Section 4.6

Section 5.1

Clinical Safety

Paragraph 5 amended to:

In all short-term placebo-controlled monotherapy trials in patients with a baseline neutrophil count ≥1.5 X 10⁹/L, the incidence of at least one occurrence of a shift to neutrophil count <1.5 X 10⁹/L, was 1.9% in patients treated with quetiapine compared to 1.3% in placebo-treated patients. The incidence of shifts to >0.5 - <1.0 X 10⁹/L was the same (0.2%) in patients treated with quetiapine as with placebo-treated patients. In all clinical trials (placebo-controlled, open-label, active comparator) in patients with a baseline neutrophil count ≥1.5 X 10⁹/L, the incidence of at least one occurrence of a shift to neutrophil count <1.5 X 10⁹/L was 2.9% and to <0.5 X 10⁹/L was 0.21% in patients treated with quetiapine.

Section 10

Date of revision changed to 25^th October 2011

Added to table in 4.8:

4.9 Overdose section – additional paragraph inserted;

Date of Revision changed to 28th June 2011

Section 4.4

Additional text under the heading Cardiovascular:

A slower titration regimen could be considered in patients with underlying cardiovascular disease.

Change of text under the heading QT prolongation – first paragraph.

Section 4.5

Change of text in 2nd paragraph:

It is also not recommended to consume grapefruit juice while on quetiapine therapy.

Section 4.8

Change to table of side effects and additional footnotes.

Section 4.9

Change to text under the heading ‘Management’

Section 10

Revision date of text: 18 February 2011

Section 1, 2, 3, 8 and 9

Includes information on 150mg strength

Section 4.1

New text regarding:

Add-on treatment of major depressive episodes in patients with Major Depressive Disorder (MDD)

Section 4.2

New text first paragraph:

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

New text regarding:

Add-on treatment of major depressive episodes in patients with Major Depressive Disorder (MDD)

Additional text under the heading Elderly:

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.

Section 4.4

New text in section regarding MDD

Additional text first and second paragraph under heading:

As Seroquel XL is indicated for the treatment of schizophrenia, bipolar disorder and add-on treatment of major depressive episodes in patients with MDD, the safety profile should be considered with respect to the individual patient’s diagnosis and the dose being administered.

Long-term efficacy and safety in patients with MDD has not been evaluated as add-on therapy, however long-term efficacy and safety has been evaluated in adult patients as monotherapy (see section 5.1 Pharmacodynamic properties).

Additional text under heading  Suicide/suicidal thoughts or clinical worsening

Additional text under heading  Extrapyramidal symptoms

Additional text under heading Somnolence and dizziness

New text under heading Weight

Revised  text under heading  Hyperglycaemia

New text under heading  Metabolic Risk

Section 4.8

Change of text in table:

Psychiatric disorders – Common

Addition of  Suicidal ideation and suicidal behaviour ¹⁹

Change of text in table (moved from ‘Investigation’ section of table:

Vascular disorders – Rare

Addition of  Venous thromboembolism¹

Additional footnotes numbers 19 and 20 under table

Section 5.1

New text regarding MDD under  the Clinical Efficacy section  and under the Clinical Safety heading

Section 10

New revision date of text: 26 August 2010

Section 4.1

Information regarding Recurrence Prevention.

Section 4.2

Additional new text regarding Recurrence Prevention

Section 4.2

Paediatric information

Section 4.2

Additional new text:

Renal impairment

Dosage adjustment is not necessary in patients with renal impairment.

Change of text:

Hepatic impairment

Quetiapine is extensively metabolised by the liver. Therefore, Seroquel XL should be used with caution in patients with known hepatic impairment, especially during the initial dosing period. Patients with known hepatic impairment should be started with 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.

Section 4.3

Additional new text.

Section 4.4

Paediatric information  - Children and adolescents (10 to 17 years of age)

Section 4.4

Additional text under the heading Extrapyramidal symptoms
”In placebo controlled clinical trials of adult patients quetiapine was associated….”

Change of text under the heading Tardive dyskinesia

Additional text under the heading Severe neutropenia

“There is no apparent dose relationship. During post-marketing experience, resolution of leucopenia and/or neutropenia has followed cessation of therapy with quetiapine.”

Additional text under the heading Lipids

To include HDL

Additional new text under the headings Concomitant illness and Venous thromboembolism

Section 4.8

Additional text 2^nd paragraph:

‘As with other antipsychotics, weight gain, syncope,…..’

Change/additional text in frequencies table.

Additional text to footnotes  9, 11, 12 and new footnote 18

Section 4.8

Additional new text regarding Paediatric information  - Children and adolescents (10 to 17 years of age)

Including table and footnotes.

Section 4.9

Change to text first paragraph

Section 5.1

Change of text throughout section

Additional new text regarding Paediatric information  - Children and adolescents (10 to 17 years of age)

Section 5.2

Additional new text regarding Paediatric information  - Children and adolescents (10 to 17 years of age)

Section 10

Section 4.4

Additional penultimate paragraph text regarding hepatic effects.

Hepatic effects:

If jaundice develops, Seroquel XL should be discontinued.

Additional paragraph regarding Lipids and change of text regarding withdrawal

Lipids
Increases in triglycerides and cholesterol have been observed in clinical trials with quetiapine (see section 4.8). Lipid increases should be managed as clinically appropriate.

Withdrawal:

Acute withdrawal symptoms such as nausea, vomiting, insomnia, headache, diarrhoea, dizziness and irritability have been described after abrupt cessation of high doses of Seroquel. Gradual withdrawal over a period of at least one to two weeks is advisable (see Section 4.8).

Section 4.8

Additional side effect under heading ‘Immune system disorders’

Very rare:    Anaphylactic reaction⁶

Additional side effect under ‘Nervous system disorders’

Uncommon:   restless leg syndrome

Additional side effect under ‘General disorders and administration site conditions’

Very common:  Withdrawal (discontinuation) symptoms ^{1, 10}

Additional side effect under ‘Investigations’

Very common:  Elevations in serum triglyceride levels ¹¹

                        Elevations in total cholesterol (predominantly LDL cholesterol) ¹²

Additional references (footnotes) numbers 10,11,12 to table

Section 10

New revision date of text: 1 April 2009