Instructions Quetixol film-coated tablets 100 mg blister No. 30
Composition
active ingredient: quetiapine;
1 film-coated tablet contains 25 mg or 100 mg or 200 mg of quetiapine fumarate equivalent to quetiapine;
Excipients: microcrystalline cellulose; povidone K29-32; calcium hydrogen phosphate dihydrate; sodium starch glycolate (type A); lactose, monohydrate; magnesium stearate;
for 25 mg: Opadry II Pink 33G34594 coating (hypromellose 6cP; titanium dioxide (E 171); lactose monohydrate; macrogol 3350; triacetin; iron oxide yellow (E 172); iron oxide red (E 172));
for 100 mg: Opadry II Yellow 33G32578 coating (hypromellose 6cP; titanium dioxide (E 171); lactose monohydrate; macrogol 3350; triacetin; iron oxide yellow (E 172));
for 200 mg: shell Opadry II White 33G28435 (hypromellose 6cP; titanium dioxide (E 171); lactose monohydrate; macrogol 3350; triacetin).
Dosage form
Film-coated tablets.
Main physicochemical properties:
film-coated tablets, 25 mg: light orange, round, biconvex, with the inscription Q on one side;
film-coated tablets, 100 mg: yellow, round, biconvex, with the inscription Q on one side;
Film-coated tablets, 200 mg: white, oval, biconvex, with the inscription Q on one side.
Pharmacotherapeutic group
Antipsychotics. ATX code N05A H04.
Pharmacological properties
Mechanism of action.
Quetiapine is an atypical antipsychotic. Quetiapine and its active metabolite norquetiapine interact with different types of neurotransmitter receptors. Quetiapine and norquetiapine have high selectivity for serotonin (5-HT2) receptors and dopamine D1 and D2 receptors in the brain. It is this combination of receptor antagonism with greater selectivity for 5-HT2 receptors over D2 receptors that is thought to contribute to the clinical antipsychotic effects and low propensity for extrapyramidal side effects of Quetiapine compared to typical antipsychotics. Quetiapine and norquetiapine also have high affinity for histaminergic and α1-adrenergic receptors, but lower affinity for α2-adrenergic and serotonin receptors.
5-HT1A receptors. Quetiapine has no affinity for cholinergic muscarinic receptors or benzodiazepine receptors, whereas norquetiapine has moderate to high affinity for several muscarinic receptor subtypes, which may explain its anticholinergic (muscarinic) effects.
Norquetiapine (NET) inhibition, as well as partial agonist action at 5HT1A receptors, may contribute to the therapeutic efficacy of Quetiapine as an antidepressant.
Pharmacodynamics
Quetiapine is known to be active in tests of antipsychotic activity, such as conditioned avoidance. Quetiapine blocks the agonistic effects of dopamine, as assessed by behavioral or electrophysiological assessments, and increases the concentration of dopamine metabolites, a neurochemical expression of D2 receptor blockade.
It is known that in preclinical studies, during which the tendency to develop extrapyramidal symptoms was tested, quetiapine had an atypical activity profile and differed from standard antipsychotic drugs. Quetiapine did not lead to excessive sensitivity of dopamine D2 receptors after long-term use. Quetiapine, at doses effective for dopamine D2 receptor blockade, caused only mild catalepsy.
Quetiapine has been shown to be selective for the limbic system after chronic administration, as demonstrated by its ability to block depolarization in A10 mesolimbic neurons, but not in A9 nigrostriatal neurons, which contain dopamine.
Clinical safety
It is known that quetiapine treatment may cause a dose-dependent decrease in thyroid hormone levels.
Available data from placebo-controlled trials in elderly patients with dementia-related psychosis show that the incidence of cardiovascular adverse events per 100 patient-years in the quetiapine group was no higher than in patients receiving placebo.
Cataract
Clinical study data evaluating the cataractogenic potential of quetiapine
(200-800 mg/day) compared with risperidone (2-8 mg/day) in patients with schizophrenia or schizoaffective disorder, showed that the percentage of patients with increased lens opacity was not higher in the group of patients taking quetiapine (4%) compared with those receiving risperidone (10%) when using the drug for at least 21 months.
Pharmacokinetics
Absorption.
Quetiapine is well absorbed and extensively metabolized after oral administration. There is no significant change in the bioavailability of quetiapine when taken after food.
At steady state, the maximum molar concentration of the active metabolite of norquetiapine is 35% of that of quetiapine. The pharmacokinetics of quetiapine and norquetiapine are linear within the approved dose range.
Distribution.
Approximately 83% of quetiapine is bound to plasma proteins.
Quetiapine is extensively metabolized in the liver, and radiolabeled quetiapine has been shown to be less than 5% metabolized and excreted unchanged in the urine or feces. In vitro studies have shown that CYP3A4 is the major enzyme responsible for the cytochrome P450-mediated metabolism of quetiapine. Norquetiapine is primarily formed and eliminated by CYP3A4.
Approximately 73% of the radioactive label is excreted in the urine and 21% in the feces.
Quetiapine and some of its metabolites (including norquetiapine) have weak in vitro inhibitory effects on cytochrome P450 isoenzymes 1A2, 2C9, 2C19, 2D6 and 3A4.
In vitro inhibition of CYP isoenzymes occurred only at concentrations 5-50 times higher than those achieved in humans at doses ranging from 300 mg to 800 mg/day. Based on these in vitro results, it is unlikely that co-administration of quetiapine with other active substances will result in clinically significant inhibition of the cytochrome P450-mediated metabolism of other active substances.
Breeding.
The elimination half-lives of quetiapine and norquetiapine are approximately 7 hours and 12 hours, respectively. The mean molar fraction of free quetiapine and the active metabolite N-desalkylquetiapine excreted in the urine is < 5% of the administered dose.
Special populations.
Sex.
The pharmacokinetics of quetiapine do not differ between women and men.
Elderly patients.
The average clearance of quetiapine in elderly patients is 30-50% lower than in patients aged 18-65 years.
Patients with renal impairment.
In patients with significant renal impairment (creatinine clearance less than 30 ml/min/1.73 m2), the mean plasma clearance of quetiapine is reduced by approximately 25%, but individual clearance values remain within the range of healthy subjects.
Patients with impaired liver function.
In patients with liver damage (compensated alcoholic cirrhosis), the average plasma clearance of quetiapine is reduced by approximately 25%. Since quetiapine is extensively metabolized in the liver, plasma concentrations of quetiapine may be increased in patients with impaired liver function, and therefore dose adjustment may be required in this group of patients (see section 4.2).
Children.
Pharmacokinetic data are available in children receiving 400 mg quetiapine twice daily. At therapeutic doses, the exposure to parent compound quetiapine in children and adolescents (10-17 years) was generally similar to that in adults, although Cmax was higher in children than in adults. The AUC and Cmax for norquetiapine were higher, approximately 62% and 49% in children (10-12 years), and 28% and 14% in adolescents (13-17 years), respectively, compared to adults.
Indication
Treatment of schizophrenia.
Treatment of bipolar disorders:
for the treatment of moderate to severe manic episodes associated with bipolar disorder;
for the treatment of major depressive episodes associated with bipolar disorder;
for the prevention of relapse in patients with bipolar disorder whose manic episodes were treated with quetiapine.
Contraindication
Hypersensitivity to any of the components of the drug.
Concomitant use of cytochrome P450 3A4 inhibitors, such as HIV protease inhibitors, azole antifungals, erythromycin, clarithromycin and nefazodone (see section "Interaction with other medicinal products and other types of interactions").
Interaction with other medicinal products and other types of interactions
Given that quetiapine primarily acts on the central nervous system (CNS), Quetiapine should be used with caution in combination with other drugs with similar effects and with alcohol.
The pharmacokinetics of lithium were not altered when co-administered with quetiapine. There is evidence that in a 6-week randomized trial comparing the combination of lithium with quetiapine and placebo with quetiapine in adult patients with acute mania, an increased incidence of extrapyramidal symptoms (particularly tremor), somnolence, and weight gain was observed in the lithium-added group compared to the placebo-added group.
There were no clinically significant changes in the pharmacokinetics of sodium valproate and quetiapine when co-administered. In a retrospective study of children and adolescents receiving sodium valproate, quetiapine, or a combination of these drugs, an increase in the incidence of leukopenia and neutropenia was observed in the group receiving both drugs compared to the groups receiving these drugs separately.
In a multiple-dose pharmacokinetic study of quetiapine administered before and during treatment with carbamazepine (a known hepatic enzyme inducer), concomitant administration of carbamazepine significantly increased quetiapine clearance. This increase in clearance reduced systemic exposure to quetiapine (as measured by AUC) to an average of 13% of that seen with quetiapine alone, although some patients had a greater effect. This interaction may result in decreased plasma concentrations, and therefore, an increase in the dose of Quetiapine should be considered for each patient based on clinical response. Concomitant administration of Quetiapine with phenytoin (another microsomal enzyme inducer) resulted in an increase in quetiapine clearance of up to 450%. For patients taking a hepatic enzyme inducer, quetiapine therapy should only be initiated if the physician considers that the benefits of quetiapine outweigh the risks associated with discontinuation of the hepatic enzyme inducer. It is important that any changes in the dose of the inducer should be gradual. The dose of quetiapine may be reduced when phenytoin, carbamazepine, or other hepatic enzyme inducers are discontinued or when a drug that does not induce hepatic microsomal enzymes is substituted (e.g., sodium valproate).
CYP3A4 is a key enzyme involved in the cytochrome P450-mediated metabolism of quetiapine. In an interaction study in healthy volunteers, co-administration of quetiapine (25 mg) with ketoconazole (a CYP3A4 inhibitor) resulted in a 5- to 8-fold increase in quetiapine AUC. Therefore, co-administration of quetiapine with CYP3A4 inhibitors is contraindicated. It is also not recommended to consume grapefruit juice during treatment with quetiapine.
The pharmacokinetics of quetiapine were not altered after co-administration with cimetidine, a known inhibitor of the P450 enzyme.
The pharmacokinetics of quetiapine were not significantly altered after co-administration with the antidepressants imipramine (a known CYP2D6 inhibitor) or fluoxetine (a known CYP3A4 and CYP2D6 inhibitor).
The drug should be prescribed with caution to patients receiving other drugs with anticholinergic (muscarinic) effects (see section "Special instructions").
No interaction studies with cardiovascular drugs have been conducted.
Caution should be exercised when administering quetiapine concomitantly with drugs that disrupt electrolyte balance or prolong the QT interval.
Cases of false-positive enzyme immunoassay results for methadone and tricyclic antidepressants have been reported in patients taking quetiapine. It is recommended that equivocal screening immunoassay results be verified by an appropriate chromatographic method.
Application features
Since quetiapine is indicated for the treatment of multiple indications, the safety profile of the drug should be carefully considered in light of the individual patient's diagnosis and the dose being taken.
Children.
Quetiapine is not recommended for use in children and adolescents under 18 years of age due to the lack of data on the use of the drug in this age group. Clinical studies of quetiapine have shown that, in addition to the known safety profile established in adults (see section "Adverse reactions"), the frequency of some adverse events is higher in children than in adults (increased appetite, increased serum prolactin levels, vomiting, rhinitis, syncope), or may have different complications in children and adolescents (extrapyramidal symptoms and irritability), and an increase in blood pressure has been determined, which was not previously observed in studies with adult patients. In addition, changes in thyroid function tests have been observed in children.
It should also be noted that the delayed effects of quetiapine treatment on growth and puberty have not been studied beyond 26 weeks. The long-term effects on cognitive and behavioral development are unknown.
In placebo-controlled clinical trials of quetiapine in paediatric patients, quetiapine treatment was associated with an increased incidence of extrapyramidal symptoms (EPS) compared to placebo in patients treated for schizophrenia, bipolar mania and depression (see section 4.8).
Suicide/suicidal thoughts or clinical worsening.
Depression is associated with an increased risk of suicidal thoughts, self-harm and suicide (suicide-related events). This risk persists until significant remission is achieved. As improvement may not be observed during the first weeks of treatment or longer, patients should be closely monitored until such improvement occurs. It is general clinical experience that the risk of suicide may be increased in the early stages of improvement.
Other psychiatric conditions for which quetiapine is prescribed may also be associated with an increased risk of suicide-related events. In addition, these conditions may occur concurrently with depressive episodes. Therefore, the same precautions should be taken when treating other psychiatric conditions as when treating depressive episodes.
Patients with a history of suicide-related events or those who demonstrate a significant degree of suicidal ideation prior to initiation of treatment are at greater risk of suicidal thoughts or suicide attempts and should receive careful monitoring during treatment. It is known that a meta-analysis of placebo-controlled clinical trials of antidepressants in adult patients with psychiatric disorders showed an increased risk of suicidal behavior with antidepressants compared with placebo in patients under 25 years of age.
Close monitoring of patients, particularly those at high risk, should accompany drug therapy, especially at the beginning of treatment and during subsequent dose changes. Patients (and caregivers of patients) should be advised to monitor for clinical worsening, suicidal behaviour or thoughts, and unusual changes in behaviour and to seek medical advice immediately if symptoms present.
In short-term placebo-controlled studies in patients with major depressive episodes in bipolar disorder, an increased risk of suicide-related events was observed in young patients (under 25 years of age) treated with quetiapine compared to those treated with placebo (3.0% vs. 0%, respectively).
Metabolic risk.
Given the changes observed in clinical trials regarding body weight, blood glucose (see hyperglycemia) and lipids, there is a possibility of a worsening of the metabolic risk profile in individual patients, in which case appropriate treatment should be prescribed (see section "Adverse reactions").
Orthostatic hypotension.
Quetiapine treatment has been associated with orthostatic hypotension and associated dizziness (see section 4.8), which, like somnolence, usually occurs during the dose titration period. These events may contribute to an increased incidence of accidental injury (falls), particularly in the elderly. Therefore, patients should be advised to exercise caution until they are familiar with the possible effects of the medicinal product.
Quetiapine should be used with caution in patients with established cardiovascular or cerebrovascular disease or other conditions that may predispose to hypotension. Quetiapine may cause orthostatic hypotension, especially during the initial titration period. If this occurs, the dose or rate of titration should be reduced. A slow titration regimen may be considered in patients with cardiovascular disease.
Convulsions.
There was no difference in the incidence of seizures between patients taking quetiapine and those taking placebo. There are no data on the incidence of seizures in patients with a history of seizure disorders. As with other antipsychotics, caution is advised when prescribing the drug to patients with a history of seizures.
Extrapyramidal symptoms.
In placebo-controlled trials, quetiapine was associated with an increased incidence of extrapyramidal symptoms (EPS) compared to placebo in adult patients treated for major depressive episodes associated with bipolar disorder (see section 4.8). Quetiapine has been associated with the development of akathisia, characterised by a subjectively unpleasant or distressing restlessness and need to move, often accompanied by an inability to sit or stand still. These events are more likely to occur within the first few weeks of treatment. Increasing the dose in patients who develop these symptoms may be harmful.
Tardive dyskinesia.
If signs and symptoms of tardive dyskinesia appear, consideration should be given to reducing the dose or discontinuing the drug.
Symptoms of tardive dyskinesia may worsen and occur even after discontinuation of therapy (see section "Adverse reactions").
Drowsiness and dizziness.
Quetiapine treatment has been associated with somnolence and related symptoms such as sedation (see section 4.8). In clinical trials in patients with bipolar depression, these symptoms were reported to occur usually within the first 3 days of treatment and were mostly mild to moderate in intensity. Patients with bipolar depression who develop somnolence may need to be monitored for 2 weeks after the onset of somnolence or until symptoms resolve, or discontinuation of treatment may be considered.
There have been reports of sleep apnea syndrome in patients taking quetiapine, therefore quetiapine should be used with caution in patients with a history of sleep apnea syndrome or at risk for its development, for example, overweight/obese patients, male patients, patients receiving concomitant therapy with CNS depressants.
Neuroleptic malignant syndrome.
Neuroleptic malignant syndrome may be associated with treatment with antipsychotics, including quetiapine. Clinical manifestations include hyperthermia, altered mental status, muscle rigidity, autonomic instability, and elevated creatine phosphokinase. In such cases, the drug should be discontinued and appropriate treatment initiated.
Severe neutropenia and agranulocytosis.
Severe neutropenia (neutrophil count < 0.5 × 109/L) has been reported in studies with quetiapine. The majority of cases of severe neutropenia have occurred within a few months of initiating quetiapine therapy. There is no apparent dose-related relationship. Cases of severe neutropenia with fatal outcome have been reported in the post-marketing setting. Possible risk factors for neutropenia include pre-existing low white blood cell count and a history of drug-induced neutropenia. Agranulocytosis has been reported in patients without pre-existing risk factors. Quetiapine should be discontinued in patients with neutrophil counts < 1.0 × 109/L. Patients should be monitored for signs of infection and neutrophil counts should be monitored (until they exceed 1.5 × 109/L).
The possibility of neutropenia should be considered in patients with infections, especially in the absence of obvious predisposing factors, and in patients with fever of unknown origin, and appropriate clinical measures should be taken. Patients should be advised to promptly report symptoms consistent with agranulocytosis or infection (e.g. fever, weakness, malaise, or sore throat) at any time during treatment with quetiapine, and to monitor WBC and ANC counts promptly, especially in the absence of precipitating factors.
Anticholinergic (muscarinic) effects.
Norquetiapine, the active metabolite of quetiapine, has moderate to high affinity for several subtypes of muscarinic receptors. This contributes to the occurrence of adverse reactions, reflecting anticholinergic effects when quetiapine is used at recommended doses, when quetiapine is used concomitantly with other drugs that have anticholinergic effects, and in overdose. Quetiapine should be used with caution in patients receiving drugs that have anticholinergic (muscarinic) effects. Quetiapine should be used with caution in patients with urinary retention, significant prostatic hypertrophy, intestinal obstruction, increased intraocular pressure or angle-closure glaucoma, present at the time of treatment or in history (see sections “Interaction with other medicinal products and other forms of interaction”, “Adverse reactions”, “Pharmacodynamic properties”, “Overdose”).
Sudden discontinuation of the drug.
Acute withdrawal symptoms such as nausea, vomiting, headache, diarrhoea, dizziness, irritability and insomnia have been reported very rarely after abrupt discontinuation of high doses of antipsychotic drugs. Recurrence of psychotic symptoms and involuntary movement disorders (e.g. akathisia, dystonia and dyskinesia) have been reported. Therefore, gradual discontinuation over a period of at least 1 to 2 weeks is recommended.
Interactions.
See also section “Interaction with other medicinal products and other types of interactions”.
Concomitant use of quetiapine with potent hepatic enzyme inducers such as carbamazepine or phenytoin significantly reduces quetiapine plasma concentrations, which may reduce its efficacy. Treatment with Quetiapine in patients receiving a hepatic enzyme inducer should only be initiated if the physician considers that the benefits of the drug outweigh the risks of withdrawing the hepatic enzyme inducer. It is important that any changes in the use of the inducer are gradual. If necessary, it should be replaced by a non-inducer (e.g. sodium valproate).
Effect on body weight.
Weight gain has been reported during treatment with quetiapine and should be monitored and managed appropriately in accordance with antipsychotic guidelines.
Hyperglycemia and/or development or exacerbation of diabetes mellitus, sometimes associated with ketoacidosis or coma, have been reported rarely, including several fatal cases (see section 4.8). In some cases, these events occurred in patients with increased body weight, which may have been a contributing factor. Appropriate clinical monitoring is recommended in accordance with the relevant guidelines for the use of antipsychotics. Patients treated with any antipsychotic agent, including quetiapine, should be observed for signs and symptoms of hyperglycemia (such as polydipsia, polyuria, polyphagia and weakness), and patients with diabetes mellitus or risk factors for diabetes mellitus should be monitored regularly for worsening of glucose control. Weight should be monitored regularly.
Lipids.
Cases of increased triglycerides, low-density lipoproteins and total cholesterol, as well as a decrease in high-density lipoproteins have been described (see section "Adverse reactions"). In case of changes in lipid levels, treatment should be carried out according to clinical indications.
Increased QT interval.
In clinical trials and when quetiapine was used as directed, no consistent increase in absolute QT interval was observed. In post-marketing experience, QT prolongation has been reported at therapeutic doses (see section 4.8) and in overdose (see section 4.8). As with other antipsychotics, caution should be exercised when prescribing quetiapine to patients with cardiovascular disease or a family history of QT prolongation. Caution should be exercised when prescribing quetiapine with drugs known to prolong the QT interval or other neuroleptics (see section 4.5), especially in the elderly, patients with congenital long QT syndrome, congestive heart failure, cardiac hypertrophy, hypokalemia, or hypomagnesemia.
Cardiomyopathy and myocarditis.
Cardiomyopathy and myocarditis have been reported with quetiapine in clinical trials and during post-marketing experience (see section 4.8). Discontinuation of quetiapine should be considered in patients suspected of developing cardiomyopathy or myocarditis.
Elderly patients with dementia-related psychosis.
Quetiapine is not approved for the treatment of psychosis associated with dementia.
In patients with dementia, an almost 3-fold increase in the risk of adverse cerebrovascular events has been observed with the use of some atypical antipsychotics. The mechanism of this increased risk is unknown. An increased risk cannot be excluded for other antipsychotics or for other patient populations. Quetiapine should be used with caution in patients with risk factors for stroke.
A meta-analysis of atypical antipsychotics has shown that elderly patients with dementia-related psychosis are at increased risk of death compared with placebo. However, in two 10-week placebo-controlled trials of quetiapine in the same population (mean age 83 years, range 56-99 years), the mortality rate in quetiapine-treated patients was 5.5% compared with 3.2% in the placebo group. The mortality rates in the studies were from a variety of causes, as expected for this patient population.
Elderly patients with Parkinson's disease/parkinsonism.
A retrospective population-based study examining the use of quetiapine in patients with major depressive disorder showed an increased risk of death in patients aged 65 years and older while taking quetiapine. This association was not observed when patients with Parkinson's disease were excluded from the study. Caution should be exercised when prescribing quetiapine to elderly patients with Parkinson's disease.
Dysphagia.
Dysphagia has been reported with quetiapine (see section 4.8). Quetiapine should be used with caution in patients at risk of aspiration pneumonia.
Constipation and intestinal obstruction.
Constipation is a risk factor for the development of intestinal obstruction. Cases of constipation and intestinal obstruction have been reported with quetiapine (see section 4.8). These reports include fatal cases in patients who are at higher risk of developing intestinal obstruction, including those receiving multiple medications that reduce intestinal motility and/or may not report symptoms of constipation. Patients with intestinal obstruction/ileus should be managed with close monitoring and emergency medical care.
Liver effects.
If jaundice occurs, quetiapine should be discontinued.
Cases of venous thromboembolism (VTE) have been reported with antipsychotic drugs. Since patients taking antipsychotics often have acquired risk factors for VTE, all possible risk factors for VTE should be identified before and during treatment with quetiapine and preventive measures should be taken.
Pancreatitis.
Cases of pancreatitis have been reported in clinical trials and during the post-marketing period. Among the reports in the marketing reports, it was noted that many, although not all, patients had factors known to be associated with pancreatitis, such as elevated triglyceride levels, gallstones, and alcohol consumption.
Additional information.
Data on the use of quetiapine in combination with divalproex or lithium in moderate to severe manic episodes are limited; however, the combination therapy was well tolerated (see sections 4.8 and 5.1). These data showed an additive effect by the third week of treatment.
Misuse and abuse.
Cases of misuse and abuse have been reported. Quetiapine should be prescribed with caution to patients with a history of alcohol or drug abuse.
Lactose.
The drug contains lactose, therefore patients with rare hereditary diseases such as galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not use this drug.
Use during pregnancy or breastfeeding
Pregnancy
The safety and efficacy of the drug during pregnancy have not been established, therefore Quetixol should be prescribed only in cases where the expected benefit to the mother outweighs the possible risk to the fetus.
The use of antipsychotics (including quetiapine) during the third trimester of pregnancy can lead to adverse reactions in the newborn, including extrapyramidal disorders and/or withdrawal syndrome, which may vary in severity and duration after delivery. There have been reports of agitation, hypertension, hypotension, somnolence, respiratory distress syndrome or feeding disorders. Therefore, newborns should be closely monitored.
Breastfeeding period
The extent of excretion of quetiapine into breast milk is not known, therefore breastfeeding should be discontinued during treatment with the drug.
Ability to influence reaction speed when driving vehicles or other mechanisms
Given that the drug primarily acts on the central nervous system, quetiapine may adversely affect activities requiring mental alertness. Therefore, patients are advised not to drive or operate machinery until individual sensitivity to such effects has been determined.
Method of administration and doses
There are different dosage regimens for each indication. It is important to ensure that the patient is prescribed the dosage that is appropriate for their condition. Quetixol can be taken with or without food.
Adults
For the treatment of schizophrenia
Quetiapine should be taken twice a day.
The total daily dose for the first 4 days of therapy is 50 mg (day 1), 100 mg
(Day 2), 200 mg (Day 3) and 300 mg (Day 4). From Day 4 onwards, the dose should be titrated to the usual effective dose of 300-450 mg per day. Depending on clinical efficacy and individual tolerability of treatment, the dose may be adjusted within 150-750 mg per day.
For the treatment of moderate to severe manic episodes associated with bipolar disorder
Quetiapine should be taken twice a day.
The total daily dose for the first four days of therapy is 100 mg (day 1), 200 mg (day 2), 300 mg (day 3) and 400 mg (day 4). Further dose increases to
800 mg/day on day 6 should be done gradually with dose increases of no more than
200 mg/day.
Depending on clinical efficacy and tolerability, the dose may range from 200 mg to 800 mg/day. The usual effective dose is in the range of 400 mg to 800 mg/day.
For the treatment of major depressive episodes associated with bipolar disorder
Quetiapine should be administered once daily at bedtime. The total daily dose for the first four days of treatment is 50 mg (on day 1), 100 mg (on day 2), 200 mg (on day 3) and 300 mg (on day 4). The recommended daily dose is 300 mg. Clinical studies have shown that the 600 mg group did not show any additional benefit compared to the 300 mg group. A dose of 600 mg may be effective in individual patients. Doses above 300 mg should be prescribed by a physician experienced in the treatment of bipolar disorder. Clinical studies have shown that in individual patients, if there are problems with intolerance, a dose reduction to the minimum of 200 mg should be considered.
For relapse prevention
