Strattera®

Composition and release form

in contour cell packs of 7 or 14 pcs.; in a cardboard pack 1 or 2 (14 pcs.) packages.

in contour cell packs of 7 or 14 pcs.; in a cardboard pack 1 or 2 (14 pcs.) packages.

in contour cell packs of 7 or 14 pcs.; in a cardboard pack 1 or 2 (14 pcs.) packages.

in contour cell packs of 7 or 14 pcs.; in a cardboard pack 1 or 2 (14 pcs.) packages.

in contour cell packs of 7 or 14 pcs.; in a cardboard pack 1 or 2 (14 pcs.) packages.

Description of the dosage form

Capsules 10 mg

- hard gelatin, size No. 3, opaque, white/white, with a dosage of “10 mg” and identification code “Lilly 3227” applied.

Capsules 18 mg

- hard gelatin, size No. 3, opaque, yellow/white, with the dosage “18 mg” and the identification code “Lilly 3238” applied.

Capsules 25 mg

- hard gelatin, size No. 3, opaque, blue/white, with a dosage of “25 mg” and identification code “Lilly 3228” applied.

Capsules 40 mg

- hard gelatin, size No. 3, opaque, blue/blue, with a dosage of “40 mg” and identification code “Lilly 3229” printed.

Capsules 60 mg

- hard gelatin, size No. 2, opaque, blue/yellow, with a dosage of “60 mg” and identification code “Lilly 3239” applied.

Capsule contents

- white to almost white powder.

Pharmacodynamics

Atomoxetine is a highly selective, potent inhibitor of presynaptic norepinephrine transporters. Atomoxetine has minimal affinity for other noradrenergic receptors or other neurotransmitter transporters or receptors.

Atomoxetine is not a psychostimulant and is not an amphetamine derivative. In clinical studies, when discontinuing the drug, there was no increase in symptoms of the disease or any adverse events associated with withdrawal syndrome.

Pharmacokinetics

Suction.

After oral administration, atomoxetine is rapidly and almost completely absorbed, reaching Cmax in plasma in approximately 1–2 hours. Atomoxetine is prescribed regardless of meals or with meals.

Distribution.

Atomoxetine is well distributed in the body. It has a high affinity for plasma proteins, primarily albumin.

Metabolism.

Atomoxetine undergoes primary metabolism with the participation of the CYP2D6 isoenzyme. The main oxidized metabolite formed, 4-hydroxyatomoxetine, is rapidly glucuronidated. In terms of pharmacological activity, 4-hydroxyatomoxetine is equivalent to atomoxetine, but circulates in plasma in much lower concentrations.

Although 4-hydroxyatomoxetine is primarily formed by CYP2D6, in people with insufficient CYP2D6 activity, 4-hydroxyatomoxetine can be formed by some other cytochrome P450 isoenzymes, but more slowly.

Atomoxetine does not inhibit or enhance the CYP2D6 cycle.

Excretion.

The average T1/2 of atomoxetine after oral administration is 3.6 hours in patients with pronounced metabolism and 21 hours in patients with reduced metabolism. Atomoxetine is primarily excreted in urine as 4-hydroxyatomoxetine-O-glucuronide.

Pharmacokinetics in special clinical situations

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

Pharmacological properties of the drug Strattera

Pharmacodynamics . Atomoxetine is a highly selective, potent inhibitor of the presynaptic norepinephrine transporter, its likely mechanism of action without direct effects on the serotonin and dopamine transporters. Atomoxetine has minimal affinity for other noradrenergic receptors or other neurotransmitter transporters or receptors. Atomoxetine has two main oxidative metabolites: 4-hydroxyatomoxetine and N-desmethylatomoxetine. 4-Hydroxyatomoxetine has the same potency as a norepinephrine transporter inhibitor as atomoxetine but, unlike the latter, this metabolite also has some serotonin transporter inhibitory activity. However, as a rule, such an effect is minimal, since the majority of 4-hydroxyatomoxetine is further metabolized and circulates in the blood plasma at much lower concentrations (1% atomoxetine concentration in active metabolizers (EMs) and 0.1% atomoxetine concentration in active metabolizers (EMs) and 0.1% atomoxetine concentration in slow metabolizers (PM)). N-desmethylatomoxetine has significantly lower pharmacological activity compared to atomoxetine. It circulates in the blood plasma at lower concentrations in active metabolizers and in concentrations comparable to those of the parent substance in poor metabolizers at steady state. Atomoxetine is not a psychostimulant or an amphetamine derivative. In a randomized, double-blind, placebo-controlled study of addictogenic potential in adult patients, atomoxetine was not associated with a response pattern indicative of stimulant or euphoriant properties when comparing the effects of atomoxetine with placebo. The drug was studied in trials involving more than 4,000 children and adolescents with attention deficit hyperactivity disorder (ADHD). The effectiveness of Strattera in the treatment of ADHD was established in six randomized, double-blind, placebo-controlled studies of 6–9 weeks duration. Signs and symptoms of ADHD were assessed by comparing mean changes from baseline to endpoint for patients receiving Strattera and placebo. Each of the 6 studies demonstrated superior efficacy of atomoxetine over placebo in reducing ADHD signs and symptoms with statistical significance. In addition, the effectiveness of atomoxetine on symptoms was demonstrated in a 1-year placebo-controlled trial of more than 400 patients, conducted primarily in Europe (about 3 months of open-label acute treatment followed by 9 months of double-blind placebo-controlled maintenance treatment ). The proportion of patients who relapsed at 1 year was 18.7% and 31.4% (atomoxetine and placebo, respectively). After 1 year of atomoxetine treatment, patients continuing atomoxetine for an additional 6 months were less likely to experience relapse or partial relapse of symptoms compared with patients who stopped active treatment and switched to placebo (2% and 12%, respectively). Children and adolescents should have ongoing assessments periodically during long-term treatment. The drug was effective when given as a single daily dose or as a divided dose given in the morning and afternoon/early evening. When administered once daily, a statistically significant reduction in the severity of ADHD symptoms was demonstrated compared to placebo, according to teachers and parents. Atomoxetine does not worsen tics in patients with ADHD and concomitant motor tics or Tourette's syndrome. A total of 536 adult patients with ADHD were enrolled in 2 randomized, double-blind, placebo-controlled clinical trials lasting 10 weeks. Patients received Strattera 2 times a day with dose titration according to clinical response within the range of 60–120 mg/day. The average final dose of the drug in these studies was approximately 95 mg/day. These studies demonstrated statistically significant improvement in ADHD symptoms with Strattera, as measured by the CAARS ADHD symptom scores. The observed rates of improvement in symptoms were lower in adults than in children. Long-term persistence of the effect in adults was not noted. Pharmacokinetics. The pharmacokinetic parameters of atomoxetine in children and adolescents are similar to those in adults. The pharmacokinetics of atomoxetine in children under 6 years of age have not been determined. Absorption : Atomoxetine is rapidly and almost completely absorbed after oral administration, reaching mean peak plasma concentrations approximately 1 to 2 hours after dosing. The absolute bioavailability of atomoxetine after oral administration was 63–94%, depending on differences in the first-pass metabolism of patients. Atomoxetine may be administered with or without food. Distribution : atomoxetine is widely distributed and actively (98%) binds to plasma proteins, primarily albumin. Biotransformation : Atomoxetine undergoes biotransformation mainly through cytochrome P450 (CYP2D6). Patients with reduced activity of this pathway (poor metabolizers) make up about 7% of the Caucasian group and have higher plasma concentrations of atomoxetine compared to people with normal activity (extensive metabolizers). For poor metabolizers, the AUC of atomoxetine is approximately 10 times higher; Steady-state and maximum concentrations are approximately 5 times higher than for active metabolizers. The main metabolite resulting from oxidation is 4-hydroxyatomoxetine, which quickly undergoes glucuronidation. 4-hydroxyatomoxetine has similar activity to atomoxetine, but circulates in the blood plasma at significantly lower concentrations. Although 4-hydroxyatomoxetine is formed primarily by CYP2D6, in subjects with insufficient CYP2D6 activity several other cytochrome P450 enzymes are involved in the formation of 4-hydroxyatomoxetine, but at a lower rate. Atomoxetine at therapeutic doses does not inhibit or induce CYP2D6. Removal . The mean elimination half-life of atomoxetine after oral administration is 3.6 hours for active metabolizers and 21 hours for poor metabolizers. Atomoxetine is excreted as an o-glucuronide, mainly in the urine. The pharmacokinetics of atomoxetine are linear over the dose range studied for both active and poor metabolizers. Special groups of patients . Liver failure leads to a decrease in the clearance of atomoxetine - an increase in the effect of atomoxetine (AUC is doubled in moderate liver failure and 4-fold in severe liver failure) and an increase in the half-life of the parent substance compared to that observed in healthy subjects (with the same genotype of the active metabolizer CYP2D6) . In patients with moderate or severe liver damage (Child-Pugh class B and C), the initial and final doses should be adjusted. The mean plasma concentrations of atomoxetine for subjects with end-stage renal disease (ESRD) were generally higher than the mean for healthy control subjects; accordingly, the maximum concentration (difference of 7%) and AUC0-∞ (difference of about 65%) increase. By adjusting the dose according to body weight, discrepancies between the two groups of subjects are minimized. The pharmacokinetics of atomoxetine and its metabolites in subjects with ESRD indicate that dose adjustment is not necessary.

Contraindications

hypersensitivity to the drug;

severe heart damage;

simultaneous use with MAO inhibitors;

angle-closure glaucoma.

Carefully

the drug should be used in patients with arterial hypertension, tachycardia, cardiovascular diseases, severe physical overload, concomitant use of psychostimulants, sudden cardiac death in a family history, cerebrovascular accident, history of seizures, as well as in conditions that can lead to arterial hypotension.

Side effects

Children and teenagers

From the digestive system:

very often (>10%) - abdominal pain (18%; including symptoms of abdominal discomfort, pain and discomfort in the epigastrium, discomfort in the stomach), loss of appetite (16%), vomiting (11%); often (1–10%) - constipation, dyspepsia, nausea (9%), anorexia. These adverse reactions are temporary and, as a rule, do not require discontinuation of the drug. Due to decreased appetite, some patients experienced a decrease in body weight at the beginning of treatment (on average about 0.5 kg), weight loss was greater at higher doses. After an initial decrease in body weight, patients taking Strattera experienced a slight increase in body weight with long-term therapy. Growth indicators (weight and height) after two years of treatment were close to normal.

Nausea (9%) and vomiting (11%) are most likely to occur during the first month of treatment, are usually mild to moderate, are temporary, and do not cause discontinuation of treatment in a significant number of cases.

From the cardiovascular system:

(0.1–1%) - palpitations, sinus tachycardia.

In placebo-controlled studies, children receiving Strattera experienced a mean increase in heart rate of 6 beats/min and a mean increase in SBP and DBP of 2 mmHg. compared to placebo.

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

From the side of the central nervous system:

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

From the side 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, fatigue, weight loss; sometimes (0.1–1%) - weakness.

Side effects in patients with slow metabolism of CYP2D6 substrates, observed in 2% of cases and 2 times more often, and also statistically significantly more often than in patients with rapid metabolism of CYP2D6 substrates: tremor (5.1 and 1.1%, respectively) , fainting (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 common side effects associated with taking atomoxetine were the gastrointestinal and urogenital tract. No serious adverse events were observed during short or long-term treatment with atomoxetine.

From the digestive system:

very often (>10%) - loss of appetite, dry mouth, nausea; often (1–10%) - abdominal pain (including symptoms of abdominal discomfort, pain and discomfort in the epigastrium, discomfort in the stomach), constipation, dyspepsia, flatulence.

From the side of the central nervous system:

very often (>10%) - insomnia (includes difficulty falling asleep and sleep disturbances in the middle of the night); often (1–10%) - decreased libido, dizziness, impaired sleep quality, sinus headache; sometimes (0.1–1%) - early morning awakening.

From the cardiovascular system:

often (1–10%) - flushing of the face, palpitations, tachycardia; sometimes (0.1–1%) - a feeling of cold in the lower extremities; very rarely (<0.01%) according to spontaneous (post-marketing reports) - peripheral vascular reactions and/or Raynaud's syndrome and the risk of recurrence of Raynaud's syndrome.

In placebo-controlled studies, adults treated with Strattera experienced a mean increase in heart rate of 6 beats/min and a mean increase in sBP (about 3 mmHg) and dBP (about 1 mmHg) compared to placebo.

From the urinary system:

often (1–10%) - dysuria, difficulty urinating.

From the reproductive system:

often (1–10%) - dysmenorrhea, ejaculation disorders, lack of ejaculation, erectile dysfunction, erectile dysfunction, menstrual irregularities, orgasm disorders; very rarely (<0.01%), according to spontaneous (post-marketing) reports, painful or prolonged erection.

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

Other:

often (1–10%) - weakness, drowsiness, chills, weight loss.

Side effects of Strattera

Children and adolescents : The side effects most commonly associated with atomoxetine are abdominal pain and decreased appetite (in approximately 18% and 16% of patients, respectively). Usually these phenomena are temporary and rarely lead to the need to stop taking the drug. Due to a decrease in appetite, some patients experienced weight loss in the early stages of therapy (on average approximately 0.5 kg), as a rule, this was observed when taking maximum doses of the drug. Subsequently, with long-term therapy after the initial loss of body weight, a slight increase was observed. Growth indicators (weight and height) after 2 years of treatment were generally normal. Nausea and vomiting are most often observed during the first month of treatment (in 9 and 11% of patients, respectively), usually mild to moderate, are temporary, and do not cause treatment discontinuation in a significant number of cases. In pediatric placebo-controlled studies, patients taking atomoxetine experienced a slight increase in heart rate of approximately 6 beats/min and a slight increase in systolic and diastolic blood pressure of approximately 2 mm. rt. Art. compared to placebo. In placebo-controlled studies in adults, a slight increase in heart rate of 6 beats per minute and a slight increase in systolic (approximately 3 mmHg) and diastolic (approximately 1 mmHg) were observed in patients taking atomoxetine. BP compared with placebo. Due to the effect on noradrenergic tone, orthostatic hypotension (0.2%, N=7) and syncope (0.8%, N=26) were observed in patients taking atomoxetine. If patients are prone to hypotension or conditions associated with sudden changes in heart rate or blood pressure, atomoxetine should be used with caution. The following table of side effects was compiled from reports of side effects, laboratory data from clinical trials in children and adults, and spontaneous reports after the drug was marketed. Table. Adverse reactions due to atomoxetine Frequency assessment: very common (≥10%), common (≥1% and ≤10%), uncommon (≥0.1% and ≤1%), rare (≥0.01% and ≤0 .1%), very rare (≤0.01%), data from spontaneous reports (frequency unknown).

* These data were obtained from spontaneous reports, so the exact frequency cannot be determined.

Poor metabolizers of CYP2D6 . These side effects were observed in at least 2% of patients who are poor metabolizers (PM) of CYP2D6, and were either 2 times more likely or statistically significantly more frequent in patients who are PM (poor metabolizers) compared to patients who are extensive metabolizers (EM) of CYP2D6: decreased appetite (24.1% PM, 17.0% EM); insomnia (10.5% PM, 6.8% EM); moderate insomnia (3.8% PM, 1.5% EM); enuresis (3.0% PM, 1.2% EM); depressed mood (3.0% PM, 1.0% EM); tremor (5.1% PM, 1.1% EM); early morning awakenings (3.0% PM, 1.1% EM); conjunctivitis (3.0% PM, 1.5% EM); fainting (2.1% PM, 0.7% EM); mydriasis (2.5% PM, 0.7% EM). The following adverse events did not meet these criteria but were reported more frequently by PM patients than by EM patients: fear (2.5% PM, 2.2% EM); depression (2.5% PM, 1.9% EM). In addition, in trials lasting up to 10 weeks, weight loss was greater in RM patients (mean 0.6 kg in EM and 1.1 kg in PM). Adults : In adults, the most commonly reported adverse events were gastrointestinal or genitourinary related. Complaints of urinary retention or bladder instability in adults should be considered as potentially related to atomoxetine. There were no safety concerns observed during acute or long-term use.

Interaction

With simultaneous use of Strattera with β2-adrenergic receptor agonists, their effect on the cardiovascular system may be enhanced (use this combination with caution). In healthy adult volunteers, the effect of salbutamol in a standard inhaled dose of 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 at a dose of 80 mg/day for 5 days did not lead to an increase in these effects of salbutamol. Heart rate after repeated inhalations of salbutamol at a dose of 800 mcg was characterized by similar values ​​in both monotherapy and in combination with atomoxetine.

Co-administration of atomoxetine with drugs that cause prolongation of the QT interval (neuroleptics, antiarrhythmics, moxifloxacin, erythromycin, tricyclic antidepressants, lithium carbonate), as well as with drugs that cause electrolyte imbalance (diuretics), and CYP2D6 inhibitors, increases the risk of prolongation of the QT interval.

Atomoxetine does not cause clinically significant inhibition or induction of isoenzymes of the cytochrome P450 system, including CYP1A2, CYP3A, CYP2D6 and CYP2C9. In patients with extensive metabolism of CYP2D6 substrates, CYP2D6 inhibitors increase the plasma CSS of atomoxetine at steady state to a level similar to that in patients with poor metabolism of CYP2D6 substrates.

Based on in vitro

It is assumed that the administration of cytochrome P450 inhibitors to patients with poor metabolism of CYP2D6 substrates does not increase the concentration of atomoxetine in the blood plasma. For patients using CYP2D6 inhibitor drugs, gradual titration of the dose of atomoxetine is recommended.

Due to the possible effect on blood pressure, Strattera should be used with caution when combined with drugs that affect blood pressure.

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

Drugs that affect the secretion of norepinephrine should be prescribed with caution simultaneously with atomoxetine (due to the possibility of synergism (increased) pharmacological effect).

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

Caution is required when using atomoxetine simultaneously with drugs that lower the threshold of convulsive activity (antidepressants, antipsychotics, mefloquine, tramadol).

Special instructions for the use of Strattera

Allergic reactions, including skin rash, angioedema and urticaria, were not common but have been reported in patients taking atomoxetine. Many patients taking atomoxetine experience a moderate increase in heart rate (average ≤10 beats/min) and/or increase in blood pressure (average ≤5 mmHg). Typically, these changes are not clinically significant. Atomoxetine should be used with caution in patients with hypertension (arterial hypertension), tachycardia, cardiovascular or cerebrovascular diseases. Heart rate and blood pressure must be monitored throughout the entire period of treatment with the drug. Due to cases of orthostatic hypotension during use of the drug, it should be used with caution in any condition where patients may be prone to hypotension. Atomoxetine should be used with caution in patients with congenital or acquired long QT syndrome or a related history of QT . In patients with manifestations of jaundice or changes in laboratory parameters indicating impaired liver function, treatment with Strattera should be discontinued. Very rarely, toxic manifestations from the liver are observed in the form of increased levels of liver transaminases or bilirubin with jaundice. It is necessary to monitor the growth and development of children during treatment with atomoxetine; if the patient does not have an increase in growth or weight gain, it is advisable to reduce the dose or discontinue therapy. There is no evidence to suggest that atomoxetine has a negative effect on cognition or puberty, although there is limited evidence from long-term studies. Therefore, patients receiving long-term therapy should be closely monitored. Suicidal behavior (suicide attempts and suicidal thoughts) was observed in patients during atomoxetine therapy. In double-blind clinical studies, suicidal behavior was observed with a frequency of 0.44% in patients treated with atomoxetine (6 of 1357 patients, 1 case of suicide attempt and 5 cases of suicidal ideation). No such behavior was observed in the placebo group (n=851). The age limits in which these phenomena were noted in children were 7–12 years. It should be noted that the number of adolescent patients included in clinical trials was low. Hostility (primarily aggression, opposition, and anger) and emotional lability were reported more frequently in clinical studies among children and adolescents receiving Strattera compared to placebo. Patients receiving therapy for ADHD should be monitored for the emergence or worsening of suicidal behavior, hostility, and emotional lability. As with other psychotropic drugs, the possibility of isolated serious cases of negative effects on the patient’s psyche cannot be excluded. Taking atomoxetine is associated with a potential risk of epileptic seizures. Atomoxetine should be used with caution in patients with a history of epileptic seizures. Discontinuation of atomoxetine is advisable for any patient who develops an attack or increases the frequency of attacks if another cause has been excluded (or not determined). Strattera is not indicated for the treatment of cases of major depression and/or anxiety, since the results of clinical studies conducted in adult patients did not show any effect compared to placebo and were therefore negative. Use during pregnancy and lactation. Clinical experience with the use of Strattera during pregnancy is insufficient. Animal studies generally do not indicate a direct negative effect on pregnancy, embryonic development, childbirth and postnatal development, therefore it should be prescribed during pregnancy only if the expected benefit of therapy to the mother significantly outweighs the potential risk to the fetus. Atomoxetine and/or its metabolites are excreted into rat milk. It is unknown whether atomoxetine is excreted into human breast milk. Due to the lack of data, the use of atomoxetine during breastfeeding should be avoided. Children . Atomoxetine is indicated for children from 6 years of age as part of a comprehensive treatment program. The safety and effectiveness of Strattera in children under 6 years of age have not been determined and the drug should not be used to treat children under 6 years of age. The ability to influence the speed of reaction when driving vehicles or other mechanisms . No studies have been conducted on the effects on driving. Atomoxetine has been associated with increased fatigue in some patients compared to placebo. Only in children did atomoxetine cause increased sleepiness compared with placebo. Patients are advised to be careful when operating vehicles and dangerous machinery until they are sure that atomoxetine does not affect their attention and ability to work.

Directions for use and doses

Inside,

regardless of meals or during meals, 1 time/day, in the morning.

Treatment should be carried out under the supervision of a physician experienced in working with patients with attention deficit hyperactivity disorder.

In case of adverse events when taking the drug once a day, patients can be recommended to take it twice a day, dividing the dose into a morning dose and a late afternoon or early evening dose.

Discontinuation of the drug does not require a gradual dose reduction.

For children and adolescents weighing up to 70 kg, the recommended initial daily dose is approximately 500 mcg/kg and increased to a therapeutic daily dose of approximately 1.2 mg/kg no earlier than after 3 days. If there is no improvement in the patient's condition, the total daily dose can be increased to a maximum dose of 1.8 mg/kg no earlier than 2-4 weeks after starting the drug.

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, the safety of single and total daily doses exceeding 1.8 mg/kg has not been systematically assessed.

For children and adolescents weighing more than 70 kg, as well as adults, the recommended initial daily dose is 40 mg and is increased to a therapeutic daily dose of about 80 mg no earlier than after 3 days. If there is no improvement in the patient's condition, the total daily dose can be increased to a maximum dose of 120 mg no earlier than 2-4 weeks after starting the drug.

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 than 120 mg and a total daily dose of more than 150 mg has not been systematically assessed.

In patients with moderate hepatic impairment (Child-Pugh class B), the initial and maintenance therapeutic dose should be reduced to 50% of the usual recommended dose. In patients with severely impaired liver function (class C on the Child-Pugh scale), the initial and maintenance therapeutic dose should be reduced to 25% of the usual dose.

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

Rules for using capsules

Strattera capsules are not intended to be opened. Atomoxetine causes eye irritation. If the contents of the capsule get into your eyes, rinse them immediately with water and consult a doctor. Hands and contact surfaces must be washed with water.

Use of the drug Strattera

Treatment should be carried out by an ADHD specialist. The diagnosis must comply with the criteria of the Diagnostic and Statistical Manual of Mental Disorders, IV revision (DSM-IV) or the basic principles of ICD-10. Intended for oral use. The drug can be used as a single daily dose in the morning with or without food. If the patient does not have a satisfactory clinical response when using Strattera as a single daily dose, twice daily use may be recommended with an even distribution of the dose in the morning and afternoon or early evening. Dosage for children/adolescents weighing up to 70 kg : Initiate treatment at a total daily dose of 0.5 mg/kg body weight. This dose should be taken for at least 7 days before increasing the dose based on clinical response and tolerability. The recommended maintenance dose is approximately 1.2 mg/kg/day (depending on the patient's body weight and previous dosing of atomoxetine). There is no additional effect from using a dose of more than 1.2 mg/kg/day. The safety of single doses greater than 1.8 mg/kg/day and total daily doses greater than 1.8 mg/kg has not been systematically evaluated. The duration of treatment is determined individually. In some cases, long-term treatment is possible (until adulthood or more). Dosage for children/adolescents weighing more than 70 kg : Initial total daily dose is 40 mg. This dose should be continued for at least 7 days before the next dose increase based on clinical response and tolerability. The recommended maintenance dose is 80 mg. There is no additional effect from using a dose of more than 80 mg. The maximum recommended total daily dose is 100 mg. The safety of single doses above 120 mg and total daily doses above 150 mg has not been systematically evaluated. The duration of treatment is determined individually. In some cases, it may be advisable to continue treatment until the patient reaches adulthood. Additional information on the safety of this drug: Atomoxetine should be used in accordance with national clinical guidelines for the treatment of ADHD, where available. No significant withdrawal symptoms were described in the research program. In cases of significant negative clinical effect, atomoxetine should be discontinued immediately or by gradually reducing the dose. If patients continue treatment with atomoxetine for more than 1 year, reassessment of the need for therapy by an ADHD specialist is recommended. For adolescents whose symptoms persist into adulthood and in whom there is a clear clinical response to treatment, continued treatment into adulthood may be appropriate. However, it is not advisable to begin treatment of a patient in adulthood. A comprehensive treatment program typically includes psychological, educational and social measures and is aimed at stabilizing children with behavioral syndrome. This syndrome is characterized by symptoms that include chronic insufficient attention span, tendency to distraction, emotional lability, impulsivity, moderate or severe hyperactivity, minor neurological symptoms and abnormalities on the EEG. Not necessary, but learning ability may be impaired. Pharmacological treatment is not indicated for all people with this syndrome, and the decision regarding the use of medication should be based on a very careful assessment of the severity of the child's symptoms, taking into account the child's age, persistence and severity of symptoms. Special groups of patients . Hepatic impairment : For patients with moderate hepatic impairment (Child-Pugh class B), the initial and maintenance therapeutic dose of Strattera should be reduced to 50% of the usual recommended dose. In patients with severely impaired liver function (class C on the Child-Pugh scale), the initial and maintenance therapeutic dose should be reduced to 25% of the usual dose. Renal failure : The systemic exposure of atomoxetine in patients with end-stage renal disease is approximately 65% ​​higher than in healthy subjects, but no difference was observed when the dose was adjusted based on body weight. Therefore, Strattera can be administered to patients with ADHD and chronic renal failure, including end-stage renal disease, using the usual dosing regimen. Atomoxetine may worsen hypertension (arterial hypertension) in patients with end-stage renal failure. Approximately 7% of Caucasians have a genotype that corresponds to a nonfunctional CYP2D6 enzyme (so-called “poor metabolizers” of CYP2D6). Patients with this genotype will experience several times greater exposure to atomoxetine compared to patients with a functional enzyme. Thus, slow metabolizers are at greater risk of side effects. For patients with a genotype corresponding to poor metabolizers, a lower initial dose and a slower dose increase are recommended. The drug is not used in elderly patients.

Overdose

Symptoms:

with monotherapy, the most common symptoms are drowsiness, agitation, hyperactivity, behavioral disturbances and gastrointestinal symptoms. Most manifestations were mild to moderate in severity. Signs and symptoms of mild to moderate activation of the sympathetic nervous system (eg, mydriasis, tachycardia, dry mouth) have also been noted. All patients experienced regression of these symptoms. In some cases, convulsions were noted.

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

Treatment:

administering activated charcoal to limit absorption, providing ventilation, monitoring cardiac function and vital signs, and providing symptomatic and supportive care. If a little time has passed after taking the drug, gastric lavage. Due to the fact that atomoxetine has a high affinity for plasma proteins, treatment of overdose by dialysis is not practical.

Strattera drug interactions

influence of other drugs on atomoxetine : MAO inhibitors - atomoxetine should not be used with MAO inhibitors. CYP2D6 inhibitors (SSRIs—eg, fluoxetine, paroxetine, quinidine, terbinafine): Atomoxetine is primarily metabolized by the oxidation of CYP2D6 to 4-hydroxyatomoxetine. In patients who are extensive CYP2D6 metabolizers, potent CYP2D6 inhibitors increase the steady-state plasma levels of atomoxetine to a level similar to that in patients with poor CYP2D6 metabolizers (poor metabolizers). In active metabolizers, when combined with atomoxetine and paroxetine or fluoxetine, the AUC of atomoxetine is approximately 6-8 times higher, and the steady-state concentration and Cmax are approximately 3-4 times higher than with atomoxetine monotherapy. For patients using CYP2D6 inhibitor drugs, gradual titration of Strattera (adjustment and slowly increasing the dose of atomoxetine) is recommended. If a CYP2D6 inhibitor is prescribed or discontinued after titration of the dose of atomoxetine, its clinical effectiveness should be re-evaluated in order to determine the need to adjust the dose of atomoxetine. Poor metabolizers should use atomoxetine with caution in combination with strong P450 inhibitors as the risk of a clinically significant increase in atomoxetine exposure has not been studied. Salbutamol . Atomoxetine should be administered with caution to patients receiving high doses of salbutamol (or other β2 adrenergic agonists) by local or systemic administration (oral or IV), as the cardiovascular effects of salbutamol may be enhanced. There is a potential for an increased risk of QT prolongation if atomoxetine is administered with other drugs known to prolong the QT interval (such as antipsychotics, Class IA and III antiarrhythmics, moxifloxacin, erythromycin, methadone, mefloquine, tricyclic antidepressants, lithium, or cisapride). that can cause electrolyte imbalance (such as thiazide diuretics) and drugs that inhibit CYP2D6. Atomoxetine is associated with a potential risk of epileptic seizures. Caution is recommended when taking concomitant medications that lower the threshold of central nervous system excitability (such as antidepressants, antipsychotics, mefloquine, buproprion or tramadol). Antihypertensive drugs : due to the possible effect on blood pressure, atomoxetine should be used with caution in combination with antihypertensive drugs. Drugs that affect the secretion of norepinephrine should be co-administered with atomoxetine with caution due to the possibility of increased or synergistic pharmacological effects, for example the antidepressants imipramine, venlafaxine and mirtazapine, contraceptives, pseudoephedrine or phenylephrine. Drugs that affect gastric pH : drugs that increase gastric pH (magnesium hydroxide/aluminum hydroxide, omeprazole) do not affect the bioavailability of atomoxetine. Drugs that bind intensively to plasma proteins : data from an in vitro showed that atomoxetine had no effect on the binding of warfarin, acetylsalicylic acid, phenytoin and diazepam to plasma albumin. Effect of atomoxetine on other drugs : In vitro indicate that atomoxetine does not cause clinically significant inhibition or induction of cytochrome P450 isoenzymes, including CYP1A2, CYP3A, CYP2D6 and CYP2C9.

special instructions

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

ADHD symptoms of impaired attention and hyperactivity (identified in more than one social environment, such as home and school) may manifest as lack of concentration, distractibility, excessive impatience, impulsivity, disorganization, restlessness, and other similar behavioral problems. The diagnosis of ADHD must meet ICD-10 criteria.

While taking the drug in clinical studies in children and adolescents, the likelihood of developing suicidal thoughts increased. In 12 clinical studies of 2,200 patients (including 1,357 patients treated with Strattera and 851 patients treated with placebo), suicidal ideation was reported in 0.37% of cases in the Strattera group (5 of 1,357 patients). In the placebo group, suicidal ideation was not detected. During these clinical studies, one suicide attempt was reported and there were no completed suicides.

In rare cases, patients taking Strattera have experienced allergic reactions - rash, angioedema, urticaria.

Atomoxetine should not be prescribed for at least 2 weeks after stopping MAO inhibitors. Treatment with MAO inhibitors should not be started within 2 weeks after discontinuation of atomoxetine.

Many patients taking atomoxetine experienced a slight increase in heart rate (on average <10 beats/min) and/or an increase in blood pressure (on average <5 mmHg). In most cases, these changes did not have a clinically significant effect. Cases of orthostatic hypotension have also been reported.

With the use of psychostimulants registered for the treatment of ADHD in the United States in children with severe heart pathology that disrupts its structure, an increased risk of sudden cardiac death has been identified. Atomoxetine does not belong to the class of psychostimulants, because has an alternative mechanism of therapeutic action in the treatment of ADHD. However, given the general registered indication for use (ADHD), caution should be exercised when using atomoxetine in patients with severe physical overload, concomitant use of psychostimulants, and a family history of sudden cardiac death. Atomoxetine should not be used in patients with severe cardiac pathology.

Rare cases of serious liver damage have been reported with atomoxetine. In patients with manifestations of jaundice or laboratory findings indicating impaired liver function, treatment with atomoxetine should be discontinued.

In clinical trials, adult patients with ADHD taking atomoxetine experienced a higher incidence of urinary retention compared with placebo. Complaints of urinary retention could potentially be regarded as a result of the use of atomoxetine.

It is necessary to stop taking atomoxetine if convulsive seizures develop that cannot be explained by other reasons. Atomoxetine should be used with caution in patients with a history of seizures.

The effectiveness of treatment with atomoxetine for more than 18 months and the safety of treatment with it for more than 2 years have not been systematically assessed.

Aggressive behavior or hostility is often observed in children and adolescents with ADHD. There is no conclusive evidence that atomoxetine can cause aggressive behavior or hostility. However, in clinical studies, aggressive behavior or hostility was observed more often in children and adolescents taking atomoxetine (without statistically significant differences compared with the placebo group). Patients being treated for ADHD should be monitored for aggressive behavior or hostility.

There are known cases of psychotic and manic symptoms, including hallucinations, delusions and pathological elevation of mood, during 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 taking atomoxetine and, if necessary, consider discontinuing the drug.

The following symptoms were noted while taking atomoxetine: anxiety, agitation, panic attacks, insomnia, irritability, impulsivity, akathisia. Patients taking atomoxetine require monitoring for the development of these symptoms.

Parents and loved ones should carefully monitor for any of the above symptoms and suicidal thoughts in children and adolescents taking atomoxetine and report them immediately to their doctor.

The safety and effectiveness of Strattera in elderly patients have not been established.

Use in pediatrics

In children under 6 years of age, there is insufficient data on the safety and effectiveness of atomoxetine.

Impact on the ability to drive vehicles and operate machinery

Taking the drug may be accompanied by drowsiness. In this regard, patients taking Strattera should exercise caution when operating high-risk mechanical equipment, incl. car until they are sure that atomoxetine does not cause any problems.

Strattera®

ADHD symptoms of impaired attention and hyperactivity (identified in more than one social environment, such as home and school) may manifest as lack of concentration, distractibility, excessive impatience, impulsivity, disorganization, restlessness, and other similar behavioral problems. A diagnosis of ADHD must meet accepted diagnostic criteria.

Suicidal thoughts and behavior.

While taking the drug in clinical studies in children and adolescents, the likelihood of developing suicidal thoughts increased. In 12 clinical studies in 2200 patients (including 1357 patients receiving atomoxetine and 851 patients receiving placebo), of which 0.37% of cases in the atomoxetine group showed the development of suicidal thoughts (5 out of 1357 patients), suicidal thoughts in the placebo group thoughts were not identified. During these clinical studies, one suicide attempt was reported and there were no completed suicides. All reactions were observed in children 12 years of age within the first month from the start of treatment. It is unknown whether the risk of developing suicidal ideation persists over a longer treatment period. In similar studies in adult patients, there was no increase in the risk of developing suicidal ideation.

Parents and loved ones of children and adolescents undergoing treatment with Strattera® should carefully monitor the appearance of unusual changes in behavior, worsening clinical manifestations, and the emergence of suicidal thoughts, especially in the first months of treatment, as well as during changes (both increases and decreases) drug dose.

When using the drug Strattera®, the following symptoms were noted: anxiety, agitation, panic attacks, insomnia, irritability, aggressiveness, impulsivity, akathisia, hypomania, mania. Despite the fact that no connection has been identified between the occurrence of these symptoms and the occurrence of suicidal phenomena, there is an assumption that such symptoms may be precursors to the development of suicidal thoughts. If these symptoms appear, a change in the dosage regimen may be required, including possible discontinuation of the drug, especially if they occur suddenly and are severe.

Parents and caregivers should be advised to monitor patients daily for agitation, irritability, unusual changes in behavior, and other symptoms described above, as well as suicidal ideation, and to promptly report such symptoms to the prescriber.

Allergic reactions.

In rare cases, patients taking atomoxetine have experienced allergic reactions in the form of rash, angioedema, and urticaria.

Monoamine oxidase inhibitors (MAOIs).

Atomoxetine should not be used for at least 2 weeks after discontinuation of an MAOI. Treatment with MAOIs should not be started within 2 weeks after discontinuation of atomoxetine.

Effect on the cardiovascular system.

Atomoxetine can affect heart rate (HR) and blood pressure (BP). It is recommended to measure heart rate and blood pressure before starting treatment and then periodically repeat measurements during treatment in order to detect a clinically significant increase in these indicators. Most patients receiving atomoxetine experienced a slight increase in heart rate (on average less than 10 beats/min) and/or an increase in blood pressure (on average less than 5 mmHg), which were not clinically significant. However, data from clinical studies of ADHD indicate that some patients (about 5-10% of children and adults) experience clinically significant changes in heart rate (20 bpm or more) and blood pressure (15-20 mmHg). Art. and more). Atomoxetine should be used with caution in patients with concomitant pathologies, such as arterial hypertension, tachycardia, and other cardiovascular and cerebrovascular disorders, in which the patient's condition may worsen if blood pressure or heart rate increases. This drug should not be used in patients with severe cardiovascular disease.

In addition, atomoxetine should be used with caution in patients with congenital or acquired prolongation of the QT interval (including due to the use of a concomitant drug), or a hereditary family history of prolongation of the QT interval. Orthostatic hypotension has also been reported, so atomoxetine should be used with caution in patients with diseases that may cause hypotension or sudden changes in blood pressure or heart rate.

Impaired liver or kidney function.

Very rarely, spontaneous observations of liver damage have been reported, which was manifested by an increase in the activity of liver enzymes and an increase in the concentration of bilirubin in the blood with the development of jaundice. Also, in very rare cases, severe liver damage up to the development of acute liver failure has been reported. Atomoxetine should be discontinued and not restarted in patients with jaundice or laboratory evidence of liver damage.

In clinical trials, adult patients with ADHD taking atomoxetine experienced a higher incidence of urinary retention compared with placebo. Complaints of urinary retention could potentially be regarded as a result of the use of atomoxetine.

Convulsive seizures.

Use with caution in patients with a history of seizures. It is necessary to stop taking atomoxetine if seizures develop that cannot be explained by reasons other than the use of atomoxetine.

Use in children.

There is insufficient data on the safety and effectiveness of atomoxetine in children under 6 years of age.
The effectiveness of treatment with atomoxetine for more than 18 months and the safety of treatment for more than 2 years have not been systematically assessed. Use in the elderly.
The safety and effectiveness of atomoxetine in elderly patients have not been studied.

Aggressive behavior or hostility.

Aggressive behavior or hostility is often observed in patients with ADHD. There is no clear evidence that atomoxetine can cause aggressive behavior or hostility. However, in clinical studies, aggressive behavior or hostility was observed more often in children, adolescents and adults taking atomoxetine (without statistically significant differences compared with the placebo group). Patients receiving treatment for ADHD should be monitored for aggressive behavior or hostility.

Priapism.

During post-marketing surveillance, rare cases of priapism (persistent painful or painless erection lasting more than 4 hours) were observed in adults and children. In cases of suspected priapism, immediate medical attention should be provided.

Effect on height and body weight.

In general, growth and corresponding weight gain in children taking atomoxetine occurred more slowly than normal during the first 9-12 months from the start of treatment. Anthropometric parameters (body weight and height) after two years of treatment were close to normal. Monitoring of growth indicators in patients taking atomoxetine is necessary.

Psychotic or manic episodes.

In children and adolescents without a history of psychotic or manic episodes, atomoxetine, when taken in usual doses, may cause the development of symptoms of these conditions, including hallucinations, delusions and manic mood disturbance. If the described symptoms occur, the possible role of taking atomoxetine in their development should be assessed and the issue of discontinuing therapy should be decided. Such symptoms were observed in approximately 0.2% of cases (in 4 of 1939 patients receiving atomoxetine for several weeks at usual doses) of atomoxetine therapy, compared with no such occurrences among 1056 patients receiving placebo, according to the results of a pooled analysis of multiple short-term placebo-controlled studies. research.

Bipolar disorder.

In general, in patients receiving therapy for ADHD with comorbid bipolar disorder, special attention should be paid to the possibility of induction of mixed/manic episodes under the influence of this therapy. It cannot be stated with certainty whether the symptoms described above can be due to such an induction. In this regard, patients with existing symptoms of depression should be carefully examined to determine the presence or absence of a risk of developing bipolar disorder before prescribing atomoxetine therapy. This evaluation should include a detailed medical history, including a family history of suicide, bipolar disorder, and depression.

Urinary retention.

In adult patients with ADHD who participated in controlled studies, the incidence of urinary retention (1.7%, 9/540) and urinary difficulty (5.6%, 30/540) was higher in patients taking atomoxetine compared with those receiving placebo (0%, 0/402; 0.5%, 2/402, respectively). Two adult patients taking atomoxetine dropped out of the study early due to urinary retention, whereas no such cases were observed among those receiving placebo. Complaints of urinary retention or difficulty urinating should be considered as potentially related to atomoxetine.

Special Populations - In controlled studies in children with ADHD and comorbid chronic motor tics or Tourette's syndrome, patients treated with atomoxetine did not experience worsening of tics compared with patients treated with placebo. In controlled studies of adolescents with ADHD and comorbid major depressive disorder, patients taking atomoxetine did not experience worsening of depressive symptoms compared with patients taking placebo. In two controlled studies (one in children and one in adults) of patients with ADHD and comorbid anxiety disorders, patients taking atomoxetine did not experience an increase in anxiety compared with patients taking placebo. During post-marketing use, there have been rare reports of anxiety and depression or worsened mood, and very rare reports of tics. The following symptoms have been reported with atomoxetine: anxiety, agitation, panic attacks, insomnia, irritability, impulsivity, akathisia, hypomania and mania.

Parents and loved ones should carefully monitor for any of the above symptoms and suicidal thoughts in children and adolescents taking atomoxetine and report them immediately to their doctor.