Instructions for Ketilept Retard prolonged-release film-coated tablets 50 mg blister No. 60
Composition
active ingredient: quetiapine;
1 film-coated, prolonged-release tablet contains 57.56 mg, 172.680 mg, 230.24 mg, 345.36 mg or 460.48 mg of quetiapine fumarate (equivalent to 50 mg, 150 mg, 200 mg, 300 mg or 400 mg of quetiapine);
excipients:
methacrylate copolymer (type A), lactose anhydrous (spray dried SD 250), crystalline maltose (Advantose 100), talc, magnesium stearate, vegetable;
shell composition: methacrylate copolymer (type A), triethyl citrate (Citrofol).
Dosage form
Film-coated, prolonged-release tablets.
Main physicochemical properties:
50 mg: white or almost white, round, biconvex tablets, engraved with the number "50" on one side;
150 mg: white or almost white, oblong, biconvex tablets, engraved with the number "150" on one side;
200 mg: white or almost white, oblong, biconvex tablets, engraved with the number "200" on one side;
300 mg: white or almost white, oblong, biconvex tablets, engraved with the number "300" on one side;
400 mg: white or almost white, oval, biconvex tablets, engraved with the number "400" on one side.
Pharmacotherapeutic group
Antipsychotics. 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 than for D2 receptors that is believed to contribute to the clinical antipsychotic effects and low incidence of extrapyramidal side effects of Ketilept® Retard compared to typical antipsychotics.
Quetiapine has no affinity for the norepinephrine transporter (NET) and has low affinity for serotonin 5HT1A receptors, while norquetiapine has high affinity for both. Norquetiapine's inhibition of 5HT1A receptors, as well as its partial agonistic effect on 5HT1A receptors, may contribute to the therapeutic efficacy of Ketilept® Retard as an antidepressant. Quetiapine and norquetiapine have high affinity for histaminergic receptors and alpha1-adrenoceptors and moderate affinity for
affinity for alpha2-adrenergic receptors. Quetiapine also has low or no affinity for muscarinic receptors, while norquetiapine has moderate to high affinity for several muscarinic receptor subtypes.
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 reached approximately 6 hours after administration of Ketilept® Retard. Peak molar concentrations at steady state of the active metabolite 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 Quetilept® Retard taken once daily and quetiapine immediate-release (quetiapine fumarate immediate-release) taken twice daily, the area under the concentration-time curve (AUC) was the same, but the maximum plasma concentration (Cmax) was 13% lower at steady state. When comparing Quetilept® Retard with quetiapine immediate-release, the AUC of the metabolite norquetiapine was 18% lower.
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 high-fat meals on the bioavailability of the drug may be greater. A light meal does not have a significant effect on Cmax and AUC of quetiapine. It is recommended that Quetiapine be taken once daily at least one hour before a meal.
Distribution
Approximately 83% of quetiapine is bound to plasma proteins.
Metabolism
Quetiapine is extensively metabolized in the liver; administration 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 radiolabel is excreted in the urine and 21% in the feces.
In humans, 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.
Special populations.
Sex
The pharmacokinetics of quetiapine do not differ between women and men.
The average 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 in patients with severe renal impairment (creatinine clearance less than 30 ml/min/1.73 m2) was reduced by approximately 25%, however individual clearance values are within the range of 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.
Indication
Ketilept® Retard is indicated for the treatment of:
schizophrenia, including prevention of relapse in patients with stable schizophrenia who received maintenance therapy with quetiapine;
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 quetiapine is effective.
As adjunctive therapy for severe 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 Ketilept® Retard.
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, Ketilept® Retard 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 an increase in AUC
quetiapine 5-8 times. Therefore, concomitant use of quetiapine with CYP3A4 inhibitors is contraindicated. It is also not recommended to consume grapefruit juice during treatment with quetiapine.
In a multiple-dose study to evaluate the pharmacokinetics of quetiapine administered before and during treatment with carbamazepine (a hepatic enzyme inducer), concomitant use of carbamazepine significantly increased the clearance of quetiapine. This increase in clearance reduced systemic exposure to quetiapine (as measured by AUC) to a level that was on average 13% of that obtained with quetiapine alone, although some patients had a greater effect. This interaction may result in lower plasma concentrations, which may affect the efficacy of therapy with Ketilept® Retard.
Concomitant use of quetiapine and phenytoin (another microsomal enzyme inducer) increased quetiapine clearance by approximately 450%. Ketilept® Retard therapy should only be initiated in patients receiving a hepatic enzyme inducer if the physician believes that the benefits of Ketilept® Retard 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 "Special instructions").
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 studies comparing the combination of lithium with Ketilept® Retard and placebo with Ketilept® Retard in adult patients suffering from acute mania, an increased incidence of extrapyramidal phenomena (especially tremor), somnolence and weight gain was observed in the lithium group compared to the placebo group.
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 Ketilept® Retard is indicated for the treatment of schizophrenia, bipolar disorder and concomitant treatment of depressive episodes in patients with MDD, the safety profile of the drug should be carefully considered in light of the specific 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
Ketilept® Retard is not recommended for use in children due to the lack of data to support its use in this age group. Clinical trial data for quetiapine have shown that, in addition to the known safety profile established for 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 has been identified that has not previously been 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. Long-term effects on cognitive and behavioral development are unknown.
In placebo-controlled clinical trials in children and adolescents, quetiapine 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 within 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 is increased in the early stages of improvement.
In addition, the potential risk of suicidality following abrupt discontinuation of quetiapine treatment should be considered.
Other psychiatric conditions for which Ketilept® Retard is prescribed are also associated with an increased risk of suicide-related events. In addition, these conditions may occur simultaneously 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 degree 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. There is an increased risk of suicidal behavior in patients under 25 years of age. Close monitoring of patients, particularly those at high risk, should accompany drug therapy, particularly at the beginning of treatment and during subsequent dose changes. Patients (and their caregivers) should be warned about the need to monitor for clinical worsening, suicidal behavior or thoughts and changes in behavior and to seek medical advice immediately if symptoms present.
An increased risk of suicide-related events has been reported in patients under 25 years of age with major depressive episodes in bipolar disorder treated with quetiapine. There is also an increased risk of suicide-related events in patients under 25 years of age with bipolar disorder treated with quetiapine.
Drowsiness
Cardiovascular diseases
Quetiapine should be used with caution in patients with cardiovascular and cerebrovascular diseases or other conditions that may lead to arterial hypotension. Quetiapine may cause orthostatic hypotension, especially at the beginning of dose titration, therefore, in such cases, a dose reduction or a longer titration period is necessary.
Convulsions
In the studies, there was no difference in the incidence of seizures between patients taking quetiapine and those taking placebo. As with other antipsychotics, caution is recommended when prescribing the drug to patients with a history of seizures.
Extrapyramidal symptoms
Quetiapine is associated with an increased incidence of extrapyramidal symptoms (EPS) 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, characterized 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, the need to reduce the dose or discontinue Ketilept® Retard should be considered. Symptoms of tardive dyskinesia may worsen and even occur after discontinuation of therapy.
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, Ketilept® Retard should be discontinued and appropriate treatment initiated.
Severe neutropenia and agranulocytosis
Severe neutropenia (neutrophil count <0.5×109/L) has been reported (uncommon) with quetiapine. Agranulocytosis (severe neutropenia with infection) has been reported rarely in patients treated with quetiapine, particularly 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. Risk factors for neutropenia include pre-existing low white blood cell counts and a history of drug-induced neutropenia. Cases of agranulocytosis have occurred in patients without risk factors. The possibility of neutropenia in patients with infection despite the absence of risk factors, as well as in patients with fever of unknown origin, should be considered and appropriate clinical measures should be taken.
It is recommended to discontinue quetiapine treatment if the blood neutrophil count falls below 1.0 × 109/L. It is advisable to monitor patients for signs of infection and monitor the neutrophil count until it exceeds < 1.5 × 109/L.
Interactions.
See also section "Interaction with other medicinal products and other forms of interaction". Concomitant use of quetiapine with a potent hepatic enzyme inducer such as carbamazepine or phenytoin significantly reduces quetiapine plasma concentrations, which may impair the efficacy of quetiapine therapy. Treatment with Ketilept® Retard in patients receiving a hepatic enzyme inducer should only be initiated if the physician considers that the benefits of using Ketilept® Retard outweigh the risks of withdrawing the hepatic enzyme inducer. It is important that any changes in the use of the inducer occur gradually. 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, sometimes associated with ketoacidosis or coma, have been reported rarely, including several fatal cases. In several cases, there was a prior increase in body weight, which may have contributed to these complications. Appropriate clinical monitoring is advisable in accordance with current antipsychotic guidelines. 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 risk factors for the development or progression of diabetes mellitus should have their glucose levels monitored regularly for worsening. Weight should be monitored regularly.
Lipids
Metabolic risk
Changes in body weight, blood glucose (see "Hyperglycemia") and lipids in individual patients increase metabolic risk, which requires appropriate treatment.
QT prolongation
Quetiapine did not cause a sustained increase in absolute QT intervals. However, QT prolongation has been observed in overdose. As with other antipsychotics, caution should be exercised when prescribing quetiapine to patients with cardiovascular disease and in patients with a family history of QT prolongation. Caution should also be exercised when prescribing quetiapine with other drugs known to prolong the QT interval or when used concomitantly with neuroleptics, especially in the elderly, patients with congenital long QT syndrome, congestive heart failure, cardiac hypertrophy, hypokalemia or hypomagnesemia.
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.
Elderly patients with dementia-related psychosis.
Ketilept® Retard is not recommended for the treatment of dementia-related psychosis. In patients with dementia, an approximately 3-fold increase in the risk of cardiovascular adverse events has been observed with the use of some atypical antipsychotics. The mechanism of this increased risk is unknown. An increased risk cannot be excluded with other antipsychotics and for other patient categories. Ketilept® Retard should be used with caution in patients with risk factors for stroke.
A meta-analysis of atypical antipsychotic trials found that elderly patients with dementia-related psychosis taking atypical antipsychotics were at increased risk of death compared with placebo. In studies of quetiapine in elderly patients with dementia, a causal relationship between quetiapine treatment and death was not established.
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), including fatal cases, in patients at higher risk of intestinal obstruction, including those receiving concomitant medications that reduce intestinal motility.
Venous thromboembolism
Cases of venous thromboembolism (VTE) have been reported with the use of neuroleptics. Since patients using neuroleptics often have acquired risk factors for VTE, precautions should be taken.
Effect on the liver
Treatment with Ketilept® Retard should be discontinued if jaundice develops.
Pancreatitis
Cases of pancreatitis have been reported during post-marketing use of quetiapine, but a causal relationship has not been established. Many of these patients had risk factors for pancreatitis, such as elevated triglycerides (see section 4.4), gallstones, and alcohol consumption.
Cardiomyopathy and myocarditis
Cardiomyopathy and myocarditis have been reported, but a causal relationship to quetiapine use has not been established. Quetiapine should be re-evaluated if cardiomyopathy or myocarditis is suspected.
Additional information
There are limited data on the use of quetiapine in combination with divalproex or lithium in moderate to severe manic episodes (see section 4.8). These data suggest an additive effect by the third week of treatment.
Lactose
Ketilept® Retard 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
There are published reports that quetiapine is excreted in human milk, although the extent of excretion is unknown. 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. 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. The following adverse reactions have been observed in neonates: agitation, hypertension, hypotension, tremor, somnolence, respiratory distress, or feeding disorders. Therefore, neonates should be closely observed.
Ability to influence reaction speed when driving vehicles or other mechanisms
Since quetiapine primarily acts on the central nervous system, patients are advised not to drive or operate machinery until individual sensitivity to such effects has been determined.
Method of administration and doses
There are different dosage regimens for each indication. It is important to ensure that the patient is prescribed the dosage that is appropriate for their condition.
Ketilept® Retard should be taken once a day 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
Ketilept® Retard should be taken at least 1 hour before meals. The daily dose at the beginning of therapy is 300 mg on the first day and 600 mg on the second day. The recommended daily dose is 600 mg, but if clinically justified, the dose can be increased to 800 mg per day. The dose should be adjusted within the effective dose range: from 400 mg to 800 mg per day - depending on the clinical response and tolerability. For maintenance therapy in schizophrenia, there is no need for dose adjustment.
For the treatment of depressive episodes in bipolar disorder
Ketilept® Retard 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. No additional benefit was observed in the 600 mg group compared to the 300 mg group (see section "Pharmacological properties"). 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. For individual patients, in case of problems associated 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 Ketilept® Retard in the emergency treatment of bipolar disorder should continue to take Ketilept® Retard at the same dose at bedtime. The dose of Ketilept® Retard can be adjusted within a dose range of 300 mg to 800 mg/day, depending on the patient's clinical response and tolerability. It is important that the lowest effective dose is used for maintenance therapy.
For the concomitant treatment of major depressive episodes in MDD.
Ketilept® Retard 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. When using higher doses of the drug, the risk of developing adverse reactions increases. Therefore, the doctor should ensure that the lowest effective dose is used for treatment, starting from 50 mg/day. Increasing the dose from 150 to 300 mg/day should be based on an assessment of the patient's condition.
Switching from quetiapine immediate-release tablets
Patients treated with single doses of quetiapine immediate-release tablets may be switched to Quetiapine Retard at an equivalent total daily dose to be taken once daily. A dose titration period may be necessary to ensure maintenance of clinical response.
As with other antipsychotics and antidepressants, Ketilept® Retard should be used with caution in elderly patients, especially at the beginning of treatment and during the dose adjustment period. A slower dose titration of Ketilept® Retard 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 patients compared to younger patients. Treatment of elderly patients should be initiated at a dose of 50 mg/day. The dose may be increased gradually by 50 mg/day until an effective dose is achieved, depending on the clinical response and tolerability of the treatment. Elderly patients with depressive episodes in TDR should be started at 50 mg/day on days 1-3, increasing the dose 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 patient's condition, 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, Ketilept® Retard should be used with caution in patients with impaired liver function, especially during the initial dose adjustment period. Treatment of patients with impaired liver function should be initiated at a dose of 50 mg/day. The dose may be increased in 50 mg/day increments to an effective dose, depending on the patient's clinical response and tolerability.
Children
Ketilept® Retard is not recommended for use in children due to the lack of data supporting its use in this age group.
Overdose
Survival has been reported following acute overdoses of up to 30 g of quetiapine. Most patients with overdoses either experienced adverse events or recovered completely. A fatal outcome has been reported following an overdose of 13.6 g of quetiapine. During post-marketing use, reports of quetiapine overdose resulting in death, coma or QT prolongation have been very rare. In addition, the following events have been reported with quetiapine overdose: QT prolongation, seizures, status epilepticus, rhabdomyolysis, respiratory depression, urinary retention, confusion, delirium and/or agitation.
Patients with severe cardiovascular disease are at increased risk of overdose effects (see section "Special warnings and precautions for use").
In general, the symptoms reported were due to an increase in the known pharmacological effects of the drug, such as drowsiness and sedation, tachycardia and hypotension. There is no specific antidote for quetiapine. In severe cases, the need for multimodality and intensive care should be considered, including the establishment and maintenance of a patent airway, adequate oxygenation and ventilation, and cardiovascular monitoring and support. Published reports describe reversal of serious central nervous system (CNS) reactions, including coma and delirium, with intravenous physostigmine (1-2 mg) under continuous ECG monitoring.
In cases of persistent hypotension in quetiapine overdose, appropriate measures should be taken, such as intravenous fluid administration and/or the use of sympathomimetics (adrenaline and dopamine should be avoided, as beta-adrenergic receptor stimulation may exacerbate hypotension in the setting of alpha-adrenergic receptor blockade caused by quetiapine).
Since prevention of absorption in case of overdose has not been studied, gastric lavage (after intubation if the patient is unconscious) and the use of activated charcoal together with a laxative should be considered. Careful medical supervision and monitoring should continue until the patient recovers.
Side effects
When taking Quetiapine
