Instructions for use of Kventiax film-coated tablets 25 mg No. 30
Composition
active ingredient: quetiapine;
1 film-coated tablet contains 25 mg or 100 mg, or 200 mg, or 300 mg of quetiapine (as quetiapine fumarate);
excipients: lactose monohydrate, calcium hydrogen phosphate dihydrate, microcrystalline cellulose, magnesium stearate, povidone, sodium starch glycolate (type A), hypromellose, titanium dioxide (E 171), macrogol 4000, yellow iron oxide (E 172) - contained in 25 mg and 100 mg tablets, red iron oxide (E 172) - contained in 25 mg tablets.
Dosage form
Film-coated tablets.
Main physicochemical properties:
· 25 mg film-coated tablets: round, pale red, film-coated tablets with a beveled edge;
· film-coated tablets, 100 mg: round, yellow-brown, film-coated tablets;
· film-coated tablets, 200 mg: round, white, film-coated tablets;
· 300 mg film-coated tablets: white, capsule-shaped, film-coated tablets.
Pharmacotherapeutic group
Antipsychotics. Quetiapine.
ATX code N05A H04.
Pharmacological properties
Pharmacodynamics.
Quetiapine is a dibenzothiazepine derivative with neuroleptic activity. Quetiapine and its active metabolite N-desalkylquetiapine interact with a wide range of neurotransmitter receptors. It remains unclear what contribution the drug makes to its pharmacological effects.
N-dealkylated metabolite.
Quetiapine exhibits affinity for the brain serotonin receptors 5HT2 and 5HT1A (in vitro Ki of 288 and 557 nM, respectively) and dopamine receptors D1 and D2 (in vitro Ki of 558 and 531 nM, respectively). This combination of receptor antagonism with relative selectivity for 5HT2 over D2 receptors is thought to underlie the clinical antipsychotic properties of the drug, as well as the relatively low incidence of extrapyramidal symptoms. Quetiapine also exhibits high affinity for histamine H1 receptors (in vitro Ki of 10 nM) and alpha 1 adrenergic receptors (in vitro Ki of 13 nM) with a lower affinity for alpha 2 adrenergic receptors (in vitro Ki of 782 nM). Quetiapine does not bind to cholinergic muscarinic and benzodiazepine receptors.
N-desalkylquetiapine, similar to quetiapine, exhibits affinity for brain serotonin receptors 5HT2 and dopamine receptors D1 and D2.
In addition, like quetiapine, N-desalkylquetiapine exhibits high affinity for serotonin 5HT1 receptors and histaminergic and alpha 1 adrenergic receptors, with a lower affinity for alpha 2 adrenergic receptors.
Pharmacokinetics.
The pharmacokinetics of quetiapine and N-desalkyl quetiapine are linear over the clinically relevant dose range. Quetiapine kinetics do not differ between males and females, smokers and non-smokers.
Absorption. Quetiapine is well absorbed from the gastrointestinal tract after oral administration. The bioavailability of quetiapine is not significantly affected by food, with Cmax and AUC values increasing by 25% and 15%, respectively. Peak plasma concentrations are reached 2 hours after oral administration. The molar concentration of the active metabolite N-desalkyl quetiapine at steady state is 35% of that of quetiapine.
Distribution: The volume of distribution of quetiapine is 10 ± 4 l/kg, and plasma protein binding is 83%.
Elimination and metabolism: The elimination half-life of quetiapine is approximately 6–7 hours after multiple dosing at clinically recommended doses. This is consistent with the
The half-life of N-desalkyl quetiapine is approximately 12 hours. The average molar fraction of free quetiapine and its active metabolite excreted in the urine is less than 5%.
When studying the drug with radioactive isotopes, it was shown that approximately 73% is excreted in the urine and 21% in the feces within one week.
Quetiapine is extensively metabolized in the liver, with the proportion of parent compound in urine and feces one week after administration of labeled quetiapine being less than 5% of the dose. Given the extensive metabolism of quetiapine in the liver, higher plasma concentrations are expected in subjects with hepatic impairment, and dose adjustment may be necessary.
The main metabolic reactions of quetiapine are oxidation of the alkyl side chain, hydroxylation of the dibenzothiazepine ring, sulfoxylation and conjugation (phase 2). The main metabolites of quetiapine in human plasma are oxidation and sulfoxidation products, none of which has pharmacological activity.
The main cytochrome P450 enzyme responsible for the metabolism of quetiapine is P450 3A4. The formation of the N-desalkyl derivative and the elimination of quetiapine occur primarily under the action of this enzyme.
In vitro studies have shown that quetiapine and some of its metabolites (including N-desalkyl-quetiapine) are weak inhibitors of cytochrome P450 enzymes 1A2, 2C9, 2C19, 2D6 and 3A4. However, such inhibition in vitro is only observed at concentrations 5-50 times higher than those in humans at doses of 300-800 mg/day.
Indication
- Treatment of schizophrenia.
- Treatment of bipolar disorder, including:
· treatment of moderate and severe manic episodes in bipolar disorder;
· treatment of severe depressive episodes in bipolar disorder;
· prevention of relapse in patients with bipolar disorder, in patients with manic or depressive episodes in whom treatment with quetiapine is effective.
Contraindication
Hypersensitivity to the active substance or to any component of the drug.
Concomitant use of cytochrome P450 3A4 inhibitors, such as HIV protease inhibitors, azole antifungals, erythromycin, clarithromycin, and nefazodone, is contraindicated.
Interaction with other medicinal products and other types of interactions
Given that quetiapine primarily acts on the central nervous system, Quetiapine® should be used with caution in combination with other drugs with similar effects and with alcohol.
It should be used with caution in patients receiving concomitant medications with anticholinergic (muscarinic) effects (see section "Special warnings and precautions for use").
Cytochrome P450 (CYP) 3A4 is the enzyme primarily responsible for the metabolism of quetiapine. In an interaction study in healthy volunteers, co-administration of quetiapine (25 mg) with ketoconazole (a CYP 3A4 inhibitor) resulted in a 5- to 8-fold increase in quetiapine AUC. Therefore, co-administration of quetiapine with CYP 3A4 inhibitors is contraindicated. It is also not recommended to consume grapefruit juice during treatment with quetiapine.
In a multiple-dose pharmacokinetic study of quetiapine administered before and during treatment with carbamazepine (a hepatic enzyme inducer), concomitant administration of carbamazepine significantly increased 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 affect the efficacy of Quetiapine therapy.
Concomitant use of quetiapine and phenytoin (another microsomal enzyme inducer) increased quetiapine clearance by approximately 450%. Initiation of treatment with Quetiapine in patients receiving a hepatic enzyme inducer should only be considered if the physician considers that the benefits of Quetiapine outweigh the risks of discontinuation of the hepatic enzyme inducer. It is important that any changes in the dose of the inducer are gradual. If necessary, a non-inducer (e.g. sodium valproate) should be substituted (see section 4.4).
The pharmacokinetics of quetiapine are not significantly altered by concomitant use of antidepressants such as imipramine (a known CYP 2D6 inhibitor) or fluoxetine (a known CYP 3A4 and CYP 2D6 inhibitor).
Concomitant use of antipsychotics such as risperidone or haloperidol did not significantly alter the pharmacokinetics of quetiapine. Concomitant use of quetiapine and thioridazine increased quetiapine clearance by approximately 70%.
The pharmacokinetics of quetiapine were not altered when co-administered with cimetidine.
The pharmacokinetics of lithium were not altered when co-administered with quetiapine.
In a 6-week randomized trial comparing the combination of lithium with Kventiax® and placebo and Kventiax® in adult patients with acute mania, an increased incidence of extrapyramidal symptoms (especially tremor), somnolence, and weight gain was observed in the lithium-added group compared to the placebo-added group (see section 5.1).
There were no clinically significant changes in the pharmacokinetics of sodium valproate and quetiapine when co-administered. In a retrospective study of children and adolescents receiving sodium valproate, quetiapine, or a combination of these drugs, an increase in the incidence of leukopenia and neutropenia was observed in the group receiving both drugs compared to the groups receiving these drugs separately.
Interaction studies with cardiovascular drugs have not been conducted.
Caution should be exercised when administering quetiapine concomitantly with drugs that disrupt electrolyte balance or prolong the QT interval.
Cases of false-positive enzyme immunoassay results for methadone and tricyclic antidepressants have been reported in patients taking quetiapine. It is recommended that equivocal screening immunoassay results be verified by an appropriate chromatographic method.
Application features
The long-term efficacy and safety of concomitant therapy in patients with TDR have not been evaluated, but the long-term efficacy and safety of monotherapy with the drug in adult patients have been studied.
Children
Quetiapine is not recommended for use in children due to the lack of data to support its use in this age group. Clinical trials of quetiapine have shown that, in addition to the known safety profile established in adults, the frequency of some adverse events is higher in children than in adults (increased appetite, increased serum prolactin levels, vomiting, rhinitis and syncope), or may have different consequences for children and adolescents (extrapyramidal symptoms and irritability), and one event was identified that was not previously observed in studies involving adult patients (increased blood pressure). In addition, changes in thyroid function tests have been observed in children and adolescents.
The delayed effects of Quetiapine® treatment on growth and sexual maturation have not been studied beyond 26 weeks. Long-term effects on cognitive and behavioral development are unknown.
In placebo-controlled clinical trials of Quetiapine in children and adolescents, quetiapine treatment was associated with an increased incidence of extrapyramidal symptoms (EPS) compared to placebo in patients treated for schizophrenia, bipolar mania and depression (see section 4.8).
Suicide/suicidal thoughts or clinical worsening
Depression in bipolar disorder is associated with an increased risk of suicidal ideation, self-harm and suicide (suicide-related events). This risk persists until significant remission is achieved. As improvement may not be apparent during the first few weeks of treatment or longer, patients should be closely monitored until such improvement occurs. It is general clinical experience that the risk of suicide may be increased in the early stages of improvement.
In addition, the potential risk of suicide-related events following abrupt discontinuation of quetiapine treatment should be considered.
Other psychiatric conditions for which Kventiax® should be prescribed may also be associated with an increased risk of suicide-related events. In addition, these conditions may occur concurrently with depressive episodes.
When treating patients with other psychiatric disorders, the same precautions should be taken as when treating patients with severe depressive episodes.
Patients with a history of suicide-related events or who demonstrate a significant level of suicidal ideation prior to initiation of therapy are at greater risk of suicidal thoughts or suicide attempts and should receive careful monitoring during treatment. A meta-analysis of placebo-controlled clinical trials of antidepressants in adult patients with psychiatric disorders has shown an increased risk of suicidal behavior in patients under 25 years of age.
Close monitoring of patients, particularly those at high risk, should accompany drug therapy, especially 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 unusual changes in behavior and to seek medical advice immediately if symptoms develop.
In short-term placebo-controlled trials in patients with major depressive episodes in bipolar disorder, an increased risk of suicide-related events was observed in young patients (<25 years of age) treated with quetiapine compared to those treated with placebo (3.0% vs. 0%, respectively). In clinical trials in patients with MDD, the incidence of suicide-related events in young patients (<25 years of age) was 2.1% (3/144) in the quetiapine group and 1.3% (1/75) in the placebo group. A population-based retrospective study of the use of quetiapine in the treatment of patients with major depressive disorder (MDD) showed an increased risk of self-harm and suicide in patients aged 25 to 64 years without a history of self-harm when quetiapine was used concomitantly with other antidepressants.
Drowsiness and dizziness
Quetiapine treatment has been associated with somnolence and related symptoms such as sedation (see section 4.8). In clinical trials in patients with bipolar depression, these symptoms typically occurred within the first 3 days of treatment and were mostly mild to moderate in intensity. Patients with bipolar depression and patients with depressive episodes in MDD who develop somnolence may require observation for 2 weeks after onset of somnolence or until symptoms resolve or treatment is discontinued.
Orthostatic hypotension
Quetiapine treatment has been associated with orthostatic hypotension and associated dizziness (see section 4.8), which, like somnolence, usually occurs during the dose titration period. These events may contribute to an increased incidence of accidental injury (falls), particularly in the elderly. Therefore, patients should be advised to exercise caution until they are familiar with the possible effects of the medicinal product.
Quetiapine should be used with caution in patients with cardiovascular or cerebrovascular disease or other conditions that may predispose to hypotension. Quetiapine may cause orthostatic hypotension, especially at the beginning of dose titration, and in such cases, a dose reduction or longer titration is necessary.
Sleep apnea syndrome
Sleep apnea syndrome has been reported in patients taking quetiapine. Quetiapine should be used with caution in patients taking concomitant central nervous system depressants and in patients with a history of, or at risk for, sleep apnea. This includes patients who are overweight/obese or male.
Convulsions
In controlled clinical trials, there was no difference in the incidence of seizures between patients taking quetiapine and those taking placebo. As with other antipsychotics, caution is advised when prescribing quetiapine to patients with a history of seizures (see section 4.8).
Extrapyramidal symptoms
In placebo-controlled trials, quetiapine was associated with an increased incidence of extrapyramidal symptoms (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, characterised by a subjectively unpleasant or distressing restlessness and need to move, often accompanied by an inability to sit or stand still. These events are more likely to occur during the first few weeks of treatment. Increasing the dose in patients who develop these symptoms may be harmful.
Tardive dyskinesia
If symptoms of tardive dyskinesia appear, consideration should be given to reducing the dose or discontinuing Kventiax®. Symptoms of tardive dyskinesia may worsen and even recur after discontinuation of therapy (see section 4.8).
Neuroleptic malignant syndrome
Neuroleptic malignant syndrome may be associated with treatment with antipsychotics, including quetiapine. Clinical manifestations include hyperthermia, altered mental status, muscle rigidity, autonomic instability, and elevated creatine phosphokinase levels. In such cases, Quetiapine should be discontinued and appropriate treatment initiated.
Severe neutropenia and agranulocytosis
Severe neutropenia (neutrophil count ≥9/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 have been fatal in the post-marketing setting. Possible risk factors for neutropenia include pre-existing low white blood cell counts and a history of drug-induced neutropenia. Agranulocytosis has been reported in patients without pre-existing risk factors. The possibility of neutropenia should be considered in patients with infection, particularly in the absence of obvious predisposing factors, and in patients with unexplained fever, and appropriate clinical management should be undertaken.
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 SR. These patients should have their white blood cell count and absolute neutrophil count (ANC) measured promptly, especially in the absence of predisposing factors.
It is recommended to discontinue quetiapine treatment when the blood neutrophil count reaches 9/L. Patients should be monitored for signs of infection and changes in neutrophil count (until the count exceeds 1.5x109/L (see section 5.1).
Anticholinergic (muscarinic) effects
Norquetiapine, the active metabolite of quetiapine, has moderate to high affinity for several subtypes of muscarinic receptors. This contributes to the occurrence of adverse reactions reflecting anticholinergic effects when quetiapine is used concomitantly at recommended doses and other drugs with anticholinergic effects in case of overdose. Quetiapine should be used with caution in patients receiving drugs with anticholinergic (muscarinic) effects.
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 (see sections 5.1, 5.2, 5.3, and 4.8).
Interactions
Concomitant use of quetiapine with a potent hepatic enzyme inducer such as carbamazepine or phenytoin significantly reduces quetiapine plasma concentrations, which may compromise the efficacy of quetiapine therapy. Treatment with Quetiapine® in patients receiving a hepatic enzyme inducer should only be initiated if the physician considers that the benefits of Quetiapine® outweigh the risks of withdrawing the hepatic enzyme inducer. It is important that any changes in the use of the inducer are gradual. If necessary, it should be replaced by a non-inducer (e.g. sodium valproate).
Effect on body weight
Weight gain has been reported in patients treated with quetiapine and should be monitored and managed as clinically appropriate in accordance with antipsychotic drug guidelines (see sections 5.1 and 4.8).
Hyperglycemia
Hyperglycaemia or exacerbation of diabetes has occasionally been associated with ketoacidosis or coma, which have been reported rarely, including a few fatal cases (see section 4.8). In a few cases, patients have been reported to have increased body weight, which may be a risk factor. Appropriate clinical monitoring is recommended 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 diabetes mellitus should be monitored regularly for worsening of glucose control. Weight should be monitored regularly.
Lipids
Increases in triglycerides, low-density lipoprotein (LDL) and total cholesterol and decreases in high-density lipoprotein (HDL) cholesterol have been observed in clinical trials with quetiapine (see section 4.8). If lipid changes occur, appropriate treatment should be administered.
Metabolic risk
Given the changes in body weight, blood glucose (see hyperglycemia) and lipids observed in clinical trials, the patient's metabolic parameters should be assessed at the start of treatment and changes in these parameters should be monitored regularly during treatment. Deterioration in these parameters should be corrected as clinically appropriate (see section "Adverse Reactions").
QT prolongation
In clinical trials and when used as directed, quetiapine did not consistently increase absolute QT intervals. In the post-marketing setting, QT prolongation has been observed with quetiapine at therapeutic doses (see section 4.8) and in overdose (see section 4.8). As with other antipsychotics, caution should be exercised when prescribing quetiapine to patients with cardiovascular disease or a family history of QT prolongation. Caution should also be exercised when prescribing quetiapine with other drugs known to prolong the QT interval, or when used concomitantly 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 types of interactions").
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 with quetiapine.
Severe cutaneous adverse reactions are accompanied by one or more of the following symptoms: widespread skin rash, which may be pruritic or pustular, exfoliative dermatitis, fever, lymphadenopathy and possible eosinophilia or neutrophilia. The majority of these reactions occurred within 4 weeks of starting quetiapine treatment, some DRESS reactions occurred within 6 weeks of starting quetiapine therapy. If signs and symptoms suggestive of these severe skin reactions appear, quetiapine should be discontinued immediately and alternative treatments considered.
Discontinuation of the drug
Acute withdrawal symptoms such as insomnia, nausea, headache, diarrhoea, vomiting, dizziness and irritability have been reported following abrupt discontinuation of quetiapine. Therefore, gradual discontinuation over a period of at least one to two weeks is recommended (see section 4.8).
Elderly patients with dementia-related psychosis
In randomized placebo-controlled trials in patients with dementia, an approximately 3-fold increase in the risk of cardiovascular adverse events has been observed with some atypical antipsychotics. The mechanism of this 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 studies in a single patient group (n=710; mean age 83 years; range 56–99 years), the mortality rate among patients treated with quetiapine was 5.5% versus 3.2% in the placebo group. The mortality rate in the studies was from a variety of causes that would be expected for this patient group.
Elderly patients with Parkinson's disease (PD)/parkinsonism
A population-based retrospective study in the treatment of patients with PD showed an increased risk of death with quetiapine in patients > 65 years of age. This finding was not confirmed when data from patients with Parkinson's disease were excluded from the analysis. Caution should be exercised when prescribing quetiapine to elderly patients with PD.
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 fatalities, in patients at increased risk of intestinal obstruction, including those receiving concomitant medications that reduce intestinal motility and/or medications that may not have been reported to cause constipation. Patients with intestinal obstruction/volvulus should be treated with close monitoring and prompt medical attention.
Venous thromboembolism
Cases of venous thromboembolism (VTE) have been reported with the use of neuroleptics. Since patients taking neuroleptics often have acquired risk factors for VTE, all possible risk factors for VTE should be identified before and during treatment with quetiapine and preventive measures should be taken.
Pancreatitis
Cases of pancreatitis have been reported in clinical trials and post-marketing experience, but a causal relationship has not been established. In post-marketing reports, many patients had risk factors for pancreatitis such as increased triglyceride levels (see section 4.4: Lipids), gallstones, and alcohol consumption.
Cardiomyopathy and myocarditis
Cardiomyopathy and myocarditis have been reported in clinical trials and post-marketing experience, but a causal relationship to quetiapine has not been established. The use of quetiapine in patients with suspected cardiomyopathy or myocarditis should be re-evaluated.
Additional information
Data on the use of quetiapine in combination with divalproex or lithium in moderate to severe manic episodes are limited, but the combination therapy was well tolerated (see sections 4.8 and 5.1). An additive effect was observed by the third week of treatment.
Irrational use and abuse
Cases of irrational use and abuse of the drug have been recorded. Quetiapine should be prescribed with caution to patients with a history of alcohol or drug abuse.
Lactose
Quetiapine 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
Pregnancy
First trimester
A moderate amount of published data on exposed pregnancies (i.e., 300 to 1000 pregnancy outcomes), including isolated reports and some observational studies, do not indicate an increased risk of malformations due to quetiapine treatment. However, based on all the available data, no definite conclusion can be drawn. Animal studies have shown reproductive toxicity. Therefore, quetiapine should be used during pregnancy only if the potential benefit justifies the potential risk.
The use of antipsychotics (including quetiapine) during the third trimester of pregnancy can lead to adverse reactions in the newborn, including extrapyramidal disorders and/or withdrawal syndrome, which may vary in severity and duration after delivery. There have been reports of agitation, hypertension, hypotension, tremor, somnolence, respiratory distress syndrome or feeding disorders. Therefore, newborns whose mothers have been treated with quetiapine during the third trimester of pregnancy should be closely observed.
Breastfeeding period
Based on very limited data from published reports on the excretion of quetiapine in human milk, the excretion of quetiapine at therapeutic doses is uncertain. 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.
Fertility
The effect of quetiapine on human fertility has not been evaluated. Effects related to elevated prolactin levels have been reported in rats, although these are not directly relevant to humans.
Ability to influence reaction speed when driving vehicles or other mechanisms
Given that 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
Different dosage regimens are prescribed for each indication. It is important to ensure that the dosage prescribed to the patient is appropriate for their condition.
Treatment of schizophrenia.
Kventiax® should be administered twice daily. The daily dose for the first four days is: 50 mg (day one), 100 mg (day two), 200 mg (day three) and 300 mg (day four). After 4 days of treatment, the dose should be titrated to a usually effective dose of 300–450 mg/day. Depending on clinical response and tolerability, the dose may be adjusted within the range of 150 mg to 750 mg/day.
Treatment of moderate to severe manic episodes in bipolar disorder
Kventiax® should be administered twice daily. The daily dose for the first four days of treatment is: Day 1 – 100 mg, Day 2 – 200 mg, Day 3 – 300 mg, Day 4 – 400 mg. The dose should then be increased (but not more than 200 mg daily) to 800 mg/day by the 6th day of treatment.
Depending on clinical efficacy and tolerability, the dose may be adjusted within the range of 200 mg to 800 mg/day. The usual effective dose is in the range of 400–800 mg/day.
Treatment of depressive episodes in bipolar disorder
Kventiax® should be administered once at bedtime. The total daily dose for the first four days of treatment is: 50 mg (day one), 100 mg (day two), 200 mg (day three) and 300 mg (day four). The recommended daily dose is 300 mg. In clinical trials, no additional benefit was observed in the 600 mg group compared to the 300 mg group (see section 5.1). A dose of 600 mg may be effective in individual patients. Doses above 300 mg should be prescribed by a physician experienced in the treatment of bipolar disorder. Clinical studies suggest that in individual patients, if the drug is poorly tolerated, a dose reduction to the minimum of 200 mg should be considered.
Prevention of relapse in bipolar disorder
For the prevention of subsequent manic, mixed, or depressive episodes in bipolar disorder, patients who have responded to the use of Quetiapine SR in the emergency treatment of bipolar disorder should continue treatment with Quetiapine at the same prescribed dose at bedtime. The dose of Quetiapine may 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 be used for maintenance therapy.
Elderly patients
As with other antipsychotics and antidepressants, Kventiax® 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 the drug K may be required.
