atomoxetine 25 MG Oral Capsule [Strattera]

Details

Generic Name: ATOMOXETINE

Brand Name: Strattera

Substance Name(s):
ATOMOXETINE HYDROCHLORIDE

OVERDOSAGE

10 10.1 Human Experience No fatal overdoses occurred in clinical trials.

There is limited clinical trial experience with STRATTERA overdose.

During postmarketing, there have been fatalities reported involving a mixed ingestion overdose of STRATTERA and at least one other drug.

There have been no reports of death involving overdose of STRATTERA alone, including intentional overdoses at amounts up to 1400 mg.

In some cases of overdose involving STRATTERA, seizures have been reported.

The most commonly reported symptoms accompanying acute and chronic overdoses of STRATTERA were somnolence, agitation, hyperactivity, abnormal behavior, and gastrointestinal symptoms.

Signs and symptoms consistent with mild to moderate sympathetic nervous system activation (e.g., mydriasis, tachycardia, dry mouth) have also been observed.

Less commonly, there have been reports of QT prolongation and mental changes, including disorientation and hallucinations.

10.2 Management of Overdose An airway should be established.

Monitoring of cardiac and vital signs is recommended, along with appropriate symptomatic and supportive measures.

Gastric lavage may be indicated if performed soon after ingestion.

Activated charcoal may be useful in limiting absorption.

Because atomoxetine is highly protein-bound, dialysis is not likely to be useful in the treatment of overdose.

DESCRIPTION

STRATTERA® (atomoxetine HCl) is a selective norepinephrine reuptake inhibitor.

Atomoxetine HCl is the R(-) isomer as determined by x-ray diffraction.

The chemical designation is (-)-N-Methyl-3-phenyl-3-(o-tolyloxy)-propylamine hydrochloride.

The molecular formula is C17H21NO•HCl, which corresponds to a molecular weight of 291.82Atomoxetine HCl is a white to practically white solid, which has a solubility of 27.8 mg/mL in water.

STRATTERA capsules are intended for oral administration only.

Each capsule contains atomoxetine HCl equivalent to 10, 18, 25, 40, 60, 80, or 100 mg of atomoxetine.

The capsules also contain pregelatinized starch and dimethicone.

The capsule shells contain gelatin, sodium lauryl sulfate, and other inactive ingredients.

The capsule shells also contain one or more of the following:

HOW SUPPLIED

Opaque Blue, Opaque White LILLY 3228 25 mg 16.2 Storage and Handling Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].

INDICATIONS AND USAGE

1 1.1 Attention-Deficit/Hyperactivity Disorder (ADHD) STRATTERA is indicated for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD).

The efficacy of STRATTERA Capsules was established in seven clinical trials in outpatients with ADHD: four 6 to 9-week trials in pediatric patients (ages 6 to 18), two 10-week trial in adults, and one maintenance trial in pediatrics (ages 6 to 15) [see Clinical Studies (14)].

1.2 Diagnostic Considerations A diagnosis of ADHD (DSM-IV) implies the presence of hyperactive-impulsive or inattentive symptoms that cause impairment and that were present before age 7 years.

The symptoms must be persistent, must be more severe than is typically observed in individuals at a comparable level of development, must cause clinically significant impairment, e.g., in social, academic, or occupational functioning, and must be present in 2 or more settings, e.g., school (or work) and at home.

The symptoms must not be better accounted for by another mental disorder.

The specific etiology of ADHD is unknown, and there is no single diagnostic test.

Adequate diagnosis requires the use not only of medical but also of special psychological, educational, and social resources.

Learning may or may not be impaired.

The diagnosis must be based upon a complete history and evaluation of the patient and not solely on the presence of the required number of DSM-IV characteristics.

For the Inattentive Type, at least 6 of the following symptoms must have persisted for at least 6 months: lack of attention to details/careless mistakes, lack of sustained attention, poor listener, failure to follow through on tasks, poor organization, avoids tasks requiring sustained mental effort, loses things, easily distracted, forgetful.

For the Hyperactive-Impulsive Type, at least 6 of the following symptoms must have persisted for at least 6 months: fidgeting/squirming, leaving seat, inappropriate running/climbing, difficulty with quiet activities, “on the go,” excessive talking, blurting answers, can’t wait turn, intrusive.

For a Combined Type diagnosis, both inattentive and hyperactive-impulsive criteria must be met.

1.3 Need for Comprehensive Treatment Program STRATTERA is indicated as an integral part of a total treatment program for ADHD that may include other measures (psychological, educational, social) for patients with this syndrome.

Drug treatment may not be indicated for all patients with this syndrome.

Drug treatment is not intended for use in the patient who exhibits symptoms secondary to environmental factors and/or other primary psychiatric disorders, including psychosis.

Appropriate educational placement is essential in children and adolescents with this diagnosis and psychosocial intervention is often helpful.

When remedial measures alone are insufficient, the decision to prescribe drug treatment medication will depend upon the physician’s assessment of the chronicity and severity of the patient’s symptoms.

STRATTERA® is a selective norepinephrine reuptake inhibitor indicated for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD).

(1.1)

BOXED WARNING

WARNING: SUICIDAL IDEATION IN CHILDREN AND ADOLESCENTS STRATTERA (atomoxetine) increased the risk of suicidal ideation in short-term studies in children or adolescents with Attention-Deficit/Hyperactivity Disorder (ADHD).

Anyone considering the use of STRATTERA in a child or adolescent must balance this risk with the clinical need.

Co-morbidities occurring with ADHD may be associated with an increase in the risk of suicidal ideation and/or behavior.

Patients who are started on therapy should be monitored closely for suicidality (suicidal thinking and behavior), clinical worsening, or unusual changes in behavior.

Families and caregivers should be advised of the need for close observation and communication with the prescriber.

STRATTERA is approved for ADHD in pediatric and adult patients.

STRATTERA is not approved for major depressive disorder.

Pooled analyses of short-term (6 to 18 weeks) placebo-controlled trials of STRATTERA in children and adolescents (a total of 12 trials involving over 2200 patients, including 11 trials in ADHD and 1 trial in enuresis) have revealed a greater risk of suicidal ideation early during treatment in those receiving STRATTERA compared to placebo.

The average risk of suicidal ideation in patients receiving STRATTERA was 0.4% (5/1357 patients), compared to none in placebo-treated patients (851 patients).

No suicides occurred in these trials [see Warnings and Precautions (5.1)].

INFORMATION FOR PATIENTS

17 PATIENT COUNSELING INFORMATION See FDA-approved Medication Guide.

17.1 General Information Physicians should instruct their patients to read the Medication Guide before starting therapy with STRATTERA and to reread it each time the prescription is renewed.

Prescribers or other health professionals should inform patients, their families, and their caregivers about the benefits and risks associated with treatment with STRATTERA and should counsel them in its appropriate use.

The prescriber or health professional should instruct patients, their families, and their caregivers to read the Medication Guide and should assist them in understanding its contents.

Patients should be given the opportunity to discuss the contents of the Medication Guide and to obtain answers to any questions they may have.

Patients should be advised of the following issues and asked to alert their prescriber if these occur while taking STRATTERA.

17.2 Suicide Risk Patients, their families, and their caregivers should be encouraged to be alert to 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 STRATTERA treatment and when the dose is adjusted.

Families and caregivers of patients should be advised to observe for the emergence of such symptoms on a day-to-day basis, since changes may be abrupt.

Such symptoms should be reported to the patient’s prescriber or health professional, especially if they are severe, abrupt in onset, or were not part of the patient’s presenting symptoms.

Symptoms such as these may be associated with an increased risk for suicidal thinking and behavior and indicate a need for very close monitoring and possibly changes in the medication.

17.3 Severe Liver Injury Patients initiating STRATTERA should be cautioned that severe liver injury may develop.

Patients should be instructed to contact their physician immediately should they develop pruritus, dark urine, jaundice, right upper quadrant tenderness, or unexplained “flu-like” symptoms [see Warnings and Precautions (5.2)].

17.4 Aggression or Hostility Patients should be instructed to call their doctor as soon as possible should they notice an increase in aggression or hostility.

17.5 Priapism Rare postmarketing cases of priapism, defined as painful and nonpainful penile erection lasting more than 4 hours, have been reported for pediatric and adult patients treated with STRATTERA.

The parents or guardians of pediatric patients taking STRATTERA and adult patients taking STRATTERA should be instructed that priapism requires prompt medical attention.

17.6 Ocular Irritant STRATTERA is an ocular irritant.

STRATTERA capsules are not intended to be opened.

In the event of capsule content coming in contact with the 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.

17.7 Drug-Drug Interaction Patients should be instructed to consult a physician if they are taking or plan to take any prescription or over-the-counter medicines, dietary supplements, or herbal remedies.

17.8 Pregnancy Patients should be instructed to consult a physician if they are nursing, pregnant, or thinking of becoming pregnant while taking STRATTERA.

17.9 Food Patients may take STRATTERA with or without food.

17.10 Missed Dose If patients miss a dose, they should be instructed to take it as soon as possible, but should not take more than the prescribed total daily amount of STRATTERA in any 24-hour period.

17.11 Interference with Psychomotor Performance 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 atomoxetine.

PV 6265 AMP

DOSAGE AND ADMINISTRATION

2 2.1 Acute Treatment Dosing of children and adolescents up to 70 kg body weight — STRATTERA should be initiated at a total daily dose of approximately 0.5 mg/kg and increased after a minimum of 3 days to a target total daily dose of approximately 1.2 mg/kg administered either as a single daily dose in the morning or as evenly divided doses in the morning and late afternoon/early evening.

No additional benefit has been demonstrated for doses higher than 1.2 mg/kg/day [see Clinical Studies (14)].

The total daily dose in children and adolescents should not exceed 1.4 mg/kg or 100 mg, whichever is less.

Dosing of children and adolescents over 70 kg body weight and adults — STRATTERA should be initiated at a total daily dose of 40 mg and increased after a minimum of 3 days to a target total daily dose of approximately 80 mg administered either as a single daily dose in the morning or as evenly divided doses in the morning and late afternoon/early evening.

After 2 to 4 additional weeks, the dose may be increased to a maximum of 100 mg in patients who have not achieved an optimal response.

There are no data that support increased effectiveness at higher doses [see Clinical Studies (14)].

The maximum recommended total daily dose in children and adolescents over 70 kg and adults is 100 mg.

2.2 Maintenance/Extended Treatment It is generally agreed that pharmacological treatment of ADHD may be needed for extended periods.

The benefit of maintaining pediatric patients (ages 6-15 years) with ADHD on STRATTERA after achieving a response in a dose range of 1.2 to 1.8 mg/kg/day was demonstrated in a controlled trial.

Patients assigned to STRATTERA in the maintenance phase were generally continued on the same dose used to achieve a response in the open label phase.

The physician who elects to use STRATTERA for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient [see Clinical Studies (14.1)].

2.3 General Dosing Information STRATTERA may be taken with or without food.

STRATTERA can be discontinued without being tapered.

STRATTERA capsules are not intended to be opened, they should be taken whole [see Patient Counseling Information (17.6)].

The safety of single doses over 120 mg and total daily doses above 150 mg have not been systematically evaluated.

2.4 Dosing in Specific Populations Dosing adjustment for hepatically impaired patients — For those ADHD patients who have hepatic insufficiency (HI), dosage adjustment is recommended as follows: For patients with moderate HI (Child-Pugh Class B), initial and target doses should be reduced to 50% of the normal dose (for patients without HI).

For patients with severe HI (Child-Pugh Class C), initial dose and target doses should be reduced to 25% of normal [see Use In Specific Populations (8.6)].

Dosing adjustment for use with a strong CYP2D6 inhibitor or in patients who are known to be CYP2D6 PMs — In children and adolescents up to 70 kg body weight administered strong CYP2D6 inhibitors, e.g., paroxetine, fluoxetine, and quinidine, or in patients who are known to be CYP2D6 PMs, STRATTERA 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 body weight and adults administered strong CYP2D6 inhibitors, e.g., paroxetine, fluoxetine, and quinidine, STRATTERA 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.