Instructions Quetiapine tablets 200 mg No. 30
Composition
active ingredient: quetiapine;
25 mg tablets: 1 film-coated tablet contains 28.78 mg of quetiapine fumarate, equivalent to 25 mg of quetiapine;
100 mg tablets: 1 film-coated tablet contains 115.13 mg of quetiapine fumarate, equivalent to 100 mg of quetiapine;
200 mg tablets: 1 film-coated tablet contains 230.27 mg of quetiapine fumarate, equivalent to 200 mg of quetiapine;
excipients:
hypromellose, calcium hydrogen phosphate dihydrate, lactose monohydrate, corn starch, sodium starch glycolate (type A), magnesium stearate, microcrystalline cellulose, talc, colloidal anhydrous silicon dioxide;
film coating:
25 mg tablets: iron oxide red (E 172), iron oxide yellow (E 172), HPMC 2910/hypromellose 5sR (E 464), titanium dioxide (E 171), macrogol/PEG 400, sunset yellow FCF aluminum lake (E 110);
100 mg tablets: iron oxide yellow (E 172), HPMC 2910/hypromellose 5sR (E 464), titanium dioxide (E 171), macrogol/PEG 400;
200 mg tablets: hydroxypropylcellulose (E 463), HPMC 2910/hypromellose 6sR (E 464), titanium dioxide (E 171), talc.
Dosage form
Film-coated tablets.
Main physicochemical properties:
25 mg tablets: round, biconvex, peach-colored film-coated tablets;
100 mg tablets: round, biconvex, yellow film-coated tablets, with a score on one side;
200 mg tablets: round, biconvex, white film-coated tablets, with a score on one side.
Pharmacotherapeutic group
Drugs acting on the nervous system. Antipsychotics. Quetiapine.
ATX code N05A H04.
Pharmacological properties
Pharmacodynamics.
Quetiapine is an atypical antipsychotic drug. Quetiapine and its active metabolite norquetiapine interact with different types of neurotransmitter receptors. Quetiapine and norquetiapine have high selectivity for serotonin receptors (5HT2) and dopamine D1- and D2- receptors in the brain. It is this combination of receptor antagonism with greater selectivity for 5HT2 receptors over D2 receptors that is thought to contribute to the clinical antipsychotic effects and low propensity for extrapyramidal side effects of quetiapine compared to typical antipsychotics. Quetiapine and norquetiapine also have high affinity for histaminergic and α1-adrenergic receptors, but lower affinity for α2-adrenergic receptors and serotonin 5HT1A receptors.
Quetiapine has no affinity for cholinergic muscarinic receptors or benzodiazepine receptors, whereas norquetiapine has moderate to high affinity for several muscarinic receptor subtypes, which may explain its anticholinergic (muscarinic) effects.
Norquetiapine's inhibition of the norepinephrine transporter (NET) as well as partial agonist action at 5HT1A receptors may contribute to the therapeutic efficacy of quetiapine as an antidepressant.
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-Darnitsa is well absorbed and rapidly metabolized after oral administration. Co-administration with food has no significant effect on the bioavailability of the drug. 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 over the approved concentration range.
Distribution.
Approximately 83% of quetiapine is bound to plasma proteins.
Metabolism.
Quetiapine is extensively metabolised in the liver, and radiolabelled quetiapine has been shown to be less than 5% metabolised and excreted unchanged in the urine or faeces. In vitro studies have shown that CYP3A4 is the major enzyme responsible for the cytochrome P450-mediated metabolism of quetiapine. Norquetiapine is predominantly formed and eliminated by CYP3A4. Quetiapine and some of its metabolites (including norquetiapine) have weak in vitro inhibition of cytochrome P450 isoenzymes 1A2, 2C9, 2C19, 2D6 and 3A4. In vitro inhibition of CYP isoenzymes occurred only at concentrations 5–50 times higher than those achieved at human doses in the range of 300 to 800 mg/day.
Based on these in vitro results, it is unlikely that co-administration of quetiapine with other active substances will result in clinically significant inhibition of the cytochrome P450-mediated metabolism of the other active substances.
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.
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 urine in humans.
Special populations.
Sex.
Elderly people.
The average clearance of quetiapine in elderly subjects is 30-50% lower than in subjects aged 18-65 years.
Patients with renal impairment.
In patients with significant renal impairment (creatinine clearance less than 30 ml/min/1.73 m2), the mean plasma clearance of quetiapine is reduced by approximately 25%, but individual clearance values remain within the range of healthy subjects.
Patients with impaired liver function.
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
Treatment of schizophrenia.
Treatment of bipolar disorder, including:
for the treatment of moderate to severe manic episodes in bipolar disorder;
for the treatment of major depressive episodes in bipolar disorder.
For the prevention of relapse in patients with bipolar disorder whose manic or depressive episodes have been treated with quetiapine.
Contraindication
Increased individual sensitivity to any of the components 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 the primary effects of quetiapine on the central nervous system (CNS), quetiapine should be used with caution in combination with other centrally acting drugs and alcohol.
Caution should be exercised when treating patients taking other drugs with anticholinergic (muscarinic) effects.
Cytochrome P450 (CYP) 3A4 is the enzyme primarily responsible for the cytochrome P450-mediated 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. Grapefruit juice is also not recommended during treatment with quetiapine.
In a multiple-dose pharmacokinetic study 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 mean of 13% of that seen with quetiapine alone, although some patients had a greater effect. This interaction may result in lower plasma concentrations, which may impact the efficacy of quetiapine therapy.
Concomitant use of quetiapine and phenytoin (an inducer of hepatic microsomal enzymes) results in an increase in quetiapine clearance by up to 450%. For patients taking a hepatic enzyme inducer, quetiapine therapy should only be initiated if the benefits of quetiapine outweigh the risks associated with discontinuation of the hepatic enzyme inducer. It is important to make any change from the inducer gradually and, if necessary, to 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 resulted in an increase in quetiapine clearance by approximately 70%.
The pharmacokinetics of quetiapine were not altered after co-administration with cimetidine.
The pharmacokinetics of lithium were not altered when co-administered with quetiapine.
The pharmacokinetics of sodium valproate and quetiapine are not altered by co-administration. It is known that in a retrospective study of children and adolescents receiving sodium valproate, quetiapine, or a combination of these drugs, an increase in the number of cases of leukopenia and neutropenia was observed in the combination treatment group compared to the monotherapy groups.
Formal interaction studies with the most common cardiovascular drugs have not been conducted. Caution should be exercised when quetiapine is used 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 is used for multiple indications, the safety profile of the drug should be carefully considered in light of the individual patient's diagnosis and the dose they are taking.
Children.
Quetiapine is not recommended for use in children and adolescents under 18 years of age due to the lack of data to support its use in this age group. Clinical trials of quetiapine have shown that, in addition to the known safety profile established in adults, the frequency of some adverse events is higher in children than in adults (increased appetite, increased serum prolactin levels, vomiting, rhinitis, syncope, or may have different consequences for children and adolescents (extrapyramidal symptoms and irritability), and an increase in blood pressure has been observed, which has not previously been observed in studies involving adult patients. In addition, changes in thyroid function tests have been observed in children and adolescents.
It should also be noted that the delayed effects of quetiapine treatment on growth and puberty have not been studied beyond 26 weeks. The long-term effects on cognitive and behavioral development are unknown.
In placebo-controlled clinical trials in paediatric patients, quetiapine treatment was associated with an increased incidence of extrapyramidal symptoms compared to placebo in patients treated for schizophrenia and bipolar mania (see section 4.8).
Suicide/suicidal thoughts or clinical worsening.
Depression is associated with an increased risk of suicidal thoughts, self-harm and suicide (suicidal events and manifestations). This risk persists until significant/credible remission occurs. As improvement may not be observed during the first few weeks or more of treatment, 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 recovery.
In addition, physicians should consider the potential risk of suicidal events and manifestations after abrupt discontinuation of quetiapine treatment due to the presence of known risk factors for the condition being treated.
Other psychiatric conditions for which quetiapine is prescribed may also be associated with an increased risk of suicidal events and manifestations. However, such conditions may occur concurrently with major depressive episodes. Therefore, the same precautions should be taken when treating patients with other psychiatric disorders as when treating patients with major depressive episodes.
Patients with a history of suicidal ideation or behavior, or those who demonstrate a significant level of suicidal ideation prior to initiation of therapy, are known to be 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 with antidepressants compared with placebo in patients under 25 years of age.
Drug therapy, especially at the beginning of treatment and during subsequent dose changes, should be accompanied by close monitoring, especially in high-risk individuals. Patients (and caregivers of patients) should be warned about the need to monitor for clinical worsening, suicidal behavior or thoughts, and unusual changes in behavior and to seek medical advice immediately if these symptoms appear.
In short-term placebo-controlled clinical trials in patients with major depressive episodes in bipolar disorder, an increased risk of suicidal events and manifestations was observed in young patients (under 25 years of age) treated with quetiapine compared to those treated with placebo (3.0% vs. 0%, respectively).
In clinical trials in patients with major depressive disorder (MDD), the incidence of suicidal events and manifestations in young patients (aged <25 years) was 2.1% (3/144) in the quetiapine group and 1.3% (1/75) in the placebo group. A population-based retrospective analysis of quetiapine in the treatment of patients with MDD found an increased risk of self-harm and suicide in patients aged 24 to 64 years without a history of self-harm when quetiapine was used with other antidepressants.
Metabolic risk.
Given the identified risk of worsening of the metabolic profile, including changes in body weight, glucose levels and blood lipids, observed during clinical studies, it is necessary to assess the patient's metabolic parameters at the beginning of treatment and monitor changes in these parameters regularly during the course of treatment. Deterioration of these parameters should be corrected as clinically appropriate.
Extrapyramidal symptoms.
The use of 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 phenomena are most likely to occur during the first few weeks of treatment. Increasing the dose in these patients may be harmful.
Tardive dyskinesia.
If signs and symptoms of tardive dyskinesia appear, consideration should be given to reducing the dose or discontinuing quetiapine. Symptoms of tardive dyskinesia may worsen or even reappear after treatment is discontinued (see section 4.8).
Drowsiness and dizziness.
Quetiapine treatment has been associated with somnolence and related symptoms, such as sedation. In clinical trials in patients with bipolar depression and MDD, such symptoms usually occurred within the first three days of treatment and were mostly mild to moderate in intensity. Patients who experience significant somnolence may require more frequent monitoring for at least 2 weeks after onset of somnolence or until symptoms resolve or treatment discontinuation is considered.
Orthostatic hypotension.
Quetiapine treatment has been associated with orthostatic hypotension and associated dizziness, which, like somnolence, usually occur during the initial dose titration period. These events may contribute to an increased incidence of accidental injury (falls), particularly in elderly patients. Patients should be advised to use the drug with caution until they are aware of the possible effects or interactions of the drug.
Quetiapine should be used with caution in patients with established cardiovascular disease, cerebrovascular disease, or other conditions that may predispose to hypotension. Dose reduction or longer titration should be considered if orthostatic hypotension occurs, especially in patients with underlying cardiovascular disease.
Sleep apnea syndrome.
Sleep apnea syndrome has been reported in patients taking quetiapine, therefore quetiapine should be used with caution in patients receiving concomitant CNS depressants and in patients with a history of or at risk for sleep apnea, such as overweight/obese patients or male patients.
Convulsive attacks.
There was no difference in the incidence of seizures between patients taking quetiapine and those taking placebo. There are no data on cases of seizures in patients with epilepsy. As with other antipsychotics, caution is recommended when treating patients with a history of seizures (see section "Adverse reactions").
Neuroleptic malignant syndrome.
Neuroleptic malignant syndrome has been associated with treatment with antipsychotics, including quetiapine. Clinical manifestations include hyperthermia, altered mental status, muscle rigidity, autonomic instability, and elevated creatine phosphokinase. In such cases, quetiapine should be discontinued and appropriate medical treatment initiated.
Severe neutropenia and agranulocytosis.
Severe neutropenia (neutrophil count < 0.5 × 109/L) has been observed in clinical trials with quetiapine. The majority of cases of severe neutropenia occurred within two months of initiating quetiapine treatment. No clear dose relationship was established. Some cases were fatal in the post-marketing setting. Risk factors include a history of low white blood cell counts and a history of drug-induced neutropenia. However, some cases have occurred in patients without pre-existing risk factors. If the neutrophil count is < 1 × 109/L, quetiapine should be discontinued. Patients should be monitored for signs of infection and neutrophil counts should be monitored until the count exceeds 1.5 × 109/L.
The possibility of neutropenia should be considered in patients with an underlying infection and fever, especially in the absence of obvious underlying disease factors, including fever of unknown origin, and appropriate clinical measures should be taken.
Patients should be advised to report promptly any signs/symptoms suggestive of agranulocytosis or infection (such as fever, malaise, lethargy, or sore throat) at any time during treatment with quetiapine. These patients should have a WBC count and absolute neutrophil count (ANC) performed promptly, especially in the absence of predisposing factors.
Anticholinergic (muscarinic) syndrome.
Quetiapine should be used with caution in patients with a current diagnosis or history of urinary retention, clinically significant prostatic hypertrophy, intestinal obstruction or related conditions, increased intraocular pressure, or angle-closure glaucoma.
Concomitant use of liver enzyme inducers.
See also section “Interaction with other medicinal products and other types of interactions”.
Concomitant use of quetiapine and a strong hepatic enzyme inducer such as carbamazepine or phenytoin significantly reduces quetiapine plasma concentrations, which may affect the efficacy of quetiapine therapy. In patients receiving a hepatic enzyme inducer, quetiapine treatment should only be initiated if, in the opinion of the physician, the benefits of quetiapine outweigh the risks of withdrawing the hepatic enzyme inducer. It is important to make any change from the inducer gradually and, if necessary, to a non-inducing agent (e.g. sodium valproate).
Weight gain.
Weight gain has been reported in patients treated with quetiapine and should be monitored and managed as clinically appropriate in accordance with antipsychotic drug guidelines.
Hyperglycemia.
Hyperglycemia and/or development or exacerbation of diabetes mellitus, sometimes associated with ketoacidosis or coma, have been reported rarely, including some fatal cases. In some cases, these events have occurred in patients with increased body weight, which may have been a contributing factor. Appropriate clinical monitoring is recommended in accordance with antipsychotic drug guidelines. Patients treated with any antipsychotic agent, including quetiapine, should be observed for signs and symptoms of hyperglycemia (such as polydipsia, polyuria, polyphagia, and weakness), and patients with diabetes mellitus or with risk factors for diabetes mellitus should have their blood glucose levels monitored regularly. Weight should be monitored regularly.
Lipids.
Increases in triglycerides, LDL-C, and total cholesterol, and decreases in HDL-C have been observed in clinical trials with quetiapine. Lipid changes should be adjusted as clinically appropriate.
Increased QT interval.
In clinical studies, the use of quetiapine according to the instructions was not accompanied by a persistent increase in the absolute value of the QT interval. In the post-marketing period, prolongation of the QT interval was observed when using quetiapine at therapeutic doses and in overdose. As with other antipsychotics, quetiapine should be prescribed with caution in patients with cardiovascular disease or a family history of QT prolongation. Caution should also be exercised when prescribing quetiapine with drugs that prolong the QT interval, with neuroleptics, especially in elderly patients, patients with congenital long QT syndrome, congestive heart failure, cardiac hypertrophy, hypokalemia or hypomagnesemia (see section "Interaction with other drugs and other interactions").
Cardiomyopathy and myocarditis.
Cardiomyopathy and myocarditis have been reported in clinical trials and during the post-marketing period (see section 4.8).
In patients with suspected cardiomyopathy or myocarditis, discontinuation of quetiapine treatment should be considered.
Severe skin adverse reactions.
Very rare cases of severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), acute generalised exanthematous pustulosis (AGEP), erythema multiforme and drug reaction with eosinophilia and systemic symptoms (DRESS), which can be life-threatening or fatal, have been reported in association with quetiapine treatment.
SCARs usually present as a combination of the following symptoms: extensive skin rash or exfoliative dermatitis, fever, lymphadenopathy and possible eosinophilia or neutrophilia. Most of these reactions have occurred within 4 weeks of initiating quetiapine therapy, some DRESS reactions within 6 weeks of initiating quetiapine therapy. If signs and symptoms suggestive of such severe skin reactions occur, quetiapine should be discontinued immediately and alternative treatment considered.
Treatment cancellation.
Abrupt discontinuation of quetiapine may cause withdrawal symptoms, including insomnia, nausea, headache, diarrhea, vomiting, dizziness, and irritability. Therefore, gradual discontinuation of the drug over a period of at least one to two weeks is recommended (see section 4.8).
Quetiapine is not approved for the treatment of patients with dementia-related psychosis. Some atypical antipsychotics have been associated with an approximately 3-fold increased risk of cerebrovascular adverse events. The mechanism of this increased risk is unknown. An increased risk cannot be excluded with other antipsychotics or in other patient populations. Quetiapine 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. In two 10-week placebo-controlled trials of quetiapine in the same patient population (n=710; mean age 83 years; range 56–99 years), the mortality rate among quetiapine-treated patients was 5.5% versus 3.2% in the placebo group. Mortality in the studies was due to a variety of causes, as expected for this patient population.
Elderly patients with Parkinson's disease.
A population-based retrospective study of quetiapine in the treatment of patients with ADHD showed an increased risk of death with quetiapine in patients >65 years of age. This association was absent when patients with parkinsonism were excluded from the analysis. Caution should be exercised when prescribing quetiapine to this group of patients.
Effect on the liver.
If jaundice occurs, quetiapine should be discontinued.
Dysphagia.
Cases of dysphagia have 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, including fatalities, have been reported with quetiapine in patients at increased risk of intestinal obstruction (including those receiving multiple medications that reduce intestinal motility, and those who are unable to report symptoms of constipation).
Patients with impaired peristalsis or intestinal obstruction should be closely monitored with the ability to provide emergency medical care.
Venous thromboembolism.
Cases of venous thromboembolism (VTE) have been reported with antipsychotic drugs. Since patients taking antipsychotics 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.
Pancreatitis.
Pancreatitis has been reported. Postmarketing reports have indicated that many, although not all, patients had factors known to be associated with pancreatitis, such as elevated triglyceride levels, gallstones, and alcohol use.
Additional information.
Data on the use of quetiapine in combination with divalproex sodium or lithium in acute manic episodes of moderate to severe severity are limited; however, this combination treatment was well tolerated. These data showed an additive effect at the third week of treatment.
Irrational use and abuse.
Cases of drug misuse and abuse have been reported. Quetiapine should be used with caution in patients with a history of alcohol or drug abuse.
Important information about excipients.
The medicine contains lactose, therefore patients with rare hereditary diseases such as galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
The medicine also contains the dye sunset yellow FCF (E 110), which may cause allergic reactions.
Use during pregnancy or breastfeeding
Pregnancy.
First trimester.
The limited amount of published data on pregnant women treated with quetiapine (300 to 1000 exposures), including isolated reports of individual reactions, does not indicate an increased risk of malformations after the use of quetiapine. However, based on all the available data, no definite conclusion can be drawn. Therefore, the drug should be prescribed during pregnancy only if the expected benefit justifies the potential risk.
Third trimester.
Neonates whose mothers have taken antipsychotics (including quetiapine) during the third trimester are at risk of adverse reactions, including extrapyramidal and/or withdrawal symptoms, which may vary in severity and duration following delivery. There have been reports of agitation, hypertension, hypotension, tremor, somnolence, respiratory distress, or feeding disorders. Therefore, neonates should be closely monitored.
Breastfeeding period.
There are limited published data that quetiapine is excreted in human milk, but this information is conflicting. 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.
The effect of quetiapine on human fertility has not been evaluated. Effects related to increased prolactin levels have been observed in rats, but these are not directly relevant to humans.
Ability to influence reaction speed when driving vehicles or other mechanisms
Given that quetiapine acts primarily on the central nervous system, the drug may adversely affect activities requiring concentration. Therefore, patients should be advised to avoid driving or operating machinery until individual sensitivity to this effect is determined.
Method of administration and doses
The medicine can be used regardless of food intake.
For the treatment of schizophrenia
Quetiapine-Darnitsa should be administered twice daily. The total daily dose for the first four days of treatment is 50 mg on the first day, 100 mg on the second day, 200 mg on the third day and 300 mg on the fourth day. Starting from the fourth day, the dose should be adjusted within the effective dose range of 300 mg/day to 450 mg/day. Depending on the clinical response and tolerability of the patient, the dose may be adjusted in the range of 150 mg/day to 750 mg/day.
For the treatment of moderate to severe manic episodes in bipolar disorder
Quetiapine-Darnitsa should be administered twice daily. The total daily dose for the first four days of treatment is 100 mg on the first day, 200 mg on the second day, 300 mg on the third day, and 400 mg on the fourth day. Dose adjustments to 800 mg/day by the sixth day should be made in increments of no more than 200 mg/day.
The dose of the drug can be adjusted within a dose range of 200 mg to 800 mg/day, depending on the clinical response and tolerability of each individual patient. The effective dose range is 400 mg to 800 mg/day.
For the treatment of major depressive episodes in bipolar disorder
Quetiapine-Darnitsa should be taken once daily 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. 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. According to clinical trials, 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 patients with bipolar disorder whose manic or depressive episodes have been treated with quetiapine
For the prevention of subsequent manic, mixed or depressive episodes in bipolar disorder, patients who have responded to quetiapine in the acute treatment of bipolar disorder should continue treatment with the drug at the same prescribed dose. The dose of Quetiapine-Darnitsa can be adjusted within a dose range of 300 mg to 800 mg/day, depending on the clinical response and tolerability of the individual patient. It is important that the lowest effective dose is used for maintenance therapy.
Elderly patients
As with other antipsychotics, Quetiapine should be used with caution in elderly patients, especially during the initial dose adjustment period. Slower titration of the drug may be required, and the daily therapeutic dose may be lower than that used in younger patients, depending on the clinical response and tolerability of the patient. The mean plasma clearance of quetiapine was 30-50% lower in elderly patients compared to younger patients.
