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  • CLASSES

    ADHD Agents, Non-stimulant
    Selective Norepinephrine Reuptake Inhibitor Antidepressants, SNeRIs

    BOXED WARNING

    Children, growth inhibition, suicidal ideation

    The safety and efficacy of atomoxetine in children less than 6 years of age have not been established. Atomoxetine is not approved for the treatment of major depressive disorder (MDD). An increased risk of suicidal ideation was noted during pediatric ADHD and enuresis studies with atomoxetine, including one suicide attempt but no completed suicides. Co-morbidities occurring with ADHD may increase the risk of suicidal ideation and/or behavior. Pediatric patients should be closely monitored for clinical worsening, as well as agitation, irritability, suicidal thinking or behaviors, and unusual changes in behavior. Such monitoring would generally include at least weekly in-person contact with patients during the first 4 weeks of treatment, then one visit at weeks 6, 8, and 12, then as indicated beyond 12 weeks. Additional contact by telephone may be appropriate between visits. Consideration should be given to changing or stopping the therapeutic regimen in patients who are experiencing symptoms that might be precursors to emerging suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient's presenting symptoms. Periodic reassessment of the need for medication is recommended. Atomoxetine should be prescribed in the smallest quantity consistent with good patient management in order to reduce the risk of overdose. Sudden death has been reported in association with atomoxetine treatment at usual doses in pediatric patients with structural cardiac abnormalities. A large retrospective cohort study including over 1.2 million children and young adults 2—24 years of age did not find an increased risk of serious cardiovascular events, including sudden cardiac death, myocardial infarction, or stroke in current users of drugs for the treatment of ADHD compared to nonusers (adjusted hazard ratio 0.75; 95% CI 0.31—1.85). The authors concluded that although the absolute magnitude of risk appears to be low, a modest increase in risk could not be ruled out. A cardiac assessment should be conducted prior to atomoxetine administration to evaluate appropriateness of treatment; careful screening and monitoring is recommended by the American Heart Association. The potential for growth inhibition in pediatric patients should be monitoring during atomoxetine therapy. Monitor height and weight at treatment 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. 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). Adverse effects such as aggression and hostility have been observed in some children and adolescents receiving medications for ADHD. Although this has not been a finding of statistical significance with administration of atomoxetine compared to placebo, patients should be closely monitored for potential onset of these effects. It should be noted that not all patients with ADHD will require medication; non-drug measures are often instituted concurrently with drug therapy.

    DEA CLASS

    Rx

    DESCRIPTION

    Selective norepinephrine reuptake inhibitor (NRI); lack of abuse potential
    Used for attention-deficit hyperactivity disorder (ADHD) in adults and pediatric patients 6 years and older
    Boxed warning regarding potential for suicidal ideation and need to monitor for changes in mood and behavior; may increase blood pressure and heart rate

    COMMON BRAND NAMES

    Strattera

    HOW SUPPLIED

    Atomoxetine/Atomoxetine Hydrochloride/Strattera Oral Cap: 10mg, 18mg, 25mg, 40mg, 60mg, 80mg, 100mg

    DOSAGE & INDICATIONS

    For the treatment of attention-deficit hyperactivity disorder (ADHD).
    Oral dosage
    Adults

    40 mg/day PO initially. After a minimum of 3 days, titrate to the target dose of 80 mg/day PO. Doses may be given as single dose in the morning or in 2 divided doses. After 2 to 4 weeks, the dose may be further titrated to 100 mg/day PO in 1 or 2 divided doses in patients with suboptimal response. Max: 100 mg/day PO. If the patient is a poor metabolizer of CYP2D6, only increase to the usual target dose of 80 mg/day PO 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. Atomoxetine is an integral part of a total treatment program for ADHD that may include other measures (psychological, educational, social). Maintenance treatment is generally needed in patients with ADHD; however, periodic reassessment is recommended to determine the need for continued therapy. DISCONTINUATION: Can discontinue without tapering.

    Children and Adolescents 6 to 17 years weighing more than 70 kg

    40 mg/day PO initially. After a minimum of 3 days, titrate to the target dose of 80 mg/day. Doses may be given as single dose in the morning or in 2 divided doses. After 2 to 4 weeks, the dose may be further titrated to 100 mg/day PO in 1 or 2 divided doses in patients with suboptimal response. Max: 100 mg/day PO. If the patient is a poor metabolizer of CYP2D6, only increase to the usual target dose of 80 mg/day PO 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. Treatment strategies must be individualized for patients based on psychosocial and comorbid factors. DISCONTINUATION: Can discontinue without tapering.

    Children and Adolescents 6 to 17 years weighing 70 kg or less

    0.5 mg/kg/day PO initially. Dose may be increased after a minimum of 3 days to a target dose of 1.2 mg/kg/day and may be given as a single daily dose in the morning or as 2 evenly divided doses in the morning and late afternoon/early evening. Max: 1.4 mg/kg/day (not to exceed 100 mg/day, whichever is less). If the patient is a poor metabolizer of CYP2D6, only increase to the usual target dose of 1.2 mg/kg/day PO 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. ADHD is a chronic condition that will require ongoing management and monitoring. Treatment strategies must be individualized for patients based on psychosocial and comorbid factors. DISCONTINUATION: Can discontinue without tapering.

    MAXIMUM DOSAGE

    Adults

    100 mg/day PO.

    Geriatric

    Safety and efficacy have not been evaluated.

    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.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    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.

    Renal Impairment

    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.

    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.

    STORAGE

    Strattera:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    - Store in a dry, well ventilated place

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    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.

    Pheochromocytoma

    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.    

    MAOI therapy

    Atomoxetine is contraindicated for concomitant use in patients receiving MAOI therapy.

    Hepatic disease, hepatotoxicity, jaundice

    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).

    Closed-angle glaucoma

    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.

    Constipation, GI obstruction, ileus, prostatic hypertrophy, urinary retention

    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.

    Seizure disorder, seizures

    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.

    Driving or operating machinery, ethanol intoxication

    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.

    Bipolar disorder, depression, mania

    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.

    Apheresis, arteriosclerosis, AV block, bradycardia, cardiomyopathy, celiac disease, cerebrovascular disease, congenital heart disease, females, fever, heart failure, human immunodeficiency virus (HIV) infection, hyperparathyroidism, hypocalcemia, hypokalemia, hypomagnesemia, hypothermia, hypothyroidism, long QT syndrome, myocardial infarction, QT prolongation, rheumatoid arthritis, sickle cell disease, sleep deprivation, stroke, systemic lupus erythematosus (SLE), tachycardia, ventricular arrhythmias, ventricular dysfunction

    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.

    Children, growth inhibition, suicidal ideation

    The safety and efficacy of atomoxetine in children less than 6 years of age have not been established. Atomoxetine is not approved for the treatment of major depressive disorder (MDD). An increased risk of suicidal ideation was noted during pediatric ADHD and enuresis studies with atomoxetine, including one suicide attempt but no completed suicides. Co-morbidities occurring with ADHD may increase the risk of suicidal ideation and/or behavior. Pediatric patients should be closely monitored for clinical worsening, as well as agitation, irritability, suicidal thinking or behaviors, and unusual changes in behavior. Such monitoring would generally include at least weekly in-person contact with patients during the first 4 weeks of treatment, then one visit at weeks 6, 8, and 12, then as indicated beyond 12 weeks. Additional contact by telephone may be appropriate between visits. Consideration should be given to changing or stopping the therapeutic regimen in patients who are experiencing symptoms that might be precursors to emerging suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient's presenting symptoms. Periodic reassessment of the need for medication is recommended. Atomoxetine should be prescribed in the smallest quantity consistent with good patient management in order to reduce the risk of overdose. Sudden death has been reported in association with atomoxetine treatment at usual doses in pediatric patients with structural cardiac abnormalities. A large retrospective cohort study including over 1.2 million children and young adults 2—24 years of age did not find an increased risk of serious cardiovascular events, including sudden cardiac death, myocardial infarction, or stroke in current users of drugs for the treatment of ADHD compared to nonusers (adjusted hazard ratio 0.75; 95% CI 0.31—1.85). The authors concluded that although the absolute magnitude of risk appears to be low, a modest increase in risk could not be ruled out. A cardiac assessment should be conducted prior to atomoxetine administration to evaluate appropriateness of treatment; careful screening and monitoring is recommended by the American Heart Association. The potential for growth inhibition in pediatric patients should be monitoring during atomoxetine therapy. Monitor height and weight at treatment 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. 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). Adverse effects such as aggression and hostility have been observed in some children and adolescents receiving medications for ADHD. Although this has not been a finding of statistical significance with administration of atomoxetine compared to placebo, patients should be closely monitored for potential onset of these effects. It should be noted that not all patients with ADHD will require medication; non-drug measures are often instituted concurrently with drug therapy.

    Dehydration, hypovolemia, orthostatic hypotension, syncope

    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.

    Pregnancy

    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.

    Breast-feeding

    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.

    Geriatric

    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.

    ADVERSE REACTIONS

    Severe

    hepatotoxicity / Delayed / 0-1.0
    rhabdomyolysis / Delayed / 0-1.0
    suicidal ideation / Delayed / 0.4-0.4
    seizures / Delayed / 0.1-0.2
    stroke / Early / Incidence not known
    myocardial infarction / Delayed / Incidence not known
    angioedema / Rapid / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    hepatic failure / Delayed / Incidence not known
    hepatic necrosis / Delayed / Incidence not known

    Moderate

    constipation / Delayed / 1.0-8.0
    impotence (erectile dysfunction) / Delayed / 8.0-8.0
    depression / Delayed / 4.0-7.0
    urinary retention / Early / 6.0-6.0
    ejaculation dysfunction / Delayed / 4.0-4.0
    blurred vision / Early / 4.0-4.0
    palpitations / Early / 3.0-3.0
    conjunctivitis / Delayed / 1.0-3.0
    dysuria / Early / 2.0-2.0
    prostatitis / Delayed / 0-2.0
    orthostatic hypotension / Delayed / 0.2-1.8
    hostility / Early / 0.4-1.6
    sinus tachycardia / Rapid / 0.3-1.5
    chest pain (unspecified) / Early / 0-1.0
    hallucinations / Early / 0-0.2
    psychosis / Early / 0-0.2
    mania / Early / 0-0.2
    hypertension / Early / Incidence not known
    QT prolongation / Rapid / Incidence not known
    peripheral vasoconstriction / Rapid / Incidence not known
    priapism / Delayed / Incidence not known
    growth inhibition / Delayed / Incidence not known
    hepatitis / Delayed / Incidence not known
    hyperbilirubinemia / Delayed / Incidence not known
    prolonged bleeding time / Delayed / Incidence not known
    jaundice / Delayed / Incidence not known
    elevated hepatic enzymes / Delayed / Incidence not known

    Mild

    weight loss / Delayed / 2.0-29.1
    nausea / Early / 7.0-26.0
    xerostomia / Early / 20.0-20.0
    headache / Early / 2.0-19.0
    abdominal pain / Early / 7.0-18.0
    insomnia / Early / 15.0-15.0
    drowsiness / Early / 8.0-11.0
    vomiting / Early / 4.0-11.0
    fatigue / Early / 6.0-10.0
    dizziness / Early / 5.0-8.0
    irritability / Delayed / 5.0-6.0
    abnormal dreams / Early / 4.0-4.0
    dyspepsia / Early / 4.0-4.0
    hyperhidrosis / Delayed / 4.0-4.0
    paresthesias / Delayed / 0-3.0
    dysmenorrhea / Delayed / 3.0-3.0
    chills / Rapid / 3.0-3.0
    flushing / Rapid / 0-3.0
    libido decrease / Delayed / 3.0-3.0
    anorexia / Delayed / 3.0-3.0
    asthenia / Delayed / 0-2.0
    tremor / Early / 0-2.0
    emotional lability / Early / 1.0-2.0
    restlessness / Early / 0-2.0
    agitation / Early / 0-2.0
    dysgeusia / Early / 0-2.0
    menstrual irregularity / Delayed / 0-2.0
    testicular pain / Early / 0-2.0
    increased urinary frequency / Early / 0-2.0
    urinary urgency / Early / 0-2.0
    orgasm dysfunction / Delayed / 0-2.0
    mydriasis / Early / 0-2.0
    pruritus / Rapid / 0-2.0
    urticaria / Rapid / 0-2.0
    rash / Early / 0-2.0
    muscle cramps / Delayed / 0-2.0
    syncope / Early / 0-0.8
    anxiety / Delayed / 0.4-0.4
    diarrhea / Early / 2.0
    back pain / Delayed / 2.0
    lethargy / Early / Incidence not known
    hypoesthesia / Delayed / Incidence not known
    pelvic pain / Delayed / Incidence not known
    alopecia / Delayed / Incidence not known

    DRUG INTERACTIONS

    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) Due to the potential for increases in blood pressure and heart rate, atomoxetine should be used cautiously with drugs with sympathomimetic activity such as pseudoephedrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if sympathomimetics are coadministered with atomoxetine.
    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; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: (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) Due to the potential for increases in blood pressure and heart rate, atomoxetine should be used cautiously with drugs with sympathomimetic activity such as pseudoephedrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if sympathomimetics are coadministered with atomoxetine.
    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) Due to the potential for increases in blood pressure and heart rate, atomoxetine should be used cautiously with drugs with sympathomimetic activity such as pseudoephedrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if sympathomimetics are coadministered with atomoxetine.
    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; Pseudoephedrine: (Moderate) Due to the potential for increases in blood pressure and heart rate, atomoxetine should be used cautiously with drugs with sympathomimetic activity such as pseudoephedrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if sympathomimetics are coadministered with atomoxetine.
    Acrivastine; Pseudoephedrine: (Moderate) Due to the potential for increases in blood pressure and heart rate, atomoxetine should be used cautiously with drugs with sympathomimetic activity such as pseudoephedrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if sympathomimetics are coadministered with atomoxetine.
    Alfuzosin: (Moderate) Use caution when administering alfuzosin with atomoxetine due to the potential for QT prolongation. Alfuzosin may prolong the QT interval in a dose-dependent manner. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose.
    Amiodarone: (Major) QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Both atomoxetine and amiodarone 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 amiodarone 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).
    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.
    Amlodipine; Celecoxib: (Moderate) Monitor patients closely for atomoxetine-related adverse reactions and consider a dosage reduction of atomoxetine if coadministration with celecoxib is necessary. Celecoxib may enhance the systemic exposure and toxicity of atomoxetine. In vitro studies indicate that celecoxib is an inhibitor of CYP2D6. Atomoxetine is a CYP2D6 substrate.
    Amoxicillin; Clarithromycin; Omeprazole: (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 clarithromycin.
    Amphetamine; Dextroamphetamine Salts: (Moderate) Consider monitoring heart rate and blood pressure at baseline and regularly throughout treatment if these agents must be used together. 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, amphetamine; dextroamphetamine combinations and atomoxetine should be used together cautiously, particularly in patients with a history of cardiac disease.
    Anagrelide: (Moderate) Torsades de pointes (TdP) and ventricular tachycardia have been reported with anagrelide. In addition, dose-related increases in mean QTc and heart rate were observed in healthy subjects. A cardiovascular examination, including an ECG, should be obtained in all patients prior to initiating anagrelide therapy. Monitor patients during anagrelide therapy for cardiovascular effects and evaluate as necessary. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with anagrelide include atomoxetine. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Atomoxetine is considered a drug with a possible risk of TdP.
    Apomorphine: (Moderate) Use apomorphine and atomoxetine together with caution due to the risk of additive QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose.
    Aripiprazole: (Moderate) Use caution when administering atomoxetine and aripiprazole concurrently. QT prolongation has occurred during therapeutic use and following overdose for both aripiprazole and atomoxetine.
    Arsenic Trioxide: (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 arsenic trioxide.
    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: (Major) Due to the potential for additive increases in blood pressure and heart rate, atomoxetine should be used cautiously with vasopressors such as epinephrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if vasopressors are coadministered with atomoxetine.
    Asenapine: (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 asenapine.
    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; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (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.
    Atropine; Edrophonium: (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; Carbetapentane; 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; 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; Hydrocodone; Pseudoephedrine: (Moderate) Due to the potential for increases in blood pressure and heart rate, atomoxetine should be used cautiously with drugs with sympathomimetic activity such as pseudoephedrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if sympathomimetics 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) Due to the potential for increases in blood pressure and heart rate, atomoxetine should be used cautiously with drugs with sympathomimetic activity such as pseudoephedrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if sympathomimetics are coadministered with atomoxetine.
    Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Due to the potential for increases in blood pressure and heart rate, atomoxetine should be used cautiously with drugs with sympathomimetic activity such as pseudoephedrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if sympathomimetics are coadministered with atomoxetine.
    Bupivacaine; Epinephrine: (Major) Due to the potential for additive increases in blood pressure and heart rate, atomoxetine should be used cautiously with vasopressors such as epinephrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if vasopressors are coadministered with atomoxetine.
    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) Caution is advised when administering rilpivirine with atomoxetine as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. QT prolongation has also occurred during therapeutic use of atomoxetine and following overdose.
    Carbetapentane; 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.
    Carbetapentane; 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.
    Carbetapentane; 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.
    Carbetapentane; 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.
    Carbetapentane; Phenylephrine; Pyrilamine: (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.
    Carbetapentane; Pseudoephedrine: (Moderate) Due to the potential for increases in blood pressure and heart rate, atomoxetine should be used cautiously with drugs with sympathomimetic activity such as pseudoephedrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if sympathomimetics are coadministered with atomoxetine.
    Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Moderate) Due to the potential for increases in blood pressure and heart rate, atomoxetine should be used cautiously with drugs with sympathomimetic activity such as pseudoephedrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if sympathomimetics are coadministered with atomoxetine.
    Carbinoxamine; Hydrocodone; 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.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (Moderate) Due to the potential for increases in blood pressure and heart rate, atomoxetine should be used cautiously with drugs with sympathomimetic activity such as pseudoephedrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if sympathomimetics are coadministered with atomoxetine.
    Carbinoxamine; 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.
    Carbinoxamine; Pseudoephedrine: (Moderate) Due to the potential for increases in blood pressure and heart rate, atomoxetine should be used cautiously with drugs with sympathomimetic activity such as pseudoephedrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if sympathomimetics are coadministered with atomoxetine.
    Celecoxib: (Moderate) Monitor patients closely for atomoxetine-related adverse reactions and consider a dosage reduction of atomoxetine if coadministration with celecoxib is necessary. Celecoxib may enhance the systemic exposure and toxicity of atomoxetine. In vitro studies indicate that celecoxib is an inhibitor of CYP2D6. Atomoxetine is a CYP2D6 substrate.
    Celecoxib; Tramadol: (Moderate) Monitor patients closely for atomoxetine-related adverse reactions and consider a dosage reduction of atomoxetine if coadministration with celecoxib is necessary. Celecoxib may enhance the systemic exposure and toxicity of atomoxetine. In vitro studies indicate that celecoxib is an inhibitor of CYP2D6. Atomoxetine is a CYP2D6 substrate.
    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) Due to the potential for increases in blood pressure and heart rate, atomoxetine should be used cautiously with drugs with sympathomimetic activity such as pseudoephedrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if sympathomimetics are coadministered with atomoxetine.
    Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Due to the potential for increases in blood pressure and heart rate, atomoxetine should be used cautiously with drugs with sympathomimetic activity such as pseudoephedrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if sympathomimetics are coadministered with atomoxetine.
    Chlophedianol; 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.
    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) Due to the potential for increases in blood pressure and heart rate, atomoxetine should be used cautiously with drugs with sympathomimetic activity such as pseudoephedrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if sympathomimetics are coadministered with atomoxetine.
    Chlorpheniramine; Dihydrocodeine; 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; Dihydrocodeine; Pseudoephedrine: (Moderate) Due to the potential for increases in blood pressure and heart rate, atomoxetine should be used cautiously with drugs with sympathomimetic activity such as pseudoephedrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if sympathomimetics are coadministered with atomoxetine.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Due to the potential for increases in blood pressure and heart rate, atomoxetine should be used cautiously with drugs with sympathomimetic activity such as pseudoephedrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if sympathomimetics are coadministered with atomoxetine.
    Chlorpheniramine; Hydrocodone; 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; Hydrocodone; Pseudoephedrine: (Moderate) Due to the potential for increases in blood pressure and heart rate, atomoxetine should be used cautiously with drugs with sympathomimetic activity such as pseudoephedrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if sympathomimetics are coadministered with atomoxetine.
    Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Due to the potential for increases in blood pressure and heart rate, atomoxetine should be used cautiously with drugs with sympathomimetic activity such as pseudoephedrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if sympathomimetics are coadministered with atomoxetine.
    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) Due to the potential for increases in blood pressure and heart rate, atomoxetine should be used cautiously with drugs with sympathomimetic activity such as pseudoephedrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if sympathomimetics are coadministered with atomoxetine.
    Chlorpromazine: (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 chlorpromazine.
    Cimetidine: (Moderate) Atomoxetine is primarily a substrate for the cytochrome P450 isozyme CYP2D6. A dosage adjustment of atomoxetine may be needed in normal populations (also known as extensive metabolizers) when atomoxetine is administered with inhibitors of the CYP2D6 enzyme, such as cimetidine. In vitro studies suggest that coadministration of CYP2D6 inhibitors to poor metabolizers will not further increase the plasma concentrations of atomoxetine.
    Cinacalcet: (Major) Dosage reduction of atomoxetine is recommended in patients receiving cinacalcet due to the potential for increased atomoxetine exposure and related adverse effects. In children and adolescents up to 70 kg receiving cinacalcet, 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 cinacalcet, 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. inacalcet 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.
    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) QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. QT prolongation and ventricular arrhythmias, including torsade de pointes (TdP) and death, have been reported with cisapride. Because of the potential for TdP, use of atomoxetine with cisapride is contraindicated.
    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) 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 clarithromycin.
    Clofazimine: (Major) Monitor ECGs for QT prolongation when clofazimine is administered with atomoxetine. QT prolongation and torsade de pointes have been reported in patients receiving clofazimine in combination with QT prolonging medications. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose.
    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) Use clozapine with caution in combination with atomoxetine. Treatment with clozapine has been associated with QT prolongation, torwade de pointes, cardiac arrest, and sudden death. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose.
    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) Due to the potential for increases in blood pressure and heart rate, atomoxetine should be used cautiously with drugs with sympathomimetic activity such as pseudoephedrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if sympathomimetics are coadministered with atomoxetine.
    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) Use dasatinib with caution in combination with atomoxetine. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose.
    Degarelix: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving atomoxetine. Androgen deprivation therapy (i.e., degarelix) may prolong the QT/QTc interval. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose.
    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) 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 halogenated anesthetics.
    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) Due to the potential for increases in blood pressure and heart rate, atomoxetine should be used cautiously with drugs with sympathomimetic activity such as pseudoephedrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if sympathomimetics are coadministered with atomoxetine.
    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) Due to the potential for increases in blood pressure and heart rate, atomoxetine should be used cautiously with drugs with sympathomimetic activity such as pseudoephedrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if sympathomimetics are coadministered with atomoxetine.
    Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Due to the potential for increases in blood pressure and heart rate, atomoxetine should be used cautiously with drugs with sympathomimetic activity such as pseudoephedrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if sympathomimetics are coadministered with atomoxetine.
    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) Due to the potential for increases in blood pressure and heart rate, atomoxetine should be used cautiously with drugs with sympathomimetic activity such as pseudoephedrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if sympathomimetics are coadministered with atomoxetine.
    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.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Moderate) Due to the potential for increases in blood pressure and heart rate, atomoxetine should be used cautiously with drugs with sympathomimetic activity such as pseudoephedrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if sympathomimetics are coadministered with atomoxetine.
    Diphenhydramine; Hydrocodone; 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.
    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) 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 disopyramide.
    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) Coadministration of dofetilide and atomoxetine is not recommended as concurrent use may increase the risk of QT prolongation. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). QT prolongation has occurred during therapeutic use of atomoxetine and following overdose.
    Dolasetron: (Moderate) Administer dolasetron with caution in combination with atomoxetine. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose.
    Dolutegravir; Rilpivirine: (Moderate) Caution is advised when administering rilpivirine with atomoxetine as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. QT prolongation has also occurred during therapeutic use of atomoxetine and following overdose.
    Donepezil: (Moderate) Use donepezil with caution in combination with atomoxetine. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose.
    Donepezil; Memantine: (Moderate) Use donepezil with caution in combination with atomoxetine. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose.
    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) QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Dronedarone administration is associated with a dose-related increase in the QTc interval. The increase in QTc is approximately 10 milliseconds at doses of 400 mg twice daily (the FDA-approved dose) and up to 25 milliseconds at doses of 1600 mg twice daily. Although there are no studies examining the effects of dronedarone in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation. Because of the potential for TdP, use of atomoxetine with dronedarone is contraindicated.
    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.
    Duloxetine: (Moderate) Patients should be monitored for adverse effects associated with atomoxetine administration, such as nausea/vomiting, drowsiness, fatigue, abdominal pain, or decreased appetite, during concurrent use of duloxetine. A dosage adjustment of atomoxetine may be needed in normal populations (also known as extensive metabolizers) when atomoxetine is administered with inhibitors of the CYP2D6 enzyme. Atomoxetine is primarily a substrate for the cytochrome P450 isozyme CYP2D6. In vitro studies suggest that coadministration of CYP2D6 inhibitors to poor metabolizers will not further increase the plasma concentrations of 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) Consider alternatives to efavirenz when coadministering with atomoxetine as the combination may increase the risk for QT prolongation. QT prolongation has been observed with use of efavirenz. QT prolongation has also occurred during therapeutic use of atomoxetine and following overdose.
    Efavirenz; Emtricitabine; Tenofovir: (Moderate) Consider alternatives to efavirenz when coadministering with atomoxetine as the combination may increase the risk for QT prolongation. QT prolongation has been observed with use of efavirenz. QT prolongation has also occurred during therapeutic use of atomoxetine and following overdose.
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Consider alternatives to efavirenz when coadministering with atomoxetine as the combination may increase the risk for QT prolongation. QT prolongation has been observed with use of efavirenz. QT prolongation has also occurred during therapeutic use of atomoxetine and following overdose.
    Eliglustat: (Moderate) Use caution when administering atomoxetine with eliglustat as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations.
    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) Caution is advised when administering rilpivirine with atomoxetine as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. QT prolongation has also occurred during therapeutic use of atomoxetine and following overdose.
    Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Moderate) Caution is advised when administering rilpivirine with atomoxetine as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. QT prolongation has also occurred during therapeutic use of atomoxetine and following overdose.
    Encorafenib: (Major) Avoid coadministration of encorafenib and atomoxetine due to QT prolongation. If concurrent use cannot be avoided, monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia and hypomagnesemia prior to treatment. Encorafenib is associated with dose-dependent prolongation of the QT interval. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose.
    Enflurane: (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 halogenated anesthetics.
    Entrectinib: (Major) Avoid coadministration of entrectinib with atomoxetine due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose.
    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: (Major) Due to the potential for additive increases in blood pressure and heart rate, atomoxetine should be used cautiously with vasopressors such as epinephrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if vasopressors are coadministered with atomoxetine.
    Eribulin: (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 eribulin.
    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.
    Erythromycin; Sulfisoxazole: (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.
    Ethanol: (Moderate) Avoid alcohol consumption with the use of atomoxetine due to an increased risk for drowsiness or other CNS-side effects.The consumption of alcohol with atomoxetine did not change the intoxicating effects of alcohol.
    Ezogabine: (Moderate) Use caution when coadministering atomoxetine and ezogabine as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Ezogabine has also been associated with QT prolongation.
    Fexofenadine; Pseudoephedrine: (Moderate) Due to the potential for increases in blood pressure and heart rate, atomoxetine should be used cautiously with drugs with sympathomimetic activity such as pseudoephedrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if sympathomimetics are coadministered with atomoxetine.
    Fingolimod: (Moderate) Use caution when administering atomoxetine with fingolimod as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Fingolimod results in decreased heart rate and may prolong the QT interval as well.
    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) When possible, avoid concurrent use of foscarnet with other drugs known to prolong the QT interval, such as atomoxetine. Foscarnet has been associated with postmarketing reports of both QT prolongation and torsade de pointes (TdP). QT prolongation has also occurred during therapeutic use of atomoxetine and following overdose. If these drugs are administered together, obtain an electrocardiogram and electrolyte concentrations before and periodically during treatment.
    Fostemsavir: (Moderate) Use atomoxetine and fostemsavir together with caution due to the potential for QT prolongation. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Supratherapeutic doses of fostemsavir (2,400 mg twice daily, four times the recommended daily dose) have been shown to cause QT prolongation. Fostemsavir causes dose-dependent QT prolongation.
    Gemifloxacin: (Moderate) Use caution if atomoxetine is administered with gemifloxacin as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Gemifloxacin may prolong the QT interval in some patients. The maximal change in QTc interval occurs approximately 5 to 10 hours following oral administration of gemifloxacin. The risk of QT prolongation with gemifloxacin may be dose-dependent.
    Gemtuzumab Ozogamicin: (Moderate) Use gemtuzumab ozogamicin and atomoxetine together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose.
    Gilteritinib: (Moderate) Use caution and monitor for additive QT prolongation if concurrent use of gilteritinib and atomoxetine is necessary. Gilteritinib has been associated with QT prolongation. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose.
    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) Consider whether the benefits of androgen deprivation therapy (i.e., goserelin) outweigh the potential risks of QT prolongation in patients receiving atomoxetine. Androgen deprivation therapy may prolong the QT/QTc interval. Prolongation of the QT interval has also occurred during therapeutic use of atomoxetine and following overdose.
    Granisetron: (Moderate) Use granisetron with caution in combination with atomoxetine due to the risk of QT prolongation. Granisetron has been associated with QT prolongation. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Due to the potential for increases in blood pressure and heart rate, atomoxetine should be used cautiously with drugs with sympathomimetic activity such as pseudoephedrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if sympathomimetics are coadministered with atomoxetine.
    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) Due to the potential for increases in blood pressure and heart rate, atomoxetine should be used cautiously with drugs with sympathomimetic activity such as pseudoephedrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if sympathomimetics are coadministered with atomoxetine.
    Halogenated Anesthetics: (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 halogenated anesthetics.
    Haloperidol: (Moderate) Caution is advisable when combining haloperidol with atomoxetine as concurrent use may increase the risk of QT prolongation. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. QT prolongation has occurred during the therapeutic use of atomoxetine and following overdose.
    Halothane: (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 halogenated anesthetics.
    Histrelin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving atomoxetine. Androgen deprivation therapy may prolong the QT/QTc interval. Prolongation of the QT interval has also occurred during therapeutic use of atomoxetine and following overdose.
    Hydrocodone; 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.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Moderate) Due to the potential for increases in blood pressure and heart rate, atomoxetine should be used cautiously with drugs with sympathomimetic activity such as pseudoephedrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if sympathomimetics are coadministered with atomoxetine.
    Hydrocodone; Pseudoephedrine: (Moderate) Due to the potential for increases in blood pressure and heart rate, atomoxetine should be used cautiously with drugs with sympathomimetic activity such as pseudoephedrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if sympathomimetics are coadministered with atomoxetine.
    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) Due to the potential for increases in blood pressure and heart rate, atomoxetine should be used cautiously with drugs with sympathomimetic activity such as pseudoephedrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if sympathomimetics are coadministered with atomoxetine.
    Ibutilide: (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 ibutilide.
    Iloperidone: (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 iloperidone.
    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) 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 halogenated anesthetics.
    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) Use itraconazole with caution in combination with atomoxetine as concurrent use may increase the risk of QT prolongation. Itraconazole has been associated with prolongation of the QT interval. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose.
    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) 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 clarithromycin.
    Lapatinib: (Moderate) Monitor for evidence of QT prolongation if lapatinib is administered with atomoxetine. Lapatinib has been associated with concentration-dependent QT prolongation; ventricular arrhythmias and torsade de pointes (TdP) have been reported in postmarketing experience with lapatinib. Prolongation of the QT interval has occurred during therapeutic use of atomoxetine as well as following overdose.
    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) Avoid coadministration of lenvatinib with atomoxetine due to the risk of QT prolongation. Prolongation of the QT interval has been reported with lenvatinib therapy. QT prolongation has also occurred during therapeutic use of atomoxetine and following overdose.
    Leuprolide: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving atomoxetine as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. Prolongation of the QT interval has also occurred during therapeutic use of atomoxetine and following overdose.
    Leuprolide; Norethindrone: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving atomoxetine as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. Prolongation of the QT interval has also occurred during therapeutic use of atomoxetine and following overdose.
    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: (Major) Due to the potential for additive increases in blood pressure and heart rate, atomoxetine should be used cautiously with vasopressors such as epinephrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if vasopressors are coadministered with atomoxetine.
    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.
    Lisdexamfetamine: (Moderate) Consider monitoring heart rate and blood pressure at baseline and regularly throughout treatment if these agents must be used together. Amphetamines increase both systolic and diastolic blood pressure; atomoxetine has been reported to also increase blood pressure and heart rate. Due to an additive pharmacodynamic effect, lisdexamfetamine and atomoxetine should be used together cautiously, particularly in patients with a history of cardiac disease.
    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) Monitor ECG if lofexidine is coadministered with atomoxetine due to the potential for additive QT prolongation. Lofexidine prolongs the QT interval. In addition, there are postmarketing reports of torsade de pointes. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose.
    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) Avoid coadministration of lopinavir with atomoxetine due to the potential for additive QT prolongation. If use together is necessary, obtain a baseline ECG to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Lopinavir is associated with QT prolongation. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose.
    Loratadine; Pseudoephedrine: (Moderate) Due to the potential for increases in blood pressure and heart rate, atomoxetine should be used cautiously with drugs with sympathomimetic activity such as pseudoephedrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if sympathomimetics are coadministered with atomoxetine.
    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) Mefloquine should be used with caution in patients receiving atomoxetine as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation.
    Mepenzolate: (Moderate) Mepenzolate and atomoxetine should be combined cautiously in patients with known cardiac disease. Mepenzolate 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.
    Meperidine; 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.
    Methadone: (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 methadone.
    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.
    Methylphenidate Derivatives: (Moderate) Use atomoxetine and methylphenidate derivatives together with caution and monitor for additive effects. Monitor heart rate and blood pressure, as well as for any changes in moods or behavior. Pulse and blood pressure should be measured at baseline, following any dose increases, and periodically while on therapy to detect possible clinically important increases. Coadministration of methylphenidate and atomoxetine did not increase the cardiovascular effects seen with administration of methylphenidate alone during clinical trials of atomoxetine. However, methylphenidate and its derivatives have sympathomimetic effects and atomoxetine may increase the blood pressure and heart rate.
    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) The concomitant use of midostaurin and atomoxetine may lead to additive QT interval prolongation. If these drugs are used together, consider obtaining electrocardiograms to monitor the QT interval. In clinical trials, QT prolongation was reported in patients who received midostaurin as single-agent therapy or in combination with cytarabine and daunorubicin. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose.
    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) 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 moxifloxacin.
    Naproxen; Pseudoephedrine: (Moderate) Due to the potential for increases in blood pressure and heart rate, atomoxetine should be used cautiously with drugs with sympathomimetic activity such as pseudoephedrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if sympathomimetics are coadministered with atomoxetine.
    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) Avoid the concomitant use of nilotinib with atomoxetine as significant prolongation of the QT interval may occur. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Sudden deaths and QT prolongation have been reported with nilotinib therapy.
    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.
    Norfloxacin: (Moderate) Use caution if atomoxetine is administered with norfloxacin as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Quinolones have been associated with a risk of QT prolongation and torsade de pointes (TdP). Although extremely rare, TdP has been reported during postmarketing surveillance of norfloxacin. These reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory.
    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).
    Octreotide: (Minor) Use octreotide with caution in combination with atomoxetine as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of torsade de pointes (TdP), the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    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) Caution is advised when administering olanzapine with atomoxetine as concurrent use may increase the risk of QT prolongation. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose.
    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) Caution is advised when administering olanzapine with atomoxetine as concurrent use may increase the risk of QT prolongation. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose.
    Olanzapine; Samidorphan: (Moderate) Caution is advised when administering olanzapine with atomoxetine as concurrent use may increase the risk of QT prolongation. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose.
    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) Monitor ECGs in patients receiving osilodrostat with atomoxetine as concurrent use may increase the risk of QT prolongation. Osilodrostat is associated with dose-dependent QT prolongation. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose.
    Osimertinib: (Major) Avoid coadministration of atomoxetine with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose.
    Oxaliplatin: (Major) Monitor ECGs and electrolytes in patients receiving oxaliplatin and atomoxetine concomitantly; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in post-marketing experience. QT prolongation has also occurred during therapeutic use of atomoxetine and following overdose.
    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) Paliperidone has been associated with QT prolongation; torsade de pointes (TdP) and ventricular fibrillation have been reported in the setting of overdose. According to the manufacturer, since paliperidone may prolong the QT interval, it should be avoided in combination with other agents also known to have this effect. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Atomoxetine is considered a drug with a possible risk of TdP. If coadministration is considered necessary and the patient has known risk factors for cardiac disease or arrhythmias, close monitoring is essential.
    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) Use caution when using pasireotide in combination with atomoxetine as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. QT prolongation has also occurred with pasireotide at therapeutic and supra-therapeutic doses.
    Pazopanib: (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 pazopanib.
    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) 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 pentamidine.
    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: (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 phentermine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if sympathomimetics are coadministered with atomoxetine.
    Phentermine; Topiramate: (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 phentermine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if sympathomimetics are coadministered with atomoxetine.
    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) Pimavanserin may cause QT prolongation and should generally be avoided in patients receiving other medications known to prolong the QT interval, such as atomoxetine. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Coadministration may increase the risk for QT prolongation.
    Pimozide: (Contraindicated) QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of atomoxetine with pimozide is contraindicated.
    Pitolisant: (Major) Avoid coadministration of pitolisant with atomoxetine as concurrent use may increase the risk of QT prolongation. Pitolisant prolongs the QT interval. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose.
    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) Use posaconazole with caution in combination with atomoxetine as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes.
    Prilocaine; Epinephrine: (Major) Due to the potential for additive increases in blood pressure and heart rate, atomoxetine should be used cautiously with vasopressors such as epinephrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if vasopressors are coadministered with atomoxetine.
    Primaquine: (Moderate) Use atomoxetine with caution in combination with primaquine as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Primaquine also has the potential to prolong the QT interval.
    Procainamide: (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 procainamide.
    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) QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Both atomoxetine and propafenone 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 propafenone 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).
    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) Due to the potential for increases in blood pressure and heart rate, atomoxetine should be used cautiously with drugs with sympathomimetic activity such as pseudoephedrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if sympathomimetics are coadministered with atomoxetine.
    Pseudoephedrine; Triprolidine: (Moderate) Due to the potential for increases in blood pressure and heart rate, atomoxetine should be used cautiously with drugs with sympathomimetic activity such as pseudoephedrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if sympathomimetics are coadministered with atomoxetine.
    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).
    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) Caution is advised when administering atomoxetine with ranolazine as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Ranolazine is associated with dose- and plasma concentration-related increases in the QTc interval.
    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) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving other QT prolonging agents such as atomoxetine. Androgen deprivation therapy (i.e., relugolix) may prolong the QT/QTc interval. QT prolongation has also occurred during therapeutic use of atomoxetine and following overdose.
    Relugolix; Estradiol; Norethindrone acetate: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving other QT prolonging agents such as atomoxetine. Androgen deprivation therapy (i.e., relugolix) may prolong the QT/QTc interval. QT prolongation has also occurred during therapeutic use of atomoxetine and following overdose.
    Ribociclib: (Major) Avoid coadministration of ribociclib with atomoxetine due to an increased risk for QT prolongation. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Concomitant use may increase the risk for QT prolongation.
    Ribociclib; Letrozole: (Major) Avoid coadministration of ribociclib with atomoxetine due to an increased risk for QT prolongation. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Concomitant use may increase the risk for QT prolongation.
    Rilpivirine: (Moderate) Caution is advised when administering rilpivirine with atomoxetine as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. QT prolongation has also occurred during therapeutic use of atomoxetine and following overdose.
    Risperidone: (Moderate) Use risperidone and atomoxetine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose.
    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) Consider monitoring electrolytes and ECGs at baseline and periodically during treatment if romidepsin is administered with atomoxetine. Romidepsin has been reported to prolong the QT interval. QT prolongation has also occurred during hterapeutic use of atomoxetine and following overdose.
    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) 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 saquinavir.
    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) Monitor ECGs more frequently for QT prolongation if coadministration of selpercatinib with atomoxetine is necessary due to the risk of additive QT prolongation. Concentration-dependent QT prolongation has been observed with selpercatinib therapy. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose.
    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) 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 halogenated anesthetics.
    Siponimod: (Major) In general, do not initiate treatment with siponimod in patients receiving atomoxetine due to the potential for QT prolongation. Consult a cardiologist regarding appropriate monitoring if siponimod use is required. Siponimod therapy prolonged the QT interval at recommended doses in a clinical study. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose.
    Solifenacin: (Moderate) Use caution if atomoxetine is administered with solifenacin as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsade de pointes has been reported with postmarketing use, although causality was not determined.
    Sorafenib: (Major) Avoid coadministration of sorafenib with atomoxetine due to the risk of additive QT prolongation. If concomitant use is unavoidable, monitor electrocardiograms and correct electrolyte abnormalities. An interruption or discontinuation of sorafenib therapy may be necessary if QT prolongation occurs. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Sorafenib is associated with QTc prolongation.
    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) Monitor for evidence of QT prolongation if sunitinib is administered with atomoxetine. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Sunitinib can prolong the QT interval.
    Tacrolimus: (Moderate) Consider ECG and electrolyte monitoring periodically during treatment if tacrolimus is administered with atomoxetine. Tacrolimus may prolong the QT interval and cause torsade de pointes (TdP). QT prolongation has occurred during therapeutic use of atomoxetine and following overdose.
    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) Use caution if telavancin is administered with atomoxetine as concurrent use may increase the risk of QT prolongation. Telavancin has been associated with QT prolongation. QT prolongation has occurred during therapeutic use o atomoxetine and following overdose.
    Telithromycin: (Moderate) Use caution if atomoxetine is administered with telithromycin as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Telithromycin is associated with QT prolongation and torsade de pointes (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) Avoid coadministration of tetrabenazine and atomoxetine. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Tetrabenazine causes a small increase in the corrected QT interval (QTc). Concurrent use may result in additive effects on the QT interval.
    Thioridazine: (Contraindicated) QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Thioridazine is considered contraindicated for use along with agents that, when combined with a phenothiazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension. Because of the potential for TdP, use of atomoxetine with thioridazine is contraindicated.
    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) Avoid coadministration of atomoxetine with toremifene if possible due to the risk of additive QT prolongation. If concomitant use is unavoidable, closely monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia or hypomagnesemia prior to administration of toremifene. Toremifene has been shown to prolong the QTc interval in a dose- and concentration-related manner. Prolongation of the QT interval has also occurred during therapeutic use of atomoxetine as well as following overdose.
    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) Monitor ECGs in patients receiving triclabendazole with atomoxetine as concurrent use may increase the risk of QT prolongation. Transient prolongation of the mean QTc interval was noted on the ECG recordings in dogs administered triclabendazole. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose.
    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) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving atomoxetine. Androgen deprivation therapy may prolong the QT/QTc interval. Prolongation of the QT interval has also occurred during therapeutic use of atomoxetine and following overdose.
    Vandetanib: (Major) Avoid coadministration of vandetanib with atomoxetine due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Prolongation of the QT interval has occurred during therapeutic use of atomoxetine and following overdose.
    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 voclosporin and atomoxetine may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Voclosporin has been associated with QT prolongation at supratherapeutic doses. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose.
    Voriconazole: (Moderate) Use caution if atomoxetine is administered with voriconazole as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Voriconazole has been associated with QT prolongation and rare cases of torsade de pointes.
    Vorinostat: (Moderate) Use caution if atomoxetine is administered with vorinostat as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Vorinostat therapy is also associated with a risk of QT prolongation.
    Ziprasidone: (Major) Concomitant use of ziprasidone and atomoxetine should be avoided due to the potential for additive QT prolongation. Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of torsade de pointes (TdP) in patients with multiple confounding factors. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose.

    PREGNANCY AND LACTATION

    Pregnancy

    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.

    MECHANISM OF ACTION

    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.

    PHARMACOKINETICS

    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).
     

    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.