IMPORTANT SAFETY INFORMATION

INDICATIONS AND USAGE

ATONCY is a selective norepinephrine reuptake inhibitor 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.

At least 14 days must elapse between discontinuation of monoamine oxidase inhibitor (MAOI) antidepressant and initiation of ATONCY.

CONTRAINDICATIONS

ATONCY is contraindicated in patients:
• With known hypersensitivity to ATONCY or other components of ATONCY. Hypersensitivity reactions that occurred with ATONCY use includes anaphylaxis, angioneurotic edema, urticaria, and rash.
• Taking, or within 14 days of stopping, a monoamine oxidase inhibitor.
• 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.
• 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

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 and observed closely for suicidal thoughts and behavior, clinical worsening, or unusual changes in behavior, especially during the initial months of therapy or at times of dosage changes, either increases or decreases. 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.

Severe Liver Injury

ATONCY should be discontinued and not restarted in patients with jaundice or laboratory evidence of liver injury.

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 such as exertional chest pain, unexplained syncope, or other symptoms suggestive of cardiac disease during atomoxetine treatment should stop ATONCY and undergo a prompt cardiac evaluation.

Increases in Blood Pressure and Heart Rate

ATONCY is contraindicated in patients with severe cardiac or vascular disorders whose condition would be expected to deteriorate if they had a clinically important increase in blood pressure or heart rate. Heart rate and blood pressure should be measured at baseline, following ATONCY dosage increases, and periodically while on therapy to detect possible clinically important increases in heart rate and blood pressure.

New Psychotic or Manic Symptoms and Activation of Mania

If psychotic or manic symptoms occur, consider discontinuing ATONCY. Psychotic symptoms (e.g., hallucinations, delusional thinking), manic symptoms (e.g., mania) even in patients without a prior history of psychotic illness or mania can be caused by ATONCY even at the recommended dosage.

Screening Patients for Bipolar Disorder

Before initiating treatment with ATONCY, patients should be adequately screened for risk factors for bipolar disorder such as 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 ATONCY.

Aggressive Behavior or Hostility

Patients initiating treatment with ATONCY should be monitored for the appearance or worsening of aggressive behavior or hostility.

Hypersensitivity Reactions

ATONCY is contraindicated in patients with a known hypersensitivity reaction to ATONCY or other components of ATONCY. Although uncommon, hypersensitivity reactions, including anaphylaxis, angioneurotic edema, urticaria, and rash, have been reported in atomoxetine-treated patients.

Effects on Urine Outflow

Urinary retention or urinary hesitancy may occur.

Priapism

Prompt medical attention is required in the event of suspected priapism in ATONCY-treated patients.

Effect on Growth in Pediatric Patients

Closely monitor growth (e.g., weight, height) in pediatric patients during ATONCY treatment.

See Full Prescribing Information for additional warnings and precautions associated with ATONCY.

ADVERSE REACTIONS

Most common adverse reactions:
• Nausea, vomiting, fatigue, decreased appetite, abdominal pain, and somnolence in pediatric patients.
• Constipation, dry mouth, nausea, decreased appetite, dizziness, erectile dysfunction, and urinary hesitation in adult patients.

See Full Prescribing Information for additional adverse reactions associated with ATONCY.

DRUG INTERACTIONS

Monoamine Oxidase Inhibitors

• Concomitant use contraindicated.

Strong CYP2D6 Inhibitors

• With concomitant use of ATONCY and strong CYP2D6 inhibitors, increase the titration intervals.

Antihypertensives

• Increase the frequency of monitoring blood pressure and adjust ATONCY dosage as clinically appropriate.

Albuterol (or other beta2 agonists)

• Increase the frequency of monitoring blood pressure and heart rate. See Full Prescribing Information for additional potential drug interactions associated with ATONCY.

USE IN SPECIFIC POPULATIONS

Pregnancy

• There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ADHD drugs, including ATONCY, during pregnancy. Atomoxetine use in pregnant women are insufficient to establish a drug associated risk of major birth defects, miscarriage, adverse maternal or fetal outcomes.

Lactation

• 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.

Females and Males of Reproductive Potential

• Based on the published literature, metoprolol may cause erectile dysfunction and inhibit sperm motility.

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. Anyone considering the use of ATONCY in a pediatric patient must consider the associated risks and benefits with the clinical need. The safety and effectiveness of ATONCY in pediatric patients less than 6 years of age have not been established.

Geriatric Use

• The safety, efficacy and pharmacokinetics of atomoxetine in geriatric patients have not been evaluated.

Patients with Hepatic Impairment

• Compared with patients with normal hepatic function, atomoxetine exposure was increased in patients with moderate and in patients with severe hepatic impairment. The recommended dosage in patients with moderate or severe hepatic impairment is lower than in patients with normal hepatic function.

Use in Genomic Subgroups

• The recommended titration interval is longer in CYP2D6 poor metabolizers than other CYP2D6 metabolizer types. Atomoxetine plasma concentrations were higher in CYP2D6 poor metabolizers which may increase the risk of atomoxetine-related adverse reactions. In pediatric and adult patients, the mean heart rate was higher in CYP2D6 poor metabolizers compared to other CYP2D6 metabolizer types.

OVERDOSAGE

• 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.

• 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.

ATONCY is available as a 4 mg/mL oral solution.

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

Please see Full Prescribing Information at atoncy.us.com

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