What is Strattera (atomoxetine)?

Strattera (atomoxetine) is a selective norepinephrine reuptake inhibitor (SNRI) used to treat childhood attention deficit and hyperactivity disorder (ADHD), as well as ADHD in adolescents and adults. 

Common side effects of Strattera include:

Other possible side effects of Strattera include:

Serious side effects of Strattera include:

Drug interactions of Strattera include monoamine oxidase inhibitors (MAOIs). Fluoxetine, paroxetine, quinidine, and other medications can block the enzyme in the liver that eliminates Strattera from the body which can increase the amount of Strattera in the blood and possibly increase the risk of side effects.

No adequate studies of Strattera have been done in pregnant women. Before prescribing Strattera to pregnant women, physicians must weigh the potential benefits against the potential and unknown risks.

Strattera is excreted in the breast milk of animals. Although not similarly studied in humans, it is likely Strattera is excreted in human breast milk as well. The benefits and potential risks of Strattera must be weighed before it is prescribed to breastfeeding mothers.

What are the important side effects of Strattera (atomoxetine)?

The most common side effects of Strattera in children and adolescents are:

The most common side effects in adults are:

  • Problems sleeping
  • Dry mouth
  • Decreased appetite
  • Upset stomach
  • Nausea or vomiting
  • Dizziness
  • Problems urinating
  • Sexual side effects

Other possible side effects include:

Possible serious side effects:

Other serious side effects and adverse events include:

  • In rare cases, Strattera causes allergic reactions, such as fluid accumulation (edema) or hives, which can be serious.
  • Strattera may increase blood pressure and heart rate. Blood pressure should be measured before starting Strattera, following increases in dose, and periodically while on therapy.
  • Strattera may cause severe liver injury, and patients should be instructed to contact their physician immediately if they develop symptoms or signs suggesting liver injury such as pruritus, dark urine, jaundice, right upper abdominal pain or unexplained "flu-like" symptoms.
  • Priapism defined as painful and nonpainful penile erection lasting more than 4 hours have been reported in pediatric and adult patients treated with stimulants. The erection usually resolves when the drug is stopped. Prompt medical attention is required in the event of suspected priapism.

Strattera (atomoxetine) side effects list for healthcare professionals

Clinical Trials Experience

Strattera was administered to 5382 children or adolescent patients with ADHD and 1007 adults with ADHD in clinical studies. During the ADHD clinical trials, 1625 children and adolescent patients were treated for longer than 1 year and 2529 children and adolescent patients were treated for over 6 months.

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.

Child And Adolescent Clinical Trials

Reasons For Discontinuation Of Treatment Due To Adverse Reactions In Child And Adolescent Clinical Trials

In acute child and adolescent placebo-controlled trials, 3.0% (48/1613) of atomoxetine subjects and 1.4% (13/945) placebo subjects discontinued for adverse reactions. For all studies, (including open-label and long-term studies), 6.3% of extensive metabolizer (EM) patients and 11.2% of poor metabolizer (PM) patients discontinued because of an adverse reaction.

Among Strattera-treated patients the following reasons for discontinuation were reported by more than 1 patient:

  • 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).
Seizures

Strattera has not been systematically evaluated in pediatric patients with seizure disorder as these patients were excluded from clinical studies during the product’s premarket testing. In the clinical development program, seizures were reported in 0.2% (12/5073) of children whose average age was 10 years (range 6 to 16 years). In these clinical trials, the seizure risk among poor metabolizers was 0.3% (1/293) compared to 0.2% (11/4741) for extensive metabolizers.

Commonly Observed Adverse Reactions In Acute Child And Adolescent, Placebo-Controlled Trials

Commonly observed adverse reactions associated with the use of Strattera (incidence of 2% or greater) and not observed at an equivalent incidence among placebo-treated patients (Strattera incidence greater than placebo) are listed in Table 2. Results were similar in the BID and the QD trial except as shown in Table 3, which shows both BID and QD results for selected adverse reactions based on statistically significant Breslow-Day tests. The most commonly observed adverse reactions in patients treated with Strattera (incidence of 5% or greater and at least twice the incidence in placebo patients, for either BID or QD dosing) were: nausea, vomiting, fatigue, decreased appetite, abdominal pain, and somnolence (see Tables 2 and 3).

Additional data from ADHD clinical trials (controlled and uncontrolled) has shown that approximately 5 to 10% of pediatric patients experienced potentially clinically important changes in heart rate (=20 beats per min) or blood pressure (=15 to 20 mm Hg).

Table 2: Common Treatment–Emergent Adverse Reactions Associated with the Use of Strattera in Acute (up to 18 weeks) Child and Adolescent Trials

Adverse ReactionaPercentage of Patients Reporting Reaction
System Organ Class/ Adverse ReactionStrattera
(N=1597)
Placebo
(N=934)
Gastrointestinal Disorders
  Abdominal painb1810
  Vomiting116
  Nausea105
General Disorders and Administration Site Conditions
  Fatigue83
  Irritability63
  Therapeutic response unexpected21
Investigations
  Weight decreased30
Metabolism and Nutritional Disorders
  Decreased appetite164
  Anorexia31
Nervous System Disorders
  Headache1915
  Somnolencec114
Dizziness52
Skin and Subcutaneous Tissue Disorders
  Rash21
a Reactions reported by at least 2% of patients treated with atomoxetine, and greater than placebo. The following reactions did not meet this criterion but were reported by more atomoxetine-treated patients than placebo-treated patients and are possibly related to atomoxetine treatment: blood pressure increased, early morning awakening (terminal insomnia), flushing, mydriasis, sinus tachycardia, asthenia, palpitations, mood swings, constipation, and dyspepsia. The following reactions were reported by at least 2% of patients treated with atomoxetine, and equal to or less than placebo: pharyngolaryngeal pain, insomnia (insomnia includes the terms, insomnia, initial insomnia, middle insomnia). The following reaction did not meet this criterion but shows a statistically significant dose relationship: pruritus.
b Abdominal pain includes the terms: abdominal pain upper, abdominal pain, stomach discomfort, abdominal discomfort, epigastric discomfort.
c Somnolence includes the terms: sedation, somnolence.

Table 3: Common Treatment-Emergent Adverse Reactions Associated with the Use of Strattera in Acute (up to 18 weeks) Child and Adolescent Trials

Adverse ReactionPercentage of Patients Reporting Reaction from BID TrialsPercentage of Patients Reporting Reaction from QD Trials
Strattera
(N=715)
Placebo
(N=434)
Strattera
(N=882)
Placebo
(N=500)
Gastrointestinal Disorders
  Abdominal paina1713187
  Vomiting118114
  Nausea76134
  Constipationb2110
General Disorders
  Fatigue6492
Psychiatric Disorders
  Mood swingsc2011
a Abdominal pain includes the terms: abdominal pain upper, abdominal pain, stomach discomfort, abdominal discomfort, epigastric discomfort.
b Constipation didn’t meet the statistical significance on Breslow-Day test but is included in the table because of pharmacologic plausibility.
c Mood swings didn’t meet the statistical significance on Breslow-Day test at 0.05 level but p-value was <0.1 (trend).

The following adverse reactions occurred in at least 2% of child and adolescent CYP2D6 PM patients and were statistically significantly more frequent in PM patients compared with CYP2D6 EM patients:

  • insomnia (11% of PMs, 6% of EMs);
  • weight decreased (7% of PMs, 4% of EMs);
  • constipation (7% of PMs, 4% of EMs);
  • depression1 (7% of PMs, 4% of EMs);
  • tremor (5% of PMs, 1% of EMs);
  • excoriation (4% of PMs, 2% of EMs);
  • middle insomnia (3% of PMs, 1% of EMs);
  • conjunctivitis (3% of PMs, 1% of EMs);
  • syncope (3% of PMs, 1% of EMs);
  • early morning awakening (2% of PMs, 1% of EMs);
  • mydriasis (2% of PMs, 1% of EMs);
  • sedation (4% of PMs, 2% of EMs).

1Depression includes the following terms: depression, major depression, depressive symptoms, depressed mood, dysphoria.

Adult Clinical Trials

Reasons For Discontinuation Of Treatment Due To Adverse Reactions In Acute Adult Placebo-Controlled Trials

In the acute adult placebo-controlled trials, 11.3% (61/541) atomoxetine subjects and 3.0% (12/405) placebo subjects discontinued for adverse reactions. Among Strattera-treated patients, the following reasons for discontinuation were reported by more than 1 patient:

Seizures

Strattera has not been systematically evaluated in adult patients with a seizure disorder as these patients were excluded from clinical studies during the product’s premarket testing. In the clinical development program, seizures were reported on 0.1% (1/748) of adult patients. In these clinical trials, no poor metabolizers (0/43) reported seizures compared to 0.1% (1/705) for extensive metabolizers.

Commonly Observed Adverse Reactions In Acute Adult Placebo-Controlled Trials

Commonly observed adverse reactions associated with the use of Strattera (incidence of 2% or greater) and not observed at an equivalent incidence among placebo-treated patients (Strattera incidence greater than placebo) are listed in Table 4. The most commonly observed adverse reactions in patients treated with Strattera (incidence of 5% or greater and at least twice the incidence in placebo patients) were:

Additional data from ADHD clinical trials (controlled and uncontrolled) has shown that approximately 5 to 10% of adult patients experienced potentially clinically important changes in heart rate (=20 beats per min) or blood pressure (=15 to 20 mm Hg).

Table 4: Common Treatment-Emergent Adverse Reactions Associated with the Use of Strattera in Acute (up to 25 weeks) Adult Trials

Adverse ReactionaPercentage of Patients Reporting Reaction
System Organ Class/ Adverse ReactionStrattera
(N=1697)
Placebo
(N=1560)
Cardiac Disorders
  Palpitations31
Gastrointestinal Disorders
  Dry mouth205
  Nausea266
  Constipation83
  Abdominal painb74
  Dyspepsia42
  Vomiting42
General Disorders and Administration Site Conditions
  Fatigue106
  Chills30
  Feeling jittery21
  Irritability53
  Thirst21
Investigations
  Weight decreased21
Metabolism and Nutritional Disorders
  Decreased appetite163
Nervous System Disorders
  Dizziness83
  Somnolencec85
  Paraesthesia30
Psychiatric Disorders
  Abnormal dreams43
  Insomniad158
  Libido decreased31
  Sleep disorder31
Renal and Urinary Disorders
  Urinary hesitatione61
  Dysuria20
Reproductive System and Breast Disorders
  Erectile dysfunctionf81
  Dysmenorrheag32
  Ejaculation delayedf and/or ejaculation disorderf41
Skin and Subcutaneous Tissue Disorders
  Hyperhidrosis41
Vascular Disorders
  Hot flush30
a Reactions reported by at least 2% of patients treated with atomoxetine, and greater than placebo. The following reactions did not meet this criterion but were reported by more atomoxetine-treated patients than placebo-treated patients and are possibly related to atomoxetine treatment: peripheral coldness, tachycardia, prostatitis, testicular pain, orgasm abnormal, flatulence, asthenia, feeling cold, muscle spasm, dysgeusia, agitation, restlessness, micturition urgency, pollakiuria, pruritus, urticaria, flushing, tremor, menstruation irregular, rash, and urinary retention.
The following reactions were reported by at least 2% of patients treated with atomoxetine, and equal to or less than placebo: anxiety, diarrhea, back pain, headache, and oropharyngeal pain.
bAbdominal pain includes the terms: abdominal pain upper, abdominal pain, stomach discomfort, abdominal discomfort,epigastric discomfort.
cSomnolence includes the terms: sedation, somnolence.
d Insomnia includes the terms: insomnia, initial insomnia, middle insomnia, and terminal insomnia.
eUrinary hesitation includes the terms: urinary hesitation, urine flow decreased.
fBased on total number of males (Strattera, N=943; placebo, N=869).
gBased on total number of females (Strattera, N=754; placebo, N=691).

The following adverse events occurred in at least 2% of adult CYP2D6 poor metaboliser (PM) patients and were statistically significantly more frequent in PM patients compared to CYP2D6 extensive metaboliser (EM) patients:

  • vision blurred (4% of PMs, 1% of EMs);
  • dry mouth (35% of PMs, 17% of EMs);
  • constipation (11% of PMs, 7% of EMs);
  • feeling jittery (5% of PMs, 2% of EMs);
  • decreased appetite (23% of PMs, 15% of EMs);
  • tremor (5% of PMs, 1% of EMs);
  • insomnia (19% of PMs, 11% of EMs);
  • sleep disorder (7% of PMs, 3% of EMs);
  • middle insomnia (5% of PMs, 3% of EMs);
  • terminal insomnia (3% of PMs, 1% of EMs);
  • urinary retention (6% of PMs, 1% of EMs);
  • erectile dysfunction (21% of PMs, 9% of EMs);
  • ejaculation disorder (6% of PMs, 2% of EMs);
  • hyperhidrosis (15% of PMs, 7% of EMs);
  • peripheral coldness (3% of PMs, 1% of EMs).
Male And Female Sexual Dysfunction

Atomoxetine appears to impair sexual function in some patients. Changes in sexual desire, sexual performance, and sexual satisfaction are not well assessed in most clinical trials because they need special attention and because patients and physicians may be reluctant to discuss them. Accordingly, estimates of the incidence of untoward sexual experience and performance cited in product labeling are likely to underestimate the actual incidence. Table 4 above displays the incidence of sexual side effects reported by at least 2% of adult patients taking Strattera in placebo-controlled trials.

There are no adequate and well-controlled studies examining sexual dysfunction with Strattera treatment. While it is difficult to know the precise risk of sexual dysfunction associated with the use of Strattera, physicians should routinely inquire about such possible side effects.

Postmarketing Spontaneous Reports

The following adverse reactions have been identified during post approval use of Strattera. Unless otherwise specified, these adverse reactions have occurred in adults and children and adolescents. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Cardiovascular systemQT prolongation, syncope.

Peripheral vascular effects: Raynaud’s phenomenon.

General disorders and administration site conditions: Lethargy.

Musculoskeletal system: Rhabdomyolysis.

Nervous system disorders: Hypoaesthesia; paraesthesia in children and adolescents; sensory disturbances; tics.

Psychiatric disorders: Depression and depressed mood; anxiety, libido changes.

Seizures Seizures have been reported in the postmarketing period. The postmarketing seizure cases include patients with pre-existing seizure disorders and those with identified risk factors for seizures, as well as patients with neither a history of nor identified risk factors for seizures. The exact relationship between Strattera and seizures is difficult to evaluate due to uncertainty about the background risk of seizures in ADHD patients.

Skin and subcutaneous tissue disorders: Alopecia, hyperhidrosis.

Urogenital system: Male pelvic pain; urinary hesitation in children and adolescents; urinary retention in children and adolescents.

What drugs interact with Strattera (atomoxetine)?

Monoamine Oxidase Inhibitors

With other drugs that affect brain monoamine concentrations, there have been reports of serious, sometimes fatal reactions (including hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs, and mental status changes that include extreme agitation progressing to delirium and coma) when taken in combination with an MAOI. Some cases presented with features resembling neuroleptic malignant syndrome. Such reactions may occur when these drugs are given concurrently or in close proximity.

Effect Of CYP2D6 Inhibitors On Atomoxetine

In extensive metabolizers (EMs), inhibitors of CYP2D6 (e.g., paroxetine, fluoxetine, and quinidine) increase atomoxetine steady-state plasma concentrations to exposures similar to those observed in poor metabolizers (PMs). In EM individuals treated with paroxetine or fluoxetine, the AUC of atomoxetine is approximately 6-to 8-fold and Css, max is about 3-to 4-fold greater than atomoxetine alone.

In vitro studies suggest that coadministration of cytochrome P450 inhibitors to PMs will not increase the plasma concentrations of atomoxetine.

Antihypertensive Drugs And Pressor Agents

Because of possible effects on blood pressure, Strattera should be used cautiously with antihypertensive drugs and pressor agents (e.g., dopamine, dobutamine) or other drugs that increase blood pressure.

Albuterol

Strattera should be administered with caution to patients being treated with systemically-administered (oral or intravenous) albuterol (or other beta2 agonists) because the action of albuterol on the cardiovascular system can be potentiated resulting in increases in heart rate and blood pressure. Albuterol (600 mcg iv over 2 hours) induced increases in heart rate and blood pressure. These effects were potentiated by atomoxetine (60 mg BID for 5 days) and were most marked after the initial coadministration of albuterol and atomoxetine. However, these effects on heart rate and blood pressure were not seen in another study after the coadministration with inhaled dose of albuterol (200-800 mcg) and atomoxetine (80 mg QD for 5 days) in 21 healthy Asian subjects who were excluded for poor metabolizer status.

Effect Of Atomoxetine On P450 Enzymes

Atomoxetine did not cause clinically important inhibition or induction of cytochrome P450 enzymes, including CYP1A2, CYP3A, CYP2D6, and CYP2C9.

CYP3A Substrate (e.g., Midazolam)

Coadministration of Strattera (60 mg BID for 12 days) with midazolam, a model compound for CYP3A4 metabolized drugs (single dose of 5 mg), resulted in 15% increase in AUC of midazolam. No dose adjustment is recommended for drugs metabolized by CYP3A.

CYP2D6 Substrate (e.g., Desipramine)

Coadministration of Strattera (40 or 60 mg BID for 13 days) with desipramine, a model compound for CYP2D6 metabolized drugs (single dose of 50 mg), did not alter the pharmacokinetics of desipramine. No dose adjustment is recommended for drugs metabolized by CYP2D6.

Alcohol

Consumption of ethanol with Strattera did not change the intoxicating effects of ethanol.

Methylphenidate

Coadministration of methylphenidate with Strattera did not increase cardiovascular effects beyond those seen with methylphenidate alone.

Drugs Highly Bound To Plasma Protein

In vitro drug-displacement studies were conducted with atomoxetine and other highly-bound drugs at therapeutic concentrations. Atomoxetine did not affect the binding of warfarin, acetylsalicylic acid, phenytoin, or diazepam to human albumin. Similarly, these compounds did not affect the binding of atomoxetine to human albumin.

Drugs That Affect Gastric pH

Drugs that elevate gastric pH (magnesium hydroxide/aluminum hydroxide, omeprazole) had no effect on Strattera bioavailability.

Drug Abuse And Dependence

Controlled Substance

Strattera is not a controlled substance.

Abuse

In a randomized, double-blind, placebo-controlled, abuse-potential study in adults comparing effects of Strattera and placebo, Strattera was not associated with a pattern of response that suggested stimulant or euphoriant properties.

Dependence

Clinical study data in over 2000 children, adolescents, and adults with ADHD and over 1200 adults with depression showed only isolated incidents of drug diversion or inappropriate self-administration associated with Strattera. There was no evidence of symptom rebound or adverse reactions suggesting a drug-discontinuation or withdrawal syndrome.

Animal Experience

Drug discrimination studies in rats and monkeys showed inconsistent stimulus generalization between atomoxetine and cocaine.

Summary

Strattera (atomoxetine) is a selective norepinephrine reuptake inhibitor (SNRI) used to treat attention deficit and hyperactivity disorder (ADHD) in children, adolescents, and adults. Common side effects of Strattera include upset stomach, decreased appetite, nausea, vomiting, dizziness, tiredness, mood swings, weight loss, problems sleeping, dry mouth, problems urinating, and sexual side effects. Other possible side effects of Strattera include sinus headache, indigestion, constipation, and irritability. No adequate studies of Strattera have been done in pregnant women. Although not similarly studied in humans, it is likely Strattera is excreted in human breast milk as well. The benefits and potential risks of Strattera must be weighed before it is prescribed to breastfeeding mothers.

Treatment & Diagnosis

Medications & Supplements

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Medically Reviewed on 5/14/2020
References
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Professional side effects and drug interactions sections courtesy of the U.S. Food and Drug Administration.
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