Strattera

Active material: Atomoxetine
When ATH: N06BA09
CCF: Centrally acting sympathomimetics. Preparation, improves the metabolism of the brain
ICD-10 codes (testimony): F90.0
When CSF: 02.14.03
Manufacturer: ELI LILLY VOSTOK S.A.. (Switzerland)

Pharmaceutical form, composition and packaging

Capsules hard gelatin, size №3, opaque, white / white, with applied dosage “10 mg” and an identification code “Lilly 3227”; contents of capsules – powder from white to almost white.

Excipients: Dimethicone, pre-gelatinized starch.

Ingredients of the capsule shell: Titanium dioxide, sodium lauryl, gelatin.

7 PC. – blisters (1) – packs cardboard.
14 PC. – blisters (1) – packs cardboard.
14 PC. – blisters (2) – packs cardboard.

Capsules hard gelatin, size №3, opaque, yellow / white, with applied dosage “18 mg” and an identification code “Lilly 3238”; contents of capsules – powder from white to almost white.

Excipients: Dimethicone, pre-gelatinized starch.

Ingredients of the capsule shell: Titanium dioxide, sodium lauryl, gelatin, dye iron oxide yellow.

7 PC. – blisters (1) – packs cardboard.
14 PC. – blisters (1) – packs cardboard.
14 PC. – blisters (2) – packs cardboard.

Capsules hard gelatin, size №3, opaque, blue/white, with applied dosage “25 mg” and an identification code “Lilly 3228”; contents of capsules – powder from white to almost white.

Excipients: Dimethicone, pre-gelatinized starch.

Ingredients of the capsule shell: Titanium dioxide, sodium lauryl, gelatin, dye indigo carmine.

7 PC. – blisters (1) – packs cardboard.
14 PC. – blisters (1) – packs cardboard.
14 PC. – blisters (2) – packs cardboard.

Capsules hard gelatin, size №3, opaque, blue / blue, with applied dosage “40 mg” and an identification code “Lilly 3229”; contents of capsules – powder from white to almost white.

Excipients: Dimethicone, pre-gelatinized starch.

Ingredients of the capsule shell: Titanium dioxide, sodium lauryl, gelatin, dye indigo carmine.

7 PC. – blisters (1) – packs cardboard.
14 PC. – blisters (1) – packs cardboard.
14 PC. – blisters (2) – packs cardboard.

Capsules hard gelatin, size №2, opaque, blue / yellow, with applied dosage “60 mg” and an identification code “Lilly 3239”; contents of capsules – powder from white to almost white.

Excipients: Dimethicone, pre-gelatinized starch.

Ingredients of the capsule shell: Titanium dioxide, sodium lauryl, gelatin, dye iron oxide yellow, dye indigo carmine.

7 PC. – blisters (1) – packs cardboard.
14 PC. – blisters (1) – packs cardboard.
14 PC. – blisters (2) – packs cardboard.

Pharmacological action

Centrally acting sympathomimetics. Atomoxetine is a highly potent inhibitor of presynaptic norepinephrine vectors. Atomoxetine has minimal affinity for other noradrenergic receptors or other neurotransmitter transporters or receptors.

Atomoxetine does not apply to psychostimulants and is not an amphetamine derivative. In clinical studies, when the drug was discontinued, there was no increase in symptoms of the disease or any adverse events, associated with withdrawal syndrome.

Pharmacokinetics

Absorption

Once inside atomoxetine rapidly and almost completely absorbed, reaching C_max in plasma after about 1-2 no. Atomoxetine is prescribed with or without food.

Distribution

Atomoxetine is widely distributed in the body. It has high affinity for plasma proteins, Firstly – albumin.

Metabolism

Atomoxetine undergoes primary metabolism with the participation of isoenzyme CYP2D6. The main image is oxidized metabolite 4-gidroksiatomoksetin quickly glyukuroniziruetsya. According to the pharmacological activity of a 4-equivalent Atomoxetine gidroksiatomoksetin, but it circulates in plasma at much lower concentrations.

Although 4-gidroksiatomoksetin initially formed with the participation of CYP2D6, in people with insufficient CYP2D6 activity, 4-hydroxyatomoxetine may be formed by some other cytochrome P450 isoenzymes, but more slowly.

Atomoxetine does not inhibit or enhance the CYP2D6 cycle.

Deduction

Average T_1/2 atomoxetine after oral administration is 3.6 h in patients with severe metabolic and 21 hours in patients with reduced metabolism. Atomoxetine is mainly excreted in the urine as 4-gidroksiatomoksetin-O-glucuronide.

Pharmacokinetics in special clinical situations

Pharmacokinetics in children and adolescents is similar to pharmacokinetics in adults. Pharmacokinetics of atomoxetine in children up to 6 years has not been studied.

Testimony

- attention deficit hyperactivity disorder (ADHD) children 6 and older, adolescents and adults.

Dosage regimen

The drug is taken orally with or without food, 1 time / day, morning. In case of adverse events while taking the drug 1 time / day may be recommended for patients receiving 2 times / day, sharing the dose on the morning welcome and reception in the late afternoon or early evening.

When the drug is discontinued, a gradual dose reduction is not required.

Children and adolescents weighing up to 70 kg the recommended starting daily dose is approximately 500 mcg / kg and increases to a therapeutic daily dose of about 1.2 mg / kg no sooner than 3 day. In the absence of improvement in the patient's condition, the total daily dose may be increased to the maximum dose. 1.8 mg / kg no sooner than 2-4 weeks after the start of dosing.

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 weighing up to 70 kg safety of a single and total daily dose, exceeding 1.8 mg / kg, not systematically evaluated.

Children and adolescents weighing more than 70 kg and adults the recommended starting daily dose is 40 mg and increased up to the therapeutic daily dose of about 80 mg not earlier than 3 day. If there is no improvement of a patient the total daily dose may be increased to a maximum of 120 mg not earlier than 2-4 weeks after the start of dosing.

The recommended maintenance dose is 80 mg. The recommended maximum daily dose is 120 mg.

In children and adolescents weighing more than 70 kg, as well as in adults, the safety of a single dose of more 120 mg and a total daily dose of more 150 mg has not been systematically evaluated.

In patients with moderate liver dysfunction (Class B for Child-Pugh) starting and supporting the therapeutic dose should be reduced to 50% from the usual recommended dose. In patients with severely impaired hepatic function (class C Child-Pugh) starting and supporting the therapeutic dose should be reduced to 25% from normal dose.

In patients with severely impaired renal function (end-stage renal disease), atomoxetine is excreted from the body more slowly, than in healthy individuals. However, no differences were noted with dose adjustments.. Therefore, the drug Strattera^® can be prescribed for ADHD patients with chronic renal failure, including terminal stage, using the usual dosing regimen. Atomoxetine may cause hypertension in patients with end-stage renal disease.

Rules for the use of capsules

Strattera capsules^® not intended for opening. Atomoxetine causes eye irritation. If the contents of the capsule get into the eyes, immediately rinse the eyes with water and consult a doctor.. Hands and contact surfaces must be rinsed with water.

Side effect

Children and adolescents

From the digestive system: Often (>10%) – abdominal pain (18%; including symptoms of abdominal discomfort, pain and discomfort in the epigastrium, stomach discomfort), decreased appetite (16%), vomiting (11%); often (1-10%) – constipation, dyspepsia, nausea (9%), anorexia. These adverse reactions are temporary and, usually, do not require discontinuation of the drug. Due to decreased appetite, some patients experienced a decrease in body weight at the beginning of treatment. (an average of about 0.5 kg), weight loss was greater at higher doses. After primary weight loss in patients, host Stratter^®, there was a slight increase in body weight during long-term therapy. Growth indicators (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 to moderate, are temporary and do not cause treatment withdrawal in a significant number of cases.

Cardio-vascular system: sometimes (0.1-1%) - palpitations, sinus tachycardia.

In placebo-controlled studies in children, receiving Stratter^®, there was an average increase in heart rate by 6 u. / min, and the average increase in systolic and diastolic pressure – on 2 mmHg. compared to placebo.

Patients, treated with atomoxetine, there was orthostatic hypotension (0.2%, n=7) and syncope (0.8%, n=26), due to its effect on noradrenergic tone.

CNS: Often (>10%) – drowsiness (including sedation); often (1-10%) – irritability, mood swings, dizziness; sometimes (0.1-1%) – early morning awakening.

On the part of the organ of vision: often (1-10%) - mydriasis.

Dermatological reactions: often (1-10%) – dermatitis, rash; sometimes (0.1-1%) - itching.

Other: often (1-10%) - flu, fatiguability, weight loss; sometimes (0.1-1%) - weakness.

Side effects in patients with slow metabolism of CYP2D6 substrates, observed in 2% cases and at the same time in 2 times more likely, and also statistically significantly more often, than in patients with a rapid metabolism of CYP2D6 substrates: tremor (4.5% and 0.9% respectively), jekskoriacija (3.9% and 1.7% respectively), fainting (2.5% and 0.7% respectively), conjunctivitis (2.5% and 1.2% respectively), early morning awakening (2.3% and 0.8% respectively), midriaz (2% and 0.6% respectively).

Adult

In adults, the most common side effects, associated with taking atomoxetine, were from the gastrointestinal tract and urogenital tract. No serious adverse events were observed during short or long term treatment with atomoxetine.

From the digestive system: Often (>10%) – decreased appetite, dry mouth, nausea; often (1-10%) – stomach ache (including symptoms of abdominal discomfort, pain and discomfort in the epigastrium, stomach discomfort), constipation, dyspepsia, flatulence.

CNS: Often (>10%) – insomnia (includes difficulty falling asleep and sleep disturbances in the middle of the night); often (1-10%) – decreased libido, dizziness, violation of the quality of sleep, sinus headache; sometimes (0.1-1%) – early morning awakening; rarely (< 0.01%) – syncope.

Cardio-vascular system: often (1-10%) – tides (blood), palpitations, tachycardia; infrequently (0.1-1.0%) – cold sensation in the lower extremities; rarely (< 0.01%) according to spontaneous (post-marketing messages) – peripheral vascular responses and / or Raynaud's syndrome and the risk of recurrence of Raynaud's syndrome.

In placebo-controlled studies in adults, receiving Stratter^®, there was an average increase in heart rate by 6 u. / min, and an average increase in systolic (about 3 mmHg.) and diastolic (about 1 mmHg.) Blood pressure compared with placebo.

From the urinary system: often (1-10%) – dizurija, urinary retention.

On the part of the reproductive system: often (1-10%) – dysmenorrhoea, abnormal ejaculation, lack of ejaculation, erectile dysfunction, erectile dysfunction, menstrual disorders, prostatitis; rarely (<0.01%) according to spontaneous (postmarketing) messages – painful or prolonged erection, pain in the external genital area in men.

Skin and subcutaneous tissue: often (1-10%) – dermatitis, increased sweating.

Other: often (1-10%) – fatiguability, chills, weight loss.

Contraindications

- Zakrыtougolynaya glaucoma;

- severe heart damage;

-the simultaneous use of MAO inhibitors;

- Hypersensitivity to the drug.

FROM caution the drug should be used in patients with arterial hypertension, taxikardiej, cardiovascular diseases, severe physical overload, simultaneous intake of psychostimulants, family history of sudden cardiac death, cerebrovascular, seizures in history, as well as for conditions, which can lead to arterial hypotension.

Pregnancy and lactation

Clinical experience with Strattera^® insufficient during pregnancy, therefore, the drug should be prescribed during pregnancy only if, if the expected benefit of therapy to the mother significantly outweighs the potential risk to the fetus.

Unknown, is atomoxetine excreted in breast milk. If it is necessary to prescribe the drug to a nursing mother, caution is required..

Cautions

The drug should be used with caution in patients with hereditary, congenital or acquired prolongation of the QT interval.

The symptoms of ADHD as impaired attention and hyperactivity (identified in more than one social environment, eg, and at home, and school) may manifest itself as a lack of concentration, distractibility, excessive impatience, impulsiveness, disorganization, restlessness, and other similar conduct disorders. The diagnosis of ADHD should meet the criteria of ICD-10.

While taking the drug in clinical trials in children and adolescents, the likelihood of developing suicidal thoughts increased.. In the course of 12 clinical trials in 2200 patients (including 1357 patients, receiving Stratter^® and 851 patient, receiving placebo), of them in the group, receiving Stratter^®, in 0.37% cases revealed the development of suicidal thoughts (5 from 1357 patients), no suicidal thoughts were detected in the placebo group. One suicide attempt has been reported in these clinical trials, there were no completed suicides.

In rare cases, patients, host Stratter^®, allergic reactions have been reported – rash, angioedema, hives.

Atomoxetine should not be administered for at least 2 weeks after discontinuation of MAO inhibitors. Treatment of MAO inhibitors should not be initiated within 2 weeks after discontinuation of atomoxetine.

Many patients, taking atomoxetine, there was a slight increase in heart rate (on average <10 u. / min) and / or increase in blood pressure (on average <5 mmHg.). In most cases, these changes were not clinically significant effect. Also, there were cases of orthostatic hypotension.

Against the background of the use of psychostimulants, registered for the treatment of ADHD in the United States in children with severe heart disease, violating its structure, an increased risk of sudden cardiac death has been identified. Atomoxetine does not belong to the class of psychostimulants, tk. has an alternative therapeutic mechanism in the treatment of ADHD. Nonetheless, taking into account the general registered indication for use (ADHD), caution should be exercised when using atomoxetine in patients with severe physical overload, simultaneous intake of psychostimulants, with a family history of sudden cardiac death. Atomoxetine should not be used in patients with severe heart disease.

Reported rare cases of serious liver damage while taking atomoxetine (Two cases are described by higher levels of liver enzymes and bilirubin in the 2 million. patients). Patients with symptoms of jaundice or laboratory parameters identified, indicative of impaired liver function, treatment with atomoxetine must be canceled.

In clinical trials in adult ADHD patients, taking atomoxetine, the incidence of urinary retention was higher compared to the placebo group. Complaints of urinary retention can potentially be regarded as a result of the use of atomoxetine.

Stop taking atomoxetine if seizures develop, which cannot be explained by other reasons. Atomoxetine should be used with caution in patients with a history of seizures.

The effectiveness of atomoxetine treatment more 18 months and the safety of treatment for them over 2 years have not been systematically evaluated.

Aggressive behavior or hostility is common in children and adolescents with ADHD. Irrefutable evidence, that atomoxetine may cause violent behavior or hostility does not exist. However, in clinical studies, aggressive behavior or hostility was observed more often in children and adolescents., taking atomoxetine (no statistically significant difference compared with placebo group). Patients, receiving treatment for ADHD, requires supervision in relation to the onset of aggressive behavior or hostility.

Cases of psychotic and manic symptoms known, including hallucinations, delirium and pathological mood elevation, against the background of the use of atomoxetine in therapeutic doses in children and adolescents. If these symptoms occur, it is recommended to assess the degree of their connection with the intake of atomoxetine and, if necessary, consider discontinuing the drug.

The following symptoms have been noted while taking atomoxetine: alarm, ažitaciâ, panic attacks, insomnia, irritability, impulsiveness, akathisia. Patients, receiving atomoxetine, monitoring is required for the development of these symptoms.

Parents and loved ones should carefully monitor the occurrence of all of the above symptoms and suicidal thoughts in children and adolescents., taking atomoxetine, and immediately inform your doctor about it.

Safety and effectiveness of Stratters^® in elderly patients have not been established.

Use in Pediatrics

In children aged 6 years insufficient data on the safety and effectiveness of atomoxetine.

Effects on ability to drive vehicles and management mechanisms

Taking the drug may be accompanied by drowsiness. In this regard, patients, host Stratter^®, care should be taken when operating hazardous mechanical means, incl. car, until, until they are confident, that atomoxetine does not cause any violations.

Overdose

Symptoms: with monotherapy, most often – drowsiness, excitation, hyperactivity, behavior disorder and gastrointestinal symptoms. Most manifestations were mild to moderate. Signs and symptoms of mild to moderate sympathetic nervous system activation have also been reported. (eg, midriaz, tachycardia, dry mouth). All patients showed regression of these symptoms.. In some cases, convulsions have been reported.

Cases of acute fatal overdose have been reported when taking atomoxetine as part of combination therapy (least, with one drug).

Treatment: it is recommended to provide ventilation of the lungs, monitor cardiac activity and vital signs, as well as symptomatic and supportive treatment. Gastric lavage may be indicated, if a little time has passed after taking the drug. Activated carbon may be beneficial to limit absorption. Unnecessarily. atomoxetine has a high affinity for plasma proteins, overdose treatment with dialysis is likely to be inappropriate.

Drug Interactions

With the simultaneous use of Strattera^® with β agonists₂-adrenergic receptors, it is possible to enhance their action on the cardiovascular system (this combination be used with caution). In healthy adult volunteers, the effect of salbutamol in a standard inhaled dose 200 mcg on hemodynamic parameters was insignificant compared with the effect of the indicated dose of this drug when administered intravenously. Simultaneous use of atomoxetine in a dose 80 mg / day for 5 days did not lead to an increase in the indicated effects of albuterol. Heart rate after multiple inhalations of albuterol in a dose 800 μg was characterized by similar values ​​in conditions as monotherapy, and in combination with the use of atomoxetine.

Simultaneous administration of atomoxetine with drugs, causing QT prolongation (neuroleptics, antiaritmiki, moxifloxacin, Erythromycin, tricyclic antidepressants, Lithium carbonate), as well as drugs, causing electrolyte imbalance (Diuretic) and CYP2D6 inhibitors, increases the risk of prolonged QT interval.

Atomoxetine does not cause clinically significant inhibition or induction of isoenzymes of the cytochrome P450 system, including CYP1A2, CYP3A, CYP2D6 и CYP2C9. In patients with pronounced metabolism of CYP2D6 substrates, CYP2D6 inhibitors increase C_ss atomoxetine in blood plasma in an equilibrium state to a level, similar to that in patients with slow metabolism of CYP2D6 substrates.

Based on in vitro studies supposed, that the administration of cytochrome P450 inhibitors to patients with a slow metabolism of CYP2D6 substrates does not increase the concentration of atomoxetine in blood plasma. Patients, use the drug inhibitors of CYP2D6, gradual titration of atomoxetine is recommended.

Due to possible effects on blood pressure, Stratter^® must be used with caution when combined with drugs, affecting blood pressure.

Preparations, increasing the pH of gastric juice (magnesium hydrochloride / aluminum hydroxide, omeprazole) do not affect the bioavailability of atomoxetine.

Preparations, affecting the secretion of norepinephrine, should be administered with caution at the same time as atomoxetine due to the possibility of enhancement or synergism of the pharmacological effect.

Atomoxetine does not affect plasma albumin binding of warfarin, acetylsalicylic acid, phenytoin and diazepam.

Caution is required with the simultaneous use of atomoxetine with drugs, lowering the threshold of seizure activity (antidepressants, neuroleptics, mefloxin, tramadol).

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

List B. The drug should be stored out of reach of children at temperature from 15 ° to 25 ° C. Shelf life - 3 year.