Atomoxetine (Strattera, Atomafutax) inhibits the reuptake of norepinephrine at the presynaptic terminal in the brain.

It is used in the treatment of attention-deficit hyperactivity disorder.

Although less effective than the stimulant drugs used to treat ADHD, it has the advantage of little abuse potential.

Atomoxetine (Strattera) Dose in Adults

Atomoxetine (strattera) Dosage in the treatment of Attention-deficithyperactivity disorder treatment:

• Atomoxetine can be discontinued without tapering.
  • Initially, 40 mg/day orally is given
  • It is increased after a minimum of 3 days to 80 mg/day
  • It may be administered as a single daily dose in the morning or as 2 evenly divided doses in the morning and late afternoon/early evening.
  • It may be increased (if an optimal response has not been achieved) to 100 mg/day after an additional 2 to 4 weeks.
  • Maximum dosage is 100 mg/day.

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  Dosage adjustment in patients using strong CYP2D6 inhibitors (eg, paroxetine, fluoxetine, quinidine) or patients who are CYP2D6 poor metabolizers:

  • Initially, 40 mg/day orally is given
  • If the patient is tolerating therapy but there is an inadequate response, then increase after a minimum of 4 weeks to 80 mg/day.

Atomoxetine (Strattera) Dose in Children

Atomoxetine (strattera) dosage in the treatment of Attention-deficit hyperactivity disorder:

• Children ≥6 years and Adolescents:

  • Patient weight ≤70 kg:

    • Initially, ~0.5 mg/kg/day orally is used;
    • It is increased after a minimum of 3 days to ~1.2 mg/kg/day
    • It may also be administered as  either once daily in the morning or in 2 evenly divided doses and given in the morning and late afternoon/early evening
    • The maximum daily dose is 1.4 mg/kg/day or 100 mg/day, one that is less.
    • Doses greater than 1.2 mg/kg/day have not been shown to provide additional benefit.

• ---

  Dosage adjustment with concurrent strong CYP2D6 inhibitors (eg, paroxetine, fluoxetine, quinidine) use or patients who are CYP2D6 poor metabolizers:

  • Initially 0.5 mg/kg/day orally is given
  • If the patient is tolerating therapy but an inadequate response, then increase after a minimum of 1 month to 1.2 mg/kg/day.

  • Patient weight >70 kg:

    • Initially 40 mg once daily orally is given
    • Then increase after a minimum of 3 days to ~80 mg daily
    • It may be administered either once daily in the morning or in 2 evenly divided doses and given in the morning and late afternoon/early evening.
    • If the optimal response does not occur after an additional 2 to 4 weeks of therapy, can be increased up to a maximum daily dose of 100 mg/day.

• ---

  Dosage adjustment with concurrent strong CYP2D6 inhibitors (eg, paroxetine, fluoxetine, quinidine) use or patients who are CYP2D6 poor metabolizers:

  • Initially 40 mg once daily orally is given
  • Then increase after a minimum of 3 days to ~80 mg daily

Pregnancy Risk Factor C

• Animal reproduction studies have shown that adverse events can be observed.
• We do not have enough information on atomoxetine pregnancy use
• For women with childbearing potential and sexually active, it is important to use appropriate contraception.

Use of strattera (atomoxetine) during breastfeeding

• It is unknown if atomoxetine excreted in breastmilk or not.
• The manufacturer suggests that nursing mothers be cautious when using atomoxetine.

Atomoxetine (Strattera) Dose in Renal Disease:

• No dosage adjustment is required in liver disease.

Atomoxetine (Strattera) Dose in Liver Disease:

• Mild impairment (Child Puugh class A)

  • There is no dosage adjustment in the manufacturer's labeling.

• Moderate impairment (Child Puugh class B)

  • Reduce the dose to half the normal dose

• Severe impairment (Child Puugh class C).

  • Reduce the dose to a quarter of the normal dose

Common Side Effects of Atomoxetine (Strattera) Include:

• Central nervous system:

  • Headache
  • Insomnia
  • Drowsiness

• Dermatologic:

  • Hyperhidrosis

• Gastrointestinal:

  • Xerostomia
  • Nausea
  • Decreased appetite
  • Abdominal pain
  • Vomiting
  • Constipation (1% to 11%)

• Genitourinary:

  • Erectile dysfunction

Less Common Side Effects of Atomoxetine (Strattera) Include:

• Cardiovascular:

  • Increased diastolic blood pressure
  • Systolic hypertension
  • Palpitations
  • Cold extremities
  • Syncope
  • Flushing
  • Orthostatic hypotension
  • Tachycardia
  • Prolonged Q-T interval on ECG

• Central nervous system:

  • Fatigue
  • Dizziness
  • Depression
  • Disturbed sleep
  • Irritability
  • Jitteriness
  • Abnormal dreams
  • Chills
  • Paresthesia
  • Anxiety
  • Hostility
  • Emotional lability
  • Agitation
  • Restlessness
  • Sensation of cold

• Dermatologic:

  • Excoriation
  • Pruritus
  • Urticaria

• Endocrine & metabolic:

  • Weight loss
  • Decreased libido
  • Hot flash
  • Increased thirst
  • Menstrual disease

• Gastrointestinal:

  • Dyspepsia
  • Anorexia
  • Dysgeusia
  • Flatulence

• Genitourinary:

  • Ejaculatory disorder
  • Urinary retention
  • Dysmenorrhea
  • Dysuria
  • Orgasm abnormal
  • Pollakiuria
  • Prostatitis,
  • Testicular pain
  • Urinary frequency

• Neuromuscular & skeletal:

  • Tremor
  • Muscle spasm
  • Weakness

• Ophthalmic:

  • Blurred vision
  • Conjunctivitis
  • Mydriasis

• Respiratory:

  • Pharyngolaryngeal pain

• Miscellaneous:

  • Therapeutic response unexpected

Contraindication to Atomoxetine (Strattera) Include:

• Hypersensitivity to atomoxetine and any part of the formulation
• MAO inhibitors should be avoided for at least 14 days
• Patients with narrow-angle vision should be avoided
• Use only if you have pheochromocytoma.
• Patients with severe cardiac and vascular conditions should be avoided.

Warnings and precautions

• Aggressive behavior
  • Atomoxetine has been shown to increase aggression and hostility, especially when it is first started therapy.
• Allergy reactions:
  • Rarely, angioneurotic swelling, urticaria and anaphylactic reactions can occur.
• Modified cardiac conduction
  • There have been cases where atomoxetine dosages overdoses can increase the QT interval. However, this was only when atomoxetine was taken with other medications that are known to prolong QT or inhibit CYP2D6.
  • Ex vivo evidence of hERG channel block has been shown for high levels of Atomoxetine.
• Cardiovascular events
  • There are serious cardiovascular events associated with Atomoxetine, including sudden death in children or adolescents, stroke in adults, and MI in patients with preexisting structural heart abnormalities or other serious issues.
  • Patients with severe structural cardiac abnormalities, cardiac disease, cardiomyopathy, heart rhythm abnormalities, or any other serious cardiac conditions should not receive Atomoxetine.
  • Before you start atomoxetine, review your medical history and family history for sudden death or ventricular arrhythmia.
  • Perform a physical exam to determine if you have any signs of cardiac disease. Patients should be further evaluated if they show evidence of cardiac disease, such as an echocardiogram or ECG.
  • Perform a cardiac evaluation on patients with exertional chest pain, unexplained systolic symptoms, or other signs of heart disease.
• Hepatotoxicity
  • The use of it may cause liver injury and even hepatic failure in rare cases.
  • If you notice any signs or symptoms of liver dysfunction, such as jaundice, dark urine and tenderness in the right upper quadrant, pruritus, jaundice or other flu-like symptoms, monitor liver enzymes.
  • Patients with jaundice and laboratory evidence of liver injury should be stopped immediately.
• Priapism
  • Rarely (rarely) have prolonged, painful, and non-painful penile erections occurred in adult and pediatric patients.
  • Reports involving methylphenidate or amphetamines or atomoxetine have shown priapism with different dosages, formulations, after dose adjustments, and during withdrawal.
  • Patients with certain hematological disorders (eg, sickle cells disease), perineal trauma and malignancies or concomitant alcohol use, illicit drugs or any medication associated with priapism may be at higher risk.
  • Patients with painful or prolonged erections that are not normal should immediately seek medical attention.
  • Avoiding stimulants and atomoxetine is a better option for patients suffering from severe priapism.
• Psychiatric effects
  • Children and adolescents can experience treatment-emergent psychotic or manic symptoms (eg, manias, hallucinations or delusional thoughts) even if they have not had a history of psychotic illness.
  • If symptoms persist, discontinue treatment.
• ADHD and comorbidities
  • Randomized controlled trials have shown that atomoxetine does no worsen anxiety in patients suffering from Tourette disorder or with anxiety disorders.
• Bipolar disorder
  • Patients with bipolar disorder comorbid should be cautious
  • Therapy can induce mixed/manic episodes.
  • Atomoxetine isn't approved for major depressive disorder
  • Bipolar disorder should be diagnosed in patients with depressive symptoms.
• Cardiovascular diseases
  • Atomoxetine may increase heart rate (HR), BP, and blood pressure.
  • CYP2D6-deficient metabolizers may experience a greater increase in BP or HR.
  • Patients with underlying conditions such as hypertension, tachycardia, or cardiovascular disease should be screened.
  • Patients with severe cardiac and vascular conditions should not use this product.
• Hepatic impairment
  • Patients with hepatic impairment should be cautious
  • In severe and moderate hepatic impairment, dosage adjustments may be necessary.
• Urinary retention
  • Patients with a history urinary retention or bladder outlet obstruction should be cautious
  • It can lead to urinary retention/hesitancy.

Atomoxetine: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitor:

• LFT (on the basis of signs and symptoms and for several weeks following discontinuation of treatment for liver dysfunction).
• Pulse and blood pressure (baseline, after treatment increases, and periodically throughout treatment).
• Children's growth (weight, height, and appetite)
• Before initiation, medical history and family history of sudden deaths or ventricular arrhythmia (or ventricular arrhythmia)
• A physical examination is performed to determine if there are any signs or symptoms of cardiac disease. Further investigations (ECG, echocardiogram) may be required if the exam results indicate that there is.
• Behavior changes (daily) - Especially during the initial months of therapy, or times when dose changes are occurring.

How to take Atomoxetine (Strattera)?

Oral:

• Don't eat.
• Do not crush, chew, or open the capsule.
• Take the entire capsule.
• Atomoxetine can cause a severe ocular irritation.
• If the capsule is accidentally opened and the contents come into contact with your eyes, flush them immediately with water and get medical advice.
• It is important to wash your hands and clean any surfaces that could be contaminated as soon as you can.

Mechanism of action of Atomoxetine:

• It inhibits norepinephrine reuptake (Ki 4.5nM), with little or no activity at other neuronal receptor pumps.

The duration of an action is uP to 24 hours It is quickly absorbed.

Protein binding98% mainly from albumin

Metabolism:

• • Mainly via the hepatic route via CYP2D6 or CYP2C19.
  • It forms metabolites, including the active metabolite 4-hydroxyatomoxetine. This is an equipotent to N-desmethylatomoxetine, which has limited activity.
  • CYP2D6 poor metabolizers have atomoxetine peak concentrations almost fivefold higher than those of extensive metabolizers.
  • Plasma concentrations of 4-hyroxyatomoxetine are very low (extensive metabolizers: 1.1% of atomoxetine levels & poor metabolizers, 0.1% of Atomoxetine Concentrations).

Bioavailability is 94% for poor metabolizers, 63% for extensive metabolizers.

Eliminating half-life:

• Atomoxetine's half-life is 5 hours. In poor metabolizers, it can last up to 24 hours.
• 4-hydroxyatomoxetine active metabolites: 6--8 hours
• N-desmethylatomoxetine takes 6-8 hours (34-40 in poor metabolizers).

Time until plasma concentration peaksUsually takes 1-2 hours. A high-fat meal can delay it by 3 hours

Excretion:

• Mainly Urine (80% as conjugated 4-hydroxymetabolite).
• Feces (17%)
• Unaltered excretion is less than 3%

International Brands of Atomoxetine:

• Abretia
• Artlex
• Atomafutix
• Atomerra
• Atomic
• Atomoxapex
• Attentho
• Attentin
• Attentrol
• Axepta
• Deaten
• MIXRE
• Omanoz
• Passiva
• Recit
• Sophos
• Stratomox
• Strattera
• Suev
• Xenocy

Atomoxetine (Strattera ) in Pakistan: