Posology : מינונים

4.2     Posology and method of administration
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.

Pediatric population:

Dosing of pediatric 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.

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 pediatric 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 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 120 mg and total daily doses above 150 mg have not been systematically evaluated.

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 evaluation 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 pediatric 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-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. (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 evaluated.

Pediatric 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.