Index of drugs

Treatment of schizophrenia. Treatment of moderate to severe manic episodes of bipolar disorder. Treatment of episodes of severe depression in the course of bipolar disorder. Prevention of recurrence of manic or depressive episodes in patients with bipolar disorder, responding to previous Quetiapine treatment.

1 tabl powl. contains 25 mg, 100 mg, 200 mg or 300 mg quetiapine (as fumarate). The preparation contains lactose.

Quetiapine is an atypical antipsychotic drug. Quetiapine and its active metabolite, norkwetiapine, interact with many receptors for neurotransmitters. Quetiapine and norquetiapine have a higher affinity for serotonin receptors (5HT₂) and Dopamine D₁ and D₂ in the brain. This type of receptor antagonism is believed to have greater selectivity for 5HT₂ relative to D-receptors₂, is responsible for the clinical antipsychotic properties of quetiapine and its minor influence on the formation of extrapyramidal symptoms. In addition, norcorapine has a high affinity for the norepinephrine transporter (NET). Quetiapine and norquetiapine also have high affinity for the histaminergic and adrenergic α receptors₁, lower affinity for α adrenergic receptors₂ and serotonin 5HT receptors_1A. Quetiapine has a slight affinity for muscarinic and benzodiazepine cholinergic receptors. Following oral administration, quetiapine is well absorbed and extensively metabolised. Taking with food does not have a significant effect on the bioavailability of the drug. It is 83% bound to plasma proteins. Quetiapine is metabolized mainly in the liver (mainly mediated by CYP3A4). About 73% of the drug is excreted in the urine and 21% in the faeces. T_0,5 in the elimination phase, it is 7 h for quetiapine and 12 h for its main metabolite.

Hypersensitivity to the active substance or other ingredients of the preparation. Concomitant use of cytochrome P450 3A4 inhibitors such as HIV protease inhibitors, antifungal azoles, Erythromycin, Clarithromycin and nefazodone.

Depression in bipolar disorder is associated with an increased risk of suicidal thoughts, self-mutilation and suicide. This risk persists until significant remission occurs. The patient should be closely monitored until improvement occurs. In clinical studies of patients with major depressive episodes in the course of bipolar disorder, an increased risk of events associated with suicidal attempts has been observed in young adult patients <25 years treated with Quetiapine, compared with patients receiving placebo. The potential risk of suicide related events should be considered after abrupt cessation of treatment due to known risk factors associated with the disease being treated. Patients with bipolar depression who are experiencing drowsiness of severe intensity may require more frequent follow-up visits for a minimum of 2 weeks after drowsiness or symptom improvement; it may be necessary to consider discontinuation of treatment. Caution should be exercised in patients with known cardiovascular disease, cerebrovascular disease and other conditions predisposing to low blood pressure. Quetiapine may induce orthostatic hypotension, especially in the initial dose escalation period - if hypotension occurs, dose reduction or slower titration should be considered. A slower dose increase in patients with cardiovascular disease should be considered. Patients using antipsychotics often have acquired risk factors for venous thromboembolism - before and during the treatment, the agents should be identified and appropriate preventive measures should be taken. Caution should be exercised in patients with a history of epilepsy. The use of quetiapine was associated with the development of akathisia. Its symptoms are more likely in the first few weeks of treatment. In these patients, increasing the dose may be detrimental.In the event of signs and symptoms of tardive dyskinesia, a dose reduction or discontinuation of treatment should be considered (symptoms of tardive dyskinesia may increase or even appear after treatment). In case of symptoms of malignant neuroleptic syndrome, the treatment should be discontinued and appropriate treatment should be given. During treatment with quetiapine, severe neutropenia (neutrophil count <0.5 x 10) may occur⁹/ L). Risk factors for neutropenia are: a pre-existing low white blood cell count and a history of drug-induced neutropenia. Patients with neutrophil counts <1.0 x 10⁹/ l, quetiapine treatment should be discontinued. Patients should be monitored for signs and symptoms of infection and neutrophil counts (until they exceed 1.5 x 10)⁹/ L). In patients using hepatic enzyme inducers, quetiapine treatment can only be started if the benefit of quetiapine exceeds the risk of withdrawal. Any changes in liver enzyme-inducing drugs should be made gradually, and if necessary, these drugs should be replaced with non-inducing liver enzymes (eg sodium valproate). The use of other neuroleptics should be avoided. Patients using antipsychotics, including quetiapine, should be monitored for signs and symptoms of hyperglycaemia (such as polydipsia, polyuria, polyphagia and asthenia). The body weight should be monitored regularly. If lipid levels increase, follow the established clinical practice. Due to the changes in body weight, blood Glucose and lipid levels observed in clinical trials, it is possible that the risk profile of metabolic changes in individual patients may deteriorate, which should be treated accordingly. Due to the risk of QT interval prolongation, caution should be exercised in patients with cardiovascular disease or family history of QT prolongation, and if quetiapine is co-administered with other QT prolonging drugs, neuroleptics, especially in elderly patients age, in patients with congenital long QT syndrome, congestive heart failure, hypertrophy of the heart muscle, hypokalaemia or hypomagnesaemia. The preparation is not suitable for the treatment of elderly patients with dementia associated with psychosis. In patients with an increased risk of stroke and an increased risk of aspiration pneumonia, use the preparation with caution. Caution should be exercised in patients with hepatic impairment and in elderly patients (especially at the beginning of treatment); the safety and efficacy of the drug have not been evaluated in patients over 65 years with episodes of depression in the course of bipolar disorder. Data on the concomitant use of quetiapine with sodium valproate or lithium in the treatment of moderate to severe manic episodes are limited, but combined treatment was well tolerated; data show that an additive effect occurs in the third week. The product is not recommended for children and adolescents under 18 years of age due to the lack of data on use in this age group. The product contains lactose, should not be used in patients with rare hereditary problems of galactose intolerance, lactase deficiency (Lapp type) or malabsorption of glucose-galactose.

The medicine can be used during pregnancy only if the benefits for the mother are greater than the potential risk to the fetus. Discontinuation symptoms were observed in newborns whose mothers took quetiapine. It is recommended to avoid breastfeeding while using quetiapine.

Very common: dizziness, drowsiness, headache, extrapyramidal symptoms; dry mouth; withdrawal symptoms (insomnia, nausea, headache, diarrhea, vomiting, dizziness and irritability); increase in serum triglycerides, increase in total blood cholesterol (mainly LDL cholesterol), decrease in HDL, weight gain, decrease in hemoglobin. Common: leukopenia, decreased neutrophil count, increased eosinophil count, hyperprolactinemia, decreased total and free T₄, decrease in total T concentration₃, increased TSH, increased appetite, increased blood glucose levels to hyperglycaemia, unpleasant dreams and nightmares, suicidal thoughts and behaviors, dysarthria, tachycardia, blurred vision, orthostatic hypotension (especially in the initial dose adjustment phase), dyspnea, constipation, indigestion, mild asthenia, peripheral edema, irritability, fever, increase in serum alanine aminotransferase (ALT), increase in γ-glutamyltransferase (GGT) activity. Uncommon: thrombocytopenia, anemia, decrease in platelet count, hypersensitivity (including cutaneous allergic reactions), hyponatremia, diabetes, convulsions, restless legs syndrome, tardive dyskinesia, syncope, QT prolongation, bradycardia, rhinitis, dysphagia, increased aspartate aminotransferase (AST), urine retention, sexual dysfunction. Rare: agranulocytosis, metabolic syndrome, sleepwalking, sleep disorders, sleep related disorders, deep vein thrombosis, pancreatitis, intestinal obstruction, jaundice, hepatitis, priapism, galactorrhea, breast swelling, menstrual disorders, neuroleptic malignant syndrome (hyponatremia, mental state disorders, muscle stiffness, autonomic autonomic dysfunction and increased creatine kinase activity), hypothermia, elevation of creatine phosphokinase. Very rare: anaphylactic reaction, maladjusted antiduretic hormone syndrome, exacerbation of existing diabetes mellitus, angioneurotic edema, Stevens-Johnson syndrome, rhabdomyolysis. Not known: neutropenia, toxic epidermal necrolysis, erythema multiforme, withdrawal symptoms in newborns. Cases of prolonged QT interval, ventricular arrhythmia, sudden-onset death, cardiac arrest and ventricular tachycardia have been observed with the use of neuroleptics. torsade de pointes. Side effects that are more common in children and adolescents (10-17 years) than in adults and side effects that were not seen in adults: very common: increased appetite, increased prolactin, increased blood pressure, extrapyramidal symptoms; often: fainting, rhinitis, vomiting, irritability.

Orally. Adults.Treatment of schizophrenia: total daily doses during the first 4 days of treatment are: 50 mg - day 1, 100 mg - day 2, 200 mg - day 3, 300 mg - day 4. From day 4, the dose should be 300-450 mg / day (usually effective dose). The dose can be adjusted in the range of 150 to 750 mg / day depending on the clinical response and tolerability of the patient. Quetiapine should be administered twice a day.Treatment of moderate to severe manic episodes in the course of bipolar disorder: total daily doses for the first 4 days of treatment are: 100 mg - day 1, 200 mg - day 2, 300 mg - day 3, 400 mg - day 4, then the dose should be increased by a maximum of 200 mg / day up to a daily dose of 800 mg / day on Day 6 of treatment. The dose can be adjusted between 200 and 800 mg / day depending on the clinical response and tolerability of the patient. The usual effective dose is 400 to 800 mg / day. Quetiapine should be administered twice a day.Treatment of episodes of depression in the course of bipolar disorder: Quetiapine should be administered once daily, in the evening before bedtime. The total daily doses during the first 4 days of treatment are: 50 mg - day 1, 100 mg - day 2, 200 mg - day 3, 300 mg - day 4. The recommended daily dose is 300 mg. In clinical trials, no additional benefit was observed in the group treated with the 600 mg dose compared to the 300 mg dose group. Individual patients may benefit from a 600 mg dose. Doses greater than 300 mg should be recommended by physicians experienced in the treatment of bipolar disorder. In some cases, depending on the patient's tolerance, a dose reduction to a minimum of 200 mg should be considered.Prevention of recurrence of episodes of bipolar disorder: to prevent relapses of bipolar, mixed and depressive episodes in the course of bipolar disorder in patients who have responded to quetiapine for the treatment of acute phase of the disease, treatment should continue at the same dose. The dose should be adjusted between 300 and 800 mg twice daily depending on the clinical response and tolerability of the patient.It is important that the lowest effective dose should be used in maintenance therapy.Special groups of patients. Caution should be exercised in elderly patients, especially in the initial dosing period; it may be necessary to increase the dose more slowly and administer a lower daily dose than in younger patients, depending on the clinical response and tolerability of the patient (mean clearance of quetiapine in the elderly decreases by 30-50% compared to younger patients). patients). Caution should be exercised when using the drug in patients with impaired hepatic function, especially during the initial period of use; administration of the drug should start with a dose of 25 mg / day; Depending on the patient's clinical response and tolerability, the dose can be increased daily by 25-50 mg until the effective dose is reached. The safety and efficacy of treatment in children and adolescents <18 years have not been evaluated, therefore this drug is not recommended in this age group.