Instructions for use Quetyron XR Asino tablets 50 mg No. 60
Composition
active ingredient: quetiapine;
1 tablet contains 57.56 mg or 172.68 mg or 345.36 mg of quetiapine fumarate, which is equivalent to 50 mg or 150 mg or 300 mg of quetiapine;
excipients: methacrylate copolymer (type A), anhydrous lactose (SD 250), crystalline maltose (Advantose 100), talc, vegetable magnesium stearate;
shell composition: methacrylate copolymer (type A), triethyl citrate (Citrofol).
Dosage form
Extended-release tablets.
Main physicochemical properties:
50 mg: white or almost white round biconvex tablets engraved with “50” on one side;
150 mg: white or almost white, oblong biconvex tablets engraved with “150” on one side;
300 mg: white or almost white, oblong biconvex tablets engraved with “300” on one side.
Pharmacotherapeutic group
Agents acting on the nervous system. Psycholeptics. Antipsychotics. Diazepines, oxazepines, thiazepines and oxepines. Quetiapine.
ATX code N05A H04.
Pharmacological properties
Pharmacodynamics
Mechanism of action
Quetiapine is an atypical antipsychotic drug. Quetiapine and its active plasma metabolite norquetiapine interact with multiple neurotransmitter receptors. Quetiapine and norquetiapine exhibit affinity for serotonin (5HT2) and dopamine D1 and D2 receptors in the brain. It is this combination of receptor antagonism with greater selectivity for 5HT2 over D2 receptors that is thought to contribute to the clinical antipsychotic effects and low extrapyramidal disorder (EPD) profile of quetiapine compared to typical antipsychotic drugs.
Quetiapine and norquetiapine do not have high affinity for benzodiazepine receptors, but they do have high affinity for histaminergic receptors and α1-adrenoceptors and moderate affinity for α2-adrenoceptors. Quetiapine also has low or no affinity for cholinergic muscarinic receptors, while norquetiapine has moderate to high affinity for several subtypes of muscarinic receptors, 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 XR Asino as an antidepressant.
Pharmacodynamic effects
Quetiapine is active 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 the course of preclinical studies on the study of EPR, it was found that quetiapine had an atypical activity profile and differed 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.
Quetiapine demonstrates selectivity for the limbic system by producing depolarizing blockade of mesolimbic but not nigrostriatal dopaminergic neurons after chronic administration. Quetiapine elicits minimal dystonic responses in haloperidol-sensitive or drug-naive monkeys after single and chronic administration (see section 4.8).
Clinical efficacy
Schizophrenia
The efficacy of quetiapine extended-release in the treatment of schizophrenia was demonstrated in one 6-week placebo-controlled study in patients who met DSM-IV criteria for schizophrenia and in one active-controlled study of switching from quetiapine immediate-release to quetiapine extended-release in clinically stable outpatients with schizophrenia.
The primary outcome variable in the placebo-controlled trial was the change from baseline to final score in the PANSS total score. Quetiapine extended-release 400 mg/day, 600 mg/day, and 800 mg/day were associated with statistically significant improvements in psychotic symptoms compared with placebo. The effect of the 600 mg and 800 mg doses was greater than that of the 400 mg dose.
In a long-term study of stable patients with schizophrenia treated with quetiapine extended-release for 16 weeks, quetiapine extended-release was more effective than placebo in preventing relapse. The estimated risk of relapse after 6 months of treatment was 14.3% in the quetiapine extended-release group compared with 68.2% in the placebo group. The median dose was 669 mg. No additional safety data were identified with quetiapine extended-release treatment for up to 9 months (median 7 months). In particular, reports of adverse reactions related to EPR and weight gain did not increase with long-term treatment with quetiapine extended-release.
Bipolar disorder
In the treatment of moderate to severe manic episodes, quetiapine demonstrated superior efficacy compared to placebo in reducing manic symptoms at 3 and 12 weeks in two monotherapy studies. The efficacy of quetiapine extended-release was further demonstrated to be significant compared to placebo in an additional 3-week study. Quetiapine extended-release was administered in a range of 400 to 800 mg/day, with a mean dose of approximately 600 mg/day. Data on the use of quetiapine in combination with divalproex or lithium in acute moderate to severe manic episodes at 3 and 6 weeks are limited, but the combination therapy was well tolerated. Data showed an additive effect at 3 weeks. A second study did not show an additive effect at 6 weeks.
In a clinical trial in patients with depressive episodes in bipolar I or II disorder, quetiapine extended-release 300 mg/day demonstrated superior efficacy compared to placebo in reducing MADRS total score.
In four additional clinical trials of quetiapine in patients with moderate to severe depressive episodes in bipolar I or bipolar II disorder of 8 weeks duration, patients treated with quetiapine immediate-release 300 mg and 600 mg demonstrated significant improvement compared to patients treated with placebo on the respective outcome measures: mean improvement in MADRS and response, defined as at least a 50% improvement in MADRS total score from baseline. There was no difference in effect size between patients treated with quetiapine immediate-release 300 mg and those treated with 600 mg.
In the extension phase of two of these studies, it was demonstrated that long-term treatment of patients who responded to quetiapine immediate-release 300 or 600 mg was effective compared to placebo treatment for depressive symptoms, but not for manic symptoms.
In two relapse prevention trials evaluating quetiapine in combination with mood stabilizers, in patients with manic, depressive, or mixed mood episodes, the combination with quetiapine was superior to mood stabilizer monotherapy in increasing the time to relapse of any mood episode (manic, mixed, or depressed). Quetiapine was administered twice daily at a total dose of 400 to 800 mg/day as add-on therapy to lithium or valproate.
In a 6-week randomized trial of lithium and quetiapine extended-release compared with placebo and quetiapine extended-release in adult patients with acute mania, the difference in mean improvement on the YMRS between the lithium add-on group and the placebo add-on group was 2.8 points, and the difference in % responders (defined as a 50% improvement from baseline on the YMRS) was 11% (79% in the lithium add-on group versus 68% in the placebo add-on group).
In one long-term study (up to 2 years of treatment) evaluating relapse prevention in patients with manic, depressive or mixed mood episodes, quetiapine was superior to placebo in increasing the time to relapse of any mood event (manic, mixed or depressed) in patients with bipolar I disorder. The number of patients with mood disorders was 91 (22.5%) in the quetiapine group, 208 (51.5%) in the placebo group and 95 (26.1%) in the lithium treatment group, respectively. In patients who responded to quetiapine, when continuing quetiapine treatment was compared with switching to lithium, the results showed that switching to lithium did not appear to be associated with an increase in time to relapse of a mood event.
Severe depressive episodes in patients with major depressive disorder (MDD)
In two short-term (6-week) studies in patients who had shown an inadequate response to at least one antidepressant, quetiapine extended-release 150 mg/day and 300 mg/day, given as add-on to current antidepressant therapy (amitriptyline, bupropion, citalopram, duloxetine, escitalopram, fluoxetine, paroxetine, sertraline, or venlafaxine), demonstrated superiority over antidepressant monotherapy in reducing depressive symptoms as measured by improvement in MADRS total score (LS mean change from placebo was 2–3.3 points).
The following studies were conducted with quetiapine extended-release as monotherapy, however quetiapine extended-release is indicated for use only as add-on therapy.
In three of four short-term (up to 8 weeks) monotherapy studies in patients with MDD, quetiapine extended-release 50 mg/day, 150 mg/day, and 300 mg/day demonstrated superior efficacy compared to placebo in reducing depressive symptoms as measured by improvement in the Montgomery-Osberg Depression Rating Scale (MADRS) total score (LS mean change from placebo was 2–4 points).
In a study of relapse prevention as monotherapy, patients with major depressive episodes who had been stable on open-label quetiapine extended-release for at least 12 weeks were randomized to receive either quetiapine extended-release once daily or placebo for 52 weeks. The mean dose of quetiapine extended-release during the randomized phase was 177 mg/day. The relapse rate was 14.2% in patients treated with quetiapine extended-release and 34.4% in patients treated with placebo.
In a short-term (9-week) study of elderly non-demented patients (aged 66 to 89 years) with major depressive disorder, quetiapine extended-release, individually dosed over a range of 50 to 300 mg/day, demonstrated superior efficacy compared to placebo in reducing depressive symptoms as measured by improvement in MADRS total score (LS mean change from placebo -7.54). In this study, patients randomized to quetiapine extended-release received a dose of 50 mg/day on days 1–3, which could be increased to 100 mg/day on day 4, 150 mg/day on day 8, and 300 mg/day based on clinical response and tolerability. The mean dose of quetiapine extended-release was 160 mg/day. Except for the incidence of extrapyramidal symptoms (see Adverse Reactions and Clinical Safety sections below), the tolerability of once-daily quetiapine prolonged-release in elderly patients was comparable to that observed in adult patients (aged 18-65 years). The proportion of patients randomised aged 75 years and over was 19%.
Clinical safety
In short-term placebo-controlled clinical trials in schizophrenia and bipolar mania, the aggregated incidence of extrapyramidal symptoms was similar to placebo (schizophrenia: 7.8% for quetiapine and 8.0% for placebo; bipolar mania: 11.2% for quetiapine and 11.4% for placebo). A higher incidence of extrapyramidal symptoms was observed in patients treated with quetiapine compared to those treated with placebo in short-term placebo-controlled clinical trials in MDD and bipolar depression. In short-term placebo-controlled trials in bipolar depression, the aggregated incidence of extrapyramidal symptoms was 8.9% for quetiapine compared to 3.8% for placebo. In short-term placebo-controlled monotherapy clinical trials in major depressive disorder, the aggregate incidence of extrapyramidal symptoms was 5.4% for quetiapine extended-release and 3.2% for placebo. In a short-term placebo-controlled monotherapy trial in elderly patients with major depressive disorder, the aggregate incidence of extrapyramidal symptoms was 9.0% for quetiapine extended-release and 2.3% for placebo. In both bipolar depression and MDD, the incidence of individual adverse reactions (e.g., akathisia, extrapyramidal disorder, tremor, dyskinesia, dystonia, restlessness, muscle contractions involuntary, psychomotor hyperactivity, and muscle rigidity) did not exceed 4% in either treatment group.
A 6-week randomized trial of lithium and quetiapine extended-release compared with placebo and quetiapine extended-release in adult patients with acute mania showed that the combination of quetiapine extended-release with lithium resulted in a higher incidence of adverse reactions (63% vs. 48% for quetiapine extended-release plus placebo). Safety results showed a higher incidence of extrapyramidal symptoms, reported in 16.8% of patients in the lithium add-on group and 6.6% in the placebo add-on group, the majority of which consisted of tremor, reported in 15.6% of patients in the lithium add-on group and 4.9% in the placebo add-on group. The incidence of somnolence was higher in the quetiapine extended-release plus lithium group (12.7%) compared to the quetiapine extended-release plus placebo group (5.5%). In addition, a higher percentage of patients in the lithium add-on group (8.0%) had weight gain (≥ 7%) at the end of treatment compared to patients in the placebo add-on group (4.7%).
The long-term relapse prevention studies had an open-label period (4 to 36 weeks) during which patients were treated with quetiapine, followed by a randomised withdrawal period during which patients were randomised to receive quetiapine or placebo. In patients randomised to receive quetiapine, the mean weight gain during the open-label period was 2.56 kg, and by week 48 of the randomisation period the mean weight gain from open-label baseline was 3.22 kg. In patients randomised to receive placebo, the mean weight gain during the open-label period was 2.39 kg, and by week 48 of the randomisation period the mean weight gain from open-label baseline was 0.89 kg.
In placebo-controlled studies in elderly patients with dementia-related psychosis, the incidence of cerebrovascular adverse reactions per 100 patient-years was not higher in patients treated with quetiapine than in patients treated with placebo.
In all short-term placebo-controlled monotherapy studies in patients with baseline neutrophil counts ≥ 1.5 x 109/L, the incidence of at least one event of a shift to neutrophil counts < 1.5 x 109/L was 1.9% in patients treated with quetiapine compared to 1.5% in patients treated with placebo. The incidence of shifts to > 0.5 - < 1.0 x 109/L was the same (0.2%) in patients treated with quetiapine as in patients treated with placebo. Across all clinical trials (placebo-controlled, open-label, active comparator) in patients with baseline neutrophil counts ≥ 1.5 x 109/L, the incidence of at least one event of a decrease in neutrophil count to < 1.5 x 109/L was 2.9% and to < 0.5 x 109/L was 0.21% in patients treated with quetiapine.
Quetiapine treatment was associated with dose-related decreases in thyroid hormone levels. The incidence of thyroid-stimulating hormone (TSH) abnormalities was 3.2% for quetiapine versus 2.7% for placebo. The incidence of reciprocal, potentially clinically significant fluctuations in either TSH or T4 or TSH in these studies was rare, and the observed changes in thyroid hormone levels were not associated with clinically symptomatic hypothyroidism. The reduction in total and free T4 was maximal within the first six weeks of quetiapine treatment with no further reduction during long-term treatment. In approximately two-thirds of all cases, discontinuation of quetiapine was associated with a reversal of the effect on total and free T4, regardless of the duration of treatment.
Cataract/clouding of the lens
In a clinical trial evaluating the cataractogenic potential of quetiapine (200–800 mg/day) compared with risperidone (2–8 mg/day) in patients with schizophrenia or schizoaffective disorder, the percentage of patients with increased lens opacity was not higher with quetiapine (4%) compared with risperidone (10%) in patients with at least 21 months of exposure.
Pediatric population
Clinical efficacy
The efficacy and safety of quetiapine were studied in a 3-week placebo-controlled study for the treatment of mania (n = 284, US patients aged 10–17 years). Approximately 45% of patients had a co-diagnosis of ADHD. In addition, a 6-week placebo-controlled study was conducted for the treatment of schizophrenia (n = 222 patients aged 13–17 years). In both studies, patients with a known lack of response to quetiapine were excluded. Quetiapine treatment was initiated at a dose of 50 mg/day and increased to 100 mg/day on day 2. The dose was then titrated to the target dose (mania: 400–600 mg/day; schizophrenia: 400–800 mg/day) in 100 mg/day increments administered twice or three times daily.
In the schizophrenia study, the difference in LS mean change from baseline in PANSS total score (active minus placebo) was -8.16 for quetiapine 400 mg/day and -9.29 for quetiapine 800 mg/day. Neither the low dose (400 mg/day) nor the high dose (800 mg/day) of quetiapine was superior to placebo in the percentage of patients achieving a response, defined as a ≥ 30% reduction from baseline in PANSS total score. In both mania and schizophrenia, higher doses resulted in numerically lower response rates.
In a third short-term placebo-controlled monotherapy study of quetiapine extended-release in children and adolescent patients (10–17 years) with bipolar depression, efficacy was not demonstrated.
There are no data on the maintenance of effect or prevention of relapse in this age group.
Clinical safety
In the short-term pediatric studies with quetiapine described above, the incidence of EPR in the active group compared to placebo was 12.9% vs. 5.3% in the schizophrenia study, 3.6% vs. 1.1% in the bipolar mania study, and 1.1% vs. 0% in the bipolar depression study. The rate of weight gain ≥ 7% from baseline in the active group compared to placebo was 17% vs. 2.5% in the schizophrenia and bipolar mania studies, and 13.7% vs. 6.8% in the bipolar depression study. The incidence of suicide-related events in the active group compared to placebo was 1.4% vs. 1.3% in the schizophrenia study, 1.0% vs. 0% in the bipolar mania study, and 1.1% vs. 0% in the bipolar depression study. During the extended post-treatment follow-up phase of the bipolar depression study, two additional suicide-related events were identified in two patients. One of these patients was taking quetiapine at the time of the event.
Long-term safety
A 26-week open-label study (n = 380 patients) with individualized dosing of quetiapine at a dose of 400-800 mg/day provided additional safety data. Increased blood pressure was reported in children and adolescents, as well as increased appetite, extrapyramidal symptoms, and increased serum prolactin levels at a higher frequency in children and adolescents than in adults (see sections 4.4 and 4.8). For weight gain, a clinically meaningful change of at least 0.5 standard deviations from baseline in body mass index (BMI) was used as a measure of long-term normal growth, with 18.3% of patients treated with quetiapine for at least 26 weeks meeting this criterion.
Pharmacokinetics
Absorption
Quetiapine is well absorbed after oral administration. Peak plasma concentrations (Tmax) of quetiapine and norquetiapine are achieved approximately 6 hours after administration of quetiapine. Peak molar concentrations at steady state of the active metabolite of norquetiapine are 35% of those of quetiapine.
The pharmacokinetics of quetiapine and norquetiapine are linear and dose proportional up to and including 800 mg once daily. When comparing the same total daily doses of quetiapine taken once daily with immediate-release quetiapine (quetiapine fumarate immediate-release) taken twice daily, the area under the concentration-time curve (AUC) was similar, but the maximum plasma concentration (Cmax) was 13% lower at steady state. When comparing extended-release and immediate-release quetiapine, the AUC of the norquetiapine metabolite was 18% lower for extended-release quetiapine.
In a study investigating the effect of food on the bioavailability of quetiapine, high-fat meals were found to cause a statistically significant increase in Cmax and AUC of quetiapine by approximately 50% and 20%, respectively. It cannot be excluded that the effect of a medicinal product containing quetiapine may be greater under the influence of a high-fat meal. A light meal has no significant effect on Cmax and AUC of quetiapine. It is recommended that quetiapine be taken once daily on an empty stomach.
Distribution
Approximately 83% of quetiapine is bound to plasma proteins.
Metabolism
Quetiapine is extensively metabolized in the liver; use of radiolabeled quetiapine has shown that less than 5% of quetiapine is not metabolized and is excreted unchanged in the urine or feces.
In vitro studies have shown that CYP3A4 is the major cytochrome P450 enzyme responsible for the metabolism of quetiapine. The formation and elimination of norquetiapine is primarily mediated by CYP3A4. Approximately 73% of the radiolabelled dose is excreted in the urine and 21% in the faeces.
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 patients with psychosis did not reveal an increase in cytochrome P450 activity following quetiapine administration.
Breeding
The elimination half-lives of quetiapine and norquetiapine are approximately 7 and 12 hours, respectively. Approximately 73% of the radioactivity is excreted in the urine and 21% in the feces. Less than 5% of the total radioactivity of the average molar fraction of the dose of free quetiapine and the active metabolite norquetiapine is excreted in the urine in humans.
Special populations
Sex
The pharmacokinetics of quetiapine do not differ between women and men.
Elderly people
The average clearance of quetiapine in elderly subjects is approximately 30-50% lower than in adults aged 18-65 years.
Kidney dysfunction
The mean plasma clearance of quetiapine was reduced by approximately 25% in patients with severe renal impairment (creatinine clearance less than 30 ml/min/1.73 m2), however, individual clearance values are within the range of those observed in healthy subjects.
Liver dysfunction
The mean plasma clearance of quetiapine is reduced by approximately 25% in patients with known hepatic impairment (stable alcoholic cirrhosis). As quetiapine is extensively metabolised in the liver, increased plasma levels are expected in patients with hepatic impairment. Dose adjustment may be required in such patients (see section 4.2).
Children
Pharmacokinetic data are available in children receiving 400 mg quetiapine twice daily. At therapeutic doses, exposure to the 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. 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.
There is no information on the use of the drug Quetyron® XR Asino in children and adolescents.
Indication
The drug Quetyron® XR Asino is indicated for the treatment of:
Schizophrenia, including prevention of relapse in patients with stable schizophrenia who received maintenance therapy with the drug Quetiapine XR Asino.
Bipolar disorder, including:
for the treatment of moderate to severe manic episodes in bipolar disorder;
for the treatment of severe depressive episodes in bipolar disorder;
for the prevention of relapse in patients with bipolar disorder, in patients with manic or depressive episodes, in whom the use of the drug Quetiapine® XR Asino is effective.
As adjunctive therapy for major depressive episodes in patients with major depressive disorder (MDD) who have had a suboptimal response to antidepressant monotherapy. Before initiating therapy, the physician should carefully review the safety profile of Quetiapine XR Asino.
Contraindication
Hypersensitivity to the active substance or to any component of the drug Quetyron® XR Asino.
Concomitant use of cytochrome P450 3A4 inhibitors, such as HIV protease inhibitors, azole antifungals, erythromycin, clarithromycin and nefazodone, is contraindicated (see section “Interaction with other medicinal products and other forms of interaction”).
Interaction with other medicinal products and other types of interactions
Given that quetiapine primarily acts on the central nervous system, the drug should be used with caution in combination with other centrally acting drugs and with alcohol.
Quetiapine should be used with caution in combination with serotonergic drugs such as monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), selective serotonin and norepinephrine reuptake inhibitors (SNRIs) or tricyclic antidepressants, as the risk of serotonin syndrome, a potentially life-threatening condition, is increased (see section 4.4).
Caution should be exercised when treating patients who are taking other medicinal products with anticholinergic (muscarinic) effects (see section "Special warnings and precautions for use").
In a multiple-dose pharmacokinetic study of quetiapine administered before and during treatment with carbamazepine (a known hepatic enzyme inducer), co-administration of carbamazepine was shown to significantly increase quetiapine clearance. This in turn 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 quetiapine, which may impact the efficacy of quetiapine therapy.
Concomitant use of quetiapine and phenytoin (another hepatic enzyme inducer) resulted in a significant increase in quetiapine clearance of approximately 450%. Quetiapine should only be initiated in patients receiving a hepatic enzyme inducer if, in the opinion of the physician, the benefit of quetiapine outweighs the risk of discontinuation of the hepatic enzyme inducer. It is important that any change from the inducer should be gradual. If necessary, it should be replaced by a non-inducer, such as sodium valproate (see section 4.4).
The pharmacokinetics of quetiapine are not significantly altered when co-administered with antidepressants such as imipramine (a known CYP2D6 inhibitor) or fluoxetine (a known CYP3A4 and CYP2D6 inhibitor).
Concomitant use of antipsychotics such as risperidone or haloperidol did not significantly alter the pharmacokinetics of quetiapine. Concomitant use of quetiapine and thioridazine increased quetiapine clearance by approximately 70%.
When cimetidine and quetiapine were co-administered, the pharmacokinetics of quetiapine were not altered.
The pharmacokinetics of lithium were 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-added group compared to the placebo-added group (see section 5.1).
No clinically significant changes in the pharmacokinetics of sodium valproate and quetiapine were observed when co-administered. A retrospective study of children and adolescents receiving valproate, quetiapine, or both drugs showed a higher incidence of leukopenia and neutropenia in the combination treatment group than in the monotherapy groups.
No formal interaction studies have been conducted with the most common cardiovascular medications.
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 an appropriate chromatographic method.
Application features
Since quetiapine is indicated for the treatment of schizophrenia, bipolar disorder and the adjunctive treatment of major depressive episodes in patients with MDD, the safety profile of Quetiapine XR should be carefully considered in light of the individual patient's diagnosis and dose.
The long-term efficacy and safety of concomitant therapy in patients with TDR have not been evaluated, however, the long-term efficacy and safety of quetiapine monotherapy in adult patients have been studied (see section 5.1).
Children
Quetiapine is not recommended for use in children under 18 years of age due to the lack of data to support its use 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 reactions is higher in children and adolescents than in adults (increased appetite, increased serum prolactin levels, vomiting, rhinitis and loss of consciousness), or may have different consequences in children and adolescents (extrapyramidal symptoms (EPS) and irritability), and one event was identified that was not previously observed in studies involving adult patients (increased blood pressure). 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. The long-term effects on cognitive and behavioral development are unknown.
In placebo-controlled clinical trials of quetiapine in children and adolescents, quetiapine treatment was associated with an increased incidence of EPS compared to placebo in patients treated for schizophrenia and bipolar mania (see section 4.8).
Suicide/suicidal thoughts or clinical worsening
Depression is associated with an increased risk of suicide
