STRATTERA* 4 mg/mL oral solution.
Each mL of oral solution contains atomoxetine hydrochloride equivalent to 4 mg of atomoxetine.
For the full list of excipients, see section 6.1.
Excipient with known effect: contains 32.97 mg of sorbitol per mL
Oral solution
Clear, colourless
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.
Additional information for the safe use of this product:
A comprehensive treatment programme typically includes psychological, educational and social measures and is aimed at stabilising patients with a behavioural syndrome characterised by symptoms which may include chronic history of short attention span, distractibility, emotional lability, impulsivity, moderate to severe hyperactivity, minor neurological signs and abnormal EEG. Learning may or may not be impaired.
Pharmacological treatment is not indicated in all patients with this syndrome and the decision to use the drug must be based on a very thorough assessment of the severity of the patient's symptoms and impairment in relation to the patient's age and the persistence of symptoms.
Posology
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 eva luated. In some cases it might be appropriate to continue treatment into adulthood.
To facilitate dosing, the Strattera oral solution will be packaged with an oral dosing device containing a 10 mL oral syringe marked in 1 mL increments and a press-in-bottle adaptor.
The oral solution should be dosed in accordance with the following table:
|
Weight Range
|
Starting Dose
|
Target Dose
|
|
(Kgs)
|
(mL/day)
|
(mL/day)
|
|
16 to 18
|
2
|
5
|
|
19
|
2
|
6
|
|
20 to 21
|
3
|
6
|
|
22 to 24
|
3
|
7
|
|
25 to 28
|
3
|
8
|
|
29 to 31
|
4
|
9
|
|
32 to 34
|
4
|
10
|
|
35
|
4
|
11
|
|
36 to 38
|
5
|
11
|
|
39 to 41
|
5
|
12
|
|
42 to 44
|
5
|
13
|
|
45 to 48
|
6
|
14
|
|
49 to 51
|
6
|
15
|
|
52-54
|
7
|
16
|
|
55-58
|
7
|
17
|
|
59
|
7
|
18
|
|
60-61
|
8
|
18
|
|
62-64
|
8
|
19
|
|
65-67
|
8
|
20
|
|
68-69
|
9
|
20
|
|
≥70
|
10
|
20
|
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 80 mg. 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 120 mg and total daily doses above 150 mg have not been systematically eva luated.
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 120 mg and total daily doses above 150 mg have not been systematically eva luated.
Additional information for the safe use of this product:
Pre-treatment screening:
Prior to prescribing it is necessary to take an appropriate medical history and conduct a baseline eva luation of a patient's cardiovascular status, including blood pressure and heart rate (see sections 4.3 and 4.4).
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. (See section 4.4).
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-eva luation 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. (See section 5.2).
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. (see section 5.2).
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 (see sections 4.8 and 5.2). 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 eva luated.
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. (See section 4.4).
Method of administration
For oral use. Strattera can be administered with or without food. It is not recommended to mix Strattera oral solution in food or water as it can prevent the patient receiving a full dose or could negatively affect the taste.
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
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 (see section 4.4 Special Warnings and Precautions for Use – Cardiovascular Effects). 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 (see section 4.4 Special Warnings and Precautions for Use – Cardiovascular Effects).
Suicide-related behaviour
Suicide related behaviour (suicide attempts and suicidal ideation) has been reported in patients treated with atomoxetine. In double blind clinical trials, suicide related behaviours were uncommon but more frequently observed among children and adolescents treated with atomoxetine compared to those treated with placebo, where there were no events. In adult double-blind clinical trials there was no difference in the frequency of suicide related behaviour between atomoxetine and placebo. Patients who are being treated for ADHD should be carefully monitored for the appearance or worsening of suicide related behaviour.
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 (mean <5 mm Hg) (see section 4.8).
However, combined data from controlled and uncontrolled ADHD clinical trials show that approximately 8-12% of children and adolescents, and 6-10% adults experience more pronounced changes in heart rate (20 beats per minute or greater) and blood pressure (15-20 mmHg or greater). Analysis of these clinical trial data showed that approximately 15-26% of children and adolescents, and 27-32% of adults experiencing such changes in blood pressure and heart rate during atomoxetine treatment had sustained or progressive increases. Long-term sustained changes in blood pressure may potentially contribute to clinical consequences such as myocardial hypertrophy.
As a result of these findings, patients who are being considered for treatment with atomoxetine should have a careful history and physical exam to assess for the presence of cardiac disease, and should receive further specialist cardiac eva luation if initial findings suggest such history or disease.
It is recommended that heart rate and blood pressure be measured and recorded before treatment is started and, during treatment, after each adjustment of dose and then at least every 6 months to detect possible clinically important increases. For paediatric patients the use of a centile chart is recommended. For adults, current reference guidelines for hypertension should be followed.
Atomoxetine should not be used in patients with severe cardiovascular or cerebrovascular disorders (see section 4.3 Contraindications – Severe Cardiovascular and Cerebrovascular Disorders). Atomoxetine should be used with caution in patients whose underlying medical conditions could be worsened by increases in blood pressure and heart rate, such as patients with hypertension, tachycardia, or cardiovascular or cerebrovascular disease.
Patients who develop symptoms such as palpitations, exertional chest pain, unexplained syncope, dyspnoea or other symptoms suggestive of cardiac disease during atomoxetine treatment should undergo a prompt specialist cardiac eva luation.
In addition, atomoxetine should be used with caution in patients with congenital or acquired long QT or a family history of QT prolongation (see sections 4.5 and 4.8).
As orthostatic hypotension has also been reported, atomoxetine should be used with caution in any condition that may predispose patients to hypotension or conditions associated with abrupt heart rate or blood pressure changes.
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, sever
