Index of drugs

Treatment of schizophrenia. Treatment of bipolar disorder: treatment of moderate to severe manic episodes; treatment of major depressive episodes; preventing the recurrence of bipolar disorder (mixed episodes, mania or depression) in patients who have responded to previous Quetiapine treatment.

1 tabl powl. contains 100 mg, 200 mg or 300 mg of quetiapine (as fumarate). The preparation contains lactose. Table. powl. 100 mg contain sunset yellow.

Quetiapine is an atypical antipsychotic drug. Quetiapine and its active metabolite nor-quetiapine have an affinity for many receptors that bind neurotransmitters. They show affinity for 5HT serotonin receptors₂ and Dopamine D₁ and D₂. Antagonism of receptors and greater selectivity towards the 5HT receptor₂ compared to D₂ they are responsible for antipsychotic properties and a low incidence of extrapyramidal symptoms. In addition, nor-quetiapine has a high affinity for the norepinephrine transporter. Quetiapine and nor-quetiapine also have high affinity for histamine and α receptors₁-adrenergic and lower affinity for α receptors₂-renergic and serotonin 5-HT_1A. Affinity to muscarinic and benzodiazepine cholinergic receptors is negligible. Following oral administration, quetiapine is well absorbed from the gastrointestinal tract 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. It is metabolized mainly in the liver (mainly involving CYP3A4). About 73% are excreted in the urine and 21% in the faeces. T_0,5 in the elimination phase is 7 h for quetiapine and 12 h for nor-quetiapine.

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

Quetiapine is not recommended for use in children and adolescents <18 years of age, due to the lack of data supporting the use in this age group (the effects of prolonged quetiapine use, over 26 weeks on growth and maturation were not investigated). Long-term effects on their cognitive and behavioral development are unknown. The safety and efficacy of the medicine has not been studied in patients> 65 years with episodes of depression in the course of bipolar disorder. Depression in the course of bipolar disorder is associated with an increased risk of suicidal thoughts, self harm and suicide; the risk persists until clinically significant remission is achieved. Because improvement may not occur for the first few weeks or more, the patient should remain under strict medical supervision until improvement occurs. General experience indicates that the risk of suicide increases in the early stages of improving the clinical condition of the patient. Patients with severe depressive episodes in bipolar disorder have been found to have an increased risk of suicidal behavior in young adult patients under 25 who have been treated with quetiapine compared to patients who received placebo. The potential risk of suicide attempts after a sudden discontinuation of the drug should be considered, taking into account known risk factors associated with the disease being treated. In patients treated for other psychiatric disorders, the same precautions should be taken as in patients with severe depressive disorder. Patients with a history of suicide-related events or patients exhibiting a significant degree of suicidal tendency before commencing treatment are considered to be at increased risk of suicidal thoughts or suicide attempts and should be closely monitored during treatment. The risk of suicidal behavior in patients under the age of 25 has been demonstrated in clinical trials with antidepressants used in adult patients with mental disorders (compared with placebo).During treatment, especially at the beginning of therapy and after dose adjustment, patients should be closely monitored, particularly those at high risk. Patients (and their carers) should be warned about the need to pay attention to any symptom of clinical disease, behavior or suicidal thoughts or abnormal changes in behavior, and in the event of their occurrence, to immediately seek medical attention. Patients with bipolar depression who are experiencing drowsiness of severe intensity may require more frequent visits for a minimum of 2 weeks after the onset of somnolence, or until they improve, and may need to consider discontinuation of treatment. Caution in patients with known cardiovascular disease, cerebrovascular disease or other conditions predisposing to hypotension (if symptoms of hypotension occur, consider reducing the dose or the rate of its increase), with history of seizures, risk factors for stroke, QT prolongation in a family history, with the risk of aspiration pneumonia. Use caution when quetiapine is used concomitantly with other QTc prolonging drugs, and neuroleptics, particularly in elderly patients and those with congenital QT prolonged-type syndrome, congestive heart failure, hypertrophy, hypokalaemia or hypomagnesaemia. A slower dose escalation regimen should be considered in patients with cardiovascular disease. The use of quetiapine is accompanied by the development of akathisia; the symptoms are more likely to occur in the first few weeks of treatment. In patients who develop symptoms, increasing the dose may be harmful. If a patient develops symptoms of tardive dyskinesia, a dose reduction or discontinuation of quetiapine should be considered. The symptoms of tardive dyskinesia may worsen or even occur after discontinuation of treatment. Patients should be monitored for signs of hyperglycaemia (such as polydipsia, polyuria, polyphagia and asthenia), body weight should be monitored regularly. In the case of a neuroleptic malignant syndrome, quetiapine should be discontinued and appropriate treatment instituted. In patients with neutrophil counts <1 x 10⁹/ l, quetiapine should be discontinued; patients should be monitored for signs of infection, and the number of neutrophils should be monitored until they exceed 1.5 x 10⁹/ L. In patients using hepatic enzyme inducers, quetiapine treatment should only be started if the benefit of quetiapine exceeds the risk of withdrawal from liver-inducers. It is important that changes in hepatic enzyme modifications are made gradually, and if necessary, these drugs should be replaced with medicines not affecting liver enzymes (eg sodium valproate). Do not use in patients with dementia-related psychosis (increased risk of side effects associated with cerebral circulation). Since patients taking antipsychotics often have acquired risk factors for thromboembolism, all potential risk factors for thromboembolism should be identified and appropriate precautions should be taken before and during treatment with quetiapine. Data on the use of quetiapine in combination with valproic acid or lithium in the treatment of moderate to severe manic episodes are limited, however, such combinations have been well tolerated; data indicate the occurrence of an additive effect in the third week of drug use. Caution should be exercised in patients with hepatic impairment and in elderly patients (especially at the beginning of treatment). Due to the lactose content, the preparation should not be used in patients with hereditary galactose intolerance, Lapp lactase deficiency or malabsorption of glucose-galactose. The 100 mg dose contains sunset yellow, which may cause allergic reactions.

It can only be used during pregnancy if the potential benefits outweigh the risks. In newborns exposed to antipsychotics in the third trimester of pregnancy, there is a risk of side effects including extrapyramidal and / or withdrawal symptoms.Excessive agitation, hypertension, hypotension, tremor, drowsiness, respiratory disorders or feeding disorders have been observed, therefore the condition of newborns should be carefully monitored. Quetiapine is excreted in human milk. You should avoid breastfeeding while taking the medicine.

Very common: decrease in hemoglobin, headache and dizziness, drowsiness, dry mouth, withdrawal symptoms (insomnia, nausea, headache and dizziness, diarrhea, vomiting and irritability), increase in triglycerides in the blood, increase in total cholesterol (mainly LDL), low HDL cholesterol, weight gain. Common: leukopenia, eosinophilia, decreased neutrophil count, hyperprolactinemia, decrease in total T₄free T₄total T₃, increased TSH, increased appetite, unusual dreams and nightmares, suicidal thoughts and behaviors, syncope, extrapyramidal symptoms, dysarthria, palpitations, tachycardia, blurred vision, orthostatic hypotension, rhinitis, apnea, constipation, indigestion, mild weakness , peripheral edema, irritability, fever, elevation of ALT and AST in the blood, elevated GGTP levels, hyperglycaemia. Uncommon: thrombocytopenia, anemia, hypersensitivity (including allergic skin reactions), decreased free T concentration₃, hypothyroidism, hyponatremia, diabetes, epileptic seizures, restless leg syndrome, tardive dyskinesia, dysphagia, sexual dysfunction, QT prolongation, bradycardia. Rare: agranulocytosis, metabolic syndrome, somnambulism and similar behaviors (such as sleep telling and eating disorders related to sleep), venous thromboembolism, pancreatitis, jaundice, hepatitis, priapism, galactorrhoea, breast swelling, menstrual disorders, malignant neuroleptic syndrome, hypothermia, elevation of creatine phosphokinase. Very rare: anaphylactic reaction, abnormal secretion of antidiuretic hormone, angioedema, Stevens-Johnson syndrome, decay of striated muscles. Not known: neutropenia, toxic epidermal necrolysis, erythema multiforme, withdrawal syndrome in the newborn. During the use of neuroleptics, cases of prolonged QT interval, ventricular arrhythmia, sudden unexplained death, cardiac arrest andtorsade de pointes. For children and adolescents, the same adverse reactions as described above in adult patients should be considered. With an increased frequency or those that have not been identified in adults, you may experience: very often - increased appetite, increased prolactin, increased blood pressure, extrapyramidal symptoms; often - 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 the 4th day of treatment, the dose should be gradually increased to an effective dose of typically 300-450 mg / day. Depending on the response and tolerance in individual patients, the dose may be adjusted in the range of 150-750 mg / day. The drug administered twice a day.Treatment of moderate to severe manic episodes in the course of bipolar disorderj: 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, further dose adjustment up to a maximum of 800 mg / day in 6 Day of treatment should be gradually increased by a value not exceeding 200 mg / day. Depending on the response and tolerance in individual patients, the dose can be adjusted in the range of 200-800 mg / day. The usual effective dose is 400-800 mg / day. The drug administered twice a day.Episode treatmentóin depression in the course of bipolar disorder: total daily doses in the first 4 days of treatment are: 50 mg - day 1, 100 mg - day 2, 200 mg - day 3 and 300 mg - day 4. The recommended daily dose is 300 mg. In clinical trials, no additional benefit was found in the 600 mg group compared to those receiving the 300 mg dose. The 600 mg dose may be beneficial in individual patients.Administration of the drug in doses above 300 mg should be started under the supervision of doctors with experience in the treatment of bipolar disorder. For drug tolerance concerns, a dose reduction of at least 200 mg should be considered. The drug administered once a day, before bedtime.Prevention of relapse of bipolar disorder(mixed episodes, mania or depression): patients who have responded to intensive quetiapine treatment for bipolar disorder should continue treatment with the same dose. The dose should be individually determined depending on the clinical response and tolerability of the treatment, in the range of 300-800 mg per day. The drug administered twice a day. In maintenance therapy, the lowest effective dose should be used. Caution should be exercised in elderly patients, especially in the initial dosing period; Depending on the clinical response and tolerability in individual patients, gradual dose increases should be performed more slowly and at lower daily doses than those used in younger patients (mean clearance of quetiapine in plasma was reduced by 30-50% in the elderly compared to younger patients ). No dose adjustment is required in patients with impaired renal function. Caution should be exercised when using the drug in patients with known hepatic impairment, especially during the initial period of use; administration of the drug should start with a dose of 25 mg / day; Depending on the clinical response and tolerability in individual patients, the dose should be increased daily by 25-50 mg until the effective dose is reached. The drug administered regardless of meals.