Seroquel/Seroquel XR Special Precautions

Suicide/suicidal thoughts or clinical worsening: Depression is associated with an increased risk of suicidal thoughts, self-harm and suicide (suicide-related events). This risk persists until significant remission occurs. As improvement may not occur 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 increase in the early stages of recovery.
Other psychiatric conditions for which quetiapine is prescribed can also be associated with an increased risk of suicide-related events. In addition, these conditions may be co-morbid with major depressive disorder. The same precautions observed when treating patients with major depressive disorder should therefore be observed when treating patients with other psychiatric disorders.
Patients with a history of suicide-related events, or those exhibiting a significant degree of suicidal ideation prior to commencement of treatment are known to be at greater risk of suicidal thoughts or suicide attempts and should receive careful monitoring during treatment. An FDA meta-analysis of placebo-controlled clinical trials of antidepressant drugs in approximately 4400 children and adolescents and 77000 adult patients with psychiatric disorders showed an increased risk of suicidal behaviour with antidepressants compared to placebo in children, adolescents, and young adult patients less than 25 years old. This meta-analysis did not include trials involving quetiapine (see Pharmacology: Pharmacodynamics under Actions).
Neutropenia and agranulocytosis: Severe neutropenia (<0.5 X 10⁹/L) without infection has been uncommonly reported in short-term placebo controlled monotherapy clinical trials with quetiapine. There have been reports of agranulocytosis (severe neutropenia with infection) among all patients treated with quetiapine during clinical trials (rare) as well as post-marketing reports (including fatal cases). Most of these cases of severe neutropenia have occurred within the first two months of starting therapy with quetiapine. There was no apparent dose relationship. Possible risk factors for neutropenia include pre-existing low white cell count (WBC) and history of drug induced neutropenia.
There have been cases of agranulocytosis in patients without pre-existing risk factors. Neutropenia should be considered in patients presenting with infection, particularly in the absence of obvious predisposing factor(s), or in patients with unexplained fever, and should be managed as clinically appropriate.
Quetiapine should be discontinued in patients with a neutrophil count <1.0 X 10⁹/L. These patients should be observed for signs and symptoms of infection and neutrophil counts followed (until they exceed 1.5 X 10⁹/L). (See Adverse Reactions).
Increases in blood glucose and hyperglycaemia: Increases in blood glucose and hyperglycaemia, and occasional reports of diabetes, have been observed in clinical trials with quetiapine. Although a causal relationship with diabetes has not been established, patients who are at risk for developing diabetes are advised to have appropriate clinical monitoring. Similarly, patients with existing diabetes should be monitored for possible exacerbation (see Adverse Reactions).
Lipids: Increases in triglycerides and cholesterol, and decreases in HDL have been observed in clinical trials with quetiapine (see Adverse Reactions). Lipid changes should be managed as clinically appropriate.
Metabolic factors: In some patients, a worsening of more than one of the metabolic factors of weight, blood glucose and lipids was observed in clinical studies. Changes in these parameters should be managed as clinically appropriate.
Pancreatitis: Pancreatitis has been reported in clinical trials and during the post marketing experience, however a causal relationship has not been established. Among the post marketing reports, many patients had factors which are known to be associated with pancreatitis such as increased triglycerides (see Lipids previously), gallstones, and alcohol consumption.
Concomitant illness: Quetiapine should be used with caution in patients with known cardiovascular disease, cerebrovascular disease, or other conditions predisposing to hypotension. Quetiapine may induce orthostatic hypotension especially during the initial dose-titration period.
In patients who have a history of or at risk for sleep apnea, and are receiving concomitant central nervous system (CNS) depressants, quetiapine should be used with caution.
Dysphagia: Dysphagia (see Adverse Reactions) and aspiration have been reported with quetiapine. Although a causal relationship with aspiration pneumonia has not been established, quetiapine should be used with caution in patients at risk for aspiration pneumonia.
Constipation and intestinal obstruction: Constipation represents a risk factor for intestinal obstruction. Constipation and intestinal obstruction have been reported with quetiapine (see Adverse Reactions). This includes fatal reports in patients who are at higher risk of intestinal obstruction, including those that are receiving multiple concomitant medications that decrease intestinal motility and/or may not report symptoms of constipation.
Seizures: In controlled clinical trials there was no difference in the incidence of seizures in patients treated with quetiapine or placebo. As with other antipsychotics, caution is recommended when treating patients with a history of seizures (see Adverse Reactions).
Tardive Dyskinesia and Extrapyramidal Symptoms (EPS): Tardive dyskinesia is a syndrome of potentially irreversible, involuntary, dyskinetic movements that may develop in patients treated with antipsychotic drugs including quetiapine. If signs and symptoms of tardive dyskinesia appear, dose reduction or discontinuation of quetiapine should be considered. The symptoms of tardive dyskinesia can worsen or even arise after discontinuation of treatment (see Adverse Reactions).
In placebo-controlled clinical trials of adult patients with schizophrenia and bipolar mania the incidence of extrapyramidal symptoms was no different from that of placebo across the recommended therapeutic dose range. This predicts that quetiapine has less potential than typical antipsychotic agents to induce tardive dyskinesia in schizophrenia and bipolar mania patients. In short-term placebo-controlled clinical trials for bipolar depression, the incidence of EPS was higher in quetiapine treated patients than in placebo treated patients (see Adverse Reactions for rates of EPS observed in all indications and ages).
Neuroleptic Malignant Syndrome: Neuroleptic malignant syndrome has been associated with antipsychotic treatment, including quetiapine (see Adverse Reactions). Clinical manifestations include hyperthermia, altered mental status, muscular rigidity, autonomic instability, and increased creatine phosphokinase. In such an event, quetiapine should be discontinued and appropriate medical treatment given.
QT Prolongation: In clinical trials quetiapine was not associated with a persistent increase in absolute QT intervals. However, in post marketing experience there were cases reported of QT prolongation with overdose (see Overdosage). As with other antipsychotics, caution should be exercised when quetiapine is prescribed in patients with cardiovascular disease or family history of QT prolongation. Also caution should be exercised when quetiapine is prescribed either with medicines known to increase QT interval or with concomitant neuroleptics, especially for patients with increased risk of QT prolongation, i.e., the elderly, patients with congenital long QT syndrome, congestive heart failure, heart hypertrophy, hypokalemia or hypomagnesemia (see Interactions).
Cardiomyopathy and Myocarditis: Cardiomyopathy and myocarditis have been reported in clinical trials and during the post-marketing experience, however, a causal relationship to quetiapine has not been established. Treatment with quetiapine should be reassessed in patients with suspected cardiomyopathy or myocarditis.
Withdrawal: Acute withdrawal symptoms such as insomnia, nausea, and vomiting have been described after abrupt cessation of antipsychotic drugs including quetiapine. Gradual withdrawal over a period of at least one to two weeks is advisable (see Adverse Reactions).
Misuse and abuse: Cases of misuse and abuse have been reported. Caution may be needed when prescribing quetiapine to patients with a history of alcohol or drug abuse.
Interactions: See also Interactions.
Concomitant use of quetiapine with hepatic enzyme inducers such as carbamazepine may substantially decrease systemic exposure to quetiapine. Depending on clinical response, higher doses of quetiapine may need to be considered if it is used concomitantly with a hepatic enzyme inducer.
During concomitant administration of drugs, which are potent CYP3A4 inhibitors (such as azole antifungals, macrolide antibiotics, and protease inhibitors) plasma concentrations of quetiapine can be significantly higher than observed in patients in clinical trials. As a consequence of this, lower doses of quetiapine should be used. Special consideration should be given in elderly and debilitated patients. The risk-benefit ratio needs to be considered on an individual basis in all patients.
Anti-cholinergic (muscarinic) effects: Norquetiapine, an active metabolite of quetiapine, has moderate to strong affinity for several muscarinic receptor subtypes. This contributes to ADRs reflecting anti-cholinergic effects when quetiapine is used at recommended doses, when used concomitantly with other medications having anti-cholinergic effects, and in the setting of overdose. Quetiapine should be used with caution in patients receiving medications having anti-cholinergic (muscarinic) effects. Quetiapine should be used with caution in patients with a current diagnosis or prior history of urinary retention, clinically significant prostatic hypertrophy, intestinal obstruction or related conditions, increased intraocular pressure or narrow angle glaucoma (see Pharmacology: Pharmacodynamics: Mechanism of action under Actions, Overdosage, Adverse Reactions and Interactions).
Effects on ability to drive and use machines: Given its primary central nervous system effects, quetiapine may interfere with activities requiring mental alertness. Therefore, patients should be advised not to drive or operate machinery, until individual susceptibility is known.
Use in Children and Adolescents (10 to 17 years of age): Although not all adverse reactions that have been identified in the adult patients have been observed in clinical trials with quetiapine in children and adolescent patients, the same special warnings and special precautions for use that appear above for adults should be considered for pediatrics. Additionally, changes in blood pressure and thyroid function tests and increases in weight and prolactin levels have been observed and should be managed as clinically appropriate (see Adverse Reactions).
Long-term safety data including growth, maturation, and behavioural development, beyond 26 weeks of treatment with quetiapine, is not available for children and adolescents (10 to 17 years of age).
Use in Elderly with dementia: Quetiapine (SEROQUEL) is not approved for the treatment of patients with dementia-related psychosis. In a meta-analysis of atypical antipsychotic drugs, it has been reported that elderly patients with dementia-related psychosis are at an increased risk of death compared to placebo. In two 10-week placebo controlled quetiapine studies in the same patient population (n=710; mean age: 83 years; range: 56-99 years) the incidence of mortality in quetiapine-treated patients was 5.5% versus 3.2% in the placebo group. The patients in these trials died from a variety of causes that were consistent with expectations for this population. These data do not establish a causal relationship between Quetiapine (SEROQUEL) treatment and death in elderly patients with dementia.