MINTRELEQ XL

Different dosing schedules exist for each indication. It must therefore be ensured that patients receive clear information on the appropriate dosage for their condition. Mintreleq XL should be administered once daily, without food. The tablets should be swallowed whole and not split, chewed or crushed.

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

Mintreleq 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 Mintreleq 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.

The most commonly reported Adverse Drug Reactions (ADRs) with quetiapine (≥10%) are somnolence, headache, dizziness, dry mouth, withdrawal (discontinuation) symptoms, elevations in serum triglyceride levels, elevations in total cholesterol (predominantly LDL cholesterol), decreases in HDL cholesterol, weight gain, decreased haemoglobin and extrapyramidal symptoms.

Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported in association with quetiapine treatment.

The incidences of ADRs associated with quetiapine therapy, are tabulated below (Table 1) according to the format recommended by the Council for International Organizations of Medical Sciences (CIOMS III Working Group 1995). Table 1 ADRs associated with quetiapine therapy The frequencies of adverse events are ranked according to the following: Very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10,000, <1/1000), very rare (<1/10,000) and not known (cannot be estimated from the available data).

4. (2) Somnolence may occur, usually during the first two weeks of treatment and generally resolves with the continued administration of quetiapine. (3) Asymptomatic elevations (shift from normal to ≥ 3 x ULN at any time) in serum transaminase (ALT, AST) or gamma-GT-levels have been observed in some patients administered quetiapine.

These elevations were usually reversible on continued quetiapine treatment. 4). (5) Calculation of Frequency for these ADR’s have only been taken from post- marketing data with the immediate release formulation of quetiapine. 1 mmol/L) on at least one occasion.

(7) An increase in the rate of dysphagia with quetiapine vs. placebo was only observed in the clinical trials in bipolar depression. (8) Based on >7 % increase in body weight from baseline. Occurs predominantly during the early weeks of treatment in adults.

As Mintreleq 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.

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