Instructions for use Kvetiron 100 film-coated tablets 100 mg No. 60
Composition
active ingredient: quetiapine;
1 tablet contains quetiapine fumarate calculated as 100% dry substance quetiapine 25 mg, 100 mg or 200 mg;
excipients: lactose monohydrate, calcium hydrogen phosphate dihydrate, microcrystalline cellulose, sodium starch glycolate, povidone, magnesium stearate; shell: Opadry II White (Kvetiron 25, Kvetiron 200) (polyethylene glycol, polyvinyl alcohol, talc, titanium dioxide (E 171)), Opadry II Yellow (Kvetiron 100) (polyethylene glycol, polyvinyl alcohol, talc, titanium dioxide (E 171), quinoline yellow (E 104), iron oxide red (E 172), iron oxide yellow (E 172)).
Dosage form
Film-coated tablets.
Main physicochemical properties:
Kvetiron 25: white film-coated tablets with a biconvex surface, round in shape.
Kvetiron 100: yellow film-coated tablets with a biconvex surface, round in shape, with a score on one side.
Kvetiron 200: white, film-coated tablets with a biconvex surface, round in shape, with a score 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 affinity 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 extrapyramidal disorder (EPD) profile of Quetiapine compared to typical antipsychotics. Quetiapine and norquetiapine do not have high affinity for benzodiazepine receptors, but they do have high affinity for histaminergic and α1-adrenergic receptors and moderate affinity for α2-adrenergic receptors.
Quetiapine has low or no affinity for cholinergic muscarinic 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 its partial agonist action at 5HT1A receptors, may contribute to the therapeutic efficacy of Quetiapine as an antidepressant.
Pharmacodynamics.
Quetiapine is known to be effective in tests of antipsychotic activity, such as conditioned avoidance.
Quetiapine blocks the effects of dopamine agonists, as evidenced by behavioral or electrophysiological assessments, and increases the concentration of dopamine metabolites, which is neurochemical evidence of D2 receptor blockade.
In preclinical studies on the study of EPR, it was found that quetiapine had an atypical activity profile and was different from typical 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.
For long-term use, quetiapine has been shown to be selective for the limbic system and to block depolarization of mesolimbic neurons, but not nigrostriatal dopaminergic neurons.
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 norquetiapine is 35% of the concentration 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.
Metabolism.
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 primary cytochrome P450 enzyme responsible for quetiapine metabolism. Norquetiapine is primarily metabolized and eliminated via the CYP3A4 isoenzyme. Approximately 73% of the radiolabeled dose 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.
Based on these in vitro results, it is unlikely that co-administration of quetiapine with other active substances would result in clinically significant inhibition of the cytochrome P450-mediated metabolism of the other active substances. Animal studies have shown that quetiapine can induce cytochrome P450 enzymes. However, a specific drug-drug interaction study in psychotic patients did not reveal an increase in cytochrome P450 activity following quetiapine administration.
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
Schizophrenia.
Bipolar disorders, including:
for the treatment of moderate to severe manic episodes in bipolar disorder;
for the treatment of severe depressive episodes in bipolar disorder;
prevention of relapse in patients with bipolar disorder whose manic or depressive episodes were treated with quetiapine.
Contraindication
Increased individual sensitivity 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
Quetiapine should be used with caution in combination with drugs that act on the central nervous system. Therefore, alcohol consumption is strictly prohibited during treatment.
The drug should be prescribed with caution to patients receiving other drugs with anticholinergic (muscarinic) effects (see section "Special warnings and precautions for use").
Cytochrome P450 (CYP) 3A4 is the enzyme primarily responsible for the cytochrome P450-mediated metabolism of quetiapine. In a drug-drug interaction study in healthy volunteers, co-administration of quetiapine (25 mg) with ketoconazole, a CYP 3A4 inhibitor, resulted in a 5- to 8-fold increase in quetiapine AUC. Therefore, co-administration of quetiapine with CYP 3A4 inhibitors is contraindicated. It is also not recommended to consume grapefruit juice during treatment with quetiapine.
It is known that in a multiple-dose study to evaluate the pharmacokinetics of quetiapine administered before and during treatment with carbamazepine (an inducer of liver microsomal enzymes), concomitant use of carbamazepine significantly increased the clearance of quetiapine.
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 lower plasma concentrations of the drug, which may affect the efficacy of quetiapine therapy.
Concomitant use of quetiapine and phenytoin (an inducer of liver microsomal enzymes) leads to an increase in quetiapine clearance by up to 450%. For patients taking a liver 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 inducer of liver microsomal enzymes. It is important that any change in inducer should be gradual and, if necessary, replaced with a drug that does not induce liver microsomal enzymes (for example, sodium valproate).
The pharmacokinetics of quetiapine are not significantly altered by co-administration with risperidone or haloperidol. Co-administration of quetiapine and thioridazine results in an increase in quetiapine clearance by approximately 70%.
The pharmacokinetics of quetiapine are not significantly altered by co-administration with cimetidine, which is a cytochrome P450 inhibitor.
The pharmacokinetics of lithium are not altered when co-administered with quetiapine.
It is known that in a 6-week randomized study comparing the use of the combination of lithium and quetiapine with the combination of placebo and quetiapine in adult patients suffering from acute mania, an increased incidence of extrapyramidal events (especially tremor), somnolence and weight gain was observed in the lithium group compared to the placebo group (see section 5.1).
The pharmacokinetics of sodium valproate and quetiapine are not altered by co-administration. It is known that 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.
Interaction studies with the most common cardiovascular drugs have not 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 to verify questionable screening immunoassay results using a reductive chromatographic method.
Application features
Since quetiapine is approved for multiple indications, the safety profile of the drug should be carefully considered in light of the individual patient's diagnosis and the dose they are taking.
Children
Quetiapine is not recommended for use in children and adolescents (under 18 years of age) due to the lack of data in this age group. Clinical trials of quetiapine have shown that, in addition to the known safety profile established in adults (see section 4.8), the frequency of some adverse events is higher in children than in adults (increased appetite, increased serum prolactin levels, vomiting, rhinitis, and syncope) or may have different consequences in children and adolescents (extrapyramidal symptoms and irritability), and an increase in blood pressure has been observed, which has not previously been observed in studies involving adult patients. In addition, changes in thyroid function tests have been observed in children and adolescents.
It should also be noted that the delayed effects of quetiapine treatment on growth and puberty have not been studied beyond 26 weeks. 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 and bipolar mania and depression (see section 4.8).
Suicide/suicidal thoughts or clinical worsening
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 major depressive episodes. Therefore, the same precautions should be observed when treating other psychiatric disorders as when treating major 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. A meta-analysis of placebo-controlled clinical trials of antidepressants in adult patients with psychiatric disorders has shown an increased risk of suicidal behaviour 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 clinical trials in patients with major depressive episodes in bipolar disorder, an increased risk of suicidal events and manifestations was observed in young patients (aged <25 years) treated with quetiapine compared to those treated with placebo (3% vs. 0%, respectively). A population-based retrospective analysis of quetiapine in the treatment of patients with major depressive disorder found an increased risk of self-harm and suicide in patients aged 24 to 64 years without a history of self-harm when quetiapine was used with other antidepressants.
Metabolic risk
Given the identified risk of worsening of the metabolic profile, including changes in body weight, blood glucose (see "Hyperglycemia") and lipids, observed during clinical studies, it is necessary to assess the patient's metabolic parameters at the beginning of treatment, and changes in these parameters should be monitored regularly during the course of treatment. Worsening of these parameters should be corrected taking into account the clinical relevance of the disorder (see section "Adverse reactions").
Extrapyramidal symptoms
In placebo-controlled trials, quetiapine has been associated with an increased incidence of extrapyramidal symptoms (EPS) compared to placebo in 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 dose reduction or discontinuation of quetiapine. Symptoms of tardive dyskinesia may worsen or even recur after discontinuation of treatment (see section 4.8).
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.
Orthostatic hypotension
Quetiapine treatment has been associated with orthostatic hypotension and dizziness (see section 4.8), which, like somnolence, usually occurs during the initial 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 disease, cerebrovascular disease, or other conditions that may predispose to hypotension. Dose reduction or longer titration should be considered if orthostatic hypotension occurs, especially in patients with underlying cardiovascular disease.
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, in patients who are overweight/obese, in male patients, and in patients receiving concomitant therapy with central nervous system depressants.
Convulsions
It is known that in controlled clinical trials there was no difference in the incidence of seizures between patients taking quetiapine and those taking placebo. There are no data on cases of seizures in patients with a history of epilepsy. As with other antipsychotics, caution is recommended when treating patients with a history of seizures (see section "Adverse reactions").
Neuroleptic malignant syndrome
Neuroleptic malignant syndrome has been associated with treatment with antipsychotics, including quetiapine (see section 4.8). Clinical manifestations of the syndrome include hyperthermia, altered mental status, muscle rigidity, autonomic instability, and elevated creatine phosphokinase. In such cases, quetiapine should be discontinued and appropriate medical treatment should be initiated.
Severe neutropenia and agranulocytosis
Severe neutropenia (neutrophil count < 0.5 x 109/l) has been reported uncommonly in studies with quetiapine. Most cases of severe neutropenia have occurred within a few months of initiating quetiapine treatment. There was no clear dose-response relationship. In post-marketing experience, some cases have been fatal. Possible risk factors for neutropenia include a history of low white blood cell counts and a history of drug-induced neutropenia. However, some cases have occurred in patients without pre-existing risk factors. Quetiapine should be discontinued in patients with neutrophil counts < 1 x 109/l. Patients should be monitored for signs and symptoms of infection and for neutrophil counts (until the count exceeds 1.5 x 109/l).
The possibility of neutropenia should be considered in patients with infection and fever, especially in the absence of obvious contributing factor(s), and appropriate clinical measures should be taken. Patients should be advised to report promptly any symptoms consistent with agranulocytosis or infection (e.g. fever, weakness, malaise or sore throat) at any time during treatment with quetiapine. These patients should have a WBC count and absolute neutrophil count (ANC) performed promptly, especially in the absence of contributing factors.
Anticholinergic (muscarinic) syndrome
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, with concomitant use of quetiapine and other drugs with anticholinergic effects in overdose conditions. Quetiapine should be used with caution in patients receiving drugs with anticholinergic (muscarinic) effects. Quetiapine should be used with caution in patients with urinary retention (urinary retention), significant prostatic hypertrophy, intestinal obstruction or related conditions, increased intraocular pressure or angle-closure glaucoma.
Interactions
See also section “Interaction with other medicinal products and other types of interactions”.
Concomitant use of quetiapine and a strong inducer of liver microsomal enzymes, such as carbamazepine or phenytoin, significantly reduces quetiapine plasma concentrations, which may reduce the effectiveness of quetiapine therapy.
Patients who have been receiving inducers of liver microsomal enzymes should only be started on quetiapine if the physician considers that the benefits of quetiapine outweigh the risks of discontinuing the inducer of liver microsomal enzymes. It is important that the change in treatment with such an inducer is carried out gradually, and if necessary, it is replaced by a non-inducer (for example, sodium valproate).
Body weight
Weight gain has been observed in patients treated with quetiapine, and weight should be monitored and adjusted as clinically indicated in accordance with appropriate antipsychotic guidelines (see section 4.8).
Hyperglycemia and/or development or exacerbation of diabetes mellitus, sometimes associated with ketoacidosis or coma, 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 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
Increased triglycerides, low-density lipoprotein (LDL) and total cholesterol levels, and decreased high-density lipoprotein (HDL) cholesterol levels (see section 4.8). If lipid levels change, treatment should be administered as clinically indicated.
QT prolongation
In clinical trials and when used as directed, quetiapine was not associated with a consistent increase in absolute QTc interval. In post-marketing experience, QTc prolongation has been observed 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 QTc prolongation. If quetiapine, like other neuroleptics, is prescribed simultaneously with drugs that increase the QTc interval, caution should be exercised (see section "Interaction with other medicinal products and other types of interactions"), especially in elderly patients, patients with congenital long QTc syndrome, heart failure, cardiac hypertrophy, hypokalemia or hypomagnesemia, as well as patients with a family history of QTc prolongation.
Cardiomyopathy and myocarditis
Cardiomyopathy and myocarditis have been reported in clinical trials and during post-marketing surveillance (see section 4.8). Discontinuation of quetiapine treatment should be considered in patients suspected of developing cardiomyopathy or myocarditis.
Severe skin adverse reactions
Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), acute generalised exanthematous pustulosis, erythema multiforme and drug reaction with eosinophilia and systemic symptoms (DRESS), which can be life-threatening or fatal, have been reported very rarely during treatment with quetiapine.
Severe cutaneous adverse reactions usually present as one or more of the following: widespread skin rash, which may be pruritic or pustular, exfoliative dermatitis, fever, lymphadenopathy, and eosinophilia or neutrophilia. The majority of these reactions occurred within 4 weeks of initiating quetiapine therapy, and some cases of DRESS syndrome were observed within 6 weeks of initiating quetiapine therapy. If signs and symptoms suggestive of these severe skin reactions occur, quetiapine should be discontinued immediately and alternative treatment options considered.
Treatment withdrawal
Abrupt discontinuation of quetiapine may result in an acute withdrawal syndrome, which may include insomnia, nausea, headache, diarrhea, vomiting, dizziness, and irritability. Therefore, it is recommended that the drug be discontinued gradually, over a period of at least one to two weeks (see section 4.8).
Elderly patients with dementia-related psychosis
Quetiapine is not recommended for the treatment of patients with dementia-related psychosis. In randomized, placebo-controlled trials in patients with dementia, some atypical antipsychotics have been associated with an approximately 3-fold increased risk of cerebrovascular adverse events. The mechanism of this increased risk is unknown. An increased risk cannot be excluded with other antipsychotics or in other patient populations. Quetiapine should be used with caution in patients with risk factors for stroke.
Elderly patients with Parkinson's disease (PD)/parkinsonism
It is known that in a retrospective study of quetiapine for the treatment of patients with major depressive disorder (MDD), an increased risk of mortality was observed with quetiapine in patients aged > 65 years. This data was not available when patients with Parkinson's disease were excluded from the analysis. 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 were at higher risk of developing intestinal obstruction, including those receiving concomitant medications that reduce intestinal motility and/or medications that may not have been reported to cause symptoms of constipation. Patients with intestinal obstruction/constipation should be closely monitored and treated promptly if necessary.
Venous thromboembolism
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 post-marketing experience. Post-marketing reports have indicated that many, although not all, patients had factors known to be associated with pancreatitis, such as elevated triglycerides, gallstones, and alcohol use.
Additional information
Data on the use of quetiapine in combination with divalproex or lithium in acute manic episodes of moderate to severe severity 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.
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
First trimester
A moderate amount of published data on exposed pregnancies (i.e., 300 to 1000 pregnancy outcomes), including isolated reports and some observational studies, do not indicate an increased risk of malformations due to quetiapine treatment. However, based on all the available data, no definite conclusion can be drawn. Animal studies have shown reproductive toxicity. Therefore, quetiapine should be used during pregnancy only if the potential benefit justifies the potential risk.
Third trimester
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, tremor, somnolence, respiratory distress syndrome or feeding disorders. Therefore, newborns whose mothers have been treated with quetiapine during the third trimester of pregnancy should be closely observed.
Breastfeeding period
Based on very limited data from published reports on the excretion of quetiapine in human milk, the excretion of quetiapine at therapeutic doses is uncertain. In the absence of reliable data, a decision should be made whether to discontinue breast-feeding or to discontinue quetiapine therapy, taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
Fertility
The effect of quetiapine on human fertility has not been evaluated. Effects related to increased prolactin levels were observed in a rat study, although these are not directly relevant to humans.
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 concentration. Therefore, patients should be advised to avoid driving or operating machinery until individual sensitivity to this effect has been determined.
Method of administration and doses
There are different dosages for each indication. The dose of the drug and the duration of the course of treatment are determined by the doctor individually for each patient, depending on the indications and severity of the disease.
For oral use.
Quetiapine can be taken regardless of meals.
Adults.
For the treatment of schizophrenia.
Quetiapine should be taken twice a day.
In the first 4 days of
