PSYQUET XL

Posology Different dosing schedules exist for each indication. It must therefore be ensured that patients receive clear information on the appropriate dose for their condition.

Adults:

For the treatment of schizophrenia and moderate to severe manic episodes in bipolar disorder Psyquet XL should be administered at least one hour before a meal. The daily dose at the start of therapy is 300 mg on Day 1 and 600 mg on Day 2.

The recommended daily dose is 600 mg, however if clinically justified the dose may be increased to 800 mg daily. The dose should be adjusted within the effective dose range of 400 mg to 800 mg per day, depending on the clinical response and tolerability of the patient.

For maintenance therapy in schizophrenia no dosage adjustment is necessary. For the treatment of major depressive episodes in bipolar disorder Psyquet XL should be administered at bedtime. The total daily dose for the first four days of therapy is 50 mg (Day 1), 100 mg (Day 2), 200 mg (Day 3) and 300 mg (Day 4).

The recommended daily dose is 300 mg. 1). Individual patients may benefit from a 600 mg dose. Doses greater than 300 mg should be initiated by physicians experienced in treating bipolar disorder. In individual patients, in the event of tolerance concerns, clinical trials have indicated that dose reduction to a minimum of 200 mg could be considered.

For preventing recurrence in bipolar disorder For preventing recurrence of manic, mixed or depressive episodes in bipolar disorder, patients who have responded to Psyquet XL for acute treatment of bipolar disorder should continue on Psyquet XL at the same dose administered at bedtime.

Psyquet XL dose can be adjusted depending on clinical response and tolerability of the individual patient within the dose range of 300 mg to 800 mg/day. It is important that the lowest effective dose is used for maintenance therapy.

For add-on treatment of major depressive episodes in MDD:

Psyquet XL should be administered prior to bedtime. The daily dose at the start of therapy is 50 mg on Day 1 and 2, and 150 mg on Day 3 and 4. 1) and at 50 mg/day in short-term monotherapy trials. There is an increased risk of adverse events at higher doses.

Clinicians should therefore ensure that the lowest effective dose, starting with 50 mg/day, is used for treatment. The need to increase the dose from 150 to 300 mg/day should be based on individual patient evaluation.

Switching from Quetiapine immediate-release tablets:

For more convenient dosing, patients who are currently being treated with divided doses of immediate release Quetiapine tablets may be switched to Psyquet XL at the equivalent total daily dose taken once daily. Individual dosage adjustments may be necessary.

Elderly:

As with other antipsychotics and antidepressants, Psyquet XL should be used with caution in the elderly, especially during the initial dosing period. The rate of dose titration of Psyquet XL may need to be slower, and the daily therapeutic dose lower, than that used in younger patients.

The mean plasma clearance of quetiapine was reduced by 30% to 50% in elderly patients when compared to younger patients. Elderly patients should be started on 50 mg/day. The dose can be increased in increments of 50 mg/day to an effective dose, depending on the clinical response and tolerability of the individual patient.

In elderly patients with major depressive episodes in MDD, dosing should begin with 50 mg/day on Days 1- 3, increasing to 100 mg/day on Day 4 and 150 mg/day on Day 8. The lowest effective dose, starting from 50 mg/day should be used.

Based on individual patient evaluation, if dose increase to 300 mg/day is required this should not be prior to Day 22 of treatment. Efficacy and safety has not been evaluated in patients over 65 years with depressive episodes in the framework of bipolar disorder.

Paediatric Population Psyquet XL is not recommended for use in children and adolescents below 18 years of age, due to a lack of data to support use in this age group. 2.

Renal impairment:

Dose adjustment is not necessary in patients with renal impairment.

Hepatic impairment:

Quetiapine is extensively metabolized by the liver. Therefore, Psyquet XL should be used with caution in patients with known hepatic impairment, especially during the initial dosing period. Patients with hepatic impairment should be started on 50 mg/day.

The dose can be increased in increments of 50 mg/day to an effective dose, depending on the clinical response and tolerability of the individual patient. Method of administration Psyquet XL should be administered once daily, without food.

The tablets should be swallowed whole and not split, chewed or crushed.

). 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.

Patients with intestinal obstruction/ileus should be managed with close monitoring and urgent care. 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.

Pancreatitis Pancreatitis has been reported in clinical trials and during post marketing experience. 4), gallstones, and alcohol consumption. 1). The data showed an additive effect at week 3.

Lactose:

Psyquet XL prolonged-release tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption should not take this medicinal product.

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. 5 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.

4). 4). Cytochrome P450 (CYP) 3A4 is the enzyme that is primarily responsible for the cytochrome P450 mediated metabolism of quetiapine. In an interaction study in healthy volunteers, concomitant administration of quetiapine (dose of 25 mg) with ketoconazole, a CYP3A4 inhibitor, caused a 5-to 8-fold increase in the AUC of quetiapine.

On the basis of this, concomitant use of quetiapine with CYP3A4 inhibitors is contraindicated. It is also not recommended to consume grapefruit juice while on quetiapine therapy. In a multiple dose trial in patients to assess the pharmacokinetics of quetiapine given before and during treatment with carbamazepine (a known hepatic enzyme inducer), co-administration of carbamazepine significantly increased the clearance of quetiapine.

This increase in clearance reduced systemic quetiapine exposure (as measured by AUC) to an average of 13% of the exposure during administration of quetiapine alone; although a greater effect was seen in some patients. 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 by approx. 450%. 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.

g. 4). 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 with approx. 70%. The pharmacokinetics of quetiapine were not altered following co-administration with cimetidine. The pharmacokinetics of lithium were not altered when co-administered with quetiapine.

1). The pharmacokinetics of sodium valproate and quetiapine were not altered to a clinically relevant extent when co-administered. A retrospective study of 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 Formal interaction studies with commonly used cardiovascular medicinal products have not been performed.

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. 7 Effects on ability to drive and use machines Given its primary […]

As Psyquet XL has several indications, the safety profile should be considered with respect to the individual patient’s diagnosis and the dose being administered. 1). Paediatric population Quetiapine is not recommended for use in children and adolescents below 18 years of age, due to a lack of data to support use in this age group.

8), certain adverse events occurred at a higher frequency in children and adolescents compared to adults (increased appetite, elevations in serum prolactin, vomiting, rhinitis and syncope) or may have different implications for children and adolescents (extrapyramidal symptoms and irritability) and one was identified that has not been previously seen in adult studies (increases in blood pressure).

Changes in thyroid function tests have also been observed in children and adolescents. Furthermore, the long-term safety implications of treatment with quetiapine on growth and maturation have not been studied beyond 26 weeks. Long-term implications for cognitive and behavioural development are not known.

8).

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. 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.

A meta analysis of placebo controlled clinical trials of antidepressant drugs in adult patients with psychiatric disorders showed an increased risk of suicidal behaviour with antidepressants compared to placebo in patients less than 25 years old.

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.

0% vs. 0%, respectively). 3% (1/75) for placebo. A population-based retrospective study of quetiapine for the treatment of patients with major depressive disorder showed an increased risk of self-harm and suicide in patients aged 25 to 64 years without a history of self-harm during use of quetiapine with other antidepressants.

Metabolic risk Given the observed risk for worsening of their metabolic profile, including changes in weight, blood glucose (see hyperglycemia) and lipids, which was seen in clinical studies, patient’s metabolic parameters should be assessed at the time of treatment initiation and changes in these parameters should be regularly controlled for during the course of treatment.

8). 1). 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:

If signs and symptoms of tardive dyskinesia appear, dose reduction or discontinuation of quetiapine should be considered. 8). 8). In […]

1. Concomitant administration of cytochrome P450 3A4 inhibitors, such as HIV- protease inhibitors, azole-antifungal agents, erythromycin, clarithromycin and nefazodone, is contraindicated. 5).