As Q-PIN has several indications, the safety profile should be considered with respect to the individual patient's diagnosis and the dose being administered.
Suicide/suicidal thoughts or clinical worsening: Depression in bipolar disorder 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 experience that the risk of suicide may increase in the early stages of recovery.
In addition, physicians should consider the potential risk of suicide-related events after abrupt cessation of Quetiapine treatment, due to the known risk factors for the disease being treated.
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 episodes. The same precautions observed when treating patients with major depressive episodes 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.
Close supervision of patients and in particular those at high risk should accompany drug therapy especially in early treatment and following dose changes. Patients (and caregivers of patients) should be alerted about the need to monitor for any clinical worsening, suicidal behaviour or thoughts and unusual changes in behaviour and to seek medical advice immediately if these symptoms present.
Extrapyramidal symptoms: The use of 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. This is most likely to occur within the first few weeks of treatment. In patients who develop these symptoms, increasing the dose may be detrimental.
Tardive dyskinesia: 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).
Somnolence and dizziness: Quetiapine treatment has been associated with somnolence and related symptoms, such as sedation (see ADVERSE REACTIONS). Bipolar depression patients experiencing somnolence of severe intensity may require more frequent contact for a minimum of 2 weeks from onset of somnolence, or until symptoms improve and treatment discontinuation may need to be considered.
Quetiapine treatment has been associated with orthostatic hypotension and related dizziness (see ADVERSE REACTIONS) which, like somnolence has onset usually during the initial dose-titration period. This could increase the occurrence of accidental injury (fall), especially in the elderly population. Therefore, patients should be advised to exercise caution until they are familiar with the potential effects of the medication.
Sleep apnoea syndrome: Sleep apnoea syndrome has been reported in patients using Quetiapine. In patients receiving concomitant central nervous system depressants and who have a history of or are at risk for sleep apnoea, such as those who are overweight/obese or are male, Quetiapine should be used with caution.
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 anticholinergic 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, significant prostatic hypertrophy, intestinal obstruction or related conditions, increased intraocular pressure or narrow angle glaucoma.
Cardiovascular: 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 and therefore, dose reduction or more gradual titration should be considered if this occurs. A slower titration regimen could be considered in patients with underlying cardiovascular disease.
Seizures: No data is available about the incidence of seizures in patients with a history of seizure disorder. As with other antipsychotics, caution is recommended when treating patients with a history of seizures (see ADVERSE REACTIONS).
Neuroleptic malignant syndrome: Neuroleptic malignant syndrome has been associated with antipsychotic treatment, including Quetiapine (see ADVERSE REACTIONS). 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.
Neutropenia and agranulocytosis: Severe neutropenia (neutrophil count < 0.5 x 109/L) without infection has been reported. There have been reports of agranulocytosis (severe neutropenia with infection) among all patients treated with Quetiapine. 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. Resolution of leucopenia and/or neutropenia has followed cessation of therapy with Quetiapine. 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 appropriately.
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).
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 pregnancy and lactation: The safety and efficacy of Quetiapine during human pregnancy have not yet been established. Following pregnancies in which Quetiapine was used, neonatal withdrawal symptoms were observed. Therefore, Quetiapine should only be used during pregnancy if the benefits justify the potential risks.
There have been published reports of Quetiapine excretion into human breast milk; however the degree of excretion was not consistent. Women who are breast-feeding should therefore be advised to avoid breast-feeding while taking Quetiapine.
Neonates exposed to antipsychotics (including Quetiapine) during the third trimester of pregnancy are at risk of adverse reactions including extrapyramidal and/or withdrawal symptoms that may vary in severity and duration following delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, or feeding disorder. Consequently, newborns should be monitored carefully.