Strattera

/ Eli Lilly

Strattera can be administered as a single daily dose in the morning. Patients who do not achieve a satisfactory clinical response (tolerability [e.g. nausea or somnolence] or efficacy) when taking Strattera as a single daily dose might benefit from taking it as twice daily evenly divided doses in the morning and late afternoon or early evening.
Paediatric population:
Dosing of paediatric population up to 70 kg Body Weight:
Strattera should be initiated at a total daily dose of approximately 0.5 mg/kg. The initial dose should be maintained for a minimum of 7 days prior to upward dose titration according to clinical response and tolerability. The recommended maintenance dose is approximately 1.2 mg/kg/day (depending on the patient’s weight and available dosage strengths of atomoxetine). No additional benefit has been demonstrated for doses higher than 1.2 mg/kg/day. The safety of single doses over 1.8 mg/kg/day and total daily doses above 1.8 mg/kg have not been systematically evaluated. In some cases it might be appropriate to continue treatment into adulthood.
Dosing of paediatric population over 70 kg Body Weight:
Strattera should be initiated at a total daily dose of 40 mg. The initial dose should be maintained for a minimum of 7 days prior to upward dose titration according to clinical response and tolerability. The recommended maintenance dose is 80mg. No additional benefit has been demonstrated for doses higher than 80 mg. The maximum recommended total daily dose is 100 mg. The safety of single doses over 120mg and total daily doses above 150mg have not been systematically evaluated.
Adults:
Strattera should be initiated at a total daily dose of 40 mg. The initial dose should be maintained for a minimum of 7 days prior to upward dose titration according to clinical response and tolerability. The recommended maintenance daily dose is 80 mg to 100 mg. The maximum recommended total daily dose is 100 mg. The safety of single doses over 120mg and total daily doses above 150 mg have not been systematically evaluated.
See prescribing information for full details.
Pre-treatment screening:
Prior to prescribing it is necessary to take an appropriate medical history and conduct a baseline evaluation of a patient’s cardiovascular status, including blood pressure and heart rate.
Ongoing monitoring:
Cardiovascular status should be regularly monitored with blood pressure and pulse recorded after each adjustment of dose and then at least every 6 months. For paediatric patients the use of a centile chart is recommended. For adults, current reference guidelines for hypertension should be followed.
Withdrawal of Treatment:
In the study programme no distinct withdrawal symptoms have been described. In cases of significant adverse effects, atomoxetine may be stopped abruptly; otherwise the drug may be tapered off over a suitable time period.
Treatment with Strattera need not be indefinite. Re-evaluation of the need for continued therapy beyond 1 year should be performed, particularly when the patient has reached a stable and satisfactory response.
Special Populations
Hepatic Insufficiency: for patients with moderate hepatic insufficiency (Child-Pugh Class B), initial and target doses should be reduced to 50% of the usual dose. For patients with severe hepatic insufficiency (Child-Pugh Class C), initial dose and target doses should be reduced to 25% of usual dose.
Renal Insufficiency: subjects with end stage renal disease had higher systemic exposure to atomoxetine than healthy subjects (about a 65% increase), but there was no difference when exposure was corrected for mg/kg dose. Strattera can therefore be administered to ADHD patients with end stage renal disease or lesser degrees of renal insufficiency using the usual dosing regimen. Atomoxetine may exacerbate hypertension in patients with end stage renal disease.
Approximately 7% of Caucasians have a genotype corresponding to a non-functional CYP2D6 enzyme (called CYP2D6 poor metabolisers). Patients with this genotype have a several fold higher exposure to atomoxetine when compared to patients with a functional enzyme. Poor metabolisers are therefore at higher risk of adverse events.
For patients with a known poor metaboliser genotype, a lower starting dose and slower up titration of the dose may be considered.
Elderly population: the use of atomoxetine in patients over 65 years of age has not been systematically evaluated.
Paediatric population under six years of age: the safety and efficacy of Strattera in children under 6 years of age have not been established. Therefore Strattera should not be used in children under 6 years of age.
Method of administration
For oral use. Strattera can be administered with or without food.

Strattera is indicated for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in children of 6 years and older, in adolescents and in adults as part of a comprehensive treatment programme. Treatment must be initiated by a specialist in the treatment of ADHD, such as a paediatrician, child/adolescent psychiatrist, or psychiatrist. Diagnosis should be made according to current DSM criteria or the guidelines in ICD.
In adults, the presence of symptoms of ADHD that were pre-existing in childhood should be confirmed. Third-party corroboration is desirable and Strattera should not be initiated when the verification of childhood ADHD symptoms is uncertain. Diagnosis cannot be made solely on the presence of one or more symptoms of ADHD. Based on clinical judgment, patients should have ADHD of at least moderate severity as indicated by at least moderate functional impairment in 2 or more settings (for example, social, academic, and/or occupational functioning), affecting several aspects of an individual’s life.

Hypersensitivity to the active substance or to any of the excipients.
Atomoxetine should not be used in combination with monoamine oxidase inhibitors (MAOI). Atomoxetine should not be used within a minimum of 2 weeks after discontinuing therapy with MAOI. Treatment with MAOI should not be initiated within 2 weeks after discontinuing atomoxetine.
Atomoxetine should not be used in patients with narrow angle glaucoma, as in clinical trials the use of atomoxetine was associated with an increased incidence of mydriasis.
Atomoxetine should not be used in patients with severe cardiovascular or cerebrovascular disorders.
Severe cardiovascular disorders may include severe hypertension, heart failure, arterial occlusive disease, angina, haemodynamically significant congenital heart disease, cardiomyopathies, myocardial infarction, potentially life-threatening arrhythmias and channelopathies (disorders caused by the dysfunction of ion channels). Severe cerebrovascular disorders may include cerebral aneurysm or stroke.
Atomoxetine should not be used in patients with pheochromocytoma or a history of pheochromocytoma.

Suicide-related behaviour
Suicide related behaviour (suicide attempts and suicidal ideation) has been reported in patients treated with atomoxetine.
Sudden death and pre-existing cardiac abnormalities
Sudden death has been reported in patients with structural cardiac abnormalities who were taking atomoxetine at usual doses. Although some serious structural cardiac abnormalities alone carry an increased risk of sudden death, atomoxetine should only be used with caution in patients with known serious structural cardiac abnormalities and in consultation with a cardiac specialist.
Cardiovascular effects
Atomoxetine can affect heart rate and blood pressure.
Most patients taking atomoxetine experience a modest increase in heart rate (mean <10 bpm) and/or increase in blood pressure.
Cerebrovascular effects
Patients with additional risk factors for cerebrovascular conditions (such as a history of cardiovascular disease, concomitant medications that elevate blood pressure) should be assessed at every visit for neurological signs and symptoms after initiating treatment with atomoxetine.
Hepatic effects
Very rarely, spontaneous reports of liver injury, manifested by elevated hepatic enzymes and bilirubin with jaundice, have been reported. Also very rarely, severe liver injury, including acute liver failure, have been reported. Strattera should be discontinued in patients with jaundice or laboratory evidence of liver injury, and should not be restarted.
Psychotic or manic symptoms
Treatment emergent psychotic or manic symptoms, e.g., hallucinations, delusional thinking, mania or agitation in patients without a prior history of psychotic illness or mania can be caused by atomoxetine at usual doses. If such symptoms occur, consideration should be given to a possible causal role of atomoxetine, and discontinuation of treatment should be considered. The possibility that Strattera will cause the exacerbation of pre-existing psychotic or manic symptoms cannot be excluded.
Aggressive behaviour, hostility or emotional lability
Hostility (predominantly aggression, oppositional behaviour and anger) was more frequently observed in clinical trials among children, adolescents and adults treated with Strattera compared to those treated with placebo. Emotional lability was more frequently observed in clinical trials among children treated with Strattera compared to those treated with placebo. Patients should be closely monitored for the appearance or worsening of aggressive behaviour, hostility or emotional lability.
Possible allergic events
Although uncommon, allergic reactions, including anaphylactic reactions, rash, angioneurotic oedema, and urticaria, have been reported in patients taking atomoxetine.
Seizures
Seizures are a potential risk with atomoxetine. Atomoxetine should be introduced with caution in patients with a history of seizure. Discontinuation of atomoxetine should be considered in any patient developing a seizure or if there is an increase in seizure frequency where no other cause is identified.
Growth and development
Growth and development should be monitored in children and adolescents during treatment with atomoxetine. Patients requiring long-term therapy should be monitored and consideration should be given to dose reduction or interrupting therapy in children and adolescents who are not growing or gaining weight satisfactorily.
New-onset or worsening of Comorbid Depression, Anxiety and Tics
There have been rare postmarketing reports of anxiety and depression or depressed mood and very rare reports of tics in patients taking atomoxetine.
Patients who are being treated for ADHD with atomoxetine should be monitored for the appearance or worsening of anxiety symptoms, depressed mood and depression or tics.
Paediatric population under six years of age
Strattera should not be used in patients less than six years of age as efficacy and safety have not been established in this age group.
Other therapeutic use
Strattera is not indicated for the treatment of major depressive episodes and/or anxiety as the results of clinical trials in adults in these conditions, where ADHD is not present, did not show an effect compared to placebo.
See prescribing information for full details.

Appetite decreased,  Anorexia (loss of appetite), Headache, somnolence, Abdominal pain, vomiting, nausea, Blood pressure increased, heart rate increased, Irritability, mood swings, insomnia3, agitation, anxiety, depression and depressed mood , tics, Dizziness, Mydriasis, Constipation, dyspepsia, Dermatitis, pruritus, rash. See prescribing information for full details.

Effects of other drugs on atomoxetine  MAOIs
Atomoxetine should not be used with MAOIs.
CYP2D6 inhibitors (SSRIs (e.g. fluoxetine, paroxetine), quinidine, terbinafine)
In patients receiving these drugs, atomoxetine exposure may be 6-to 8-fold increased and Css max 3 to 4 times higher, because it is metabolised by the CYP2D6 pathway. Slower titration and final lower dosage of atomoxetine may be necessary in patients who are already taking CYP2D6 inhibitor drugs. If a CYP2D6 inhibitor is prescribed or discontinued after titration to the appropriate atomoxetine dose has occurred, the clinical response and tolerability should be re-evaluated for that patient to determine if dose adjustment is needed.

Caution is advised when combining atomoxetine with potent inhibitors of cytochrome P450 enzymes other than CYP2D6 in patients who are poor CYP2D6 metabolisers as the risk of clinically relevant increases in atomoxetine exposure in vivo is unknown.
Salbutamol (or other beta2 agonists)
Atomoxetine should be administered with caution to patients treated with high dose nebulised or systemically administered salbutamol (or other beta2 agonists) because cardiovascular effects can be potentiated.
Anti-hypertensive drugs
Atomoxetine should be used cautiously with antihypertensive drugs. Because of a possible increase in blood pressure, atomoxetine may decrease the effectiveness of antihypertensive drugs / drugs used to treat hypertension. Attention should be paid to monitoring of blood pressure and review of treatment of atomoxetine or antihypertensive drugs may be justified in the case of significant changes of blood pressure.
Pressor agents or drugs that increase blood pressure
Because of possible increase in effects on blood pressure, atomoxetine should be used cautiously with pressor agents or medications that may increase blood pressure (such as salbutamol). Attention should be paid to monitoring of blood pressure, and review of treatment for either atomoxetine or pressor agents may be justified in the case of significant change in blood pressure.
Drugs that Affect Noradrenaline
Drugs that affect noradrenaline should be used cautiously when co-administered with atomoxetine because of the potential for additive or synergistic pharmacological effects. Examples include antidepressants such as imipramine, venlafaxine and mirtazapine, or the decongestants pseudoephedrine or phenylephrine.
Drugs that Affect Gastric pH
Drugs that elevate gastric pH (magnesium hydroxide/aluminium hydroxide, omeprazole) had no effect on atomoxetine bioavailability.
Drugs Highly Bound to Plasma Protein
In vitro drug-displacement studies were conducted with atomoxetine and other highly bound drugs at therapeutic concentrations. Warfarin, acetylsalicylic acid, phenytoin, or diazepam did not affect the binding of atomoxetine to human albumin. Similarly, atomoxetine did not affect the binding of these compounds to human albumin.

Pregnancy
Animal studies in general do not indicate direct harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development. Atomoxetine should not be used during pregnancy unless the potential benefit justifies the potential risk to the foetus.
See prescribing information for full details.
Lactation
It is not known if atomoxetine is excreted in human milk. Because of the lack of data, atomoxetine should be avoided during breastfeeding.
See prescribing information for full details.

Signs and symptoms
During postmarketing, there have been reports of non-fatal acute and chronic overdoses of atomoxetine alone. The most commonly reported symptoms accompanying acute and chronic overdoses were gastrointestinal symptoms somnolence, dizziness, tremor and abnormal behaviour. 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) were also observed and reports of pruritus and rash have been received. Most events were mild to moderate. In some cases of overdose involving atomoxetine, seizures have been reported and very rarely QT prolongation. There have also been reports of fatal, acute overdoses involving a mixed ingestion of atomoxetine and at least one other drug.
There is limited clinical trial experience with atomoxetine overdose.
Management
An airway should be established. Activated charcoal may be useful in limiting absorption if the patient presents within 1 hour of ingestion. Monitoring of cardiac and vital signs is recommended, along with appropriate symptomatic and supportive measures. The patient should be observed for a minimum of 6 hours. Because atomoxetine is highly protein-bound, dialysis is not likely to be useful in the treatment of overdose.

Hard capsules 10-60 mg: Store below 30°C in the original package in order to protect from light and moisture.
Hard capsules  80-100 mg: Store below 25°C in the original package in order to protect form light and moisture.