Apo-Quetiapine Special Precautions

Elderly patients with dementia: Quetiapine 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 treatment and death in elderly patients with dementia.
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).
Severe Neutropenia: Severe neutropenia (<0.5 X 10⁹/L) has been uncommonly reported in quetiapine clinical trials. Most 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. 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 Hyperglycemia: 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.)
Hyperglycemia or exacerbation of pre-existing diabetes has been reported in very rare cases during treatment with atypical antipsychotics, including quetiapine. Assessment of the association between atypical antipsychotic use and glucose abnormalities is complicated by the possibility of an increased background risk of diabetes mellitus in patients with schizophrenia, and the increasing incidence of diabetes mellitus in the general population.
Some epidemiological studies suggest an increased risk of treatment-emergent hyperglycemia-related adverse events in patients treated with the atypical antipsychotics. Patients with an established diagnosis of diabetes mellitus should be monitored regularly for worsening of glucose control. Appropriate clinical monitoring is advised for patients with risk factors for diabetes mellitus (e.g., obesity, family history of diabetes) and those who develop symptoms of hyperglycemia during treatment with atypical antipsychotics.
Patients treated with atypical antipsychotics should be monitored for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness.
Lipids: Increases in triglycerides and cholesterol have been observed in clinical trials with quetiapine (see Adverse Reactions). Lipid increases should be managed as clinically appropriate.
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.)
Cardiovascular disease: 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; this is more common in elderly patients than in younger patients.
In clinical trials, quetiapine was not associated with a persistent increase in QTc 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 QTc interval, and 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).
Extrapyramidal symptoms (EPS) and Tardive dyskinesia: 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 standard antipsychotic agents to induce tardive dyskinesia in schizophrenia and bipolar mania patients. In short-term placebo-controlled clinical trials of adult patients with 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). If signs and symptoms of tardive dyskinesia appear, dose reduction or discontinuation of quetiapine should be considered.
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.
Acute withdrawal reactions: Acute withdrawal symptoms such as insomnia, nausea and vomiting have been described after abrupt cessation of antipsychotic drugs including quetiapine. Recurrence of psychotic symptoms may also occur, and the emergence of involuntary movement disorders (such as akathisia, dystonia and dyskinesia) has been reported. Gradual withdrawal over a period of at least one to two weeks is advisable (see Adverse Reactions).
Venous thromboembolism: Cases of venous thromboembolism (VTE) have been reported with antipsychotic drugs. Since patients treated with antipsychotics often present with acquired risk factors for VTE, all possible risk factors for VTE should be identified before and during treatment with quetiapine and preventive measures undertaken.
Dysphagia: Dysphagia (see Adverse Reactions) and aspiration pneumonia 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 of aspiration pneumonia.
Severe Cutaneous Adverse Reactions: Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS) are potentially life threatening adverse drug reactions that have been reported during quetiapine exposure. SCARs commonly present as a combination of the following symptoms: extensive cutaneous rash or exfoliative dermatitis, fever, lymphadenopathy and possible eosinophilia. Discontinue quetiapine if severe cutaneous adverse reactions occur.
Psychiatric Disorders: There is a potential risk of somnambulisn (sleep walking) and sleep-related eating disorder (see Adverse Reactions) with the use of atypical antipsychotics drugs, including quetiapine.
EFFECTS ON ABILITY TO DRIVE AND USE MACHINES: Because quetiapine may cause somnolence, patients should be cautioned about operating hazardous machines, including motor vehicles.