Quentiax, tablets 25 mg, 60 pcs.

an antipsychotic (neuroleptic)

Active ingredient

Composition

1 film-coated tablet, 25 mg contains:

nucleus

Active substance:

Quetiapine fumarate (quetiapine hemifumarate) 28.78 mg (equivalent to quetiapine 25 mg)

Auxiliary substances:lactose monohydrate, calcium hydrophosphate dihydrate, microcrystalline cellulose, type 101, microcrystalline cellulose, type 102, povidone K-25, sodium carboxymethyl starch (type A), magnesium stearate

Shell film

Hypromellose, titanium dioxide (E171), macrogol-4000, iron oxide yellow dye (E172), iron oxide red dye (E172)

1 film-coated tablet, 100 mg contains:

nucleus

Active substance:

Quetiapine fumarate (quetiapine hemifumarate) 115.13 mg (equivalent to quetiapine 100 mg)

Auxiliary substances:lactose monohydrate, calcium hydrophosphate dihydrate, microcrystalline cellulose, type 101, microcrystalline cellulose, type 102, povidone K-25, sodium carboxymethyl starch (type A), magnesium stearate

coating film

Hypromellose, titanium dioxide (E171), macrogol-4000, iron oxide yellow dye (E172)

1 film-coated tablet, 200 mg/300 mg contains:

nucleus

Active substance:

Quetiapine fumarate (quetiapine hemifumarate) 230.26 mg (equivalent to quetiapine 200 mg)/Quetiapine fumarate (quetiapine hemifumarate) 345.39 mg (equivalent to quetiapine 300 mg)

Auxiliary substances:lactose monohydrate, calcium hydrophosphate dihydrate, microcrystalline cellulose, type 101, microcrystalline cellulose, type 102, povidone K-25, sodium carboxymethyl starch (type A), magnesium stearate

Shell film

Hypromellose, titanium dioxide (E171), macrogol-4000

How to take, the dosage

Orally, 2 times a day regardless of meal time.

Adults

The treatment of schizophrenia

The daily dose for the first 4 days of therapy is: 1st day – 50 mg, 2nd day – 100 mg, 3rd day – 200 mg, 4th day – 300 mg.

Starting on the 4th day, the dose should be adjusted to an effective one, usually within 300-450 mg/day. Depending on the clinical effect and individual tolerance of the drug, the dose may vary from 150 mg/day to 750 mg/day. The maximum recommended daily dose is 750 mg.

Treatment of manic episodes in the structure of bipolar disorder

The drug Quentiax® is recommended as monotherapy or in combination with drugs with normotensive effects.

The daily dose for the first 4 days of therapy is: 1st day – 100 mg, 2nd day – 200 mg, 3rd day – 300 mg, 4th day – 400 mg. By the 6th day of therapy, the daily dose can be increased to 800 mg. Increase in daily dose should not exceed 200 mg/day. Depending on clinical effect and individual tolerance of the drug, the dose may vary from 200 mg/day to 800 mg/day. Usually, the effective dose is between 400 mg/day and 800 mg/day. The maximum recommended daily dose is 800 mg.

Treatment of depressive episodes in the structure of bipolar disorder

The drug Quentiax® is prescribed once daily at night. The daily dose for the first 4 days of therapy is: 1st day – 50 mg, 2nd day – 100 mg, 3rd day – 200 mg, 4th day – 300 mg. Recommended daily dose is 300 mg. The maximum recommended daily dose of Quentiax® is 600 mg.

The antidepressant effect of quetiapine has been confirmed when used at 300 and 600 mg/day.

Doses in excess of 300 mg should be initiated under the supervision of a physician experienced in the therapy of bipolar disorders. In individual patients, in case of suspected poor tolerance of the drug, it is possible to reduce the dose to a minimum of 200 mg/day according to the results of clinical trials.

Elderly patients

Quentiax®, like other neuroleptics, should be used with caution in elderly patients, especially at the beginning of therapy. The dose should be titrated more slowly and the daily therapeutic dose should be lower than in younger patients, depending on clinical response and individual tolerability. Mean clearance of quetiapine was reduced by 30-50% in elderly patients compared to younger patients.

Efficacy and safety have not been studied in patients over 65 years of age with depressive episodes in the structure of bipolar disorder.

Patients with renal impairment

Dose adjustment is not required.

Patients with hepatic insufficiency

Quetiapine is extensively metabolized in the liver. Therefore, caution should be exercised when using Quetiax ® in patients with hepatic impairment, especially at the beginning of therapy. It is recommended to start therapy with a dose of 25 mg/day and increase the dose daily by 25-50 mg until an effective dose is achieved.

Interaction

Caution should be exercised when using Quentiax ® concomitantly with other CNS-acting drugs and with alcohol.

Caution should be exercised in patients taking other cholinergic (muscarinic) receptor antagonists.

The cytochrome Р450 3A4 system is the main isoenzyme responsible for the metabolism of quetiapine through the cytochrome Р450 system. In healthy volunteers, concomitant use of quetiapine (in dose 25 mg) with ketoconazole, CYP3A4 isoenzyme inhibitor, resulted in 5-8 times increase of area under “concentration-time” curve (AUC) of quetiapine.

Therefore, simultaneous use of quetiapine and CYP3A4 isoenzyme inhibitors is contraindicated. It is not recommended to eat grapefruit juice during quetiapine therapy.

In a pharmacokinetic study, use of quetiapine in different dosages before or simultaneously with carbamazepine resulted in a significant increase in quetiapine clearance and a corresponding decrease in AUC, on average by 13%, compared with quetiapine administration without carbamazepine. In some patients, the decrease in AUC was even more pronounced. This interaction is accompanied by a decrease in plasma concentration of quetiapine and may reduce the effectiveness of quetiapine therapy. Concomitant use of quetiapine with phenytoin, another inducer of microsomal liver enzymes, was accompanied by even more pronounced (by about 450 %) increase in clearance of quetiapine. Quetiapine use in patients receiving microsomal liver enzymes inducers is possible only if the expected benefit from quetiapine therapy exceeds the risk associated with withdrawal of the microsomal liver enzymes inducer drug. Changes in the dose of microsomal enzyme inducers should be gradual. If necessary, their substitution with drugs that do not induce microsomal liver enzymes (for example, valproic acid preparations) is possible.

The pharmacokinetics of quetiapine did not change significantly with concomitant use of the antidepressant imipramine (CYP2D6 isoenzyme inhibitor) or fluoxetine (CYP3A4 and CYP2D6 isoenzyme inhibitor).

Pharmacokinetics of quetiapine is not significantly altered when used concomitantly with the antipsychotic drugs risperidone or haloperidol. However, concomitant use of quetiapine and thioridazine led to an increase in clearance of quetiapine by about 70%.

Pharmacokinetics of quetiapine is not significantly changed by concomitant use of cimetidine.

Pharmacokinetics of lithium preparations are not altered when using quetiapine concomitantly.

When quetiapine was used concomitantly with lithium drugs, a higher incidence of EPS-related adverse reactions (particularly tremor), somnolence, and weight gain was noted in adult patients with an acute manic episode compared to patients who took quetiapine with placebo in a 6-week randomized trial.

No clinically significant changes in valproic acid and quetiapine pharmacokinetics were observed when valproate seminatria and quetiapine were used simultaneously.

A retrospective study involving children and adolescents who received sodium valproate and quetiapine separately or both drugs simultaneously found a higher rate of leukopenia and neutropenia in the combination therapy group compared to the monotherapy group.

Pharmacokinetic studies to study the interaction of Quentiax® with drugs used in cardiovascular diseases have not been conducted.

Caution should be exercised when using Quetiapine concomitantly with drugs that can cause electrolyte imbalance and QTc interval prolongation.

False-positive screening tests for methadone and tricyclic antidepressants by enzyme immunoassay have been reported in patients taking quetiapine. A chromatographic study is recommended to confirm the screening results.

Lorazepam clearance decreases by approximately 20% when taking 2 mg of lorazepam once while taking quetiapine at a dose of 250 mg twice daily.

Quetiapine did not induce induction of microsomal liver enzymes involved in phenazone metabolism.

Special Instructions

Patient use in patients with cardiovascular and cerebrovascular disease or other conditions predisposing to arterial hypotension, use in elderly patients, hepatic impairment, history of seizures, risk of stroke and aspiration pneumonia.

While the efficacy and safety of quetiapine in children and adolescents aged 10-17 years have been studied in clinical trials, the use of Quetiax® in patients under 18 years is not indicated.

Elderly patients

Quentiax®, like other neuroleptics, should be used with caution in elderly patients, especially at the beginning of therapy. The dose should be titrated more slowly and the daily therapeutic dose should be lower than in younger patients, depending on clinical response and individual tolerability. Mean clearance of quetiapine was reduced by 30-50% in elderly patients compared to younger patients.

Efficacy and safety have not been studied in patients over 65 years of age with depressive episodes in the structure of bipolar disorder.

Patients with renal impairment

Dose adjustment is not required.

Patients with hepatic insufficiency

Quetiapine is extensively metabolized in the liver. Therefore, caution should be exercised when using Quetiax ® in patients with hepatic impairment, especially at the beginning of therapy. It is recommended to start therapy with a dose of 25 mg/day and increase daily by 25-50 mg until an effective dose is achieved.

Because Quentiax® has multiple indications for use, its safety profile is determined depending on the patient’s diagnosis and dose of the drug.

Children and adolescents (ages 10 to 17)

Quentiax® is not indicated for use in children and adolescents under the age of 18 years due to insufficient data on use in this age group. According to the results of clinical trials, some adverse reactions (increased appetite, increased serum prolactin concentration, vomiting, rhinitis and syncope) in children and adolescents were observed with higher frequency than in adult patients or had different clinical manifestations (EPS and irritability). There was also an increase in blood pressure not observed in adult patients. Changes in thyroid function were also observed in children and adolescents.

The effects on growth, puberty, mental development and behavioral responses with long-term use (over 26 weeks) of quetiapine were not studied.

In placebo-controlled studies in children and adolescents with schizophrenia and mania as part of bipolar disorder, the incidence of EPS was higher with quetiapine compared to placebo.

Suicidal ideation/suicidal thoughts or clinical deterioration

Depression in bipolar disorder is associated with an increased risk of suicidal ideation, self-harm, and suicide (suicide-related events). This risk persists until the onset of significant remission. Due to the fact that it may take several weeks or more before a patient’s condition improves from the start of treatment, patients should be under close medical supervision until improvement occurs. In the early stages of remission, the risk of suicide may increase, according to generally accepted clinical experience.

Patients (especially those at high risk for suicide) and their caregivers should be warned to monitor for clinical deterioration, suicidal behavior or thoughts, unusual changes in behavior, and to seek immediate medical attention if they occur.

In short-term placebo-controlled clinical trials in depressed patients with bipolar disorder, the risk of suicidal events was 3.0% (7/233) for quetiapine and 0% (0/120) for placebo in patients aged 18-24 years, 1.8% (19/1616) for quetiapine and 1.8% (11/622) for placebo in patients over 25 years. A population-based retrospective study of quetiapine use in patients with major depressive disorder found an increased risk of self-harm and suicide attempts in patients aged 25 to 64 years without a history of self-harm taking quetiapine with other antidepressants.

Other psychiatric disorders treated with quetiapine are also associated with an increased risk of suicide-related events. In addition, such conditions may be comorbid with a depressive episode. Thus, the precautions used when treating patients with a depressive episode should also be taken when treating patients with other psychiatric disorders.

The potential risk of suicidal events should be considered when quetiapine therapy is abruptly discontinued.

Patients with a history of suicidal events, as well as patients clearly expressing suicidal thoughts before initiating therapy, are at increased risk for suicidal intentions and suicide attempts and should be closely monitored during treatment. An FDA (Food and Drug Administration, USA) meta-analysis of placebo-controlled trials of antidepressants, summarizing data from approximately 4,400 children and adolescents and 7,700 adult patients with psychiatric disorders, found an increased risk of suicidal behavior on antidepressants compared to placebo in children, adolescents and adult patients under 25 years of age. This meta-analysis does not include studies with quetiapine (see subsection “Pharmacodynamics”).

The incidence of suicide-related events was 0.8% for both quetiapine (76/9327) and placebo (37/4845), according to short-term placebo-controlled studies in all indications and in all age groups.

In these studies, patients with schizophrenia had a 1.4% (3/212) risk of suicidal events for quetiapine and 1.6% (1/62) for placebo in patients aged 18-24 years, 0.8% (13/1663) for quetiapine and 1.1% (5/463) for placebo in patients older than 25 years, and 1.4% (2/147) for quetiapine and 1.3% (1/75) for placebo in patients under 18 years of age.

In patients with bipolar mania, the risk of suicidal events was 0% (0/60) for quetiapine and 0% (0/58) for placebo in patients aged 18-24 years, 1.2% (6/496) for quetiapine and 1.2% (6/503) for placebo in patients over 25 years, and 1.0% (2/193) for quetiapine and 0% (0/90) for placebo in patients under 18 years.

Metabolic disorders

Given the risk of worsening of the metabolic profile, including changes in body weight, plasma glucose and lipid concentrations reported in clinical trials, patients’ metabolic parameters should be evaluated at the beginning of therapy and should be regularly monitored during therapy. If these parameters deteriorate, appropriate treatment should be undertaken.

Extrapyramidal symptoms

An increased incidence of EPS when taking quetiapine was noted in adult patients with a major depressive episode of bipolar disorder or major depressive disorder compared with placebo (see side effects).

Quetiapine use has been associated with the development of akathisia, which is characterized by subjectively unpleasant anxiety or restlessness and often accompanied by an inability to sit or stand still. These phenomena are most commonly noted in the first few weeks of treatment. Increasing the dose in patients who develop such symptoms may have a negative impact.

Late dyskinesia

If symptoms of late dyskinesia develop, it is recommended to reduce the dose of the drug or withdraw it gradually. Symptoms of tardive dyskinesia may worsen or even occur after discontinuation of the drug (see section “Side effects”).

Sleepiness and dizziness

Sleepiness and related symptoms, such as sedation, may occur during quetiapine therapy (see side effects). In clinical trials involving patients with bipolar depression and depressive episode, somnolence usually developed during the first three days of therapy. The severity of this adverse reaction was mostly mild to moderate. If severe somnolence develops, patients with depression in the structure of bipolar disorder and patients with a depressive episode may require more frequent visits to the physician within 2 weeks from the onset of somnolence or until the severity of symptoms decreases. In some cases, it may be necessary to discontinue quetiapine therapy.

During quetiapine therapy, orthostatic hypotension and dizziness may occur (see section “Side effects”) usually during dose adjustment at the beginning of therapy. Patients, especially elderly patients, should be careful to avoid accidental injuries (falls).

Patients with cardiovascular disease

Caution should be exercised when using quetiapine in patients with cardiovascular disease, cerebrovascular disease, and other conditions that predispose to arterial hypotension. In such patients, the dose should be adjusted more slowly. Orthostatic hypotension may occur during quetiapine therapy, especially during dose adjustment at the beginning of therapy. If orthostatic hypotension occurs it may be necessary to decrease the dose or adjust it more gradually.

Sleep apnea syndrome

Sleep apnea syndrome was noted in patients taking quetiapine. Quetiapine should be used with caution in patients concomitantly taking CNS-depressant drugs or who have a history of sleep apnea (e.g., overweight/obese patients, male patients).

Convulsive seizures

No differences were found in the incidence of seizures in patients taking quetiapine or placebo. However, as with therapy with other antipsychotic medications, caution is recommended when treating patients with a history of seizures (see section “Side effects”).

Malignant neuroleptic syndrome

Malignant neuroleptic syndrome may develop while taking antipsychotics, including quetiapine (see side effects section. See Side Effects). Clinical manifestations of the syndrome include hyperthermia, altered mental status, muscle rigidity, autonomic nervous system lability, and increased creatine phosphokinase activity. In such cases it is necessary to stop quetiapine administration and conduct an appropriate treatment.

Severe neutropenia and agranulocytosis

In short-term placebo-controlled clinical trials of quetiapine monotherapy, severe neutropenia (neutrophil count < 0.5 x 109/l) without infection was infrequently reported. Agranulocytosis (severe neutropenia associated with infections) has been reported in patients receiving quetiapine as part of clinical trials (rare), as well as during post-registration use (including fatal). Most of these cases of severe neutropenia occurred within 2 months of starting quetiapine therapy. No dose-dependent effects were detected. Leukopenia and/or neutropenia resolved after discontinuation of quetiapine therapy. A possible risk factor for the occurrence of neutropenia is a previous reduced leukocyte count and a history of drug-induced neutropenia. The development of agranulocytosis has also been noted in patients without risk factors. The possibility of neutropenia development in patients with infection, especially in the absence of obvious predisposing factors, or in patients with unexplained fever should be considered; these cases should be managed according to clinical guidelines.

In patients with a neutrophil count < 1.0 x 109/L, quetiapine should be discontinued. The patient should be monitored for possible symptoms of infection and neutrophil counts should be monitored (until they increase to 1.5 x 109/l).

Patients should be informed and immediately report signs/symptoms of agranulocytosis or infection (e.g., fever, weakness, lethargy, sore throat) throughout Quentiax ® therapy.

Anticholinergic (muscarinic) effects

Norquetiapine, the active metabolite of quetiapine, exhibits moderate to high affinity for several muscarinic receptor subtypes, which explains the development of NLR due to anticholinergic action when quetiapine is used at recommended doses, when other anticholinergic drugs are used simultaneously, and when overdosed. Caution should be exercised when using quetiapine in patients taking cholinergic (muscarinic) receptor antagonists, as well as in patients with urinary retention, including in anamnesis, clinically significant prostatic hypertrophy, intestinal obstruction or related conditions, with elevated intraocular pressure or closed-angle glaucoma.

Interaction with other medicinal products

Also see “Interaction with other medicinal products”.

Concomitant use of quetiapine with potent inducers of microsomal liver enzymes, such as carbamazepine and phenytoin, decreases the plasma concentration of quetiapine and may decrease the effectiveness of quetiapine therapy®.

The use of Quentiax® in patients receiving microsomal liver enzyme inducers is possible only if the expected benefit from the drug therapy exceeds the risk associated with withdrawal of microsomal liver enzyme inducers. Changes in the dose of microsomal liver enzyme inducers should be gradual. If necessary, their substitution with drugs that do not induce microsomal liver enzymes (for example, valproic acid preparations) is possible.

body weight

An increase in body weight was noted during quetiapine administration. Clinical monitoring of patients is recommended according to the accepted standards of therapy (see section “Side effects”).

Hyperglycemia

During quetiapine treatment, hyperglycemia and/or development and exacerbation of diabetes mellitus may occur, sometimes accompanied by ketoacidosis or coma, including fatal. including fatal. In some cases there has been a previous increase in body weight, which may be a predisposing factor. Regular monitoring of body weight and symptoms of hyperglycemia, such as polydipsia, polyuria, polyphagia, and weakness, in patients taking neuroleptics, including quetiapine, is recommended. Clinical monitoring of patients with diabetes mellitus, patients with risk factors for diabetes mellitus is recommended (see section “Side effects”).

Lipid concentration

An increase in triglyceride, total cholesterol, and LDL cholesterol concentrations, and a decrease in plasma HDL concentrations may occur during quetiapine administration (see section “Side effects”). These changes should be corrected in accordance with the current recommendations.

QT interval prolongation

No relationship between quetiapine administration and persistent increase in absolute QT interval value was found. However, prolongation of the QT interval was observed when using quetiapine in therapeutic doses and in case of quetiapine overdose (see section “Overdose”). Caution should be exercised when using vetiapine, as well as other antipsychotic drugs, in patients with cardiovascular diseases and with a history of QT interval prolongation. Caution is also required when using quetiapine concomitantly with agents that prolong the QT interval c, other neuroleptics, especially in elderly patients, patients with congenital QT interval prolongation syndrome, chronic heart failure, myocardial hypertrophy, hypokalemia or hypomagnesemia (see section “Interaction with other medicinal products”).

Cardiomyopathy and myocarditis

Cases of cardiomyopathy and myocarditis have been reported during clinical trials and post-registration use, but a causal relationship to drug administration has not been established. The appropriateness of quetiapine therapy in patients with suspected cardiomyopathy or myocarditis should be evaluated.

Acute reactions associated with drug withdrawal

The following acute reactions (withdrawal syndrome) – nausea, vomiting, insomnia, headache, dizziness, and irritability – may occur if quetiapine is abruptly withdrawn. Therefore, withdrawal of Quentiax ® is recommended to be done gradually over at least one or two weeks.

Elderly patients with dementia

The drug Quentiax® is not indicated for the treatment of psychosis associated with dementia. Some atypical neuroleptics in randomized placebo-controlled trials increased the risk of cerebrovascular complications in patients with dementia by approximately 3-fold. The mechanism of this increased risk is not understood. A similar risk of increased incidence of cerebrovascular complications cannot be ruled out for other antipsychotic medications or other patient groups. Quentiax® should be used with caution in patients at risk of stroke.

An analysis of the use of atypical neuroleptics to treat psychosis associated with dementia in elderly patients found an increased mortality rate in the group of patients receiving the drugs in this group compared with the placebo group. Two 10-week placebo-controlled trials of quetiapine in a similar group of patients (n=710, mean age: 83 years, age range: 56-99 years) showed that mortality was 5.5% in the patient group receiving quetiapine and 3.2% in the placebo group. The causes of death observed in these patients were consistent with those expected in this population. No causal relationship was found between quetiapine treatment and the risk of increased mortality in elderly patients with dementia.

PElderly patients with Parkinson’s disease/parkinsonism

A population-based retrospective study of quetiapine use in patients with major depressive disorder found an increased risk of mortality in patients aged > 65 years. The increased risk was not determined when patients with Parkinson’s disease were excluded from the analysis. Caution should be exercised when prescribing quetiapine to elderly patients with Parkinson’s disease.

Dysphagia

Dysphagia (see side effects) and aspiration were observed with quetiapine therapy. A causal relationship of aspiration pneumonia with quetiapine administration has not been established. However, caution should be exercised when using Quetiax ® in patients at risk of aspiration pneumonia.

constipation and bowel obstruction

Constipation is a risk factor for bowel obstruction. Constipation and bowel obstruction have been reported with quetiapine (see side effects), including fatal cases in patients at high risk for bowel obstruction, including those receiving multiple concomitant medications that reduce bowel motility, even in the absence of constipation complaints. Patients with intestinal obstruction/ileus need urgent measures and close monitoring.

Venous thromboembolism

Venous thromboembolism has been reported with neuroleptics. Risk factors should be evaluated before and during therapy with antipsychotics, including quetiapine, and preventive measures should be taken.

Pancreatitis

Cases of pancreatitis have been reported during clinical trials and post-registration use, but a causal relationship to drug administration has not been established. Post-registration reports indicate that many patients had risk factors for pancreatitis, such as elevated triglyceride concentrations (see subsection “Lipid concentrations”), cholelithiasis, and alcohol consumption.

Liver disorders

Quetiapine should be stopped if jaundice develops.

Advanced information

There are limited data on concomitant use of quetiapine with divalproate or lithium during acute moderate to severe manic episodes. Good tolerability of this combination therapy and additive effect at 3 weeks of treatment have been noted.

Misuse and abuse

Cases of misuse and abuse have been reported. Caution should be used when prescribing quetiapine to patients with a history of alcohol or drug abuse.

Special information on excipients

The drug Quentiax® contains lactose and therefore should not be used in the following conditions: lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome.

The drug Quentiax® may cause somnolence, therefore during the treatment period the patients should not operate machinery requiring high concentration, including driving vehicles.

Synopsis

Tablets 25 mg

Round, biconvex, film-coated tablets with brownish-red color, beveled.

Breakage appearance: a rough white mass with a brownish-red film coating.

Tablets 100 mg

Round, biconvex, film-coated pale yellow tablets.

Breakage appearance: a rough white mass with light yellow film coating.

Tablets 200 mg

Round, biconvex, film-coated white tablets.

Breakage appearance: rough white mass with white film coating.

Tablets 300 mg

Oval, biconvex, film-coated white tablets.

Breakage appearance: a rough mass of white color with white film coating.

Contraindications

While the efficacy and safety of quetiapine in children and adolescents aged 10-17 years have been studied in clinical trials, the use of Quetiax ® in patients under 18 years is not indicated.

Overdose

Symptoms

The symptoms noted in overdose were mainly the result of an increase in the known pharmacological effects of quetiapine, such as drowsiness and sedation, tachycardia, decreased blood pressure, and anticholinergic effects.

Overdose may result in prolongation of the QT interval, seizures, status epilepticus, rhabdomyolysis, respiratory depression, urinary retention, confusion, delirium and/or agitation, coma and death.

In patients with a history of severe cardiovascular disease, the risk of side effects in overdose may increase (see section “Special Precautions”).

Treatment

There are no specific antidotes to quetiapine. In cases of severe intoxication, it is necessary to remember about the possibility of overdose with several drugs. Measures aimed at maintaining respiratory and cardiovascular function and ensuring adequate oxygenation and ventilation are recommended. There have been published reports of resolution of severe adverse central nervous system (CNS) effects, including coma and delirium, after intravenous administration of physostigmine (in a dose of 1-2 mg) under continuous electrocardiogram (ECG) monitoring. This treatment is not recommended as standard treatment because of the potential negative effect of physostigmine on cardiac conduction. Physostigmine may be used only in the absence of ECG abnormalities. Physostigmine should not be used in case of cardiac rhythm disorders, blockade of any degree or when the QRS complex is dilated.

In case of refractory arterial hypotension in quetiapine overdose, treatment should be performed by intravenous administration of fluid and/or sympathomimetic agents (epinephrine and dopamine should not be used because stimulation of β-adrenoreceptors may cause increased decrease of blood pressure against blockade of α-adrenoreceptors by quetiapine).

Gastric lavage (after intubation if the patient is unconscious) and administration of activated charcoal and laxatives may facilitate excretion of unabsorbed quetiapine, however the effectiveness of these measures has not been studied.

Close medical monitoring should continue until the patient’s condition improves.

Pregnancy use

Pregnancy

Published data on use during pregnancy (300-1000 pregnancy outcomes), including individual reports and data from observational studies, have not shown an increased risk of malformations during treatment. Nevertheless, no definite conclusion can be drawn from the available data. Animal studies have revealed the presence of reproductive toxicity. As a consequence, during pregnancy, quetiapine should only be used if the expected benefit to the mother justifies the potential risk to the fetus.

The use of antipsychotic drugs, including quetiapine, in the third trimester of pregnancy in newborns raises the risk of adverse reactions of varying severity and duration, including EPS and/or withdrawal syndrome. Agitation, hypertension, hypotension, tremor, somnolence, respiratory distress syndrome, or feeding disturbances have been reported. In this regard, the condition of newborns should be closely monitored.

Breastfeeding

The excretion of quetiapine with breast milk has been reported, but the extent of excretion has not been determined. Because of the lack of reliable data, the decision should be made whether to stop breastfeeding or to stop Quetiax®.

Similarities