Strattera, 25 mg capsules 7 pcs

Pharmacodynamics

Atomoxetine is a highly selective potent inhibitor of presynaptic noradrenaline 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. No increase in disease symptoms or adverse events related to withdrawal have been seen in clinical studies.

Pharmacokinetics

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

Intake. Atomoxetine is rapidly and almost completely absorbed after oral administration, reaching maximum plasma concentration (Cmax) in approximately 1 to 2 hours. Atomoxetine is prescribed regardless of meals or with meals.

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

Metabolism. Atomoxetine is primarily biotransformed through the cytochrome P450 2D6 (CYP2D6) enzyme cycle. The main resulting oxidized metabolite, 4-hydroxyatomoxetine, is rapidly glucuronized. 4-Hydroxyatomoxetine is equivalent in action to atomoxetine, but circulates in the plasma at much lower concentrations.

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

Atomoxetine neither inhibits nor enhances the CYP2D6 cycle.

Elimation.
The average half-life of atomoxetine after oral administration is 3.6 hours in patients with significant metabolism and 21 hours in patients with decreased metabolism. Atomoxetine is mainly excreted in the urine as 4-hydroxyatomoxetine-O-glucuronide.

Indications

Attention Deficit Hyperactivity Disorder (ADHD) in children 6 years and older, adolescents and adults.

Active ingredient

Composition

Each capsule contains:

the active ingredient:

atomoxetine hydrochloride,

equivalent to 25 atomoxetine;

auxiliary substances:

capsule contents – dimethicone, pregelatinized starch;

capsule shell – titanium dioxide, sodium lauryl sulfate, gelatin, indigo carmine dye

How to take, the dosage

Orally, regardless of meals (or with meals), once a day in the morning or, in case of side effects, twice a day (morning and late afternoon or early evening). Children and adolescents with body weight up to 70 kg: recommended initial daily dose is 0.5 mg/kg, which is increased to 1.2 mg/kg not earlier than in 3 days.

If there is no improvement, the daily dose can be increased to a maximum of 1.8 mg/kg (or 120 mg) not earlier than 2-4 weeks after starting the drug.

The recommended maintenance dose is 1.2 mg/kg/day. Children and adolescents with body weight over 70 kg and adults: Recommended initial daily dose is 40 mg, which is increased to 80 mg not earlier than in 3 days. In case of no improvement of the condition the daily dose may be increased to the maximum dose of 120 mg not earlier than 2-4 days after the start of the drug.

The recommended maintenance dose is 80 mg. In patients with moderate hepatic impairment (class B according to Child-Pugh classification) the initial and maintenance dose is reduced by 50%. In patients with severe hepatic impairment (Child-Pugh class C), the initial and maintenance dose is reduced to 25% of the usual dose.

Interaction

Beta-adrenergic receptor agonists.

Atomoxetine should be used with caution in patients taking beta2 agonists, because their effects on the cardiovascular system may increase. In healthy adult volunteers, the effect of salbutamol at a standard inhaled dose of 200 mcg on hemodynamic parameters was insignificant compared to 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 increase the above effects of albuterol. Heart rate after multiple inhalations of albuterol in a dose of 800 mcg was characterized by similar values both with monotherapy and in combination with atomoxetine. Concomitant administration of atomoxetine with drugs that cause QT interval prolongation (neuroleptics, antiarrhythmic drugs, moxifloxacin, erythromycin, tricyclic antidepressants, lithium carbonate), as well as with drugs that cause electrolyte imbalance (diuretics) and CYP2D6 inhibitors increases the risk of QT interval prolongation.

Cytochrome P450 enzymes. Atomoxetine does not cause clinically significant inhibition or induction of cytochrome P450 enzymes, including CYP1A2, CYP3A, CYP2D6 and CYP2C9. In patients with significant CYP2D6 metabolism, CYP2D6 inhibitors increase continuous plasma levels of atomoxetine to levels similar to those in patients with reduced CYP2D6 metabolism.

In vitro studies suggest that administration of cytochrome P450 inhibitors to patients with decreased CYP2D6 metabolism does not increase the plasma concentration of atomoxetine. Gradual titration of atomoxetine is recommended in patients using CYP2D6 inhibitor drugs.

Drugs affecting blood pressure. Because of the possible effect on blood pressure, atomoxetine should be used with caution when combined with drugs affecting blood pressure.

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

Drugs affecting norepinephrine secretion. Drugs that affect norepinephrine secretion should be administered with caution together with atomoxetine because of the possibility of increased or synergistic pharmacological effects.

Drugs with high affinity for plasma proteins. Atomoxetine does not affect the binding of warfarin, acetylsalicylic acid, phenytoin and diazepam to human albumin.

Drugs with known effect of lowering the seizure threshold

(antidepressants, neuroleptics, mefloquine, tramadol). Caution should be exercised when prescribing concomitantly.

Special Instructions

Symptoms of ADHD in the form of impaired attention and hyperactivity (found in more than one social setting, such as both home and school) can manifest as lack of concentration, distractibility, excessive impatience, impulsivity, disorganization, restlessness and other similar behavior disorders. A diagnosis of ADHD must meet ICD-10 criteria.

Suicidal thoughts and behavior. Children and adolescents in clinical studies had an increased likelihood of developing suicidal ideation while taking the drug. In 12 clinical trials in 2200 patients (including 1357 patients who received atomoxetine and 851 patients who received placebo), of whom 0.37% of the atomoxetine group developed suicidal thoughts (5 of 1357 patients); no suicidal thoughts were detected in the placebo group. One suicide attempt was reported in these clinical trials; there were no completed suicides.

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

Monoamine oxidase inhibitors (MAOIs).Atomoxetine should not be used for at least 2 weeks after withdrawal of an MAOI. IMAO treatment should not be started within 2 weeks of atomoxetine withdrawal. Cardiovascular System. In many patients taking atomoxetine, some increase in heart rate (on average by

acquired prolongation of the QT interval has been noted.

An increased risk of sudden cardiac death has been found in children with grossly abnormal cardiac abnormalities in the United States using psychostimulants registered for the treatment of ADHD. Atomoxetine is not in the class of psychostimulants because it has an alternative mechanism of therapeutic action in the treatment of ADHD. However, given the common registered indication for use (ADHD), caution should be exercised when using atomoxetine in patients with (1) severe physical exertion, (2) concomitant administration of psychostimulants, (3) a family history of sudden cardiac death. Atomoxetine should not be used in patients with gross cardiac pathology.

Hepatic or renal impairment. Rare cases of serious liver damage have been reported with atomoxetine (two cases of marked elevation of liver enzymes and bilirubin in 2 million patients have been described). In patients with manifestations of jaundice or detected laboratory parameters indicating liver dysfunction, treatment with atomoxetine should be discontinued.

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

Take with caution in patients with a history of seizures. Atomoxetine should be discontinued if seizures develop that cannot be explained by other causes.

Preventive use in children. There are insufficient data on the safety and efficacy of atomoxetine in children under 6 years of age.

The efficacy of treatment with atomoxetine over 18 months and its safety over 2 years have not been systematically evaluated.

The use in the elderly. The safety and efficacy of atomoxetine in elderly patients have not been established.

Aggressive behavior or hostility. Aggressive behavior or hostility is often seen in children and adolescents with ADHD. There is no conclusive evidence that atomoxetine can cause aggressive behavior or hostility. However, aggressive behavior or hostility has been observed more frequently in children and adolescents taking atomoxetine in clinical studies (with no statistically significant difference compared to the placebo group). Patients treated for ADHD should be monitored for the occurrence of aggressive behavior or hostility.

Psychotic and manic symptoms.

Psychotic and manic symptoms, including hallucinations, delirium, and pathological mood elevation, are known to occur with atomoxetine at therapeutic doses in children and adolescents. If these symptoms occur, it is recommended to evaluate the extent to which they are related to atomoxetine administration and, if necessary, consider withdrawing the drug.

The following symptoms have been reported with atomoxetine: anxiety, agitation, panic attacks, insomnia, irritability, impulsivity, akathisia. Patients taking atomoxetine should be monitored by a physician regarding 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 notify the treating physician.

Driving and performing work that requires extra attention
Taking the drug may be accompanied by drowsiness. Therefore, patients taking atomoxetine should be cautious about driving dangerous motor vehicles, including automobiles, until they are sure that atomoxetine does not cause any impairment.

Contraindications

Cautious
With caution./li> Open angle glaucoma Serious heart disease

With caution
In patients with hypertension, tachycardia, cardiovascular disease, severe physical exertion, concurrent use of psychostimulants, sudden cardiac death in a family history, impaired cerebral circulation, history of seizures, and conditions that may lead to hypotension

Side effects

Children and adolescents

Digestive system disorders: very common (>10%) – abdominal pain (18%; including abdominal discomfort phenomena, pain and discomfort in the epigastrium, stomach discomfort), decreased appetite (16%), vomiting (11%); common (1-10%) – constipation, dyspepsia, nausea (9%), anorexia. These adverse reactions are temporary and usually do not require withdrawal of the drug. Due to decreased appetite, some patients had weight loss (about 0.5 kg on average) at the beginning of treatment, weight loss was greater at higher doses. After the initial weight loss, patients taking Strattera showed a slight increase in body weight during long-term therapy. Height scores (weight and height) after two years of treatment were close to normal.

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

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

In placebo-controlled studies in children who received Strattera, there was a mean increase in HR of 6 bpm and a mean increase in BP and DAH of 2 mmHg compared to placebo.

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

CNS disorders: very common (>10%) – somnolence (including sedation); common (1-10%) – irritability, mood swings, dizziness; sometimes (0.1-1%) – early morning awakening.

An organ of vision: often (1-10%) – mydriasis.

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

Others: often (1-10%) – flu, fatigue, weight loss; sometimes (0.1-1%) – weakness.

The side effects in patients with slow metabolism of CYP2D6 substrates observed in 2% of cases and at the same time twice as often and statistically significantly more often than in patients with fast metabolism of CYP2D6 substrates: tremor (5.1 and 1.1%, respectively), syncope (2.1 and 0.7%, respectively), conjunctivitis (3 and 1.5%, respectively), early morning awakening (3 and 1.1%, respectively), and mydriasis (2.5 and 0.7%, respectively).

Adults

In adults, the most frequent adverse effects associated with atomoxetine administration were observed in the gastrointestinal and urogenital tracts. No serious adverse events were observed during short or long-term treatment with atomoxetine.

Gastrointestinal system disorders: very common (>10%) – decreased appetite, dry mouth, nausea; common (1-10%) – abdominal pain (including abdominal discomfort, pain and discomfort in epigastrium, stomach discomfort), constipation, dyspepsia, flatulence.

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

Cardiovascular system disorders:Frequent (1-10%) – facial flushes, palpitations, tachycardia; occasional (0.1-1%) – sensation of coldness in lower extremities; very rare (

In placebo-controlled studies in adults receiving Strattera, there was a mean increase in HR of 6 bpm, a mean increase in BP (about 3 mm HgBP (about 3 mm Hg) and dAP (about 1 mm Hg) compared to placebo.

Urinary system disorders: often (1-10%) – dysuria, difficult urination.

Social system: often (1-10%) – dysmenorrhea, impaired ejaculation, lack of ejaculation, erectile dysfunction, menstrual cycle disorder, orgasm disorder; very rare (

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

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

Overdose

Signs and Symptoms. The most common symptoms of acute and chronic overdose with atomoxetine monotherapy were somnolence, agitation, hyperactivity, conduct disorder, and GI symptoms.

The majority of manifestations were mild to moderate in severity. Mild to moderate signs and symptoms of sympathetic nervous system activation (e.g., mydriasis, tachycardia, dry mouth) were also noted. All patients showed regression of such symptoms. In some cases of atomoxetine overdose, seizures have been reported. Cases of acute overdose with fatal outcome have also been reported when atomoxetine is taken in combination with at least one other drug.

Treatment in overdose. Ventilation of the lungs, monitoring of cardiac activity and basic vital signs, and symptomatic and supportive treatment are recommended. Gastric lavage may be indicated if not much time has passed after taking the drug. Activated charcoal to limit absorption may be helpful. Because atomoxetine has a high affinity for plasma proteins, treatment of overdose by dialysis is not likely to be feasible.

Pregnancy use

Because of insufficient experience with the use of atomoxetine during pregnancy, the drug should only be prescribed during pregnancy if the potential benefit to the patient significantly exceeds the potential risk to the fetus.

It is not known whether atomoxetine is excreted with the breast milk.

Caution should be exercised when prescribing the drug to a nursing woman.