Azenapine - instructions for use, dose, side effects, contraindications

Clinical and pharmacological group: & nbsp

Neuroleptics

Included in the formulation

Safris®

pills n / az.

Organon, N.V. Netherlands

Included in the list (Order of the Government of the Russian Federation No. 2782-r of 30.12.2014):

ONLS

АТХ:

N.05.A.H.05 Asenapine

Pharmacodynamics:

Antagonist of dopamine D₂ and serotonin 5-HT₂Areceptors, to a lesser extent interacts with serotonin 5-HT₁A-, 5-HT₁B-, 5-HT₂C-, 5-HT₆-, 5-HT₇-, dopamine D₃- and α₂-adrenoceptors.

Reduces the manifestations of psychosis: delusions and hallucinations. Antipsychotic effect associated with blockade of dopamine D₂receptors in the mesolimbic and mesocortical system. Block of dopamine D₂-receptor chemoreceptor trigger zone of the vomiting center determines the antiemetic effect. Oppression of dopamine D₂receptors in the basal ganglia (nigrostriral zone) leads to drug parkinsonism (extrapyramidal disorders).

Block of central α₂-adrenergic and H₁-gistaminovyh receptors - a sedative effect. Peripheral α-adrenoblocking and H₁-gistaminoblocking effects are manifested by lowering blood pressure and antiallergic effect.

Pharmacokinetics:

After sublingual admission asenapine quickly absorbed, C_max in plasma is achieved after 0.5-1.5 hours. Absolute bioavailability of asenapine in a dose of 5 mg with sublingual application is 35%.Absolute bioavailability during ingestion is low (less than 2%). Taking water after 2 or 5 minutes after using asenapine led to a decrease in the concentration of asenapine in the blood (by 19% and 10%, respectively). In this regard, within 10 minutes after taking asenapine should not drink or eat. The connection with plasma proteins is 95%. Metabolized in the liver, half-life is 24 hours. Asenapine is a weak inhibitor of the isoenzyme CYP2D6. It does not induce induction of CYP1A2 or CYP3A4 isoenzymes in the culture of human hepatocytes. Excreted by the kidneys (about 50%) and the gastrointestinal tract (about 40%). The predominant metabolite of the drug is asenapine-N+ -glucuronide.

Indications:

Bipolar affective disorder, schizophrenia.

ICD-10

V.F20-F29.F20 Schizophrenia

V.F20-F29.F21 Chrysotile disorder

V.F20-F29.F22 Chronic delusional disorders

V.F20-F29.F23 Acute and transient psychotic disorders

V.F20-F29.F25 Schizoaffective disorder

V.F20-F29.F29 Inorganic psychosis, unspecified

V.F30-F39.F31 Bipolar affective disorder

Contraindications:

Hypersensitivity. Children under 18 years of age (effectiveness and safety not studied), lactation period (breastfeeding).

Carefully:

Convulsive conditions in the anamnesis, simultaneous reception with substrates and inhibitors CYP2D6.

Elderly patients with psychosis on the background of dementia.

Malignant neuroleptic syndrome (hyperthermia, rigidity of muscles, instability of the autonomic nervous system, impaired consciousness and increased serum creatinophosphinase, myoglobinuria, rhabdomyolysis, acute renal failure).

Convulsive seizures.

Suicide attempts.

Orthostatic hypotension.

Late dyskinesia.

Hyperprolactinemia.

Changing the QT interval.

Hyperglycemia and diabetes mellitus.

Dysphagia.

Violation of thermoregulation.

Patients with severe impairment of liver function.

Pregnancy and lactation:

Category FDA - C. In pregnancy, the use of the drug is possible only if the potential benefit to the mother exceeds the potential harm for the child.

Dosing and Administration:

A single dose of 5-10 mg, a daily dose of 10-20 mg. Take 2 times a day. The duration of treatment is determined by the attending physician. With combined treatment, the drug is taken last.

Sublingually. The patient should be instructed,that for optimal absorption it is necessary to place the tablet under the tongue and allow it to dissolve completely (the tablet dissolves in the saliva within a few seconds). Sublingual tablets can not be crushed, chewed or swallowed. Do not eat and drink within 10 minutes after taking asenapine.

The dose is selected individually depending on the indications, tolerability, concomitant therapy with other psychotropic drugs.

Side effects:

From the cardiovascular system: interval lengthening QT on the ECG, sinus bradycardia, orthostatic hypotension, blockade of the foot of the Hisnia, arterial hypotension, neutropenia.

From the respiratory system: pulmonary embolism.

From the nervous system: akathisia, drowsiness, dystonia, dyskinesia, dizziness, parkinsonism, sedation, extrapyramidal disorders, dysarthria, syncope, convulsive seizures, anxiety.

On the part of the reproductive system: amenorrhea, sexual dysfunction, galactorrhea, gynecomastia.

From the side of metabolism: hyperglycemia, increased appetite, weight gain.

From the musculoskeletal system: rhabdomyolysis, stiffness.

Other: withdrawal syndrome in a newborn, allergic reactions.

Overdose:

Agitation, confusion. Treatment - maintenance therapy, ensuring airway patency, adequate oxygenation and ventilation. In the case of hypotension and vascular collapse - intravenous administration of fluid and / or sympathomimetics (epinephrine and dopamine should not be used, since beta-stimulation can aggravate hypotension in conditions of an asenapine-induced alpha blockade). In the case of severe extrapyramidal symptoms, anticholinergic drugs should be prescribed. The specific antidote is unknown.

Interaction:

Poorly studied.

Take care when taking concomitantly with substrates and inhibitors CYP2D6, as well as with other drugs with systemic effects on the central nervous system. When simultaneous application with fluvoxamine (inhibitor of the isoenzyme CYP1A2) at the full therapeutic dose fluvoxamine can cause a more pronounced increase in the concentration of asenapine in plasma.

Due to asenapine has α₁-adrenoblokiruyuschim properties and is able to cause orthostatic hypotension, with a combination of possible amplification of the effects of certain antihypertensive drugs.

Asenapine has a weak inhibitory effect on the isoenzyme CYP2D6.Use with caution in combination with preparations that are substrates or inhibitors of the isoenzyme CYP2D6.

Simultaneous single administration of 20 mg of paroxetine (a substrate and an inhibitor of the isoenzyme CYP2D6) during the administration of asenapine at a dose of 5 mg twice a day in healthy male volunteers resulted in an almost 2-fold increase in paroxetine AUC. but asenapine can enhance the inhibitory effects of paroxetine on their own metabolism.

Special instructions:

In elderly patients, the risk of death is increased.

During treatment, patients should avoid drinking alcohol.

Impact on the ability to drive vehicles and manage mechanisms

The drug may have a sedative effect, it is not recommended to drive a car while taking the drug or perform work associated with increased concentration of attention.

Instructions

Asenapine (Azenapinum)