Atomoxetine
When ATH:
N06BA09
Pharmacological action
Centrally acting sympathomimetics. Atomoxetine is a highly potent inhibitor of presynaptic norepinephrine vectors. Atomoxetine It has minimal affinity for other noradrenergic receptors or other receptors or transporters of neurotransmitters.
Atomoxetine does not apply to psychostimulants and is not an amphetamine derivative. In clinical studies it was observed amplification of symptoms or any adverse events, associated with withdrawal syndrome.
Pharmacokinetics
Once inside atomoxetine rapidly and almost completely absorbed, reaching Cmax in plasma after about 1-2 hours. Atomoxetine is widely distributed in the body. It has high affinity for plasma proteins, Firstly – albumin. 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 activity CYP2D6 gidroksiatomoksetin 4 can be formed by some other isozymes of cytochrome P450, but more slowly. Atomoxetine does not inhibit or induce CYP2D6 cycle.
Average T1/2 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.
Testimony
Attention Deficit Hyperactivity Disorder (ADHD) children 6 and older, adolescents and adults.
Dosage regimen
Is the inside, regardless of the meal or during a meal, as a single daily dose in the 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.
For children and adolescents weighing up 70 kg the recommended initial daily dose is approximately 0.5 mg / kg and increased up to the therapeutic daily dose of approximately 1.2 mg / kg no sooner than 3 day. If there is no improvement of a patient the total daily dose may be increased to a maximum of 1.8 mg / kg no sooner than 2-4 weeks after initiation 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.
For children and adolescents weighing more than 70 kg and adults recommended initial 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 initiation of treatment. The recommended maintenance dose is 80 mg. The recommended maximum daily dose is 120 mg.
In patients with moderate hepatic impairment (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.
Side effect
Side effects in patients with poor metabolism : decreased appetite, insomnia, violation of the quality of sleep, enuresis, Bad mood, tremor, early morning awakening, conjunctivitis, fainting, midriaz.
From the digestive system: Often – decreased appetite, dry mouth, nausea; often – stomach ache, constipation, dyspepsia, flatulence.
CNS: Often – insomnia; often – early morning awakening, decreased libido, sleep disturbance, dizziness, violation of the quality of sleep, sinus headache, drowsiness.
Cardio-vascular system: often – tides (blood), palpitations, tachycardia; sometimes – cold sensation in the lower extremities; rarely – peripheral vascular responses and / or Raynaud's syndrome and the risk of recurrence of Raynaud's syndrome. In placebo-controlled studies in adults, receiving atomoxetine noted an average increase in heart rate 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 – strangury, urinary retention.
On the part of the reproductive system: often – dysmenorrhoea, abnormal ejaculation, lack of ejaculation, erectile dysfunction, erectile dysfunction, menstrual disorders, violation of orgasm, prostatitis; rarely – according to spontaneous reports – painful or prolonged erection.
Dermatological reactions: often – dermatitis, increased sweating.
Other: often – weakness, chills, weight loss.
Contraindications
Concomitant use with MAO inhibitors, zakrыtougolynaya glaucoma, Hypersensitivity to atomoxetine.
Pregnancy and lactation
Use in pregnancy and lactation is possible only in the case, when the expected benefit of therapy for mother considerably exceeds the potential risk to the fetus or infant.
Unknown, whether atomoxetine is released in breast milk in humans.
Cautions
Caution should be used in patients with hypertension, taxikardiej, cardiovascular diseases, cerebrovascular, as well as any state, which can lead to the development of hypotension, tk. Cases of orthostatic hypotension.
Atomoxetine can cause hypertension in patients with end-stage renal disease.
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.
In clinical studies in children and adolescents during treatment with atomoxetine increase the likelihood of suicidal thoughts.
In rare cases, patients in patients receiving atomoxetine marked allergic reactions – rash, angioedema, hives.
Atomoxetine should not be used 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.
It was reported about rare cases of serious liver dysfunction in patients receiving 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, suggestive of hepatic dysfunction atomoxetine should be abolished.
The effectiveness of atomoxetine treatment more 18 months or more of treatment safety 2 years have not been systematically evaluated.
Patients (especially children and adolescents), receiving treatment for ADHD, requires supervision in relation to the onset of aggressive behavior or hostility.
Patients, receiving atomoxetine, It requires monitoring because of the risk of occurrence of the following symptoms: alarm, ažitaciâ, panic attacks, insomnia, irritability, impulsiveness, akathisia, gipomaniya and mania.
Effects on ability to drive vehicles and management mechanisms
Patients should exercise caution in the management of hazardous mechanical means, incl. car, until, until they are confident, that atomoxetine does not cause any violations.
Drug Interactions
With simultaneous use of atomoxetine with β agonists2-adrenergic receptors may enhance their action on the cardiovascular system (this combination be used with caution).
In patients with severe metabolic CYP2D6 inhibitors of CYP2D6 increase atomoxetine content in plasma at steady state to the level of, similar to those of patients with low CYP2D6 metabolism.
Based on in vitro studies supposed, that the appointment of inhibitors of cytochrome P450 patients with reduced metabolism of CYP2D6 not increase the concentration in plasma atomoxetine. Patients, use the drug inhibitors of CYP2D6, It recommended a very slow increase in the dose atomoxetine.
In an application with drugs, affecting the blood pressure may change in blood pressure.
