Atoncy
Atomoxetine hydrochloride · Solution · Oral
Uses
1 INDICATIONS AND USAGE ATONCY is indicated for the treatment of attention-deficit/hyperactivity disorder (ADHD) in adult and pediatric patients 6 years of age and older. ATONCY is indicated as an integral part of a total treatment program for ADHD that may include other measures (psychological, educational, social) for patients with ADHD. ATONCY is a selective norepinephrine reuptake inhibitor (SNRI) indicated for the treatment of ADHD in adults and pediatric patients 6 years of age and older. ( 1 )
Dosage and administration
Prior to initiating treatment with ATONCY: Screen patients for a personal or family history of bipolar disorder, mania, or hypomania. ( 2.1 , 5.6 ) Consider genetic testing to determine the patient’s CYP2D6 metabolizer status prior to dosing. ( 2.1 , 2.5 ) See table below for the recommended ATONCY dosage. ( 2.3 ) Age and Body Weight Starting Dosage Target Dosage 1 Maximum Total Daily Dose 1 Pediatrics who weigh less than 70 kg 0.5 mg/kg/day 1.2 mg/kg/day 1.4 mg/kg/day or 100 mg/day (whichever is less) Pediatrics who weigh 70 kg or more and adults 40 mg/day 80 mg/day 100 mg/day 1 Administer either as once daily dosage in the morning or as evenly divided twice daily dosage in the morning and late afternoon/early evening For the recommended dosage in patients with hepatic impairment, see Full Prescribing Information. ( 2.4 ) For the recommended dosage with concomitant use of a strong CYP2D6 inhibitor or in CYP2D6 poor metabolizers, see Full Prescribing Information. ( 2.5 ) 2.1 Recommendations Prior to Initiating ATONCY Treatment Prior to initiating treatment with ATONCY: Screen patients for a personal or family history of bipolar disorder, mania, or hypomania [see Warnings and Precautions (5.6) ] . Consider genetic testing to determine the patient’s CYP2D6 metabolizer status [see Dosage and Administration (2.5) ] . 2.2 Administration Instructions ATONCY may be taken with or without food. Instruct patients to only use the supplied syringe and bottle adapter to measure and take ATONCY [see Instructions for Use ] . 2.3 Recommended Dosage Table 1 includes the recommended dosage of ATONCY in adult patients and pediatric patients 6 years of age and older for treatment of ADHD. Table 1: Recommended Dosage of ATONCY for the Treatment of ADHD Age and Body Weight Starting Dosage Titration Interval Target Dosage Maximum Dosage Pediatric patients who weigh less than 70 kg 0.5 mg/kg/day Minimum of 3 days 1.2 mg/kg/day a,b 1.4 mg/kg/day or 100 mg/day, whichever is less a Pediatric patients who weigh 70 kg or more and adult patients 40 mg/day Minimum of 3 days 80 mg/day a 100 mg/day a,c a Administered either as a single daily dose in the morning or as evenly divided doses in the morning and late afternoon/early evening. b No additional benefit has been demonstrated with atomoxetine dosages higher than 1.2 mg/kg/day [see Clinical Studies (14) ] . c If a patient has not achieved an optimal response at 80 mg/day after 2 to 4 additional weeks, may increase dosage to a maximum of 100 mg/day. There are no data that support increased effectiveness at a dosage higher than 100 mg/day [see Clinical Studies (14) ] . The health care provider who elects to use ATONCY for extended periods should periodically reevaluate the long-term usefulness of ATONCY for the individual patient. 2.4 Recommended Dosage in Patients with Hepatic Impairment For patients 6 years of age or older with: Severe hepatic impairment (HI) (Child-Pugh Class C), the recommended initial and target dosage is 25% of recommended dosage in patients with normal hepatic function [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3) ] . Moderate HI (Child-Pugh Class B), the recommended initial and target dosage is 50% of the recommended dosage in patients with normal hepatic function [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3) ] . Mild HI (Child-Pugh Class A) the recommended initial and target dosage is the same as those with normal hepatic function. 2.5 Recommended Dosage with Concomitant Use of Strong CYP2D6 Inhibitors or in CYP2D6 Poor Metabolizers Table 2 includes the recommended ATONCY dosage in adult patients and pediatric patients aged 6 years of age or older with concomitant use of a strong CYP2D6 inhibitor or in CYP2D6 poor metabolizers [see Drug Interactions (7) and Use in Specific Populations (8.7) ] . The recommended titration interval in these patients is every four weeks (if ADHD symptoms fail to improve and the initial dosage is well tolerated). For other CYP2D6 metabolizer types (ultrarapid, normal, and intermediate), follow the recommended dosage, including the recommended titration interval (minimum of 3 days), as outlined in Table 1 [see Dosage and Administration (2.3) ] . Table 2: Recommended Dosage of ATONCY with Concomitant Use of a Strong CYP2D6 Inhibitor or in CYP2D6 Poor Metabolizers Age and Body Weight Starting Dosage Titration Interval a Target Dosage d Pediatric patients who weigh less than 70 kg 0.5 mg/kg/day 4 weeks 1.2 mg/kg/day b,c Pediatric patients who weigh 70 kg or more and adult patients 40 mg/day 4 weeks 80 mg/day b a Titrate if ADHD symptoms fail to improve and the initial dosage is well tolerated. b Administered either as a single daily dose in the morning or as evenly divided doses in the morning and late afternoon/early evening. c No additional benefit has been demonstrated with atomoxetine dosages higher than 1.2 mg/kg/day [see Clinical Studies (14) ] . d Maximum dosage has not been established with concomitant use of a strong CYP2D6 inhibitor or in CYP2D6 poor metabolizers. 2.6 Switching to or from a Monoamine Oxidase Inhibitor Antidepressant At least 14 days must elapse between discontinuation of a monoamine oxidase inhibitor (MAOI) antidepressant and initiation of ATONCY. In addition, at least 14 days must elapse after stopping ATONCY before starting an MAOI antidepressant. 2.7 Recommendations for a Missed Dose If the ATONCY dose is missed, take the dose as soon as possible, but do not take more than the prescribed total daily amount of ATONCY in any 24-hour period. 2.8 Recommendations for Discontinuation When discontinuing atomoxetine, no taper is needed [see Drug Abuse and Dependence (9.3) ] .
Dosage forms and strengths
Oral Solution: Each mL contains 4 mg of atomoxetine (equivalent to 4.57 mg of atomoxetine hydrochloride), clear colorless solution, free from any visible foreign and particulate matter, free of precipitation and hazy mass. Supplied with a 10 mL oral syringe and a bottle adapter. Oral solution: Each mL contains 4 mg of atomoxetine
Contraindications
4 CONTRAINDICATIONS ATONCY is contraindicated in patients: With known hypersensitivity reaction to ATONCY or other components of ATONCY. Hypersensitivity reactions that occurred with ATONCY use included anaphylaxis, angioneurotic edema, urticaria, and rash [see Warnings and Precautions (5.8) ] . Taking, or within 14 days of stopping, a monoamine oxidase inhibitor (MAOI) [see Drug Interactions (7) ] . With narrow angle glaucoma. In clinical trials, ATONCY use was associated with an increased risk of mydriasis. With pheochromocytoma or a history of pheochromocytoma. Serious reactions, including elevated blood pressure and tachyarrhythmia, have been reported in patients with pheochromocytoma or a history of pheochromocytoma who received ATONCY. With severe cardiac or vascular disorders whose condition would be expected to deteriorate if they had clinically important increase in blood pressure or heart rate (e.g., 15 to 20 mm Hg in blood pressure or 20 beats per minute in heart rate) [see Warnings and Precautions (5.4) ] . Contraindicated in patients ( 4 ): With known hypersensitivity to ATONCY or other components of ATONCY Taking or within 14 days of stopping, a monoamine oxidase inhibitor (MAOI) With narrow angle glaucoma. With pheochromocytoma or history of pheochromocytoma. With severe cardiac or vascular disorders whose condition would be expected to deteriorate with clinically important increases in blood pressure or heart rate.
Warnings and precautions
Severe Liver Injury: ATONCY should be discontinued and not restarted in patients with jaundice or laboratory evidence of liver injury. ( 5.2 ) Serious Cardiovascular Reactions: Prior to ATONCY treatment, patients should have a careful history and physical exam to assess for presence of cardiovascular (CV) disease. ATONCY generally should not be used in pediatric patients with known serious cardiac abnormalities, cardiomyopathy, serious arrhythmias. Consideration should be given to not using ATONCY in adults with clinically significant cardiac abnormalities. Patients who develop symptoms suggestive of cardiac disease during ATONCY treatment should stop ATONCY and undergo a prompt cardiac evaluation. ( 5.3 ) Increase in Blood Pressure and Heart Rate: Heart rate and blood pressure should be measured at baseline, following ATONCY dosage increases, and periodically while on therapy. ( 5.4 ) New Psychotic or Manic Symptoms and Activation of Mania: If psychotic or manic symptoms occur, consider discontinuing ATONCY. ( 5.5 ) Aggressive Behavior or Hostility: Monitor for the appearance or worsening of aggressive behavior or hostility. ( 5.7 ) Effects on Urine Outflow: Urinary retention or hesitancy may occur. ( 5.8 ) Priapism: Prompt medical attention is required in the event of suspected priapism. ( 5.9 ) Effect on Growth in Pediatric Patients: Closely monitor growth (e.g., weight, height) in pediatric patients. ( 5.11 ) 5.1 Suicidal Thoughts and Behaviors in Pediatric Patients 6 Years of Age and Older All pediatric patients 6 years of age and older treated with ATONCY should be monitored observed closely for clinical worsening, suicidal thoughts and behavior, and unusual changes in behavior, especially during the initial few months of ATONCY therapy, or at times of dose changes, either increases or decreases. Families and caregivers of pediatric patients 6 years of age and older treated with ATONCY should be alerted about the need to monitor patients daily for the emergence of agitation, irritability, unusual changes in behavior, and mental health-related symptoms, as well as the emergence of suicidal thoughts and behavior, and to report such symptoms immediately to a health care provider. Consider changing the therapeutic regimen, including stopping ATONCY, in patients who experience emergent suicidality or symptoms that might be precursors to emerging suicidal thoughts and behavior, especially if these symptoms are severe or abrupt in onset, or were not part of the patient’s presenting symptoms. Atomoxetine increased the risk of suicidal ideation in pediatric patients 6 years of age and older with ADHD in pooled placebo-controlled short-term studies (6 to 18 weeks). In 12 studies (11 studies in patients with ADHD and 1 in another clinical study ) with over 2,200 pediatric patients, the mean incidence of suicidal ideation in pediatric patients treated with another atomoxetine product was 0.4% (5/1357) (including one patient with a suicide attempt) compared to 0% (0/851) in placebo-treated pediatric patients. No suicides occurred in these studies. All the suicidal ideations occurred in pediatric patients 6 to 12 years of age, and all occurred during the first month of treatment with the other atomoxetine product. It is unknown whether the risk of suicidal ideation in pediatric patients extends to longer-term use. A similar analysis in adult patients treated with atomoxetine for ADHD did not reveal an increased risk of suicidal ideation or behavior. The following psychiatric symptoms have been reported with the use of atomoxetine: anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania and mania. Although a causal link between the emergence of such symptoms and the emergence of suicidal impulses has not been established, there is a concern that such symptoms may represent precursors to emerging suicidality. 5.2 Severe Liver Injury ATONCY should be discontinued and not restarted in patients with jaundice or laboratory evidence of liver injury. Liver enzyme and function tests should be obtained upon the first symptom or sign of liver dysfunction (e.g., pruritus, dark urine, jaundice, right upper quadrant tenderness, or unexplained “flu like” symptoms). Postmarketing reports indicate that atomoxetine can cause severe liver injury. Although no evidence of liver injury was detected in clinical trials of about 6,000 patients, there have been rare cases of clinically significant liver injury that were considered probably or possibly related to atomoxetine use during postmarketing use. Rare cases of liver failure have been reported during postmarketing use, including a case that resulted in a liver transplant. Reported cases of liver injury occurred within 120 days of initiation of atomoxetine in most cases and some patients presented with markedly elevated liver enzymes (>20 times upper limit of normal (ULN)), and jaundice with significantly elevated bilirubin levels (>2 times ULN), followed by recovery upon atomoxetine discontinuation. In one patient, liver injury, manifested by elevated hepatic enzymes up to 40 times ULN and jaundice with bilirubin up to 12 times ULN, recurred upon rechallenge, and was followed by recovery upon atomoxetine discontinuation, providing evidence that atomoxetine likely caused the liver injury. Such reactions may occur several months after ATONCY is started, but laboratory abnormalities may continue to worsen for several weeks after ATONCY is stopped.
Side effects
Most common adverse reactions (≥5% and at least twice the incidence of placebo patients) Pediatric Clinical Studies: Nausea, vomiting, fatigue, decreased appetite, abdominal pain, and somnolence ( 6.1 ) Adult Clinical Studies: Constipation, dry mouth, nausea, decreased appetite, dizziness, erectile dysfunction, and urinary hesitation. ( 6.1 ) Patients should be instructed to use caution when driving a car or operating hazardous machinery (because of somnolence) until they are reasonably certain that their performance is not affected by ATONCY ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Validus Pharmaceuticals LLC at 1-866-982-5438 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of ATONCY has been established from adequate and well-controlled studies of atomoxetine capsules (also referred to as another atomoxetine product) in patients 6 years of age and older with ADHD Clinical Studies (14) ] . Below is a display of the adverse reactions of [atomoxetine capsules in these adequate and well-controlled studies. Atomoxetine capsules were administered to 5,382 pediatric patients 6 years of age and older in clinical ADHD studies (Studies 1, 2, 3, 4, and 5) [see Clinical Studies (14.1) ] and 1,007 adults in clinical ADHD studies (Studies 6 and 7) [see Clinical Studies (14.2) ] . In the ADHD clinical trials, 2,529 pediatric patients were treated for over 6 months, which included 1,625 pediatric patients who were treated for longer than 1 year. Adverse Reactions in the Clinical Trials of Pediatric Patients 6 Years of Age and Older with ADHD Discontinuation of Treatment Due to Adverse Reactions in the Clinical Studies of Pediatric Patients 6 Years of Age and Older: In the acute placebo-controlled studies of pediatric patients 6 years of age and older with ADHD, 3% (48/1,613) of atomoxetine capsules-treated pediatric patients and 1.4% (13/945) of placebo-treated pediatric patients discontinued due to an adverse reaction. Among atomoxetine capsules treated patients, irritability (0.3%, N=5); somnolence (0.3%, N=5); aggression (0.2%, N=4); nausea (0.2%, N=4); vomiting (0.2%, N=4); abdominal pain (0.2%, N=4); constipation (0.1%, N=2); fatigue (0.1%, N=2); feeling abnormal (0.1%, N=2); and headache (0.1%, N=2) were the reasons for discontinuation reported by more than one patient. For all studies, (including open-label and long-term studies), 6% of atomoxetine capsules-treated pediatric patients who were other CYP2D6 metabolizer types (ultrarapid, normal, and intermediate) and 11% of those who were CYP2D6 poor metabolizers discontinued due to an adverse reaction. Common Adverse Reactions in the Clinical Studies of Pediatric Patients 6 Years of Age and Older: Common adverse reactions (incidence of 2% or greater in atomoxetine capsules-treated patients and with a higher incidence in atomoxetine capsules-treated patients compared to placebo-treated patients) in pediatric patients 6 years of age and older with ADHD are listed in Table 3. The most commonly observed adverse reactions in atomoxetine capsules-treated patients (incidence of ≥5% and ≥twice the incidence in placebo-treated patients), for either twice daily or once daily dosing were: nausea, vomiting, fatigue, decreased appetite, abdominal pain, and somnolence (see Tables 3 and 4). Table 3: Common Adverse Reactions a in Acute Studies (up to 18 weeks) in Pediatric Patients 6 Years and Older with ADHD Atomoxetine Capsules (N=1,597) Placebo (N=934) Headache 19% 15% Abdominal pain b 18% 10% Decreased appetite 16% 4% Somnolence c 11% 4% Vomiting 11% 6% Nausea 10% 5% Fatigue 8% 3% Irritability 6% 3% Dizziness 5% 2% Decrease weight 3% 0% Anorexia 3% 1% Rash 2% 1% a Adverse reactions reported by at least 2% of atomoxetine capsules-treated patients and greater than placebo-treated patients. b Abdominal pain includes the terms: upper abdominal pain and epigastric discomfort. c Somnolence includes the term sedation. Adverse reaction in the atomoxetine capsules-treated patients who received twice daily, and once daily dosing are shown in Table 4 (adverse reactions based on statistically significant Breslow-Day tests). Table 4: Common Adverse Reactions in Acute studies (up to 18 weeks) in Pediatric Patients 6 Years and Older with ADHD ADHD Studies with Twice Daily Dosing ADHD Studies with Once Daily Dosing Atomoxetine Capsules (N=715) Placebo (N=434) Atomoxetine Capsules (N=882) Placebo (N=500) Abdominal pain a 17% 13% 18% 7% Vomiting 11% 8% 11% 4% Nausea 7% 6% 13% 4% Fatigue 6% 4% 9% 2% Mood swings b 2% 0% 1% 1% Constipation c 2% 1% 1% 0% a Abdominal pain includes the terms: upper abdominal pain upper, epigastric discomfort. b Mood swings didn’t meet the statistical significance on Breslow-Day test at 0.05 level, but p-value was <0.1 (trend). c Constipation didn’t meet the statistical significance on Breslow-Day test but is included in the table because of pharmacologic plausibility. Common Adverse Reactions by CYP2D6 Metabolizer Status in the Clinical Studies of Pediatric Patients 6 Years of Age and Older: Table 5 displays adverse reactions occurred in at least 2% of atomoxetine capsules-treated pediatric patients who were CYP2D6 poor metabolizers and were statistically significantly more frequent in CYP2D6 poor metabolizers compared with other CYP2D6 metabolizer types (ultrarapid, normal, and intermediate).
Drug interactions
See Table 9 for clinically significant drug interactions with ATONCY and other drugs. Table 9: Clinically Significant Drug Interactions with ATONCY and Other Drugs Monoamine Oxidase Inhibitors (MAOIs) Prevention or Management ATONCY is contraindicated in patients taking MAOIs, including MAOIs such as linezolid or intravenous methylene blue, or in patients who stopped an MAOI within 14 days. Mechanism and Clinical Effect(s) As with other drugs affecting brain monoamine concentrations, there have been reports of serious, sometimes fatal reactions (hyperthermia, rigidity, myoclonus, autonomic instability with fluctuations of vital signs, extreme agitation progressing to delirium/coma) with concomitant use of ATONCY and an MAOI. Some cases presented with features resembling neuroleptic malignant syndrome. Strong CYP2D6 Inhibitors Prevention or Management With concomitant use of ATONCY and a strong CYP2D6 inhibitor 1 , increase the titration interval [see Dosage and Administration (2.5) and Clinical Pharmacology (12.3) ] . Mechanism and Clinical Effect(s) Atomoxetine is a CYP2D6 substrate. Concomitant use of ATONCY and a strong CYP2D6 inhibitor increases atomoxetine exposure [see Dosage and Administration (2.5) and Clinical Pharmacology (12.3) ] . Antihypertensive Drugs Prevention or Management Increase the frequency of monitoring blood pressure and adjust ATONCY dosage as clinically appropriate. Mechanism and Clinical Effect(s) Because of increased risk of increased blood pressure, ATONCY should be used cautiously with antihypertensive drugs, other drugs that increase blood pressure or pressor drugs (e.g., dopamine, dobutamine). Albuterol or Other Beta 2 (β2) Agonists Prevention or Management Increase the frequency of monitoring blood pressure and heart rate and adjust ATONCY dosage as clinically appropriate. Mechanism and Clinical Effect(s) Systemically administered albuterol (e.g., oral) can be potentiated by ATONCY, resulting in increases in heart rate and blood pressure Clinical Pharmacology (12.3) ] . 1 See www.fda.gov/CYPandTransporterInteractingDrugs for examples of strong CYP2D6 inhibitors. Monoamine Oxidase Inhibitors: Concomitant use contraindicated. ( 4 , 7 ) Strong CYP2D6 Inhibitors: With concomitant of ATONCY and strong CYP2D6 inhibitors, increase the titration intervals. ( 7 ) Antihypertensives: Increase the frequency of monitoring blood pressure and adjust ATONCY dosage as clinically appropriate. ( 7 ) Albuterol (or other beta 2 agonists): Increase the frequency of monitoring blood pressure and heart rate. ( 7 )
Use in specific populations
Hepatic Impairment: Increased exposure (AUC) to atomoxetine in subjects with moderate (Child-Pugh Class B) (2-fold increase) and severe (Child-Pugh Class C) (4-fold increase) compared to subjects with normal liver function. ( 8.6 and 12.3 ) Use in Genomic Subgroups: CYP2D6 poor metabolizers may have a greater risk of atomoxetine-related adverse reactions compared to other CYP2D6 metabolizer types (ultrarapid, normal, and intermediate) ( 8.7 ) 8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ADHD drugs, including ATONCY, during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for ADHD Medications at 1-866-961-2388 or visiting https://womensmentalhealth.org/adhd-medications/ . Risk Summary Available published studies with atomoxetine use in pregnant women are insufficient to establish a drug- associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Some animal reproduction studies of atomoxetine had adverse developmental outcomes. One of 3 studies in pregnant rabbits dosed during organogenesis resulted in decreased live fetuses and an increase in early resorptions, as well as slight increases in the incidences of atypical origin of 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 other CYP2D6 metabolizer types (ultrarapid, normal, and intermediate) and poor metabolizers receiving the maximum recommended human dose (MRHD), respectively. 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 on a mg/m 2 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 5-6 times the MRHD on a mg/m 2 basis. No adverse fetal effects were seen in pregnant rats dosed during the organogenesis period (see Data) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15- 20%, respectively. Data Animal Data : Pregnant rabbits were treated with up to 100 mg/kg/day of atomoxetine by gavage throughout the period of organogenesis. At this dose, in 1 of 3 studies, a decrease in live fetuses and an increase in early resorptions was observed. Slight increases in the incidences of atypical origin of carotid artery and absent subclavian artery were observed. These findings were observed at doses that caused slight maternal toxicity. The no-effect dose for these findings was 30 mg/kg/day. The 100 mg/kg dose is approximately 23 times the MRHD on a mg/m 2 basis; plasma levels (AUC) of atomoxetine at this dose in rabbits are estimated to be 3.3 times (other CYP2D6 metabolizer types) or 0.4 times (CYP2D6 poor metabolizers) those in humans receiving the MRHD. Rats were treated with up to approximately 50 mg/kg/day of atomoxetine (approximately 6 times the MRHD on a mg/m 2 basis) in the diet from 2 weeks (females) or 10 weeks (males) prior to mating through the periods of organogenesis and lactation. In 1 of 2 studies, decreases in pup weight and pup survival were observed. The decreased pup survival was also seen at 25 mg/kg (but not at 13 mg/kg). In a study in which rats were treated with atomoxetine in the diet from 2 weeks (females) or 10 weeks (males) prior to mating throughout the period of 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 40 mg/kg/day (approximately 5 times the MRHD on a mg/m 2 basis) but not at 20 mg/kg/day. No adverse fetal effects were seen when pregnant rats were treated with up to 150 mg/kg/day of atomoxetine (approximately 17 times the MRHD on a mg/m 2 basis) by gavage throughout the period of organogenesis. 8.2 Lactation Risk Summary 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. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ATONCY and any potential adverse effects on the breastfed child from atomoxetine hydrochloride or from the underlying maternal condition. 8.4 Pediatric Use The safety and effectiveness of ATONCY for the treatment of ADHD have been established in pediatric patients 6 years of age and older. Use of ATONCY for this indication is supported by evidence from another atomoxetine product in seven clinical trials in outpatients with ADHD: four acute treatment 6 to 9-week trials in pediatric subjects (ages 6 to 18 years), two acute treatment 10-week trials in adults, and one maintenance trial in pediatric subjects (ages 6 to 15 years) [see Clinical Studies (14) ] . ATONCYincreases the risk of suicidal ideation in pediatric patients. Anyone considering the use of ATONCY in a pediatric patient must balance the potential risks with the clinical need [see Boxed Warning and Warnings and Precautions ( 5.1 , 5.3 , 5.4 , 5.10 )] . The safety and effectiveness of ATONCY in pediatric patients less than 6 years of age have not been established.
Overdosage
During postmarketing use, there have been fatalities reported involving a mixed ingestion overdose of atomoxetine and at least one other drug. There have been no reports of death involving overdose of atomoxetine alone, including intentional overdoses at amounts up to 1,400 mg (14 times the maximum recommended dosage). The most commonly reported symptoms with acute and chronic overdoses of atomoxetine were gastrointestinal symptoms, somnolence, dizziness, tremor, and abnormal behavior. Hyperactivity and agitation have also been reported. Signs and symptoms consistent with mild to moderate sympathetic nervous system activation (e.g., tachycardia, blood pressure increased, mydriasis, dry mouth) have also been observed. Most events were mild to moderate. In some cases of overdose involving atomoxetine, seizures have been reported. Less commonly, there have been reports of QT prolongation and mental changes, including disorientation and hallucinations [see Clinical Pharmacology (12.2) ] . If an overdose occurs, consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdose management recommendations. Because atomoxetine is highly protein-bound, dialysis is not likely to be useful in the treatment of overdose of ATONCY.
Description
(atomoxetine) is a selective norepinephrine reuptake inhibitor. Atomoxetine hydrochloride is the R (-) isomer as determined by x-ray diffraction and its chemical designation is (-)- N -Methyl-3-phenyl-3-( o -tolyloxy)-propylamine hydrochloride and its molecular formula is C 17 H 21 NO
• HCl, which corresponds to a molecular weight of 291.82. The chemical structure is: Atomoxetine hydrochloride is a white to almost white powder, which has a solubility of 27.8 mg/mL in water. ATONCY oral solution is for oral administration only. Each mL contains 4 mg of atomoxetine (equivalent to 4.57 mg of atomoxetine hydrochloride) and the following inactive ingredients: grape flavor, maltitol solution, monobasic sodium phosphate, phosphoric acid, purified water, sodium benzoate, sodium hydroxide, sorbitol crystallizing solution, sucralose, and xylitol. ATONCY is a clear colorless solution, free from any visible foreign and particulate matter, free of precipitation and hazy mass with pH 3.0-5.0. "Image Description"
How supplied
16.1 How Supplied ATONCY TM (atomoxetine) oral solution is supplied in a 100 mL, amber glass bottles with child-resistant cap, and is co-packaged with a 10 mL calibrated oral dosing syringe and bottle adapter: NDC 30698-456- 02. Each mL contains 4 mg of atomoxetine (equivalent to 4.57 mg of atomoxetine hydrochloride), clear colorless solution, free from any visible foreign and particulate matter, free of precipitation and hazy mass. Supplied with a 10 mL syringe and a bottle adapter. 16.2 Storage and Handling Store at 20°C to 25°C (68° to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). [See USP Controlled Room Temperature]. Discard unused ATONCY remaining in the bottle, 45 days after first opening the bottle.
Patient information
Advise the patient to read the FDA-approved patient labeling ( Medication Guide and Instructions for Use ). Suicide Risk Patients, their families, and their caregivers should be alerted about the need to monitor patients daily for the emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, mania, other unusual changes in behavior, depression, and suicidal ideation, especially early during ATONCY treatment and when the dosage is adjusted. Such symptoms should be reported to the patient’s health care provider immediately [see Warnings and Precautions (5.1) ] . Severe Liver Injury Patients initiating ATONCY should be cautioned that severe liver injury may develop. Patients should be instructed to contact their healthcare provider immediately should they develop pruritus, dark urine, jaundice, right upper quadrant tenderness, or unexplained “flu-like” symptoms [see Warnings and Precautions (5.2) ] . Serious Cardiovascular Reactions Patients who develop symptoms such as exertional chest pain, unexplained syncope, or other symptoms suggestive of cardiac disease during ATONCY treatment should stop ATONCY and contact a health care provider [see Warnings and Precautions (5.3) ] . Increased Blood Pressure or Heart Rate Atomoxetine can increase the blood pressure and heart rate [see Warnings and Precautions (5.4) ] . Emergence of New Psychotic or Manic Symptoms and Activation of Mania Instruct patients and their caregivers to look for signs of activation of mania/hypomania and psychosis [see Warnings and Precautions (5.5) ] . Aggression or Hostility Instruct patients and their caregivers to contact their healthcare provider as soon as possible should they notice an increase in aggression or hostility [see Warnings and Precautions (5.7) ] . Priapism The parents or guardians of pediatric patients taking ATONCY and adult patients taking atomoxetine should be instructed that priapism requires prompt medical attention [see Warnings and Precautions (5.10) ] . Ocular Irritant Atomoxetine is an ocular irritant. In the event ATONCY comes in contact with an eye, the affected eye should be flushed immediately with water, and medical advice obtained. Hands and any potentially contaminated surfaces should be washed as soon as possible. Drug-Drug Interactions Patients should be instructed to consult a healthcare provider if they are taking or plan to take any prescription or over-the-counter drugs, dietary supplements, or herbal remedies [see Drug Interactions (7) ] . Sexual Dysfunction Advise patients that ATONCY may impair sexual function. Advise patients if they experience sexual dysfunction, they should contact their health care provider [see Adverse Reactions (6.1) ] . Pregnancy Registry Advise patients that there is a pregnancy registry that monitors pregnancy outcomes in women exposed to atomoxetine during pregnancy [see Use in Specific Populations (8.1) ] . Food Patients may take ATONCY with or without food. Missed Dose If patients miss an ATONCY dose, they should be instructed to take it as soon as possible, but should not take more than the prescribed total daily amount of ATONCY in any 24-hour period. Somnolence The incidence of somnolence was higher in atomoxetine-treated patients than placebo-treated patients [see Adverse Reactions (6.1) ] . Patients should be instructed to use caution when driving a car or operating hazardous machinery until they are reasonably certain that their performance is not affected by ATONCY. Manufactured by: Rubicon Research Limited, Satara, 415004, India Distributed by: Validus Pharmaceuticals LLC Parsippany, NJ 07054 www.validuspharma.com 1-866-982-5438 © 2026 Validus Pharmaceuticals LLC
Label text from the FDA structured product label by Validus Pharmaceuticals LLC (revised Apr 2, 2026). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Atomoxetine Hydrochloride in 1 product
Atoncy NDC products (1)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 30698-456 | Atomoxetine Hydrochloride 4 mg/mL Solution | Validus Pharmaceuticals LLC | NDA |
Frequently asked questions
What is Atoncy used for?
1 INDICATIONS AND USAGE ATONCY is indicated for the treatment of attention-deficit/hyperactivity disorder (ADHD) in adult and pediatric patients 6 years of age and older. ATONCY is indicated as an integral part of a total treatment program for ADHD that may include other measures (psychological, educational, social) for patients with ADHD. ATONCY is a selective norepinephrine reuptake inhibitor…
What are the side effects of Atoncy?
Most common adverse reactions (≥5% and at least twice the incidence of placebo patients) Pediatric Clinical Studies: Nausea, vomiting, fatigue, decreased appetite, abdominal pain, and somnolence ( 6.1 ) Adult Clinical Studies: Constipation, dry mouth, nausea, decreased appetite, dizziness, erectile dysfunction, and urinary hesitation. ( 6.1 ) Patients should be instructed to use caution when… See the full label for the complete list.
Who makes Atoncy?
Atoncy is listed by 1 labeler in the FDA NDC directory, including Validus Pharmaceuticals LLC.