state plasma concentrations by approximately 6 to 8-fold. This increase is similar to exposures observed in poor metabolizers. Concurrent use of a strong CYP2D6 inhibitor with atomoxetine in poor metabolizers is not expected to increase atomoxetine exposure.
Darunavir: (Moderate) The plasma concentrations of atomoxetine may be elevated when administered concurrently with darunavir. Clinical monitoring for adverse effects, such as dizziness, drowsiness, hypertension, and other cardiac adverse events, is recommended during coadministration and dosage adjustments for atomoxetine may be warranted. Darunavir is a CYP2D6 inhibitor, and atomoxetine is a CYP2D6 substrate.
Darunavir; Cobicistat: (Moderate) The plasma concentrations of atomoxetine may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as dizziness, drowsiness, hypertension, and other cardiac adverse events, is recommended during coadministration and dosage adjustments for atomoxetine may be warranted. Cobicistat is a CYP2D6 inhibitor and atomoxetine is a CYP2D6 substrate. (Moderate) The plasma concentrations of atomoxetine may be elevated when administered concurrently with darunavir. Clinical monitoring for adverse effects, such as dizziness, drowsiness, hypertension, and other cardiac adverse events, is recommended during coadministration and dosage adjustments for atomoxetine may be warranted. Darunavir is a CYP2D6 inhibitor, and atomoxetine is a CYP2D6 substrate.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) The plasma concentrations of atomoxetine may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as dizziness, drowsiness, hypertension, and other cardiac adverse events, is recommended during coadministration and dosage adjustments for atomoxetine may be warranted. Cobicistat is a CYP2D6 inhibitor and atomoxetine is a CYP2D6 substrate. (Moderate) The plasma concentrations of atomoxetine may be elevated when administered concurrently with darunavir. Clinical monitoring for adverse effects, such as dizziness, drowsiness, hypertension, and other cardiac adverse events, is recommended during coadministration and dosage adjustments for atomoxetine may be warranted. Darunavir is a CYP2D6 inhibitor, and atomoxetine is a CYP2D6 substrate.
Dasatinib: (Moderate) Concomitant use of atomoxetine and dasatinib may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Degarelix: (Moderate) Concomitant use of atomoxetine and androgen deprivation therapy (i.e., degarelix) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Delavirdine: (Major) Because atomoxetine is primarily metabolized by CYP2D6, concurrent use of CYP2D6 inhibitors such as delavirdine may increase the risk of atomoxetine-induced adverse effects. Monitor for adverse effects, such as dizziness, drowsiness, nervousness, insomnia, and cardiac effects (e.g., hypertension, QT prolongation).
Desflurane: (Major) Concomitant use of atomoxetine and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Desipramine: (Minor) Atomoxetine should be used cautiously with tricyclic antidepressants (TCAs) such as desipramine as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Tricyclic antidepressants share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
Desloratadine; Pseudoephedrine: (Moderate) Use atomoxetine with caution and monitor blood pressure in patients receiving concomitant pseudoephedrine due to potential effects on blood pressure.
Desvenlafaxine: (Major) Desvenlafaxine is a serotonin norepinephrine reuptake inhibitor (SNRI) and atomoxetine selectively inhibits norepinephrine reuptake; the drugs have some additive pharmacology that may lead to increases in blood pressure or heart rate. Although clinical studies have shown that desvenlafaxine does not have a clinically relevant effect on CYP2D6 inhibition at doses of 100 mg/day, the manufacturer of desvenlafaxine recommends that the dose of primary substrates of CYP2D6, such as atomoxetine, be reduced by up to one-half if co-administered with desvenlafaxine 400 mg/day. Monitor for adverse effects, such as dizziness, drowsiness, nervousness, insomnia, and cardiac effects (e.g., hypertension, increased pulse rate, QT prolongation) during concurrent use.
Deutetrabenazine: (Minor) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and atomoxetine. Deutetrabenazine may prolong the QT interval, but the degree of QT prolongation is not clinically significant when deutetrabenazine is administered within the recommended dosage range. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose.
Dexbrompheniramine; Pseudoephedrine: (Moderate) Use atomoxetine with caution and monitor blood pressure in patients receiving concomitant pseudoephedrine due to potential effects on blood pressure.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Use atomoxetine with caution and monitor blood pressure in patients receiving concomitant pseudoephedrine due to potential effects on blood pressure.
Dexmedetomidine: (Minor) QT/QTc prolongation can occur with concomitant use of dexmedetomidine and atomoxetine although the risk of developing torsade de pointes (TdP) is low. Additional steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, may be considered in patients with additional risk factors for TdP.
Dextroamphetamine: (Moderate) Monitor blood pressure during concomitant amphetamine; dextroamphetamine and atomoxetine use. Because of possible effects on blood pressure, atomoxetine should be used cautiously with other drugs that affect blood pressure, such as amphetamine; dextroamphetamine.
Dextromethorphan; Bupropion: (Major) Dosage reduction of atomoxetine is recommended in patients receiving bupropion due to the potential for increased atomoxetine exposure and related adverse effects. In children and adolescents up to 70 kg receiving bupropion, atomoxetine 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 the initial dose is well-tolerated. In children and adolescents over 70 kg and adults receiving bupropion, atomoxetine 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. Bupropion is a strong CYP2D6 inhibitor; atomoxetine is a CYP2D6 substrate. Coadministration of a strong CYP2D6 inhibitor and atomoxetine in extensive metabolizers of CYP2D6, increased atomoxetine steady-state plasma concentrations by approximately 6 to 8-fold. This increase is similar to exposures observed in poor metabolizers. Concurrent use of a strong CYP2D6 inhibitor with atomoxetine in poor metabolizers is not expected to increase atomoxetine exposure.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Due to the potential for additive increases in blood pressure and heart rate, atomoxetine should be used cautiously with vasopressors such as phenylephrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if vasopressors are coadministered with atomoxetine.
Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Due to the potential for additive increases in blood pressure and heart rate, atomoxetine should be used cautiously with vasopressors such as phenylephrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if vasopressors are coadministered with atomoxetine.
Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Use atomoxetine with caution and monitor blood pressure in patients receiving concomitant pseudoephedrine due to potential effects on blood pressure.
Dextromethorphan; Quinidine: (Major) If possible, quinidine should be avoided in patients receiving atomoxetine. Coadministration of quinidine with atomoxetine may result in additive QT prolongation and increased exposure to atomoxetine. When administered as quinidine; dextromethorphan, coadministration with atomoxetine is contraindicated. Quinidine is a CYP2D6 inhibitor that is associated with QT prolongation and torsade de pointes (TdP). Atomoxetine is a CYP2D6 substrate. In children and adolescents up to 70 kg receiving quinidine, atomoxetine 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 the initial dose is well tolerated. In children and adolescents over 70 kg and adults receiving quinidine, atomoxetine 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. Coadministration of a strong CYP2D6 inhibitor and atomoxetine in extensive metabolizers of CYP2D6, increased atomoxetine steady-state plasma concentrations by approximately 6 to 8-fold. This increase is similar to exposures observed in poor metabolizers. Concurrent use of a strong CYP2D6 inhibitor with atomoxetine in poor metabolizers is not expected to increase atomoxetine exposure.
Diethylpropion: (Major) Atomoxetine, an inhibitor of norepinephrine reuptake used for treatment of ADHD, has been shown to increase heart rate and blood pressure. Diethylpropion also inhibits norepinephrine reuptake. The combination of atomoxetine with diethylpropion should be used extremely cautiously, if at all, due to the potential for serious increases in blood pressure and/or heart rate. If these agents must be used concomitantly, consider monitoring blood pressure and heart rate at baseline and regularly throughout treatment.
Diphenhydramine; Phenylephrine: (Moderate) Due to the potential for additive increases in blood pressure and heart rate, atomoxetine should be used cautiously with vasopressors such as phenylephrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if vasopressors are coadministered with atomoxetine.
Diphenoxylate; Atropine: (Major) Atropine and atomoxetine should be combined cautiously in patients with known cardiac disease. Atropine or scopolamine may alter the heart rate; the predominant clinical effect is sinus tachycardia. An additive effect on heart rate may occur as atomoxetine may elevate heart rate as well as blood pressure.
Disopyramide: (Major) Concomitant use of disopyramide and atomoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Dobutamine: (Major) Due to the potential for increases in blood pressure and heart rate, atomoxetine should be used cautiously with drugs with sympathomimetic activity, including dobutamine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if sympathomimetics are coadministered with atomoxetine.
Dofetilide: (Major) Concomitant use of atomoxetine and dofetilide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Dolasetron: (Moderate) Concomitant use of atomoxetine and dolasetron may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Dolutegravir; Rilpivirine: (Moderate) Concomitant use of atomoxetine and rilpivirine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Donepezil: (Moderate) Concomitant use of atomoxetine and donepezil may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Donepezil; Memantine: (Moderate) Concomitant use of atomoxetine and donepezil may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Dopamine: (Major) Due to the potential for additive increases in blood pressure and heart rate, atomoxetine should be used cautiously with vasopressors, such as dopamine. Consider monitoring the patients blood pressure and heart rate at baseline and regularly if vasopressors are coadministered with atomoxetine.
Doxepin: (Minor) Atomoxetine should be used cautiously with tricyclic antidepressants (TCAs) such as doxepin as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Tricyclic antidepressants share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
Dronedarone: (Contraindicated) Avoid concomitant use of dronedarone and atomoxetine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Droperidol: (Major) QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Atomoxetine is considered a drug with a possible risk of torsade de pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with atomoxetine include droperidol.
Droxidopa: (Major) Due to the potential for increases in blood pressure and heart rate, atomoxetine should be used cautiously with vasopressors such as droxidopa. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if vasopressors are coadministered with atomoxetine.
Edoxaban: (Major) Coadministration of edoxaban with other drugs that affect hemostasis, such as selective norepinephrine reuptake inhibitors (SNRIs), increases the risk of bleeding. If these drugs are administered together, instruct patients to monitor for signs and symptoms of bleeding, and to promptly report any bleeding events to their practitioner.
Efavirenz: (Moderate) Concomitant use of atomoxetine and efavirenz may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Concomitant use of atomoxetine and efavirenz may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Concomitant use of atomoxetine and efavirenz may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Eliglustat: (Moderate) Concomitant use of atomoxetine and eliglustat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) The plasma concentrations of atomoxetine may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as dizziness, drowsiness, hypertension, and other cardiac adverse events, is recommended during coadministration and dosage adjustments for atomoxetine may be warranted. Cobicistat is a CYP2D6 inhibitor and atomoxetine is a CYP2D6 substrate.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) The plasma concentrations of atomoxetine may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as dizziness, drowsiness, hypertension, and other cardiac adverse events, is recommended during coadministration and dosage adjustments for atomoxetine may be warranted. Cobicistat is a CYP2D6 inhibitor and atomoxetine is a CYP2D6 substrate.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Concomitant use of atomoxetine and rilpivirine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Concomitant use of atomoxetine and rilpivirine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Encorafenib: (Major) Concomitant use of encorafenib and atomoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Entrectinib: (Major) Concomitant use of entrectinib with atomoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ephedrine: (Major) Due to the potential for increases in blood pressure and heart rate, atomoxetine should be used cautiously with drugs with significant vasopressor effects like ephedrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if vasopressors are coadministered with atomoxetine.
Ephedrine; Guaifenesin: (Major) Due to the potential for increases in blood pressure and heart rate, atomoxetine should be used cautiously with drugs with significant vasopressor effects like ephedrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if vasopressors are coadministered with atomoxetine.
Epinephrine: (Moderate) Use atomoxetine with caution and monitor blood pressure in patients receiving concomitant epinephrine due to potential effects on blood pressure.
Eribulin: (Major) Concomitant use of atomoxetine and eribulin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Erythromycin: (Major) Concomitant use of atomoxetine and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Escitalopram: (Moderate) Concomitant use of atomoxetine and escitalopram may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Etrasimod: (Minor) QT/QTc prolongation can occur with concomitant use of etrasimod and atomoxetine although the risk of developing torsade de pointes (TdP) is low. Additional steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, may be considered in patients with additional risk factors for TdP. Etrasimod has a limited effect on the QT/QTc interval at therapeutic doses but may cause bradycardia and atrioventricular conduction delays which may increase the risk for TdP in patients with a prolonged QT/QTc interval.
Fexinidazole: (Major) Concomitant use of fexinidazole and atomoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Fexofenadine; Pseudoephedrine: (Moderate) Use atomoxetine with caution and monitor blood pressure in patients receiving concomitant pseudoephedrine due to potential effects on blood pressure.
Fingolimod: (Moderate) Concomitant use of atomoxetine and fingolimod may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Flecainide: (Major) Concomitant use of atomoxetine and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Fluconazole: (Moderate) Concomitant use of atomoxetine and fluconazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Fluoxetine: (Major) Monitor for evidence of QT prolongation and increased atomoxetine-related adverse effects during coadministration with fluoxetine. Dosage reduction of atomoxetine is recommended in patients receiving fluoxetine due to the potential for increased atomoxetine exposure and related adverse effects. In children and adolescents up to 70 kg receiving fluoxetine, atomoxetine 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 the initial dose is well-tolerated. In children and adolescents over 70 kg and adults receiving fluoxetine, atomoxetine 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. Fluoxetine is a strong CYP2D6 inhibitor; atomoxetine is a CYP2D6 substrate. Coadministration of a strong CYP2D6 inhibitor and atomoxetine in extensive metabolizers of CYP2D6, increased atomoxetine steady-state plasma concentrations by approximately 6 to 8-fold. This increase is similar to exposures observed in poor metabolizers. Concurrent use of a strong CYP2D6 inhibitor with atomoxetine in poor metabolizers is not expected to increase atomoxetine exposure.
Fluphenazine: (Minor) Use caution if atomoxetine is administered with fluphenazine as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Fluphenazine is also associated with a possible risk for QT prolongation.
Fluvoxamine: (Minor) Coadminister atomoxetine and fluvoxamine with caution as concurrent use may increase the risk of QT prolongation. There may be an increased risk for QT prolongation and torsade de pointes (TdP) during concurrent use of these medications. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. QT prolongation and TdP have been reported during post-marketing use of fluvoxamine.
Foscarnet: (Major) Concomitant use of atomoxetine and foscarnet increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Fostemsavir: (Moderate) Concomitant use of atomoxetine and fostemsavir may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with fostemsavir is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 4 times the recommended daily dose.
Gemifloxacin: (Moderate) Concomitant use of atomoxetine and gemifloxacin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Gemtuzumab Ozogamicin: (Moderate) Concomitant use of atomoxetine and gemtuzumab ozogamicin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Gilteritinib: (Moderate) Concomitant use of atomoxetine and gilteritinib may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Givosiran: (Major) Avoid concomitant use of givosiran and atomoxetine due to the risk of increased atomoxetine-related adverse reactions. If use is necessary, consider reducing the atomoxetine dose. Atomoxetine is a sensitive CYP2D6 substrate. Givosiran may moderately reduce hepatic CYP2D6 enzyme activity because of its pharmacological effects on the hepatic heme biosynthesis pathway.
Glasdegib: (Major) Avoid coadministration of glasdegib with atomoxetine due to the potential for additive QT prolongation. If coadministration cannot be avoided, monitor patients for increased risk of QT prolongation with increased frequency of ECG monitoring. Glasdegib therapy may result in QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose.
Goserelin: (Moderate) Concomitant use of atomoxetine and androgen deprivation therapy (i.e., goserelin) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Granisetron: (Moderate) Concomitant use of atomoxetine and granisetron may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Guaifenesin; Phenylephrine: (Moderate) Due to the potential for additive increases in blood pressure and heart rate, atomoxetine should be used cautiously with vasopressors such as phenylephrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if vasopressors are coadministered with atomoxetine.
Guaifenesin; Pseudoephedrine: (Moderate) Use atomoxetine with caution and monitor blood pressure in patients receiving concomitant pseudoephedrine due to potential effects on blood pressure.
Halogenated Anesthetics: (Major) Concomitant use of atomoxetine and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Haloperidol: (Moderate) Concomitant use of atomoxetine and haloperidol may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The intravenous route may carry a higher risk for haloperidol-induced QT/QTc prolongation than other routes of administration.
Histrelin: (Moderate) Concomitant use of atomoxetine and androgen deprivation therapy (i.e., histrelin) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Hydroxychloroquine: (Major) Concomitant use of hydroxychloroquine and atomoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Hydroxyzine: (Moderate) Concomitant use of atomoxetine and hydroxyzine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Ibuprofen; Pseudoephedrine: (Moderate) Use atomoxetine with caution and monitor blood pressure in patients receiving concomitant pseudoephedrine due to potential effects on blood pressure.
Ibutilide: (Major) Concomitant use of ibutilide and atomoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Iloperidone: (Major) Concomitant use of iloperidone and atomoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Imatinib: (Major) Administer atomoxetine and imatinib, STI-571 with caution. Because atomoxetine is primarily metabolized by CYP2D6, concurrent use of strong CYP2D6 inhibitors such as imatinib may theoretically increase the risk of atomoxetine-induced adverse effects. In children and adolescents up to 70 kg receiving a strong CYP2D6 inhibitor or who are known CYP2D6 poor metabolizers (PMs), atomoxetine 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 the initial dose is well tolerated. In children and adolescents over 70 kg and adults receiving a strong CYP2D6 inhibitor or who are known CYP2D6 poor metabolizers, atomoxetine 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. If concurrent use is necessary, monitor for adverse effects, such as dizziness, drowsiness, nervousness, insomnia, and cardiac effects (e.g., hypertension, increased pulse rate, QT prolongation) during concurrent use.
Imipramine: (Minor) Atomoxetine should be used cautiously with tricyclic antidepressants (TCAs) such as imipramine as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Tricyclic antidepressants share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab ozogamicin with atomoxetine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose.
Iobenguane I 131: (Major) Discontinue selective norepinephrine reuptake inhibitors for at least 5 half-lives before the administration of the dosimetry dose or a therapeutic dose of iobenguane I-131. Do not restart selective norepinephrine reuptake inhibitors until at least 7 days after each iobenguane I-131 dose. Drugs that reduce catecholamine uptake or deplete catecholamine stores, such as selective norepinephrine reuptake inhibitors, may interfere with iobenguane I-131 uptake into cells and interfere with dosimetry calculations resulting in altered iobenguane I-131 efficacy.
Isocarboxazid: (Contraindicated) The use of selective norepinephrine reuptake inhibitors with monoamine oxidase inhibitors (MAOIs) is contraindicated. At least 2 weeks should elapse between the discontinuation of a drug with MAO inhibiting activity and the start of selective norepinephrine reuptake inhibitors, or vice-versa. Selective norepinephrine reuptake inhibitors potentiate certain catecholamines by inhibiting neuronal reuptake. Reactions with MAOIs may include confusion, seizures, and severe hypertension as well as less severe symptoms.
Isoflurane: (Major) Concomitant use of atomoxetine and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Isoniazid, INH: (Contraindicated) The use of atomoxetine with monoamine oxidase inhibitors (MAOIs) is contraindicated. Isoniazid (INH) possesses weak MAO-inhibiting activity. Atomoxetine is one of the selective norepinephrine reuptake inhibitors. Since norepinephrine is deaminated by monoamine oxidase, administration of drugs that inhibit this enzyme concurrently with atomoxetine can lead to serious reactions. These reactions may include confusion, seizures, and severe hypertension as well as less severe symptoms. Atomoxetine should not be taken with any MAOI, or within 2 weeks after discontinuing a MAOI and vice versa.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Contraindicated) The use of atomoxetine with monoamine oxidase inhibitors (MAOIs) is contraindicated. Isoniazid (INH) possesses weak MAO-inhibiting activity. Atomoxetine is one of the selective norepinephrine reuptake inhibitors. Since norepinephrine is deaminated by monoamine oxidase, administration of drugs that inhibit this enzyme concurrently with atomoxetine can lead to serious reactions. These reactions may include confusion, seizures, and severe hypertension as well as less severe symptoms. Atomoxetine should not be taken with any MAOI, or within 2 weeks after discontinuing a MAOI and vice versa.
Isoniazid, INH; Rifampin: (Contraindicated) The use of atomoxetine with monoamine oxidase inhibitors (MAOIs) is contraindicated. Isoniazid (INH) possesses weak MAO-inhibiting activity. Atomoxetine is one of the selective norepinephrine reuptake inhibitors. Since norepinephrine is deaminated by monoamine oxidase, administration of drugs that inhibit this enzyme concurrently with atomoxetine can lead to serious reactions. These reactions may include confusion, seizures, and severe hypertension as well as less severe symptoms. Atomoxetine should not be taken with any MAOI, or within 2 weeks after discontinuing a MAOI and vice versa.
Itraconazole: (Moderate) Concomitant use of atomoxetine and itraconazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Ivosidenib: (Major) Avoid coadministration of ivosidenib with atomoxetine due to an increased risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QTc prolongation and monitor electrolytes; correct any electrolyte abnormalities as clinically appropriate. An interruption of therapy and dose reduction of ivosidenib may be necessary if QT prolongation occurs. Prolongation of the QTc interval and ventricular arrhythmias have been reported in patients treated with ivosidenib. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose.
Ketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and atomoxetine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. QT prolongation has been reported postmarketing with atomoxetine; ketoconazole is associated with QT prolongation and TdP.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Concomitant use of atomoxetine and clarithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Lapatinib: (Moderate) Concomitant use of atomoxetine and lapatinib may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Lefamulin: (Major) Avoid coadministration of lefamulin with atomoxetine as concurrent use may increase the risk of QT prolongation. If coadministration cannot be avoided, monitor ECG during treatment. Lefamulin has a concentration dependent QTc prolongation effect. The pharmacodynamic interaction potential to prolong the QT interval of the electrocardiogram between lefamulin and other drugs that effect cardiac conduction is unknown. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose.
Lenvatinib: (Major) Concomitant use of lenvatinib and atomoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Leuprolide: (Moderate) Concomitant use of atomoxetine and androgen deprivation therapy (i.e., leuprolide) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Leuprolide; Norethindrone: (Moderate) Concomitant use of atomoxetine and androgen deprivation therapy (i.e., leuprolide) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Levofloxacin: (Moderate) Concomitant use of levofloxacin and atomoxetine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Levoketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and atomoxetine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. QT prolongation has been reported postmarketing with atomoxetine; ketoconazole is associated with QT prolongation and TdP.
Levomilnacipran: (Moderate) Levomilnacipran is a serotonin norepinephrine reuptake inhibitor (SNRI) and atomoxetine selectively inhibits norepinephrine reuptake; the drugs have some additive pharmacology that may lead to increases in blood pressure or heart rate.
Lidocaine; Epinephrine: (Moderate) Use atomoxetine with caution and monitor blood pressure in patients receiving concomitant epinephrine due to potential effects on blood pressure.
Linezolid: (Major) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Atomoxetine should not be taken with any MAOI, or within 2 weeks after discontinuing a MAOI and vice versa. Atomoxetine, a selective norepinephrine reuptake inhibitor, is contraindicated with the use of any MAOI due to the potential for serious reactions. Clinically, the potential for interaction between linezolid and atomoxetine has not been studied.
Lithium: (Moderate) Concomitant use of atomoxetine and lithium may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Lofexidine: (Moderate) Concomitant use of atomoxetine and lofexidine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Loperamide: (Moderate) Concomitant use of atomoxetine and loperamide may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Loperamide; Simethicone: (Moderate) Concomitant use of atomoxetine and loperamide may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Lopinavir; Ritonavir: (Major) Concomitant use of lopinavir and atomoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Loratadine; Pseudoephedrine: (Moderate) Use atomoxetine with caution and monitor blood pressure in patients receiving concomitant pseudoephedrine due to potential effects on blood pressure.
Macimorelin: (Major) Avoid concurrent administration of macimorelin with drugs that prolong the QT interval, such as atomoxetine. Use of these drugs together may increase the risk of developing torsade de pointes-type ventricular tachycardia. Sufficient washout time of drugs that are known to prolong the QT interval prior to administration of macimorelin is recommended. Treatment with macimorelin has been associated with an increase in the corrected QT (QTc) interval. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose.
Maprotiline: (Minor) Use caution when administering atomoxetine with maprotiline as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Mefloquine: (Moderate) Concomitant use of atomoxetine and mefloquine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Methadone: (Major) Concomitant use of methadone and atomoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Methamphetamine: (Major) Due to the potential for increases in blood pressure and heart rate, atomoxetine should be used cautiously with drugs with sympathomimetic activity such as methamphetamine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if sympathomimetics are coadministered with atomoxetine.
Methscopolamine: (Moderate) Methscopolamine and atomoxetine should be combined cautiously in patients with known cardiac disease. Methscopolamine may alter the heart rate; the predominant clinical effect is sinus tachycardia. An additive effect on heart rate may occur as atomoxetine may elevate heart rate as well as blood pressure.
Metronidazole: (Moderate) Concomitant use of metronidazole and atomoxetine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Midodrine: (Major) Due to the potential for additive increases in blood pressure and heart rate, atomoxetine should be used cautiously with vasopressors such as midodrine. Consider monitoring the patients blood pressure and heart rate at baseline and regularly if vasopressors are coadministered with atomoxetine.
Midostaurin: (Major) Concomitant use of midostaurin and atomoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Mifepristone: (Major) Concomitant use of atomoxetine and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Mirabegron: (Moderate) Because atomoxetine is primarily metabolized by CYP2D6, concurrent use of CYP2D6 inhibitors such as mirabegron may theoretically increase the risk of atomoxetine-induced adverse effects. Monitor for adverse effects, such as dizziness, drowsiness, nervousness, insomnia, and cardiac effects (e.g., hypertension, QT prolongation).
Mirtazapine: (Moderate) Concomitant use of atomoxetine and mirtazapine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Mobocertinib: (Major) Concomitant use of mobocertinib and atomoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Monoamine oxidase inhibitors: (Contraindicated) The use of selective norepinephrine reuptake inhibitors with monoamine oxidase inhibitors (MAOIs) is contraindicated. At least 2 weeks should elapse between the discontinuation of a drug with MAO inhibiting activity and the start of selective norepinephrine reuptake inhibitors, or vice-versa. Selective norepinephrine reuptake inhibitors potentiate certain catecholamines by inhibiting neuronal reuptake. Reactions with MAOIs may include confusion, seizures, and severe hypertension as well as less severe symptoms.
Moxifloxacin: (Major) Concomitant use of moxifloxacin and atomoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Naproxen; Pseudoephedrine: (Moderate) Use atomoxetine with caution and monitor blood pressure in patients receiving concomitant pseudoephedrine due to potential effects on blood pressure.
Nicardipine: (Moderate) Monitor for adverse effects, such as dizziness, drowsiness, nervousness, insomnia, and cardiac effects (e.g., hypertension, increased pulse rate, QT prolongation) if concurrent use of nicardipine and atomoxetine is necessary. Because atomoxetine is primarily metabolized by CYP2D6, concurrent use of CYP2D6 inhibitors such as nicardipine may theoretically increase the risk of atomoxetine-induced adverse effects.
Nilotinib: (Major) Concomitant use of atomoxetine and nilotinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Nitroglycerin: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antidepressants. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with antidepressants.
Norepinephrine: (Moderate) Due to the potential for additive increases in blood pressure and heart rate, atomoxetine should be used cautiously with vasopressors such as norepinephrine. Consider monitoring blood pressure and heart rate at baseline and regularly if vasopressors are coadministered with atomoxetine.
Nortriptyline: (Minor) Atomoxetine should be used cautiously with tricyclic antidepressants (TCAs) such as nortriptyline as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Tricyclic antidepressants share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
Ofloxacin: (Moderate) Concomitant use of ofloxacin and atomoxetine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Olanzapine: (Moderate) Concomitant use of atomoxetine and olanzapine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Olanzapine; Fluoxetine: (Major) Monitor for evidence of QT prolongation and increased atomoxetine-related adverse effects during coadministration with fluoxetine. Dosage reduction of atomoxetine is recommended in patients receiving fluoxetine due to the potential for increased atomoxetine exposure and related adverse effects. In children and adolescents up to 70 kg receiving fluoxetine, atomoxetine 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 the initial dose is well-tolerated. In children and adolescents over 70 kg and adults receiving fluoxetine, atomoxetine 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. Fluoxetine is a strong CYP2D6 inhibitor; atomoxetine is a CYP2D6 substrate. Coadministration of a strong CYP2D6 inhibitor and atomoxetine in extensive metabolizers of CYP2D6, increased atomoxetine steady-state plasma concentrations by approximately 6 to 8-fold. This increase is similar to exposures observed in poor metabolizers. Concurrent use of a strong CYP2D6 inhibitor with atomoxetine in poor metabolizers is not expected to increase atomoxetine exposure. (Moderate) Concomitant use of atomoxetine and olanzapine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Olanzapine; Samidorphan: (Moderate) Concomitant use of atomoxetine and olanzapine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Ondansetron: (Major) Concomitant use of ondansetron and atomoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Oritavancin: (Moderate) Atomoxetine is metabolized by CYP2D6; oritavancin is a weak CYP2D6 inducer. Plasma concentrations and efficacy of atomoxetine may be reduced if these drugs are administered concurrently.
Osilodrostat: (Moderate) Concomitant use of atomoxetine and osilodrostat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Osimertinib: (Major) Concomitant use of osimertinib and atomoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Oxaliplatin: (Major) Concomitant use of oxaliplatin and atomoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ozanimod: (Major) In general, do not initiate ozanimod in patients taking atomoxetine due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). Increased blood pressure or hypertensive crisis may also be possible, as atomoxetine may increase heart rate and blood pressure. If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose.
Pacritinib: (Major) Concomitant use of pacritinib and atomoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Paliperidone: (Major) Concomitant use of paliperidone and atomoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Panobinostat: (Major) The co-administration of panobinostat and atomoxetine is not recommended. If concomitant use cannot be avoided, closely monitor patients for signs and symptoms of atomoxetine toxicity. Panobinostat is a CYP2D6 inhibitor and atomoxetine is a CYP2D6-sensitive substrate. When a single-dose of a CYP2D6-sensitive substrate was administered after 3 doses of panobinostat (20 mg given on days 3, 5, and 8), the CYP2D6 substrate Cmax increased by 20% to 200% and the AUC value increased by 20% to 130% in 14 patients with advanced cancer; exposure was highly variable (coefficient of variance > 150%).
Paroxetine: (Major) Dosage reduction of atomoxetine is recommended in patients receiving paroxetine due to the potential for increased atomoxetine exposure and related adverse effects. In children and adolescents up to 70 kg receiving paroxetine, atomoxetine 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 the initial dose is well-tolerated. In children and adolescents over 70 kg and adults receiving paroxetine, atomoxetine 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. Paroxetine is a strong CYP2D6 inhibitor; atomoxetine is a CYP2D6 substrate. Coadministration of a strong CYP2D6 inhibitor and atomoxetine in extensive metabolizers of CYP2D6 increased atomoxetine steady-state plasma concentrations by approximately 6 to 8-fold. This increase is similar to exposures observed in poor metabolizers. Concurrent use of a strong CYP2D6 inhibitor with atomoxetine in poor metabolizers is not expected to increase atomoxetine exposure.
Pasireotide: (Moderate) Concomitant use of atomoxetine and pasireotide may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Pazopanib: (Major) Concomitant use of pazopanib and atomoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Peginterferon Alfa-2b: (Moderate) Monitor for adverse effects associated with increased exposure to atomoxetine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while atomoxetine is a CYP2D6 substrate.
Pentamidine: (Major) Concomitant use of pentamidine and atomoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Perphenazine: (Minor) Use caution when administering atomoxetine with perphenazine as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Additionally, perphenazine is associated with a possible risk for QT prolongation.
Perphenazine; Amitriptyline: (Minor) Use caution when administering atomoxetine with perphenazine as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Additionally, perphenazine is associated with a possible risk for QT prolongation.
Phendimetrazine: (Major) Due to the potential for increases in blood pressure and heart rate, atomoxetine should be used cautiously with drugs with sympathomimetic activity such as phendimetrazine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if sympathomimetics are coadministered with atomoxetine.
Phenelzine: (Contraindicated) The use of selective norepinephrine reuptake inhibitors with monoamine oxidase inhibitors (MAOIs) is contraindicated. At least 2 weeks should elapse between the discontinuation of a drug with MAO inhibiting activity and the start of selective norepinephrine reuptake inhibitors, or vice-versa. Selective norepinephrine reuptake inhibitors potentiate certain catecholamines by inhibiting neuronal reuptake. Reactions with MAOIs may include confusion, seizures, and severe hypertension as well as less severe symptoms.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Atropine and atomoxetine should be combined cautiously in patients with known cardiac disease. Atropine or scopolamine may alter the heart rate; the predominant clinical effect is sinus tachycardia. An additive effect on heart rate may occur as atomoxetine may elevate heart rate as well as blood pressure. (Moderate) Scopolamine and atomoxetine should be combined cautiously in patients with known cardiac disease. Scopolamine may alter the heart rate; the predominant clinical effect is sinus tachycardia. An additive effect on heart rate may occur as atomoxetine may elevate heart rate as well as blood pressure.
Phentermine: (Moderate) Use atomoxetine with caution and monitor blood pressure in patients receiving concomitant phentermine due to potential effects on blood pressure.
Phentermine; Topiramate: (Moderate) Use atomoxetine with caution and monitor blood pressure in patients receiving concomitant phentermine due to potential effects on blood pressure.
Phenylephrine: (Moderate) Due to the potential for additive increases in blood pressure and heart rate, atomoxetine should be used cautiously with vasopressors such as phenylephrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if vasopressors are coadministered with atomoxetine.
Pimavanserin: (Major) Concomitant use of pimavanserin and atomoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Pimozide: (Contraindicated) Avoid concomitant use of pimozide and atomoxetine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Pitolisant: (Major) Concomitant use of pitolisant and atomoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ponesimod: (Major) In general, do not initiate ponesimod in patients taking atomoxetine due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ponesimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ponesimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose.
Posaconazole: (Moderate) Concomitant use of atomoxetine and posaconazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Prilocaine; Epinephrine: (Moderate) Use atomoxetine with caution and monitor blood pressure in patients receiving concomitant epinephrine due to potential effects on blood pressure.
Primaquine: (Moderate) Concomitant use of atomoxetine and primaquine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Procainamide: (Major) Concomitant use of procainamide and atomoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Procarbazine: (Contraindicated) Procarbazine is a weak monoamine oxidase inhibitor (MAOI). The use of atomoxetine with monoamine oxidase inhibitors (MAOIs) is contraindicated. Atomoxetine should not be taken with any MAOI, or within 2 weeks after discontinuing a MAOI and vice versa. Atomoxetine is one of the selective norepinephrine reuptake inhibitors (SNRIs). Since norepinephrine is deaminated by monoamine oxidase, administration of drugs that inhibit this enzyme concurrently with atomoxetine can lead to serious reactions. These reactions may include confusion, seizures, and severe hypertension as well as less severe symptoms.
Prochlorperazine: (Minor) Use atomoxetine with caution in combination with prochlorperazine as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Prochlorperazine is also associated with a possible risk for QT prolongation.
Promethazine: (Moderate) Concomitant use of atomoxetine and promethazine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Promethazine; Dextromethorphan: (Moderate) Concomitant use of atomoxetine and promethazine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Promethazine; Phenylephrine: (Moderate) Concomitant use of atomoxetine and promethazine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. (Moderate) Due to the potential for additive increases in blood pressure and heart rate, atomoxetine should be used cautiously with vasopressors such as phenylephrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if vasopressors are coadministered with atomoxetine.
Propafenone: (Major) Concomitant use of propafenone and atomoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Protriptyline: (Minor) Atomoxetine should be used cautiously with tricyclic antidepressants (TCAs) such as protriptyline as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Tricyclic antidepressants share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
Pseudoephedrine: (Moderate) Use atomoxetine with caution and monitor blood pressure in patients receiving concomitant pseudoephedrine due to potential effects on blood pressure.
Pseudoephedrine; Triprolidine: (Moderate) Use atomoxetine with caution and monitor blood pressure in patients receiving concomitant pseudoephedrine due to potential effects on blood pressure.
Quetiapine: (Major) Concomitant use of atomoxetine and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Quinidine: (Major) If possible, quinidine should be avoided in patients receiving atomoxetine. Coadministration of quinidine with atomoxetine may result in additive QT prolongation and increased exposure to atomoxetine. When administered as quinidine; dextromethorphan, coadministration with atomoxetine is contraindicated. Quinidine is a CYP2D6 inhibitor that is associated with QT prolongation and torsade de pointes (TdP). Atomoxetine is a CYP2D6 substrate. In children and adolescents up to 70 kg receiving quinidine, atomoxetine 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 the initial dose is well tolerated. In children and adolescents over 70 kg and adults receiving quinidine, atomoxetine 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. Coadministration of a strong CYP2D6 inhibitor and atomoxetine in extensive metabolizers of CYP2D6, increased atomoxetine steady-state plasma concentrations by approximately 6 to 8-fold. This increase is similar to exposures observed in poor metabolizers. Concurrent use of a strong CYP2D6 inhibitor with atomoxetine in poor metabolizers is not expected to increase atomoxetine exposure.
Quinine: (Major) QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Both atomoxetine and quinine are considered drugs with a possible risk of torsade de pointes (TdP); therefore, the combination should be used cautiously and with close monitoring. In addition, because atomoxetine is primarily metabolized by CYP2D6, concurrent use of CYP2D6 inhibitors such as quinine may theoretically increase the risk of atomoxetine-induced adverse effects. Monitor for adverse effects, such as dizziness, drowsiness, nervousness, insomnia, and cardiac effects (e.g., hypertension, increased pulse rate, QT prolongation).
Quizartinib: (Major) Concomitant use of quizartinib and atomoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Racepinephrine: (Major) Due to the potential for additive increases in blood pressure and heart rate, atomoxetine should be used cautiously with sympathomimetic agents such as racepinephrine. If a patient is taking atomoxetine, then they should seek health care professional advice prior to the use of racepinephrine. Consider monitoring the patients blood pressure and heart rate at baseline and regularly if racepinephrine inhalation is medically necessary in a patient coadministered atomoxetine.
Ranolazine: (Moderate) Concomitant use of atomoxetine and ranolazine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Rasagiline: (Contraindicated) The use of selective norepinephrine reuptake inhibitors (such as atomoxetine) with monoamine oxidase inhibitors (MAOIs) is contraindicated. At least 2 weeks should elapse between the discontinuation of a drug with MAO inhibiting activity and the start of selective norepinephrine reuptake inhibitors, or vice-versa. Selective norepinephrine reuptake inhibitors potentiate certain catecholamines by inhibiting neuronal reuptake. Reactions with MAOIs may include confusion, seizures, and severe hypertension as well as less severe symptoms.
Relugolix: (Moderate) Concomitant use of atomoxetine and androgen deprivation therapy (i.e., relugolix) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Relugolix; Estradiol; Norethindrone acetate: (Moderate) Concomitant use of atomoxetine and androgen deprivation therapy (i.e., relugolix) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Ribociclib: (Major) Concomitant use of ribociclib and atomoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ribociclib; Letrozole: (Major) Concomitant use of ribociclib and atomoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Rilpivirine: (Moderate) Concomitant use of atomoxetine and rilpivirine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Risperidone: (Moderate) Concomitant use of atomoxetine and risperidone may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Rivaroxaban: (Major) Coadministration of rivaroxaban with other drugs that affect hemostasis, such as selective norepinephrine reuptake inhibitors (SNRIs), increases the risk of bleeding. If these drugs are administered together, instruct patients to monitor for signs and symptoms of bleeding, and to promptly report any bleeding events to their practitioner.
Rolapitant: (Major) Use caution if atomoxetine and rolapitant are used concurrently, and monitor for atomoxetine-related adverse effects. Atomoxetine is a CYP2D6 substrate and rolapitant is a moderate CYP2D6 inhibitor; the inhibitory effect of rolapitant is expected to persist beyond 28 days for an unknown duration. Exposure to another CYP2D6 substrate, following a single dose of rolapitant increased about 3-fold on Days 8 and Day 22. The inhibition of CYP2D6 persisted on Day 28 with a 2.3-fold increase in the CYP2D6 substrate concentrations, the last time point measured.
Romidepsin: (Moderate) Concomitant use of atomoxetine and romidepsin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Safinamide: (Contraindicated) The use of selective norepinephrine reuptake inhibitors (such as atomoxetine) with monoamine oxidase inhibitors (MAOIs) is contraindicated. At least 2 weeks should elapse between the discontinuation of a drug with MAO inhibiting activity and the start of selective norepinephrine reuptake inhibitors, or vice-versa. Selective norepinephrine reuptake inhibitors potentiate certain catecholamines by inhibiting neuronal reuptake. Reactions with MAOIs may include confusion, seizures, and severe hypertension as well as less severe symptoms.
Saquinavir: (Major) Concomitant use of saquinavir and atomoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Scopolamine: (Moderate) Scopolamine and atomoxetine should be combined cautiously in patients with known cardiac disease. Scopolamine may alter the heart rate; the predominant clinical effect is sinus tachycardia. An additive effect on heart rate may occur as atomoxetine may elevate heart rate as well as blood pressure.
Selegiline: (Contraindicated) Selective norepinephrine reuptake inhibitors are contraindicated for use with selegiline because of a possible increased risk of hypertensive crisis. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with a selective norepinephrine reuptake inhibitor. After stopping treatment with the reuptake inhibitor, a time period equal to 4 to 5 half-lives of the reuptake inhibitor or any active metabolite should elapse before starting therapy with selegiline.
Selpercatinib: (Major) Concomitant use of selpercatinib and atomoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Sertraline: (Moderate) Concomitant use of atomoxetine and sertraline may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with sertraline is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 2 times the maximum recommended dose.
Sevoflurane: (Major) Concomitant use of atomoxetine and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Siponimod: (Major) Concomitant use of siponimod and atomoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Sodium Stibogluconate: (Moderate) Concomitant use of sodium stibogluconate and atomoxetine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Solifenacin: (Moderate) Concomitant use of atomoxetine and solifenacin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Sorafenib: (Major) Concomitant use of sorafenib and atomoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Sotalol: (Major) Concomitant use of atomoxetine and sotalol increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Sunitinib: (Moderate) Concomitant use of atomoxetine and sunitinib may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Tacrolimus: (Moderate) Concomitant use of atomoxetine and tacrolimus may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Tamoxifen: (Moderate) Concomitant use of tamoxifen and atomoxetine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Tapentadol: (Major) Caution is advised when tapentadol is coadministered with selective norepinephrine reuptake inhibitors. The combined use of these drugs may result in excessive concentrations of norepinephrine, increasing the risk of adverse cardiac effects. If concomitant treatment is clinically warranted, careful observation of the patient is advised, especially during initiation of the second therapy and after dosage adjustments (increases) of either agent.
Telavancin: (Moderate) Concomitant use of atomoxetine and telavancin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Terbinafine: (Major) Dosage reduction of atomoxetine is recommended in patients receiving terbinafine due to the potential for increased atomoxetine exposure and related adverse effects. In children and adolescents up to 70 kg receiving terbinafine, atomoxetine 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 the initial dose is well tolerated. In children and adolescents over 70 kg and adults receiving terbinafine, atomoxetine 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. Terbinafine is a strong CYP2D6 inhibitor; atomoxetine is a CYP2D6 substrate. Coadministration of a strong CYP2D6 inhibitor and atomoxetine in extensive metabolizers of CYP2D6, increased atomoxetine steady-state plasma concentrations by approximately 6 to 8-fold. This increase is similar to exposures observed in poor metabolizers. Concurrent use of a strong CYP2D6 inhibitor with atomoxetine in poor metabolizers is not expected to increase atomoxetine exposure.
Tetrabenazine: (Major) Concomitant use of tetrabenazine and atomoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Thioridazine: (Contraindicated) Avoid concomitant use of thioridazine and atomoxetine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Tipranavir: (Major) Dosage reduction of atomoxetine is recommended in patients receiving tipranavir due to the potential for increased atomoxetine exposure and related adverse effects. In children and adolescents up to 70 kg receiving tipranavir, atomoxetine 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 the initial dose is well tolerated. In children and adolescents over 70 kg and adults receiving tipranavir, atomoxetine 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. Tipranavir is a strong CYP2D6 inhibitor; atomoxetine is a CYP2D6 substrate. Coadministration of a strong CYP2D6 inhibitor and atomoxetine in extensive metabolizers of CYP2D6, increased atomoxetine steady-state plasma concentrations by approximately 6 to 8-fold. This increase is similar to exposures observed in poor metabolizers. Concurrent use of a strong CYP2D6 inhibitor with atomoxetine in poor metabolizers is not expected to increase atomoxetine exposure.
Tolterodine: (Moderate) Use caution when coadministering atomoxetine and tolterodine as concurrent use may increase the risk of QT prolongation. Tolterodine has been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose.
Toremifene: (Major) Concomitant use of toremifene and atomoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Tranylcypromine: (Contraindicated) The use of selective norepinephrine reuptake inhibitors with monoamine oxidase inhibitors (MAOIs) is contraindicated. At least 2 weeks should elapse between the discontinuation of a drug with MAO inhibiting activity and the start of selective norepinephrine reuptake inhibitors, or vice-versa. Selective norepinephrine reuptake inhibitors potentiate certain catecholamines by inhibiting neuronal reuptake. Reactions with MAOIs may include confusion, seizures, and severe hypertension as well as less severe symptoms.
Trazodone: (Major) Concomitant use of atomoxetine and trazodone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Triclabendazole: (Moderate) Concomitant use of triclabendazole and atomoxetine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Trifluoperazine: (Minor) Use atomoxetine with caution in combination with trifluoperazine as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Trifluoperazine is associated with a possible risk for QT prolongation.
Trimipramine: (Minor) Atomoxetine should be used cautiously with tricyclic antidepressants (TCAs) such as trimipramine as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Tricyclic antidepressants share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
Triptorelin: (Moderate) Concomitant use of atomoxetine and androgen deprivation therapy (i.e., triptorelin) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Vandetanib: (Major) Concomitant use of vandetanib and atomoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Vardenafil: (Moderate) Concomitant use of atomoxetine and vardenafil may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Vemurafenib: (Major) QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Both atomoxetine and vemurafenib are considered drugs with a possible risk of torsade de pointes (TdP); therefore, the combination should be used cautiously and with close monitoring. In addition, because atomoxetine is primarily metabolized by CYP2D6, concurrent use of CYP2D6 inhibitors such as vemurafenib may theoretically increase the risk of atomoxetine-induced adverse effects. Monitor for adverse effects, such as dizziness, drowsiness, nervousness, insomnia, and cardiac effects (e.g., hypertension, increased pulse rate, QT prolongation).
Venlafaxine: (Moderate) The concomitant use of atomoxetine and venlafaxine may lead to additive effects on blood pressure, heart rate, or QT interval prolongation. Venlafaxine is a serotonin norepinephrine reuptake inhibitor (SNRI) and atomoxetine selectively inhibits norepinephrine reuptake; the drugs have some additive pharmacology that may lead to increases in blood pressure or heart rate. Venlafaxine is associated with a possible risk of QT prolongation; torsade de pointes (TdP) has been reported with postmarketing use. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose.
Viloxazine: (Major) Avoid concomitant use of atomoxetine and viloxazine. This combination may represent duplicate therapy and additive toxicities may occur. Additionally, atomoxetine exposure may increase. Atomoxetine is a CYP2D6 substrate and viloxazine is a weak CYP2D6 inhibitor.
Voclosporin: (Moderate) Concomitant use of atomoxetine and voclosporin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Concomitant use of atomoxetine and clarithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Voriconazole: (Moderate) Concomitant use of atomoxetine and voriconazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Vorinostat: (Moderate) Concomitant use of atomoxetine and vorinostat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Ziprasidone: (Major) Concomitant use of ziprasidone and atomoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Although the precise mechanism by which atomoxetine produces beneficial effects in Attention-Deficit/Hyperactivity Disorder (ADHD) is unknown, it is thought that the drug exerts its effect through selective inhibition of the pre-synaptic norepinephrine (NE) transporter. Atomoxetine, the R(-) isomer, selectively inhibits the neuronal reuptake of norepinephrine (NE). Atomoxetine binding sites in the brain are consistent with the known distribution of NE-containing neurons. It is hypothesized that the atomoxetine-induced increase in NE in the prefrontal cortex, a region involved in attention and memory, mediates the therapeutic effect of atomoxetine in ADHD. Increased concentrations of NE ultimately result in desensitization of beta-adrenoreceptors. Atomoxetine has minimal to no affinity for other neurotransmitter transporter or receptor sites (e.g., dopamine or serotonin).
With once-daily dosing of atomoxetine, plasma drug concentrations are low in most patients by late afternoon. How the drug's clinical effects persist with once-daily dosing despite low drug concentrations is uncertain. One investigator suggests that brain pharmacokinetics may be different than plasma, or neuroregulatory changes may exist beyond the time the drug is at the receptor site.
Atomoxetine is administered orally. Extensive metabolizers (EM) of CYP2D6 metabolized drugs are those with a normal metabolic pathway. Poor metabolizers (PM) of CYP2D6 metabolized drugs (roughly 7% of Caucasians and 2% of African Americans) have reduced activity via this pathway, leading to elevated levels of atomoxetine. Bioavailability is roughly 94% in PM and 63% in EM. In PM, the AUC is increased roughly 10-fold, and peak plasma concentrations and half-life are elevated 5-fold compared to EMs. Coadministration of atomoxetine with potent inhibitors of CYP2D6 isoenzymes in extensive metabolizers (EM) results in elevated plasma concentrations of atomoxetine. In vivo data indicate that administration of paroxetine, a potent CYP2D6 inhibitor, to PMs of 2D6 does not further decrease the clearance of atomoxetine compared to EMs receiving paroxetine. Thus, it can be concluded that coadministration of potent CYP2D6 inhibitors and atomoxetine produces a similar pharmacokinetic profile to 2D6 poor metabolizers in CYP2D6-mediated inhibition of atomoxetine conversion. The major oxidative metabolite of atomoxetine is 4-hydroxyatomoxetine, regardless of CYP2D6 status; however, 4-hydroxyatomoxetine is formed at a slower rate by several other CYP isoenzymes in poor metabolizers. 4-Hydroxyatomoxetine is as potent as atomoxetine, but circulates in much lower concentrations (i.e., 1% of atomoxetine concentration in EM and 0.1% in PM). A second metabolite, N-desmethylatomoxetine, is formed by CYP2C19 and other isoenzymes, but has substantially less pharmacological activity compared with atomoxetine and circulates in plasma at lower concentrations (5% of atomoxetine concentration in EMs and 45% of atomoxetine concentration in PMs). Plasma clearance of atomoxetine in adult EMs is 0.35L/hr/kg and the elimination half-life is 6-8 hours, but in PMs the clearance drops to 0.03 L/hr/kg and the half-life increases to 19 hours. Accumulation of atomoxetine occurs in PMs but not EMs. Biotransformation is extensive, with < 3% of a dose being excreted as the parent drug. Atomoxetine is excreted primarily in the urine (> 80%) as 4-hydroxyatomoxetine-O-glucuronide and is excreted to a lesser extent in the feces (< 17%).
With once-daily dosing of atomoxetine, plasma drug concentrations are low in most patients by late afternoon (half-life of 4 hours in extensive metabolizers). How the drug's clinical effects persist with once-daily dosing despite low drug concentrations is uncertain. One investigator suggests that brain pharmacokinetics may be different than plasma pharmacokinetics, or neuroregulatory changes may exist beyond the time the drug is at the receptor site.
Affected cytochrome P450 isoenzymes and drug transporters: CYP2D6
Atomoxetine is a primary substrate of CYP2D6. Atomoxetine has not been shown to inhibit or induce CYP enzymes 1A2, 3A, 2D6, or 2C9. Dosage adjustments are not recommended for other drugs metabolized by the 2D6 or 3A4 enzyme system when coadministered. However, dosage adjustments of atomoxetine are recommended in pediatric and adult patients who are either receiving a strong CYP2D6 inhibitor or who are 2D6 poor metabolizers (PM).
-Route-Specific Pharmacokinetics
Oral Route
Atomoxetine is rapidly absorbed from the GI tract. Drugs that elevate gastric pH have not been shown to affect atomoxetine bioavailability. The Cmax occurs 1-2 hours after dosing. Food does not effect the overall extent of absorption (AUC) of atomoxetine in adults, but does reduced the rate of absorption, reducing Cmax by 37% and Tmax by 3 hours. The volume of distribution is roughly 0.85 L/kg indicating that atomoxetine distributes primarily into total body water. Atomoxetine is 98% protein-bound, primarily to albumin.
-Special Populations
Hepatic Impairment
The AUC for atomoxetine is increased in EM patients with moderate or severe hepatic impairment compared to EM subjects with normal hepatic function; dosage adjustments are required in patients with hepatic impairment.
Renal Impairment
EM patients with end-stage renal disease had higher systemic exposure to atomoxetine vs. healthy subjects, but there was no difference when exposure was adjusted for weight and no dosage adjustments are recommended for patients with renal impairment.
Pediatrics
Similar pharmacokinetic variables for atomoxetine have been seen in children >= 6 years, adolescents and adults regardless of gender when adjusted for weight.
Geriatric
The pharmacokinetics of atomoxetine in the elderly have not been evaluated.
Ethnic Differences
Ethnicity does not affect atomoxetine pharmacokinetics, except that PMs are more common in Caucasians. Poor metabolizers (PM) of CYP2D6 metabolized drugs (roughly 7% of Caucasians and 2% of African Americans) have reduced activity via this pathway, leading to elevated levels of atomoxetine. Bioavailability is roughly 94% in PM. In PM, the AUC is increased roughly 10-fold, and peak plasma concentrations and half-life are elevated 5-fold compared to EMs. Laboratory tests are available to identify poor metabolizers via CYP2D6 but are not used in routine clinical practice. It appears poor metabolizers (PM) are able to compensate for the lack of 2D6 by converting atomoxetine to its active metabolite via multiple low affinity CYP enzymes. One in-vitro study reported the coadministration of CYP2D6 inhibitors to PMs of 2D6 substrates would not decrease the clearance of atomoxetine in these subjects. The major oxidative metabolite of atomoxetine is 4-hydroxyatomoxetine. 4-Hydroxyatomoxetine is as potent as atomoxetine, but circulates in much lower concentrations (i.e., 0.1% of atomoxetine concentration in PM). Plasma clearance of atomoxetine in PMs drops to 0.03 L/hr/kg and the half-life increases to 19 hours. Accumulation of atomoxetine occurs in PMs.