Instructions Quetixol XR film-coated tablets prolonged-release 300 mg No. 30
Composition
active ingredient: quetiapine fumarate;
1 prolonged-release film-coated tablet contains quetiapine fumarate equivalent to quetiapine 50 mg, 150 mg, 200 mg, 300 mg or 400 mg;
excipients: hypromellose, microcrystalline cellulose, sodium citrate anhydrous, magnesium stearate, titanium dioxide (E 171), polyethylene glycol 400, polysorbate 80;
for 50 mg and 300 mg tablets – yellow iron oxide (E 172), red iron oxide (E 172), black iron oxide (E 172);
for 200 mg tablets – iron oxide yellow (E 172), iron oxide red (E 172).
Dosage form
Film-coated tablets, prolonged-release.
Main physicochemical properties:
50 mg: oval-shaped tablets with a biconvex surface, film-coated, brown in color, embossed with “Q50” on one side;
150 mg: oval-shaped tablets with a biconvex surface, film-coated, white in color, embossed with “Q150” on one side;
200 mg: oval-shaped tablets with a biconvex surface, film-coated, yellow in color, embossed with “Q200” on one side;
300 mg: oval-shaped tablets with a biconvex surface, film-coated, light yellow in color, embossed with “Q300” on one side;
400 mg: oval-shaped tablets with a biconvex surface, film-coated, white in color, embossed with “Q400” on one side.
Pharmacotherapeutic group
Antipsychotics. ATX code N05A H04.
Pharmacological properties
Pharmacodynamics.
Mechanism of action.
Quetiapine is an atypical antipsychotic. Quetiapine and its active metabolite norquetiapine interact with different types of neurotransmitter receptors. Quetiapine and norquetiapine have high selectivity for serotonin (5-HT2) receptors and dopamine D1 and D2 receptors in the brain. It is this combination of receptor antagonism with greater selectivity for 5-HT2 receptors over D2 receptors that is thought to account for the clinical antipsychotic effects and low propensity for extrapyramidal side effects of quetiapine compared with typical antipsychotics. Quetiapine and norquetiapine also have high affinity for histaminergic and α1-adrenergic receptors, but lower affinity for α2-adrenergic receptors and serotonin 5-HT1A 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 (NET) inhibition, as well as partial agonist activity at 5HT1A receptors, may contribute to the therapeutic efficacy of Quetiapine XR as an antidepressant.
Pharmacodynamic effects.
Quetiapine is known to be active in tests of antipsychotic activity, such as conditioned avoidance. Quetiapine blocks the agonistic effects of dopamine, as assessed by behavioral or electrophysiological assessments, and increases the concentration of dopamine metabolites, a neurochemical expression of D2 receptor blockade.
It is known that in preclinical studies, during which the tendency to develop extrapyramidal symptoms was checked, quetiapine had an atypical activity profile and differed from standard antipsychotic drugs. Quetiapine did not lead to excessive sensitivity of dopamine D2 receptors after long-term use. Quetiapine, at doses effective for dopamine D2 receptor blockade, caused only mild catalepsy.
Quetiapine has been shown to be selective for the limbic system after chronic administration, as demonstrated by its ability to block depolarization in A10 mesolimbic neurons, but not in A9 nigrostriatal neurons, which contain dopamine.
Clinical safety
It is known that quetiapine treatment may cause a dose-dependent decrease in thyroid hormone levels.
Available data from placebo-controlled trials in elderly patients with dementia-related psychosis show that the incidence of cardiovascular adverse events per 100 patient-years in the quetiapine group was no higher than in patients receiving placebo.
Cataract
Data from a clinical trial evaluating the cataractogenic potential of quetiapine (200-800 mg/day) compared with risperidone (2-8 mg/day) in patients with schizophrenia or schizoaffective disorder showed that the percentage of patients with increased lens opacity was not higher in the group of patients taking quetiapine (4%) compared to those receiving risperidone (10%) when using the drug for at least 21 months.
Pharmacokinetics.
Absorption
The pharmacokinetics of quetiapine and norquetiapine are linear and dose proportional up to and including 800 mg once daily. When comparing the same total daily doses of Quetiapine XR once daily with Quetiapine immediate-release (quetiapine fumarate immediate-release) twice daily, the area under the concentration-time curve (AUC) was similar, but the maximum plasma concentration (Cmax) was 13% lower at steady state. When comparing Quetiapine XR to Quetiapine immediate-release, the AUC of the metabolite norquetiapine was 18% lower.
In a study investigating the effect of food on the bioavailability of quetiapine, high-fat meals were found to cause a statistically significant increase in Cmax and AUC of Quetiapine XR by approximately 50% and 20%, respectively. It cannot be excluded that the effect of a high-fat meal on the dosage form may be greater. A light meal has no significant effect on Cmax and AUC of quetiapine. Quetiapine XR is recommended to be taken once daily on an empty stomach.
Distribution
Approximately 83% of quetiapine is bound to plasma proteins.
Metabolism
Quetiapine is extensively metabolized in the liver. The use of radiolabeled quetiapine has shown that less than 5% of quetiapine is not metabolized and is excreted unchanged in the urine or feces.
Breeding
The elimination half-lives (t1/2) of quetiapine and norquetiapine are approximately 7 and 12 hours, respectively. Approximately 73% of the radioactivity is excreted in the urine and 21% in the faeces. Less than 5% of the total radioactivity of the average molar fraction of the dose of free quetiapine and the active metabolite norquetiapine is excreted in the urine in humans.
Special populations
Sex
The pharmacokinetics of quetiapine do not differ between women and men.
Elderly patients
The average clearance of quetiapine in elderly patients is 30-50% lower than in patients 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 liver dysfunction
In patients with liver damage (compensated alcoholic cirrhosis), the average plasma clearance of quetiapine is reduced by approximately 25%. Since quetiapine is extensively metabolized in the liver, plasma concentrations of quetiapine may be increased in patients with impaired liver function, and dose adjustment may be required in this group of patients (see section 4.2).
Indication
Quetiapine XR is indicated for the treatment of:
- schizophrenia, including prevention of relapse in patients with stable schizophrenia who received maintenance therapy with Quetiapine XR;
- 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, in patients with manic or depressive episodes in whom treatment with quetiapine is effective;
- as adjunctive therapy for major depressive episodes in patients with major depressive disorder (MDD) who have had a suboptimal response to antidepressant monotherapy; before initiating therapy, the physician should carefully review the safety profile of Quetiapine XR (see section 4.4).
Contraindication
- Hypersensitivity 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 (see section "Interaction with other medicinal products and other types of interactions").
Interaction with other medicinal products and other types of interactions
Given that quetiapine acts primarily on the central nervous system (CNS), it should be used with caution in combination with other drugs with similar effects and with alcohol.
Quetiapine should be used with caution with serotonergic drugs such as MAO inhibitors, selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs) or tricyclic antidepressants, as the risk of developing serotonin syndrome, a potentially life-threatening condition, is increased (see section 4.4).
The drug should be prescribed with caution to patients receiving other drugs that exhibit anticholinergic (muscarinic) effects (see section "Special warnings and precautions for use").
In a multiple-dose study to evaluate the pharmacokinetics of quetiapine administered before and during treatment with carbamazepine (a known hepatic enzyme inducer), concomitant use of carbamazepine significantly increased quetiapine clearance. 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 decreased plasma concentrations, and therefore, an increase in the dose of Quetiapine XR should be considered for each patient based on clinical response. Coadministration of quetiapine with phenytoin (another microsomal enzyme inducer) resulted in an increase in quetiapine clearance of up to 450%. For patients taking a hepatic enzyme inducer, quetiapine therapy should only be initiated if the physician considers that the benefits of quetiapine outweigh the risks associated with discontinuation of the hepatic enzyme inducer. It is important that any changes in the dose of the inducer should be gradual. The dose of quetiapine may be reduced when phenytoin, carbamazepine or other hepatic enzyme inducers are discontinued or when a non-inducing agent is substituted (e.g. sodium valproate) (see section 4.4).
The pharmacokinetics of quetiapine were not significantly altered after co-administration with the antidepressants imipramine (a known CYP 2D6 inhibitor) or fluoxetine (a known CYP 3A4 and CYP 2D6 inhibitor).
The pharmacokinetics of quetiapine are not significantly altered by co-administration with risperidone or haloperidol. Co-administration of quetiapine and thioridazine results 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. There is evidence that in a 6-week randomized trial comparing the combination of lithium with quetiapine and placebo with quetiapine in adult patients with acute mania, an increased incidence of extrapyramidal symptoms (particularly tremor), somnolence, and weight gain was observed in the lithium-added group compared to the placebo-added group.
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.
No interaction studies with cardiovascular drugs have 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
Because Quetiapine XR is indicated for the treatment of multiple indications, the safety profile of the drug should be carefully considered in light of the individual patient's diagnosis and the dose being taken.
The long-term efficacy and safety of concomitant therapy in patients with VDR 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 and adolescents under 18 years of age due to the lack of data on its use in this age group. Clinical studies of quetiapine have shown that, in addition to the known safety profile established in adults (see section "Adverse reactions"), 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 complications in children and adolescents (extrapyramidal symptoms and irritability), and an increase in blood pressure has been determined, which was not previously observed in studies with 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 of quetiapine in paediatric patients, 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).
Depression is associated with an increased risk of suicidal thoughts, self-harm and suicide (suicide-related events). This risk persists until significant remission is achieved. As improvement may not be observed during the first 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 recovery.
In addition, the potential risk of suicide-related events following abrupt discontinuation of quetiapine should be considered due to 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 suicide-related events. In addition, these conditions may occur concurrently with depressive episodes. Therefore, the same precautions should be taken when treating other psychiatric disorders as when treating depressive episodes.
Patients with a history of suicide-related events or those who demonstrate a significant degree of suicidal ideation prior to initiation of treatment are at greater risk of suicidal thoughts or suicide attempts and should receive careful monitoring during treatment. It is known that a meta-analysis of placebo-controlled clinical trials of antidepressants in adult patients with psychiatric disorders showed an increased risk of suicidal behavior with antidepressants compared with placebo 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 caregivers of patients) should be advised to monitor for clinical worsening, suicidal behaviour or thoughts, and unusual changes in behaviour and to seek medical advice immediately if symptoms present.
In short-term placebo-controlled studies in patients with major depressive episodes in bipolar disorder, an increased risk of suicide-related events 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 MDD, the incidence of suicide-related events 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 MDD found an increased risk of self-harm and suicide in patients aged 24 to 64 years with no history of self-harm when quetiapine was used with other antidepressants.
Metabolic risk
Given the changes observed in clinical trials regarding body weight, blood glucose (see hyperglycemia) and lipids, there is a possibility of a risk of worsening of the metabolic profile in individual patients, in which case appropriate treatment should be prescribed (see section "Adverse reactions").
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 increase the risk 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 established cardiovascular and cerebrovascular diseases or other conditions that may lead to hypotension.
Quetiapine may cause orthostatic hypotension, especially during the initial dose titration period. If this occurs, the dose or rate of dose titration should be reduced. A slow titration regimen may be considered in patients with cardiovascular disease.
Convulsions
There was no difference in the incidence of seizures between patients taking quetiapine and those taking placebo. There are no data on the incidence of seizures in patients with a history of seizure disorders. As with other antipsychotics, caution is advised when prescribing the drug to patients with a history of seizures (see section "Adverse reactions").
EPS
Quetiapine is known to be associated with an increased incidence of EPS compared to placebo in adult patients treated for major depressive episodes associated with bipolar disorder in placebo-controlled trials (see section 4.8).
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
Symptoms of tardive dyskinesia may worsen and occur even after discontinuation of therapy (see section "Adverse reactions").
Drowsiness and dizziness
Quetiapine treatment has been associated with somnolence and related symptoms such as sedation (see section 4.8). In clinical trials, it has been reported that in patients with bipolar depression, such symptoms usually occurred within the first 3 days of treatment and were mostly mild to moderate in intensity. Patients with bipolar depression who develop somnolence may need to be monitored for 2 weeks after the onset of somnolence or until symptoms resolve, or discontinuation of treatment may be considered.
Sleep apnea syndrome
Sleep apnea syndrome has been reported in patients taking quetiapine, therefore quetiapine should be used with caution in patients with a history of sleep apnea syndrome or at risk for its development (e.g., overweight/obese patients, male patients, patients receiving concomitant therapy with CNS depressants).
Neuroleptic malignant syndrome
Neuroleptic malignant syndrome may be associated with treatment with antipsychotics, including quetiapine (see section 4.8). Clinical manifestations include hyperthermia, altered mental status, muscle rigidity, autonomic instability and elevated creatine phosphokinase. In such cases, the drug should be discontinued and appropriate treatment initiated.
Serotonin syndrome
Concomitant use of Quetiapine XR and other serotonergic drugs, such as monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs) or tricyclic antidepressants, may lead to serotonin syndrome, a potentially life-threatening condition (see section “Interaction with other medicinal products and other forms of interaction”).
If concomitant treatment with other serotonergic drugs is clinically warranted, close monitoring of the patient is recommended, especially at the beginning of treatment and when the dose is increased. Symptoms of serotonin syndrome may include mental status changes, autonomic instability, neuromuscular disorders and/or gastrointestinal symptoms.
If serotonin syndrome is suspected, dose reduction or discontinuation of therapy should be considered, depending on the severity of symptoms.
Severe neutropenia and agranulocytosis
Severe neutropenia (neutrophil count < 0.5 × 109/L) has been reported in studies with quetiapine. The majority of cases of severe neutropenia have occurred within a few months of initiating quetiapine therapy. There is no apparent dose-related relationship. Cases of severe neutropenia with fatal outcome have been reported in the post-marketing setting. Possible risk factors for neutropenia include pre-existing low white blood cell count and a history of drug-induced neutropenia. Agranulocytosis has been reported in patients without pre-existing risk factors. Quetiapine should be discontinued in patients with neutrophil counts < 1.0 × 109/L. Patients should be monitored for signs of infection and neutrophil counts should be monitored until they exceed 1.5 × 109/L.
The possibility of neutropenia should be considered in patients with infection, especially in the absence of obvious contributing factors, and in patients with fever of unknown origin, and appropriate clinical measures should be taken.
Patients should be advised to promptly report symptoms suggestive of agranulocytosis or infection (e.g. fever, weakness, malaise or sore throat) at any time during treatment with quetiapine and to monitor WBC and ANC counts promptly, especially in the absence of precipitating factors.
Anticholinergic (muscarinic) effects
Norquetiapine, the active metabolite of quetiapine, has moderate to high affinity for several subtypes of muscarinic receptors. This results in adverse reactions reflecting anticholinergic effects when quetiapine is used at recommended doses, when quetiapine is used concomitantly with other drugs that have anticholinergic effects, and in cases of overdose. Quetiapine should be used with caution in patients receiving drugs that exhibit anticholinergic (muscarinic) effects. Quetiapine should be used with caution in patients with current or history of urinary retention, significant prostatic hypertrophy, intestinal obstruction, increased intraocular pressure, or narrow-angle glaucoma (see sections 5.1, 5.2, 5.3, and 4.8).
Acute withdrawal symptoms such as insomnia, nausea, headache, diarrhoea, vomiting, dizziness and irritability have been reported following abrupt discontinuation of quetiapine. Therefore, gradual withdrawal over a period of at least one to two weeks is recommended (see section 4.8).
Interactions
See also section “Interaction with other medicinal products and other types of interactions”.
Concomitant use of quetiapine with potent hepatic enzyme inducers such as carbamazepine or phenytoin significantly reduces quetiapine plasma concentrations, which may reduce its efficacy. Quetiapine should only be initiated in patients receiving a hepatic enzyme inducer if the physician considers that the benefits of the drug 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 during treatment with quetiapine and should be monitored and managed appropriately in accordance with antipsychotic guidelines (see section 4.8).
Hyperglycemia
Hyperglycaemia and/or development or exacerbation of diabetes mellitus, sometimes associated with ketoacidosis or coma, have been reported rarely, including several fatal cases (see section 4.8). In some cases, these events have occurred in patients with increased body weight, which may be a contributing factor. Appropriate clinical monitoring is recommended in accordance with the relevant guidelines for the use of antipsychotics. Patients treated with any antipsychotic agent, including quetiapine, should be observed for signs and 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
Cases of increased triglycerides, low-density lipoprotein (LDL) and total cholesterol levels, as well as decreased high-density lipoprotein (HDL) levels have been described (see section 4.8). In case of changes in lipid levels, treatment should be carried out according to clinical indications.
QT prolongation
In clinical trials and when quetiapine was used as directed, no consistent increase in the absolute value of the QT interval was observed. In the post-marketing period, prolongation of the QT interval has been observed 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 prolonged QT. When prescribing quetiapine simultaneously with drugs that increase the QT interval or other neuroleptics, caution should be exercised (see section "Interaction with other medicinal products and other types of interactions"), especially in elderly patients, patients with congenital long QT syndrome, congestive heart failure (CHF), cardiac hypertrophy, hypokalemia or hypomagnesemia (see section "Interaction with other medicinal products and other types of interactions").
Cardiomyopathy and myocarditis
Cardiomyopathy and myocarditis have been reported with quetiapine in clinical trials and post-marketing experience (see section 4.8). Discontinuation of quetiapine should be considered in patients suspected of developing cardiomyopathy or myocarditis.
Severe adverse skin reactions
Very rare cases of severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), acute generalised exanthematous pustulosis, 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 typically present as a combination of the following symptoms: a widespread skin rash that may be pruritic or pustular, exfoliative dermatitis, fever, lymphadenopathy, and eosinophilia or neutrophilia. The majority of these reactions have occurred within 4 weeks of initiating quetiapine therapy, and some cases of DRESS have occurred 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.
Elderly patients with dementia-related psychosis
In patients with dementia, an almost 3-fold increased risk of cerebrovascular adverse events has been observed with some atypical antipsychotics. The mechanism of this increased risk is unknown. An increased risk cannot be excluded for other antipsychotics or for 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. However, in two 10-week placebo-controlled trials of quetiapine in the same population (mean age 83 years, range 56-99 years), the mortality rate in quetiapine-treated patients was 5.5% compared with 3.2% in the placebo group. Mortality in patients in the trials was from a variety of causes, as expected for this patient population.
Elderly patients with Parkinson's disease/parkinsonism
A retrospective population-based study of quetiapine in patients with MND showed an increased risk of death in patients aged 65 years and older when taking quetiapine. This association was not observed when patients with Parkinson's disease were excluded from the study. Caution should be exercised when prescribing quetiapine to elderly patients with Parkinson's disease.
Dysphagia
Dysphagia has been reported with quetiapine (see section 4.8). Quetiapine should be used with caution in patients at risk of aspiration pneumonia.
Constipation and intestinal obstruction
Constipation is a risk factor for the development of intestinal obstruction. Cases of constipation and intestinal obstruction have been reported with quetiapine (see section 4.8). These reports include fatal cases in patients who are at higher risk of developing intestinal obstruction, including those receiving multiple medications that reduce intestinal motility and/or may not report symptoms of constipation. Patients with intestinal obstruction/ileus should be managed with close monitoring and emergency medical care.
Liver effects
If jaundice occurs, quetiapine should be discontinued.
Venous thromboembolism (VTE)
Cases of VTE have been reported with antipsychotic medications. 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
Cases of pancreatitis have been reported in clinical trials and during the post-marketing period. Post-marketing reports indicated that many patients had factors known to be associated with pancreatitis, such as elevated triglyceride levels, gallstones, and alcohol consumption.
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 section 4.8). These data showed an additive effect at week 3 of treatment.
Irrational use and abuse
Cases of misuse and abuse have been reported. Quetiapine should be prescribed with caution to patients with a history of alcohol or drug abuse.
Use during pregnancy or breastfeeding
Pregnancy
I trimester
There is only a small amount of published data on the effects of quetiapine
