An antipsychotic drug. The mechanism of action of asenapine has not been fully understood, however, its receptor pharmacology suggests that the efficacy of asenapine is associated with a combination of antagonistic activity against D-receptors.2 and 5-HT2A. Clinical activities of asenapine may also result from effects on other receptors, including 5-HT1A, 5-HT1B, 5-HT2C, 5-HT6, 5-HT7, D3 and α receptors2-Adrenergic. After sublingual administration, asenapine is rapidly absorbed and reaches a peak plasma concentration within 0.5-1.5 hours. Absolute bioavailability after sublingual administration of 5 mg asenapine is 35%. The drug is strongly (95%) bound to plasma proteins, including albumin and α1acidic glycoprotein. Asenapine is rapidly metabolised. The main metabolic pathways of asenapine are direct glucuronidation (via UGT1A4), oxidation mediated by cytochrome P450 (mainly CYP1A2, involving 2D6 and 3A4) and demethylation. Asenapine is a weak inhibitor of CYP2D6, it does not induce CYP1A2 or CYP3A4. The drug is quickly eliminated. Approx. 50% of the dose is excreted in the urine and about 40% in the faeces; only a small amount is excreted in the faeces (5-16%) in unchanged form. After the initial, faster distribution phase of T0,5 asenapine in the elimination phase is approx. 24 h.
Contraindications:
Hypersensitivity to the active substance or to any of the excipients.
Precautions:
The preparation has not been approved for the treatment of patients with psychosis associated with dementia - it is not recommended to use in this group of patients. If the patient develops signs and symptoms of a neuroleptic malignant syndrome, the preparation should be discontinued. The drug should be used with caution in patients with a history of epilepsy and in patients who have conditions associated with a tendency to convulsions. Due to the risk of suicidal behavior, antipsychotic treatment should be accompanied by close supervision of patients at high risk. Asenapine may induce orthostatic hypotension and syncope, especially at an early stage of treatment - the drug should be used with caution in elderly patients and patients with known cardiovascular disease (eg heart failure, myocardial infarction or ischemic heart disease, conduction disorders, cerebrovascular disease) or diseases in the course of which there is hypotension, e.g. dehydration and hypovolemia). If during the treatment with asenapine the patient develops signs and symptoms of tardive dyskinesia, discontinuation of treatment should be considered. Elevations of prolactin have been seen in some patients treated with the product. Caution should be exercised in patients with known cardiovascular disease or a family history of QT prolongation, as well as concomitant use of other drugs that may prolong the QT interval. Due to the risk of hyperglycaemia or exacerbation of pre-existing diabetes, appropriate clinical monitoring of patients with diabetes mellitus and patients with risk factors for diabetes development is recommended. Patients using antipsychotics may experience abnormalities in esophageal muscle contractility and aspiration; Dysfagia cases have been reported in patients treated with the preparation. Antipsychotics may impair the body's ability to lower the internal and external body temperature - it is recommended that patients be cautiously exposed to factors that may contribute to the increase in body temperature, such as forced exercise, very high ambient temperature, simultaneous intake of the drug. preparations with anticholinergic activity or dehydration. In patients with severe hepatic impairment (Child-Pugh C) exposure to asenapine increases seven-fold - not recommended in this patient group.In some patients with moderate hepatic impairment (Child-Pugh B), the possibility of increased plasma concentrations of asenapine can not be ruled out - caution is advised in such cases. When prescribing antipsychotics, including asenapine, patients with Parkinson's disease or dementia with Lewy bodies (DLB), the benefit-risk ratio should be carefully considered, because both groups may be at increased risk of neuroleptic malignant syndrome and increased sensitivity to drugs antipsychotics. This increased sensitivity, in addition to the induction of extrapyramidal symptoms, may also manifest, among others confusion, oblivion of consciousness and instability of posture combined with frequent falling. There is no experience regarding the use of asenapine in the treatment of patients with severe renal impairment whose creatinine clearance was below 15 ml / min. Caution should be exercised when using the preparation in elderly patients - insufficient data on efficacy in patients aged 65 years and older. The safety and efficacy of the preparation in children below 18 years have not been established; data on the safety of use in adolescents are limited.
Pregnancy and lactation:
Do not use the product during pregnancy unless it is necessary and the potential benefits outweigh the potential risk to the fetus. In animal studies, asenapine did not show teratogenic properties while maternal and fetal toxicity was found. Newborns exposed to antipsychotics (including asenapine) during the third trimester of pregnancy are at risk for adverse reactions, including extrapyramidal disorder and / or withdrawal symptoms, which may vary depending on the severity of the course and the duration of the delivery to be made. We observed agitation, increased tension, decreased tension, tremor, drowsiness, respiratory distress syndrome or feeding disorders in newborns - newborns should be carefully monitored. Women taking the drug should not breastfeed.
Side effects:
Very common: anxiety, drowsiness, increased alanine aminotransferase. Common: weight gain, increased appetite, dystonia, akathisia, dyskinesia, parkinsonism, sedation, dizziness, taste disorder, oral hypoesthesia, muscle stiffness, fatigue. Uncommon: hyperglycemia, syncope, extrapyramidal disorder, impaired speech, sinus bradycardia, bundle branch block, prolonged QT interval on ECG, sinus tachycardia, orthostatic hypotension, hypotension, swollen tongue, dysphagia, hyperalgesia, paresthesias in the cavity oral, sexual dysfunction, amenorrhea. Rare: neutropenia, neuroleptic malignant syndrome, visual disturbances, pulmonary embolism, rhabdomyolysis, gynecomastia, amlobia. Frequency unknown: allergic reactions, restless legs syndrome, nausea, changes in oral mucosa (ulceration, blistering and inflammation), excessive salivation, withdrawal syndrome in the newborn. Cerebrovascular events have been reported in asenapine-treated patients, however, there is no evidence that their incidence exceed those expected in adults (18-65 years). The drug has anesthetic properties - immediately after administration of the drug may occur hypoaesthesia and paresthesia in the mouth; these conditions usually disappear within 1 h. In the post-marketing period, severe hypersensitivity reactions, including anaphylactic / anaphylactoid reactions such as lymphedema (throat swelling) have been reported in asenapine-treated patients.
Dosage:
Adults. Manic episode: the recommended initial dose as monotherapy is 10 mg, given twice a day, in the morning and in the evening. The dose can be reduced to 5 mg 2 times a day after prior clinical evaluation. For combination therapy, an initial dose of 5 mg 2 times daily is recommended. The dose can be increased to 10 mg 2 times a day depending on the patient's clinical response and tolerability. No dose adjustment is required in patients with impaired renal function or in patients with mild hepatic impairment. Remove the tablet from the blister only when the patient is ready to take it. Tablets touch with dry hands. Do not squeeze the tablet through the blister. Packaging should not be cut or torn. Separate the foil from the blister and then gently remove the tablet. Do not crush the tablet. Place the tablet under the tongue until it is completely dissolved; the tablet will dissolve in saliva within a few seconds. The tablets should not be chewed or swallowed. Do not eat food or drinks for 10 minutes after taking the tablet. When used in combination with other medicines, the preparation should be taken last. Treatment with the preparation is not recommended in patients who are unable to adhere to this method of administration because the bioavailability of asenapine is low (<2% for oral tablets).