Section 4.2

New Paragraph at start of section.

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

Section 4.4

New Paragraph at start of section.

Section 4.6

Section 5.1

Clinical Efficacy

Paragraph 8 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 chagned to 25^th October 2011.

Added to table in 4.8:

·         Decreased haemoglobin

·         Somnambulism

·         Palpitations

·         Dyspnea

·         Decreases in total T4, free T4, total T3, free T3 and increases in TSH

·         Vomiting

·         Pyrexia

·         Hypothermia

Also Hepatitis frequency changed;

Paragraph on thyroid hormones updated (under the table in section 4.8);

4.9 Overdose section – additional paragraph inserted;

Date of revision changed to 28th June 2011 

Section 4.2

Additional text under the heading for Elderly.

Section 4.3

Change of text in first paragraph to:  Hypersensitivity to the active substance or to any of the excipients of this product.

Section 4.4

Additional text under the heading ‘Suicide/suicidal thoughts or clinical worsening’

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.

Section 4.4

Additional text under the heading ‘Cardiovascular disease’

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

Section 4.4

New heading ‘Weight’ with new text

Weight

Weight gain has been reported in patients who have been treated with quetiapine, and should be monitored and managed as clinically appropriate as in accordance with utilised antipsychotic guidelines (see Section 4.8 Undesirable effects and 5.1 Pharmacodynamic properties).

Section 4.4

Change of text under the heading ‘Hyperglycaemia’

Section 4.4

New heading ‘Metabolic Risk’ with new text

Metabolic Risk

Given the observed changes in weight, blood glucose (see hyperglycaemia) and lipids seen in clinical studies, there may be possible worsening of the metabolic risk profile in individual patients, which should be managed as clinically appropriate (see also Section 4.8 Undesirable effects).

Section 4.4

Change of text under heading ‘QT Prolongation’

Section 4.5

Change in text

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

Section 4.5

Additional paragraph

Formal interaction studies with commonly used cardiovascular medicinal products have not been performed.

Section 4.8

Change to table and  additional footnotes 19and 20

Additional text 2^nd paragraph after footnotes:

(e.g. akathisia, extrapyramidal disorder, tremor, dyskinesia, dystonia, restlessness, muscle contractions involuntary, psychomotor hyperactivity and muscle rigidity)

Section 10

Revision date of text: 18 February 2011

Section 1

Name change to include strengths and formulation.

Additionally black triangle monitoring:  preventing recurrence in bipolar disorder

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 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 25 mg/day. The dosage should be increased daily with increments of 25 - 50 mg/day until an effective dosage, 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 Cardiovascular:

“Dose reduction or more gradual titration should be considered if this occurs.”

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 SEROQUEL.”

Change of text under the heading Interactions

Additional text under the heading Lipids

To include HDL

Additional text under the heading Elderly patients with dementia-related psychosis

New text: third paragraph.

Additional new text under the headings Concomitant illness and Venous thromboembolism

New text under the heading Additional Information

Section 4.5

Change of text throughout section

Section 4.6

Change of text.

Section 4.7

Change of text.

Section 4.8

Additional text 2^nd paragraph:

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

Change/additional text in frequencies table.

Change of text to footnotes 4, 9, 11, 12 and change of text to 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 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

Change of text

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

Section 5.3

Change of text

Section 10

Section 4.4

New text on QT Prolongation

QT Prolongation

In clinical trials and use in accordance with the SPC, quetiapine was not associated with a persistent increase in absolute QT intervals. However, with overdose (see section 4.9) QT prolongation was observed. As with other antipsychotics, caution should be exercised when quetiapine is prescribed in patients with cardiovascular disease or family history of QT prolongation. Also, caution should be exercised when quetiapine is prescribed with medicines known to increase QTc interval, and concomitant neuroleptics, especially in the elderly, in patients with congenital long QT syndrome, congestive heart failure, heart hypertrophy, hypokalaemia or hypomagnesaemia (see Section 4.5).

Additionally, change of text for sub heading Acute withdrawal reactions

Acute withdrawal reactions

Acute withdrawal symptoms such as insomnia, nausea, headache, diarrhoea, vomiting, dizziness and irritability have been described after abrupt cessation of Seroquel. Recurrence of psychotic symptoms may also occur, and the emergence of involuntary movement disorders (such as akathisia, dystonia and dyskinesia) has been reported. Gradual withdrawal over a period of at least one to two weeks is advisable (see section 4.8).

Additional new last paragraph to section 4.4

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.

Section 4.5

New additional last paragraph text to section

Caution should be exercised when quetiapine is used concomitantly with drugs known to cause electrolyte imbalance or to increase QTc interval.

Section 4.8

Additional side effects in table ‘Very common’

Additional references (footnotes) to table

New text after footnotes of table

Cases of QT prolongation, ventricular arrhythmia, sudden unexplained death, cardiac arrest and torsades de pointes have been reported very rarely with the use of neuroleptics and are considered class effects (see Section 4.4 Special warnings and special precautions for use).

Section 10

New revision date of text: 16 March 2009

Section 4.4 – Additional new text last paragraph

Elderly patients with dementia-related psychosis

Seroquel is not approved for the treatment of patients with dementia-related psychosis.

An approximately 3-fold increased risk of cerebrovascular adverse events have been seen in randomised placebo controlled clinical trials in the dementia population with some atypical antipsychotics. The mechanism for this increased risk is not known. An increased risk cannot be excluded for other antipsychotics or other patient populations. Quetiapine should be used with caution in patients with risk factors for stroke.

Section 4.5

Interaction of quetiapine with protease inhibitors

Section 4.8 - Change to Table

Uncommon - Nervous system disorders

Restless leg syndrome

Very rare - Immune system disorders  

Anaphylactic reaction

Additional reference (9) under Table for

-Diabetes Mellitus

-Blood glucose increased to hyperglycaemic levels

Reference:

(9)                Calculation of frequency for these ADRs have been taken from post-marketing data only.

Section 5.1

Additional/change of text regarding Mechanism of Action

Section 10 – New revision date of text

Section 5.1

Change to therapeutic classification from N05A H to

Therapeutic classification: N05A H04

Change of text in the Mechanism of action:

Quetiapine is an atypical antipsychotic agent. Quetiapine and the active human plasma metabolite, N-desalkyl quetiapine interact with a broad range of neurotransmitter receptors. Quetiapine and N-desalkyl quetiapine exhibit affinity for brain serotonin (5HT₂) and dopamine D₁- and D₂- receptors. Quetiapine exhibits a higher affinity for serotonin (5HT₂) receptors in the brain than it does for dopamine D₁ and D₂ receptors in the brain. Additionally, N-desalkyl quetiapine has high affinity at serotonin 5HT₁ receptors. Quetiapine and N-desalkyl quetiapine also have high affinity at histaminergic and adrenergic a₁ receptors, with a lower affinity at adrenergic a₂-receptors. Quetiapine has no appreciable affinity at cholinergic muscarinic or benzodiazepine receptors.

Quetiapine is active in tests for antipsychotic activity, such as conditioned avoidance. The extent to which the N-desalkyl quetiapine metabolite contributes to the pharmacological activity of Seroquel in humans is not known.

Section 5.2

Change of text throughout the section.

Section 10

Section 5.1

Change to therapeutic classification from N05A H to

Therapeutic classification: N05A H04

Change of text in the Mechanism of action:

Quetiapine is an atypical antipsychotic agent. Quetiapine and the active human plasma metabolite, N-desalkyl quetiapine interact with a broad range of neurotransmitter receptors. Quetiapine and N-desalkyl quetiapine exhibit affinity for brain serotonin (5HT₂) and dopamine D₁- and D₂- receptors. Quetiapine exhibits a higher affinity for serotonin (5HT₂) receptors in the brain than it does for dopamine D₁ and D₂ receptors in the brain. Additionally, N-desalkyl quetiapine has high affinity at serotonin 5HT₁ receptors. Quetiapine and N-desalkyl quetiapine also have high affinity at histaminergic and adrenergic a₁ receptors, with a lower affinity at adrenergic a₂-receptors. Quetiapine has no appreciable affinity at cholinergic muscarinic or benzodiazepine receptors.

Quetiapine is active in tests for antipsychotic activity, such as conditioned avoidance. The extent to which the N-desalkyl quetiapine metabolite contributes to the pharmacological activity of Seroquel in humans is not known.

Section 5.2

Change of text throughout the section.

Section 10

New revision date of text: 30 November 2006