Concomitant use of Quetiapine with a strong hepatic enzyme inducer such as Carbamazepine or Phenytoin substantially decreases Quetiapine plasma concentrations, which could affect the efficacy of Quetiapine therapy. In patients receiving a hepatic enzyme inducer, initiation of Quetiapine treatment should only occur if the physician considers that the benefits of Quetiapine outweigh the risks of removing the hepatic enzyme inducer. It is important that any change in the inducer is gradual, and if required, replaced with a non-inducer (e.g. Sodium valproate).
Weight: Weight gain has been reported in patients who have been treated with Quetiapine, and should be monitored and managed appropriately as in accordance with utilized antipsychotic guidelines (see ADVERSE REACTIONS).
Hyperglycaemia: Hyperglycaemia and/or development or exacerbation of diabetes occasionally associated with ketoacidosis or coma has been reported, including some fatal cases (see ADVERSE REACTIONS). In some cases, a prior increase in body weight has been reported which may be a predisposing factor. Appropriate monitoring is advisable in accordance with utilised antipsychotic guidelines. 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 with risk factors for diabetes mellitus should be monitored regularly for worsening of glucose control. Weight should be monitored regularly.
Lipids: Increases in triglycerides, LDL and total cholesterol, and decreases in HDL cholesterol have been observed with Quetiapine (see ADVERSE REACTIONS). Lipid changes should be managed appropriately.
Metabolic risk: Given the observed changes in weight, blood glucose (see hyperglycaemia as mentioned) and lipids, patients (including those with normal baseline value) may experience worsening of their metabolic risk profile, which should be managed appropriately (see ADVERSE REACTIONS).
QT Prolongation: 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 in the elderly, in patients with congenital long QT syndrome, congestive heart failure, heart hypertrophy, hypokalaemia or hypomagnesaemia.
Cardiomyopathy and myocarditis: Cardiomyopathy and myocarditis have been reported, however a causal relationship to Quetiapine has not been established. Treatment with Quetiapine should be reassessed in patients with suspected cardiomyopathy or myocarditis.
Withdrawl: Acute withdrawl symptoms such as insomnia, nausea, headache, diarrhoea, vomiting, dizziness, and irritability have been described after abrupt cessation of 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.
Elderly patients with dementia: Quetiapine is not approved for the treatment of dementia-related psychosis.
Dysphagia: Dysphagia (see ADVERSE REACTIONS) and aspiration have been reported with Quetiapine. Although a casual relationship with aspiration pneumonia has not been established, Quetiapine should be used with caution in patients at risk for aspiration pneumonia.
Venous thromboembolism (VTE): 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.
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.
Pancreatitis: Pancreatitis has been reported, many patients had factors which are known to be associated with pancreatitis such as increased triglycerides (see PRECAUTIONS), 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 are at risk for sleep apnoea, and are receiving concomitant central nervous system (CNS) depressants, Quetiapine should be used with caution.
Additional information: Quetiapine data in combination with Divalproex or Lithium in acute moderate to severe manic episodes is limited.
Lactose: Q-PIN Tablet contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicine.
Interaction with other medicinal products and other forms of interaction: Given the primary central nervous system effects of Quetiapine, Quetiapine should be used with caution in combination with other centrally acting medicinal products and alcohol.
Cytochrome P450 (CYP) 3A4 is the primary enzyme responsible for the cytochrome P450 mediated metabolism of Quetiapine.
Concomitant use of Quetiapine with CYP3A4 inhibitors is contraindicated. It is also not recommended to consume grapefruit juice while on Quetiapine therapy.
Co-administration of Carbamazepine (a known hepatic enzyme inducer) significantly increased the clearance of Quetiapine. As a consequence of this interaction, lower plasma concentrations can occur, which could affect the efficacy of Quetiapine therapy.
Co-administration of Quetiapine and Phenytoin (another microsomal enzyme inducer) caused a greatly increased clearance of Quetiapine. In patients receiving a hepatic enzyme inducer, initiation of Quetiapine treatment should only occur if the physician considers that the benefits of Quetiapine outweigh the risks of removing the hepatic enzyme inducer. It is important that any change in the inducer is gradual, and if required, replaced with a non-inducer (e.g. sodium valproate) (see PRECAUTIONS).
The pharmacokinetics of Quetiapine were not significantly altered by co-administration of the antidepressants Imipramine (a known CYP 2D6 inhibitor) or Fluoxetine (a known CYP 3A4 and CYP 2D6 inhibitor).
The pharmacokinetics of Quetiapine were not significantly altered by co-administration of the antipsychotics Risperidone or Haloperidol.
Concomitant use of Quetiapine and Thioridazine caused an increased clearance of Quetiapine.
The pharmacokinetics of Quetiapine were not altered following co-administration with Cimetidine.
The pharmacokinetics of Lithium were not altered when co-administered with Quetiapine.
The pharmacokinetics of Sodium valproate and Qetiapine were not altered to a relevant extent when co-administered. Children and adolescents who received Valproate, Quetiapine, or both, found a higher incidence of leucopenia and neutropenia in the combination group versus the monotherapy groups.
Caution should be exercised treating patients receiving other medications having anticholinergic (muscarinic) effects (see PRECAUTIONS).
Caution should be exercised when Quetiapine is used concomitantly with medicinal products known to cause electrolyte imbalance or to increase QT interval.
There have been reports of false positive results in enzyme immunoassays for Methadone and tricyclic antidepressants in patients who have taken Quetiapine. Confirmation of questionable immunoassay screening results by an appropriate chromatographic technique is recommended.