Quentiax SR prolonged. 200 mg, 60 pcs.

• Schizophrenia, including:

prevent relapse in stable patients.

• Bipolar disorders, including:

moderate and severe manic episodes in the structure of bipolar disorder;

severe episodes of depression in the structure of bipolar disorder;

prevent relapses of bipolar disorder in patients with prior effective quetiapine therapy for manic or depressive episodes in the structure of bipolar disorder.

• Depressive episode:

combination therapy for suboptimal response to antidepressant monotherapy.

Active ingredient

Composition

1 film-coated sustained release tablet, 150 mg contains:

Kernel

Active substance:

Quetiapine hemifumarate 172.70 mg, equivalent to quetiapine 150.00 mg

Associates: Hypromellose 4000 mPas, hypromellose 100 mPas, lactose monohydrate, microcrystalline cellulose, sodium hydrophosphate dihydrate, magnesium stearate

Shell film

Opadray II HP white, iron oxide red dye (E172), iron oxide yellow dye (E172)

Opadray II HP white contains: partially hydrolyzed polyvinyl alcohol, titanium dioxide (E171), macrogol/PEG 3000, talc

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

Kernel

Active substance:

Quetiapine hemifumarate 230.27 mg/345.40 mg, equivalent to quetiapine 200.00 mg/300.00 mg

Associates: Hypromellose 4000 mPas, hypromellose 100 mPas, lactose monohydrate, microcrystalline cellulose, sodium hydrophosphate dihydrate, magnesium stearate

Shell film

Opadray II HP white, iron oxide yellow dye (E172)

Opadray II HP white contains: partially hydrolyzed polyvinyl alcohol, titanium dioxide (E171), macrogol/PEG 3000, talc

How to take, the dosage

Adminally, once a day, on an empty stomach (at least 1 hour before a meal).

The tablets should be swallowed whole, not divided, chewed or crushed.

Adults

Treatment of schizophrenia, moderate and severe manic episodes in the structure of bipolar disorder

The drug Quentiax® SR should be taken at least 1 hour before a meal.

The daily dose for the first 2 days of therapy is: 1st day – 300 mg, 2nd day – 600 mg. The recommended daily dose is 600 mg, but if necessary it can be increased to 800 mg/day. Depending on the clinical effect and individual tolerance of the patient, the dose may vary from 400 to 800 mg/day. For maintenance therapy in schizophrenia no dose adjustment is required after relieving an exacerbation.

Treatment of episodes of depression in the structure of bipolar disorder

The drug Quentiax® SR should be taken before bedtime. 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. Depending on clinical effect and individual tolerance of a patient, a dose can be increased up to 600 mg. No advantages of using Quentiax® SR at a daily dose of 600 mg compared to 300 mg have been observed. Quentiax® XR at a dose greater than 300 mg should be prescribed by a physician experienced in bipolar disorder therapy.

Prevention of bipolar relapses in patients with prior effective quetiapine therapy for manic or depressive episodes in the structure of bipolar disorder

To prevent relapses of manic, depressive, and mixed episodes in bipolar disorder, patients with a positive response to treatment with Quentiax® SR should continue therapy at the same daily dose as when therapy was initiated. Quentiax® SR should be taken before bedtime. Depending on the clinical effect and individual tolerance of the patient, the dose may vary from 300 to 800 mg/day. For maintenance therapy, the lowest effective dose of Quentiax ® SR is recommended.

Combined therapy for depressive episode in suboptimal response to antidepressant monotherapy

The drug Quentiax® SR should be taken before bedtime. The minimum effective dose should be used, starting therapy at 50 mg/day. The daily dose is: 1st and 2nd day, 50 mg; 3rd and 4th day, 150 mg. Increasing the dose from 150 mg/day to 300 mg/day should be based on the individual assessment of the patient’s condition. When using high doses, the risk of side effects increases.

Transfer from taking quetiapine in the form of fast-release tablets to taking Quetiax® SR

For ease of administration, patients currently receiving fractional therapy with quetiapine in the form of fast-release tablets may be switched to taking Quetiax® SR once daily at a dose equivalent to the total daily dose of quetiapine in the form of fast-release tablets. Dose adjustment may be necessary in individual cases.

Elderly patients

As with other neuroleptics, Quentiax ® SR should be used with caution in elderly patients, especially at the beginning of therapy. The selection of an effective dose of Quentiax ® SR in elderly patients may be slower and the daily therapeutic dose is lower than in younger patients. The average plasma clearance of quetiapine in elderly patients is 30-50% lower than in younger patients. In elderly patients, the starting dose of Quetiax ® SR is 50 mg/day. The dose may be increased by 50 mg/day until an effective dose, depending on clinical response and individual patient tolerability.

In elderly patients with a depressive episode, the daily dose for the first 3 days of therapy is 50 mg/day with an increase to 100 mg/day on the 4th day and to 150 mg/day on the 8th day. The minimum effective dose of the drug should be used, starting treatment with 50 mg/day. If necessary, the drug dose can be increased to 300 mg/day, but not earlier than day 22 of therapy.

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

Kidney function impairment

Dose adjustment is not required for patients with renal impairment.

Hepatic dysfunction

Quetiapine is extensively metabolized in the liver. As a consequence, caution should be exercised when using Quetiax ® SR in patients with hepatic impairment, especially at the beginning of therapy. It is recommended that therapy with Quentiax ® SR be started at a dose of 50 mg/day and increased daily by 50 mg until an effective dose is achieved.

Interaction

Cautious concomitant use of Quetiax ® SR with other drugs acting on the central nervous system, as well as with alcohol should be observed.

Cautiousness should be observed when using Quetiapine concomitantly with other drugs with anticholinergic (muscarinic-like) effects (see “Caution.

The cytochrome P450 (CYP) 3A4 is the main isoenzyme responsible for the metabolism of quetiapine via the cytochrome P450 system. In healthy volunteers, concomitant use of quetiapine (in dose of 25 mg) with ketoconazole, an inhibitor of CYP3A4, resulted in 5-8 times increase of AUC of quetiapine.

To prevent the simultaneous use of quetiapine and CYP3A4 isoenzyme inhibitors. It is not recommended to eat grapefruit juice during quetiapine therapy.

In a pharmacokinetic study, the use of quetiapine in different dosages before or simultaneously with carbamazepine resulted in a significant increase in quetiapine clearance and, accordingly, a decrease in AUC by an average of 13% compared to 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. The use of quetiapine in patients receiving microsomal liver enzymes inducers is possible only if the expected benefit of 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.

Pharmacokinetics of quetiapine was not significantly changed with concomitant use of antidepressant imipramine (CYP2D6 isoenzyme inhibitor) or fluoxetine (CYP3A4 and CYP2D6 isoenzyme inhibitor).

Pharmacokinetics of quetiapine is not significantly altered when concomitantly used with antipsychotic drugs risperidone or haloperidol. However, concomitant use of quetiapine and thioridazine resulted in increased clearance of quetiapine by approximately 70%.

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

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

The pharmacokinetics of lithium preparations are not changed when taking quetiapine simultaneously. No clinically significant changes in valproic acid and quetiapine pharmacokinetics have been observed with concomitant use of valproate and quetiapine.

Concomitant use of quetiapine with lithium preparations in adult patients with an acute manic episode showed a higher incidence of EPS-related adverse reactions (particularly tremor), somnolence, and weight gain compared to patients taking quetiapine with placebo in a 6-week randomized trial.

Pharmacokinetic studies of the interaction of Quetiax® SR with drugs used for cardiovascular disease have not been conducted.

Cautiousness should be observed when using Quetiapine concomitantly with drugs that can cause electrolyte imbalance and prolongation of QTc interval.

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

False positive screening tests for methadone and tricyclic antidepressants by enzyme immunoassay have been reported in patients taking quetiapine. Chromatographic testing is recommended to confirm screening results.

Special Instructions

Performance 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.

Quentiax® SR is not indicated for use in children and adolescents under 18 years of age due to insufficient data on use in this age group.

Elderly patients

As with other neuroleptics, Quentiax ® SR should be used with caution in elderly patients, especially at the beginning of therapy. The selection of an effective dose of Quentiax ® SR in elderly patients may be slower and the daily therapeutic dose is lower than in younger patients. The average plasma clearance of quetiapine in elderly patients is 30-50% lower than in younger patients. In elderly patients, the starting dose of Quetiax ® SR is 50 mg/day. The dose may be increased by 50 mg/day until an effective dose, depending on clinical response and individual patient tolerability.

In elderly patients with a depressive episode, the daily dose for the first 3 days of therapy is 50 mg/day with an increase to 100 mg/day on the 4th day and to 150 mg/day on the 8th day. The minimum effective dose of the drug should be used, starting treatment with 50 mg/day. If necessary, the drug dose can be increased to 300 mg/day, but not earlier than day 22 of therapy.

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

Kidney function impairment

Dose adjustment is not required for patients with renal impairment.

Hepatic dysfunction

Quetiapine is extensively metabolized in the liver. As a consequence, caution should be exercised when using Quetiax ® SR in patients with hepatic impairment, especially at the beginning of therapy. It is recommended that therapy with Quentiax® SR be started with a dose of 50 mg/day and increased daily by 50 mg until an effective dose is achieved.

children and adolescents (ages 10 to 17)

Quentiax® SR is not indicated for use in children and adolescents under 18 years of age 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 have not been studied with long-term use (more than 26 weeks) of quetiapine.

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/suicidal thoughts or clinical deterioration

Depression 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 based on common clinical experience.

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 aged ≥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 in therapy for patients with a depressive episode should also be taken when treating patients with other psychiatric disorders.

The potential risk of suicide-related events should be considered when abruptly discontinuing quetiapine therapy.

Patients with a history of suicidal events, as well as patients clearly expressing suicidal thoughts before starting therapy, are at increased risk of suicidal intentions and suicide attempts and should be closely monitored during treatment.

In patients with mania in bipolar disorder, 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 aged ≥25 years, 1.0% (2/193) for quetiapine and 0% (0/90) for placebo in patients under 18 years.

In patients with schizophrenia, the risk of suicidal events was 1.4% (3/212) 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 aged ≥25 years, and 1.4% (2/147) for quetiapine and 1.3% (1/75) for placebo in patients aged

Synopsis

Tablets 150 mg

Circular biconvex orange-pink film-coated tablets.

Tablets 200 mg

Oval biconvex brown-yellow film-coated tablets.

Tablets 300 mg

Capsule-shaped biconvex pills, film-coated in light yellow.

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 ® SR in patients under 18 years is not indicated.

Overdose

Symptoms

A fatal outcome was reported when a patient participating in a clinical trial took 13.6 g of quetiapine, as well as a fatal outcome after taking 6 g of quetiapine in a post-registration study of the drug. At the same time, there is a case of quetiapine administered in dose higher than 30 g without lethal outcome.

There are reports of very rare cases of quetiapine overdose leading to QTc interval prolongation, death or coma.

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

The symptoms noted in overdose were mainly a consequence of an increase in the known pharmacological effects of quetiapine, such as drowsiness and sedation, tachycardia, decreased blood pressure, and anticholinergic effects. There have also been reports of single cases of quetiapine overdose resulting in rhabdomyolysis, respiratory depression, urinary retention, confusion, delirium, and agitation. Overdose with prolonged-release quetiapine causes delayed maximum sedation and peak heart rate and a longer recovery time compared to overdose with rapid-release quetiapine.

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. It is recommended to carry out measures aimed at maintaining respiratory function and cardiovascular system, ensuring adequate oxygenation and ventilation.

We have published reports on resolution of severe adverse effects on the central nervous system (CNS), including coma and delirium, after intravenous administration of physostigmine (in dose of 1-2 mg) under continuous control of electrocardiogram (ECG). 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 patient is unconscious) and administration of activated charcoal and laxatives may assist in the excretion of unabsorbed quetiapine, however the effectiveness of these measures has not been studied.

Continuous 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, Quentiax® SR should be used during pregnancy only 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 presents a 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 period

The excretion of quetiapine with breast milk has been reported, but the extent of excretion has not been determined. Women should be advised to avoid breastfeeding while taking quetiapine.

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