ATROLAK Prolonged-release tablet Ref.[7063] Active ingredients: Quetiapine

Posology

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

Adults

For the treatment of schizophrenia and moderate to severe manic episodes in bipolar disorder

Atrolak XL 50 mg should be administrated 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

Atrolak XL 50 mg 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. In clinical trials, no additional benefit was seen in the 600 mg group compared to the 300 mg group (see Section 5.1). 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 Atrolak XL 50 mg for acute treatment of bipolar disorder should continue on Atrolak XL 50 mg at the same dose administered at bedtime. Atrolak XL 50 mg 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

Atrolak XL 50 mg 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. Antidepressant effect was seen at 150 and 300 mg/day in short-term trials as add-on therapy (with amitriptyline, bupropion, citalopram, duloxetine, escitalopram, fluoxetine, paroxetine, sertraline and venlafaxine – see Section 5.1) 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 Atrolak XL 50 mg at the equivalent total daily dose taken once daily. Individual dosage adjustments may be necessary.

Elderly

As with other antipsychotics and antidepressants, Atrolak XL 50 mg should be used with caution in the elderly, especially during the initial dosing period. The rate of dose titration of Atrolak XL 50 mg 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

Atrolak XL 50 mg 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. The available evidence from placebo-controlled clinical trials with Quetiapine tablet is presented in Sections 4.4, 4.8, 5.1 and 5.2.

Renal impairment

Dosage adjustment is not necessary in patients with renal impairment.

Hepatic impairment

Quetiapine is extensively metabolized by the liver. Therefore, Atrolak XL 50 mg 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

Atrolak XL50mg should be administered once daily, without food. The tablets should be swallowed whole and not split, chewed or crushed.

Symptoms

In general, reported signs and symptoms were those resulting from an exaggeration of the active substance’s known pharmacological effects, ie, drowsiness and sedation, tachycardia, hypotension and anti-cholinergic effects.

Overdose could lead to QT-prolongation, seizures, status epilepticus, rhabdomyolysis, respiratory depression, urinary retention, confusion, delirium, and/or agitation, coma and death.

Patients with pre-existing severe cardiovascular disease may be at an increased risk of the effects of overdose. (see Section 4.4, Orthostatic Hypotension).

Management of overdose

There is no specific antidote to quetiapine. In cases of severe signs, the possibility of multiple drug involvement should be considered, and intensive care procedures are recommended, including establishing and maintaining a patent airway, ensuring adequate oxygenation and ventilation, and monitoring and support of the cardiovascular system.

Based on public literature, patients with delerium and agitation and a clear anti-cholinergic syndrome may be treated with physostigmine, 1-2 mg (under continuous ECG monitoring). This is not recommended as standard treatment, because of potential negative effect of physostigmine on cardiac conductance. Physostigmine may be used if there are no ECG aberrations. Do not use physostigmine in case of dysrhythmias, any degree of heart block or QRS-widening.

Whilst the prevention of absorption in overdose has not been investigated, gastric lavage can be indicated in severe poisonings and if possible to perform within one hour of ingestion. The administration of activated charcoal should be considered.

In cases of quetiapine overdose, refractory hypotension should be treated with appropriate measures such as intravenous fluids and/or sympathomimetic agents. Epinephrine and dopamine should be avoided, since beta stimulation may worsen hypotension in the setting of quetiapine-induced alpha blockade.

In case of overdose with extended-release quetiapine there is a delayed peak sedation and peak pulse and prolonged recovery compared with IR Quetiapine overdose.

In case of a quetiapine extended-release overdose gastric bezoar formation has been reported and appropriate diagnostic imaging is recommended to further guide patient management.

Endoscopic pharmacobezoar removal has been performed successfully in some cases.

Close medical supervision and monitoring should be continued until the patient recovers.

30 months.

This medicinal product does not require any special storage conditions.

PVC/PVDC-Alu blister pack or OPA/Alu/PVC–Alu blister pack. Pack size of 6, 10, 20, 28, 30, 50, 60, 90 and 100 tablets per pack.

Not all pack sizes may be marketed.

No special requirements for disposal.