RISPERDAL 1 MGML

Israel - English - Ministry of Health

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Active ingredient:
RISPERIDONE
Available from:
J-C HEALTH CARE LTD
ATC code:
N05AX08
Pharmaceutical form:
SOLUTION
Composition:
RISPERIDONE 1 MG / 1 ML
Administration route:
PER OS
Prescription type:
Required
Manufactured by:
JANSSEN PHARMACEUTICA N.V.,BELGIUM
Therapeutic group:
RISPERIDONE
Therapeutic area:
RISPERIDONE
Therapeutic indications:
Risperdal is indicated for the management of schizophrenia and manifestation of psychotic disorders. The antipsychotic efficacy of Risperdal was established in short-term (6 to 8-weeks) controlled trials of schizophrenic inpatients. Risperdal is also effective in maintaining the clinical improvement during continuation therapy in patients who have shown an initial treatment response.Risperdal is indicated for the short-term treatment (up to 6 weeks) of persistent aggression in patients with moderate to severe Alzheimer’s dementia unresponsive to non-pharmacological approaches and when there is a risk of harm to self or others. Conduct and other disruptive disorders: Treatment of behavioral disorders expressed by impulse control disorders or self-alienated-aggressive or treatment-requiring behavioral disorders with reduced or substandard intelligence. Treatment should not be given to children under the age of 5 years.Risperdal is indicated for the treatment of mania in bipolar disorder. These episodes are cha
Authorization number:
114 74 29633 00
Authorization date:
2014-06-30

Documents in other languages

Patient Information leaflet Patient Information leaflet - Arabic

24-01-2021

Patient Information leaflet Patient Information leaflet - Hebrew

29-01-2019

עעבקנהזןולעטמרופ " לערשואוקדבנונכותותואירבהדרשמי ודי

5.12

םיחקורהתונקתיפלןכרצלןולע ) םירישכת ( משתה " ו

) X ( אפורםשרמבתבייחוזהפורתה

הפורתבשמתשתםרטבופוסדעןולעהתאןויעבארק :

. ותרוצורישכתהםש

רפסיר לד 1 מ " תוילבטג לדרפסיר 2 מ " תוילבטג

לדרפסיר 3 מ " תוילבטג לדרפסיר 4 מ " תוילבטג

לדרפסיר 1 מ " מבג " היתשלהסימתל

. בכרה : רמוחה ) םי ( ליעפה ) םי ( םתומכו / םזוכיר :

risperidone 1 מ " ג risperidone 2 מ " ג

risperidone 3 מ " ג risperidone 4 מ " ג

לכ 1 מ " ליכמהיתשלהסימתל risperidone 1 מ " ג

ןוגכםיביכרמליכמהרישכתל : רכוס , ןרתנ , וכוםטרפסא , ' ןונימדיחיבםתלוכתתאןייצלשי .

תוילבטלדרפסיר

Lactose monohydrate, Maize starch, Microcrystallinecellulose, Hypromellose 2910 15 mPa.s,

Magnesiumstearate, Colloidal anhydrous silica, Sodium laurylsulfate, Hypromellose 2910 5

mPa.s, Propylene glycol,Titanium dioxide (1) , Talc (1) , Quinoline yellow (2) , Indigotindisulfonate

aluminum lake (3) , Orange yellowS aluminum lake (4)

Onlyin 2 mg, 3 mg, 4 mg tablets , (2) Onlyin 3 mg, 4 mg tablets, (3) Onlyin 4mgtablets,

Onlyin 2 mg tablets,

לדרפסירתוילבט 1 מ " ג , 2 מ " ג , 3 מ " וג - 4 מ " תוליכמג 131 מ " ג , 130 מ " ג , 195 מ " וג - 260 מ " זוטקלג

המאתהבטרדיהונמ .

היתשלהסימתלדרפסיר :

Tartaric acid, Benzoic acid, Sodium hydroxide,Purified water

. תיאופרתוליעפ ] ןושלבהלועפהןפואותוליעפהלערצקרבסה הלוחלתנבומ :[

תיטיופרתהצובק : יטוכיספיטנארישכת

תויטוכיספתוערפהלשםינימסתבלופיטל , היצנמדלשםייטוכיספםייוטיבב הינרפוזיכסבו , ל הערפהבלופיט

תירלופיבתינאמ . הלחמהבצמבהבטההתארמשלידכבחווטךוראלופיטלדעוימףסונב . ןכומכ

טלדעוימלדרפסיר תוגהנתהתוערפהבלופי תומילאןוגכ , תונפקותותויביסלופמיא תימצע ליגלעמםידליב 5

םינש ו ב םילבגומהםירגובמ הניחבמ תילכש .

X ( רישכתבשמתשהלןיאיתמ ?

) X ( העודיםאשמתשהלןיא ךל ורתהיביכרממדחאלתושיגר הפ

( לופיטהתלחתהינפלאפורבץעוויהלילבמהפורתבשמתשהלןיא

) X ( ואןוירהבךנהםא שמתשהלךלרתומםאהטילחירשאאפורבץעוויהלשיןוירהלסנכיהלתננכתמ

לדרפסירב . דער , תושקונ םירירש ו / השלוחוא , תוינונשי , הדרח , ואהמישניישק םילולעהליכאיישק

שחרתהל םישנלודלונשתוקוניתב בושמתשהש ןוירההלשןורחאהשילשבלדרפסיר .

( הקינמךיניהרשאכהזרישכתבישמתשתלא . הזהרקמבאפורביצעוויה .

לבוסךנהםא / דוקפתביוקילמרבעבתלבסשואת :

) X ( בלה ו/ וא םדהילכ , אמגודל : דוחייב רידסאלבלבצק , יקתאלתילמשחהכלוה הנ לש בלה ךניהםאוא

בלהלשתילמשחהתוליעפהתאתונשמרשאתופורתלטונ םדץחלרתייבלופיטלתופורתלטונוא . תליטנ

לולעםדץחלרתייבלופיטלתופורתםעדחילדרפסיר ה ךומנםדץחללםורגל

) X ( תוילכה

) X ( דבכה

) X ( לעבךנהםא / בתוקללןוכיסימרוגת יחומץבש , לבוסךנהםאלשמל / הובגםדץחלמת , תוערפה

חומבםדהילכבתויעבמואםדהתכרעמב .

) X ( לבוסךנהםא / ואןוסניקרפהתלחממת מ היצנמד יווליפוגםע .

) X ( לבוסךנהםא / תרכוסהתלחממת .

) X ( לבוסךנהםא / היספליפאמת .

) X ( לבוסךנהםא / מת שישואםדישירקתורצוויה ךתחפשמב םדישירקתורצוויהלשהירוטסיה . םדישירק

לדרפסירבםישמתשמהםילוחבונחבוהםיילגרבותואירב . תויהלםילולעתואירבםדישירק

םיינלטק .

7 . ךלשםויםויהייחלעהפורתהעיפשתךיא ?

) X ( תונרעבםוגפללולעוזהפורתבשומישה בכרבגוהנלאלץלמומןכלעו , אלותונכוסמתונוכמליעפהלאל

תונרעתבייחמהתוליעפלכבקוסעל , אפורהרושיאבאלא .

) X ( םעלופיטהתפוקתבםיפירחתואקשמואתונייתותשלןיא לדרפסיר . לולעלדרפסיר תעפשהתאריבגהל

לוהוכלאה .

) (X לקשמבהילעלםורגללולעלדרפסיר , הסנ / תוניתמבלוכאלי .

. תורהזא :

בםירקחמ היצנמדמםילבוסהםישישקםילוח דימסורופםעבולישבואודבלחקלנהלדרפסיריכוארה , רושק

תוומלןוכיסבהילעב . לטונךנהםאאפורלחוודלשי / דימסורופת . תנתינההפורתהניהדימסורופ , םיתיעל ,

םדץחלבלופיטל הובג יטלוא םילזונלשהריגאמתעבונהםינושףוגיקלחלשתוחיפנבלופ .

היצנמדמםילבוסהםישישקםילוחב , וניחבה ב הםינימסת םיאב : השלוחואילטנמהבצמבימואתפיוניש

תימואתיפ השוחתןדבאוא / לומנתשוחת תימואתיפ םינפב , ב ואתועורז ב םיילגר , דוחייב ףוגהלשדחאדצב

לבלובמרובידוא . שחךנהםא / וללהםינימסתהמדחאבה , רצקןמזלוליפא , תידיימאפורלתונפלשי .

( לדרפסירםילטונהםילוחבתורידנםיתיעל , ךומנרפסמבןחבוה , ןכוסמןפואב , םישרדנהםינבלםדיאתלש

םימוהיזינפמהנגהל . ךלשםינבלהםדהיאתתריפסתאקודביךאפורוןכתי .

עדיי /י םינבלםדיאתלשהכומנהריפסמרבעבתלבסםאאפורהתא ) שומישבקעומרגנוןכתירשא

תורחאתופורתב .(

. תויתפורתןיבתובוגת

לטונךנהםא / תפסונהפורתת , התעהזתרמגםאוא ידכלפטמהאפורלחוודלךילעתרחאהפורתבלופיט

יאואםינוכיסעונמל - בוגתמםיעבונהתוליעי תויתפורתןיבתו ) . X ( דחוימב , תואבהתוצובקהמתופורתיבגל :

( תיזכרמהםיבצעהתכרעמלעתועיפשמהתופורת ) ןוגכ : העגרהלתופורת , הנישל , םירישכת

םימיוסמ תויגרלאדגנ , םייטוקרנםיבאכיככשמוןואכידדגנםימיוסמםירישכת ( יבגהללולעלדרפסירןכש ר

ןתעפשהתא ולאתופורתלש .

( ןוסניקרפתלחמבלופיטלתופורת ןימפודלשםיטסינוגאומכ ) ןוגכ : הפודובל (

( םדץחלרתיבלופיטלתופורת , ןכש תליטנ םעדחין לולעלדרפסיר ה םורגל הכומנהמרלתדרלםדהץחלל

ידמ

( תוליעפהלעעיפשהלתולולעהתופורת בלהלשתילמשחה לשמלומכ ) קראלךא ( : תופורת

הירלמל , בלהבצקבתוערפהבלופיטלתופורת ) ןידיניווקאמגודל ( , היגרלאלתופורת , ואןואכידדגנתופורת

תורחאתויטוכיספיטנאתופורת , תונתשמתופורת ףוגבםיחלמהןזאמלעתועיפשמהתורחאתופורתוא ) ןרתנ ,

גלשא ן , םויזנגמ .(

( ןיפזמברק , ואהיספליפאבלופיטלרקיעבתשמשמההפורת ףקתהב ארקנהםינפבםיבאכלשרומח

שלושמהבצעהלשהיגלרינ . לופיטהתאתקספההתעהזשואןיפזמברקלטונךנהםאאפורלעידוהלשי

וזהפורתב .

וןיטסקואולפ ןיטסקורפ , תופורת ופיטלרקיעבתושמשמה בל ןואכיד ו ב הדרחתוערפהןווגמ , תולעהלםילולע

תא תמר םדבלדרפסירה , ןכלע , לטונךנהםאאפורלעידוהלשי / תאתקספההתעהזשואולאתופורתת

ולאתופורתבלופיטה .

ןידיטמיס ןידיטנרו , הביקהתויצמוחתדרוהלתושמשמהתופורתיתש , תמרתאטעמתולעהלתולולע

לדרפסירהתעפשהתאונשישריבסאלךאםדבלדרפסירה .

( ןיצימורתיראל , הקיטויביטנא , םדבלדרפסירהתמרלעהעפשהןיא .

טל טמריפו הנרגימוהיספליפאבלופיטלתשמשמה , רלעתיתועמשמהעפשהןיא םדבלדרפסירהתמ .

( תושמשמהליזפנודוןימטנלגל היצנמידבלופיטל , פשהןיא לדרפסירלעהע .

( ןיסקוגידלעואהינאמבלופיטלתושמשמהטאורפלווואםויתיללעהעפשהשישהארנאללדרפסירל ,

בלתויעבבלופיטלהפורת .

( דימסורופםעבולישבלדרפסירתליטנ ) םדץחלרתיובלתקיפסיאבלופיטל ( לולע ה תועפשהלםורגל

תוקיזמ דמםילבוסהםישישקםילוחב היצנמ . לטונךנהםאאפורלחוודלשי / דימסורופת .

10 . יאוולתועפות

הפורתהלשהיוצרהתוליעפלףסונב , עיפוהלתולולעהבשומישהןמזב תועפות יאוול .

דאמתוצופניאוולתועפות ) לצאושחרתהשולאכ מרתוי - 1 ךותמ 10 םישמתשמ :(

הנישלשבצמבראשיהלואםדריהלישוק .

ניקרפ באטבתמהןוס : תיטיאואהיוקלתויתעונת , םיצווכמואםישקונםירירשלשהשוחת ) םימרוגה

העונתבתוויעל ( תףאםיתיעלו אבהוולמההעונתבןואפיקלשהשוח ןכמרחאלהעונתהלוחת . םינמיס

לולכלםילוכיםיפסונ : תיטיאםיילגרתרירג , החונמןמזבדער , וקורהלשרתיתשרפה / תרבגהוא

םינפהתעבהדוביאורוירה .

תוינונשי תונרעבהעיגפוא

שארבאכ

תוצופניאוולתועפות ) לצאושחרתהשולאכ רתוי מ - 1 ךותמ 100 םישמתשמ :(

תואירתקלד , תונופמיסתקלד ) סיטיכנורב ( , תוררקתהלשםינימסת , םיסוניסבםוהיז , יכרדבםוהיז

ןתשה , םיינזאתקלד , תעפשתיומדהלחמ .

דרפסיר לוכיל ןיטקלורפןומרוההלשםיכרעבהיילעלםורגל , םדתוקידבבתולגלןתינשיפכ , רשא

לוכי ה , ךא חרכהבאל , םימוטפמיסתעפוהלםורגל . םימוטפמיס לולכלםילוכיהלא : לשתוחפנתה

םירבגלצאםיידשה , רחאינימדוקפתרסוחואהילערומשלואהפקזלעיגהלתלוכירסוח . םישנב

מוטפמיסה לולכלםילוכיםי : םיידשבתוחונרסוחתשוחת , םיידשהמבלחתשרפה , ואתסוורדעה

רוזחמהלשתורחאתוערפה ישדוחה .

לקשמבהיילע , רבגומןובאית , ןובאיתהתתחפהואתרבגה .

הנישתוערפה , תונבצע , ןואכיד , הדרח , החונמרסוח .

הינוטסיד : אלותכשוממואתיטיאתוצווכתהברעמהבצמוהז םירירשהלשתינוצר . הזבצמשתורמל

ףוגבקלחלכברעללוכי ) ו אטבתהללוכי הניקתאלהביציב ( , םינפהירירשועפשויללכךרדב . הזבצמ

אלתועונתללוכ תוניקת םייניעהלש , ה הפ , ה ואןושל ה תסל .

תרוחרחס .

היזניקסיד : ועונתלולכללוכירשאתוינוצראלםירירשתועונתברעמהבצמוהז תויוצווכתהואת

תונשנותורזוח , ואתויתיווע תויולתפתה .

דער .

תלפרועמהייאר , תימחלהתקלדואםייניעתקלד .

ריהמבלבצק , הובגםדץחל , המישנרצוק .

ןורגבאכ , לועיש , ףאהמםומיד , ףאבשדוג .

ןטבבתוחוניאואבאכ , תואקה , תוליחב , תוריצע , םילושלש , לוכיעיישק , בוי הפבש , םיינישבאכ .

החירפ , רועבתוימומדא .

םירירשתוצווכתה , םירירשואתומצעיבאכ , בגיבאכ , םיקרפמיבאכ .

ןתשתפילד ) קפאתהלתלוכירסוח .(

ףוגהתוחפנתה , ה םיידי , וא ה םיילגר , םוח , הזחבתוחוניא , השלוח , תופייע , באכ .

תוליפנ .

תוצופנאליאוולתועפות ) אושחרתהשולאכ לצ רתוי מ - 1 ךותמ 1000 םישמתשמ :(

המישנהיכרדבםוהיז , ןתשהתיחופלשבםוהיז , םייניעתקלד , םידקשתקלד , לשיתיירטפםוהיז

םיינרופיצה , רועבםוהיז , ףוגהלשקלחוארועהלשדיחירוזאללבגומהםוהיז , ילאריוםוהיז , תקלד

האצותכתמרגנהרוע הפישחמ ל תידרק .

יאתתמרבהדירי ה םד ה םימוהיזדגנכהנגהבםיעייסמהםינבל , הכומנםינבלםדיאתתריפס , הדירי

תויסטהתמרב ) םומידתריצעבםיעייסמשםדיאת ( , הימנא , יאתתמרבהדירי ה םד ה םימודא , היילע

םיליפוניזואאב ) םינבלםדיאתלשגוס ( םדב .

תיגרלאהבוגת .

תרכוסלשהרמחהואתרכוס , םדברכוסלשההובגהמר , םימלשתמזגומהייתש .

לקשמדוביא , ןובאיתדוביאמעבונהךומנףוגלקשמואהנוזתתת .

תמרבהיילע ה םדבלורטסלוכ .

םמורמחורבצמ ) הינאמ ( , לובלב , ינימרציבהדירי , םיטויס .

היזניקסידבידראט : לתויתיוועואתוימואתפתועונת םינפבתוטלשנא , ב ואןושל ב לשםירחאםיקלח

ףוגה . תאוהדימב / ןושלהלשתוינוצראלתועונתהווחה , ה והפ ה םינפ , עדי / דימךאפורתאי . ןכתיי

ךלהרויאפורהו לדרפסירבלופיטהתאקיספהל .

חמלםדתקפסהלשתימואתפהקספה ) ואץבש " ינימ " ץבש .(

יוריגלהבוגתרסוח , הרכהדוביא , מר הרכהלשהכומנה .

תויוצווכתה , תויופלעתה .

ףוגהלשםיקלחזיזהלידימתךרוצ , יוושבתוערפה ה לקשמ , הניקתאלהיצנידרואוק , תרוחרחס

הדימעבצמלרבעמב , בלתמושתבתוערפה , רובידבתויעב , שוחדוביא ה ןיקתאלםעטשוחואםעט ,

עגמובאכלרועהתשוחתבהדירי , ץוצקעתשוחת , תוריקד רועבלומינוא .

רואלםייניעהלשרתיתושיגר , תושביםייניע , תועמדתשרפהבהרבגה , םייניעבתוימומדא .

תרוחרחסתשוחת ) וגיטרו ( , םיינזואבםילוצלצ , םיינזואבאכ .

רידסאלבלבצק , בלהלשןותחתהקלחלןוילעהקלחהןיבשהכלוהבהערפה , אלתילמשחהכלוה

בלהלשהניקת , וורמתכראה ח QT בלהלש , יטיאבלבצק , הקידב ילמשחהחתמהלשהניקתאל

בלב ) ואםרגוידרקורטקלא ECG ( , תוניקתאלבלתומיעפלתועדומ ) תויצטיפלפ .(

ךומנםדץחל , הדימעלרבעמבךומנםדץחל ) ךכמהאצותכ , לדרפסירםילטונהםימיוסמםישנא

השלוחשוחלםילולע , רבעמבףלעתהלםילולעואתרוחרחס ימואתפןפואבהבישיואהדימעבצמל ( ,

הקמסה .

ןוזמתפיאשמהאצותכתואירתקלד , תואירבשדוג , יכרדבשדוג ה המישנ , האירהמשורשרתולוק ,

םירוחרח , בהערפה לוק , המישנהיכרדבהערפה .

םוהיז ב ואםייעמ ב ןטב , הטילשרסוח ) קפאתהלתלוכירסוח ( האוצןתמב , דואמהשקהאוצ , ישוק

עולבל , לוכיעהתכרעמבםיזגלשהרבגה .

תלרח ) רועבהחירפ ( , דוריג , רעישתרישנ , רועהיוביע , המזקא , רועבשבוי , רועהעבציוניש , הנקא ,

םישקשק , רועתויעב , רועבםיעצפ .

תומרבהיילע CPK ) ןיטארק זאניקופסופ ( םדב , רירשבקזנואהעיגפמהאצותכררחתשמהםיזנא .

החונת / יצי אלהב הניקת , םיקרפמתוישק , םיקרפמתוחפנתה , םירירשתשלוח , ראווציבאכ .

ןתשןתמבתופיכת , תלוכירסוח תתל ןתש , ןתשןתמבםיבאכ .

הפקזלעיגהלתלוכייא , ערזתטילפבתוערפה .

תסוורדעה , רוזחמהלשתרחאהערפהלכואתסווהלשרוחיא ישדוחה .

םירבגבםיידשתוחתפתה , בלחתשרפה םיידשהמ , ינימדוקפתרסוח , םיידשבתוחוניא , השרפה

קיתרנהמ .

םינפהתוחפנתה , ה הפ , ה ואםייניע ה םייתפש .

תורומרמצ , ףוגהתרוטרפמטבהיילע .

הכילההתרוצביוניש .

אמצתשוחת , הבוטאלהשוחת , דוריחורבצמ , תוחוניא .

םדבדבכהמתוזנימאסנארטתומרבהיילע , תמרבהיילע GGT ) יזנא לימטולגאמגםשבדבכם

סארפסנארט ( םדב , ימיזנאתמרבהיילע ה םדבדבכ .

לופיטתלבקןמזבבאכ .

תורידניאוולתועפות ) לצאושחרתהשולאכ רתוי מ - 1 ךותמ 10000 םישמתשמ :(

םוהיז .

ןתשהחפנתאתסוומהןומרוהלשהניקתאלהשרפה .

ןתשברכוסתואצמיה , םדבהכומנרכוסתמר , גירטתמר םדבההובגםידירציל ) ןמוש .(

שגררדעה , ינימקופיסלעיגהלתלוכירסוח ) המזגרוא .(

הריאממתיטפלוריונתנומסת ) Neuroleptic malignant syndrome :( לובלב , ואדוביא הדירי

הרכה , הרומחםירירשתושקונוהובגםוח .

חמבשםדהילכבתויעב .

המוק ) תמדרת ( תנזואמיתלבתרכוסמהאצותכ .

שארהלשדער .

המוקואלג ) הובגיניעךותץחל ( , בתוערפה תעונת םייניעה , םייניעלוגלג , םייפעפעהילושבםורק .

ןיקתאלבלבצק .

םיילגרבםדישירק , תואירבםדישירק .

המישניישק ) םושנלתלוכירסוח ( הנישןמזב , תיחטשוהריהמהמישנ .

בלבלבתקלד , םייעמתמיסח .

החופנןושל , יתפש תוקודסםי , הלעהחירפ רוע הפורתהתליטנלהרושקה .

קוריפ םירירשיבאכורירשהיביס .

תסווברוחיא , םיידשבתוטולבהתלדגה , םיידשתלדגה , םיידשהמהשרפה .

ףוגהתרוטרפמטבהדירי , םיילגרבוםיידיברוקתשוחת .

תופורתמהלימגינימסת

םייניעהורועהלשהבהצה ) תבהצ .(

רתויבתורידניאוולתועפות ) לצאושחרתהשולאכ מתוחפ - 1 ךותמ 10,000 םישמתשמ :(

תנזואמאלתרכוסמםיעבונהםייחינכסמםיכוביס .

המישניישקלליבוהלוןורגהתאברעלהלוכירשאתוחיפנבהוולמהרומחתיגרלאהבוגת .

העודייתלבתורידתילעביאוולתועפות :

פסמבתנכוסמהדירי הנגהלשרדנהגוסהמםינבלםדיאתר מ םימוהיזינפ .

הפירחתיגרלאהבוגת םוחבתנייפואמה , הפבתוחיפנ , םינפב , ןושלבואםייתפשב , המישנרצוק ,

דוריג , םדץחלתליפנםימעפלורועהלעהחירפ

ףוגהתאתנכסמהרתויבתמזגומםימתייתש .

ןילוסניאתמרבהיילע םדב ) וה תאתסוומהןומר ףוגברכוסהתומר ( .

הדימעבצמלרבעמבתוריהמבלתומיעפ .

תכשוממהפקז תיגרוריכתוברעתהשורדלהלולערשא

רועהתושקתה .

( תדחוימתוסחייתהתובייחמהתועפות :

אפורלןולעבןיוצמלםאתהבאלומיהזףיעס [

( נפבינוצראלתוויעשחרתהללולעלדרפסירםעחווטךוראשומישב םי . שחרתמהזכתוויעוהרקמב , שי

ץעייתהל אפורהםע .

( לובליב , הרכההתמרבהדירי , םוח ואהובג ק י םירירשןויש שחרתהלםילולע ) דאמרידנ ( - , ולאםא

םישחרתמ הנפ / תידיימאפורלי ותואעדייו לטונךנהיכ / לדרפסירת .

( בגרכוסתמרלשםירקמוחוודתורידנםיתיעל םדבההו . שחךנהוהדימבאפורלתונפלשי / םינימסתבה

ןוגכ : תרבגומהנתשהוארבגומאמצ .

ווחהתאםא ה םיאבהמדחא , אפורלדימהנפ , הפורתלשיגרהתאוןכתיי : רועבהחירפ , דרג , ואהמישנרצוק

םינפהלשתוחיפנ

רתייןונימתלטנוהדימב , הםימוטפמיסהמדחאתאשיגרתוןכתיי םיאב : תונריעבהדירי , תוינונשי , דער

םזגומ , םזגומםירירשןוישיק , ךומנםדץחלובלהבצקבהיילע . בלבהניקתאלתילמשחהכלוהלשםירקמ

עטקמתכראה QT ( וחוודםגםיסוכריפו . םעדחיתורחאתופורתתליטנבםגשחרתהללוכירתייןונימ

לדרפסיר . ווחךניהםא ה ימוטפמיסהמדחאתא וראותשם , אפורלדימהנפ .

( תאוהדימבםלואולאתועפותמתחאףאושיגריאללדרפסירבםישמתשמהםישנאהתיברמ / שחה

הנפיהשלכיאוולתעפותב / חקורלואאפורלי .

שיגרמךניהובשהרקמלכב / עפותה ו הזןולעבונייוצאלשיאוולת , תיללכהךתשגרהביונישלחםאוא , ךילע

ץעייתהל דימאפורהםע .

. ןונימ ] : םשרמםערישכתבהזףיעסיולימ רישכתלכלשופוגללקשייאפור [

) X ( דבלבאפורהתארוהיפלןונימ .

) X ( לעעבקנשיפכםיבוצקםינמזבוזהפורתבשמתשהלשי - לפטמהאפורהידי .

) X ( ההנמהלערובעלןיא החכשנשהנמלעתוצפלידכהלופכהנמתחקלןיאותצלמומ .

) X ( אפורהתארוהיפלעתאזולדרפסירלשתחפומןונימבשמתשהלשיםישישקםילוחב .

) X ( םידלילללכךרדבתדעוימהניאוזהפורת . ליגלעמםידליבתוגהנתהתוערפהבלפטלןתינ

5 תהלןתינובילמינימהליגהםינש אפורהידילעעבקיתורחאתויוותהללדרפסירבלופיטליח .

( תוילכואדבכתויעבמםילבוסהםילוח : יפלעתאזולדרפסירלשתתחפומהנמלוטילשיולאםילוחב

אפורהתוארוה .

( רישכתבלופיטהתפוקתתליחתבהנמתחקלתחכשםא , דימהחכשנשהנמהתאתחקלשי

תרכזנשכ , ו האבההנמהלעגלדל .

ותליחתלךומסאלולופיטהתפוקתךלהמבהנמתחכשםא , לעגלדלשי ה הנמהתאתחקלוהחכשנשהנמ

יונישאלללופיטבךישמהלוליגרההדעומבהאבה , אפורההרוהשיפכ .

) X ( הרקמלכב , לשןונימלערובעלןיא 16 מ " םוילג

. בלםיש !

) X ( תאקיספהלןיא תושרופמךלהרוהאפורםאאלאהפורתהםעלופיטה . םורגלהלולעלופיטתקספה

הלחמהלשםימוטפמיסהתרזחל .

) X ( תקספהלעהרויאפורהוהדימב ה לופיט , יתגרדהןפואבןונימהתאןיטקהלשי אפורהתוארוהיפלע .

. שומישהןפוא :

ראהןיבואםעלדרפסירהתאתחקלןתינ תוחו .

תוילבטלדרפסירבשומישה

( סועללןיא !

שי םימםעתוילבטהתאעולבל

היתשלהסימתלדרפסירבשומישה

שיהיתשלהסימתהתא בברעל םע לכ לוהוכלאליכמוניאשהקשמ , התדבלמ .

הדידמקרזמםעהעיגמהסימתה . תקיודמהתומכהתאדודמלידכהדידמהקרזמבשמתשהלשי .

תואבהתוארוההיפלעלע :

רויא 1 : תאחותפלתנמלע קקפהלעץוחללשיקובקבה ןועשהןוויכדגנבוביסידכךותהטמיפלכ .

רויא 2 : הדידמהקרזמתאסינכהלשי קובקבהךותל , טבזוחאל ךושמלוהנותחתהתעב הנוילעהתעבטהתא

ךילעשםימרגילימואםירטילילימהרפסמלםיאתמהןמיסהדע לוטיל .

רויא 3 : הנותחתהתעבטבהזיחאךות , ותואןקורלוקובקבהןמהדידמהקרזמתאאיצוהלשי , לע לעהציחלידי

הטמיפלכהנוילעהתעבטה , ל לכ ילוהוכלאאלהקשמ ) דבלמ הת .(

הדידמהקרזמתאףוטשלוקובקבהתארוגסלשי

םימב .

. לכותדציכ / לופיטהתחלצהלעייסלי

( ורתבלופיטהקיספהלןיאךתואירבבצמברופישלחםאםג אפורםעתוצעייתהאללהפ .

. הלערהענמ !

וםידלילשםדיגשיהלץוחמרוגסםוקמברומשלשיתרחאהפורתלכווזהפורת / ידילעותוקוניתוא - ךכ ענמת /י

הלערה .

הפורתהןמדליעלבתועטבםאוארתיתנמתלטנםא , ןוימרדחלדימהנפ לש תיב - תזיראאבהוםילוח

ךתאהפורתה .

לא האקהלםורגת אפורמתשרופמהארוהאלל !

. ךתלחמבלופיטלךלהמשרנוזהפורת . קיזהלהלולעאיהרחאהלוחב . ךיבורקלוזהפורתןתיתלא , ךינכש

ךירכמוא .

. ךשוחבתופורתלוטילןיא !

הנמהותיוותהקודב םעפלכב הפורתלטונךניהש . בכרה / םהלקוקזךניהםאםייפקשמי .

. א הנסח :

( רדחהתרוטרפמטב ) °C 15-30 ) ( X ( איפקהלןיא היתשלהסימתהתא

הזיראהיאנתיפלםג / םיצלמומההנסחא , דבלבתלבגומהפוקתלתורמשנתופורת .

רישכתהלשהגופתהךיראתלבלםישלאנ ! קפסלשהרקמלכב , הפורתהתאךלקפיסשחקורבץעוויהלךילע .

אבתונושתופורתןסחאלןיא הזיראהתו .

סמ ' הפורתהםושיר

לדרפסיר 1 מ " תוילבטג 1447828260-01

לדרפסיר 2 מ " תוילבטג 1447928261-01

לדרפסיר 3 מ " תוילבטג 1448028262-01

לדרפסיר 4 מ " תוילבטג 144812826301

לדרפסיר 1 מ " מבג " היתשלהסימתל 1147429633-00

ןרצי :

טלדרפסיר תוילב : י א גליסןסנ , הניטל , הילטיא

לדרפסיר היתשלהסימת :י א הסריבהקיטבצמרפןסנ , היגלב

םושירהלעב : ג ' תלהיסיי ' עברק " םייפשץוביקמ

Risperdal

®

1.

NAME OF THE MEDICINAL PRODUCT

RISPERDAL

1mg film coated tablets

RISPERDAL

2mg film coated tablets

RISPERDAL

3mg film coated tablets

RISPERDAL

4mg film coated tablets

RISPERDAL

1mg/ml ORAL SOLUTION

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION

Film coated Tablets:

Each film-coated tablet contains 1 mg of risperidone

Each film-coated tablet contains 2 mg of risperidone

Each film-coated tablet contains 3 mg of risperidone

Each film-coated tablet contains 4 mg of risperidone

Excipients with known effect:

Each 1mg film-coated tablet contains 131 mg lactose monohydrate

Each 2mg film-coated tablet contains 130 mg lactose monohydrate and 0.05mg orange yellow

S aluminium lake (sunset yellow) E110

Each 3mg film-coated tablet contains 195 mg lactose monohydrate

Each 4mg film-coated tablet contains 260 mg lactose monohydrate

For the full list excipients, see section 6.1

Oral Solution:

1 ml oral solution contains 1 mg of risperidone

Excipients with known effect

1 ml oral solution contains 2 mg benzoic acid (E 210).

For the full list of excipients, see section 6.1

3.

PHARMACEUTICAL FORM

Film coated Tablets:

Film-coated tablets for oral use:

1 mg risperidone as white half-scored oblong biconvex tablets of 10.5 mm x 5 mm;

2 mg risperidone as orange half-scored oblong biconvex tablets of 10.5 mm x 5 mm;

3 mg risperidone as yellow half-scored oblong biconvex tablets of 13.5 mm x 5 mm;

4 mg risperidone as green half-scored oblong biconvex tablets 15 mm x 6.5 mm;

The score line is only to facilitate breaking for ease of swallowing and not to divide into equal

doses.

Film-coated tablets are etched on one side with RIS 1, RIS 2, RIS 3, and RIS 4 respectively.

Additionally JANSSEN may be etched on the other side

Oral Solution:

The Oral solution 1 mg/ml is clear and colorless.

4.

CLINICAL PARTICULARS

4.1.

Therapeutic Indications

Risperdal

(risperidone)

indicated

management

schizophrenia,

manifestations

psychotic

disorders.

antipsychotic

efficacy

Risperdal

established in short-term (6 to 8-weeks) controlled trials of schizophrenic inpatients.

Risperdal

is also effective in maintaining the clinical improvement during continuation

therapy in patients who have shown an initial treatment response

Risperdal

is indicated for the short-term treatment (up to 6 weeks) of persistent aggression in

patients with moderate to severe Alzheimer’s dementia unresponsive to non-pharmacological

approaches and when there is a risk of harm to self or others.

Conduct and other disruptive disorders:

Treatment of behavioral disorders expressed by impulse control disorders or self-alienated-

aggressive

treatment-requiring

behavioral

disorders

with

reduced

substandard

intelligence. Treatment should not be given to children under the age of 5 years.

Risperdal is indicated for the treatment of mania in bipolar disorder. These episodes are

characterized by symptoms such as elevated, expansive or irritable mood, inflated self-esteem,

decreased need for sleep, pressured speech, racing thoughts, distractibility, or poor judgment,

including disruptive or aggressive behaviors.

4.2.

Posology and method of administration

RISPERDAL

may be given as oral tablets or oral solution.

Risperdal 0.5mg tabs are not registered in Israel, therefore the Risperdal 1mg/ml Oral solution

should be used for 0.5mg dose adjustments.

Schizophrenia

Adults

RISPERDAL

may be given once daily or twice daily.

Patients should start with 2 mg/day RISPERDAL

. The dosage may be increased on the

second day to 4 mg. From then on the dosage can be maintained unchanged, or further

individualized, if needed. Most patients will benefit from daily doses between 4 and 6 mg. In

some patients, a slower titration phase and a lower starting and maintenance dose may be

appropriate.

Doses above 10 mg/day have not been shown to be superior in efficacy to lower doses and

may cause extrapyramidal symptoms. Since the safety of doses above 16 mg/day has not been

evaluated, doses above this level should not be used.

A benzodiazepine may be added to RISPERDAL

when additional sedation is required.

Elderly (65 years and older)

A starting dose of 0.5 mg twice daily is recommended. This dosage can be individually

adjusted with 0.5 mg twice daily increments to 1 to 2 mg twice daily.

Adolescents (13-17 years)

A starting dose of 0.5 mg daily is recommended, administered as a single-daily dose either in

the morning or evening. If indicated, this dosage can then be adjusted at intervals not less than

24 hours in increments of 0.5 or 1 mg/day, as tolerated, to a recommended dose of 3 mg/day.

Efficacy has been demonstrated at doses between 1 and 6 mg/day. Doses higher than 6 mg/day

have not been studied.

Patients experiencing persistent somnolence may benefit from administering half the daily

dose twice daily.

Children

Experience in schizophrenia is lacking in children aged less than 13 years of age.

Bipolar mania

Adults

RISPERDAL

should be administered on a once daily schedule, starting with 2 or 3 mg.

Dosage adjustments, if indicated, should occur at intervals of not less than 24 hours and in

dosage increments of 1 mg per day. Efficacy was demonstrated in flexible doses over a range

of 1 to 6 mg per day.

As with all symptomatic treatments, the continued use of RISPERDAL

must be evaluated

and justified on an ongoing basis.

Children and Adolescents

(10-17 years of age)

A starting dose of 0.5mg once daily is recommended, administered as a single-daily dose in

either the morning or evening. If indicated, this dosage can then be adjusted at intervals not

less than 24 hours in increments of 0.5 or 1 mg/day, as tolerated, to a recommended dose of

2.5 mg/day. Although efficacy has been demonstrated at doses between 0.5 and 6 mg/day. No

additional benefit was seen above 2.5 mg/day, and higher doses were associated with more

adverse events. Doses higher than 6 mg/day have not been studied.

Patients experiencing persistent somnolence may benefit from administering half the daily

dose twice daily.

As with all symptomatic treatments, the continued use of RISPERDAL

must be evaluated

and justified on an ongoing basis.

Experience is lacking in bipolar mania in children less than 10 years of age.

Psychotic manifestations of dementia

A starting dose of 0.25 mg twice daily is recommended. This dosage can be individually

adjusted by increments of 0.25 mg twice daily not more frequently than every other day, if

needed. The optimum dose is 0.5 mg twice daily for most patients. Some patients, however,

may benefit from doses up to 1 mg twice daily

RISPERDAL should not be used more than 6 weeks in patients with persistent aggression in

Alzheimer's dementia. During treatment, patients must be evaluated frequently and regularly,

and the need for continuing treatment reassessed.

Conduct and other disruptive behavior disorders (5-18 years of age)

Subjects

50 kg

A starting dose of 0.5 mg once daily is recommended. This dosage can be individually

adjusted by increments of 0.5 mg once daily not more frequently than every other day, if

needed. The optimum dose is 1 mg once daily for most patients. Some patients, however, may

benefit from 0.5 mg once daily while others may require 1.5 mg once daily.

Subjects < 50 kg

A starting dose of 0.25 mg once daily is recommended. This dosage can be individually

adjusted by increments of 0.25 mg once daily not more frequently than every other day, if

needed. The optimum dose is 0.5 mg once daily for most patients. Some patients, however,

may benefit from 0.25 mg once daily while others may require 0.75 mg once daily.

As with all symptomatic treatments, the continued use of RISPERDAL

must be evaluated

and justified on an ongoing basis.

Experience is lacking in children aged less than 5 years of age.

Renal and Hepatic Impairment

Patients with renal impairment have less ability to eliminate the active antipsychotic fraction

than

normal

adults.

Patients

with

impaired

hepatic

function

have

increases

plasma

concentration of the free fraction of risperidone.

Irrespective of the indication, starting and consecutive dosing should be halved, and dose

titration should be slower for patients with renal or hepatic impairment.

RISPERDAL

should be used with caution in these groups of patients.

Method of administration

Risperdal is for oral use. Food does not affect the absorption of RISPERDAL

Upon discontinuation, gradual withdrawal is advised. Acute withdrawal symptoms, including

nausea, vomiting, sweating, and insomnia have very rarely been described after abrupt

cessation of high doses of antipsychotic medicines (see section 4.8) . Recurrence of psychotic

symptoms may also occur, and the emergence of involuntary movement disorders (such as

akathisia, dystonia and dyskinesia) has been reported.

Switching from other antipsychotics.

When

medically

appropriate,

gradual

discontinuation

previous

treatment

while

RISPERDAL

therapy is initiated is recommended. Also, if medically appropriate, when

switching patients from depot antipsychotics, initiate RISPERDAL

therapy in place of the

next scheduled injection. The need for continuing existing anti-Parkinson medications should

be re-evaluated periodically.

4.3.

Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1

4.4.

Special Warnings and Precautions for Use

Elderly patients with dementia

Increased mortality in elderly people with dementia

In a meta-analysis of 17 controlled trials of atypical antipsychotics, including RISPERDAL,

elderly patients with dementia treated with atypical antipsychotics have an increased mortality

compared to placebo. In placebo-controlled trials with oral RISPERDAL in this population,

the incidence of mortality was 4.0% for RISPERDAL-treated patients compared to 3.1% for

placebo-treated patients. The odds ratio (95% exact confidence interval) was 1.21 (0.7, 2.1).

The mean age (range) of patients who died was 86 years (range 67-100). Data from two large

observational

studies

showed

that

elderly

people

with

dementia

treated

with

conventional antipsychotics are also at a small increased risk of death compared with those

who are not treated. There are insufficient data to give a firm estimate of the precise

magnitude of the risk and the cause of the increased risk is not known. The extent to which the

findings of increased mortality in observational studies may be attributed to the antipsychotic

drug as opposed to some characteristic(s) of the patients is not clear.

Concomitant use with furosemide

Risperdal

placebo-controlled

trials

elderly

patients

with

dementia,

higher

incidence of mortality was observed in patients treated with furosemide plus risperidone

(7.3%; mean age 89 years, range 75-97) when compared to patients treated with risperidone

alone (3.1%; mean age 84 years, range 70-96) or furosemide alone (4.1%; mean age 80 years,

range 67-90). The increase in mortality in patients treated with furosemide plus risperidone

was observed in two of the four clinical trials.Concomitant use of risperidone with other

diuretics (mainlythiazide diuretics used in low dose) was not associated with similar findings.

pathophysiological

mechanism

been

identified

explain

this

finding,

consistent pattern for cause of death observed. Nevertheless, caution should be exercised and

the risks and benefits of this combination or co-treatment with other potent diuretics should be

considered prior to the decision to use. There was no increased incidence of mortality among

patients taking other diuretics as concomitant treatment with risperidone. Irrespective of

treatment, dehydration was an overall risk factor for mortality and should therefore be

carefully avoided in elderly patients with dementia.

Cerebrovascular adverse events (CVAE)

An approximately 3-fold increased risk of cerebrovascular adverse events have been seen in

randomized placebo controlled clinical trials in the dementia population with some atypical

antipsychotics. The pooled data from six placebo-controlled studies with RISPERDAL in

mainly elderly patients (>65 years of age) with dementia showed that CVAEs (serious and

non-serious, combined) occurred in 3.3% (33/1,009) of patients treated with risperidone and

1.2% (8/712) of patients treated with placebo. The odds ratio (95% exact confidence interval)

was 2.96 (1.34, 7.50). The mechanism for this increased risk is not known. An increased risk

cannot be excluded for other antipsychotics or other patient populations.

RISPERDAL should be used with caution in patients with risk factors for stroke.

The risk of CVAEs was significantly higher in patients with mixed or vascular type of

dementia when compared to Alzheimer’s dementia. Therefore, patients with other types of

dementias than Alzheimer’s should not be treated with risperidone.

Physicians are advised to assess the risks and benefits of the use of RISPERDAL in elderly

patients with dementia, taking into account risk predictors for stroke in the individual patient.

Patients/caregivers should be cautioned to immediately report signs and symptoms of potential

CVAEs such as sudden weakness or numbness in the face, arms or legs, and speech or vision

problems. All treatment options should be considered without delay, including discontinuation

of risperidone.

RISPERDAL should only be used short term for persistent aggression in patients with

moderate to severe Alzheimer’s dementia to supplement non-pharmacological approaches

which have had limited or no efficacy and when there is potential risk of harm to self or

others.

Patients should be reassessed regularly, and the need for continuing treatment reassessed.

Orthostatic hypotension

alpha-blocking

activity

risperidone,

(orthostatic)

hypotension

occur,

especially during the initial dose-titration period. Clinically significant hypotension has been

observed postmarketing with concomitant use of risperidone and antihypertensive treatment.

RISPERDAL

should be used with caution in patients with known cardiovascular disease

(e.g. heart failure, myocardial infarction, conduction abnormalities, dehydration, hypovolemia,

or cerebrovascular disease), and the dosage should be gradually titrated as recommended (see

section 4.2 Posology and method of administration). A dose reduction should be considered if

hypotension occurs.

Leukopenia, neutropenia, and agranulocytosis

Events of leucopenia, neutropenia and agranulocytosis have been reported with antipsychotic

agents, including RISPERDAL

. Agranulocytosis has been reported very rarely (< 1/10,000

patients) during post-marketing surveillance.

Patients with a history of a clinically significant low white blood cell count (WBC) or a drug-

induced leukopenia/neutropenia should be monitored during the first few months of therapy

and discontinuation of RISPERDAL

should be considered at the first sign of a clinically

significant decline in WBC in the absence of other causative factors.

Patients with clinically significant neutropenia should be carefully monitored for fever or other

symptoms or signs of infection and treated promptly if such symptoms or signs occur. Patients

with

severe

neutropenia

(absolute

neutrophil

count

<

should

discontinue

RISPERDAL

and have their WBC followed until recovery.

Tardive dyskinesia/extrapyramidal symptoms (TD/EPS)

Medicines with dopamine receptor antagonistic properties have been associated with the

induction

tardive

dyskinesia

characterized

rhythmical

involuntary

movements,

predominantly of the tongue and/or face. The onset of extrapyramidal symptoms is a risk

factor

tardive

dyskinesia.

signs

symptoms

tardive

dyskinesia

appear,

discontinuation of all antipsychotic drugs should be considered.

Neuroleptic Malignant Syndrome (NMS)

Neuroleptic Malignant Syndrome, characterized by hyperthermia, muscle rigidity, autonomic

instability, altered consciousness and elevated serum creatine phosphokinase levels has been

reported

occur

with

antipsychotics.

Additional

signs

include

myoglobinuria

(rhabdomyolysis)

acute

renal

failure.

this

event,

antipsychotics,

including

RISPERDAL

, should be discontinued.

Parkinson’s disease and dementia with Lewy bodies

Physicians

should

weigh

risks

versus

benefits

when

prescribing

antipsychotics,

including RISPERDAL

, to patients with Parkinson’s disease or Dementia with Lewy Bodies

(DLB). Parkinson’s disease may worsen with risperidone. Both groups may be at increased

risk

Neuroleptic

Malignant

Syndrome

well

having

increased

sensitivity

antipsychotic

medicinal

products;

these

patients

were

excluded

from

clinical

trials.

Manifestation

this

increased

sensitivity

include

confusion,

obtundation,

postural

instability with frequent falls, in addition to extrapyramidal symptoms.

Hyperglycaemia and diabetes mellitus

Hyperglycemia, diabetes mellitus and exacerbation of pre-existing diabetes have been reported

during treatment with RISPERDAL

In some cases, a prior increase in body weight has been

reported which may be a predisposing factor. Association with ketoacidosis has been reported

very rarely and rarely with diabetic coma. Appropriate clinical monitoring is advisable in

accordance

with

utilized

antipsychotic

guidelines.

Patients

treated

with

atypical

antipsychotic, including RISPERDAL

should be monitored for symptoms of hyperglycemia

(such as polydipsia, polyuria, polyphagia and weakness) and patients with diabetes mellitus

should be monitored regularly for worsening of glucose control.

Weight gain

Significant weight gain has been reported with RISPERDAL use. Weight should be monitored

regularly

Hyperprolactinaemia

Hyperprolactinaemia is a common side-effect of treatment with RISPERDAL. Evaluation of

the prolactin plasma level is recommended in patients with evidence of possible prolactin-

related side-effects (e.g. gynaecomastia, menstrual disorders, anovulation, fertility disorder,

decreased libido, erectile dysfunction, and galactorrhea).

Tissue culture studies suggest that cell growth in human breast tumours may be stimulated by

prolactin. Although no clear association with the administration of antipsychotics has so far

been demonstrated in clinical and epidemiological studies, caution is recommended in

patients with relevant medical history. RISPERDAL should be used with caution in patients

with pre-existing hyperprolactinaemia and in patients with possible prolactin-dependent

tumours.

QT prolongation

QT prolongation has very rarely been reported post-marketing. As with other antipsychotics,

caution

should

exercised

when

risperidone

prescribed

patients

with

known

cardiovascular

disease,

family

history

prolongation,

bradycardia,

electrolyte

disturbances (hypokalaemia, hypomagnesaemia), as it may increase the risk of arrythmogenic

effects, and in concomitant use with medicines known to prolong the QT interval.

Seizures

RISPERDAL

should be used cautiously in patients with a history of seizures or other

conditions that potentially lower the seizure threshold.

Priapism

Priapism may occur with RISPERDAL treatment due to its alpha-adrenergic blocking effects.

Body temperature regulation

Disruption of the body’s ability to reduce core body temperature has been attributed to

antipsychotic medicines. Appropriate care is advised when prescribing RISPERDAL® to

patients who will be experiencing conditions which may contribute to an elevation in core

body

temperature,

e.g., exercising

strenuously,

exposure

extreme

heat,

receiving

concomitant treatment with anticholinergic activity, or being subject to dehydration.

Antiemetic effect

An antiemetic effect was observed in preclinical studies with risperidone. This effect, if it

occurs in humans, may mask the signs and symptoms of overdosage with certain medicines

or of conditions such as intestinal obstruction, Reye’s syndrome, and brain tumour.

Renal and hepatic impairment

Patients with renal impairment have less ability to eliminate the active antipsychotic fraction

than adults with normal renal function. Patients with impaired hepatic function have increases

in plasma concentration of the free fraction of risperidone (see section 4.2).

Venous thromboembolism

Cases of venous thromboembolism (VTE) have been reported with antipsychotic drugs. Since

patients treated with antipsychotics often present with acquired risk factors for VTE, all

possible

risk

factors

should

identified

before

during

treatment

with

RISPERDAL

and preventative measures undertaken.

Intraoperative Floppy Iris Syndrome

Intraoperative Floppy Iris Syndrome (IFIS) has been observed during cataract surgery in

patients

treated

with

medicines

with

alpha1a-adrenergic

antagonist

effect,

including

RISPERDAL

(see section 4.8).

IFIS may increase the risk of eye complications during and after the operation. Current or

past use of medicines with alpha1a-adrenergic antagonist effect should be made known to

the ophthalmic surgeon in advance of surgery. The potential benefit of stopping alpha1

blocking therapy prior to cataract surgery has not been established and must be weighed

against the risk of stopping the antipsychotic therapy.

Paediatric population

Before risperidone is prescribed to a child or adolescent with conduct disorder they should

be fully assessed for physical and social causes of the aggressive behaviour such as pain

or inappropriate environmental demands.

The sedative effect of risperidone should be closely monitored in this population because

of possible consequences on learning ability. A change in the time of administration of

risperidone could improve the impact of the sedation on attention faculties of children and

adolescents.

Risperidone was associated with mean increases in body weight and body mass index

(BMI). Baseline weight measurement prior to treatment and regular weight monitoring are

recommended. Changes in height in the long-term open-label extension studies were

within expected age-appropriate norms. The effect of long-term risperidone treatment on

sexual maturation and height has not been adequately studied.

Because of the potential effects of prolonged hyperprolactinemia on growth and sexual

maturation in children and adolescents, regular clinical evaluation of endocrinological

status should be considered, including measurements of height, weight, sexual maturation,

monitoring of menstrual functioning, and other potential prolactin-related effects.

Results from a small post-marketing observational study showed that risperidone-exposed

subjects between the ages of 8-16 years were on average approximately 3.0 to 4.8 cm

taller than those who received other atypical antipsychotic medications. This study was

not adequate to determine whether exposure to risperidone had any impact on final adult

height, or whether the result was due to a direct effect of risperidone on bone growth, or

the effect of the underlying disease itself on bone growth, or the result of better control of

the underlying disease with resulting increase in linear growth.

During treatment with risperidone regular examination for extrapyramidal symptoms and

other movement disorders should also be conducted.

For specific posology recommendations in children and adolescents see section 4.2.

Excipients

The

film-coated

tablets

contain

lactose.

Patients

with

rare

hereditary

problems

galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should

not take this medicine. (Pertains only to the film-coated tablets.)

Contains sunset yellow (E110). May cause allergic reactions. (pertains only to the 2 mg

film coated tablets).

The 1 ml oral solution

contains benzoic acid (E 210). Increase in bilirubinaemia following its

displacement from albumin may increase neonatal jaundice which may develop into

kernicterus (non-conjugated bilirubin deposits in the brain tissue).

4.5.

Interaction with Other medicinal products and Other Forms of Interaction

Pharmacodynamic-related Interactions

Drugs known to prolong the QT interval

with

other

antipsychotics,

caution

advised when

prescribing

risperidone

with

medicinal products known to prolong the QT interval, such as antiarrhythmics (e.g.,

quinidine,

dysopiramide,

procainamide,

propafenone,

amiodarone,

sotalol),

tricyclic

antidepressant (i.e., amitriptyline), tetracyclic antidepressants (i.e., maprotiline), some

antihistamines, other antipsychotics, some antimalarials (i.e., quinine and mefloquine),

and with medicines causing electrolyte imbalance (hypokalaemia, hypomagnesaemia),

bradycardia, or those which inhibit the hepatic metabolism of risperidone. This list is

indicative and not exhaustive.

Centrally-acting drugs and alcohol

Risperidone should be used with caution in combination with other centrally-acting

substances notably including alcohol, opiates, antihistamines and benzodiazepines due to

the increased risk of sedation.

Levodopa and dopamine agonists

RISPERDAL

may antagonize the effect of levodopa and other dopamine agonists. If

this combination is deemed necessary, particularly in end-stage Parkinson’s disease, the

lowest effective dose of each treatment should be prescribed.

Drugs with hypotensive effect

Clinically significant hypotension has been observed post-marketing with concomitant use

of risperidone and antihypertensive treatment.

Paliperidone

Concomitant

oral

RISPERDAL

with

paliperidone

recommended

paliperidone is the active metabolite of risperidone and the combination of the two may

lead to additive active antipsychotic fraction exposure.

Pharmacokinetic-related interactions

Food does not affect the absorption of RISPERDAL.

Risperidone is mainly metabolized through CYP2D6, and to a lesser extent through

CYP3A4. Both risperidone and its active metabolite 9-hydroxy- risperidone are substrates

of P-glycoprotein (P-gp). Substances that modify CYP2D6 activity, or substances strongly

inhibiting or inducing CYP3A4 and/or P-gp activity, may influence the pharmacokinetics

of the risperidone active antipsychotic fraction.

Strong CYP2D6 inhibitors

Co-administration of RISPERDAL with a strong CYP2D6 inhibitor may increase the

plasma concentrations of risperidone, but less so of the active antipsychotic fraction.

Higher doses of a strong CYP2D6 inhibitor may elevate concentrations of the risperidone

active

antipsychotic fraction

(e.g.,

paroxetine, see below).

expected

that other

CYP2D6

inhibitors,

such

quinidine,

affect

plasma

concentrations

risperidone in a similar way. When concomitant paroxetine, quinidine, or another strong

CYP2D6 inhibitor, especially at higher doses, is initiated or discontinued, the physician

should re-evaluate the dosing of RISPERDAL.

CYP3A4 and/or P-gp inhibitors

Co-administration of RISPERDAL with a strong CYP3A4 and/or P-gp inhibitor may

substantially

elevate

plasma

concentrations

risperidone

active

antipsychotic

fraction. When concomitant itraconazole or another strong CYP3A4 and/or P-gp inhibitor

is initiated or discontinued, the physician should re-evaluate the dosing of RISPERDAL.

CYP3A4 and/or P-gp inducers

Co-administration of RISPERDAL with a strong CYP3A4 and/or P-gp inducer may

decrease the plasma concentrations of the risperidone active antipsychotic fraction. When

concomitant carbamazepine or another strong CYP3A4 and/or P-gp inducer is initiated or

discontinued, the physician should re-evaluate the dosing of RISPERDAL. CYP3A4

inducers exert their effect in a time-dependent manner, and may take at least 2 weeks to

reach

maximal

effect

after

introduction.

Conversely,

discontinuation,

CYP3A4

induction may take at least 2 weeks to decline.

Highly protein-bound drugs

When RISPERDAL is taken together with highly protein-bound drugs, there is no

clinically relevant displacement of either drug from the plasma proteins.

When using concomitant medication, the corresponding label should be consulted for

information on the route of metabolism and the possible need to adjust dosage.

Paediatric population

Interaction studies have only been performed in adults. The relevance of the results from

these studies in paediatric patients is unknown.

The combined use of psychostimulants (e.g., methylphenidate) with RISPERDAL in

children and adolescents did not alter the pharmacokinetics and efficacy of RISPERDAL.

Examples

Examples of drugs that may potentially interact or that were shown not to interact with

risperidone are listed below:

Effect of other medicinal products on the pharmacokinetics of risperidone

Antibacterials:

Erythromycin, a moderate CYP3A4 inhibitor and P-gp inhibitor, does not change the

pharmacokinetics of risperidone and the active antipsychotic fraction.

Rifampicin, a strong CYP3A4 inducer and a P-gp inducer, decreased the plasma

concentrations of the active antipsychotic fraction.

Anticholinesterases:

Donepezil and galantamine, both CYP2D6 and CYP3A4 substrates, do not show a clinically

relevant effect on the pharmacokinetics of risperidone and the active antipsychotic fraction.

Antiepileptics:

Carbamazepine, a strong CYP3A4 inducer and a P-gp inducer, has been shown to decrease

the plasma concentrations of the active antipsychotic fraction of risperidone. Similar effects

may be observed with e.g. phenytoin and phenobarbital which also induce CYP3A4 hepatic

enzyme, as well as P-glycoprotein.

Topiramate modestly reduced the bioavailability of risperidone, but not that of the active

antipsychotic fraction. Therefore, this interaction is unlikely to be of clinical significance.

Antifungals:

Itraconazole, a strong CYP3A4 inhibitor and a P-gp inhibitor, at a dosage of 200 mg/day

increased the plasma concentrations of the active antipsychotic fraction by about 70%, at

risperidone doses of 2 to 8 mg/day.

Ketoconazole, a strong CYP3A4 inhibitor and a P-gp inhibitor, at a dosage of 200 mg/day

increased the plasma concentrations of risperidone and decreased the plasma concentrations of

9-hydroxy-risperidone.

Antipsychotics:

Phenothiazines may increase the plasma concentrations of risperidone but not those of the

active antipsychotic fraction.

Antivirals:

Protease inhibitors: No formal study data are available; however, since ritonavir is a strong

CYP3A4 inhibitor and a weak CYP2D6 inhibitor, ritonavir and ritonavir-boosted protease

inhibitors potentially raise concentrations of the risperidone active antipsychotic fraction.

Beta blockers:

Some beta-blockers may increase the plasma concentrations of risperidone but not those of

the active antipsychotic fraction.

Calcium channel blockers:

Verapamil, a moderate inhibitor of CYP3A4 and an inhibitor of P-gp, increases the plasma

concentration of risperidone and the active antipsychotic fraction.

Gastrointestinal drugs:

H2-receptor antagonists: Cimetidine and ranitidine, both weak inhibitors of CYP2D6 and

CYP3A4, increased the bioavailability of risperidone, but only marginally that of the active

antipsychotic fraction.

SSRIs and tricyclic antidepressants:

Fluoxetine, a strong CYP2D6 inhibitor, increases the plasma concentration of risperidone,

but less so of the active antipsychotic fraction.

Paroxetine, a strong CYP2D6 inhibitor, increases the plasma concentrations of risperidone,

but, at dosages up to 20 mg/day, less so of the active antipsychotic fraction. However, higher

doses of paroxetine may elevate concentrations

of the risperidone active antipsychotic fraction.

Tricyclic antidepressants may increase the plasma concentrations of risperidone but not those

of the active antipsychotic fraction. Amitriptyline does not affect the pharmacokinetics of

risperidone or the active antipsychotic fraction.

Sertraline, a weak inhibitor of CYP2D6, and fluvoxamine, a weak inhibitor of CYP3A4, at

dosages up to 100 mg/day are not associated with clinically significant changes in

concentrations of the risperidone active antipsychotic fraction.

However, doses higher than 100 mg/day of sertraline or fluvoxamine may elevate

concentrations of the risperidone active antipsychotic fraction.

Effect of risperidone on the pharmacokinetics of other medicinal products

Antiepileptics:

Risperidone does not show a clinically relevant effect on the pharmacokinetics of valproate

or topiramate.

Antipsychotics:

Aripiprazole, a CYP2D6 and CYP3A4 substrate: Risperidone tablets or injections did not

affect the pharmacokinetics of the sum of aripiprazole and its active metabolite,

dehydroaripiprazole.

Digitalis glycosides:

Risperidone does not show a clinically relevant effect on the pharmacokinetics of digoxin.

Lithium:

Risperidone does not show a clinically relevant effect on the pharmacokinetics of lithium.

Concomitant use of risperidone with furosemide

See section 4.4 regarding increased mortality in elderly patients with dementia concomitantly

receiving furosemide.

4.6.

Fertility, pregnancy and lactation

Pregnancy

There are no adequate data from the use of risperidone in pregnant women. Risperidone was

not teratogenic in animal studies but other types of reproductive toxicity were seen (see

section 5.3). The potential risk for humans is unknown.

Neonates exposed to antipsychotics (including RISPERDAL) during the third trimester of

pregnancy are at risk of adverse reactions including extrapyramidal and/or withdrawal

symptoms that may vary in severity and duration following delivery. There have been reports

of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, or feeding

disorder. Consequently, newborns should be monitored carefully.

RISPERDAL should not be used during pregnancy unless clearly necessary. If discontinuation

during pregnancy is necessary, it should not be done abruptly.

Breast-feeding

In animal studies, risperidone and 9-hydroxy-risperidone are excreted in the milk. It has been

demonstrated that risperidone and 9-hydroxy-risperidone are also excreted in human breast

milk in small quantities. There are no data available on adverse reactions in breast-feeding

infants. Therefore, the advantage of breast-feeding should be weighed against the potential

risks for the child.

Fertility

As with other drugs that antagonize dopamine D2 receptors, RISPERDAL elevates prolactin

level. Hyperprolactinemia may suppress hypothalamic GnRH, resulting in reduced pituitary

gonadotropin secretion. This, in turn, may inhibit reproductive function by impairing gonadal

steroidogenesis in both female and male patients.

There were no relevant effects observed in the non-clinical studies.

4.7.

Effects on ability to drive and use machines

RISPERDAL can have minor or moderate influence on the ability to drive and use machines

due to potential nervous system and visual effects (see section 4.8)

Therefore, patients should be advised not to drive or operate machinery until their individual

susceptibility is known.

4.8.

Undesirable effects

most

frequently

reported

adverse

drug

reactions

(ADRs)

(incidence

≥10%)

are:

Parkinsonism,sedation/somnolence, headache, and insomnia.

The ADRs that appeared to be dose-related included parkinsonism and akathisia.

The following are all the ADRs that were reported in clinical trials and post-marketing

experience with risperidone by frequency category estimated from RISPERDAL clinical trials.

The following terms and frequencies are applied: very common (≥1/10), common (≥1/100 to

<1/10),

uncommon

(≥1/1000

<1/100),

rare

(≥1/10,000

<1/1000)

very

rare

(<1/10,000).

Within each frequency grouping, undesirable effects are presented in order of decreasing

seriousness.

System

Organ

Adverse Drug

Frequen

Very

Common

Common

Uncommon

Rare

Very

Rare

Infections

and

infestations

pneumonia, bronchitis,

upper respiratory tract

infection, sinusitis,

urinary tract infection,

ear infection,

influenza

respiratory tract

infection, cystitis, eye

infection, tonsillitis,

onychomycosis, cellulitis

localised infection,

viral infection,

acarodermatitis

infection

Blood

and

lymphati

c system

disorders

neutropenia, white blood

cell count decreased,

thrombocytopenia,

anaemia, haematocrit

decreased,

eosinophil count increased

agranulocytosis

Immune

system

disorders

hypersensitivity

anaphylactic reaction

Endocrin

e

disorders

hyperprolactinaemia

inappropriate

antidiuretic

hormone secretion,

glucose

urine present

Metabolism

and nutrition

disorders

weight increased,

increased appetite,

decreased appetite

diabetes mellitus

hyperglycaemia,

polydipsia, weight

decreased, anorexia,

blood cholesterol

increased

water intoxication

hypoglycaemia,

hyperinsulinaemia

, blood

triglycerides

increased

diab

etic

keto

acid

osis

Psychiatri

c

disorders

insomnia

sleep disorder,

agitation,

depression, anxiety

mania, confusional state,

libido decreased,

nervousness,

nightmare

somnambulism

, sleep-related

eating disorder

blunted

affect,

anorgasmia

Nervous

system

disorder

s

sedation/

somnolence,

parkinsonism

, headache

akathisia

dystonia

dizziness,

dyskinesia

tremor

tardive dyskinesia, cerebral

ischaemia, unresponsive to

stimuli, loss of

consciousness, depressed

level of

consciousness, convulsion

syncope, psychomotor

hyperactivity, balance

disorder, coordination

abnormal, dizziness

postural, disturbance in

attention, dysarthria,

dysgeusia, hypoaesthesia,

paraesthesia

neuroleptic

malignant syndrome,

cerebrovascular

disorder, diabetic

coma, head titubation

Eye disorders

vision

blurred,

conjunctivi

photophobia, dry eye,

lacrimation increased,

ocular hyperaemia

glaucoma, eye

movement disorder,

eye rolling, eyelid

margin crusting,

floppy iris syndrome

(intraoperative)

Ear and

labyrint

h

disorders

vertigo, tinnitus, ear pain

Cardiac

disorder

s

tachycardia

atrial fibrillation,

atrioventricular block,

conduction disorder,

electrocardiogram QT

prolonged, bradycardia,

electrocardiogram

abnormal,

palpitations

sinus arrhythmia

Vascula

r

disorder

s

hypertension

hypotension,

orthostatic

hypotension, flushing

pulmonary

embolism, venous

thrombosis

Respirator

y, thoracic

and

mediastina

l disorders

dyspnoea,

pharyngolaryngeal

pain, cough,

epistaxis, nasal

congestion

pneumonia aspiration,

pulmonary congestion,

respiratory tract

congestion, rales,

wheezing, dysphonia,

respiratory disorder

sleep apnoea

syndrome,

hyperventilation

Gastrointestin

al disorders

abdominal pain,

abdominal

discomfort, vomiting,

nausea, constipation,

diarrhoea, dyspepsia,

mouth, toothache

faecal incontinence,

faecaloma, gastroenteritis,

dysphagia, flatulence

pancreatitis,

intestinal obstruction,

swollen tongue,

cheilitis

ileus

Skin and

subcutaneous

tissue

disorders

rash, erythema

urticaria, pruritus, alopecia,

hyperkeratosis, eczema, dry

skin, skin discolouration,

acne, seborrhoeic

dermatitis, skin

disorder, skin lesion

drug eruption,

dandruff

angioed

Musculoskele

tal and

connective

tissue

disorders

muscle spasms,

musculoskeletal pain,

back pain, arthralgia

blood creatine

phosphokinase increased,

posture abnormal, joint

stiffness, joint swelling

muscular weakness, neck

pain

rhabdomyolysis

Renal

and

urinary

disorders

urinary incontinence

pollakiuria, urinary

retention, dysuria

Pregnancy,

puerperiu

m, and

neonatal

conditions

drug withdrawal

syndrome

neonatal

Reproductive

system and

breast

disorders

erectile dysfunction,

ejaculation disorder,

amenorrhoea,

menstrual

disorder

, gynaecomastia,

galactorrhoea, sexual

dysfunction, breast pain,

breast

discomfort, vaginal

discharge

priapism

menstruation

delayed, breast

engorgement, breast

enlargement, breast

discharge

General

disorders

and

administrati

on site

conditions

oedema

, pyrexia,

chest pain, asthenia,

fatigue, pain

face oedema, chills, body

temperature increased,

gait abnormal, thirst,

chest discomfort,

malaise, feeling

abnormal, discomfort

hypothermia, body

temperature

decreased, peripheral

coldness, drug

withdrawal

syndrome, induration

Hepatobilia

ry disorders

transaminases increased,

gamma-

glutamyltransferase

increased, hepatic

enzyme

increased

jaundice

Injury,

poisoning

and

procedural

complications

fall

procedural pain

Hyperprolactinemia can in some cases lead to gynaecomastia, menstrual disturbances,

amenorrhoea, anovulation, galactorrhea, fertility disorder, decrease libido, erectile

dysfunction.

In placebo-controlled trials diabetes mellitus was reported in 0.18% in

risperidone-treated subjects compared to a rate of 0.11% in placebo group. Overall

incidence from all clinical trials was 0.43% in all risperidone-treated subjects.

Not observed in RISPERDAL clinical studies but observed in post-marketing

environment with risperidone.

Extrapyramidal disorder may occur:

Parkinsonism

(salivary hypersecretion,

musculoskeletal stiffness, parkinsonism, drooling, cogwheel rigidity, bradykinesia,

hypokinesia, masked facies, muscle tightness, akinesia, nuchal rigidity, muscle

rigidity, parkinsonian gait, and glabellar reflex abnormal, parkinsonian rest tremor),

akathisia

( akathisia, restlessness, hyperkinesia, and

restless leg

syndrome), tremor,

dyskinesia

(dyskinesia, muscle twitching, choreoathetosis, athetosis, and myoclonus),

dystonia.

Dystonia

includes dystonia, hypertonia, torticollis, muscle contractions involuntary,

muscle contracture, blepharospasm, oculogyration, tongue paralysis, facial spasm,

laryngospasm, myotonia, opisthotonus, oropharyngeal spasm, pleurothotonus, tongue

spasm, and trismus. It should be noted that a broader spectrum of symptoms are

included, that do not necessarily have an extrapyramidal origin.

Insomnia

includes: initial insomnia, middle insomnia;

Convulsion

includes: Grand mal

convulsion;

Menstrual disorder

includes: Menstruation irregular, oligomenorrhoea;

Oedema

includes: generalised oedema, oedema peripheral, pitting oedema.

Undesirable effects noted with paliperidone formulations

Paliperidone is the active metabolite of risperidone, therefore, the adverse reaction profiles of

these compounds (including both the oral and injectable formulations) are relevant to one

another. In addition to the above adverse reactions, the following adverse reaction has been

noted with the use of paliperidone products and can be expected to occur with RISPERDAL.

Cardiac disorders:

Postural orthostatic tachycardia syndrome

Class effects

As with other antipsychotics, very rare cases of QT prolongation have been reported post-

marketing with risperidone. Other class-related cardiac effects reported with antipsychotics

which prolong QT interval include ventricular arrhythmia, ventricular fibrillation, ventricular

tachycardia, sudden death, cardiac arrest and Torsades de Pointes.

Venous thromboembolism

Cases of venous thromboembolism, including cases of pulmonary embolism and cases of deep

vein thrombosis, have been reported with antipsychotic drugs (frequency unknown).

Weight gain

proportions

RISPERDAL

placebo-treated

adult

patients

with

schizophrenia

meeting a weight gain criterion of ≥7% of body weight were compared in a pool of 6- to 8-

week, placebo-controlled trials, revealing a statistically significantly greater incidence of

weight gain for RISPERDAL (18%) compared to placebo (9%). In a pool of placebo-

controlled 3-week studies in adult patients with acute mania, the incidence of weight increase

of ≥ 7% at endpoint was comparable in the RISPERDAL (2.5%) and placebo (2.4%) groups,

and was slightly higher in the active-control group (3.5%).

In a population of children and adolescents with conduct and other disruptive behaviour

disorders, in long-term studies, weight increased by a mean of 7.3 kg after 12 months of

treatment. The expected weight gain for normal children between 5-12 years of age is 3 to 5

kg per year. From 12-16 years of age, this magnitude of gaining 3 to 5 kg per year is

maintained for girls, while boys gain approximately 5 kg per year.

Additional information on special populations

Adverse drug reactions that were reported with higher incidence in elderly patients with

dementia or paediatric patients than in adult populations are described below:

Elderly patients with dementia

Transient ischaemic attack and cerebrovascular accident were ADRs reported in clinical trials

with a frequency of 1.4% and 1.5%, respectively, in elderly patients with dementia. In

addition, the following ADRs were reported with a frequency ≥5% in elderly patients with

dementia and with at least twice the frequency seen in other adult populations: urinary tract

infection, peripheral oedema, lethargy, and cough.

Paediatric population

In general, type of adverse reactions in children is expected to be similar to those observed in

adults.

The following ADRs were reported with a frequency ≥5% in paediatric patients (5 to 17 years)

and with at least twice the frequency seen in clinical trials in adults: somnolence/sedation,

fatigue, headache, increased appetite, vomiting, upper respiratory tract infection, nasal

congestion, abdominal pain, dizziness, cough, pyrexia, tremor, diarrhoea, and enuresis.

The effect of long-term risperidone treatment on sexual maturation and height has not been

adequately studied (see section 4.4, subsection “Paediatric population).

Reporting of suspected adverse reactions

Reporting

suspected

adverse

reactions

after

authorisation

medicinal

product

important. It allows continued monitoring of the benefit/risk balance of the medicinal product.

Any suspected adverse events should be reported to the Ministry of Health according to the

National Regulation by using an online form

http://forms.gov.il/globaldata/getsequence/getsequence.aspx?formType=AdversEffectMedic@

moh.gov.il

4.9.

Overdose

Symptoms

In general, reported signs and symptoms have been those resulting from an exaggeration of the

known

pharmacological

effects

risperidone.

These

include

drowsiness

sedation,

tachycardia and hypotension, and extrapyramidal symptoms. In overdose, QT-prolongation

and convulsions have been reported. Torsade de pointes has been reported in association with

combined overdose of RISPERDAL® and paroxetine.

In case of acute overdose, the possibility of multiple drug involvement should be considered.

Treatment

Establish and maintain a clear airway and ensure adequate oxygenation and ventilation.

Gastric lavage (after intubation, if the patient is unconscious) and administration of activated

charcoal together with a laxative should be considered only when drug intake was less than

hour

before.

Cardiovascular

monitoring

should

commence

immediately

should

include continuous electrocardiographic monitoring to detect possible arrhythmias.

There is no specific antidote to RISPERDAL

. Therefore, appropriate supportive measures

should be instituted. Hypotension and circulatory collapse should be treated with appropriate

measures such as intravenous fluids and/or sympathomimetic agents. In case of severe

extrapyramidal symptoms, an anticholinergic medicinal product should be administered. Close

medical supervision and monitoring should continue until the patient recovers.

5.

PHARMACOLOGICAL PROPERTIES

5.1.

Pharmacodynamic properties

Pharmacotherapeutic group: Other antipsychotics, ATC code: N05AX08

Mechanism of action

Risperidone is a selective monoaminergic antagonist with unique properties. It has a high

affinity for serotoninergic 5-HT

and dopaminergic D

receptors. Risperidone binds also to

alpha

-adrenergic

receptors,

and,

with

lower

affinity,

-histaminergic

alpha

adrenergic

receptors.

Risperidone

affinity

cholinergic

receptors.

Although

risperidone is a potent D

antagonist, which is considered to improve the positive symptoms of

schizophrenia, it causes less depression of motor activity and induction of catalepsy than

classical antipsychotics. Balanced central serotonin and dopamine antagonism may reduce

extrapyramidal side effect liability and extend the therapeutic activity to the negative and

affective symptoms of schizophrenia.

Pharmacodynamic effects

Clinical efficacy

Schizophrenia

The efficacy of risperidone in the short-term treatment of schizophrenia was established in

four studies, 4-to 8-weeks in duration, which enrolled over 2,500 patients who met DSM-IV

criteria

schizophrenia.

6-week,

placebo-controlled

trial

involving

titration

risperidone in doses up to 10 mg/day administered twice daily, risperidone was superior to

placebo on the Brief Psychiatric Rating Scale (BPRS) total score. In an 8-week, placebo-

controlled

trial

involving

four

fixed

doses

risperidone

mg/day,

administered twice daily), all four risperidone groups were superior to placebo on the Positive

and Negative Syndrome Scale (PANSS) total score. In an 8-week, dose comparison trial

involving five fixed doses of risperidone (1, 4, 8, 12, and 16 mg/day administered twice-

daily), the 4, 8, and 16 mg/day risperidone dose groups were superior to the 1 mg risperidone

dose group on PANSS total score. In a 4-week, placebo-controlled dose comparison trial

involving two fixed doses of risperidone (4 and 8 mg/day administered once daily), both

risperidone dose groups were superior to placebo on several PANSS measures, including total

PANSS and a response measure (>20% reduction in PANSS total score). In a longer-term trial,

adult outpatients predominantly meeting DSM-IV criteria for schizophrenia and who had been

clinically stable for at least 4 weeks on an antipsychotic medicinal product were randomised to

risperidone 2 to 8 mg/day or to haloperidol for 1 to 2 years of observation for relapse. Patients

receiving risperidone experienced a significantly longer time to relapse over this time period

compared to those receiving haloperidol.

Manic episodes in bipolar disorder

The efficacy of risperidone monotherapy in the acute treatment of manic episodes associated

with

bipolar

disorder

demonstrated

three

double-blind,

placebo-controlled

monotherapy studies in approximately 820 patients who had bipolar I disorder, based on

DSM-IV criteria. In the three studies, risperidone 1 to 6 mg/day (starting dose 3 mg in two

studies and 2 mg in one study) was shown to be significantly superior to placebo on the pre-

specified primary endpoint, i.e., the change from baseline in total Young Mania Rating Scale

(YMRS) score at week 3. Secondary efficacy outcomes were generally consistent with the

primary outcome. The percentage of patients with a decrease of ≥ 50% in total YMRS score

from baseline to the 3-week endpoint was significantly higher for risperidone than for placebo.

One of the three studies included a haloperidol arm and a 9-week double-blind maintenance

phase. Efficacy was maintained throughout the 9-week maintenance treatment period. Change

from baseline in total YMRS showed continued improvement and was comparable between

risperidone and haloperidol at week 12.

The efficacy of risperidone in addition to mood stabilisers in the treatment of acute mania was

demonstrated in one of two 3-week double-blind studies in approximately 300 patients who

met the DSM-IV criteria for bipolar I disorder. In one 3-week study, risperidone 1 to 6 mg/day

starting at 2 mg/day in addition to lithium or valproate was superior to lithium or valproate

alone on the pre-specified primary endpoint, i.e., the change from baseline in YMRS total

score at week 3. In a second 3-week study, risperidone 1 to 6 mg/day starting at 2 mg/day,

combined with lithium, valproate, or carbamazepine was not superior to lithium, valproate, or

carbamazepine alone in the reduction of YMRS total score. A possible explanation for the

failure of this study was induction of risperidone and 9-hydroxy-risperidone clearance by

carbamazepine, leading to subtherapeutic levels of risperidone and 9-hydroxy-risperidone.

When the carbamazepine group was excluded in a post-hoc analysis, risperidone combined

with lithium or valproate was superior to lithium or valproate alone in the reduction of YMRS

total score.

Persistent aggression in dementia

The efficacy of risperidone in the treatment of Behavioural and Psychological Symptoms of

Dementia (BPSD), which includes behavioural disturbances, such as aggressiveness, agitation,

psychosis,

activity,

affective

disturbances

demonstrated

three

double-blind,

placebo-controlled studies in 1,150 elderly patients with moderate to severe dementia. One

study included fixed risperidone doses of 0.5, 1, and 2 mg/day. Two flexible-dose studies

included risperidone dose groups in the range of 0.5 to 4 mg/day and 0.5 to 2 mg/day,

respectively. Risperidone showed statistically significant and clinically important effectiveness

in treating aggression and less consistently in treating agitation and psychosis in elderly

dementia patients (as measured by the Behavioural Pathology in Alzheimer’s Disease Rating

Scale [BEHAVE-AD] and the Cohen-Mansfield Agitation Inventory [CMAI]). The treatment

effect of risperidone was independent of Mini-Mental State Examination (MMSE) score (and

consequently of the severity of dementia); of sedative properties of risperidone; of the

presence or absence of psychosis; and of the type of dementia, Alzheimer’s, vascular, or

mixed. (see also section 4.4)

Paediatric population

Conduct disorder

efficacy

risperidone

short-term

treatment

disruptive

behaviours

demonstrated in two double-blind placebo-controlled studies in approximately 240 patients 5

to 12 years of age with a DSM-IV diagnosis of disruptive behaviour disorders (DBD) and

borderline intellectual functioning or mild or moderate mental retardation/learning disorder. In

the two studies, risperidone 0.02 to 0.06 mg/kg/day was significantly superior to placebo on

the pre-specified primary endpoint, i.e., the change from baseline in the Conduct Problem

subscale of the Nisonger-Child Behaviour Rating Form (N-CBRF) at week 6.

5.2.

Pharmacokinetic properties

RISPERDAL oral solution is bioequivalent to RISPERDAL film-coated tablets.

Risperidone is metabolised to 9-hydroxy-risperidone, which has a similar pharmacological

activity to risperidone (see Biotransformation and Elimination).

Absorption

Risperidone

completely

absorbed

after

oral

administration,

reaching

peak

plasma

concentrations within 1 to 2 hours. The absolute oral bioavailability of risperidone is 70%

(CV=25%). The relative oral bioavailability of risperidone from a tablet is 94% (CV=10%)

compared with a solution. The absorption is not affected by food and thus risperidone can be

given with or without meals. Steady-state of risperidone is reached within 1 day in most

patients. Steady-state of 9-hydroxy-risperidone is reached within 4-5 days of dosing.

Distrtibution

Risperidone

rapidly

distributed.

volume

distribution

1-2 l/kg.

plasma,

risperidone is bound to albumin and alpha

-acid glycoprotein. The plasma protein binding of

risperidone is 90 %, that of 9-hydroxy-risperidone is 77%.

Biotransformation and elimination

Risperidone

metabolized

CYP2D6

9-hydroxy-risperidone,

which

similar

pharmacological activity as risperidone. Risperidone plus 9-hydroxy-risperidone form the

active

antipsychotic

fraction.

CYP2D6

subject

genetic

polymorphism.

Extensive

CYP2D6 metabolisers convert risperidone rapidly into 9-hydroxy-risperidone, whereas poor

CYP2D6 metabolisers convert it much more slowly. Although extensive metabolisers have

lower risperidone and higher 9-hydroxy-risperidone concentrations than poor metabolisers, the

pharmacokinetics

risperidone

9-hydroxy-risperidone

combined

(i.e.,the

active

antipsychotic fraction), after single and multiple doses, are similar in extensive and poor

metabolisers of CYP2D6.

Another metabolic pathway of risperidone is N-dealkylation.

In vitro

studies in human liver

microsomes showed that risperidone at clinically relevant concentration does not substantially

inhibit the metabolism of medicines metabolised by cytochrome P450 isozymes, including

CYP1A2, CYP2A6, CYP2C8/9/10, CYP2D6, CYP2E1, CYP3A4, and CYP3A5. One week

after administration, 70% of the dose is excreted in the urine and 14% in the faeces. In urine,

risperidone plus 9-hydroxy-risperidone represent 35- 45% of the dose. The remainder is

inactive metabolites. After oral administration to psychotic patients, risperidone is eliminated

with a half-life of about 3 hours. The elimination half-life of 9-hydroxy-risperidone and of the

active antipsychotic fraction is 24 hours.

Linearity/non-linearity

Risperidone plasma concentrations are dose-proportional within the therapeutic dose-range.

Elderly, hepatic and renal impairment

A single-dose PK-study with oral risperidone showed on average a 43% higher active

antipsychotic fraction plasma concentrations a 38% longer half-life and a reduced clearance of

the active antipsychotic fraction by 30% in the elderly.

In adults with moderate renal disease the clearance of the active moiety was ~48% of the

clearance in young healthy adults. In adults with severe renal disease the clearance of the

active moiety was ~31% of the clearance in young healthy adults. The half-life of the active

moiety was 16.7 h in young adults, 24.9 h in adults with moderate renal disease (or ~1.5 times

as long as in young adults), and 28.8 h in those with severe renal disease (or ~1.7 times as long

as in young adults). Risperidone plasma concentrations were normal in patients with liver

insufficiency, but the mean free fraction of risperidone in plasma was increased by 37.1%.

The oral clearance and the elimination half-life of risperidone and of the active moiety in

adults with moderate and severe liver impairment were not significantly different from those

parameters in young healthy adults.

Paediatric population

The pharmacokinetics of risperidone, 9-hydroxy-risperidone and the active antipsychotic

fraction in children are similar to those in adults.

Gender, race and smoking habits

A population pharmacokinetic analysis revealed no apparent effect of gender, race or smoking

habits on the pharmacokinetics of risperidone or the active antipsychotic fraction.

5.3.

Preclinical safety data

In (sub)chronic toxicity studies, in which dosing was started in sexually immature rats and

dogs, dose-dependent effects were present in male and female genital tract and mammary

gland. These effects were related to the increased serum prolactin levels, resulting from the

dopamine D2-receptor blocking activity of risperidone. In addition, tissue culture studies

suggest that cell growth in human breast tumours may be stimulated by prolactin. Risperidone

was not teratogenic in rat and rabbit. In rat reproduction studies with risperidone, adverse

effects were seen on mating behaviour of the parents, and on the birth weight and survival of

the offspring. In rats, intrauterine exposure to risperidone was associated with cognitive

deficits in adulthood. Other dopamine antagonists, when administered to pregnant animals,

have caused negative effects on learning and motor development in the offspring.

toxicity

study

juvenile

rats,

increased

mortality

delay

physical

development was observed. In a 40-week study with juvenile dogs, sexual maturation was

delayed. Based on AUC, long bone growth was not affected in dogs at 3.6-times the maximum

human

exposure

adolescents

(1.5

mg/day);

while

effects

long

bones

sexual

maturation were observed at 15 times the maximum human exposure in adolescents.

Risperidone was not genotoxic in a battery of tests. In oral carcinogenicity studies of

risperidone in rats and mice, increases in pituitary gland adenomas (mouse), endocrine

pancreas adenomas (rat), and mammary gland adenomas (both species) were seen. These

tumours can be related to prolonged dopamine D2 antagonism and hyperprolactinaemia. The

relevance of these tumour findings in rodents in terms of human risk is unknown. In vitro and

vivo,

animal

models

show

that

high

doses

risperidone

cause

interval

prolongation, which has been associated with a theoretically increased risk of Torsade de

Pointes in patients.

6.

PHARMACEUTICAL PARTICULARS

6.1.

List of excipients

Risperdal Film

-coated tablets:

Tablet core

Lactose monohydrate

Maize starch

Microcrystalline cellulose

Hypromellose 2910 15 mPa.s

Magnesium stearate

Colloidal anhydrous silica

Sodium lauryl sulfate

Film-coating

Risperdal 1 mg

Hypromellose 2910 5 mPa.s

Propylene glycol

Risperdal 2 mg

Hypromellose 2910 5 mPa.s

Titanium dioxide

Talc

Propylene glycol

Orange yellow S aluminum lake

Risperdal 3 mg

Hypromellose 2910 5 mPa.s

Titanium dioxide

Talc

Propylene glycol

Quinoline yellow

Risperdal 4 mg

Hypromellose 2910 5 mPa.s

Titanium dioxide

Talc

Propylene glycol

Quinoline yellow

Indigotindisulfonate aluminum lake

Risperdal 1mg/ml Oral solution:

Tartaric acid

Benzoic acid

Sodium hydroxide

Purified water

6.2.

Incompatibilities

RISPERDAL

tablets.not applicable

RISPERDAL

oral solution: incompatible with most types of tea including black tea.

6.3.

Shelf life

The expiry date of the product is indicated on the packaging materials

6.4.

Special precautions for storage

RISPERDAL

oral tablets store below 30

RISPERDAL

oral solution store below 30

C and do not freeze

Keep out of reach of children.

After first opening the bottle, use within 3 months.

6.5.

Nature and contents of container

Oral Tablets:

PVC-PE-PVDC/Al blister consisting of aluminum foil

RISPERDAL

1, 2, 3 and 4 mg tablets are individually packaged in a blister card containing

10 tablets. Blisters are packed in a cardboard box (2 blisters per box).

Oral solution:

RISPERDAL

Oral

Solution

provided

amber

glass

bottles

with

plastic

(polypropylene) child resistant closures. A dosing pipette is also provided

The pipette supplied with the 30 ml bottle is graduated in milligrams and milliliters with a

minimum volume of 0.25 ml and a maximum volume of 3 ml. Graduation marks in 0.25 ml

(equals 0.25 mg oral solution) increments up to 3 ml (equals 3mg oral solution) are printed on

this pipette.

6.6.

Instructions for Use/Handling

Oral Solution

Fig. 1: The bottle comes with a child-

resistant

cap,

should

opened as follows:

Push

plastic

screw

down

while

turning

counter clockwise.

Remove the unscrewed cap.

Fig. 2: Insert the pipette into the bottle.

While holding the bottom ring,

pull the top ring up to the mark

that corresponds to the number

of milliliters or milligrams you

need to give.

Fig. 3: Holding

bottom

ring,

remove the entire pipette from

the bottle.

Empty the pipette into any non-

alcoholic drink, except for tea,

by sliding the upper ring down.

Close the bottle. Rinse the

pipette with some water.

7.

MANUFCTURER:

Risperdal 1mg/ml

Janssen Pharmaceutica N.V.

TURNHOUTSEWEG 30, B-2340, Beerse, Belgium

Risperdal 1mg, 2mg, 3mg

and 4mg tablets

Janssen Cilag S.p.A.

VIA C. JANSSEN 04010, BORGO S. MICHELE, Latina, Italy

8.

REGISTRATION HOLDER:

J-C Health Care Ltd

Kibbutz Shefayim 6099000,

Israel

The content of this leaflet was approved by the Ministry of Health in April 2016 and updated

according to the guidelines of the Ministry of Health in November 2018

מ"עב רק 'תלה יס יי'ג

םייפש ץוביק

60990

לארשי

09-959-1111

'לט

09-958-3636

סקפ

ראוני

2019

ה/דבכנ ה/אפור

ה/דבכנ ת/חקור

ןודנה

ןוכדע

ולעב ןכרצלו אפורל םינ

לש

םירישכתה

isperdal tabs, Risperdal Oral solution

וננוצרב

איבהל

םכתעידיל

ןוכדע לח יכ

ולע םינ

אפורל

ןכרצלו

ישכתה לש םיר

Risperdal tabs, Risperdal

Oral solutio

יוותהה תו

מושרה תו

:ץרא

Risperdal

(risperidone) is indicated for the management schizophrenia, and the manifestations of

psychotic disorders. The antipsychotic efficacy of Risperdal

was established in short-term (6 to 8-

weeks) controlled trials of schizophrenic inpatients.

Risperdal

is also effective in maintaining the clinical improvement during continuation therapy in

patients who have shown an initial treatment response

Risperdal

is indicated for the short-term treatment (up to 6 weeks) of persistent aggression in

patients

with

moderate

severe

Alzheimer’s

dementia

unresponsive

non-pharmacological

approaches and when there is a risk of harm to self or others.

Conduct and other disruptive disorders:

Treatment of behavioral disorders expressed by impulse control disorders or self-alienated-aggressive

or treatment-requiring behavioral disorders with reduced or substandard intelligence. Treatment

should not be given to children under the age of 5 years.

Risperdal is indicated for the treatment of mania in bipolar disorder. These episodes are characterized

by symptoms such as elevated, expansive or irritable mood, inflated self-esteem, decreased need for

sleep, pressured speech, racing thoughts, distractibility, or poor judgment, including disruptive or

aggressive behaviors.

אפורל ןולעב :םיפיעסב ןוקית לח

4.4 Special Warnings and Precautions for Use

Excipients

The 1 ml oral solution

contains benzoic acid (E 210). Increase in bilirubinaemia following its

displacement from albumin may increase neonatal jaundice which may develop into

kernicterus (non-conjugated bilirubin deposits in the brain tissue).

4.8 Undesirable Effectseffects

מ"עב רק 'תלה יס יי'ג

םייפש ץוביק

60990

לארשי

09-959-1111

'לט

09-958-3636

סקפ

Psychiatric

disorders

insomnia

sleep disorder,

agitation, depression,

anxiety

mania, confusional state,

libido decreased,

nervousness,

nightmare

somnambulism,

sleep-related eating

disorder blunted

affect, anorgasmia

:םיאבה םיפיעסב ןוקית לח ןכרצל ןולעב

הפורתה לש םיביכרמהמ קלח לע בושח עדימ

.זוטקל ארקנה רכוס לש גוס תוליכמ לדרפסיר תוילבט

םא ךנה

ץעוויהל שי ,םימיוסמ םירכוסל תוליבס רסוחמ לבוס .לדרפסיר תוילבט תליטנ םרט אפורב

לדרפסיר תוילבט

2

ביכרה תא תוליכמ ג"מ

sunset yellow (E110)

.תויגרלא תובוגתל םורגל לולעה

תיאוזנב הצמוח ליכמ הייתשל הסימת לדרפסיר הליכמ הפורתה .

לכב תיאוזנב הצמוח ג"מ

.הייתשל הסימת ל"מ הלולע תיאוזנב הצמוח םורגל ליגל דע) םידולייב (םייניעהו רועה לש הבהצה) תבהצב היילעל

.(תועובש

תוחיכש ןניאש יאוול תועפות

) uncommon (

ב תועיפומש תועפות

1-10

ךותמ םישמתשמ

1,000

הדירי ,לובלב ,(הינאמ) םמורמ חור בצמ רציב קשחב

,ינימ תונבצע

יטויס

הליל

ת

תועפו

יאוול

תורידנ

)

rare

(

תועפות

תועיפומש

ב

10

-

1

םישמתשמ

ךותמ

10,000

.הניש ידכ ךות הכילה

שקה הליכא תוערפה

הנישל תור

שה ולעב םינמוסמ םייוני

רוצמה

שגדומה טסקטה רשאכ קוחמה טסקטה וליאו ןולעל ףסוה

שגדומ

.הצוח וק םע

אפורל ןולעה

םוסרפל חלשנ אולמב

ש תופורתה רגאמ .תואירבה דרשמ רתאב

,ןכ ומכ לבקל ןתינ

ןופלטל ונילא הינפב ספדומ

09-9591111

,הכרבב

ןהכ רירפצ

נוממ חקור

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