- Approval Id
- ef8dfc8d84d5ef35
- Drug Approval Emc Name
- Seroquel XL 400 mg prolonged-release tablets
- Drug Name
- Seroquel XL 400 mg prolonged-release tablets
- Company Address
- Surrey Technology Centre, 40 Occam Road, Surrey Research Park, Guildford, GU2 7YG
- Company Medical Info Email
- [email protected]
- Atc Code
- N05AH04
- Legal Category
- Prescription only medicine
- Authorisation Holder
- 7. Marketing authorisation holder Luye Pharma Limited Surrey Technology Centre, 40 Occam Road Surrey Research Park Guilford GU2 7YG United Kingdom
- Authorisation Number
- 8. Marketing authorisation number(s) 50 mg: 150 mg: 200 mg: 300 mg: 400 mg: PL 50827/0006 PL 50827/0007 PL 50827/0008 PL 50827/0009 PL 50827/0010
- Authorisation Date
- 9. Date of first authorisation/renewal of the authorisation Date of first authorisation: 10th September 2008 (50 mg, 200 mg, 300 mg, 400 mg) 12th March 2010 (150 mg) Date of latest renewal: 23rd November 2015
- Instruction Authorisation Holder
- 7. Marketing authorisation holder Luye Pharma Limited Surrey Technology Centre, 40 Occam Road Surrey Research Park Guilford GU2 7YG United Kingdom
- Instruction Authorisation Number
- 8. Marketing authorisation number(s) 50 mg: 150 mg: 200 mg: 300 mg: 400 mg: PL 50827/0006 PL 50827/0007 PL 50827/0008 PL 50827/0009 PL 50827/0010
- Instruction Authorisation Date
- 9. Date of first authorisation/renewal of the authorisation Date of first authorisation: 10th September 2008 (50 mg, 200 mg, 300 mg, 400 mg) 12th March 2010 (150 mg) Date of latest renewal: 23rd November 2015
- Instruction Composition
- 2. Qualitative and quantitative composition Seroquel XL 50 mg contains 50 mg quetiapine (as quetiapine fumarate) Seroquel XL 150 mg contains 150 mg quetiapine (as quetiapine fumarate) Seroquel XL 200 mg contains 200 mg quetiapine (as quetiapine fumarate) Seroquel XL 300 mg contains 300 mg quetiapine (as quetiapine fumarate) Seroquel XL 400 mg contains 400 mg quetiapine (as quetiapine fumarate) Excipients with known effect: Seroquel XL 50 mg contains 119 mg lactose (anhydrous) per tablet Seroquel XL 150 mg contains 71 mg lactose (anhydrous) per tablet Seroquel XL 200 mg contains 50 mg lactose (anhydrous) per tablet Seroquel XL 300 mg contains 47 mg lactose (anhydrous) per tablet Seroquel XL 300 mg contains 27 mg sodium per tablet Seroquel XL 400 mg contains 15 mg lactose (anhydrous) per tablet Seroquel XL 400 mg contains 27 mg sodium per tablet For a full list of excipients, see section 6.1.
- Instruction Dosage Form
- 3. Pharmaceutical form Prolonged-release tablet Seroquel XL 50 mg tablets are peach-coloured and engraved with “XR 50” on one side. Seroquel XL 150 mg tablets are white and engraved with “XR 150” on one side. Seroquel XL 200 mg tablets are yellow and engraved with “XR 200” on one side. Seroquel XL 300 mg tablets are pale yellow and engraved with “XR 300” on one side. Seroquel XL 400 mg tablets are white and engraved with “XR 400” on one side.
- Instruction Clinical Particulars
- 4. Clinical particulars 4.1 Therapeutic indications Seroquel XL is indicated for: • treatment of schizophrenia • treatment of bipolar disorder: - For the treatment of moderate to severe manic episodes in bipolar disorder - For the treatment of major depressive episodes in bipolar disorder - For the prevention of recurrence of manic or depressed episodes in patients with bipolar disorder who previously responded to quetiapine treatment. • add-on treatment of major depressive episodes in patients with Major Depressive Disorder (MDD) who have had sub-optimal response to antidepressant monotherapy (see section
- Instruction Pharmacology
- 5. Pharmacological properties 5.1 Pharmacodynamic properties Pharmacotherapeutic group: Antipsychotics; Diazepines, oxazepines and thiazepines ATC code: N05A H04 Mechanism of action Quetiapine is an atypical antipsychotic agent. Quetiapine and the active human plasma metabolite, norquetiapine interact with a broad range of neurotransmitter receptors. Quetiapine and norquetiapine exhibit affinity for brain serotonin (5HT2) and dopamine D1- and D2-receptors. It is this combination of receptor antagonism with a higher selectivity for 5HT2 relative to D2-receptors, which is believed to contribute to the clinical antipsychotic properties and low extrapyramidal side effect (EPS) liability of Seroquel compared to typical antipsychotics. Quetiapine and norquetiapine have no appreciable affinity at benzodiazepine receptors but high affinity at histaminergic and adrenergic alpha1 receptors and moderate affinity at adrenergic alpha2 receptors. Quetiapine also has low or no affinity for muscarinic receptors, while norquetiapine has moderate to high affinity at several muscarinic receptors, which may explain anti-cholinergic (muscarinic effects). Inhibition of NET and partial agonist action at 5HT1A sites by norquetiapine may contribute to Seroquel XL's therapeutic efficacy as an antidepressant. Pharmacodynamic effects Quetiapine is active in tests for antipsychotic activity, such as conditioned avoidance. It also blocks the action of dopamine agonists, measured either behaviourally or electrophysiologically, and elevates dopamine metabolite concentrations, a neurochemical index of D2-receptor blockade. In pre-clinical tests predictive of EPS, quetiapine is unlike typical antipsychotics and has an atypical profile. Quetiapine does not produce dopamine D2-receptor supersensitivity after chronic administration. Quetiapine produces only weak catalepsy at effective dopamine D2-receptor blocking doses. Quetiapine demonstrates selectivity for the limbic system by producing depolarisation blockade of the mesolimbic but not the nigrostriatal dopamine-containing neurones following chronic administration. Quetiapine exhibits minimal dystonic liability in haloperidol-sensitised or drug-naive Cebus monkeys after acute and chronic administration (see section 4.8). Clinical efficacy Schizophrenia The efficacy of Seroquel XL in the treatment of schizophrenia was demonstrated in one 6-week placebo-controlled trial in patients who met DSM-IV criteria for schizophrenia, and one active-controlled Seroquel IR-to-Seroquel XL switching study in clinically stable outpatients with schizophrenia. The primary outcome variable in the placebo-controlled trial was change from baseline to final assessment in the PANSS total score. Seroquel XL 400 mg/day, 600 mg/day and 800 mg/day were associated with statistically significant improvements in psychotic symptoms compared to placebo. The effect size of the 600 mg and 800 mg doses was greater than that of the 400 mg dose. In the 6-week active-controlled switching study the primary outcome variable was the proportion of patients who showed lack of efficacy, i.e. who discontinued study treatment due to lack of efficacy or whose PANSS total score increased 20% or more from randomisation to any visit. In patients stabilised on Seroquel immediate release 400 mg to 800 mg, efficacy was maintained when patients were switched to an equivalent daily dose of Seroquel XL given once daily. In a long-term study in stable schizophrenic patients who had been maintained on Seroquel XL for 16 weeks, Seroquel XL was more effective than placebo in preventing relapse. The estimated risks of relapse after 6 months treatments was 14.3% for the Seroquel XL treatment group compared to 68.2% for placebo. The average dose was 669 mg. There were no additional safety findings associated with treatment with Seroquel XL for up to 9 months (median 7 months). In particular, reports of adverse events related to EPS and weight gain did not increase with longer-term treatment with Seroquel XL. Bipolar disorder In the treatment of moderate to severe manic episodes, Seroquel demonstrated superior efficacy to placebo in reduction of manic symptoms at 3 and 12 weeks, in two monotherapy trials. The efficacy of Seroquel XL was further demonstrated with significance versus placebo in an additional 3-week study. Seroquel XL was dosed in the range of 400 to 800 mg/day and the mean dose was approximately 600 mg/day. Seroquel data in combination with divalproex or lithium in acute moderate to severe manic episodes at 3 and 6 weeks is limited; however, combination therapy was well tolerated. The data showed an additive effect at week 3. A second study did not demonstrate an additive effect at week
- Instruction Pharmaceutical Particulars
- 6. Pharmaceutical particulars 6.1 List of excipients Core Cellulose, microcrystalline Sodium citrate Lactose monohydrate Magnesium stearate Hypromellose 2208 Coating Hypromellose 2910 Macrogol 400 Titanium dioxide (E171) Iron oxide, yellow (E172) (50 mg, 200 mg, and 300 mg tablets) Iron oxide, red (E172) (50 mg tablets) 6.2 Incompatibilities Not applicable. 6.3 Shelf life 3 years 6.4 Special precautions for storage This medicinal product does not require any special storage conditions. 6.5 Nature and contents of container Polychlorotrifluoroethylene and polyvinylchloride with aluminium blister Tablet Strength Carton (pack) contents Blisters 50 mg, 150 mg 200 mg, 300 mg and 400 mg tablets 10 tablets 1 blister of 10 tablets 30 tablets 3 blisters of 10 tablets 50 tablets 10 blisters of 5 tablets 5 blisters of 10 tablets 60 tablets 6 blisters of 10 tablets 100 tablets 10 blisters of 10 tablets 100 blisters of 1 tablet Not all pack sizes may be marketed. 6.6 Special precautions for disposal and other handling No special requirements.
- Instruction Content
- ## Composition
2. Qualitative and quantitative composition Seroquel XL 50 mg contains 50 mg quetiapine (as quetiapine fumarate) Seroquel XL 150 mg contains 150 mg quetiapine (as quetiapine fumarate) Seroquel XL 200 mg contains 200 mg quetiapine (as quetiapine fumarate) Seroquel XL 300 mg contains 300 mg quetiapine (as quetiapine fumarate) Seroquel XL 400 mg contains 400 mg quetiapine (as quetiapine fumarate) Excipients with known effect: Seroquel XL 50 mg contains 119 mg lactose (anhydrous) per tablet Seroquel XL 150 mg contains 71 mg lactose (anhydrous) per tablet Seroquel XL 200 mg contains 50 mg lactose (anhydrous) per tablet Seroquel XL 300 mg contains 47 mg lactose (anhydrous) per tablet Seroquel XL 300 mg contains 27 mg sodium per tablet Seroquel XL 400 mg contains 15 mg lactose (anhydrous) per tablet Seroquel XL 400 mg contains 27 mg sodium per tablet For a full list of excipients, see section 6.1.
## Pharmaceutical Form
3. Pharmaceutical form Prolonged-release tablet Seroquel XL 50 mg tablets are peach-coloured and engraved with “XR 50” on one side. Seroquel XL 150 mg tablets are white and engraved with “XR 150” on one side. Seroquel XL 200 mg tablets are yellow and engraved with “XR 200” on one side. Seroquel XL 300 mg tablets are pale yellow and engraved with “XR 300” on one side. Seroquel XL 400 mg tablets are white and engraved with “XR 400” on one side.
## Clinical Particulars
4. Clinical particulars 4.1 Therapeutic indications Seroquel XL is indicated for: • treatment of schizophrenia • treatment of bipolar disorder: - For the treatment of moderate to severe manic episodes in bipolar disorder - For the treatment of major depressive episodes in bipolar disorder - For the prevention of recurrence of manic or depressed episodes in patients with bipolar disorder who previously responded to quetiapine treatment. • add-on treatment of major depressive episodes in patients with Major Depressive Disorder (MDD) who have had sub-optimal response to antidepressant monotherapy (see section
## Pharmacological Properties
5. Pharmacological properties 5.1 Pharmacodynamic properties Pharmacotherapeutic group: Antipsychotics; Diazepines, oxazepines and thiazepines ATC code: N05A H04 Mechanism of action Quetiapine is an atypical antipsychotic agent. Quetiapine and the active human plasma metabolite, norquetiapine interact with a broad range of neurotransmitter receptors. Quetiapine and norquetiapine exhibit affinity for brain serotonin (5HT2) and dopamine D1- and D2-receptors. It is this combination of receptor antagonism with a higher selectivity for 5HT2 relative to D2-receptors, which is believed to contribute to the clinical antipsychotic properties and low extrapyramidal side effect (EPS) liability of Seroquel compared to typical antipsychotics. Quetiapine and norquetiapine have no appreciable affinity at benzodiazepine receptors but high affinity at histaminergic and adrenergic alpha1 receptors and moderate affinity at adrenergic alpha2 receptors. Quetiapine also has low or no affinity for muscarinic receptors, while norquetiapine has moderate to high affinity at several muscarinic receptors, which may explain anti-cholinergic (muscarinic effects). Inhibition of NET and partial agonist action at 5HT1A sites by norquetiapine may contribute to Seroquel XL's therapeutic efficacy as an antidepressant. Pharmacodynamic effects Quetiapine is active in tests for antipsychotic activity, such as conditioned avoidance. It also blocks the action of dopamine agonists, measured either behaviourally or electrophysiologically, and elevates dopamine metabolite concentrations, a neurochemical index of D2-receptor blockade. In pre-clinical tests predictive of EPS, quetiapine is unlike typical antipsychotics and has an atypical profile. Quetiapine does not produce dopamine D2-receptor supersensitivity after chronic administration. Quetiapine produces only weak catalepsy at effective dopamine D2-receptor blocking doses. Quetiapine demonstrates selectivity for the limbic system by producing depolarisation blockade of the mesolimbic but not the nigrostriatal dopamine-containing neurones following chronic administration. Quetiapine exhibits minimal dystonic liability in haloperidol-sensitised or drug-naive Cebus monkeys after acute and chronic administration (see section 4.8). Clinical efficacy Schizophrenia The efficacy of Seroquel XL in the treatment of schizophrenia was demonstrated in one 6-week placebo-controlled trial in patients who met DSM-IV criteria for schizophrenia, and one active-controlled Seroquel IR-to-Seroquel XL switching study in clinically stable outpatients with schizophrenia. The primary outcome variable in the placebo-controlled trial was change from baseline to final assessment in the PANSS total score. Seroquel XL 400 mg/day, 600 mg/day and 800 mg/day were associated with statistically significant improvements in psychotic symptoms compared to placebo. The effect size of the 600 mg and 800 mg doses was greater than that of the 400 mg dose. In the 6-week active-controlled switching study the primary outcome variable was the proportion of patients who showed lack of efficacy, i.e. who discontinued study treatment due to lack of efficacy or whose PANSS total score increased 20% or more from randomisation to any visit. In patients stabilised on Seroquel immediate release 400 mg to 800 mg, efficacy was maintained when patients were switched to an equivalent daily dose of Seroquel XL given once daily. In a long-term study in stable schizophrenic patients who had been maintained on Seroquel XL for 16 weeks, Seroquel XL was more effective than placebo in preventing relapse. The estimated risks of relapse after 6 months treatments was 14.3% for the Seroquel XL treatment group compared to 68.2% for placebo. The average dose was 669 mg. There were no additional safety findings associated with treatment with Seroquel XL for up to 9 months (median 7 months). In particular, reports of adverse events related to EPS and weight gain did not increase with longer-term treatment with Seroquel XL. Bipolar disorder In the treatment of moderate to severe manic episodes, Seroquel demonstrated superior efficacy to placebo in reduction of manic symptoms at 3 and 12 weeks, in two monotherapy trials. The efficacy of Seroquel XL was further demonstrated with significance versus placebo in an additional 3-week study. Seroquel XL was dosed in the range of 400 to 800 mg/day and the mean dose was approximately 600 mg/day. Seroquel data in combination with divalproex or lithium in acute moderate to severe manic episodes at 3 and 6 weeks is limited; however, combination therapy was well tolerated. The data showed an additive effect at week 3. A second study did not demonstrate an additive effect at week
## Pharmaceutical Particulars
6. Pharmaceutical particulars 6.1 List of excipients Core Cellulose, microcrystalline Sodium citrate Lactose monohydrate Magnesium stearate Hypromellose 2208 Coating Hypromellose 2910 Macrogol 400 Titanium dioxide (E171) Iron oxide, yellow (E172) (50 mg, 200 mg, and 300 mg tablets) Iron oxide, red (E172) (50 mg tablets) 6.2 Incompatibilities Not applicable. 6.3 Shelf life 3 years 6.4 Special precautions for storage This medicinal product does not require any special storage conditions. 6.5 Nature and contents of container Polychlorotrifluoroethylene and polyvinylchloride with aluminium blister Tablet Strength Carton (pack) contents Blisters 50 mg, 150 mg 200 mg, 300 mg and 400 mg tablets 10 tablets 1 blister of 10 tablets 30 tablets 3 blisters of 10 tablets 50 tablets 10 blisters of 5 tablets 5 blisters of 10 tablets 60 tablets 6 blisters of 10 tablets 100 tablets 10 blisters of 10 tablets 100 blisters of 1 tablet Not all pack sizes may be marketed. 6.6 Special precautions for disposal and other handling No special requirements.
- Company Detail Path
- /organization/luye-pharma
