Atomoxetine

Name: Atomoxetine

Why is this medication prescribed?

Atomoxetine is used as part of a total treatment program to increase the ability to pay attention and decrease impulsiveness and hyperactivity in children and adults with ADHD. Atomoxetine is in a class of medications called selective norepinephrine reuptake inhibitors. It works by increasing the levels of norepinephrine, a natural substance in the brain that is needed to control behavior.

How should this medicine be used?

Atomoxetine comes as a capsule to take by mouth. It is usually taken either once a day in the morning, or twice a day in the morning and late afternoon or early evening. Atomoxetine may be taken with or without food. Take atomoxetine at around the same time(s) every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take atomoxetine exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Swallow atomoxetine capsules whole; do not open, chew, or crush them. If a capsule is accidentally broken or opened, wash away the loose powder with water right away. Try not to touch the powder and be especially careful not to get the powder in your eyes. If you do get powder in your eyes, rinse them with water right away and call your doctor.

Your doctor will probably start you on a low dose of atomoxetine and increase your dose after at least 3 days. Your doctor may increase your dose again after 2–4 weeks. You may notice improvement in your symptoms during the first week of your treatment, but it may take up to one month for you to feel the full benefit of atomoxetine.

Atomoxetine may help to control the symptoms of ADHD but will not cure the condition. Continue to take atomoxetine even if you feel well. Do not stop taking atomoxetine without talking to your doctor.

What other information should I know?

Keep all appointments with your doctor and the laboratory. Your doctor may order certain lab tests to check your body's response to atomoxetine.

Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.

Strattera Dosage

What Is a Typical Dose of Strattera?

Strattera is a capsule that you take by mouth, usually once or twice a day either with or without food. It's important to take it at about the same time every day.

Take Strattera whole. Don't open, chew, or crush the drug. If the capsules accidentally break, make sure you wash away the loose powder. Try not to get any of the powder in your eyes, but if you do, rinse them with water and call your doctor right away.

Your doctor will probably prescribe a low dose of Strattera at first, but may increase it after at least three days. Although your symptoms may begin to improve in the first few days, it can take up to four weeks to get the full benefit of the medication.

What Happens If I Take Too Much Strattera and Overdose?

Take Strattera exactly as your doctor prescribed.

It's unknown whether one dose of more than 120 mg or total daily doses above 150 mg are safe to take.

Symptoms of a Strattera overdose may include:

  • Sleepiness
  • Agitation
  • An unusual increase in activity or talking
  • Other abnormal behavior
  • Stomach problems
  • Wide or dilated pupils
  • Fast heartbeat
  • Dry mouth

If you or someone else has symptoms of an overdose, call a poison control center at 1-800-222-1222. If someone collapses or isn't breathing, call 911.

What Happens If I Miss a Dose of Strattera or Don't Take It as Prescribed?

Strattera is not a cure for ADHD. You should continue taking the drug, even if you feel well or have no symptoms. Don't stop taking it without talking to your doctor first.

If you miss a dose of Strattera, take the missed dose as soon as you remember. If it's already close to your next dose, skip the missed dose and take your next dose as scheduled. Don't take two capsules at once to make up for a missed dose.

Is atomoxetine available as a generic drug?

GENERIC AVAILABLE: Yes

Do I need a prescription for atomoxetine?

Yes

Atomoxetine Usage

  • Take atomoxetine exactly as prescribed. Atomoxetine comes in different dose strength capsules.Your doctor may adjust the dose until it is right for you.
  • Do not chew, crush, or open the capsules. Swallow atomoxetine capsules whole with water or other liquids. Tell your doctor if you cannot swallow atomoxetine whole. A different medicine may need to be prescribed.
  • Avoid touching a broken atomoxetine capsule. Wash hands and surfaces that touched an open atomoxetine capsule. If any of the powder gets in your eyes rinse them with water right away and call your doctor.
  • Atomoxetine can be taken with or without food.
  • Atomoxetine is usually taken once or twice a day. Take atomoxetine at the same time each day to help you remember. If you miss a dose of atomoxetine, take it as soon as you remember that day. If you miss a day of atomoxetine, do not double your dose the next day. Just skip the day you missed.
  • From time to time, your doctor may stop atomoxetine treatment for a while to check ADHD symptoms.
  • Your doctor may do regular checks of the blood, heart, and blood pressure while taking atomoxetine. Children should have their height and weight checked often while taking atomoxetine. Atomoxetine treatment may be stopped if a problem is found during these check-ups.

Atomoxetine Dosage

Take atomoxetine exactly as prescribed by your doctor. Follow the directions on your prescription label carefully. Your doctor will determine the best dose for you.

Acute Treatment: Dosing of children and adolescents up to 70 kg body weight — atomoxetine 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.

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 — atomoxetine 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.

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

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 atomoxetine 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 atomoxetine 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 atomoxetine for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient.

 

What other drugs will affect atomoxetine?

Tell your doctor about all your current medicines and any you start or stop using, especially:

  • an antidepressant;

  • asthma medication;

  • blood pressure medicine; or

  • a cold or allergy medicine that contains a decongestant such as pseudoephedrine or phenylephrine.

This list is not complete. Other drugs may interact with atomoxetine, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

Overdosage

Human Experience

There is limited clinical trial experience with Atomoxetine capsule overdose. During postmarketing, there have been fatalities reported involving a mixed ingestion overdose of Atomoxetine capsules and at least one other drug. There have been no reports of death involving overdose of Atomoxetine capsules alone, including intentional overdoses at amounts up to 1400 mg. In some cases of overdose involving Atomoxetine capsules, seizures have been reported. The most commonly reported symptoms accompanying acute and chronic overdoses of Atomoxetine capsules 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. Less commonly, there have been reports of QT prolongation and mental changes, including disorientation and hallucinations [see Clinical Pharmacology (12.2)].

Management of Overdose

Consult with a Certified Poison Control Center for up to date guidance and advice. Because Atomoxetine is highly protein-bound, dialysis is not likely to be useful in the treatment of overdose.

Clinical Studies

ADHD studies in Children and Adolescents

Acute Studies The effectiveness of Atomoxetine capsules in the treatment of ADHD was established in 4 randomized, double-blind, placebo-controlled studies of pediatric patients (ages 6 to 18). Approximately one-third of the patients met DSM-IV criteria for inattentive subtype and two-thirds met criteria for both inattentive and hyperactive/impulsive subtypes.

Signs and symptoms of ADHD were evaluated by a comparison of mean change from baseline to endpoint for Atomoxetine capsule- and placebo-treated patients using an intent-to-treat analysis of the primary outcome measure, the investigator administered and scored ADHD Rating Scale-IV-Parent Version (ADHDRS) total score including hyperactive/impulsive and inattentive subscales. Each item on the ADHDRS maps directly to one symptom criterion for ADHD in the DSM-IV.

In Study 1, an 8-week randomized, double-blind, placebo-controlled, dose-response, acute treatment study of children and adolescents aged 8 to 18 (N=297), patients received either a fixed dose of Atomoxetine capsules (0.5, 1.2, or 1.8 mg/kg/day) or placebo. Atomoxetine capsules were administered as a divided dose in the early morning and late afternoon/early evening. At the 2 higher doses, improvements in ADHD symptoms were statistically significantly superior in Atomoxetine capsule-treated patients compared with placebo-treated patients as measured on the ADHDRS scale. The 1.8 mg/kg/day Atomoxetine capsule dose did not provide any additional benefit over that observed with the 1.2 mg/kg/day dose. The 0.5 mg/kg/day Atomoxetine capsule dose was not superior to placebo.

In Study 2, a 6-week randomized, double-blind, placebo-controlled, acute treatment study of children and adolescents aged 6 to 16 (N=171), patients received either Atomoxetine capsule or placebo. Atomoxetine capsules were administered as a single dose in the early morning and titrated on a weight-adjusted basis according to clinical response, up to a maximum dose of 1.5 mg/kg/day. The mean final dose of Atomoxetine capsules were approximately 1.3 mg/kg/day. ADHD symptoms were statistically significantly improved on Atomoxetine capsules compared with placebo, as measured on the ADHDRS scale. This study shows that Atomoxetine capsules are effective when administered once daily in the morning.

In 2 identical, 9-week, acute, randomized, double-blind, placebo-controlled studies of children aged 7 to 13 (Study 3, N=147; Study 4, N=144), Atomoxetine capsules and methylphenidate were compared with placebo. Atomoxetine capsules were administered as a divided dose in the early morning and late afternoon (after school) and titrated on a weight-adjusted basis according to clinical response. The maximum recommended Atomoxetine capsule dose was 2.0 mg/kg/day. The mean final dose of Atomoxetine capsules for both studies was approximately 1.6 mg/kg/day. In both studies, ADHD symptoms statistically significantly improved more on Atomoxetine capsules than on placebo, as measured on the ADHDRS scale.

Examination of population subsets based on gender and age (<12 and 12 to 17) did not reveal any differential responsiveness on the basis of these subgroupings. There was not sufficient exposure of ethnic groups other than Caucasian to allow exploration of differences in these subgroups.

Maintenance Study The effectiveness of Atomoxetine capsules in the maintenance treatment of ADHD was established in an outpatient study of children and adolescents (ages 6-15 years). Patients meeting DSM-IV criteria for ADHD who showed continuous response for about 4 weeks during an initial 10 week open-label treatment phase with Atomoxetine capsules (1.2 to 1.8 mg/kg/day) were randomized to continuation of their current dose of Atomoxetine capsules (N=292) or to placebo (N=124) under double-blind treatment for observation of relapse. Response during the open-label phase was defined as CGI-ADHD-S score ≤2 and a reduction of at least 25% from baseline in ADHDRS-IV-Parent:Inv total score. Patients who were assigned to Atomoxetine capsules and showed continuous response for approximately 8 months during the first double-blind treatment phase were again randomized to continuation of their current dose of Atomoxetine capsules (N=81) or to placebo (N=82) under double-blind treatment for observation of relapse. Relapse during the double-blind phase was defined as CGI-ADHD-S score increases of at least 2 from the end of open-label phase and ADHDRS-IV-Parent:Inv total score returns to ≥90% of study entry score for 2 consecutive visits. In both double-blind phases, patients receiving continued Atomoxetine capsule treatment experienced significantly longer times to relapse than those receiving placebo.

ADHD studies in Adults

The effectiveness of Atomoxetine capsules in the treatment of ADHD was established in 2 randomized, double-blind, placebo-controlled clinical studies of adult patients, age 18 and older, who met DSM-IV criteria for ADHD.

Signs and symptoms of ADHD were evaluated using the investigator-administered Conners Adult ADHD Rating Scale Screening Version (CAARS), a 30-item scale. The primary effectiveness measure was the 18-item Total ADHD Symptom score (the sum of the inattentive and hyperactivity/impulsivity subscales from the CAARS) evaluated by a comparison of mean change from baseline to endpoint using an intent-to-treat analysis.

In 2 identical, 10-week, randomized, double-blind, placebo-controlled acute treatment studies (Study 5, N=280; Study 6, N=256), patients received either Atomoxetine capsules or placebo. Atomoxetine capsules were administered as a divided dose in the early morning and late afternoon/early evening and titrated according to clinical response in a range of 60 to 120 mg/day. The mean final dose of Atomoxetine capsules for both studies was approximately 95 mg/day. In both studies, ADHD symptoms were statistically significantly improved on Atomoxetine capsules, as measured on the ADHD Symptom score from the CAARS scale.

Examination of population subsets based on gender and age (<42 and ≥42) did not reveal any differential responsiveness on the basis of these subgroupings. There was not sufficient exposure of ethnic groups other than Caucasian to allow exploration of differences in these subgroups.

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral:

Strattera: 10 mg, 18 mg

Strattera: 25 mg, 40 mg, 60 mg, 80 mg, 100 mg [contains fd&c blue #2 (indigotine)]

Generic: 10 mg, 18 mg, 25 mg, 40 mg, 60 mg, 80 mg, 100 mg

Dosing Pediatric

ADHD treatment: Oral: Note: Atomoxetine may be discontinued without the need for tapering dose.

Children ≥6 years and ≤70 kg:

Initial: 0.5 mg/kg/day, increase after minimum of 3 days to ~1.2 mg/kg/day; may administer as either a single daily dose or 2 evenly divided doses in morning and late afternoon/early evening. Maximum daily dose: 1.4 mg/kg or 100 mg, whichever is less.

Dosage adjustment in patients receiving strong CYP2D6 inhibitors (eg, paroxetine, fluoxetine, quinidine) or patients known to be CYP2D6 poor metabolizers: Initial: 0.5 mg/kg/day; if tolerating therapy but inadequate response, may increase after minimum of 4 weeks to 1.2 mg/kg/day.

Children ≥6 years and >70 kg: Refer to adult dosing.

Dosing Renal Impairment

No dosage adjustment necessary.

Dosing Hepatic Impairment

Mild impairment (Child-Pugh class A): No dosage adjustment provided in manufacturer’s labeling.

Moderate impairment (Child-Pugh class B): All doses should be reduced to 50% of normal.

Severe impairment (Child-Pugh class C): All doses should be reduced to 25% of normal.

Storage

Store at 25°C (77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F).

Monitoring Parameters

Patient growth (weight/height gain in children); attention, hyperactivity, anxiety, worsening of aggressive behavior or hostility; blood pressure and pulse (baseline and following dose increases and periodically during treatment)

Family members and caregivers need to monitor patient daily for emergence of irritability, agitation, unusual changes in behavior, and suicide ideation. Pediatric patients should be monitored closely for suicidality, clinical worsening, or unusual changes in behavior, especially during the initial for months of therapy or at times of dose changes. Appearance of symptoms needs to be immediately reported to healthcare provider.

Thoroughly evaluate for cardiovascular risk. Monitor heart rate, blood pressure, and consider obtaining ECG prior to initiation (Martinez-Raga, 2013; Vetter, 2008). Periodically reevaluate the long-term usefulness of the drug for the individual patient.

Usual Pediatric Dose for Attention Deficit Disorder

70 kg or Less:
-Initial Dose: 0.5 mg/kg/day orally.
-Maintenance dose: Increase dose to 1.2 mg/kg/day after a minimum of 3 days at the initial dose.
-Maximum dose: 1.4 mg/kg/day or 100 mg/day, whichever is less.

Over 70 kg:
-Initial Dose: 40 mg/day orally.
-Maintenance dose: Increase dose to 80 mg/day after a minimum of 3 days at the initial dose.
-Maximum dose: After 2 to 4 additional weeks, the dose may be increased up to 100 mg/day in patients who have not achieved an optimal response.

Comments: Take dose once a day in the morning OR as evenly divided doses in the morning and late afternoon/early evening.

Use: Treatment of Attention Deficit Hyperactivity Disorder (ADHD) in pediatric patients age 6 and older.

Other Comments

Administration Advice:
-Take this drug with or without food.
-Swallow drug capsules whole and not opened.
-Do not mix the oral solution formulation in food or water as it can prevent the patient from receiving a full dose or could negatively affect the taste.
-Take a missed dose as soon as possible; however, do not take more than the prescribed total daily amount in any 24-hour period.
-This drug can be discontinued without being tapered.

General:
-In pediatric patients 70 kg or less, no additional benefit has been demonstrated for doses higher than 1.2 mg/kg/day and the safety of single doses over 1.8 mg/kg and total daily doses above 1.8 mg/kg/day have not been systematically evaluated.
-In pediatric patients over 70 kg and adults, no additional benefit has been demonstrated for doses higher than 80 mg and the safety of single doses over 120 mg and total daily doses above 150 mg have not been systematically evaluated.
-This drug has not been associated with a pattern of response that suggests stimulant or euphoriant properties, and there is no evidence of symptom rebound or adverse reactions suggesting drug-discontinuation or withdrawal symptoms.
-Overdosage: Activated charcoal may be useful in limiting absorption; dialysis is not likely to be useful as this drug is highly protein-bound.

Monitoring:
-Cardiovascular: Blood pressure and heart rate (baseline, at dose adjustments, periodically)
-Other: Height and weight in pediatric patients; long-term usefulness of drug (periodically)
-Psychiatric: Emergence or worsening of aggression/hostility, suicidal thinking and behavior, clinical worsening, unusual changes in behavior (periodically)

Patient Advice:
-If the contents of a drug capsule or the oral solution make contact with your eye, flush that eye immediately with water and wash your hands and any potentially contaminated surfaces as soon as possible.
-Avoid driving and other potentially dangerous activities such as operating machinery until you know how this drug affects you.

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