Instructions for use of Kventiax SR prolonged-release tablets 50 mg No. 60
Composition
active ingredient: quetiapine;
1 prolonged-release tablet contains 50 mg of quetiapine (as quetiapine fumarate);
excipients: hypromellose, lactose monohydrate, microcrystalline cellulose, sodium citrate dihydrate, magnesium stearate;
film coating: Opadry white (a mixture of hypromellose, titanium dioxide (E 171) and macrogol 3000).
Dosage form
Extended-release tablets.
Main physicochemical properties:
50 mg prolonged-release tablets: film-coated, white or almost white, capsule-shaped, slightly biconvex with beveled edges and engraved with “50” on one side of the tablet.
Pharmacotherapeutic group
Antipsychotics. Quetiapine.
ATX code N05A H04.
Pharmacological properties
Pharmacodynamics
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 propensity for extrapyramidal side effects of Quetiapine® SR compared to typical antipsychotics.
Quetiapine has no affinity for the norepinephrine transporter (NET) and has low affinity for serotonin 5HT1A receptors, whereas norquetiapine has high affinity for both. Inhibition by norquetiapine (NET) as well as partial agonist activity at 5HT1A receptors may contribute to the therapeutic efficacy of Quetiapine® SR as an antidepressant. Quetiapine and norquetiapine have high affinity for histaminergic receptors and alpha1-adrenoceptors and moderate affinity for alpha2-adrenoceptors. Quetiapine also has low or no affinity for muscarinic receptors, whereas norquetiapine has moderate or high affinity for several subtypes of muscarinic receptors.
Pharmacodynamic effects
Quetiapine is active in tests of antipsychotic activity, such as conditioned avoidance. It also blocks the effects of dopamine agonists, measured either behaviorally or electrophysiologically, and increases concentrations of dopamine metabolites, a neurochemical index of D2 receptor inhibition.
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 SR. The peak molar concentration at steady state of the active metabolite norquetiapine is 35% of that 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 SR once daily with doses of Quetiapine immediate-release (quetiapine fumarate immediate-release) 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 Quetiapine SR with Quetiapine immediate-release, the AUC of the metabolite norquetiapine was 18% lower.
In a study of the effect of food on the bioavailability of quetiapine, it was found that high-fat meals caused a statistically significant increase in Cmax and AUC of Quetiapine® SR by approximately 50% and 20%, respectively. It cannot be excluded that the effect of high-fat meals on the drug may be greater. A light meal does not have a significant effect on Cmax and AUC of quetiapine. Quetiapine® SR is recommended to be taken once daily without food.
Distribution
Approximately 83% of quetiapine is bound to plasma proteins.
Metabolism
Quetiapine is extensively metabolized in the liver. The use of radiolabeled quetiapine has shown that less than 5% of quetiapine is not metabolized and is excreted unchanged in the urine or feces.
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 mean clearance of quetiapine in elderly subjects is approximately 30–50% lower than in adults aged 18–65 years.
Renal impairment
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 volunteers.
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).
Indication
Treatment of schizophrenia.
Treatment of bipolar disorder, including:
- moderate to severe manic episodes associated with bipolar disorders;
- major depressive episodes associated with bipolar disorders;
Prevention of relapse in patients with bipolar disorder whose manic or depressive episodes have been treated with quetiapine.
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 SR.
Contraindication
Hypersensitivity to the active substance or to any component of the drug.
Concomitant use of cytochrome P450 3A4 inhibitors, such as HIV protease inhibitors, azole antifungals, erythromycin, clarithromycin, and nefazodone, is contraindicated.
Interaction with other medicinal products and other types of interactions
Given that quetiapine primarily acts on the central nervous system, Quetiapine SR should be used with caution in combination with other drugs with similar effects and with alcohol.
Cytochrome P450 (CYP) 3A4 is the enzyme primarily responsible for the metabolism of quetiapine. In an 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.
In a multiple-dose pharmacokinetic study of quetiapine administered before and during treatment with carbamazepine (a 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 a mean of 13% of that seen with quetiapine alone, although some patients had greater effects. This interaction may result in decreased plasma concentrations of quetiapine, which may impact the efficacy of Quetiapine SR therapy.
Concomitant use of quetiapine and phenytoin (another microsomal enzyme inducer) increased quetiapine clearance by approximately 450%. Initiation of therapy with Quetiapine SR in patients receiving a hepatic enzyme inducer should only be considered if the physician considers that the benefits of Quetiapine SR 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. If necessary, it should be replaced by a non-inducer (e.g. sodium valproate) (see section 4.4).
The pharmacokinetics of quetiapine are not significantly altered by concomitant use of antidepressants such as imipramine (a known CYP 2D6 inhibitor) or fluoxetine (a known CYP 3A4 and CYP 2D6 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%.
The pharmacokinetics of quetiapine were not altered when co-administered with cimetidine.
The pharmacokinetics of lithium were not altered when co-administered with quetiapine.
In a 6-week randomized trial comparing the combination of lithium and Kventiax SR with placebo and Kventiax SR in adult patients with acute mania, an increased incidence of extrapyramidal symptoms (especially tremor), somnolence, and weight gain was observed in the lithium-added group compared to the placebo-added group (see section 5.2).
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.
Interaction studies with 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 that equivocal screening immunoassay results be verified by an appropriate chromatographic method.
Application features
Since Quetiapine® SR is indicated for the treatment of schizophrenia, bipolar disorder, and the concomitant treatment of major depressive episodes in patients with MDD, the safety profile of the drug should be carefully considered in light of the individual patient's diagnosis and the dose being taken.
The long-term efficacy and safety of concomitant therapy in patients with TDR have not been evaluated, but the long-term efficacy and safety of monotherapy with the drug in adult patients have been studied.
Children
Quetiapine is not recommended for use in children 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, the frequency of some adverse events is higher in children than in adults (increased appetite, increased serum prolactin levels and extrapyramidal symptoms), and one event not previously observed in studies involving adult patients (increased blood pressure) has also been identified. 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 studies involving children and adolescents, quetiapine treatment was associated with an increased incidence of extrapyramidal symptoms (EPS) compared to placebo in patients treated for schizophrenia and bipolar mania (see section 4.8).
Suicide/suicidal thoughts or clinical worsening
Depression in bipolar disorder is associated with an increased risk of suicidal ideation, self-harm and suicide (suicide-related events). This risk persists until significant remission is achieved. As improvement may not be apparent during the first few 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.
In addition, the potential risk of suicide-related events following abrupt discontinuation of quetiapine should be considered due to known risk factors for the condition being treated.
Other psychiatric conditions for which Quetiapine SR is prescribed may also be associated with an increased risk of suicide-related events. In addition, these conditions may occur concurrently with depressive episodes.
When treating patients with other psychiatric disorders, the same precautions should be taken as when treating patients with severe depressive episodes.
Patients with a history of suicide-related events or who demonstrate a significant level of suicidal ideation prior to initiation of therapy 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 behavior in patients under 25 years of age.
Close monitoring of patients, particularly those at high risk, should be closely followed by full drug therapy, especially at the start of treatment and with 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 trials in patients with major depressive episodes in bipolar disorder, an increased risk of suicide-related events was observed in young patients (<25 years of age) treated with quetiapine compared to those treated with placebo (3.0% vs. 0%, respectively). In clinical trials in patients with MDD, the incidence of suicide-related events in young patients (<25 years of age) was 2.1% (3/144) in the quetiapine group and 1.3% (1/75) in the placebo group.
Drowsiness
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 typically occurred within the first 3 days of treatment and were mostly mild to moderate in intensity. For patients with bipolar depression and patients with depressive episodes in MDD who develop somnolence, observation may be necessary for 2 weeks after the onset of somnolence or until symptoms resolve, or discontinuation of treatment may be considered.
Quetiapine treatment has been associated with orthostatic hypotension and associated dizziness, which, like somnolence, usually occur during the dose titration period. These events may contribute to an increased incidence of accidental injury (falls), particularly in elderly patients. Therefore, patients should be advised to exercise caution until they are familiar with the possible effects of the drug.
Quetiapine SR should be used with caution in patients with known cardiovascular or cerebrovascular disease or other conditions that may predispose to hypotension. Quetiapine may cause orthostatic hypotension, especially at the beginning of dose titration, and in such cases, a dose reduction or longer titration may be necessary.
Convulsions
In controlled clinical trials, there was no difference in the incidence of seizures between patients taking quetiapine and those taking placebo. As with other antipsychotics, caution is advised when prescribing quetiapine to patients with a history of seizures (see section 4.8).
Extrapyramidal symptoms
In placebo-controlled trials, quetiapine was associated with an increased incidence of extrapyramidal symptoms compared to placebo in patients treated for major depressive episodes associated with bipolar disorder and major depressive disorder.
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 during the first few weeks of treatment. Increasing the dose in patients who develop these symptoms may be harmful.
Tardive dyskinesia
If symptoms of tardive dyskinesia appear, consideration should be given to reducing the dose or discontinuing Kventiax SR. Symptoms of tardive dyskinesia may worsen and even recur after discontinuation of therapy (see section 4.8).
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 levels. In such cases, Quetiapine SR should be discontinued and appropriate treatment initiated.
Severe neutropenia and agranulocytosis
Severe neutropenia (neutrophil count <9/L) has been uncommonly observed in clinical trials with quetiapine. Agranulocytosis (severe neutropenia with infection) has been reported rarely in patients treated with quetiapine in clinical trials and in the post-marketing setting (including fatal cases). The majority of cases of severe neutropenia have occurred within two months of initiating quetiapine therapy. No clear dose relationship has been established. During the post-marketing setting, recovery of leukopenia and/or neutropenia has occurred after discontinuation of quetiapine. Possible risk factors for neutropenia include pre-existing low white blood cell counts and a history of drug-induced neutropenia. Agranulocytosis has been reported in patients without pre-existing risk factors. The possibility of neutropenia should be considered in patients with infection, especially in the absence of obvious contributing factors, and in patients with fever of unknown origin, and appropriate clinical measures should be taken.
It is recommended to discontinue quetiapine treatment when the blood neutrophil count reaches 9/L. Patients should be monitored for signs of infection and changes in neutrophil count until the count exceeds 9/L (see section 5.1).
Interactions
See also section “Interaction with other medicinal products and other types of interactions”.
Concomitant use of quetiapine with a potent hepatic enzyme inducer such as carbamazepine or phenytoin significantly reduces quetiapine plasma concentrations, which may reduce the efficacy of quetiapine therapy. Treatment with Quetiapine SR in patients receiving a hepatic enzyme inducer should only be initiated if the physician considers that the benefits of Quetiapine SR 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, which should be monitored and managed clinically when using antipsychotic medications.
Hyperglycemia
Hyperglycaemia and/or development or exacerbation of diabetes mellitus have occasionally been associated with ketoacidosis or coma, including several fatal cases (see section 4.8). A few cases have been reported with a prior increase in body weight, which may be a contributing factor. Appropriate clinical monitoring is advisable in accordance with existing guidelines for the use of antipsychotics. Patients treated with any antipsychotic medicinal product, including quetiapine, should be observed for symptoms of hyperglycaemia (such as polydipsia, polyuria, polyphagia and weakness), and patients with diabetes mellitus or with risk factors for diabetes mellitus should be monitored regularly for worsening of glucose control. The weight of such patients should be monitored regularly.
Increases in triglycerides, LDL-C and total cholesterol and decreases in HDL-C have been observed in clinical trials with quetiapine (see section 4.8). If lipid levels change, appropriate treatment should be administered.
Metabolic risk
Given the changes in body weight, blood glucose (see hyperglycemia) and lipids observed during clinical trials, there is a possibility of a worsening of the metabolic risk profile in individual patients, in which case appropriate treatment should be prescribed.
QT prolongation
In clinical trials and when used as directed, quetiapine did not consistently increase absolute QT intervals. However, QT prolongation has been observed with overdose. 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 also be exercised when prescribing quetiapine with other medicinal products known to prolong the QT interval or with concomitant neuroleptics, especially in the elderly, patients with congenital long QT syndrome, congestive heart failure, cardiac hypertrophy, hypokalaemia or hypomagnesaemia (see section 4.5).
Discontinuation of the drug
Acute withdrawal symptoms such as insomnia, nausea, headache, diarrhoea, vomiting, dizziness and irritability have been reported following abrupt discontinuation of quetiapine. Therefore, gradual discontinuation over a period of at least one to two weeks is recommended (see section 4.8).
Elderly patients with dementia-related psychosis
Quetiapine® SR is not recommended for the treatment of psychosis associated with dementia.
In randomized, placebo-controlled trials in patients with dementia, an approximately 3-fold increase in the risk of cardiovascular adverse events has been observed with some atypical antipsychotics. The mechanism of this increase is unknown. An increased risk cannot be excluded for other antipsychotics or for other patient populations. Quetiapine® SR 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, two 10-week placebo-controlled trials of quetiapine in elderly patients with dementia did not establish a causal relationship between quetiapine treatment and death.
Dysphagia
Dysphagia has been reported with quetiapine. Quetiapine should be used with caution in patients at risk of aspiration pneumonia.
Constipation and intestinal obstruction
Constipation is a risk factor for intestinal obstruction. Cases of constipation and intestinal obstruction have been reported with quetiapine (see section 4.8). These reports include fatalities in patients at increased risk of intestinal obstruction, including patients receiving multiple medicinal products that reduce intestinal motility and/or medicinal products that may not have been reported to cause constipation.
Venous thromboembolism
Cases of venous thromboembolism (VTE) have been reported with the use of neuroleptics. Since patients taking neuroleptics 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.
Effect on the liver
Treatment with Quetiapine SR should be discontinued if jaundice develops.
Pancreatitis
Cases of pancreatitis have been reported in clinical trials and during post-marketing use, but a causal relationship has not been established. In the post-marketing reports, many patients had factors known to be associated with pancreatitis, such as increased triglyceride levels (see section 4.4, Lipids), gallstones, and alcohol abuse.
Cardiomyopathy and myocarditis
Cardiomyopathy and myocarditis have been reported in clinical trials and during the post-marketing period, but a causal relationship to quetiapine has not been established. The use of quetiapine in patients with suspected cardiomyopathy or myocarditis should be re-evaluated.
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.
Quetiapine SR tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Use during pregnancy or breastfeeding
The safety and efficacy of quetiapine in pregnant women have not been established. There is currently no evidence of adverse effects in animal studies. The potential effects on fetal vision have not been studied. Neonatal withdrawal symptoms have been reported in newborns from several pregnancies exposed to quetiapine. Therefore, Quetiapine SR should be used during pregnancy only if the potential benefit justifies the potential risk. Withdrawal symptoms have been observed in newborns whose mothers took quetiapine during pregnancy.
There is published evidence that quetiapine is excreted in human milk, although the extent of this excretion is unknown. Breastfeeding women should discontinue breastfeeding during treatment with quetiapine.
Neonates whose mothers have taken antipsychotics (including quetiapine) during the third trimester of pregnancy are at risk of adverse reactions, including extrapyramidal and/or withdrawal symptoms, which may vary in severity and duration. The following adverse reactions have been observed: agitation, hypertension, hypotension, tremor, somnolence, respiratory distress or feeding disorders. Therefore, neonates should be closely monitored.
Ability to influence reaction speed when driving vehicles or other mechanisms
Given that the drug mainly acts on the central nervous system, quetiapine may adversely affect mental performance. Therefore, patients are advised not to drive or operate machinery until their individual response to the drug is 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.
Kventiax® SR should be taken once daily on an empty stomach. The tablets should be swallowed whole, without breaking, chewing or crushing them.
For the treatment of schizophrenia and moderate to severe manic episodes in bipolar disorder
Kventiax® SR should be taken at least 1 hour before a meal. The initial daily dose is 300 mg on the first day and 600 mg on the second day. The recommended daily dose is 600 mg, but if clinically indicated, the dose may be increased to 800 mg per day. The dose should be adjusted within the effective dose range of 400 mg to 800 mg per day, depending on clinical response and tolerability. No dose adjustment is necessary for maintenance therapy in schizophrenia.
For the treatment of depressive episodes in bipolar disorder
Quetiapine SR should be taken 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. In clinical trials, no additional benefit was observed in the 600 mg group compared to the 300 mg group (see section 5.1). 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 suggest that in individual patients, if there are problems with drug intolerance, a dose reduction to the minimum of 200 mg should be considered.
For the prevention of relapse in bipolar disorder
To prevent subsequent manic, mixed, or depressive episodes in bipolar disorder, patients who have responded to Quetiapine SR in the acute treatment of bipolar disorder should continue Quetiapine SR at the same prescribed dose at bedtime. The dose of Quetiapine SR may be adjusted within a range of 300 mg to 800 mg/day based on the clinical response and tolerability of the individual patient. It is important that the lowest effective dose be used for maintenance therapy.
For the concomitant treatment of major depressive episodes in MDD.
Kventiax® SR should be taken at bedtime. The daily dose at the beginning of therapy is 50 mg on days 1 and 2, and 150 mg on days 3 and 4. In short-term studies of concomitant therapy (with amitriptyline, bupropion, citalopram, duloxetine, escitalopram, fluoxetine, paroxetine, sertraline and venlafaxine), an antidepressant effect was observed at doses of 150 and 300 mg/day and at a dose of 50 mg/day in a short-term monotherapy study. The risk of adverse reactions increases with higher doses of the drug. Therefore, the physician should ensure that the lowest effective dose is used, starting with 50 mg/day. The need for a dose increase from 150 to 300 mg/day should be based on an assessment of the individual patient.
For convenience of dosing, patients treated with single doses of Quetiapine (immediate-release tablets) may be switched to Quetiapine SR at an equivalent total daily dose to be taken once daily. Dose titration may be necessary to ensure maintenance of clinical response.
Elderly patients
As with other antipsychotics and antidepressants, Kventiax® SR should be used with caution in elderly patients, especially during initiation of treatment and dose adjustment. A slower titration of Kventiax® SR may be required, and the daily therapeutic dose may be lower than that used in younger patients. The mean plasma clearance of quetiapine was reduced by 30-50% in elderly subjects compared with younger patients. Elderly patients should be initiated at a dose of 50 mg/day. The dose may be increased in 50 mg/day increments to an effective dose based on the clinical response and tolerability of the treatment in the individual patient. Elderly patients with depressive episodes in MDD should be initiated at 50 mg/day on days 1-3, increasing to 100 mg/day on day 4 and 150 mg/day on day 8. The lowest effective dose should be used, starting at 50 mg/day. If, based on an assessment of the individual patient, an increase in the dose to 300 mg/day is necessary, this should not be done earlier than after 22 days of treatment.
Safety and efficacy have not been studied in patients over 65 years of age with depressive episodes in bipolar disorder.
Kidney dysfunction
No dose adjustment is necessary for patients with renal impairment.
Liver dysfunction
Quetiapine is extensively metabolized in the liver. Therefore, Quetiapine® SR should be used with caution in patients with known hepatic impairment, especially during the initial dose titration period. Treatment of patients with hepatic impairment should be initiated at a dose of 50 mg/day. The dose may be increased in 50 mg/day increments to an effective dose, based on clinical response and tolerability in the individual patient.
Children.
Quetiapine® SR is not recommended for use in children due to the lack of data supporting its use in this age group.
Overdose
Symptoms
Survival has been reported in acute overdoses of up to 30 g of quetiapine. Most patients with overdoses reported no adverse events or fully recovered from such events. A fatal outcome was reported in a clinical trial following an overdose of 13.6 g of quetiapine. In post-marketing experience with 6 g of quetiapine as monotherapy, reports of overdoses of quetiapine resulting in fatal outcome or coma or QT prolongation were very rare. In addition, the following events have been reported with overdoses of quetiapine as monotherapy: QT prolongation, seizures, status epilepticus, rhabdomyolysis, respiratory depression, urinary retention, confusion, delirium and/or agitation.
Patients with pre-existing severe cardiovascular disease are at increased risk of overdose (see section "Special warnings and precautions for use").
In general, the signs and symptoms reported were due to an increase in the known pharmacological effects of the drug, such as drowsiness and sedation, tachycardia and hypotension.
Treatment
There is no specific antidote for quetiapine. In the event of severe overdose, multimodal and intensive care measures should be considered, including establishing and maintaining a patent airway, ensuring adequate oxygenation and, in
