Expiration date: 12/2025
The composition and form of issue:
Capsules 10 mg. 1 capsule contains:
Atomoxetine hydrochloride (equivalent to Atomoxetine) 10 mg
Excipients: Dimethicone, starch pregelatinization
composition of capsule shell: titanium dioxide, sodium lauryl sulfate, gelatin
in packages contour cell for 7 or 14 PCs. in cardboard pack 1 or 2 (14 PCs) packing.
Capsules 18 mg. 1 capsule contains:
Atomoxetine hydrochloride (equivalent to Atomoxetine) 18 mg
Excipients: Dimethicone, starch pregelatinization
composition of capsule shell: titanium dioxide, sodium lauryl sulfate, gelatin, colouring agent iron oxide yellow
in packages contour cell for 7 or 14 PCs. in cardboard pack 1 or 2 (14 PCs) packing.
Capsules 25 mg. 1 capsule contains:
Atomoxetine hydrochloride (equivalent to Atomoxetine) 25 mg
Excipients: Dimethicone, starch pregelatinization
composition of capsule shell: titanium dioxide, sodium lauryl sulfate, gelatin, Indigo Carmine dye
in packages contour cell for 7 or 14 PCs. in cardboard pack 1 or 2 (14 PCs) packing.
Capsules 40 mg. 1 capsule contains:
Atomoxetine hydrochloride (equivalent to Atomoxetine) 40 mg
Excipients: Dimethicone, starch pregelatinization
composition of capsule shell: titanium dioxide, sodium lauryl sulfate, gelatin, Indigo Carmine dye
in packages contour cell for 7 or 14 PCs. in cardboard pack 1 or 2 (14 PCs) packing.
Capsules 60 mg. 1 capsule contains:
Atomoxetine hydrochloride (equivalent to Atomoxetine) 60 mg
Excipients: Dimethicone, starch pregelatinization
composition of capsule shell: titanium dioxide, sodium lauryl sulfate, gelatin, colouring agent iron oxide yellow, Indigo Carmine dye
in packages contour cell for 7 or 14 PCs. in cardboard pack 1 or 2 (14 PCs) packing.
Description pharmaceutical form:
Capsules 10 mg — hard gelatin, size ?3, opaque, white/white, with applied dose "10 mg" and an identification code "Lilly 3227".
Capsules 18 mg — hard gelatin, size ?3, opaque, yellow/white, with applied dose "18 mg" and an identification code "Lilly 3238".
Capsules 25 mg — hard gelatin, size ?3, opaque, blue/white, with applied dose "25 mg" and an identification code "Lilly 3228".
Capsules 40 mg — hard gelatin, size ?3, opaque, blue/blue, with applied dosage "40 mg" and an identification code "Lilly 3229".
Capsules 60 mg — hard gelatin, size ?2, opaque, blue/yellow, with applied dose "60 mg" and an identification code "Lilly 3239".
The contents of capsules — powder from white to almost white.
Feature:
Sympathomimetic Central action.
Pharmacokinetics:
Suction. After ingestion of Atomoxetine is rapidly and almost completely absorbed, reaching Cmax in the plasma after about 1-2 hours of Atomoxetine administered regardless of meals or during meals.
Distribution. Tomoxetin well distributed in the body. Has a high affinity to plasma proteins, primarily to albumin.
Metabolism. Atomoxetine undergoes primary metabolism with participation of isoenzyme CYP2D6. The main of the resulting oxidized metabolite 4-hydroxyatomoxetine quickly glukuronidiruetsa. Pharmacological activity of 4-hydroxyatomoxetine equivalent to Atomoxetine, but circulates in plasma at much lower concentrations.
Although 4-hydroxyatomoxetine initially formed with the participation of CYP2D6, in people with insufficient activity of CYP2D6 4-hydroxyatomoxetine may be formed of some other cytochrome P450 isoenzymes, but more slowly.
Atomoxetine not inhibited and does not increase the cycle of CYP2D6.
Excretion. The average T1/2 of Atomoxetine after oral administration is 3.6 hours in patients with severe metabolism and 21 hours in patients with reduced metabolism. Atomoxetine mainly excreted in the urine as 4-hydroxyatomoxetine-O-glucuronide.
Pharmacokinetics in special clinical cases
Pharmacokinetics in children and adolescents is similar to the pharmacokinetics in adults. The pharmacokinetics of Atomoxetine in children under 6 years has not been studied.
Description pharmacological action:
Atomoxetine is a highly selective potent inhibitor of presynaptic norepinephrine vectors. Atomoxetine has a minimal affinity for other noradrenergic receptors or to other carriers or receptors of neurotransmitters.
Atomoxetine does not apply to psychostimulants and is not a derivative of amphetamine. In clinical studies with drug discontinuation were not observed amplification of symptoms or any adverse events related to the syndrome.
Indications:
The attention deficit disorder with hyperactivity (ADHD) in children 6 years and older, adolescents and adults.
Contraindications:
- hypersensitivity to the drug
- the heavy defeat of the heart
- concurrent use with MAO inhibitors
- angle-closure glaucoma.
With caution should use the drug in patients with hypertension, tachycardia, cardiovascular diseases, heavy physical strain, the simultaneous intake of stimulants, sudden cardiac death, family history, violation of cerebral circulation, convulsive seizures in history, as well as for conditions which can cause arterial hypotension.
Application of pregnancy and breast-feeding:
Clinical experiences with Strattera during pregnancy is insufficient, so the drug should be administered during pregnancy only if the expected benefit of therapy to the mother greatly outweighs the potential risk to the fetus.
It is not known whether Atomoxetine stands out with breast milk. If necessary, the appointment of the drug to nursing mothers with caution.
Side effects:
Children and adolescents
From the digestive system: very often (>10%) — abdominal pain (18% including the phenomenon of abdominal discomfort, pain and discomfort in epigastria, discomfort in the stomach), decreased appetite (16%), vomiting (11%), often (1-10%) — constipation, dyspepsia, nausea (9%), anorexia. These side effects are temporary and usually do not require discontinuation of the drug. In connection with reduced appetite in some patients at the beginning of treatment was observed a decrease in body weight (average about 0.5 kg), loss of body weight was greater at higher doses. After the initial weight loss in patients taking the Strater, witnessed a slight increase in body mass with long-term therapy. Growth rates (weight and height) after two years of treatment were close to normal.
Nausea (9%) and vomiting (11%) most likely during the first month of treatment, usually mild and moderate severity, are temporary and do not cause discontinuation of treatment in a significant number of cases.
From the side of cardiovascular system: (0,1–1%) — palpitations, sinus tachycardia.
In placebo-controlled trials in children treated with the Strater, it was noted the average increase in heart rate by 6 beats/min, and the average increase in SBP and DBP by 2 mm Hg.St. compared to a placebo.
Patients who received Atomoxetine, orthostatic hypotension observed (0,2%, n=7) and syncope (0.8 percent, n=26), due to its effect on noradrenergic tone.
CNS: very common (>10%) — somnolence (including sedation) often (1-10%) — irritability, mood swings, dizziness sometimes (0,1–1%) — early morning awakening.
Side of body: often (1-10%) — mydriasis.
Dermatological reactions: often (1-10%) — dermatitis, rashes sometimes (0,1–1%) — itching.
Other: often (1-10%) — flu, fatigue, weight loss sometimes (0,1–1%) — weakness.
Side effects in patients with slow metabolizers of CYP2D6 substrates observed in 2% of cases and in 2 times more often, and statistically significantly more often than patients with a rapid metabolism of substrates of CYP2D6: tremor (5.1 and 1.1 percent, respectively), syncope (2.1 and 0.7%, respectively), conjunctivitis (3 and 1.5%, respectively), early morning awakening (3 and 1.1%, respectively), mydriasis (2.5 and 0.7%, respectively).
Adults
In adults, the most frequent side effects associated with the use of Atomoxetine, it was noted from the gastrointestinal tract and the urogenital tract. Serious adverse events during short or prolonged treatment with Atomoxetine was not observed.
From the digestive system: very often (>10%) — loss of appetite, dry mouth, nausea, often (1-10%) — abdominal pain (including the phenomenon of abdominal discomfort, pain and discomfort in epigastria, discomfort in the stomach), constipation, dyspepsia, flatulence.
CNS: very common (>10%), insomnia (including difficulty falling asleep and sleep disturbance at night), often (1-10%) — decreased libido, dizziness, violation of sleep quality, sine headache sometimes (0,1–1%) — early morning awakening.
Of the cardiovascular system: often (1-10%) — tides of blood to face, palpitations, tachycardia sometimes (0,1–1%) — feeling cold in the lower extremities is very rare (<0,01%) according to the spontaneous (post-marketing reports) peripheral vascular responses and/or Raynaud's syndrome, and the risk of recurrence of Raynaud's syndrome.
In placebo-controlled studies of adults receiving the Strater, it was noted the average increase in heart rate by 6 beats/min, the average increase of the garden (about 3 mm Hg.St.) and DBP (approximately 1 mm Hg.St.) compared to a placebo.
From the urinary system: often (1-10%) — dysuria, difficulty urinating.
Part of the reproductive system: often (1-10%) — dysmenorrhea, violation of ejaculation, absence of ejaculation, erectile dysfunction, erectile dysfunction, menstrual disorders, impaired orgasm very rarely (<0.01 percent), according to the spontaneous (post-marketing) messages — painful or prolonged erection.
The skin and subcutaneous tissue: often (1-10%) — dermatitis, excessive sweating.
Other: often (1-10%) — weakness, drowsiness, chills, reducing body weight.
Drug interactions:
While the use of Strattera with agonists &beta2-adrenergic receptors may increase their action on the cardiovascular system (this combination use with caution). In healthy adult volunteers the effect of salbutamol in the standard ingaliruemogo a dose of 200 mcg in hemodynamics was insignificant in comparison with the effect of specified doses of the drug at/in the introduction. Concomitant use of Atomoxetine at a dose of 80 mg/day for 5 days did not lead to the reinforcement of these effects salbutamol. Heart rate after multiple inhalations of salbutamol in a dose of 800 mg was characterized by similar values in terms of as monotherapy and in combination with the use of Atomoxetine.
The simultaneous appointment of Atomoxetine with drugs, causing elongation QT interval (antipsychotics, antiaritmiki, moxifloxacin, erythromycin, tricyclic antidepressants, lithium carbonate), and with drugs that cause electrolyte imbalance (diuretics) and inhibitors of CYP2D6, increases the risk of extending the QT interval.
Atomoxetine does not cause clinically significant inhibition or induction of isoenzymes of cytochrome P450, including CYP1A2, CYP3A, CYP2D6 and CYP2C9. In patients with severe metabolism of substrates of CYP2D6 inhibitors of CYP2D6 increase CSS Atomoxetine in plasma at steady state to a level similar to that in patients with slow metabolizers of CYP2D6 substrates.
On the basis of in vitro studies it is assumed that the appointment of inhibitors of cytochrome P450 patients with slow metabolizers of CYP2D6 substrates does not increase the concentration of Atomoxetine in blood plasma. Patients using drugs inhibitors CYP2D6, recommended gradual dose titration of Atomoxetine.
Because of the possible impact on AD the Strater should be used with caution in combination with drugs, influencing the HELL.
Drugs that increase gastric pH (magnesium hydroxide/aluminium hydroxide, omeprazole) does not affect the bioavailability of Atomoxetine.
Drugs affecting the secretion of norepinephrine, it should be carefully administered concurrently with Atomoxetine (because of the possibility of synergies (greater) pharmacological effect).
Atomoxetine no effect on binding to albumin plasma warfarin, acetylsalicylic acid, phenytoin and diazepam.
Caution is required with concomitant use of Atomoxetine with drugs, lowering the threshold sudorojna activity (antidepressants, antipsychotics, mefloquine, tramadol).
Method of application and dose:
Inside, regardless of meals or during meals, 1 time/day, in the morning.
Treatment should be under the supervision of a doctor with experience of working with patients with attention deficit disorder with hyperactivity.
In case of adverse events while taking the drug 1 time/day patients recommend administration 2 times/day, split dose morning welcome and reception in the late afternoon or early evening.
Medication discontinuation requires a gradual reduction of the dose.
Children and adolescents weighing up to 70 kg the recommended initial daily dose is about 500 mg/kg and increased to therapeutic daily dose of approximately 1.2 mg/kg no earlier than 3 days. In the absence of improvement in the condition of the patient, the total daily dose may be increased to maximum dose of 1.8 mg/kg no earlier than 2-4 weeks after start of treatment.
The recommended maintenance dose is approximately 1.2 mg/kg/day. The recommended maximum daily dose is 1.8 mg/kg or 120 mg.
In children and adolescents with a body weight of 70 kg, the safety of single and total daily doses above 1.8 mg/kg, are not systematically evaluated.
Children and adolescents weighing over 70 kg and adults the recommended initial daily dose is 40 mg and increased to therapeutic daily dose of around 80 mg no earlier than 3 days. In the absence of improvement of a patient the total daily dose may be increased to a maximum dose of 120 mg not earlier than 2-4 weeks after start of treatment.
The recommended maintenance dose is 80 mg. the recommended maximum daily dose is 120 mg.
In children and adolescents weighing more than 70 kg and in adults, the safety of single doses over 120 mg and total daily doses > 150 mg are not systematically evaluated.
In patients with moderate impaired liver function (class b on a scale child-Pugh) primary and supportive therapeutic dose should be reduced to 50% of the normal recommended dose. Patients with severely impaired liver function (class C child-Pugh) primary and supportive therapeutic dose should be reduced to 25% of the usual dose.
In patients with severe renal dysfunction (end-stage chronic renal failure) Atomoxetine excreted from the body more slowly than in healthy individuals. However, when dose adjustment of differences were noted. Therefore, the drug Strater can be administered to patients with ADHD with chronic renal insufficiency, including end-stage, applying the usual dosing regime. Atomoxetine may cause arterial hypertension in patients with end-stage renal disease.
Rules of caps
Capsule drug Strater is not intended for opening. Atomoxetine causes eye irritation. In case of contact with contents of capsule in eyes, immediately rinse them with water and consult a doctor. Hands and contact surfaces must be rinsed with water.
Overdose:
Symptoms: in monotherapy, the most frequently — drowsiness, agitation, hyperactivity, behavioral disorders and symptoms from the blood. Most of the manifestations were mild and moderate severity. It was also noted signs and symptoms of activation of the sympathetic nervous system mild and moderate (e.g., mydriasis, tachycardia, dry mouth). All patients had marked regression of these symptoms. In some cases convulsions.
Reported cases of acute overdose fatalities while taking Atomoxetine in a combination therapy (at least one drug).
Treatment: use activated charcoal to limit absorption, providing ventilation, monitoring of cardiac and vital signs, as well as symptomatic and supportive treatment. If some time passed after ingestion, gastric irrigation. Due to the fact that Atomoxetine has a high affinity to proteins in plasma, the treatment of overdose by dialysis impractical.
Special instructions:
With caution should use the drug in patients with hereditary, congenital or acquired prolonged QT interval.
Symptoms of ADHD in the form of impaired attention and hyperactivity (identified in more than one social environment, e.g. at home and at school) can manifest as lack of concentration, distractibility, excessive impatience, impulsiveness, disorganization, restlessness, and other similar conduct disorder. The diagnosis of ADHD must meet the criteria of ICD-10.
On the background of the drug in clinical trials among children and adolescents increased likelihood of suicidal thoughts. In the course of 12 clinical trials in 2200 patients (including 1357 patients receiving the Strater, and 851 patients who received placebo), including in the group receiving the Strater, 0.37% of cases revealed the development of suicidal thoughts (5 out of 1357 patients) in the placebo group suicidal thoughts have not been identified. During these clinical studies reported a single suicide attempt, completed suicide was not.
In rare cases in patients receiving the Strater, it was noted allergic reactions — rash, angioneurotic edema, urticaria.
Atomoxetine should not be administered for at least 2 weeks after discontinuation of MAO inhibitors. Treatment MAO inhibitors should not begin within 2 weeks after discontinuation of Atomoxetine.
Many patients taking Atomoxetine, there was a slight increase in heart rate (average of <10 beats/min) and/or increased blood pressure (on average <5 mm Hg.St.). In most cases, these changes were not clinically significant effect. There are also cases of orthostatic hypotension.
On the background of the use of psychostimulants, registered for the treatment of ADHD in U.S. children with gross pathology of the heart, breaking its structure was identified increased risk of sudden cardiac death. Atomoxetine does not belong to the class of stimulants, since it has an alternative mechanism of therapeutic action in the treatment of ADHD. However, given the General was the indication for use (ADHD), caution should be exercised in the application of Atomoxetine in patients with heavy physical strain, the simultaneous intake of stimulants, family history of sudden cardiac death. You should not use Atomoxetine in patients with gross pathology of the heart.
It was reported about rare cases of serious liver damage in patients receiving Atomoxetine. In patients with manifestations of jaundice or laboratory parameters identified indicating the abnormal liver function, treatment with Atomoxetine to cancel.
In clinical studies in adults with ADHD, host Atomoxetine, the incidence of urinary retention was higher in comparison with the placebo group. Complaints of urinary retention could potentially be regarded as a result of the use of Atomoxetine.
It is necessary to stop reception of Atomoxetine in the case of seizures, which cannot be explained on other grounds. Caution should be used Atomoxetine in patients with convulsive seizures in history.
The effectiveness of the treatment Atomoxetine for more than 18 months and safety of the treatment them for more than 2 years have not been evaluated systematically.
Aggressive behavior or hostility is often observed in children and adolescents with ADHD. Irrefutable evidence that Atomoxetine can cause aggressive behavior or hostility does not exist. However, in clinical trials, aggressive behavior or hostility was more frequently observed in children and adolescents taking Atomoxetine (without statistically significant differences compared with the placebo group). Patients receiving treatment for ADHD requires observation in relation to the cause of aggressive behavior or hostility.
A well-known occurrence of psychotic and manic symptoms, including hallucinations, delusions and abnormal mood elevation, on the background of the use of Atomoxetine at therapeutic doses in children and adolescents. If you experience these symptoms, it is recommended to assess the extent of their connection with the admission of Atomoxetine and, if necessary, consider drug discontinuation.
On a background of reception of Atomoxetine was marked by the following symptoms: anxiety, agitation, panic attacks, insomnia, irritability, impulsivity, akathisia. Patients receiving Atomoxetine, requires supervision in relation to the development of these symptoms.
Parents and relatives should closely monitor the appearance of all of the above symptoms and suicidal thoughts in children and adolescents taking Atomoxetine, and immediately inform the doctor.
The safety and efficacy of Strattera from elderly patients is not established.
Use in Pediatrics
In children under 6 years of age insufficient data on safety and efficacy of Atomoxetine.
Effects on ability to drive vehicles and management mechanisms
The drug may be accompanied by sleepiness. In this regard, patients receiving Strater, caution should be exercised in the management of mechanical means of increased danger, including a car, until then, until they are sure that Atomoxetine does not cause any violations.
