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Sycrest 5mg and 10mg sublingual tablets

Last Updated on eMC 09-Nov-2015 View document  | Lundbeck Limited Contact details

When a pharmaceutical company changes an SPC or PIL, a new version is published on the eMC.  For each version, we show the dates it was published on the eMC and the reasons for change.

Updated on 09-Nov-2015 and displayed until Current

Reasons for adding or updating:

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 28-Oct-2015

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

$0Text has been added and deleted as follows:-$0$0 4.2          Posology and method of administration$0$0Posology$0$0The recommendedstarting dose of Sycrest as monotherapy is 105 mg twice daily. One dose should be taken in the morning and one dose shouldbe taken in the evening. The dose can be reduced to5 increased to 10 mg twice daily based on individual clinical response and tolerability according to clinical assessment. See section 5.1. For combination therapy a startingdose of 5 mg twice daily is recommended. Depending on the clinical response andtolerability in the individual patient, the dose can be increased to 10 mgtwice daily.$0$0$0$0$0Text was added as follows:-$0$04.8          Undesirableeffects$0$0 Description ofselected adverse reactions$0$0Weight increase$0$0In the combinedshort-term and long-term schizophrenia and bipolar mania trials in adults, themean change in body weight for asenapine was 0.8 kg. The proportion ofsubjects with clinically significant weight gain (≥ 7 % weight gainfrom baseline at endpoint) in the short-term schizophrenia trials was5.3 % for asenapine compared to 2.3 % for placebo. The proportion ofsubjects with clinically significant weight gain (≥ 7 % weight gainfrom baseline at endpoint) in the short-term, flexible-dosebipolar mania trials was 6.5 % for asenapine compared to 0.6 %for placebo.$0$0$0$0Text was added as follows:-$0$05.            PHARMACOLOGICAL PROPERTIES$0$0 5.1          Pharmacodynamicproperties$0$0 Clinical efficacy$0$0Clinicalefficacy in bipolar I disorder$0$0The efficacy ofasenapine in the treatment of a DSM-IV manic or mixed episode of bipolar Idisorder with or without psychotic features was evaluated in two similarly designed3-week, randomized, double-blind, flexible-dose,placebo- and active controlled (olanzapine) monotherapy trials involving 488and 489 patients, respectively. All patients met the Diagnostic and StatisticalManual of Mental Disorders, 4th Edition (DSM-IV) diagnostic criteria forbipolar I disorder, current episode manic (DSM-IV 296.4x), or mixed (DSM-IV296.6x) and had a Young Mania Rating Scale (Y-MRS) score of ≥ 20 at screeningand baseline. Patients with rapid cycling were excluded from these studies.Asenapine demonstrated superior efficacy to placebo in the reduction of manicsymptoms over 3 weeks. Point estimates [95 % CI] for the change frombaseline to endpoint in YMRS using LOCF analysis in the two studies were asfollows: $0$0-11.5 [-13.0, -10.0] forasenapine vs -7.8 [-10.0, -5.6] for placebo and $0$0-10.8 [-12.3, -9.3]for asenapine vs -5.5 [-7.5, -3.5] for placebo. $0$0A statisticallysignificant difference between asenapine and placebo was seen as early as day 2.$0$0 Patients from the twopivotal 3 week trials were studied for a further 9 weeks an extension trial.Maintenance of effect during the episode after 12 weeks of randomised treatmentwas demonstrated in this trial.$0$0In onedouble‑blind, fixed‑dose, parallel‑group, 3‑week placebo controlled trial insubjects with bipolar I disorder experiencing an acute manic or mixed episodeinvolving 367 patients of which 126 received placebo, 122 receivedasenapine 5 mg twice daily (BID), and 119 received asenapine 10 mgBID, the primary efficacy hypothesis was met. Both asenapine doses (5 mgBID and 10 mg BID) were superior to placebo and showed statisticallysignificant improvement in change from baseline in Y‑MRS total score atDay 21 compared with placebo. Based upon a LOCF analysis including allpatients treated, the difference in least squares (LS) mean change frombaseline to Day 21 in the Y‑MRS total score between asenapine 5 mgBID and placebo was -3.1 points (95 % CI [‑5.7, ‑0.5]; p‑value =0.0183). The difference in LS mean change from baseline to Day 21 in the Y‑MRStotal score between asenapine 10 mg BID and placebo was ‑3.0 points(95 % CI [‑5.6, -0.4]; p‑value = 0.0244). A statistically significantdifference between asenapine and placebo was seen as early as day 2. Inthis short‑term, fixed‑dose controlled trial there was no evidence of addedbenefit with a 10 mg twice daily dose compared to 5 mg twice daily.$0$0$0$0$0Text was deleted as follows:-$0$05.2          Pharmacokineticproperties$0$0 Pharmacokinetics in specialpopulations$0$0Paediatric population (children and adolescents)$0$0In a second PK studyusing flavoured sublingual tablets, at the 5 mg and10 mg twice daily dose level, asenapine pharmacokinetics in a paediatricpopulation (10 to 17 years of age, inclusive) are similar to those observed inadults. Tthe 10 mg twice daily dose in a paediatric population (10to 17 years of age, inclusive) resulted in an approximate dose-proportionalincrease in asenapine exposure compared to 5 mg twice daily.$0$0 10.          DATE OF REVISION OF THE TEXT$0$0 Changedto: 28 October 2015$0$0 $0

Updated on 01-Nov-2015 and displayed until 09-Nov-2015

Reasons for adding or updating:

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 9 - Date of first authorisation/renewal of the authorisation
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 24-Sep-2015

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

$0Section 4.2 (posology) has been modified as follows:-$0$0From this:-$0$0Paediatric population$0$0Apharmacokinetic study and a short term efficacy and safety study were performedin a paediatric population (ages 10‑17 years) with manic or mixed episodesassociated with bipolar I disorder. The long term safety of Sycrest in children aged below 18 yearshas not been established. Limited safety data with Sycrest are available inpaediatric patients. Currentlyavailable data are described in sections 4.8, 5.1 and 5.2 but no recommendationon a posology can be made.$0$0To this:-$0$0Paediatric population$0$0Apharmacokinetic study and a short term efficacy and safety study were performedin a paediatric population (ages 10‑17 years) with manic or mixed episodesassociated with bipolar I disorder. Long term safety inthis population was explored in a 50‑week, open‑label, uncontrolled extensionstudy. Currently available data aredescribed in sections 4.8, 5.1 and 5.2 but no recommendation on a posologycan be made.$0$0Section 4.8 (undesirable effects)$0$0Weight increase$0$0…In a 3-week, placebo-controlled, randomized, fixed-dose efficacy andsafety trial in paediatric patients 10 to 17 years of age with bipolar Idisorder, the mean change from baseline to endpoint in weight for placebo andasenapine 2.5 mg, 5 mg, and 10 mg twice daily, was 0.48, 1.72, 1.62, and 1.44kg, respectively. The proportion of subjects with clinically significant weightgain (≥ 7 % weight gain from baseline at endpoint Day 21) was 14.1 % for asenapine 2.5 mg twice daily,8.9 % for asenapine 5 mg twice daily, and 9.2 % for asenapine 10 mg twicedaily, compared to 1.1 % for placebo. In the long‑term extension trial (50 weeks), a total of 34.8%of subjects experienced clinically significant weight increase (i.e. ≥7 %increase in body weight at endpoint). Overall mean (SD) weight gain at studyendpoint was 3.5 (5.76 %)kg.$0$0Section 5.1 (Pharmacodynamic properties)$0$0Paediatric population$0$0Asenapine is not indicatedfor the treatment of children and adolescent patients below 18 years (seesection 4.2).$0$0The safety and efficacy ofSycrest was evaluated in 403 paediatric patients with bipolar I disorder whoparticipated in a single, 3-week, placebo-controlled, double-blind trial, ofwhom 302 patients received Sycrest at fixed doses ranging from 2.5 mg to 10 mgtwice daily. Study results showed statistically significant superiority for allthree Sycrest doses in improving the Young Mania Rating Scale (YMRS) totalscore as measured by the change from baseline to Day 21, as compared withplacebo. Long term efficacy could not be established ina 50‑week, uncontrolled, open‑label extension trial. The clinically relevantadverse reactions identified in the paediatric trials were generally similar tothose observed in the adult trials. However, adverse effects of treatment onweight gain and on plasma lipid profile appeared to be greater than effectsobserved in the adult trials. However, the clinical relevance of the efficacyfindings has not been established. No long term data are available with regardto the efficacy and the safety of asenapine in this population.$0$0Section 9 (authorisation/renewal of the authorisation)$0$0Date of first authorisation:       01September 2010$0$0Date of latest renewal: 05 May 2015$0$0Section 10 (date of revision of the text)$0$0$0$024September 2015$0

Updated on 22-Sep-2015 and displayed until 01-Nov-2015

Reasons for adding or updating:

  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 06-Aug-2015

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



·         Section 4.8 – Undesirable effects:

·         The following Adverse Drug Reactions (ADRs) have been deleted from the ‘Unknown’ frequency and assigned the ‘Uncommon’ frequency

·         Allergic reactions

·         Restless legs syndrome

·         Oral mucosal lesions (ulcerations, blistering and inflammation)

·         The following Adverse Drug Reactions (ADRs) have been deleted from the ‘Unknown’ frequency and assigned the ‘Common’ frequency

·         Nausea

·         Salivary hypersecretion

Updated on 28-May-2015 and displayed until 22-Sep-2015

Reasons for adding or updating:

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.6 - Fertility, pregnancy and lactation
  • Change to section 4.7 - Effects on ability to drive and use machines
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 9 - Date of first authorisation/renewal of the authorisation
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 05-May-2015

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

4.2 Posology - para heading have been standardised; paediatrics para has moved to the end of this section$04.4. Special warnings - Parkinson’s disease anddementia with Lewy bodies$0$0Physicians should weigh therisks versus the benefits when prescribing antipsychotic medicinal products, including Sycrest, to patients with Parkinson’s disease ordementia with Lewy Bodies (DLB) since both groups may be at increased risk ofneuroleptic malignant syndrome as well as having an increased sensitivity toantipsychotics. Manifestation of this increased sensitivity can includeconfusion, obtundation, postural instability with frequent falls, in additionto extrapyramidal symptoms.$0$04.5 Interactions - at the end of the section removed: To ensure optimalabsorption, eating and drinking should be avoided for 10 minutes afteradministration.$0$0$0$04.6 Pregnancy - neonates changed to newborn infants throughout section.$0$04.7 Effects on ability todrive and use machines - changed to:-$0$0$0$0No studies on theeffects on the ability to drive and use machines have been performed. Asenapine may cause somnolence and sedation.Therefore, patients should be cautioned about driving and using machines operatingmachinery, including motor vehicles,until they are reasonably certain that Sycrest therapy does not affect themadversely. $0$04.8 Undesirable effects: tabulated entry for "system organ class" removed.$0$05.1 Pharmacodynamic properties$0$0Mechanism of action$0$0The mechanism of action of asenapine aswith other medicinal products having efficacy in bipolar disorder is not fullyunderstood.$0$05.2 Pharmacokinetic properties$0$0Distribution$0$0Asenapine israpidly distributed and has a large volume of distribution (approximately 1700l l20‑25 L/kg), indicating extensive extravasculardistribution. Asenapine is highly bound (95 %) to plasma proteins,including albumin and α1-acid glycoprotein.$0$010. Date of revision$0$0Amended to 5 may 2015$0$0$0$0

Updated on 13-Jan-2015 and displayed until 28-May-2015

Reasons for adding or updating:

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties

Date of revision of text on the SPC: 20-Nov-2014

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Section 4.2 – Additional information on special populations

Paediatric population  now reads

A pharmacokinetic study and a short term efficacy and safety study was performed in adolescent patients a paediatric population (ages 10-17 years) with manic or mixed episodes associated with bipolar I disorder. The long term safety of Sycrest in children aged below 18 years has not been established. Limited safety data with Sycrest are available in paediatric patients. Currently available data are described in sections 4.8, 5.1 and 5.2 but no recommendation on a posology can be made.

 

Sections 4.8, 5.1 and 5.2- Now include new data from further clinical trials in the paediatric population

 

 

 

Section 4.8 Undesirable effects

Addition of:

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

 

Updated on 05-Nov-2014 and displayed until 13-Jan-2015

Reasons for adding or updating:

  • Removal of black triangle

Date of revision of text on the SPC: 21-Feb-2013

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Black triangle has been removed - everything else (including revision date) remains the same

Updated on 18-Apr-2013 and displayed until 05-Nov-2014

Reasons for adding or updating:

  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 21-Feb-2013

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:

Revision of the following text in Section 4.8, with the addition of angiodoema.

"There have been postmarketing reports of serious hypersensitivity reactions in patients treated with asenapine, including anaphylactic/anaphylactoid reactions, angioedema, swollen tongue and swollen throat (pharyngeal oedema). "

Updated on 29-Jan-2013 and displayed until 18-Apr-2013

Reasons for adding or updating:

  • Change to section 4.8 - Undesirable effects
  • Change to section 9 - Date of first authorisation/renewal of the authorisation

Date of revision of text on the SPC: 13-Dec-2012

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:


Section 4.8

Addition of 'salivary hypsecretion' frequency 'unknown' in the table of undesirable effects.

Updated on 19-Nov-2012 and displayed until 29-Jan-2013

Reasons for adding or updating:

  • Change to section 4.8 - Undesirable Effects
  • Change to section 10 date of revision of the text

Date of revision of text on the SPC: 17-Oct-2012

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:

In Section 4.8 (undesirable effects), sinus tachycardia has been added to the table under Cardiac conditions, with a frequency of 'uncommon'

In Section 9, Date of revision is: 17 October 2012 

Updated on 07-Aug-2012 and displayed until 19-Nov-2012

Reasons for adding or updating:

  • Change to section 4.8 - Undesirable Effects
  • Change to section 10 date of revision of the text

Date of revision of text on the SPC: 27-Jun-2012

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:




Section 4.8 Undesirable effects

Addition of:

 

Restless legs syndrome, Nausea, Oral mucosal lesions (ulcerations, blistering and

inflammation) (frequency not known).

 

In addition the following sentence has been revised (added text in red).

 

There have been postmarketing reports of serious hypersensitivity reactions in patients treated with asenapine, including anaphylactic/ anaphylactoid reactions, such as swollen tongue and swollen throat (pharyngeal oedema).

Updated on 16-Jan-2012 and displayed until 07-Aug-2012

Reasons for adding or updating:

  • New SPC for new product

Legal Category:POM

Black Triangle (CHM): YES

Company contact details

Lundbeck Limited

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Address

Building K1, Timbold Drive, Kents Hill, Milton Keynes, MK7 6BZ

Fax

+44 (0)1908 638959

Medical Information e-mail
Telephone

+44 (0)1908 649 966

Medical Information Direct Line

+44 (0)1908 638 972

Customer Care direct line

+44 (0)1908 638 935

Before you contact this company: often several companies will market medicines with the same active ingredient. Please check that this is the correct company before contacting them. Why?

Active ingredients

asenapine maleate

Legal categories

POM - Prescription Only Medicine

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