סימפוני

ישראל - עברית - Ministry of Health

קנה את זה

עלון מידע עלון מידע (PIL)

25-10-2018

מרכיב פעיל:
GOLIMUMAB
זמין מ:
J-C HEALTH CARE LTD
קוד ATC:
L04AB06
טופס פרצבטיות:
תמיסה להזרקה
הרכב:
GOLIMUMAB 50 MG / 0.5 ML
מסלול נתינה (של תרופות):
תת-עורי
סוג מרשם:
מרשם נדרש
תוצרת:
CILAG AG, SWITZERLAND
קבוצה תרפויטית:
GOLIMUMAB
איזור תרפויטי:
GOLIMUMAB
סממני תרפויטית:
Rheumatoid Arthritis :Simponi, in combination with methotrexate, is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis when the response to disease-modifying anti-rheumatic drug (DMARD) therapy including MTX has been inadequate.Psoriatic Arthritis :Simponi, alone or in combination with methotrexate, is indicated for the treatment of adult patients with active and progressive psoriatic arthritis when the response to previous disease-modifying anti-rheumatic drug (DMARD) therapy has been inadequate.Ankylosing Spondylitis :Simponi is indicated for the treatment of adult patients with severe active ankylosing spondylitis who have responded inadequately to conventional therapy.
מספר אישור:
147 32 33213 00
תאריך אישור:
2017-01-31

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עלון מידע עלון מידע - ערבית

30-11-2020

1986 - ו"משתה )םירישכת( םיחקורה תונקת יפל ןכרצל ןולע דבלב אפור םשרמ יפ לע תקוושמ הפורתה קזוחהו ותרוצ רישכתה םש

,

TM

ינופמיס ,יטמוטוא טע קרזמ / שומישל ןכומ קרזמ ל"מ 0.5 -ב ג"מ 50

,

TM

ינופמיס ,יטמוטוא טע קרזמ / שומישל ןכומ קרזמ ל"מ 1.0 -ב ג"מ 100 הקרזהל הסימת ןונימ תדיחיב ותומכו ליעפה רמוחה

Golimumab 50 mg/0.5 ml

ל"מ 0.5/ג"מ 50 במומילוג ."ףסונ עדימ“ 6 ףיעס האר - רישכתב םיינגרלאו םיליעפ יתלב םירמוח ליכמ הז ןולע .הפורתב שמתשת םרטב ופוס דע ןולעה תא ןויעב ארק לא וא אפורה לא הנפ ,תופסונ תולאש ךל שי םא .הפורתה לע יתיצמת עדימ .חקורה קיזהל הלולע איה .םירחאל התוא ריבעת לא .ךתלחמב לופיטל המשרנ וז הפורת .המוד םתלחמ יכ ךל הארנ םא וליפא םהל .םירגובמל תדעוימ הפורתה סיטרכ .לפוטמל תוחיטב עדימ סיטרכ םייק ינופמיס רישכתל ,ןולעל ףסונב ךלהמבו לופיטה תלחתה ינפל תעדל ךילעש ,בושח יתוחיטב עדימ ליכמ הז לפוטמל תוחיטב עדימ סיטרכב ןייעל שי .ויפ לע לועפלו ינופמיסב לופיטה סיטרכה תא רומשל שי .רישכתב שומישה תליחת םרטב ןכרצל ןולעבו .ךרוצה תדימב ףסונ ןויעל ?הפורתה תדעוימ המל .1 םירגובמב תשמשמו "

ימסוח“ תוארקנה תופורת תצובקל תכייש ינופמיס םיקרפמ תקלדב ,)

Rheumatoid

Arthritis

( תינורגש םיקרפמ תקלדב לופיטל תקלד תללוכה ,סיטירטראולידנופס לאיסקאב ,)

Psoriatic

Arthritis

( תיתחפס אלל סיטירטראולידנופס לאיסקאו

(Ankylosing

Spondylitis

( תחשקמ תוילוח תיביכ תקלדבו )

Non‑radiographic Axial Spondyloarthritis

( תויפרגוידר תויודע

Ulcerative

Colitis

( סגה יעמה לש םיכילהתב ברועמה

ארקנש ןובלח תמיסח תועצמאב תלעופ ינופמיס .ףוגב יתקלדה בצמה תתחפהל תמרוג ותמיסח .ףוגב םייתקלד תינורכ םיקרפמ תקלדב לופיטל תשמשמ ינופמיס ,ג"ק 40 תוחפל םילקושה םידליב

.(Polyarticular Juvenile Idiopathic Arthritis

( תודליה ליג לש תיתפוידיא

ימסוח :תיטיופרת הצובק הפורתב שומישה ינפל .2 :םא רישכתב שמתשהל ןיא םיפסונה םיביכרמהמ דחא לכל וא במומילוג ליעפה רמוחל )יגרלא( שיגר התא עדימ“ 6 ףיעס האר ,םיפסונה םיביכרמה תמישרל .הפורתה הליכמ רשא ."ףסונ .רחא רומח םוהיז לכמ וא תפחשמ לבוס התא .הרומח וא הנותמ בל תקיפס יאמ לבוס התא :הפורתב שומישל תועגונה תודחוימ תורהזא :םיאבה םיבצמהמ לבוס ךנה םא אפורל רפס ,ינופמיסב לופיטה ינפל םימוהיז ∘ םא וא םוהיז לש םהשלכ םינימסתמ לבוס רבכ התא םא ,דימ אפורל רפס

םיללוכ םוהיזל םינימסת .וירחאל וא ינופמיסב לופיטה ךלהמב םיעיפומ םה תויעב ,םיעצפ ,לושלש ,תעפש ייומד םינימסת ,המישנ רצוק ,לועיש ,םוח .ןתש ןתמ ןמזב הבירצ תשוחת וא םיינישב .תולק רתיב םימוהיזב תוקלל לולע התא ,ינופמיסב שומישה ןמזב םימוהיז ,ףסונב .רתוי םירומח תויהלו רתוי רהמ םדקתהל םילולע םימוהיזה .שדחמ עיפוהל םילולע םימדוק תפחש וא לופיטה ךלהמב תפחש לש םינימסת םיעיפומ םא דימ ךאפורל רפס

.וירחאל תועזה וא םוח ,תופייע ,לקשמב הדירי ,ךשמתמ לועיש :םיללוכ תפחש ינימסת

.הליל ףא םירידנ םירקמב ,ינופמיסב ולפוטש םילפוטמב וחווד תפחש ירקמ םא תוארל ידכ ךתוא קודבי אפורה .תפחשל תופורתב ולפוטש םילוחב תוחיטב עדימ סיטרכ"ב ןחבמה תואצות תא דעתי אפורה .תפחש ךל שי .ךתושרבש "לפוטמל תייה םא וא ,תפחשמ םעפ יא תלבס םא ךאפורל רמאתש דואמ בושח .תפחש ול התייהש וא ול שיש והשימ םע בורק עגמב דגנכ תופורתב לפוטתש ןכתיי ,תפחשל ןוכיסב התאש ששוח ךאפור םא .ינופמיסב שמתשהל ליחתתש ינפל תפחש

B

גוסמ תבהצה ףיגנ

הלחמהמ תלבסש וא לבוס התאש וא ףיגנה לש אשנ התא םא ךאפורל רפס .ינופמיסב לופיטה ינפל ,רבעב תבהצב קבדיהל ןוכיסב תויהל לולע התאש בשוח התא םא ךאפורל רפס

גוסמ תיפיגנ

גוסמ תיפיגנ תבהצ לש תואצמיהל ךתוא קודבל רומא ךאפור לש תשדוחמ העפוהל םורגל לולע ינופמיס תמגוד

ימסוחב לופיטה תויהל לולעה רבד ,הז ףיגנ םיאשונה םילפוטמב

גוסמ תיפיגנ תבהצ .םימיוסמ םירקמב םייח ןכסמ םיינשלופ םייתיירטפ םימוהיז

םיוסמ גוס ידי לע םימרגנה םימוהיז םיצופנ וב רוזאב תלייטש וא תייח םא תוארקנ( םירחא ףוג יקלח לע וא תואירה לע עיפשהל תולוכיה תוירטפ לש .דימ ךאפורל רפס ,)סיזוקימוטסלב וא סיזוקימודוידיסקוק ,סיזומסלפוטסיה ,תלייט וא תייח וב רוזאב םיצופנ הלא םייתיירטפ םימוהיז םא עדוי ךניא םא .ךאפור תא לאש המופמילו ןטרס ∘ המופמיל הלוחכ תנחבוא םעפ יא םא ךאפורל רפס ,ינופמיסב שמתשתש ינפל

.רחא ןטרס גוס לכ וא )םד ןטרס לש גוס( חתפל ךלש ןוכיסה ,םירחא

ימסוחב וא ינופמיסב שמתשמ התא םא .לודגל לולע ,רחא ןטרס וא המופמיל תויתקלד תולחממ וא הרומח תינורגש םיקרפמ תקלדמ םילבוסה םילפוטמ .המופמיל חתפל רתוי הובג ןוכיסב תויהל םילולע ,בר ןמז הזמ תורחא ,םינוש םיגוסמ ןטרס ירקמ ולגתה ,

יבכעמ ולטנש םירגבתמבו םידליב .תוומב םימעפל ומייתסה רשא םיגירח םיגוס ללוכ

Hepatosplenic T-cell lymphoma

יורקה המופמיל לש רומחו םיוסמ גוס םירגבתמ םבור .

TNF

ימסוח םילבקמה םילוחב םירידנ םירקמב הלגתנ לכ טעמכ .תוומב םייתסה ללכ ךרדב ןטרס לש הז גוס .םיריעצ םירבג וא םא אפורל רפס .ןירופוטפקרמ 6 וא ןירפויטאזא םג ולביק וללה םילוחה .ינופמיסל ליבקמב ןירופוטפקרמ 6 וא ןירפויטאזא לטונ ךנה תואיר תלחממ ,)המתסא( תכשמתמ הרומח תרצקמ םילבוסה םילפוטמ ןוכיסב תויהל םילולע ,םידבכ םינשעמ םהש וא ,)

COPD

( תינורכ תיתמיסח ,תכשמתמ תרצקמ לבוס התא םא .ינופמיסב לופיטה תחת ןטרסל רבגומ םע חחושל ךילע ,דבכ ןשעמ התאש וא תינורכ תיתמיסח תואיר תלחממ .ךל םיאתמ

םסוחב לופיטה םא ךאפור רועה ןטרס לש םימיוסמ םיגוס וחתיפ ינופמיסב ולפוטש םימיוסמ םילוח

רועה לע םילודיגב וא רועה הארמב םייונישב ןיחבמ ךנה םא .המונלמ ןוגכ .ךאפורל חווד ,ינופמיסב לופיטה רחאל וא ךלהמב בל תקיפס יא

םינימסתב הרמחה וא םישדח םינימסת הווח התא םא דימ ךאפורל רפס

המישנ רצוק םיללוכ בל תקיפס יא לש םינימסת .בל תקיפס יא לש םימייק .םיילגרב תוחיפנ וא ללוכ ,

ימסוחב םילפוטמב החווד בל תקיפס יא לש הרמחה וא העפוה .ורטפנ הלא םילוחמ קלח .ינופמיס תויהל ךילע ,ינופמיסב לפוטמ התאו הלק בל תקיפס יאמ לבוס התא םא .ךאפור לש ינדפק בקעמב םיבצעה תכרעמ לש תולחמ ∘ תולחמ לש םינימסת תחתיפש וא םעפ יא תנחבוא םא דימ ךאפורל רפס

.הצופנ תשרט ןוגכ ,םייבצעה םיביסה לש ןילאימה תבכש תעגפנ ןהבש לומינ ,םיילגרב וא תועורזב השלוח ,הייארב םייוניש לולכל םילולע םינימסתה .ינופמיס לבקל לוכי ךנה םא טילחי ךאפור .ךפוגמ קלח לכב ץוצקע וא םיילטנד םיכילה וא םיחותינ ∘ .והשלכ ילטנד ךילה וא חותינ רובעל דמוע התא םא ךאפורל רפס לפוטמ התאש ,ילטנדה ךילהה תא עצבמש םיינישה אפורל וא חתנמל רפס ."לפוטמל תוחיטב עדימ סיטרכ" לש הגצה ידי לע ינופמיסב תוינומיאוטוא תולחמ ∘ םינימסתה .תבאז תארקנה הלחמ לש םינימסת חתפמ התא םא ךאפורל רפס

.תופייעו ,םיקרפמ יבאכ ,םוח ,תכשמתמ החירפ םיללוכ .תבאז וחתיפ

ימסוחב ולפוטש םישנא םירידנ םירקמב םד תולחמ ∘ ךפוגל םירזועה םדה יאת לש ףוגב רוצייה עגפיהל לולע ,םימיוסמ םילפוטמב

םא ,דרוי אלש םוח חתפמ התא םא .םימומיד רוצעל וא םימוהיזב םחליהל ךאפור לא רשקתה רוויח דואמ הארנ וא הבר תולקב םמדמ וא לבחנ התא .לופיטה תא קיספהל טילחי ךאפורו ןכתיי .דימ ךאפור םע חחוש ,ךילע לח הלעמ ראותמהמ רתוי וא דחא םא חוטב ךניא םא

.ינופמיסב שומישה ינפל חקורה וא םינוסיח ∘ .ןוסיח לבקל ךילעש וא תלביק םא ךאפורל רפס

םיביכרת( םימיוסמ םינוסיח לבקל רומא ךניא ינופמיסב שומישה ןמזב .)םייח ,ןויריהה ךלהמב ינופמיס תלביק םא .םוהיזל םורגל םילולע םימיוסמ םינוסיח םישדוח השישכ דע הזכ םוהיזב תוקלל רתוי הובג ןוכיסב תויהל לולע ךקונית לש ואפורל ירפסתש בושח .ןויריהה ךלהמב תלביקש הנורחאה הנמהמ ןויריהה ךלהמב ינופמיסב תשמתשהש לע םירחא יאופר תווצ ישנאלו ךקונית .והשלכ ןוסיח ךקוניתל תתל ןתינ םא טילחהל ולכויש ידכב ךדלי לע ,ירשפא םא ,ךדליל ןוסיח ןתמ יבגל אפורה םע ץעייתהל ךילע .ינופמיסב שומישה ינפל םישרדנה םינוסיחה לכ תא לבקל קבדמ ביכר םע לופיט

] ןוגכ( קבדמ ביכר םע לופיט לבקל רומא ךנהש וא הנורחאל תלביק םא

.)ןטרסב לופיטל

Bacillus

Calmette

Guérin

תיגרלא הבוגת ∘ רחאל תיגרלא הבוגת לש םינימסת חתפמ התא םא דימ ךאפורל רפס

תוחפנתה לולכל םילולע תיגרלא הבוגת לש םינימסתה .ינופמיסב שומישה ,המישנב וא העילבב ישוקל םורגל הלולעש ןורגה וא הפה ,םייתפשה ,םינפה ,)רועב תדרגמו תימוקמ תימומדא החירפ - הירקיטרוא( תלרח ,רועב החירפ .םיילוסרקה וא םיילגרה ,םיידיה לש תוחפנתה תונכסמ תורידנ םיתיעל וא תורומח תויהל תולולע וללה תובוגתהמ קלח .םייח ןושארה שומישה רחאל שחרתהל תולולע וללה תובוגתהמ קלח .ינופמיסב םירגבתמו םידליב שומיש תצלמומ הניא ל"מ 0.5 -ב ג"מ 50 ,יטמוטוא טע קרזמ/שומישל ןכומ קרזמ ,ינופמיס תיתפוידיא תינורכ םיקרפמ תקלד םע ג"ק 40 -מ תוחפ םילקושה םידליב שומישל .רחא יאופר בצמ לכל 18 ליגל תחתמ םירגבתמו םידליב וא תודליה ליג לש הניא ,ל"מ 1.0 -ב ג"מ 100 ,יטמוטוא טע קרזמ/שומישל ןכומ קרזמ ,ינופמיס .18 ליגל תחתמ םירגבתמו םידליב שומישל תצלמומ אלל תופורת ללוכ תורחא תופורת ,הנורחאל תלטנ םא וא ,חקול התא םא תרחא הפורת לכ ללוכ .חקורל וא אפורל ךכ לע רפס ,הנוזת יפסותו םשרמ תקלדב ,)

Rheumatoid

Arthritis

( תינורגש םיקרפמ תקלדב לופיטל חקול ךנהש

Polyarticular Juvenile Idiopathic

( תודליה ליג לש תיתפוידיא תינורכ םיקרפמ תוילוח תקלדבו )

Psoriatic

Arthritis

( תיתחפס םיקרפמ תקלדב ,)

Arthritis

תויודע אלל סיטירטראולידנופס לאיסקא ,)

Ankylosing

Spondylitis

( תחשקמ לש תיביכ תקלדב וא )

Non‑radiographic Axial Spondyloarthritis

( תויפרגוידר .סגה יעמה :חקול התא םא חקורה וא אפורה תא עדייל שי דחוימב םע דחיב תחקל ןיא ,)תוינורגש תולחמב לופיטל( טפסאטאבא וא הרניקנא .ינופמיס .ןוסיחה תכרעמ לע תועיפשמה תופסונ תופורת שומישה ןמזב )םייח םיביכרמ םיליכמה( םימיוסמ םינוסיח לבקל ןיא - םינוסיח .ינופמיסב הקנהו ןויריה תויהל תננכתמ וא ןויריהב תא םא ינופמיסב שומישה ינפל אפורב ץעוויהל שי

ינופמיסב שומישה .תועודי ןניא ןויריהב םישנ לע ינופמיס לש היתועפשה .ןויריהב .ץלמומ וניא ןויריהב םישנב שומיש ידי לע ןויריהל סנכיהלמ ענמיהל ךיילע ,ינופמיסב תלפוטמ תא םא

ירחא תוחפל םישדוח 6 ךשמלו לופיטה ךלהמב םימיאתמ העינמ יעצמאב .ינופמיס לש הנורחאה הקירזה ךלופיטמ םישדוח 6 תוחפל רובעל םיכירצ ,קיניהל יליחתתש ינפל - הקנה

.ינופמיסב ןורחאה .ינופמיס לבקל הרומא תא םא קיניהל קיספהל ךיילע

רתוי הובג ןוכיסב תויהל לולע ךקונית ,ןויריהה ךלהמב ינופמיס תלביק םא םירחא יאופר תווצ ישנאלו ךקונית לש ואפורל ירפסתש בושח .םוהיזב תוקלל והשלכ ןוסיח לבקי ךקוניתש ינפל ,ןויריהה ךלהמב ינופמיסב תשמתשהש לע םימוהיזל רתוי הובג ןוכיסב ךקונית תא דימעהל םייושע םימיוסמ םינוסיחו רחאמ .)"םינוסיח“ ףיעס יאר ףסונ עדימל( שומישה ינפל חקורב וא אפורב ץעוויהל שי הקינימ וא ןויריהב ךנה םא .תופורתב תונוכמב שומישו הגיהנ וא םילכב שמתשהל ,גוהנל ךתלוכי לע הלק העפשה תויהל הלולע ינופמיסל רבדה םא .תרוחרחס עיפוהל הלולע ,ינופמיסב שומישה רחאל .תונוכמ ליעפהל .תונוכמ ליעפהל וא םילכב שמתשהל ,גוהנל ןיא ,הרוק ינופמיס לש םיביכרמהמ קלח לע בושח עדימ סקטלל תושיגר .סקטל ליכמ ,טחמה יוסיכ ,יטמוטואה טעה קרזמ/שומישל ןכומה קרזמהמ קלח שומישה ינפל ,ךאפורל רפס ,הרומח תיגרלא הבוגתל םורגל לולע סקטלש םושמ .סקטלל םישיגר ךב לפטמה וא התא םא ,ינופמיסב לוטיברוסל תוליבס יא ,םימיוסמ םירכוסל תוליבס יאמ לבוס ךנה םא .)

E420

( לוטיברוס הליכמ ינופמיס .הפורתב שומישה ינפל ךאפור םע רשק רוצ ?הפורתב שמתשת דציכ .3 אפורה םע קודבל ךילע .אפורה תוארוהל םאתהבו דימת רישכתב שמתשהל שי .רישכתב לופיטה ןפואו ןונימל עגונב חוטב ךניא םא חקורה וא .דבלב אפורה ידי לע ועבקי לופיטה ןפואו ןונימה ,סיטירטראולידנופס לאיסקאבו תיתחפס םיקרפמ תקלדב ,תינורגש םיקרפמ תקלדב סיטירטראולידנופס לאיסקאו )

Ankylosing Spondylitis

( תחשקמ תוילוח תקלד תללוכה

Non‑radiographic Axial Spondyloarthritis

( תויפרגוידר תויודע אלל יטמוטוא טע קרזמ/שומישל ןכומ קרזמ תלוכת( ג"מ 50 :אוה לבוקמה ןונימה .שדוח לכב ךיראתה ותואב ,שדוחב םעפ )ג"מ 50 לש דחא ךישמהל ךילע םאה טילחי אפורה .תיעיברה הנמה תקרזה ינפל ךאפורב ץעוויה .ינופמיסב לופיטב ינש תלוכת( ג"מ 100 -ל לדגת הנמהו ןכתיי ,ג"ק 100 לעמ לקוש התא םא קרזמ תלוכת וא ג"מ 50 לש םייטמוטוא טע יקרזמ/שומישל םינכומ םיקרזמ ותואב שדוחב םעפ )ג"מ 100 לש דחא יטמוטוא טע קרזמ/שומישל ןכומ דחא .שדוח לכב ךיראת :תודליה ליג לש תיתפוידיא תינורכ םיקרפמ תקלדב לופיטל לבוקמה ןונימה .שדוח לכב ךיראתה ותואב ,שדוחב םעפ ג"מ 50 תצלמומה הנמה אפורה לע .תיעיברה הנמה תא לבקמ ךדליש ינפל דליה לש ואפורב ץעוויה .ינופמיסב לופיטב ךישמהל ךדלי לע םאה עובקל

Ulcerative Colitis

( סגה יעמה לש תיביכ תקלדב לופיטב לבוקמה ןונימה /שומישל םינכומ םיקרזמ 4 תלוכת( ג"מ 200 לש תיתלחתה הנמ :לופיט תלחתה יקרזמ/שומישל םינכומ םיקרזמ 2 תלוכת וא ג"מ 50 לש םייטמוטוא טע יקרזמ םיקרזמ 2 תלוכת( ג"מ 100 ןכמ רחאל םייעובשו )ג"מ 100 לש םייטמוטוא טע ןכומ דחא קרזמ תלוכת וא ג"מ 50 לש םייטמוטוא טע יקרזמ/שומישל םינכומ .)ג"מ 100 לש דחא יטמוטוא טע קרזמ/שומישל :הקוזחת ןונימ /שומישל ןכומ קרזמ תלוכת( ג"מ 50 :ג"ק 80 -מ תוחפ םילקושה םילוחב תועובש 4 לכו ןורחאה לופיטה רחאל תועובש 4 )ג"מ 50 לש יטמוטוא טע קרזמ .ןכמ רחאל /שומישל םינכומ םיקרזמ 2 תלוכת( ג"מ 100 :רתויו ג"ק 80 םילקושה םילוחב טע קרזמ/שומישל ןכומ דחא קרזמ תלוכת וא ג"מ 50 לש םייטמוטוא טע יקרזמ תועובש 4 לכו ןורחאה לופיטה רחאל תועובש 4 )ג"מ 100 לש דחא יטמוטוא .ןכמ רחאל .תצלמומה הנמה לע רובעל ןיא :שומישה ןפוא .)תירוע תת( רועל תחתמ הקרזהב תנתינ ינופמיס םייושע ךאפורו התא ,םלוא ,הפורתה תא וקירזי תוחאה וא אפורהו ןכתיי ,הליחתב הכרדה לבקת ,הזכ הרקמב .ךמצעב ינופמיסה תא קירזהל לוכי התאש טילחהל .תאז תושעל דציכ .ךמצעל הקירזה ןתמל רשקב ןהשלכ תולאש ךל שי םא אפורה םע חחוש .הז ןולע ףוסב תוטרופמ ,"ןתמל תויחנה"ה ללגב וא רתוי הלודג הנמ תקרזה ללגב םא( רתוי הובג ןונימ תועטב תלטנ םא תזירא אבהו םילוח תיב לש ןוימ רדחל וא אפורל דימ הנפ )ידמ הפוכת הקרזה .ךתיא הפורתה דימ החכשנש הנמה תא קרזה ,עבקנש דעומב הפורתה תא לוטיל תחכש םא .החכשנש הנמה לע תוצפל ידכב הלופכ הנמ קירזהל ןיא .תרכזנשכ ?האבה הנמה תא קירזהל יתמ קרזה ,הקירזה תא לבקל רומא תייה וב דעומהמ םייעובשמ תוחפ ופלח םא .ירוקמה םינמזה חול יפל לופיטב ךשמהו תרכזנשכ דימ החכשנש הנמה תא תא קרזה ,הקירזה תא לבקל רומא תייה וב דעומהמ םייעובשמ רתוי ופלח םא

הקרזהה דעומ יבגל חקורב וא אפורב ץעוויהו תרכזנשכ דימ החכשנש הנמה .אבה .חקורה םע וא אפורה םע ץעייתה ףלח ןמז המכ חוטב ךניא םא

אפורה ידי לע ץלמוהש יפכ לופיטב דימתהל שי םרט חקורב וא אפורב ץעוויה הפורתה תליטנ תא קיספהל לקוש התא םא .הקספהה .הפורת לטונ ךנהש םעפ לכב הנמהו תיוותה קודב !ךשוחב תופורת לוטיל ןיא .םהל קוקז ךנה םא םייפקשמ בכרה .חקורב וא אפורב ץעוויה ,הפורתב שומישל עגונב תופסונ תולאש ךל שי םא יאוול תועפות .4 .םישמתשמהמ קלחב יאוול תועפותל םורגל לולע ינופמיסב שומישה ,הפורת לכב ומכ .ןהמ תחא ףאמ לובסת אלו ןכתיי .יאוולה תועפות תמישר ארקמל להבית לא .לופיטל קקדזהל םילולעו תורומח יאוול תועפותמ לובסל םילולע םימיוסמ םילפוטמ ןונימ תמועל ג"מ 100 לש ןונימב רתוי לודג תומיוסמ יאוול תועפות לש ןוכיסה הקרזהה רחאל םישדוח רפסמ דע עיפוהל תויושע יאוול תועפות .ג"מ 50 לש .הנורחאה תואבה תורומחה יאוולה תועפות תועיפומ םא אפורל דימ תונפל שי :תוללוכה םייח תונכסמ תורידנ םיתיעל וא ,תורומח תויהל תולוכיה תויגרלא תובוגת ,םייתפשה ,םינפה תוחפנתה לולכל םילוכי תיגרלא הבוגת לש םינימסת .)רידנ( תלרח ,רועב החירפ ,המישנב וא העילבב ישוקל םורגל הלולעש ןורגה וא הפה ,םיידיה לש תוחפנתה ,)רועב תדרגמו תימוקמ תימומדא החירפ - הירקיטרוא( ןתמה רחאל שחרתהל םילולע הלא םינימסתמ קלח .םיילוסרקה וא םיילגרה .ינופמיס לש ןושארה םירומח םד ימוהיז ללוכ םייקדייח םימוהיז ,תפחש ללוכ( םירומח םימוהיז )םירחא םייטסינוטרופוא םימוהיז וא רומח יתיירטפ םוהיז ,תואיר תקלדו ,)ךשמתמ( לועיש ,תופייע ,םוח לולכל םילוכי םוהיז לש םינימסת .)חיכש( ,לושלש ,הליל תועזה ,לקשמב הדירי ,תעפש ייומד םינימסת ,המישנ רצוק .ןתש ןתמ ןמזב הבירצ תשוחת וא םיינישב תויעב ,םיעצפ סיטיטפה ךל היהש וא אשנ ךנה םא

B

גוסמ תבהצה ףיגנ לש היצביטקאר םוח עבצב ןתש ,םייניעהו רועה תבהצה לולכל םילוכי םינימסת .)רידנ( רבעב

B

תופייע תשוחת ,תואקה ,הליחב תשוחת ,םוח ,ןטבה לש ןימי דצב באכ ,ההכ .הדבכ הלחמ לש םינימסת .)רידנ( הצופנ תשרט ןוגכ םיבצעה תכרעמ לש הלחמ ,םיידיב וא םיילגרב השלוח ,הייארב םייוניש לולכל םילוכי םיבצעה תכרעמ לש .ףוגה לש קלח לכב ץוצקע וא השוחת רסוח םילוכי המופמיל לש םינימסת .)רידנ( )המופמיל( הפמילה תוטולב לש ןטרס .םוח וא לקשמ דוביא ,הפמילה ירשק לש תוחפנתה לולכל וא המישנ רצוק לולכל םילוכי יבבל לשכ לש םינימסת .)רידנ( יבבל לשכ .םיילגרה תופכ לש תוחפנתה :תוארקנה ןוסיחה תכרעמ לש תוערפה לש םינמיס וא םייחלה לע החירפ וא םיקרפמב באכ לולכל םילוכי םינימסת .)רידנ( תבאז

.שמשל השיגרה תועורז ,המישנ רצוק ,ךשמתמ לועיש לולכל םילוכי םינימסת .)רידנ( סיזודיאוקרס רועב תוחירפ ,לקשמב הדירי ,הפמילה תוטולב לש תוחפנתה ,םוח ,הזחב באכ .תשטשוטמ הייארו לולכל םילוכי םינימסת .)רידנ( )סיטילוקסו( םינטק םד ילכ לש תוחפנתה רסוח ןוגכ תויבצע תויעבו החירפ ,הליל תועזה ,לקשמב הדירי ,שאר באכ ,םוח .ץוצקעו השוחת םילודיג וא רועה הארמב םייוניש לולכל םילוכי םינימסת .)ץופנ אל( רועה ןטרס .רועה ינפ לע ,דרוי אלש םוח לולכל םילוכי םד תלחמ לש םינימסת .)חיכש( םד תלחמ .ןורוויח וא הבר תולקב םומיד וא העיצפ ,תופייע תשוחת ,םוח לולכל םילוכי םינימסת .)רידנ( )הימקול( םדה ןטרס

.הליל תועזהו תולקב תועצפיה ,םיפוכת םימוהיז רתויב תועיפומש תועפות )

very common

( דואמ תוחיכש יאוול תועפות :הרשעמ דחא שמתשממ .תלזנ ,תודירצ וא ןורג באכ ,תונוילעה המישנה יכרדב םימוהיז םישמתשמ 1-10 -ב תועיפומש תועפות )

common

( תוחיכש יאוול תועפות :100 ךותמ תוקידב ךלהמב תולגתמה )דבכ ימיזנאב היילע( תוגירח דבכ תוקידב תואצות אפורה ידי לע תועצובמה םד תרוחרחס תשוחת שאר יבאכ ץוצקע תשוחת וא השוחת רדעה םייחטש םייתיירטפ םימוהיז תוסרומ )סיטילולצ ןוגכ( םייקדייח םימוהיז םימודא םד יאת לש תוכומנ תוריפס םינבל םד יאת לש תוכומנ תוריפס תבאזל תיבויח םד תקידב תויגרלא תובוגת לוכיע יישק ןטב יבאכ הליחב תעפש )סיטיכנורב( תונופמס תקלד םיסוניסב םוהיז רוק יעצפ הובג םד ץחל םוח םיפוצפצ ,המישנ רצוק ,)המתסא( תרצק סגה יעמה לשו הביקה ןפוד לש תקלד תוללוכה םייעמבו הביקב תוערפה םוחל םורגל תויושעה הפב םיביכו םיבאכ ,דוריג ,תורובח ,באכ ,תוחישק ,תוימומדא תוברל( הקרזהה םוקמב תובוגת )יוריגו ץוצקע רעיש דוביא רועב דוריגו החירפ הניש יישק ןואכיד השלוח תשוחת תומצעב םירבש הזחב תוחונ יא 1-10 -ב תועיפומש תועפות )

uncommon

( תוחיכש ןניאש יאוול תועפות :1,000 ךותמ םישמתשמ הילכב םוהיז רועב תומוש ללוכ ,םיינטרס אל םישוג וא םילודיגו רועה ןטרס תוברל ,ןטרס

רועב םיעצפ תויחופלש תרוצב וא/ו םיילגרה תופכ וא/ו םיידיה תופכב ללוכ ,סיזאירוספ( תחפס )רועב הכומנ תויסט תריפס םינבלו םימודא םד יאתו םד תויסט לש תבלושמ הכומנ הריפס סירתה תטולבב תוערפה םדב רכוסה תומרב היילע םדב לורטסלוכה תומרב היילע לקשמה יווישב תוערפה הייארב תוערפה רידס אל ןפואב םעופ בלהש השוחת בלב םדה ילכ תורציה םד ישירק הקמסה תוריצע תואירב ינורכ יתקלד בצמ )טשוה הלעמב הביקה לש יצמוחה לזונה לש המירז( יצמוח רזחה הרמ ינבא דבכב תוערפה דשב תוערפה תסווב תוערפה םישמתשמ 1-10 -ב תועיפומש תועפות )

rare

( תורידנ יאוול תועפות :10,000 ךותמ םצעה חמ ידי לע םד יאת רוצייב לשכ םינבלה םיאתה רפסמב הרומח הדירי

םתוא תפטועה המקרה וא םיקרפמה לש םוהיז המלחהב תוקל םיימינפ םירביאב םדה ילכ לש תקלד הימקיול )רועה ןטרס לש גוס( המונלמ )רוע ןטרס לש גוס(

Merkel cell carcinoma

ףלקתמ ,ישקשק רוע

הפמילה ירשקו ,רועה ,תואירה לע עיפשהל הלולעה ןוסיחה תכרעמב הערפה

)סיזודיאוקרסכ רקיעב תאטבתמ( םיילגרה וא םיידיה תועבצא עבצב םייונישו םיבאכ

םעטה שוחב תוערפה

ןתשה תיחופלשב תוערפה

תוילכב תוערפה

החירפל תמרוג רשא רועב םדה ילכ לש תקלד

:)העבקנ םרט ןתוחיכשש תועפות( העודי הניא התוחיכשש יאוול תעפות

Hepatosplenic T-cell

( םיריעצ םישנא רקיעב ףקותה םדה ןטרס לש רידנ גוס

lymphoma

התא רשאכ וא ,הרימחמ יאוולה תועפותמ תחא םא ,יאוול תעפות העיפוה םא .אפורה םע ץעייתהל ךילע ,ןולעב הרכזוה אלש יאוול תעפותמ לבוס חוויד" רושיקה לע הציחל תועצמאב תואירבה דרשמל יאוול תועפות לע חוודל ןתינ תואירבה דרשמ רתא לש תיבה ףדב אצמנש "יתפורת לופיט בקע יאוול תועפות לע .יאוול תועפות לע חווידל ןווקמה ספוטל הנפמה )

www.health.gov.il

?הפורתה תא ןסחאל ךיא .5 גשיהל ץוחמ רוגס םוקמב רומשל שי תרחא הפורת לכו וז הפורת !הלערה ענמ םורגת לא .הלערה ענמת ךכ ידי לעו תוקונית וא/ו םידלי לש םתייאר חווטו םדי .אפורהמ תשרופמ הארוה אלל האקהל יבג לע עיפומה )

exp. date

( הגופתה ךיראת ירחא הפורתב שמתשהל ןיא .שדוח ותוא לש ןורחאה םויל סחייתמ הגופתה ךיראת .הזיראה .)יתיב ררקמב בור יפ לע ררוש הז תורוטרפמט חווט :

2°C‑8°C

( רוריקב ןסחא .איפקהל ןיא ןוטרקה תזיראב יטמוטואה טעה קרזמ/שומישל ןכומה קרזמה תא רומשל שי

.רואמ הפורתה לע ןגהל ידכב תירוקמה תינוציחה ףסונ עדימ .6 :םג הליכמ הפורתה ליעפה רמוחה לע ףסונ

Sorbitol, L‑histidine, polysorbate 80 and water for injections

.)"לוטיברוסל תוליבס יא" האר(

Sorbitol

E420

( הליכמ הפורתה סקטל ליכמ ,טחמה יוסיכ ,יטמוטואה טעה קרזמ/שומישל ןכומה קרזמהמ קלח .)"סקטלל תושיגר" האר( :הזיראה ןכות המו הפורתה תיארנ דציכ ג"מ 50 יטמוטוא טע קרזמב/שומישל ןכומ קרזמב הסימתכ העיגמ ינופמיס

.ל"מ 1.0 -ב ג"מ 100/ל"מ 0.5 -ב דע עבצ תרסח ,)הנינפ יומד קרב תלעב( תצקמב הקירבמ דע הלולצ הסימתה

םינבל דע הצחמל םיפוקש םינטק םיקיקלח רפסמ ליכהל היושעו הריהב הבוהצ וא הרוכע ,העבצ תא הנשמ הסימתה םא ינופמיסב שמתשת לא .ןובלח לש .רתוי םילודג םיקיקלח הב תוארל ןתינש .לארשי ,6099000 םייפש ץוביק ,מ"עב רק 'תלה יס-יי'ג :ותבותכו םושירה לעב דנלוה ,ןדיאל ,101 גווניטסניא ,סקיגולויב ןסנאי :ותבותכו ןרציה םש :תואירבה דרשמב יתכלממה תופורתה סקנפב הפורתה םושיר רפסמ

147323321300

הפורתה ,תאז ףא לע .רכז ןושלב חסונ הז ןולע ,האירקה תלקהלו תוטשפה םשל .םינימה ינש ינבל תדעוימ םאתהב ןכדועו 01/2017 ךיראתב תואירבה דרשמ י"ע רשואו קדבנ הז ןולע 30/04/2018 ךיראתב תואירבה דרשמ תוארוהל יטמוטוא טע קרזמ - ןתמל תויחנה .ןולעה לש ינשה ודצב םיעיפומ ןלהל םירכזומה םירויאה עוצקמ שיא ידי לע הכרדה לבקל ךילע ,ךמצעל ינופמיס קירזהל ךנוצרב םא רוצ אנא ,הכרדה תלביק אל םא .ךמצעל התוא תתלו הקירז ןיכהל דציכ יאופר .הכרדהל השיגפ םאתל ידכ ךלש חקורה וא תוחאה ,אפורה םע רשק יטמוטואה טעה קרזמ הארנ דציכ הארמ )1 רויא האר( ןלהלש םישרתה םימעפל רצוקי "

SmartJect

" יטמוטואה טעה קרזמ הז ןולעב ."

SmartJect

"

."יטמוטואה קרזמה"ל שומישל יטמוטואה קרזמה תנכה .1 .יטמוטואה קרזמה תא רענת לא םעפ ףא .הקרזהה ינפל דימ דע יטמוטואה קרזמה ןמ הסכמה תא ריסת לא םייטמוטואה םיקרזמה רפסמ תא קודב :יכ אדוול תנמ לע םייטמוטואה םיקרזמה תא קודב .ןוכנ קזוחהו םייטמוטואה םיקרזמה רפסמ - .ג"מ 50 לש דחא יטמוטוא קרזמ לבקת ,ג"מ 50 אוה ךלש ןונימה םא

ג"מ 50 לש םייטמוטוא םיקרזמ ינש לבקת ,ג"מ 100 אוה ךלש ןונימה םא * 100 לש דחא יטמוטוא קרזמ לבקתש וא ,תוקירז יתש ךמצעל קירזהל ךרטצתו .ג"מ הקרזה ירתא ינש רחב ,ג"מ 50 לש םייטמוטוא םיקרזמ ינש לבקמ ךנה םא

תא קרזהו )לאמש ךריל היינש הקירזו ןימי ךריל תחא הקירז ,לשמל( םינוש .היינשה ירחא תחא תוקירזה ג"מ 50 לש םייטמוטוא םיקרזמ העברא לבקת ,ג"מ 200 אוה ךלש ןונימה םא * לש םייטמוטוא םיקרזמ ינש לבקתש וא ,תוקירז עברא ךמצעל קירזהל ךרטצתו .תוקירז יתש ךמצעל קירזהל ךרטצתו ג"מ 100 ירתא העברא רחב ,ג"מ 50 לש םייטמוטוא םיקרזמ העברא לבקמ ךנה םא

.היינשה ירחא תחא תוקירזה תא קרזהו םינוש הקרזה הקרזה ירתא ינש רחב ,ג"מ 100 לש םייטמוטוא םיקרזמ ינש לבקמ ךנה םא

.היינשה ירחא תחא תוקירזה תא קרזהו םינוש הגופתה ךיראת תא קודב קרזמה לע )"

" תויתואה ירחא ןיוצמה( הגופתה ךיראת תא קודב

.יטמוטואה .ןוטרקה תספוק לע ספדומה הגופתה ךיראת תא קודבל םג לוכי התא הגופתה ךיראת .ףלח הגופתה ךיראת םא יטמוטואה קרזמב שמתשת לא ךלש חקורה םע וא אפורה םע רשק רוצ אנא .שדוחב ןורחאה םויל סחייתמ .הרזע תלבקל ןוחטיבה םתוח תא קודב .יטמוטואה קרזמה הסכמל ביבסמש ןוחטיבה םתוח תא קודב אפורה םע רשק רוצ אנא .עורק םתוחה םא יטמוטואה קרזמב שמתשת לא .ךלש חקורה םע וא תרוטרפמטל עיגהל יטמוטואה קרזמל רשפאל תנמ לע תוקד 30 ןתמה רדחה רדחה תרוטרפמטב דומעל יטמוטואה קרזמל חנה ,התואנ הקרזה אדוול תנמ לע .םידלי לש םדי גשיהל ץוחמ תוקד 30 ךשמל אספוקל ץוחמ ותוא םמחת לא ,אמגודל( תרחא ךרד לכב יטמוטואה קרזמה תא םמחת לא .)םימח םימב וא לגורקימב תרוטרפמטל עיגהל ול רשפאמ התאש ןמזב יטמוטואה קרזמה הסכמ תא ריסת לא

.רדחה ךל שורדה דויצה ראש תא ןכה דפ תוברל ,ךל שרדייש דויצה ראש תא ןיכהל לוכי התא ,ןיתממ התאש ןמזב .םידח םיצפח ןוסחאל םיאתמ לכימו הזג וא ןפג רמצ רודכ ,לוהוכלא יטמוטואה קרזמב לזונה תא קודב קירבמ דע לולצ יטמוטואה קרזמב לזונהש אדוול ידכ הייפצה תינולח ךרד טבה ליכהל הלוכי הסימתה .ריהב בוהצ דע עבצ לוטנו )הנינפ יומד קרב לעב( תצקמב שמתשהל ןתינ .ןובלח לש ,םינבל וא הצחמל םיפוקש ,םינטק םיקיקלח טעמ .הב .ןיקת רבדה ,ריוא תעובב םג ןיחבהל ןתינ ליכמ וא רוכע ,ןוכנ אל עבצב אוה לזונה םא יטמוטואה קרזמב שמתשת לא .ךלש חקורה םע וא אפורה םע חחוש ,הזכ הרקמב .רתוי םילודג םיקיקלח )2 רויא האר( ותנכהו הקרזהה םוקמ תריחב .2 .םייכריה זכרמ תיזחל הפורתה תא םיקירזמ ללכ ךרדב תורישי מ"ס 5 לש רוזאל דבלמ ,רובטה וקל תחתמ ,ןטבל םג קירזהל לוכי התא .רובטל תחתמ ףוגה לדוגל וא הנבמל רשק אלל ,תומוקמה ינשמ דחא לכל קירזהל לוכי התא .ךלש שיש וא השק וא ישקשק ,םודא ,לובח ,שיגר רועה םהב םירוזאל קירזת לא .החיתמ ינמיס וא תוקלצ םהב םירוזאב תוקירזה תא קירזהל שי ,ןתמה ותואב תחא הקירזמ רתויב ךרוצ שי םא

.ףוגה לש םינוש ךמצעב הקירזה תא קירזמ ךניא םא םילפטמ ידי לע הקרזהה םוקמ תריחב )3 רויא האר( לש ינוציחה רוזאב םג שמתשהל לוכי אוה ,הקירזה תא ךל קירזמ לפטמ םא .תועורזה לש ןוילעה קלחה וא הנבמל רשק אלל ,ורכזוהש תומוקמה לכב שמתשהל ןתינ ,הז הרקמב םג .ךלש ףוגה לדוגל הקרזהה םוקמ תנכה .םימח םימו ןובס םע בטיה ךידי תא ץחר .לוהוכלא דפ םע הקרזהה םוקמ תא הקנ .יקנה רוזאה לע ףושנת וא ףנפנת לא .הקרזהה ינפל שבייתהל רועל חנה .הקירזה ןתמ ינפל בוש הז רוזאב עגית לא הפורתה תקרזה .3 .הפורתה תא קירזהל ןכומ התאש דע הסכמה תא ריסהל ןיא .הסכמה תרסהמ תוקד 5 ךותב הפורתה תא קירזהל שי

)4 רויא האר( הסכמה תא רסה םתוח תא עורקל ידכ הסכמה תא טעמ בבוס ,קירזהל ןכומ התא רשאכ .ןוחטיבה .ותוא קורזו הכישמב הסכמה תא רסה קרזמה ךותבש טחמל קזנ םורגל לולע רבדה יכ ומוקמל הסכמה תא ריזחת לא .יטמוטואה .ומוקמב היה אל הסכמה רשאכ לפנ אוה םא יטמוטואה קרזמב שמתשת לא .ךלש חקורה םע וא אפורה םע רשק רוצ ,הזכ הרקמב )6 -ו 5 רויא האר( רועה דגנכ הקזוחב יטמוטואה קרזמה תא ץחל .הז ןמזב רותפכה לע ץחלת לא .תוחונב ךדיב יטמוטואה קרזמה תא זוחא הנומת( תצלמומ הניה רועה תטיבצ אלל הקרזה .הקרזה תוטיש יתש ןיב רחב רוציל תנמ לע רועה תא טובצל לוכי התא ,ףידעמ ךנה םא ,תאז םע .)'א 5 .)'ב 5 הנומת( הקרזהל רתוי ביצי חטשמ הרשי תיווזב ךרוע דגנכ הקזוחב יטמוטואה קרזמה לש חותפה הצקה תא ץחל ףוקשה יוסיכה ךות לא ואולמב קילחמ תוחיטבה לוורש רשא דע )תולעמ 90( .)6 רויא( )7 רויא האר( קירזהל ידכ רותפכה לע ץחל קלחה לע ץחלו ךרוע דגנכ הקזוחב יטמוטואה קרזמה תא ץוחלל ךשמה לע ץוחלל ןתינ אל .לדוגאה וא תועבצאה תועצמאב רותפכה לש םרומה תוחיטבה לוורשו רועה דגנכ הקזוחב ץוחל יטמוטואה קרזמה םא אלא רותפכה .ףוקשה יוסיכה ךותל קילחמ וילע ליעפהל ךישמהל ךרוצ ןיאש ךכ ץוחל ראשי אוה ,ץחלנ רותפכהש עגרב .ץחל טחמהש אוה ןושארה "קילק"ה שוריפ .להבית לא - קזח "קילק" עמשת

.אלש ןכתייו טחמה תריקד תא שיגרתו ןכתיי .הליחתה הקרזההשו הרדחוה יטמוטואה קרזמה תמרהב .ךרועמ יטמוטואה קרזמה תא ןיידע םירת לא .הפורתה תנמ אולמ תא לבקל אלש לולע התא ךרועמ )8 רויא האר( ינשה "קילק"ה דע ץוחלל ךשמה עמשתש דע ךרוע דגנכ הקזוחב יטמוטואה קרזמה תא זוחאל ךשמה 15 דע תחקל םג לוכי ךא ,תוינש 3-6 חקול ללכ ךרדב הז .ינש "קילק" .ינשה "קילק"ה עמשיש דע תוינש קרזמה ךותל הרזח הסנכנ טחמהו המייתסה הקרזההש אוה ינשה "קילק"ה שוריפ לע תצחל ובש עגרה ןמ תוינש 15 רופס ,העימש תייעב ךל שי םא .יטמוטואה .הקרזהה םוקממ יטמוטואה קרזמה תא םרה זאו הנושארל רותפכה .הקרזהה םוקממ יטמוטואה קרזמה תא םרה

הקרזהה רחאל .4 הזגב וא ןפג רמצ רודכב שמתשה .ןיקת רבדה .הקרזהה םוקמב לזונ וא םד לש הנטק תומכ ןכתית .תוינש 10 ךשמל הקרזהה םוקמ דגנכ הזג וא ןפג רמצ רודכ ץוחלל ןתינ .ןטק קבדמ דגא תועצמאב הקרזהה םוקמ תא תוסכל ןתינ ,ץוחנ רבדה םא .ךרוע תא ףשפשת לא רויא האר( הניקת הקרזה רשאמ בוהצ ןמס - הייפצה תינולח תא קודב

)9

וניא בוהצה ןמסה םא .יטמוטואה טעה קרזמ לש הנכובל רבוחמ בוהצה ןמסה .השחרתה אל הקרזההו יוארכ המדקתה אל הנכובה ,הייפצה תינולחב הארנ .ילמרונ רבדה .הייפצה תינולחמ תיצחמכ הסכי בוהצה ןמסה הייפצה תינולחב הארנ אל בוהצה ןמסהו הדימב חקורה וא אפורה םע חחוש אלל תפסונ הנמ קירזת לא .הנמה אולמ תא תלביק אל יכ דשוח ךנה םא וא .אפורה םע תוצעייתה יטמוטואה קרזמה תא קורז תויחנהה יפל ,םידח םיצפחל םיאתמה לכימל ךלש יטמוטואה קרזמה תא ךלשה .ךלש תוחאה ןמ וא אפורה ןמ תלביקש אפורה םע רבד ,חוטב ךניא םא וא שבתשה הקרזהב והשמש שיגרמ התא םא .ךלש חקורה םע וא שומישל ןכומ קרזמ - ןתמל תויחנה .ןולעה לש ינשה ודצב םיעיפומ ןלהל םירכזומה םירויאה עוצקמ שיא ידי לע הכרדה לבקל ךילע ,ךמצעל ינופמיס קירזהל ךנוצרב םא רוצ אנא ,הכרדה תלביק אל םא .ךמצעל התוא תתלו הקירז ןיכהל דציכ יאופר .הכרדהל השיגפ םאתל ידכ ךלש חקורה וא תוחאה ,אפורה םע רשק ןולעב .שומישל ןכומה קרזמה הארנ דציכ הארמ )10 רויא האר( ןלהלש םישרתה ."קרזמ"ל םימעפל רצוקי "שומישל ןכומ קרזמ" הז שומישל קרזמה תנכה .1 קרזמה ףוגב קרזמה תא זוחא .טחמה הסכמב וא טחמה ןגמ יפנכב ,הנכובב ,הנכובה שארב קיזחת לא

.הרוחא הנכובה תא ךושמת לא םעפ ףא

.קרזמה תא רענת לא םעפ ףא

.תאז תושעל היחנה לבקתש דע קרזמה טחממ הסכמה תא ריסת לא

ידכ ,)10 רויאב * תויבכוכב םינמוסמ( טחמה ןגמ תלעפהל םיקדהמב עגית לא .טחמה ןגמ ידי לע טחמה לש םדקומ יוסיכ עונמל םיקרזמה רפסמ תא קודב :יכ אדוול תנמ לע םיקרזמה תא קודב .ןוכנ קזוחהו םיקרזמה רפסמ - .ג"מ 50 לש דחא קרזמ לבקת ,ג"מ 50 אוה ךלש ןונימה םא * קירזהל ךרטצתו ג"מ 50 לש םיקרזמ ינש לבקת ,ג"מ 100 אוה ךלש ןונימה םא * .ג"מ 100 לש דחא קרזמ לבקתש וא ,תוקירז יתש ךמצעל ,לשמל( םינוש הקרזה ירתא ינש רחב ,ג"מ 50 לש םיקרזמ ינש לבקמ ךנה םא

תחא תוקירזה תא קרזהו )לאמש ךריל היינש הקירזו ןימי ךריל תחא הקירז .היינשה ירחא ךרטצתו ג"מ 50 לש םיקרזמ העברא לבקת ,ג"מ 200 אוה ךלש ןונימה םא * ךרטצתו ג"מ 100 לש םיקרזמ ינש לבקתש וא ,תוקירז עברא ךמצעל קירזהל .תוקירז יתש ךמצעל קירזהל םינוש הקרזה ירתא העברא רחב ,ג"מ 50 לש םיקרזמ העברא לבקמ ךנה םא

.היינשה ירחא תחא תוקירזה תא קרזהו קרזהו םינוש הקרזה ירתא ינש רחב ,ג"מ 100 לש םיקרזמ ינש לבקמ ךנה םא

.היינשה ירחא תחא תוקירזה תא )11 רויא האר( הגופתה ךיראת תא קודב ידי לע תיוותה לעש )"

" תויתואה ירחא ןיוצמה( הגופתה ךיראת תא קודב .קרזמה ףוגב תמקוממה הייפצה תינולח ךרד תוננובתה תא זוחא ,הייפצה תינולח ךרד הגופתה ךיראת תא תוארל לגוסמ ךניא םא םע הגופתה ךיראת תא רשייל ידכ טחמה הסכמ תא בבוסו ופוגב קרזמה .הייפצה תינולח .ןוטרקה תספוק לע ספדומה הגופתה ךיראת תא קודבל םג ןתינ ןורחאה םויל סחייתמ הגופתה ךיראת .ףלח הגופתה ךיראת םא קרזמב שמתשת לא .הרזע תלבקל ךלש חקורה םע וא אפורה םע רשק רוצ אנא .שדוחה לש רדחה תרוטרפמטל עיגהל קרזמל רשפאל תנמ לע תוקד 30 ןתמה ץוחמ רדחה תרוטרפמטב דומעל קרזמל חנה ,התואנ הקרזה אדוול תנמ לע .םידלי לש םדי גשיהל ץוחמ תוקד 30 ךשמל אספוקל לגורקימב ותוא םמחת לא ,אמגודל( תרחא ךרד לכב קרזמה תא םמחת לא .)םימח םימב וא עיגהל ול רשפאמ התאש ןמזב קרזמה לש טחמה הסכמ תא ריסת לא .רדחה תרוטרפמטל ךל שורדה דויצה ראש תא ןכה דפ תוברל ,ךל שרדייש דויצה ראש תא ןיכהל לוכי התא ,ןיתממ התאש ןמזב .םידח םיצפח ןוסחאל םיאתמ לכימו הזג וא ןפג רמצ רודכ ,לוהוכלא קרזמב לזונה תא קודב .הטמ יפלכ תינפומ הסוכמה טחמה רשאכ ופוגב קרזמה תא זוחא תצקמב קירבמ דע לולצ אוהש אדוו קרזמה לש הייפצה תינולח ךרד לזונב טבה ליכהל הלוכי הסימתה .ריהב בוהצ דע עבצ לוטנו )הנינפ יומד קרב לעב( שמתשהל ןתינ .ןובלח לש ,םינבל וא הצחמל םיפוקש ,םינטק םיקיקלח טעמ .הסימתב ופוגב קרזמה תא זוחא ,הייפצה תינולח ךרד לזונה תא תוארל לגוסמ ךניא םא רויא האר( הייפצה תינולח םע לזונה תא רשייל ידכ טחמה הסכמ תא בבוסו

.)11

םילודג םיקיקלח ליכמ וא רוכע ,ןוכנ אל עבצב אוה לזונה םא קרזמב שמתשת לא .ךלש חקורה םע וא אפורה םע חחוש ,הזכ הרקמב .רתוי )12 רויא האר( ותנכהו הקרזהה םוקמ תריחב .2 .םייכריה זכרמ תיזחל הפורתה תא םיקירזמ ללכ ךרדב תורישי מ"ס 5 לש רוזאל דבלמ ,רובטה וקל תחתמ ,ןטבל םג קירזהל לוכי התא .רובטל תחתמ שיש וא השק וא ישקשק ,םודא ,לובח ,שיגר רועה םהב םירוזאל קירזת לא .החיתמ ינמיס וא תוקלצ םהב םירוזאב תוקירזה תא קירזהל שי ,ןתמה ותואב תחא הקירזמ רתויב ךרוצ שי םא .ףוגב םינוש )13 רויא האר( םילפטמ ידי לע הקרזהה םוקמ תריחב ןוילעה קלחה לש ינוציחה רוזאב םג שמתשהל לוכי אוה ,ךל קירזמ לפטמ םא .תועורזה לש וא הנבמל רשק אלל ,ורכזוהש תומוקמה לכב שמתשהל ןתינ ,הז הרקמב םג .ךלש ףוגה לדוגל הקרזהה םוקמ תנכה .םימח םימו ןובס םע תוידוסיב ךידי תא ץחר .לוהוכלא דפ םע הקרזהה םוקמ תא הקנ .יקנה רוזאה לע ףושנת וא ףנפנת לא .הקרזהה ינפל שבייתהל רועל חנה .הקירזה ןתמ ינפל בוש הז רוזאב עגית לא הפורתה תקרזה .3 קירזהל שי .הפורתה תא קירזהל ןכומ התאש דע טחמה הסכמ תא ריסהל ןיא .טחמה הסכמ תרסהמ תוקד 5 ךותב הפורתה תא .טחמה הסכמ תרסה ךלהמב הנכובב עגית לא )14 רויא האר( טחמה הסכמ תא רסה .תחא דיב קרזמה ףוג תא זוחא ,קירזהל ןכומ התא רשאכ עגית לא ,תאז השוע התאש ןמזב .ותוא קורזו הכישמב טחמה הסכמ תא רסה .הנכובב םיבצמה ינש .טחמה הצקב לזונ תפיטב וא קרזמב ריוא תעובב ןיחבתש ןכתיי

.הפיטה תא ריסהל וא ריואה תא איצוהל ךרוצ ןיאו םיניקת .טחמה הסכמ תרסה רחאל דימ הנמה תא קרזה .חטשמ לכב תעגל הל רשפאת לאו טחמב עגית לא הרקמב .ומוקמב היה אל טחמה הסכמ רשאכ לפנ אוה םא קרזמב שמתשת לא .ךלש חקורה םע וא אפורה םע רשק רוצ ,הזכ הקרזהה ךרוצל קרזמה תא םקמ )15 רויאב האר( הרומה עבצאל המאה ןיב ,תחא דיב קרזמה ףוג תא זוחא תונידעב טובצל ידכ היינשה דיב שמתשה .הנכובה שאר לע לדוגאה תא חנהו .הקזוחב זוחא .םדוק תיקינש רועה רוזא תא .הרוחא הנכובה תא ךושמת לא םעפ ףא הפורתה תא קרזה טחמה תא רדחה .ץוחלה רועה ןמ תולעמ 45 ךרעב לש תיווזב טחמה תא םקמ

.)15 רויא האר( הריהמ תחא העונתב ,עיגת איהש ןכיהל דע ,רועה ךרד ותומלשב אצמנ הנכובה שארש דע הנכובה לע הציחלב הפורתה לכ תא קרזה .)16 רויא האר( טחמה ןגמ יפנכ ןיב לע ץחל ליעפהל ךשמה ,עיגהל הלוכי איהש ןכיהל דע הצוחל הנכובה רשאכ .)17 רויא האר( רועה תא ררחשו טחמה תא ףולש ,הנכובה שאר יפלכ עונל קירה קרזמל רשפאל ידכ הנכובה שארמ תונידעב ךלדוגא תא דרוה

.18 רויאב הארנש יפכ ,טחמה ןגמ ידי לע הסוכמ הלוכ טחמה רשא דע הלעמ הקרזהה רחאל .4 הזגב וא ןפג רמצ רודכב שמתשה .ןיקת רבדה .הקרזהה םוקמב לזונ וא םד לש הנטק תומכ היהת יכ ןכתיי

10 ךשמל קיזחהלו הקרזהה םוקמ לע הזג וא ןפג רמצ רודכ ץוחלל ןתינ .תוינש .ןטק קבדמ דגא תועצמאב הקרזהה םוקמ תא תוסכל ןתינ ,ץוחנ רבדה םא

.ךרוע תא ףשפשת לא קרזמה תא קורז תלביקש תויחנהה יפל ,םידח םיצפחל םיאתמה לכימל קרזמה תא דימ ךלשה .ךלש תוחאה ןמ וא אפורה ןמ .שדחמ טחמה תא תוסכל הסנת לא םתוחיטב ןעמלו ךתואירבו ךתוחיטב ןעמל ,טחמב רזוח שומיש השעת לא םלועל .םירחא לש אפורה םע חחוש ,חוטב ךניא םא וא שבתשה הקרזהב והשמש שיגרמ התא םא .ךלש חקורה םע וא הפורתה ,תאז ףא לע .רכז ןושלב חסונ הז ןולע ,האירקה תלקהלו תוטשפה םשל .םינימה ינש ינבל תדעוימ

Simponi Pen/Syringe PL+PHY SH 07/18

Simponi

Simponi

PATIENT PACKAGE INSERT IN ACCORDANCE WITH THE

PHARMACISTS’ REGULATIONS (PREPARATIONS) - 1986

The medicine is dispensed with a doctor’s prescription only

Name of the preparation, its form and strength

Simponi

®

,

Pre-filled syringe / auto-injector pen,

50 mg in 0.5 ml

Simponi

®

,

Pre-filled syringe / auto-injector pen,

100 mg in 1.0 ml

Solution for injection

The active ingredient and its quantity in a dosage unit

Golimumab 50 mg/0.5 ml

Inactive ingredients and allergens in the preparation ‑ see section 6 “Further

Information”.

Read this leaflet carefully in its entirety before using the medicine. This

leaflet contains concise information about the medicine. If you have further

questions, refer to the doctor or pharmacist.

This medicine has been prescribed for the treatment of your ailment. Do not

pass it on to others. It may harm them even if it seems to you that their

ailment is similar.

The medicine is intended for adults.

In addition to this leaflet, Simponi is provided with a Patient Safety

Information Card. This card contains important safety information you

should be aware of and adhere to before starting and during treatment

with Simponi. Read the Patient Safety Information Card and the patient

leaflet before you start using the preparation. Keep the card for further

reading, if necessary.

1. WHAT IS THE MEDICINE INTENDED FOR?

Simponi belongs to a group of medicines called “TNF blockers” and is used

in adults for the treatment of rheumatoid arthritis, psoriatic arthritis, axial

spondyloarthritis, which includes ankylosing spondylitis and non‑radiographic

axial spondyloarthritis, and ulcerative colitis.

Simponi works by blocking a protein called TNF‑

, which is involved in

inflammatory processes in the body. Blocking it leads to a reduction of

inflammation in the body.

In children weighing at least 40 kg, Simponi is used for the treatment of

polyarticular juvenile idiopathic arthritis.

Therapeutic group: TNF blockers.

2. BEFORE USING THE MEDICINE:

Do not use the preparation if:

you are sensitive (allergic) to the active ingredient golimumab or to any

of the other ingredients contained in the medicine. For a list of the other

ingredients, see section 6 “Further Information”.

you have tuberculosis or any other severe infection.

you suffer from moderate or severe heart failure.

Special warnings regarding use of the medicine:

Before treatment with Simponi, tell the doctor if you suffer from any of the

following conditions:

Infections

Tell the doctor immediately if you already have any symptoms of infection

or if they occur during or after your treatment with Simponi. Symptoms

of infection include fever, cough, shortness of breath, flu‑like symptoms,

diarrhea, sores, dental problems or a burning sensation when urinating.

You may get infections more easily while using Simponi.

Infections may progress more rapidly and may be more severe. In

addition, some previous infections may recur.

Tuberculosis

Tell your doctor immediately if symptoms of tuberculosis occur during or

after the treatment.

Symptoms of tuberculosis include: persistent cough, weight loss, tiredness,

fever or night sweats.

Cases of tuberculosis have been reported in patients treated with

Simponi, in rare cases even in patients treated with medicines for

tuberculosis. The doctor will check you to see if you have tuberculosis.

The doctor will record the test results on your “Patient Safety Information

Card”.

It is very important that you tell your doctor if you have ever suffered

from tuberculosis, or if you have been in close contact with someone

who has or had tuberculosis.

If your doctor is concerned that you are at risk for tuberculosis, you

may be treated with medicines for tuberculosis before you begin using

Simponi.

Hepatitis B virus (HBV)

Tell your doctor if you are a carrier of the virus or if you suffer, or have

suffered in the past, from the disease, before treatment with Simponi.

Tell your doctor if you think you might be at risk of contracting viral

hepatitis B.

Your doctor should test you for the presence of hepatitis B virus.

Treatment with TNF blockers such as Simponi may result in reactivation

of viral hepatitis B in patients who carry this virus, which may be

life‑threatening in some cases.

Invasive fungal infections

If you have lived in or traveled to an area where infections caused by

specific types of fungi that can affect the lungs or other parts of the

body (called histoplasmosis, coccidioidomycosis, or blastomycosis)

are common, tell your doctor immediately. If you do not know whether

these fungal infections are common in the area in which you have lived

or traveled, ask your doctor.

Cancer and lymphoma

Before you use Simponi, tell your doctor if you have ever been diagnosed

with lymphoma (a type of blood cancer) or any other type of cancer.

If you use Simponi or other TNF blockers, your risk for developing

lymphoma or another cancer may increase.

Patients suffering for a long time from severe rheumatoid arthritis

or other inflammatory diseases may be at higher risk for developing

lymphoma.

In children and adolescents who had taken TNF blockers, cases of

cancer of different types were discovered, including unusual types which

sometimes resulted in death.

In rare cases, a certain severe type of lymphoma called hepatosplenic

T-cell lymphoma was discovered in patients receiving TNF blockers.

Most are adolescents or young men. This type of cancer usually

ends in death. Almost all of these patients also received azathioprine

or 6‑mercaptopurine. Tell the doctor if you take azathioprine or

6‑mercaptopurine concomitantly with Simponi.

Patients suffering from severe persistent asthma, chronic obstructive

pulmonary disease (COPD), or who are heavy smokers may be at

increased risk for cancer when under treatment with Simponi. If you have

persistent asthma, COPD or are a heavy smoker, you should discuss

with your doctor whether treatment with a TNF blocker is appropriate

for you.

Some patients treated with Simponi developed certain types of skin

cancer such as melanoma. If you notice changes in the appearance of

the skin or growths on the skin during or after treatment with Simponi,

tell your doctor.

Heart failure

Tell your doctor immediately if you experience new symptoms or worsening

of existing symptoms of heart failure. Symptoms of heart failure include

shortness of breath or swelling of the feet.

New or worsening heart failure has been reported in patients treated

with TNF blockers, including Simponi. Some of these patients died.

If you suffer from mild heart failure and you are being treated with

Simponi, you must be closely monitored by your doctor.

Nervous system diseases

Tell your doctor immediately if you have ever been diagnosed with

or developed symptoms of a demyelinating disease such as multiple

sclerosis. Symptoms may include changes in your vision, weakness in

your arms or legs, numbness or tingling in any part of your body. Your

doctor will decide if you can receive Simponi.

Operations or dental procedures

Tell your doctor if you are due to undergo any operation or dental

procedure.

Tell the surgeon or dentist performing the dental procedure that you

are under treatment with Simponi, by showing the “Patient Safety

Information Card”.

Autoimmune diseases

Tell your doctor if you develop symptoms of a disease called lupus.

Symptoms include persistent rash, fever, joint pain and tiredness.

On rare occasions, people treated with TNF blockers have developed

lupus.

Blood diseases

In some patients, the production of blood cells that help your body fight

infections or stop bleeding may be impaired. If you develop a fever that

does not go away, if you bruise or bleed very easily or look very pale, call

your doctor immediately. Your doctor may decide to stop treatment.

If you are not sure if any of the above apply to you, talk to your doctor or

pharmacist before using Simponi.

Vaccinations

Tell your doctor if you have had, or are due to have, a vaccination.

While using Simponi, you should not receive certain vaccinations (live

vaccines).

Certain vaccinations may cause infections. If you received Simponi

while you were pregnant, your baby may be at higher risk for getting

such an infection for up to approximately six months after the last dose

you received during pregnancy. It is important that you tell your baby’s

doctor and other healthcare professionals that you used Simponi during

pregnancy so they can decide if your baby can be given any vaccine.

Consult the doctor before vaccinating your child. If possible, your child

should get all the required vaccinations before using Simponi.

Treatment with an infectious agent

If you have recently received, or are about to receive, treatment with an

infectious agent (e.g., Bacillus Calmette‑Guérin [BCG] for treatment of

cancer).

Allergic reaction

Tell your doctor immediately if you develop symptoms of an allergic

reaction after using Simponi. Symptoms of an allergic reaction may include

swelling of the face, lips, mouth or throat which may cause difficulty in

swallowing or breathing, skin rash, hives (urticaria ‑ a local itchy red skin

rash), swelling of the hands, feet or ankles.

Some of these reactions may be serious or, rarely, life‑threatening.

Some of these reactions may occur after the first administration of

Simponi.

Use in children and adolescents

Simponi pre‑filled syringe/auto‑injector pen, 50 mg in 0.5 ml is not recommended

for use in children weighing less than 40 kg with polyarticular juvenile idiopathic

arthritis or in children and adolescents under 18 years of age for any other

medical condition.

Simponi pre‑filled syringe/auto‑injector pen, 100 mg in 1.0 ml is not

recommended for use in children and adolescents under 18 years of age.

If you are taking, or if you have recently taken, other medicines, including

non‑prescription medicines and nutritional supplements, tell the doctor or

pharmacist; this includes any other medicine you are taking for the treatment of

rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, psoriatic arthritis

and ankylosing spondylitis, non‑radiographic axial spondyloarthritis or ulcerative

colitis.

You should especially inform the doctor or pharmacist if you are taking:

anakinra or abatacept (for treatment of rheumatic diseases). Do not take

them concomitantly with Simponi.

other medicines that affect the immune system.

vaccinations ‑ do not receive certain vaccinations (that contain live

components) while using Simponi.

Pregnancy and breastfeeding

Consult the doctor before using Simponi if you are pregnant or are planning

to become pregnant. The effects of Simponi on pregnant women are not

known. The use of Simponi in pregnant women is not recommended.

If you are being treated with Simponi, you must avoid becoming pregnant

by using adequate contraception during treatment and for at least 6 months

after the last Simponi injection.

Breastfeeding ‑ At least 6 months must elapse from your last treatment with

Simponi before you begin breastfeeding.

You must stop breastfeeding if you are due to receive Simponi.

If you received Simponi during your pregnancy, your baby may be at higher

risk for getting an infection. It is important that you tell your baby’s doctor

and other healthcare professionals that you used Simponi during your

pregnancy before your baby receives any vaccine since certain vaccines

may put your baby at higher risk of infection (for more information see

“Vaccinations” section).

If you are pregnant or breastfeeding, consult the doctor or pharmacist before

using medicines.

Driving and using machines

Simponi may have a minor effect on your ability to drive, use tools or operate

machines. Dizziness may occur after you take Simponi. If this happens, do

not drive, use any tools or operate machines.

Important information about some of the ingredients of Simponi

Latex sensitivity

A part of the pre‑filled syringe/auto‑injector pen, the needle cover, contains

latex. Because latex may cause a severe allergic reaction, tell your doctor before

using Simponi if you or your caregiver are allergic to latex.

Sorbitol intolerance

Simponi contains sorbitol (E420). If you are intolerant to some sugars, contact

your doctor before using this medicine.

3. HOW SHOULD THE MEDICINE BE USED?

Always use the preparation according to the doctor’s instructions. Check with

the doctor or pharmacist if you are uncertain about the dosage and treatment

regimen of the preparation.

The dosage and treatment regimen will be determined by the doctor only.

For rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis which

includes ankylosing spondylitis and non‑radiographic axial spondyloarthritis:

The usual dosage is: 50 mg (the contents of one 50 mg pre‑filled syringe/

auto‑injector pen) once a month, on the same date each month.

Consult your doctor before taking your fourth dose. The doctor will determine

whether you should continue Simponi treatment.

If you weigh more than 100 kg, the dose might be increased to 100 mg (the

contents of two 50 mg pre‑filled syringes/auto‑injector pens or the contents

of one 100 mg pre‑filled syringe/auto‑injector pen) once a month, on the

same date each month.

The usual dosage for treating polyarticular juvenile idiopathic arthritis:

The recommended dose is 50 mg, once a month, on the same date each

month.

Consult the child’s doctor before your child receives the fourth dose.

The doctor will determine whether the child should continue Simponi

treatment.

The usual dosage for treating ulcerative colitis:

Initiation of treatment: A starting dose of 200 mg (the contents of four

50 mg pre‑filled syringes/auto‑injector pens or the contents of two 100 mg

pre‑filled syringes/auto‑injector pens) followed by 100 mg (the contents

of two 50 mg pre‑filled syringes/auto‑injector pens or the contents of one

100 mg pre‑filled syringe/auto‑injector pen) 2 weeks afterwards.

Maintenance dosage:

In patients weighing less than 80 kg: 50 mg (the contents of one 50 mg pre‑

filled syringe/auto‑injector pen) 4 weeks after the last treatment and every 4

weeks thereafter.

In patients weighing 80 kg and more: 100 mg (the contents of two 50 mg

pre‑filled syringes/auto‑injector pens or the contents of one 100 mg pre‑filled

syringe/auto‑injector pen) 4 weeks after the last treatment and every

4 weeks thereafter.

Do not exceed the recommended dose.

Directions for use:

Simponi is given by injection under the skin (subcutaneously).

At the start, the doctor or nurse may inject the medicine. However, you and

your doctor may decide that you can inject Simponi yourself. In this case, you

will receive training on how to do this.

Talk to the doctor if you have any questions about giving yourself an

injection.

“Instructions for administration” are detailed at the end of this leaflet.

If you accidentally take a higher dosage (either by injecting a higher dose or

by using it too often), immediately refer to the doctor or proceed to a hospital

emergency room and bring the package of the medicine with you.

If you forget to use the medicine on your set date, inject the forgotten dose

as soon as you remember. Never inject a double dose to compensate for the

missed dose.

When to inject your next dose?

If less than two weeks have passed from the day you were supposed to

receive an injection, inject the forgotten dose as soon as you remember and

carry on with the treatment according to the original schedule.

If more than two weeks have passed from the day you were supposed

to receive an injection, inject the forgotten dose as soon as you remember

and consult the doctor or pharmacist about when you need to take the next

dose.

If you are unsure about how much time has passed, consult the doctor or

pharmacist

Adhere to the treatment regimen recommended by the doctor.

If you are considering discontinuing use of the medicine, consult the doctor

or pharmacist before stopping.

Do not take medicines in the dark! Check the label and the dose

each time you take medicine. Wear glasses if you need them.

If you have any further questions regarding use of the medicine, consult the

doctor or pharmacist.

4. SIDE EFFECTS

As with any medicine, use of Simponi may cause side effects in some users.

Do not be alarmed when reading the list of side effects. You may not suffer

from any of them.

Some patients may experience serious side effects and may require treatment.

The risk of certain side effects is greater with the 100 mg dosage compared

with the 50 mg dosage. Side effects may appear up to several months after

the last injection.

Refer to the doctor immediately if any of the following serious side effects

occur, including:

Allergic reactions which can be severe, or rarely, life-threatening (rare).

Symptoms of an allergic reaction can include swelling of the face, lips, mouth

or throat which may cause difficulty in swallowing or breathing, skin rash,

hives (urticaria ‑ a local itchy red skin rash), swelling of the hands, legs or

ankles. Some of these symptoms may occur after the first administration of

Simponi.

Severe infections (including tuberculosis, bacterial infections including

severe blood infections and pneumonia, severe fungal infection or

other opportunistic infections) (common). Symptoms of an infection

can include fever, tiredness, cough (persistent), shortness of breath, flu‑like

symptoms, weight loss, night sweats, diarrhea, sores, dental problems or a

burning sensation when urinating.

Reactivation of hepatitis B virus (HBV) if you are a carrier or if you have

had hepatitis B in the past (rare). Symptoms can include yellowing of the

skin and eyes, dark brown‑colored urine, right‑sided abdominal pain, fever,

nausea, vomiting, feeling very tired.

A disease of the nervous system such as multiple sclerosis (rare).

Symptoms of nervous system disease can include changes in vision,

weakness of the legs or hands, numbness or tingling in any part of the

body.

Cancer of the lymph nodes (lymphoma) (rare). Symptoms of lymphoma

can include swelling of the lymph nodes, weight loss or fever.

Heart failure (rare). Symptoms of heart failure can include shortness of

breath or swelling of the feet.

Signs of disturbances in the immune system called:

lupus (rare). Symptoms can include joint pain or a rash on the cheeks or

arms that is sensitive to the sun.

sarcoidosis (rare). Symptoms can include persistent cough, shortness

of breath, chest pain, fever, swelling of the lymph nodes, weight loss, skin

rashes and blurred vision.

Swelling of small blood vessels (vasculitis) (rare). Symptoms can include

fever, headache, weight loss, night sweats, rash and nerve problems, such

as numbness and tingling.

Skin cancer (uncommon). Symptoms can include changes in skin

appearance or growths on the surface of the skin.

Blood disease (common). Symptoms of blood disease can include a fever

that does not go away, bruising or bleeding very easily or paleness.

Blood cancer (leukemia) (rare). Symptoms can include fever, feeling tired,

frequent infections, bruising easily, and night sweats.

Very common side effects – effects that occur in more than one in ten

users:

Upper respiratory tract infections, sore throat or hoarseness, runny nose.

Common side effects – effects that occur in 1-10 in 100 users:

Abnormal liver test results (elevated liver enzymes) found during blood tests

done by the doctor

Feeling dizzy

Headaches

Numbness or tingling feeling

Superficial fungal infections

Abscesses

Bacterial infections (such as cellulitis)

Low red blood cell counts

Low white blood cell counts

Positive blood test for lupus

Allergic reactions

Indigestion

Abdominal pain

Nausea

Flu

Bronchitis

Sinus infection

Cold sores

High blood pressure

Fever

Asthma, shortness of breath, wheezing

Stomach and bowel disorders which include inflammation of the stomach

lining and colon, which may cause fever

Pain and ulcers in the mouth

Injection site reactions (including redness, hardness, pain, bruising, itching,

tingling and irritation)

Hair loss

Rash and itching of the skin

Difficulty sleeping

Depression

Feeling weak

Bone fractures

Chest discomfort

Uncommon side effects – effects that occur in 1-10 in 1,000 users:

Infection in the kidney

Cancer, including skin cancer and non‑cancerous growths or lumps, including

skin moles

Skin sores

Psoriasis (including on the palms of the hands and/or the soles of the feet

and/or in the form of skin blisters)

Low platelet count

Combined low platelet, red, and white blood cell counts

Thyroid disorders

Increase in blood sugar levels

Increase in blood cholesterol levels

Balance disorders

Vision disturbances

Sensation of heart beating irregularly

Narrowing of the blood vessels in the heart

Blood clots

Flushing

Constipation

Chronic inflammatory condition of the lungs

Acid reflux (backflow of stomach acids into the esophagus)

Gallstones

Liver disorders

Breast disorders

Menstrual disorders

Rare side effects – effects that occur in 1-10 in 10,000 users:

Failure of the bone marrow to produce blood cells

Severe reduction in the number of white cells

Infection of the joints or the tissue around them

Impaired healing

Inflammation of blood vessels in internal organs

Leukemia

Melanoma (a type of skin cancer)

Merkel cell carcinoma (a type of skin cancer)

Scaly, peeling skin

Immune system disorder that could affect the lungs, skin and lymph nodes

(most commonly presenting as sarcoidosis)

Pain and discoloration of the fingers or toes

Taste disturbances

Bladder disorders

Kidney disorders

Inflammation of the blood vessels in the skin which results in rash

Side effect of unknown frequency (effects whose frequency has not yet

been determined): a rare type of blood cancer affecting mostly young people

(hepatosplenic T-cell lymphoma)

If a side effect occurs, if one of the side effects worsens, or if you suffer from

a side effect not listed in the leaflet, consult with the doctor.

Side effects can be reported to the Ministry of Health by clicking on the link

“Report Side Effects of Drug Treatment” found on the Ministry of Health

homepage (www.health.gov.il) that directs you to the online form for reporting

side effects.

5. HOW SHOULD THE MEDICINE BE STORED?

Avoid poisoning! This medicine and any other medicine must be kept in a

safe place out of the reach and sight of children and/or infants in order to

avoid poisoning. Do not induce vomiting unless explicitly instructed to do

so by the doctor.

Do not use the medicine after the expiry date (exp. date) appearing on the

package. The expiry date refers to the last day of that month.

Store under refrigeration (2°C‑8°C: this temperature range is predominant

in most household refrigerators).

Do not freeze.

Keep the pre‑filled syringe/auto‑injector pen in the original outer carton

package in order to protect the medicine from light.

6. FURTHER INFORMATION

In addition to the active ingredient the medicine also contains:

Sorbitol, L‑histidine, polysorbate 80 and water for injections

The medicine contains sorbitol (E420) (see “Sorbitol intolerance”).

A part of the pre‑filled syringe/auto‑injector pen, the needle cover, contains

latex (see “Latex sensitivity”).

What the medicine looks like and the contents of the package:

Simponi is supplied as a solution in a pre‑filled syringe/auto‑injector pen

50 mg in 0.5 ml/100 mg in 1.0 ml.

The solution is clear to slightly opalescent (having a pearl‑like shine),

colorless to light yellow, and may contain a few small translucent or white

particles of protein. Do not use Simponi if the solution is discolored, cloudy

or you can see larger particles in it.

Registration Holder and address: J‑C Health Care Ltd., Kibbutz Shefayim

6099000, Israel.

Name and address of manufacturer: Janssen Biologics, Einsteinweg 101,

Leiden, The Netherlands

Registration number of the medicine in the National Drug Registry of the

Ministry of Health: 147323321300

This leaflet was checked and approved by the Ministry of Health in January

2017 and updated on April 30th, 2018, in accordance with the Ministry of

Health guidelines.

Instructions for administration

Auto-injector pen

The figures mentioned below are on the reverse side of the leaflet.

If you would like to self-inject Simponi, you must be trained by a healthcare

professional how to prepare an injection and give it to yourself. If you

have not been trained, please contact your doctor, nurse or pharmacist

to schedule a training session.

The diagram below (see Fig. 1) shows what the auto‑injector pen “SmartJect”

looks like. In this leaflet the auto‑injector pen “SmartJect” will sometimes be

shortened to “auto‑injector”.

1. Preparing the auto-injector for use

Never shake the auto‑injector.

Do not remove the cap from the auto‑injector until immediately before the

injection.

Check the number of auto-injectors

Check the auto‑injectors to ensure that:

‑ the number and strength of the auto‑injectors are correct.

* If your dosage is 50 mg, you will receive one 50 mg auto‑injector.

* If your dosage is 100 mg, you will receive two 50 mg auto‑injectors and will

have to give yourself two injections, or you will receive one 100 mg auto‑

injector.

If you receive two 50 mg auto‑injectors, choose two different injection sites

(e.g., one injection into the right thigh and the other injection into the left

thigh) and inject the injections one after the other.

* If your dosage is 200 mg, you will receive four 50 mg auto‑injectors and will

have to give yourself four injections, or you will receive two 100 mg auto‑

injectors and will have to give yourself two injections.

If you receive four 50 mg auto‑injectors, choose four different injection sites

and inject the injections one after the other.

If you receive two 100 mg auto‑injectors, choose two different injection sites

and inject the injections one after the other.

Check the expiry date

Check the expiry date (marked after the letters “EXP”) on the auto‑

injector.

You can also check the expiry date printed on the carton box.

Do not use the auto‑injector if the expiry date has passed. The expiry date

refers to the last day of that month. Please contact your doctor or pharmacist

for assistance.

Check the security seal

Check the security seal around the cap of the auto‑injector.

Do not use the auto‑injector if the seal is broken. Please contact your doctor

or pharmacist.

Wait 30 minutes to allow the auto-injector to reach room temperature

To ensure proper injection, allow the auto‑injector to sit at room temperature

outside the box for 30 minutes, out of the reach of children.

Do not warm the auto‑injector in any other way (for example, do not warm

it in a microwave or in hot water).

Do not remove the auto‑injector’s cap while allowing it to reach room

temperature.

Prepare the rest of your required equipment

While you are waiting, you can prepare the rest of your required equipment,

including an alcohol swab, a cotton ball or gauze and an appropriate sharps

container.

Check the liquid in the auto-injector

Look through the viewing window to make sure that the liquid in the auto‑

injector is clear to slightly opalescent (having a pearl‑like shine) and colorless

to light yellow. The solution may contain a few small translucent or white

particles of protein. The solution can be used.

You will also notice an air bubble, which is normal.

Do not use the auto‑injector if the liquid is the wrong color, cloudy or contains

larger particles. If this happens, talk to your doctor or pharmacist.

2. Choosing and preparing the injection site (see Fig. 2)

The medicine is usually injected into the front middle of the thighs.

You can also inject into the abdomen below the belly button line, except for

the 5 cm area directly beneath the belly button.

You can inject into either of the two sites, regardless of your body type or

size.

Do not inject into areas where the skin is tender, bruised, red, scaly or hard

or has scars or stretch marks.

If more than one injection is required at a single dosing session, inject them

into different sites on the body.

Injection site selection by caregivers, if you do not self-inject (see Fig.

3)

If a caregiver is giving you the injection, he/she can also use the outer area

of the upper arms.

In this case too, all sites mentioned can be used, regardless of your body

type or size.

Preparing the injection site

Wash your hands thoroughly with soap and warm water.

Wipe the injection site with an alcohol swab.

Allow the skin to dry before injecting. Do not fan or blow on the clean

area.

Do not touch this area again before giving the injection.

3. Injecting the medicine

Do not remove the cap until you are ready to inject the medicine.

The medicine should be injected within 5 minutes of removing the cap.

Remove the cap (see Fig. 4)

When you are ready to inject, twist the cap slightly to break the security

seal.

Pull the cap off and throw it away.

Do not put the cap back on because it may damage the needle inside the

auto‑injector.

Do not use the auto‑injector if it has fallen without the cap in place. If this

happens, contact your doctor or pharmacist.

Firmly press the auto-injector against the skin (see Fig. 5 and 6)

Hold the auto‑injector comfortably in your hand. Do not press on the button

at this time.

Choose one of two injection methods. Injection without pinching the skin

is recommended (Fig. 5a). However, if you prefer, you can pinch the skin in

order to make a firmer surface for injection (Fig. 5b).

Firmly press the open end of the auto‑injector at a right angle (90 degrees)

against your skin until the safety sleeve fully slides into the clear cover (Fig.

Press the button to inject (see Fig. 7)

Continue to press the auto-injector firmly against your skin and press

on the raised part of the button with the aid of the fingers or thumb.

The button cannot be pressed unless the auto‑injector is firmly pressed

against the skin and the safety sleeve slides into the clear cover.

Once the button is pressed, it will remain pressed in so that you do not need

to keep applying pressure on it.

You will hear a loud “click” - do not be alarmed. The first “click” means

that the needle has been inserted and the injection has started. You may or

may not feel a needle prick.

Do not lift the auto-injector away from your skin yet. If you pull the

auto-injector away from your skin, you may not get the full dose of the

medicine.

Continue to press until the second “click” (see Fig. 8)

Continue to hold the auto-injector down firmly against your skin until

you hear a second “click”. It usually takes 3-6 seconds, but may take

up to 15 seconds until the second “click” is heard.

The second “click” means that the injection is finished and the needle has

gone back into the auto‑injector. If you have a hearing problem, count 15

seconds from the time you first press the button and then lift the auto‑injector

from the injection site.

Lift the auto‑injector from the injection site.

4. After the injection

Use a cotton ball or gauze

There may be a small amount of blood or liquid at the injection site. This is

normal.

You can press a cotton ball or gauze over the injection site and hold for 10

seconds.

If necessary, you may cover the injection site with a small adhesive

bandage.

Do not rub your skin.

Check the viewing window – a yellow indicator confirms a proper injection

(see Fig. 9)

The yellow indicator is connected to the plunger of the auto‑injector pen. If

the yellow indicator is not visible in the viewing window, the plunger did not

advance properly and the injection was not delivered.

The yellow indicator will cover about half of the viewing window. This is

normal.

Talk to your doctor or pharmacist if the yellow indicator is not visible in the

viewing window or if you suspect that you did not receive the full dose. Do

not inject an additional dose without consulting the doctor.

Throw the auto-injector away

Discard your auto‑injector in an appropriate sharps container, according to

the instructions you received from your doctor or nurse.

If you feel that something has gone wrong with the injection or if you are not

sure, talk to your doctor or pharmacist.

Instructions for administration

Pre-filled syringe

The figures mentioned below are on the reverse side of the leaflet.

If you would like to self-inject Simponi, you must be trained by a healthcare

professional how to prepare an injection and give it to yourself. If you

have not been trained, please contact your doctor, nurse or pharmacist

to schedule a training session.

The diagram below (see Fig. 10) shows what the pre‑filled syringe looks like. In

this leaflet, “pre‑filled syringe” may sometimes be shortened to “syringe”.

1. Preparing the syringe for use

Hold the syringe by the body of the syringe

Do not hold by the plunger head, the plunger, the needle guard wings, or

the needle cover.

Never pull back on the plunger.

Never shake the syringe.

Do not remove the cover from the syringe needle until instructed to do so.

Do not touch the needle guard activation clips (indicated by asterisks * in Fig.

10), to prevent prematurely covering the needle with the needle guard.

Check the number of syringes

Check the syringes to ensure that:

‑ the number and strength of the syringes are correct.

* If your dosage is 50 mg, you will receive one 50 mg syringe.

* If your dosage is 100 mg, you will receive two 50 mg syringes and will have

to give yourself two injections, or you will receive one 100 mg syringe.

If you receive two 50 mg syringes, choose two different injection sites (e.g.,

one injection into the right thigh and the other injection into the left thigh)

and inject the injections one after the other.

* If your dosage is 200 mg, you will receive four 50 mg syringes and will have

to give yourself four injections, or you will receive two 100 mg syringes and

will have to give yourself two injections.

If you receive four 50 mg syringes, choose four different injection sites and

inject the injections one after the other.

If you receive two 100 mg syringes, choose two different injection sites and

inject the injections one after the other.

Check the expiry date (see Fig. 11)

Check the expiry date (marked after the letters “EXP”) on the label by looking

through the viewing window located in the body of the syringe.

If you cannot see the expiry date through the viewing window, hold the

syringe by its body and rotate the needle cover to line up the expiry date

with the viewing window.

You can also check the expiry date printed on the carton box.

Do not use the syringe if the expiry date has passed. The expiry date refers

to the last day of that month. Please contact your doctor or pharmacist for

assistance.

Wait 30 minutes to allow the syringe to reach room temperature

To ensure proper injection, allow the syringe to sit at room temperature

outside the box for 30 minutes, out of the reach of children.

Do not warm the syringe in any other way (for example, do not warm it in a

microwave or in hot water).

Do not remove the syringe’s needle cover while allowing it to reach room

temperature.

Prepare the rest of your required equipment

While you are waiting, you can prepare the rest of your required equipment,

including an alcohol swab, a cotton ball or gauze and an appropriate sharps

container.

Check the liquid in the syringe

Hold the syringe by its body with the covered needle pointing downward.

Look at the liquid through the viewing window of the syringe and make sure

that it is clear to slightly opalescent (having a pearl‑like shine) and colorless

to light yellow. The solution may contain a few small translucent or white

particles of protein. The solution can be used.

If you cannot see the liquid through the viewing window, hold the syringe

by its body and rotate the needle cover to line up the liquid with the viewing

window (see Fig. 11).

Do not use the syringe if the liquid is the wrong color, cloudy, or contains larger

particles. If this happens, talk to your doctor or pharmacist.

2. Choosing and preparing the injection site (see Fig. 12)

The medicine is usually injected into the front middle of the thighs.

You can also inject into the abdomen below the belly button line, except for

the 5 cm area directly beneath the belly button.

Do not inject into areas where the skin is tender, bruised, red, scaly or hard

or has scars or stretch marks.

If more than one injection is required at a single dosing session, inject them

into different sites on the body.

Injection site selection by caregivers (see Fig. 13)

If a caregiver is giving you the injection, he/she can also use the outer area

of the upper arms.

In this case too, all sites mentioned can be used, regardless of your body

type or size.

Preparing the injection site

Wash your hands thoroughly with soap and warm water.

Wipe the injection site with an alcohol swab.

Allow the skin to dry before injecting. Do not fan or blow on the clean

area.

Do not touch this area again before giving the injection.

3. Injecting the medicine

The needle cover should not be removed until you are ready to inject the

medicine. The medicine should be injected within 5 minutes of removing the

needle cover.

Do not touch the plunger while removing the needle cover.

Remove the needle cover (see Fig. 14)

When you are ready to inject, hold the body of the syringe with one hand.

Pull the needle cover straight off and throw it away. Do not touch the plunger

while you do this.

You may notice an air bubble in the syringe or a drop of liquid at the end of

the needle. These are both normal and there is no need to expel the air or

remove the drop.

Inject the dose immediately after removing the needle cover.

Do not touch the needle or allow it to touch any surface.

Do not use the syringe if it is dropped without the needle cover in place. If this

happens, contact your doctor or pharmacist.

Position the syringe for injection

Hold the body of the syringe with one hand between the middle and index

fingers (see Fig. 15) and place the thumb on top of the plunger head. Use

the other hand to gently pinch the area of skin that you previously cleaned.

Hold firmly.

Never pull back on the plunger.

Inject the medicine

Place the needle at approximately a 45‑degree angle to the pinched skin.

In a single and swift motion, insert the needle through the skin as far as it

will go (see Fig. 15).

Inject all of the medicine by pushing in the plunger until the plunger head is

completely between the needle guard wings (see Fig. 16).

When the plunger is pushed as far as it will go, continue to keep the pressure

on the plunger head, take out the needle and let go of the skin (see Fig.

17).

Gently take your thumb off the plunger head to allow the empty syringe to

move up until the entire needle is covered by the needle guard, as shown

in Fig. 18.

4. After the injection

Use a cotton ball or gauze

There may be a small amount of blood or liquid at the injection site. This is

normal.

You can press a cotton ball or gauze over the injection site and hold for 10

seconds.

If necessary, you may cover the injection site with a small adhesive

bandage.

Do not rub your skin.

Throw the syringe away

Immediately discard the syringe in an appropriate sharps container, according

to the instructions received from your doctor or nurse.

Do not attempt to recap the needle.

Never re‑use a needle, for your safety and health and for the safety of

others.

If you feel that something has gone wrong with the injection or if you are not

sure, talk to your doctor or pharmacist.

Simponi Pen/Syringe PL+PHY SH 07/18

Simponi Pen/Syringe PL+PHY SH 07/18

J‑C 2018

יטמוטוא טע קרזמ

Auto-injector pen

שומישל ןכומ קרזמ

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Pre-filled syringe

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.רועה לע )תולעמ 90( הרשי תיווזב יטמוטואה קרזמה לש חותפה הצקה תא םקמ * .ףוקשה יוסיכה ךות לא קילחמ תוחיטבה לוורש רשא דע רועה דגנכ הקזוחב יטמוטואה קרזמה תא ץחל *

Place the open end of the auto-injector at a right angle (90 degrees) on the skin.

Firmly press the auto-injector against the skin until the safety sleeve slides into the transparent cover.

PRESCRIBING INFORMATION

1.

NAME OF THE MEDICINAL PRODUCT

Simponi

®

solution for injection

in auto-injector pen or pre-filled syringe

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION

One 0.5 ml auto-injector pen / pre-filled syringe contains 50 mg of golimumab*.

One 1.0 ml auto-injector pen / pre-filled syringe contains 100 mg of golimumab*.

* Human IgG1

monoclonal antibody produced by a murine hybridoma cell line with recombinant DNA technology.

Excipient:

Each auto-injector pen / pre-filled syringe contains 20.5 mg sorbitol per 50 mg dose.

Each auto-injector pen / pre-filled syringe contains 41.0 mg sorbitol per 100 mg dose.

For a full list of excipients, see section 6.1.

3.

PHARMACEUTICAL FORM

Solution for injection in auto-injector pen (injection), SmartJect / pre-filled syringe (injection)

The solution is clear to slightly opalescent, colourless to light yellow.

Patient safety information card

The marketing of Simponi should include a “patient safety information card”. The “patient safety information card”

emphasizes important safety information that the patient should be aware of before and during treatment. Please

explain to the patient the need to review the card before starting treatment.

4.

CLINICAL PARTICULARS

4.1

Therapeutic indications

Rheumatoid Arthritis:

Simponi, in combination with methotrexate, is indicated for the treatment of adult patients with moderately to severely

active rheumatoid arthritis when the response to disease-modifying anti-rheumatic drug (DMARD) therapy including

MTX has been inadequate.

Juvenile Idiopathic Arthritis:

Polyarticular juvenile idiopathic arthritis (pJIA)

Simponi in combination with MTX is indicated for the treatment of polyarticular juvenile idiopathic arthritis in children

with a body weight of at least 40 kg, who have responded inadequately to previous therapy with MTX.

Simponi 100 mg is not recommended in children aged less than 18.

Psoriatic Arthritis:

Simponi, alone or in combination with methotrexate, is indicated for the treatment of adult patients with active and

progressive psoriatic arthritis when the response to previous disease-modifying anti-rheumatic drug (DMARD) therapy

has been inadequate.

Axial Spondyloarthritis:

Ankylosing Spondylitis (AS)

Simponi is indicated for the treatment of adult patients with severe active ankylosing spondylitis who have responded

inadequately to conventional therapy.

Non‑radiographic Axial Spondyloarthritis (nr‑Axial SpA)

Simponi is indicated for the treatment of adults with severe, active non-radiographic axial spondyloarthritis with objective

signs of inflammation as indicated by elevated C-reactive protein (CRP) and/or magnetic resonance imaging (MRI) evidence,

who have had an inadequate response to, or are intolerant to non-steroidal anti-inflammatory drugs (NSAIDs).

Ulcerative Colitis:

Simponi is indicated for treatment of moderately to severely active ulcerative colitis in adult patients who have had an

inadequate response to conventional therapy including corticosteroids and 6-mercaptopurine (6-MP) or azathioprine

(AZA), or who are intolerant to or have medical contraindications for such therapies.

4.2

Posology and method of administration

Simponi treatment is to be initiated and supervised by qualified physicians experienced in the diagnosis and treatment of

rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, psoriatic arthritis or ankylosing spondylitis, non-radiographic

axial spondyloarthritis, or ulcerative colitis.

Patients treated with Simponi should be given the Patient Alert Card.

Posology

Rheumatoid arthritis

Simponi 50 mg given once a month, on the same date each month.

Simponi should be given concomitantly with MTX.

Psoriatic arthritis, ankylosing spondylitis, or non‑radiographic axial spondyloarthritis

Simponi 50 mg given once a month, on the same date each month.

For all the above indications, available data suggest that clinical response is usually achieved within 12 to 14 weeks of

treatment (after 3-4 doses). Continued therapy should be reconsidered in patients who show no evidence of therapeutic

benefit within this time period.

Patients with body weight greater than 100 kg

For all the above indications, in patients with RA, PsA, AS, or nr-Axial SpA with a body weight of more than 100 kg

who do not achieve an adequate clinical response after 3 or 4 doses, increasing the dose of golimumab to 100 mg once

a month may be considered, taking into account the increased risk of certain serious adverse drug reactions with the

100 mg dose compared with the 50 mg dose (see section 4.8). Continued therapy should be reconsidered in patients

who show no evidence of therapeutic benefit after receiving 3 to 4 additional doses of 100 mg.

Ulcerative colitis

Patients with body weight less than 80 kg

Simponi given as an initial dose of 200 mg, followed by 100 mg at week 2, then 50 mg every 4 weeks, thereafter (see

section 5.1).

Patients with body weight greater than or equal to 80 kg

Simponi given as an initial dose of 200 mg, followed by 100 mg at week 2, then 100 mg every 4 weeks, thereafter (see

section 5.1).

During maintenance treatment, corticosteroids may be tapered in accordance with clinical practice guidelines.

Available data suggest that clinical response is usually achieved within 12-14 weeks of treatment (after 4 doses). Continued

therapy should be reconsidered in patients who show no evidence of therapeutic benefit within this time period.

Missed dose

If a patient forgets to inject Simponi on the planned date, the forgotten dose should be injected as soon as the patient

remembers. Patients should be instructed not to inject a double dose to make up for the forgotten dose.

The next dose should be administered based on the following guidance:

if the dose is less than 2 weeks late, the patient should inject his/her forgotten dose and stay on his/her original monthly

schedule.

if the dose is more than 2 weeks late, the patient should inject his/her forgotten dose and a new schedule should be

established from the date of this injection.

Special population

Elderly people (

65 years)

No dose adjustment is required in the elderly.

Renal and hepatic impairment

Simponi has not been studied in these patient populations. No dose recommendations can be made.

Paediatric population

Simponi 50 mg:

The safety and efficacy of Simponi in patients aged less than 18 for indications other than pJIA have not been

established.

Polyarticular juvenile idiopathic arthritis

Simponi 50 mg administered once a month, on the same date each month, for children with a body weight of at least

40 kg.

Available data suggest that clinical response is usually achieved within 12 to 14 weeks of treatment (after 3-4 doses). Continued

therapy should be reconsidered in children who show no evidence of therapeutic benefit within this time period.

Simponi 100 mg:

Simponi 100 mg is not recommended in children aged less than 18.

Method of administration

For subcutaneous use. After proper training in subcutaneous injection technique, patients may self-inject with Simponi

if their physician determines that this is appropriate, with medical follow-up as necessary. Patients should be instructed

to inject the full amount of Simponi according to the comprehensive instructions for administration provided in the

package leaflet.

If multiple injections are required, the injections should be administered at different sites on the body.

For administration instructions, see section 6.6.

4.3

Contraindications

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

Active tuberculosis (TB) or other severe infections such as sepsis, and opportunistic infections (see section 4.4).

Moderate or severe heart failure (NYHA class III/IV) (see section 4.4).

4.4

Special warnings and precautions for use

Infections

Patients must be monitored closely for infections including tuberculosis before, during and after treatment with Simponi.

Because the elimination of golimumab may take up to 5 months, monitoring should be continued throughout this period.

Further treatment with Simponi must not be given if a patient develops a serious infection or sepsis (see section 4.3).

Simponi should not be given to patients with a clinically important, active infection. Caution should be exercised when

considering the use of Simponi in patients with a chronic infection or a history of recurrent infection. Patients should be

advised of, and avoid exposure to, potential risk factors for infection as appropriate.

Patients taking TNF-blockers are more susceptible to serious infections.

Bacterial (including sepsis and pneumonia), mycobacterial (including TB), invasive fungal and opportunistic infections,

including fatalities, have been reported in patients receiving Simponi. Some of these serious infections have occurred

in patients on concomitant immunosuppressive therapy that, in addition to their underlying disease, could predispose

them to infections. Patients who develop a new infection while undergoing treatment with Simponi should be monitored

closely and undergo a complete diagnostic evaluation. Administration of Simponi should be discontinued if a patient

develops a new serious infection or sepsis, and appropriate antimicrobial or antifungal therapy should be initiated until

the infection is controlled. For patients who have resided in or travelled to regions where invasive fungal infections such

as histoplasmosis, coccidioidomycosis, or blastomycosis are endemic, the benefits and risks of Simponi treatment should

be carefully considered before initiation of Simponi therapy.

In at-risk patients treated with Simponi, an invasive fungal infection should be suspected if they develop a serious systemic

illness. Diagnosis and administration of empiric antifungal therapy in these patients should be made in consultation with

a physician with expertise in the care of patients with invasive fungal infections, if feasible.

Tuberculosis

There have been reports of tuberculosis in patients receiving Simponi. It should be noted that in the majority of these

reports, tuberculosis was extrapulmonary presenting as either local or disseminated disease.

Before starting treatment with Simponi, all patients must be evaluated for both active and inactive (‘latent’) tuberculosis.

This evaluation should include a detailed medical history with personal history of tuberculosis or possible previous contact

with tuberculosis and previous and/or current immunosuppressive therapy. Appropriate screening tests, i.e., tuberculin skin

or blood test and chest X-ray, should be performed in all patients (local recommendations may apply). It is recommended

that the conduct of these tests should be recorded in the patient’s alert card. Prescribers are reminded of the risk of false

negative tuberculin skin test results, especially in patients who are severely ill or immunocompromised.

If active tuberculosis is diagnosed, Simponi therapy must not be initiated (see section 4.3).

If latent tuberculosis is suspected, a physician with expertise in the treatment of tuberculosis should be consulted. In all

situations described below, the benefit/risk balance of Simponi therapy should be very carefully considered.

If inactive (‘latent’) tuberculosis is diagnosed, treatment for latent tuberculosis must be started with anti-tuberculosis

therapy before the initiation of Simponi, and in accordance with local recommendations.

In patients who have several or significant risk factors for tuberculosis and have a negative test for latent tuberculosis,

anti-tuberculosis therapy should be considered before the initiation of Simponi. Use of anti-tuberculosis therapy should

also be considered before the initiation of Simponi in patients with a past history of latent or active tuberculosis in whom

an adequate course of treatment cannot be confirmed.

Cases of active tuberculosis have occurred in patients treated with Simponi during and after treatment for latent tuberculosis.

Patients receiving Simponi should be monitored closely for signs and symptoms of active tuberculosis, including patients

who tested negative for latent tuberculosis, patients who are on treatment for latent tuberculosis, or patients who were

previously treated for tuberculosis infection.

All patients should be informed to seek medical advice if signs/symptoms suggestive of tuberculosis (e.g., persistent cough,

wasting/weight loss, low-grade fever) appear during or after Simponi treatment.

Hepatitis B virus reactivation

Reactivation of hepatitis B has occurred in patients receiving a TNF-antagonist including Simponi, who are chronic carriers

of this virus (i.e., surface antigen positive). Some cases have had fatal outcome.

Patients should be tested for HBV infection before initiating treatment with Simponi. For patients who test positive for

HBV infection, consultation with a physician with expertise in the treatment of hepatitis B is recommended.

Carriers of HBV who require treatment with Simponi should be closely monitored for signs and symptoms of active

HBV infection throughout therapy and for several months following termination of therapy. Adequate data on treating

patients who are carriers of HBV with anti-viral therapy in conjunction with TNF-antagonist therapy to prevent HBV

reactivation are not available. In patients who develop HBV reactivation, Simponi should be stopped and effective

anti-viral therapy with appropriate supportive treatment should be initiated.

Malignancies and lymphoproliferative disorders

The potential role of TNF-blocking therapy in the development of malignancies is not known. Based on the current

knowledge, a possible risk for the development of lymphomas, leukaemia or other malignancies in patients treated with

a TNF-antagonist cannot be excluded. Caution should be exercised when considering TNF-blocking therapy for patients

with a history of malignancy or when considering continuing treatment in patients who develop malignancy.

Paediatric malignancy

Malignancies, some fatal, have been reported among children, adolescents and young adults (up to 22 years of age) treated

with TNF-blocking agents (initiation of therapy

18 years of age) in the post-marketing setting. Approximately half the

cases were lymphomas. The other cases represented a variety of different malignancies and included rare malignancies

usually associated with immunosuppression. A risk for the development of malignancies in children and adolescents

treated with TNF-blockers cannot be excluded.

Lymphoma and leukaemia

In the controlled portions of clinical trials of all the TNF-blocking agents including Simponi, more cases of lymphoma have

been observed among patients receiving anti-TNF treatment compared with control patients. During the Simponi Phase

IIb and Phase III clinical trials in RA, PsA and AS, the incidence of lymphoma in Simponi-treated patients was higher than

expected in the general population. Cases of leukaemia have been reported in patients treated with Simponi. There is

an increased background risk for lymphoma and leukaemia in rheumatoid arthritis patients with long-standing, highly

active, inflammatory disease, which complicates risk estimation.

Rare post-marketing cases of hepatosplenic T-cell lymphoma (HSTCL) have been reported in patients treated with other

TNF-blocking agents (see section 4.8). This rare type of T-cell lymphoma has a very aggressive disease course and is

usually fatal. The majority of cases have occurred in adolescent and young adult males with nearly all on concomitant

treatment with azathioprine (AZA) or 6-mercaptopurine (6-MP) for inflammatory bowel disease. The potential risk with the

combination of AZA or 6-MP and Simponi should be carefully considered. A risk for the development for hepatosplenic

T-cell lymphoma in patients treated with TNF-blockers cannot be excluded.

Malignancies other than lymphoma

In the controlled portions of the Simponi Phase IIb and Phase III clinical trials in RA, PsA, AS and UC, the incidence of non-lymphoma

malignancies (excluding non-melanoma skin cancer) was similar between the Simponi and the control groups.

Colon dysplasia/carcinoma

It is not known if golimumab treatment influences the risk for developing dysplasia or colon cancer.

All patients with ulcerative colitis who are at increased risk for dysplasia or colon carcinoma (for example, patients with

long-standing ulcerative colitis or primary sclerosing cholangitis), or who had a prior history of dysplasia or colon carcinoma

should be screened for dysplasia at regular intervals before therapy and throughout their disease course. This evaluation

should include colonoscopy and biopsies per local recommendations. In patients with newly diagnosed dysplasia treated

with Simponi, the risks and benefits to the individual patient must be carefully reviewed and consideration should be

given to whether therapy should be continued.

In an exploratory clinical trial evaluating the use of Simponi in patients with severe persistent asthma, more malignancies

were reported in patients treated with Simponi compared with control patients (see section 4.8). The significance of this

finding is unknown.

In an exploratory clinical trial evaluating the use of another anti-TNF agent, infliximab, in patients with moderate to severe

chronic obstructive pulmonary disease (COPD), more malignancies, mostly in the lung or head and neck, were reported

in infliximab-treated patients compared with control patients. All patients had a history of heavy smoking. Therefore,

caution should be exercised when using any TNF-antagonist in COPD patients, as well as in patients with an increased

risk of malignancy due to heavy smoking.

Skin cancers

Melanoma and Merkel cell carcinoma have been reported in patients treated with TNF-blocking agents, including Simponi

(see section 4.8). Periodic skin examination is recommended particularly for patients with risk factors for skin cancer.

Congestive heart failure (CHF)

Cases of worsening congestive heart failure (CHF) and new onset CHF have been reported with TNF-blockers, including

Simponi. Some cases had a fatal outcome. In a clinical trial with another TNF-antagonist, worsening congestive heart failure

and increased mortality due to CHF have been observed. Simponi has not been studied in patients with CHF. Simponi

should be used with caution in patients with mild heart failure (NYHA class I/II). Patients should be closely monitored and

Simponi must be discontinued in patients who develop new or worsening symptoms of heart failure (see section 4.3).

Neurological events

Use of TNF-blocking agents, including Simponi, has been associated with cases of new onset or exacerbation of clinical

symptoms and/or radiographic evidence of central nervous system demyelinating disorders, including multiple sclerosis

and peripheral demyelinating disorders.

In patients with pre-existing or recent onset of demyelinating disorders, the benefits and risks of anti-TNF treatment

should be carefully considered before initiation of Simponi therapy. Discontinuation of Simponi should be considered if

these disorders develop (see section 4.8).

Surgery

There is limited safety experience of Simponi treatment in patients who have undergone surgical procedures, including

arthroplasty. The long half-life should be taken into consideration if a surgical procedure is planned. A patient who requires

surgery while on Simponi should be closely monitored for infections, and appropriate actions should be taken.

Immunosuppression

The possibility exists for TNF-blocking agents, including Simponi, to affect host defences against infections and malignancies

since TNF mediates inflammation and modulates cellular immune responses.

Autoimmune processes

The relative deficiency of TNF-

caused by anti-TNF therapy may result in the initiation of an autoimmune process. If a

patient develops symptoms suggestive of a lupus-like syndrome following treatment with Simponi and is positive for

antibodies against double-stranded DNA, treatment with Simponi should be discontinued (see section 4.8).

Haematologic reactions

There have been reports of pancytopenia, leukopenia, neutropenia, agranulocytosis, aplastic anaemia, and thrombocytopenia

in patients receiving TNF-blockers, including Simponi. All patients should be advised to seek immediate medical attention if they

develop signs and symptoms suggestive of blood dyscrasias (e.g., persistent fever, bruising, bleeding, pallor). Discontinuation

of Simponi therapy should be considered in patients with confirmed significant haematologic abnormalities.

Concurrent administration of TNF-antagonists and anakinra

Serious infections and neutropenia were seen in clinical studies with concurrent use of anakinra and another TNF-blocking

agent, etanercept, with no added clinical benefit. Because of the nature of the adverse events seen with this combination

therapy, similar toxicities may also result from the combination of anakinra and other TNF-blocking agents. The combination

of Simponi and anakinra is not recommended.

Concurrent administration of TNF-antagonists and abatacept

In clinical studies concurrent administration of TNF-antagonists and abatacept has been associated with an increased

risk of infections including serious infections compared to TNF-antagonists alone, without increased clinical benefit. The

combination of Simponi and abatacept is not recommended.

Concurrent administration with other biological therapeutics

There is insufficient information regarding the concomitant use of Simponi with other biological therapeutics used to treat

the same conditions as Simponi. The concomitant use of Simponi with these biologics is not recommended because of

the possibility of an increased risk of infection, and other potential pharmacological interactions.

Switching between biological DMARDs

Care should be taken and patients should continue to be monitored when switching from one biologic to another, since

overlapping biological activity may further increase the risk for adverse events, including infection.

Vaccinations/therapeutic infectious agents

Patients treated with Simponi may receive concurrent vaccinations, except for live vaccines (see sections 4.5 and 4.6).

In patients receiving anti-TNF therapy limited data are available on the response to vaccination with live vaccines, or on

the secondary transmission of infection by live vaccines. Use of live vaccines could result in clinical infections, including

disseminated infections.

Other uses of therapeutic infectious agents such as live attenuated bacteria (e.g., BCG bladder instillation for the treatment

of cancer) could result in clinical infections, including disseminated infections. It is recommended that therapeutic infectious

agents not be given concurrently with Simponi.

Allergic reactions

In post-marketing experience, serious systemic hypersensitivity reactions (including anaphylactic reaction) have been

reported following Simponi administration. Some of these reactions occurred after the first administration of Simponi.

If an anaphylactic reaction or other serious allergic reactions occur, administration of Simponi should be discontinued

immediately and appropriate therapy initiated.

Latex sensitivity

The needle cover on the auto-injector pen / pre-filled syringe is manufactured from dry natural rubber containing latex,

and may cause allergic reactions in individuals sensitive to latex.

Special populations

Elderly people (

65 years)

In the Phase III studies in RA, PsA, AS and UC, no overall differences in adverse events (AEs), serious adverse events (SAEs),

and serious infections in patients age 65 or older who received Simponi were observed compared with younger patients.

However, caution should be exercised when treating the elderly and particular attention paid with respect to occurrence

of infections. There were no patients age 45 and over in the nr-Axial SpA study.

Renal and hepatic impairment

Specific studies of Simponi have not been conducted in patients with renal or hepatic impairment. Simponi should be

used with caution in subjects with impaired hepatic function (see section 4.2).

Paediatrics

Vaccinations

If possible, it is recommended that prior to initiating Simponi therapy, paediatric patients be brought up to date with all

immunisations in agreement with current immunisation guidelines.

Excipients

Simponi contains sorbitol (E420). Patients with rare hereditary problems of fructose intolerance should not take Simponi.

Potential for medication errors

Simponi is registered in 50 mg and 100 mg strengths for subcutaneous administration. It is important that the right

strength is used to administer the correct dose as indicated in the posology (see section 4.2). Care should be taken to

provide the right strength to ensure that patients are not underdosed or overdosed.

4.5

Interaction with other medicinal products and other forms of interaction

No interaction studies have been performed.

Concurrent use with other biological therapeutics

The combination of Simponi with other biological therapeutics used to treat the same conditions as Simponi, including

anakinra and abatacept is not recommended (see section 4.4).

Live vaccines/therapeutic infectious agents

Live vaccines should not be given concurrently with Simponi (see sections 4.4 and 4.6).

Therapeutic infectious agents should not be given concurrently with Simponi (see section 4.4).

Methotrexate

Although concomitant use of MTX results in higher steady-state trough concentrations of Simponi in patients with RA,

PsA or AS, the data do not suggest the need for dose adjustment of either Simponi or MTX (see section 5.2).

4.6

Fertility, pregnancy and lactation

Women of childbearing potential

Women of childbearing potential must use adequate contraception to prevent pregnancy and continue its use for at least

6 months after the last golimumab treatment.

Pregnancy

There are no adequate data on the use of golimumab in pregnant women. Due to its inhibition of TNF, golimumab

administered during pregnancy could affect normal immune responses in the newborn. Studies in animals do not indicate

direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal

development (see section 5.3). The use of golimumab in pregnant women is not recommended; golimumab should be

given to a pregnant woman only if clearly needed.

Golimumab crosses the placenta. Following treatment with a TNF-blocking monoclonal antibody during pregnancy, the

antibody has been detected for up to 6 months in the serum of the infant born to the treated woman. Consequently,

these infants may be at increased risk of infection. Administration of live vaccines to infants exposed to golimumab

in utero is not recommended for 6 months following the mother’s last golimumab injection during pregnancy (see

sections 4.4 and 4.5).

Breast-feeding

It is not known whether golimumab is excreted in human milk or absorbed systemically after ingestion. Golimumab was

shown to pass over to breast milk in monkeys, and because human immunoglobulins are excreted in milk, women must

not breast-feed during and for at least 6 months after golimumab treatment.

Fertility

No animal fertility studies have been conducted with golimumab. A fertility study in mice, using an analogous antibody

that selectively inhibits the functional activity of mouse TNF-

, showed no relevant effects on fertility (see section 5.3).

4.7

Effects on ability to drive and use machines

Simponi may have a minor influence on the ability to drive and use machines. Dizziness may occur following administration

of Simponi (see section 4.8).

4.8

Undesirable effects

Summary of the safety profile

In the controlled period of the pivotal trials in RA, PsA, AS, nr-Axial SpA, and UC, upper respiratory tract infection was the

most common adverse drug reaction (ADR) reported in 12.6% of golimumab-treated patients compared with 11.0% of

control patients. The most serious ADRs that have been reported for golimumab include serious infections (including sepsis,

pneumonia, TB, invasive fungal and opportunistic infections), demyelinating disorders, HBV reactivation, CHF, autoimmune

processes (lupus-like syndrome), haematologic reactions, serious systemic hypersensitivity (including anaphylactic reaction),

vasculitis, lymphoma and leukaemia (see section 4.4).

Tabulated list of adverse reactions

ADRs observed in clinical studies and reported from world-wide post-marketing use of golimumab are listed in Table 1.

Within the designated system organ classes, the adverse drug reactions are listed under headings of frequency and using

the following convention: Very common (

1/10); Common (

1/100 to < 1/10); Uncommon (

1/1,000 to < 1/100); Rare

1/10,000 to < 1/1,000); Very rare (< 1/10,000); Not known (cannot be estimated from the available data). Within each

frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Table 1

Tabulated list of ADRs

Infections and infestations

Very common:

Upper respiratory tract infection (nasopharyngitis, pharyngitis, laryngitis and

rhinitis)

Common:

Bacterial infections (such as cellulitis), lower respiratory tract infection (such as

pneumonia), viral infections (such as influenza and herpes), bronchitis, sinusitis,

superficial fungal infections, abscess

Uncommon:

Sepsis including septic shock, pyelonephritis

Rare:

Tuberculosis, opportunistic infections (such as invasive fungal infections

[histoplasmosis, coccidioidomycosis, pneumocytosis], bacterial, atypical

mycobacterial infection and protozoal), hepatitis B reactivation, bacterial arthritis,

infective bursitis

Neoplasms, benign, malignant

and unspecified

Uncommon:

Neoplasms (such as skin cancer, squamous cell carcinoma and melanocytic

naevus)

Rare:

Lymphoma, leukaemia, melanoma; Merkel cell carcinoma

Not known*:

Hepatosplenic T-cell lymphoma

Blood and lymphatic system

disorders

Common:

Leukopenia (including neutropaenia), anaemia

Uncommon:

Thrombocytopenia, pancytopenia

Rare:

Aplastic anaemia, agranulocytosis

Immune system disorders

Common:

Allergic reactions (bronchospasm, hypersensitivity, urticaria), autoantibody

positive

Rare:

Serious systemic hypersensitivity reactions (including anaphylactic reaction),

vasculitis (systemic), sarcoidosis

Endocrine disorders

Uncommon:

Thyroid disorder (such as hypothyroidism, hyperthyroidism and goitre)

Metabolism and nutrition

disorders

Uncommon:

Blood glucose increased, lipids increased

Psychiatric disorders

Common:

Depression, insomnia

Nervous system disorders

Common:

Dizziness, paraesthesia, headache

Uncommon:

Balance disorders

Rare:

Demyelinating disorders (central and peripheral), dysguesia

Eye disorders

Uncommon:

Visual disorders (such as blurred vision and decreased visual acuity), conjunctivitis,

eye allergy (such as pruritis and irritation)

Cardiac disorders

Uncommon:

Arrhythmia, ischemic coronary artery disorders

Rare:

Congestive heart failure (new onset or worsening)

Vascular disorders

Common:

Hypertension

Uncommon:

Thrombosis (such as deep venous and aortic), flushing

Rare:

Raynaud’s phenomenon

Respiratory, thoracic and

mediastinal disorders

Common:

Asthma and related symptoms (such as wheezing and bronchial hyperactivity)

Uncommon:

Interstitial lung disease

Gastrointestinal disorders

Common:

Dyspepsia, gastrointestinal and abdominal pain, nausea, gastrointestinal

inflammatory disorders (such as gastritis and colitis), stomatitis

Uncommon:

Constipation, gastro-oesophageal reflux disease

Hepatobiliary disorders

Common:

Alanine aminotransferase increased, aspartate aminotransferase increased

Uncommon:

Cholelithiasis, hepatic disorders

Skin and subcutaneous tissue

disorders

Common:

Alopecia, pruritus, rash, dermatitis

Uncommon:

Psoriasis (new onset or worsening of pre-existing psoriasis, palmar/plantar and

pustular), urticaria, bullous skin reactions

Rare:

Skin exfoliation, vasculitis (cutaneous)

Musculoskeletal and connective

tissue disorders

Rare:

Lupus-like syndrome

Renal and urinary disorders

Rare:

Bladder disorders, renal disorders

Reproductive system and breast

disorders

Uncommon:

Breast disorders, menstrual disorders

General disorders and

administration site conditions

Common:

Pyrexia, asthenia, injection site reaction (such as injection site erythema, urticaria,

induration, pain, bruising, pruritus, irritation and paraesthesia), chest discomfort

Rare:

Impaired healing

Injury, poisoning and procedural

complications

Common:

Bone fractures

* Observed with other TNF-blocking agents.

Throughout this section, median duration of follow-up (approximately 4 years) is generally presented for all golimumab

use. Where golimumab use is described by dose, the median duration of follow-up varies (approximately 2 years for

50 mg dose, approximately 3 years for 100 mg dose) as patients may have switched between doses.

Description of selected adverse drug reactions

Infections

In the controlled period of pivotal trials, upper respiratory tract infection was the most common adverse reaction reported

in 12.6% of golimumab-treated patients (incidence per 100 subject-years: 60.8; 95% CI: 55.0, 67.1) compared with

11.0% of control patients (incidence per 100 subject-years: 54.5; 95% CI: 46.1, 64.0). In controlled and uncontrolled

portions of the studies with a median follow-up of approximately 4 years, the incidence per 100 subject-years of upper

respiratory tract infections was 34.9 events; 95% CI: 33.8, 36.0 for golimumab-treated patients.

In the controlled period of pivotal trials, infections were observed in 23.0% of golimumab-treated patients (incidence

per 100 subject-years: 132.0; 95% CI: 123.3, 141.1) compared with 20.2% of control patients (incidence per 100

subject-years: 122.3; 95% CI: 109.5, 136.2). In controlled and uncontrolled portions of the trials with a median

follow-up of approximately 4 years, the incidence per 100 subject-years of infections was 81.1 events; 95% CI: 79.5,

82.8 for golimumab-treated patients.

In the controlled period of RA, PsA, AS, and nr-Axial SpA trials, serious infections were observed in 1.2% of golimumab-

treated patients and 1.2% of control-treated patients. The incidence of serious infections per 100 subject-years of follow-up

in the controlled period of RA, PsA, AS and nr-Axial SpA trials was 7.3; 95% CI: 4.6, 11.1 for the golimumab 100 mg

group, 2.9; 95% CI: 1.2, 6.0 for the golimumab 50 mg group and 3.6; 95% CI: 1.5, 7.0 for the placebo group. In the

controlled period of UC trials of golimumab induction, serious infections were observed in 0.8% of golimumab-treated

patients compared with 1.5% of control-treated patients. Serious infections observed in golimumab-treated patients

included tuberculosis, bacterial infections including sepsis and pneumonia, invasive fungal infections and other opportunistic

infections. Some of these infections have been fatal. In the controlled and uncontrolled portions of the pivotal trials with a

median follow-up of up to 3 years, there was a greater incidence of serious infections, including opportunistic infections

and TB in patients receiving golimumab 100 mg compared with patients receiving golimumab 50 mg. The incidence per

100 subject-years of all serious infections was 4.1; 95% CI: 3.6, 4.5 in patients receiving golimumab 100 mg and 2.5;

95% CI: 2.0, 3.1 in patients receiving golimumab 50 mg.

Malignancies

Lymphoma

The incidence of lymphoma in golimumab-treated patients during the pivotal trials was higher than expected in the

general population. In the controlled and uncontrolled portions of these trials with a median follow-up of up to 3 years,

a greater incidence of lymphoma was observed in patients receiving golimumab 100 mg compared with patients receiving

golimumab 50 mg. Lymphoma was diagnosed in 11 subjects (1 in the golimumab 50 mg treatment groups and 10 in the

golimumab 100 mg treatment groups) with an incidence (95% CI) per 100 subject-years of follow-up of 0.03 (0.00, 0.15)

and 0.13 (0.06, 0.24) events for golimumab 50 mg and 100 mg, respectively, and 0.00 (0.00, 0.57) events for the placebo.

The majority of lymphomas occurred in study GO-AFTER, which enrolled patients previously exposed to anti-TNF agents

who had longer disease duration and more refractory disease (see section 4.4).

Malignancies other than lymphoma

In the controlled periods of pivotal trials and through approximately 4 years of follow-up, the incidence of non-lymphoma

malignancies (excluding non-melanoma skin cancer) was similar between the golimumab and the control groups. Through

approximately 4 years of follow-up, the incidence of non-lymphoma malignancies (excluding non-melanoma skin cancer)

was similar to the general population.

In the controlled and uncontrolled periods of pivotal trials with a median follow-up of up to 3 years, non-melanoma skin

cancer was diagnosed in 5 placebo-treated, 10 golimumab 50 mg-treated and 31 golimumab 100 mg-treated subjects

with an incidence (95% CI) per 100 subject-years of follow-up of 0.36 (0.26, 0.49) for combined golimumab and 0.87

(0.28, 2.04) for placebo.

In the controlled and uncontrolled period of pivotal trials with a median follow-up of up to 3 years, malignancies

besides melanoma, non-melanoma skin cancer and lymphoma were diagnosed in 5 placebo-treated, 21 golimumab

50 mg-treated and 34 golimumab 100 mg-treated subjects with an incidence (95% CI) per 100 subject-years of

follow-up of 0.48 (0.36, 0.62) for combined golimumab and 0.87 (0.28, 2.04) for placebo (see section 4.4).

Cases reported in clinical studies in asthma

In an exploratory clinical study, patients with severe persistent asthma received a golimumab loading dose (150% of the

assigned treatment dose) subcutaneously at week 0 followed by golimumab 200 mg, golimumab 100 mg or golimumab

50 mg every 4 weeks subcutaneously through week 52.

Eight malignancies in the combined golimumab treatment group (n = 230) and none in the placebo treatment group

(n = 79) were reported. Lymphoma was reported in 1 patient, non-melanoma skin cancer in 2 patients, and other

malignancies in 5 patients. There was no specific clustering of any type of malignancy.

During the placebo-controlled portion of the study, the incidence (95% CI) of all malignancies per 100 subject-years of

follow-up was 3.19 (1.38, 6.28) in the golimumab group. In this study, the incidence (95% CI) per 100 subject-years of

follow-up in golimumab-treated subjects was 0.40 (0.01, 2.20) for lymphoma, 0.79 (0.10, 2.86) for non-melanoma skin

cancers, and 1.99 (0.64, 4.63) for other malignancies. For placebo subjects, the incidence (95% CI) per 100 subject-years

of follow-up of these malignancies was 0.00 (0.00, 2.94). The significance of this finding is unknown.

Neurological events

In the controlled and uncontrolled periods of the pivotal trials with a median follow-up of up to 3 years, a greater incidence

of demyelination was observed in patients receiving golimumab 100 mg compared with patients receiving golimumab

50 mg (see section 4.4).

Liver enzyme elevations

In the controlled period of RA and PsA pivotal trials, mild ALT elevations (> 1 and < 3 x upper limit of normal (ULN))

occurred in similar proportions of golimumab and control patients in the RA and PsA studies (22.1% to 27.4% of patients);

in the AS and nr-Axial SpA studies, more golimumab-treated patients (26.9%) than control patients (10.6%) had mild

ALT elevations. In the controlled and uncontrolled periods of the RA and PsA pivotal trials, with a median follow-up of

approximately 5 years, the incidence of mild ALT elevations was similar in golimumab-treated and control patients in

RA and PsA studies. In the controlled period of the UC pivotal trials of golimumab induction, mild ALT elevations (> 1

and < 3 x ULN) occurred in similar proportions of golimumab-treated and control patients (8.0% to 6.9%, respectively).

In controlled and uncontrolled periods of the UC pivotal trials with a median follow-up of approximately 2 years, the

proportion of patients with mild ALT elevations was 24.7% in patients receiving golimumab during the maintenance

portion of the UC study.

In the controlled period of RA and AS pivotal trials, ALT elevations

5 x ULN were uncommon and seen in more

golimumab-treated patients (0.4% to 0.9%) than control patients (0.0%). This trend was not observed in the PsA

population. In the controlled and uncontrolled periods of RA, PsA and AS pivotal trials, with a median follow-up of

5 years, the incidence of ALT elevations

5 x ULN was similar in both golimumab-treated and control patients. In

general, these elevations were asymptomatic and the abnormalities decreased or resolved with either continuation

or discontinuation of golimumab or modification of concomitant medicinal products. No cases were reported in the

controlled and uncontrolled periods of the nr-Axial SpA study (up to 1 year). In the controlled periods of the pivotal

UC trials, of golimumab induction, ALT elevations

5 x ULN occurred in similar proportions of golimumab-treated

patients compared to placebo-treated patients (0.3% to 1.0%, respectively). In the controlled and uncontrolled

periods of the pivotal UC trials with a median follow-up of approximately 2 years, the proportion of patients with ALT

elevations

5 x ULN was 0.8% in patients receiving golimumab during the maintenance portion of the UC study.

Within the RA, PsA, AS, and nr-Axial SpA pivotal trials, one patient in an RA trial with pre-existing liver abnormalities and

confounding medicinal products treated with golimumab developed non-infectious fatal hepatitis with jaundice. The role

of golimumab as a contributing or aggravation factor cannot be excluded.

Injection site reactions

In the controlled periods of pivotal trials, 5.4% of golimumab-treated patients had injection site reactions compared with

2.0% in control patients. The presence of antibodies to golimumab may increase the risk of injection site reactions. The

majority of the injection site reactions were mild and moderate and the most frequent manifestation was injection site

erythema. Injection site reactions generally did not necessitate discontinuation of the medicinal product.

In controlled Phase IIb and/or III trials in RA, PsA, AS, nr-Axial SpA, severe persistent asthma, and Phase II/III trials in UC,

no patients treated with golimumab developed anaphylactic reactions.

Autoimmune antibodies

In the controlled and uncontrolled periods of pivotal trials through 1 year of follow-up, 3.5% of golimumab-treated

patients and 2.3% of control patients were newly ANA-positive (at titres of 1:160 or greater). The frequency of anti-dsDNA

antibodies at 1 year of follow-up in patients anti-dsDNA negative at baseline was 1.1%.

Paediatric population

Polyarticular juvenile idiopathic arthritis

The safety of golimumab has been studied in a phase III study of 173 pJIA patients from 2 to 17 years of age. The average

follow-up was approximately two years. In this study, the type and frequency of adverse events reported were generally

similar to those seen in adult RA studies.

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. 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.health.gov.il

4.9

Overdose

Single doses up to 10 mg/kg intravenously have been administered in a clinical study without dose-limiting toxicity. In

case of an overdose, it is recommended that the patient be monitored for any signs or symptoms of adverse effects and

appropriate symptomatic treatment be instituted immediately.

5.

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties

Pharmacotherapeutic group: Immunosuppressants, tumour necrosis factor alpha (TNF-

) inhibitors,

ATC code: L04AB06

Mechanism of action

Golimumab is a human monoclonal antibody that forms high-affinity, stable complexes with both the soluble and

transmembrane bioactive forms of human TNF-

, which prevents the binding of TNF-

to its receptors.

Pharmacodynamic effects

The binding of human TNF by golimumab was shown to neutralise TNF-

-induced cell-surface expression of the adhesion

molecules E-selectin, vascular cell adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-1 by human

endothelial cells. In vitro, TNF-induced secretion of interleukin (IL)-6, IL-8 and granulocyte-macrophage colony stimulating

factor (GM-CSF) by human endothelial cells was also inhibited by golimumab.

Improvement in C-reactive protein (CRP) levels was observed relative to placebo groups and treatment with Simponi

resulted in significant reductions from baseline in serum levels of IL-6, ICAM-1, matrix-metalloproteinase (MMP)-3 and

vascular endothelial growth factor (VEGF) compared to control treatment. In addition, levels of TNF-

were reduced in

RA and AS patients and levels of IL-8 were reduced in PsA patients. These changes were observed at the first assessment

(week 4) after the initial Simponi administration and were generally maintained through week 24.

Clinical efficacy

Rheumatoid arthritis

The efficacy of Simponi was demonstrated in three multi-centre, randomised, double-blind, placebo-controlled studies in

over 1500 patients

18 years of age with moderately to severely active RA diagnosed according to American College of

Rheumatology (ACR) criteria for at least 3 months prior to screening. Patients had at least 4 swollen and 4 tender joints.

Simponi or placebo were subcutaneously administered every 4 weeks.

GO-FORWARD evaluated 444 patients who had active RA despite a stable dose of at least 15 mg/week of MTX and who

had not been previously treated with an anti-TNF agent. Patients were randomised to receive placebo + MTX, Simponi

50 mg + MTX, Simponi 100 mg + MTX or Simponi 100 mg + placebo. Patients receiving placebo + MTX were switched

to Simponi 50 mg + MTX after week 24. At week 52, patients entered an open-label, long-term extension.

GO-AFTER evaluated 445 patients who were previously treated with one or more of the anti-TNF agents adalimumab,

etanercept, or infliximab. Patients were randomised to receive placebo, Simponi 50 mg, or Simponi 100 mg. Patients

were allowed to continue concomitant DMARD therapy with MTX, sulfasalazine (SSZ), and/or hydroxychloroquine (HCQ)

during the study. The stated reasons for discontinuation of prior anti-TNF therapies were lack of efficacy (58%), intolerance

(13%), and/or reasons other than safety or efficacy (29%, mostly for financial reasons).

GO-BEFORE evaluated 637 patients with active RA who were MTX-naïve and had not previously been treated with an

anti-TNF agent. Patients were randomised to receive placebo + MTX, Simponi 50 mg + MTX, Simponi 100 mg + MTX or

Simponi 100 mg + placebo. At week 52, patients entered an open-label, long-term extension in which patients receiving

placebo + MTX who had at least 1 tender or swollen joint were switched to Simponi 50 mg + MTX.

In GO-FORWARD, the (co-)primary endpoints were the percentage of patients achieving an ACR 20 response at week 14

and the improvement from baseline in Health Assessment Questionnaire (HAQ) at week 24. In GO-AFTER, the primary

endpoint was the percentage of patients achieving an ACR 20 response at week 14. In GO-BEFORE, the co-primary

endpoints were the percentage of patients achieving ACR 50 response at week 24 and the change from baseline in the

van der Heijde-modified Sharp (vdH-S) score at week 52. In addition to the primary endpoint(s), additional assessments

of the impact of Simponi treatment on the signs and symptoms of arthritis, radiographic response, physical function and

health-related quality of life were performed.

In general, no clinically meaningful differences in measures of efficacy were observed between the Simponi 50 mg and

100 mg dosing regimens with concomitant MTX, through week 104 in GO-FORWARD and GO-BEFORE and through

week 24 in GO-AFTER. In each of the RA studies by study design, patients in the long-term extension may have switched

between the 50 mg and 100 mg Simponi doses at the discretion of the study physician.

Signs and symptoms

Key ACR results for the Simponi 50 mg dose at weeks 14, 24 and 52 for GO-FORWARD, GO-AFTER and GO-BEFORE

are shown in Table 2 and are described below. Responses were observed at the first assessment (week 4) after the initial

Simponi administration.

In GO-FORWARD, among 89 subjects randomised to Simponi 50 mg + MTX, 48 were still on this treatment at week 104.

Among those, 40, 33 and 24 patients had ACR 20/50/70 response, respectively, at week 104. Among patients remaining

in the study and treated with Simponi, similar rates of ACR 20/50/70 response was observed from week 104 through

week 256.

In GO-AFTER, the percentage of patients achieving an ACR 20 response was greater for patients receiving Simponi than for

patients receiving placebo regardless of the reason reported for discontinuation of one or more prior anti-TNF therapies.

Table 2

Key efficacy outcomes from the controlled portions of

GO-FORWARD, GO-AFTER and GO-BEFORE

GO-FORWARD

Active RA despite MTX

GO-AFTER

Active RA, previously treated with

one or more

anti-TNF agent(s)

GO-BEFORE

Active RA, MTX Naïve

Placebo

Simponi

50 mg

Placebo

Simponi

50 mg

Placebo

Simponi

50 mg

Responders, % of patients

ACR 20

Week 14

33%

55%*

18%

35%*

Week 24

60%*

31% p=0.002

Week 52

ACR 50

Week 14

35%*

15% p=0.021

Week 24

37%*

16%*

29%

40%

Week 52

ACR 70

Week 14

14% p=0.008

10% p=0.005

Week 24

20%*

9% p=0.009

Week 52

n reflects randomised patients; actual number of patients evaluable for each endpoint may vary by timepoint

0.001

NA Not Applicable

In GO-BEFORE the primary analysis in patients with moderate to severe rheumatoid arthritis (combined Simponi 50 and

100 mg + MTX groups vs. MTX alone for ACR50) was not statistically significant at week 24 (p = 0.053). At week 52 in

the overall population, the percentage of patients in the Simponi 50 mg + MTX group who achieved an ACR response

was generally higher but not significantly different when compared with MTX alone (see Table 2). Additional analyses

were performed in subsets representative of the indicated population of patients with severe, active and progressive RA.

A generally greater effect of Simponi 50 mg + MTX versus MTX alone was demonstrated in the indicated population

compared with the overall population.

In GO-FORWARD and GO-AFTER, clinically meaningful and statistically significant responses in Disease Activity Scale

(DAS)28 were observed at each prespecified time point, at week 14 and at week 24 (p

0.001). Among patients who

remained on the Simponi treatment to which they were randomised at study start, DAS28 responses were maintained

through week 104. Among patients remaining in the study and treated with Simponi, DAS28 responses were similar

from week 104 through week 256.

In GO-BEFORE, major clinical response, defined as the maintenance of an ACR 70 response over a continuous 6-month

period, was measured. At week 52, 15% of patients in the Simponi 50 mg + MTX group achieved a major clinical response

compared with 7% of patients in the placebo + MTX group (p = 0.018). Among 159 subjects randomised to Simponi

50 mg + MTX, 96 were still on this treatment at week 104. Among those, 85, 66 and 53 patients had ACR 20/50/70

response, respectively, at week 104. Among patients remaining in the study and treated with Simponi, similar rates of

ACR 20/50/70 response were observed from week 104 through week 256.

Radiographic response:

In GO-BEFORE the change from baseline in the vdH-S score, a composite score of structural damage that radiographically

measures the number and size of joint erosions and the degree of joint space narrowing in hands/wrists and feet, was used to

assess the degree of structural damage. Key results for the Simponi 50 mg dose at week 52 are presented in Table 3.

The number of patients with no new erosions or a change from baseline in total vdH-S score

0 was significantly higher

in the Simponi treatment group than in the control group (p = 0.003). The radiographic effects observed at week 52 were

maintained through week 104. Among patients remaining in the study and treated with Simponi, radiographic effects

were similar from week 104 through week 256.

Table 3

Radiographic mean (SD) changes from baseline in total vdH-S score at week 52

in the overall population of GO-BEFORE

Placebo + MTX

Simponi 50 mg + MTX

160

159

Total Score

Baseline

19.7 (35.4)

18.7 (32.4)

Change from baseline

1.4 (4.6)

0.7 (5.2)*

Erosion Score

Baseline

11.3 (18.6)

10.8 (17.4)

Change from baseline

0.7 (2.8)

0.5 (2.1)

JSN Score

Baseline

8.4 (17.8)

7.9 (16.1)

Change from baseline

0.6 (2.3)

0.2 (2.0)**

n reflects randomised patients

p = 0.015

** p = 0.044

Physical function and health‑related quality of life

Physical function and disability were assessed as a separate endpoint in GO-FORWARD and GO-AFTER using the disability

index of the HAQ DI. In these studies, Simponi demonstrated clinically meaningful and statistically significant improvement

in HAQ DI from baseline versus control at week 24. Among patients who remained on the Simponi treatment to which they

were randomised at study start, improvement in HAQ DI was maintained through week 104. Among patients remaining

in the study and treated with Simponi, improvement in HAQ DI was similar from week 104 through week 256.

In GO-FORWARD clinically meaningful and statistically significant improvements were demonstrated in health-related

quality of life as measured by the physical component score of the SF-36 in patients treated with Simponi versus placebo

at week 24. Among patients who remained on the Simponi treatment to which they were randomised at study start,

improvement of the SF-36 physical component was maintained through week 104. Among patients remaining in the

study and treated with Simponi, improvement of the SF-36 physical component was similar from week 104 through

week 256. In GO-FORWARD and GO-AFTER, statistically significant improvements were observed in fatigue as measured

by functional assessment of chronic illness therapy-fatigue scale (FACIT-F).

Psoriatic arthritis

The safety and efficacy of Simponi were evaluated in a multi-centre, randomised, double-blind, placebo-controlled

study (GO-REVEAL) in 405 adult patients with active PsA (

3 swollen joints and

3 tender joints) despite non-steroidal

anti-inflammatory (NSAID) or DMARD therapy. Patients in this study had a diagnosis of PsA for at least 6 months and had

at least mild psoriatic disease. Patients with each sub-type of psoriatic arthritis were enrolled, including polyarticular arthritis

with no rheumatoid nodules (43%), asymmetric peripheral arthritis (30%), distal interphalangeal (DIP) joint arthritis (15%),

spondylitis with peripheral arthritis (11%), and arthritis mutilans (1%). Previous treatment with an anti-TNF agent was

not allowed. Simponi or placebo were administered subcutaneously every 4 weeks. Patients were randomly assigned to

placebo, Simponi 50 mg, or Simponi 100 mg. Patients receiving placebo were switched to Simponi 50 mg after week 24.

Patients entered an open-label, long-term extension at week 52. Approximately forty-eight percent of patients continued

on stable doses of methotrexate (

25 mg/week). The co-primary endpoints were the percentage of patients achieving

ACR 20 response at week 14 and change from baseline in total PsA modified vdH-S score at week 24.

In general, no clinically meaningful differences in measures of efficacy were observed between the Simponi 50 mg and

100 mg dosing regimens through week 104. By study design, patients in the long-term extension may have switched

between the 50 mg and 100 mg Simponi doses at the discretion of the study physician.

Signs and symptoms

Key results for the 50 mg dose at weeks 14 and 24 are shown in Table 4 and described below.

Table 4

Key efficacy outcomes from GO-REVEAL

Placebo

Simponi

50 mg*

Responders, % of patients

ACR 20

Week 14

9%

51%

Week 24

ACR 50

Week 14

Week 24

ACR 70

Week 14

Placebo

Simponi

50 mg*

Week 24

PASI

b

75

c

Week 14

Week 24

* p < 0.05 for all comparisons

n reflects randomised patients; actual number of patients evaluable for each endpoint may vary by timepoint

Psoriasis Area and Severity Index

Based on the subset of patients with

3% BSA involvement at baseline, 79 patients (69.9%) in the placebo group

and 109 (74.3%) in the Simponi 50 mg group

Responses were observed at the first assessment (week 4) after the initial Simponi administration. Similar ACR 20 responses

at week 14 were observed in patients with polyarticular arthritis with no rheumatoid nodules and asymmetric peripheral

arthritis PsA subtypes. The number of patients with other PsA subtypes was too small to allow meaningful assessment.

Responses observed in the Simponi-treated groups were similar in patients receiving and not receiving concomitant MTX.

Among 146 patients randomised to Simponi 50 mg, 70 were still on this treatment at week 104. Of these 70 patients,

64, 46 and 31 patients had an ACR 20/50/70 response, respectively. Among patients remaining in the study and treated

with Simponi, similar rates of ACR 20/50/70 response was observed from week 104 through week 256.

Statistically significant responses in DAS28 were also observed at weeks 14 and 24 (p < 0.05).

At week 24 improvements in parameters of peripheral activity characteristic of psoriatic arthritis (e.g., number of swollen

joints, number of painful/tender joints, dactylitis and enthesitis) were seen in the Simponi-treated patients. Simponi treatment

resulted in significant improvement in physical function as assessed by HAQ DI, as well as significant improvements in

health-related quality of life as measured by the physical and mental component summary scores of the SF-36. Among

patients who remained on the Simponi treatment to which they were randomised at study start, DAS28 and HAQ DI

responses were maintained through week 104. Among patients remaining in the study and treated with Simponi, DAS28

and HAQ DI responses were similar from week 104 through week 256.

Radiographic response:

Structural damage in both hands and feet was assessed radiographically by the change from baseline in the vdH-S score,

modified for PsA by addition of hand distal interphalangeal (DIP) joints.

Simponi 50 mg treatment reduced the rate of progression of peripheral joint damage compared with placebo treatment

at week 24 as measured by change from baseline in total modified vdH-S score (mean + SD score was 0.27 + 1.3 in the

placebo group compared with -0.16 + 1.3 in the Simponi group; p = 0.011). Out of 146 patients who were randomized

to Simponi 50 mg, 52 week X-ray data were available for 126 patients, of whom 77% showed no progression compared

to baseline. At week 104, X-ray data were available for 114 patients, and 77% showed no progression from baseline.

Among patients remaining in the study and treated with Simponi, similar rates of patients showed no progression from

baseline from week 104 through week 256.

Axial spondyloarthritis:

Ankylosing spondylitis

The safety and efficacy of Simponi were evaluated in a multi-centre, randomised, double-blind, placebo-controlled study

(GO-RAISE) in 356 adult patients with active ankylosing spondylitis (defined as a Bath Ankylosing Spondylitis Disease

Activity Index (BASDAI)

4 and a VAS for total back pain of

4, on a scale of 0 to 10 cm). Patients enrolled in this study

had active disease despite current or previous NSAID or DMARD therapy and had not previously been treated with anti-TNF

therapy. Simponi or placebo were administered subcutaneously every 4 weeks. Patients were randomly assigned to placebo,

Simponi 50 mg and Simponi 100 mg and were allowed to continue concomitant DMARD therapy (MTX, SSZ and/or HCQ).

The primary endpoint was the percentage of patients achieving Ankylosing Spondylitis Assessment Study Group (ASAS)

20 response at week 14. Placebo-controlled efficacy data were collected and analysed through week 24.

Key results for the 50 mg dose are shown in Table 5 and described below. In general, no clinically meaningful differences

in measures of efficacy were observed between the Simponi 50 mg and 100 mg dosing regimens through week 24. By

study design, patients in the long-term extension may have switched between the 50 mg and 100 mg Simponi doses at

the discretion of the study physician.

Table 5

Key efficacy outcomes from GO-RAISE

Placebo

Simponi

50 mg*

Responders, % of patients

ASAS 20

Week 14

22%

59%

Week 24

ASAS 40

Week 14

Week 24

ASAS 5/6

Week 14

Week 24

0.001 for all comparisons

n reflects randomised patients; actual number of patients evaluable for each endpoint may vary by timepoint

Among patients remaining in the study and treated with Simponi, the proportion of patients with an ASAS 20 and ASAS

40 response was similar from week 24 through week 256.

Statistically significant responses in BASDAI 50, 70 and 90 (p

0.017) were also seen at weeks 14 and 24. Improvements

in key measures of disease activity were observed at the first assessment (week 4) after the initial Simponi administration

and were maintained through week 24. Among patients remaining in the study and treated with Simponi, similar rates

of change from baseline in BASDAI were observed from week 24 through week 256. Consistent efficacy was seen in

patients regardless of use of DMARDs (MTX, sulfasalazine and/or hydroxychloroquine), HLA-B27 antigen status or baseline

CRP levels as assessed by ASAS 20 responses at week 14.

Simponi treatment resulted in significant improvements in physical function as assessed by changes from baseline in BASFI

at weeks 14 and 24. Health-related quality of life as measured by the physical component score of the SF-36 was also

improved significantly at weeks 14 and 24. Among patients remaining in the study and treated with Simponi, improvements

in physical function and health-related quality of life were similar from week 24 through week 256.

Non‑radiographic axial spondyloarthritis

The safety and efficacy of Simponi were evaluated in a multi-centre, randomised, double-blind, placebo-controlled

study (GO-AHEAD) in 197 adult patients with severe active nr-Axial SpA (defined as those patients meeting the ASAS

classification criteria of axial spondyloarthritis but did not meet the modified New York criteria for AS). Patients enrolled

in this study had active disease (defined as a BASDAI

4 and a Visual Analogue Scale (VAS) for total back pain of

each on a scale of 0-10 cm) despite current or previous NSAID therapy and had not previously been treated with any

biological agents including anti-TNF therapy. Patients were randomly assigned to placebo or Simponi 50 mg administered

subcutaneously every 4 weeks. At week 16, patients entered an open-label period in which all patients received Simponi

50 mg administered subcutaneously every 4 weeks through week 48 with efficacy assessments performed through week 52

and safety follow-up through week 60. Approximately 93% of patients who were receiving Simponi at the beginning

of the open-label extension (week 16) remained on treatment through the end of the study (week 52). Analyses were

performed on both the All Treated (AT, N = 197) and Objective Signs of Inflammation (OSI, N = 158, defined by elevated

CRP and/or evidence of sacroiliitis on MRI at baseline) populations. Placebo-controlled efficacy data were collected and

analysed through week 16. The primary endpoint was the proportion of patients achieving ASAS 20 response at week 16.

Key results are shown in Table 6 and described below.

Table 6

Key efficacy outcomes from GO-AHEAD at week 16

Improvements in signs and symptoms

All treated population (AT)

Objective signs of inflammation

population (OSI)

Placebo

Simponi 50 mg

Placebo

Simponi 50 mg

Responders, % of patients

ASAS 20

71%**

77%**

ASAS 40

57%**

60%**

ASAS 5/6

54%**

63%**

ASAS Partial Remission

33%*

35%*

ASDAS-C

< 1.3

33%*

35%*

BASDAI 50

58%**

59%**

Inhibition of inflammation in sacroiliac (SI) joints as measured by MRI

Placebo

Simponi 50 mg

Placebo

Simponi 50 mg

Mean change in SPARCC

MRI sacroiliac joint score

-0.9

-5.3**

-1.2

-6.4**

n reflects randomised and treated patients

Ankylosing Spondylitis Disease Activity Score C-Reactive Protein (AT-Placebo, N = 90; AT-Simponi 50 mg,

N = 88; OSI-Placebo, N = 71; OSI-Simponi 50 mg, N = 71)

n reflects number of patients with baseline and week 16 MRI data

SPARCC (Spondyloarthritis Research Consortium of Canada)

** p < 0.0001 for Simponi vs. placebo comparisons

* p < 0.05 for Simponi vs. placebo comparisons

Statistically significant improvements in signs and symptoms of severe active nr-Axial SpA were demonstrated in patients

treated with Simponi 50 mg compared to placebo at week 16 (Table 6). Improvements were observed at the first

assessment (week 4) after the initial Simponi administration. SPARCC score as measured by MRI showed statistically

significant reductions in SI joint inflammation at week 16 in patients treated with Simponi 50 mg compared to placebo

(Table 6). Pain as assessed by the Total Back Pain and Nocturnal Back Pain VAS, and disease activity as measured by

ASDAS-C also showed statistically significant improvement from baseline to week 16 in patients treated with Simponi

50 mg compared to placebo (p < 0.0001).

Statistically significant improvements in spinal mobility as assessed by BASMI (Bath Ankylosing Spondylitis Metrology Index)

and in physical function as assessed by the BASFI were demonstrated in Simponi 50 mg-treated patients as compared

to placebo-treated patients (p < 0.0001). Patients treated with Simponi experienced significantly more improvements in

health-related quality of life as assessed by ASQoL, EQ-5D, and physical and mental components of SF-36, and experienced

significantly more improvements in productivity as assessed by greater reductions in overall work impairment and in activity

impairment as assessed by the WPAI questionnaire than patients receiving placebo.

For all of the endpoints described above, statistically significant results were also demonstrated in the OSI population

at week 16.

In both the AT and OSI populations, the improvements in signs and symptoms, spinal mobility, physical function, quality

of life, and productivity observed at week 16 among patients treated with Simponi 50 mg continued in those remaining

in the study at week 52.

Ulcerative colitis

The efficacy of Simponi was evaluated in two randomized, double-blind, placebo-controlled clinical studies in adult

patients.

The induction study (PURSUIT-Induction) evaluated patients with moderately to severely active ulcerative colitis (Mayo score

6 to 12; Endoscopy subscore

2) who had an inadequate response to or failed to tolerate conventional therapies, or were

corticosteroid dependent. In the dose confirming portion of the study, 761 patients were randomized to receive either 400 mg

Simponi SC at week 0 and 200 mg at week 2, 200 mg Simponi SC at week 0 and 100 mg at week 2, or placebo SC at

weeks 0 and 2. Concomitant stable doses of oral aminosalicylates, corticosteroids, and/or immunomodulatory agents

were permitted. The efficacy of Simponi through week 6 was assessed in this study.

The results of the maintenance study (PURSUIT-Maintenance) were based on evaluation of 456 patients who achieved clinical

response from previous induction with Simponi. Patients were randomized to receive Simponi 50 mg, Simponi 100 mg

or placebo administered subcutaneously every 4 weeks. Concomitant stable doses of oral aminosalicylates, and/or

immunomodulatory agents were permitted. Corticosteroids were to be tapered at the start of the maintenance study. The

efficacy of Simponi through week 54 was assessed in this study. Patients who completed the maintenance study through

week 54 continued treatment in a study-extension, with efficacy evaluated through week 216. Efficacy evaluation in the

study extension was based on changes in corticosteroid use, Physician’s Global Assessment (PGA) of disease activity, and

improvement in quality of life as measured by Inflammatory Bowel Disease Questionnaire (IBDQ).

Table 7

Key efficacy outcomes from PURSUIT-Induction and PURSUIT-Maintenance

PURSUIT-Induction

Placebo

N = 251

Simponi

200/100 mg

N = 253

Percentage of patients

Patients in clinical response at week 6

51%**

Patients in clinical remission at week 6

18%**

Patients with mucosal healing at week 6

42%**

PURSUIT-Maintenance

Placebo

d

N = 154

Simponi

50 mg

N = 151

Simponi

100 mg

N = 151

Percentage of patients

Maintenance of response

(Patients in clinical response through week

47%*

50%**

Sustained remission (Patients in clinical remission

at both week 30 and week 54)

28%*

N = number of patients

** p

0.001

0.01

Defined as a decrease from baseline in the Mayo score by

30% and

3 points, accompanied by a decrease in the

rectal bleeding subscore of

1 or a rectal bleeding subscore of 0 or 1

Defined as a Mayo score

2 points, with no individual subscore > 1

Defined as 0 or 1 on the endoscopy subscore of the Mayo score

Simponi induction only

Patients were assessed for UC disease activity by partial Mayo score every 4 weeks (loss of response was confirmed

by endoscopy). Therefore, a patient who maintained response was in a state of continuous clinical response at each

evaluation through week 54

A patient had to be in remission at both weeks 30 and 54 (without demonstrating a loss of response at any time

point through week 54) to achieve durable remission

In patients weighing less than 80 kg, a greater proportion of patients who received 50 mg maintenance therapy

showed sustained clinical remission compared with those who received placebo

More Simponi-treated patients demonstrated sustained mucosal healing (patients with mucosal healing at both week

30 and week 54) in the 50 mg group (42%, nominal p < 0.05) and 100 mg group (42%, p < 0.005) compared with

patients in the placebo group (27%).

Among the 54% of patients (247/456) who were receiving concomitant corticosteroids at the start of PURSUIT-Maintenance,

the proportion of patients who maintained clinical response through week 54 and were not receiving concomitant

corticosteroids at week 54 was greater in the 50 mg group (38%, 30/78) and 100 mg group (30%, 25/82) compared with

the placebo group (21%, 18/87). The proportion of patients who eliminated corticosteroids by week 54 was greater in the

50 mg group (41%, 32/78) and 100 mg group (33%, 27/82) compared with the placebo group (22%, 19/87).

Among patients who entered the study extension, the proportion of subjects who remained corticosteroid free was

generally maintained through week 216.

At week 6, Simponi significantly improved quality of life as measured by change from baseline in a disease specific measure,

IBDQ (inflammatory bowel disease questionnaire). Among patients who received Simponi maintenance treatment, the

improvement in quality of life as measured by IBDQ was maintained through week 54. Approximately 63% of patients

who were receiving Simponi at the beginning of the study extension (week 56), remained on treatment through the end

of the study (last golimumab administration at week 212).

Immunogenicity

Across the Phase III RA, PsA and AS studies through week 52, antibodies to golimumab were detected by the enzyme

immunoassay (EIA) method in 5% (105/2062) of golimumab-treated patients and, where tested, nearly all antibodies

were neutralising in vitro. Similar rates were shown across rheumatologic indications. Treatment with concomitant MTX

resulted in a lower proportion of patients with antibodies to golimumab than patients receiving golimumab without MTX

(approximately 3% [41/1235] versus 8% [64/827], respectively).

In nr-Axial SpA, antibodies to golimumab were detected in 7% (14/193) of golimumab-treated patients through week

52 by the EIA method.

In the Phase II and III UC studies through week 54, antibodies to golimumab were detected by the EIA method in

3% (26/946) of golimumab-treated patients. Sixty-eight percent (21/31) of antibody-positive patients had neutralising

antibodies in vitro. Treatment with concomitant immunomodulators (azathioprine, 6-mercaptopurine and MTX) resulted in a

lower proportion of patients with antibodies to golimumab than patients receiving golimumab without immunomodulators

(1% (4/308) versus 3% (22/638), respectively). Of patients that continued in the study extension and had evaluable samples

through week 228, antibodies to golimumab were detected in 4% (23/604) of golimumab-treated patients. Eighty-two

percent (18/22) of antibody-positive patients had neutralising antibodies in vitro.

A drug-tolerant EIA method was used in the pJIA study for the detection of antibodies to golimumab. Due to the higher

sensitivity and the improved drug tolerance, a higher incidence of antibodies to golimumab was expected to be detected

with the drug-tolerant EIA method compared to the EIA method. In the Phase III pJIA study through week 48, antibodies

to golimumab were detected by the drug-tolerant EIA method in 40% (69/172) of golimumab-treated children of which a

majority had a titre lower than 1:1000. An effect on serum golimumab concentrations was seen at titres of > 1:100 while

an effect on efficacy was not seen until titres of > 1:1000, though the numbers of children with titres of > 1:1000 were low

(N = 8). Among the children who tested positive for antibodies to golimumab, 39% (25/65) had neutralising antibodies.

The higher incidence of antibodies with the drug-tolerant EIA method, because they were mainly low titre antibodies, did

not have an apparent impact on drug levels, efficacy and safety and therefore does not represent any new safety signal.

The presence of antibodies to golimumab may increase the risk of injection site reactions (see section 4.4). The small

number of patients positive for antibodies to golimumab limits the ability to draw definitive conclusions regarding the

relationship between antibodies to golimumab and clinical efficacy or safety measures.

Because immunogenicity analyses are product- and assay-specific, comparison of antibody rates with those from other

products is not appropriate.

Paediatric population

Polyarticular juvenile idiopathic arthritis

The safety and efficacy of Simponi was evaluated in a randomised, double-blind, placebo-controlled, withdrawal study

(GO-KIDS) in 173 children (2 to 17 years of age) with active pJIA with at least 5 active joints and an inadequate response

to MTX. Children with polyarticular course JIA (rheumatoid factor positive or negative polyarthritis, extended oligoarthritis,

juvenile psoriatic arthritis or systemic JIA with no current systemic symptoms) were included in the study. The baseline

median number of active joints was 12, and median CRP was 0.17 mg/dL.

Part 1 of the study consisted of a 16-week open-label phase in which 173 enrolled children received Simponi 30 mg/m

(maximum 50 mg) subcutaneously every 4 weeks and MTX. The 154 children who achieved an ACR Ped 30 response at

week 16 entered Part 2 of the study, the randomised withdrawal phase, and received Simponi 30 mg/m

(maximum 50 mg)

+ MTX or placebo + MTX every 4 weeks. After disease flare, children received Simponi 30 mg/m

(maximum 50 mg)

+ MTX. At week 48, children entered a long-term extension.

Children in this study demonstrated ACR Ped 30, 50, 70, and 90 responses as early as week 4.

At week 16, 87% of children were ACR Ped 30 responders, and 79%, 66%, and 36% of children were ACR Ped 50, ACR

Ped 70, and ACR Ped 90 responders, respectively. At week 16, 34% of children had inactive disease defined as having

the presence of all of the following: no joints with active arthritis; no fever, rash, serositis, splenomegaly, hepatomegaly,

or generalised lymphadenopathy attributable to JIA; no active uveitis; normal ESR (< 20 mm/h) or CRP (< 1.0 mg/dL);

physician global assessment of disease activity (

5 mm on the VAS); duration of morning stiffness < 15 minutes.

At week 16, all ACR Ped components demonstrated clinically relevant improvement from baseline (see Table 8).

Table 8

Improvements from baseline in ACR Ped components at week 16

a

Median percent improvement

Simponi 30 mg/m

= 173

Physician’s global assessment of disease (VAS

0-10 cm)

Subject/parent global assessment of overall well-being (VAS 0-10 cm)

Number of active joints

Number of joints with limited range of motion

Physical function by CHAQ

ESR (mm/h)

baseline = week 0

“n” reflects enrolled patients

VAS: Visual Analogue Scale

CHAQ: Child Health Assessment Questionaire

ESR (mm/h): Erythrocyte Sedimentation Rate (millimetres per hour)

The primary endpoint, the proportion of children who were ACR Ped 30 responders at week 16 and who did not experience

a flare between week 16 and week 48, was not achieved. The majority of children did not experience a flare between

week 16 and week 48 (59% in the Simponi + MTX and 53% in the placebo + MTX groups, respectively; p = 0.41).

Pre-specified subgroup analyses of the primary endpoint by baseline CRP (

1 mg/dL vs. < 1 mg/dL) demonstrated higher

flare rates in placebo + MTX vs. Simponi + MTX-treated subjects among subjects with baseline CRP

1 mg/dL (87% vs.

40% p = 0.0068).

At week 48, 53% and 55% of children in the Simponi + MTX group and placebo + MTX group, respectively, were ACR

Ped 30 responders, and 40% and 28% of children in the Simponi + MTX group and placebo + MTX group, respectively,

achieved inactive disease.

The European Medicines Agency has deferred the obligation to submit the results of studies with Simponi in the paediatric

population in ulcerative colitis (see section 4.2 for information on paediatric use).

5.2

Pharmacokinetic properties

Absorption

Following a single subcutaneous administration of golimumab to healthy subjects or patients with RA, the median time

to reach maximum serum concentrations (T

) ranged from 2 to 6 days. A subcutaneous injection of 50 mg golimumab

to healthy subjects produced a mean ± standard deviation maximum serum concentration (C

) of 3.1 ± 1.4

g/ml.

Following a single subcutaneous injection of 100 mg, the absorption of golimumab was similar in the upper arm,

abdomen, and thigh, with a mean absolute bioavailability of 51%. Since golimumab exhibited approximately

dose-proportional PK following a subcutaneous administration, the absolute bioavailability of the golimumab 50 mg or

200 mg dose is expected to be similar.

Distribution

Following a single IV administration, the mean volume of distribution was 115 ± 19 ml/kg.

Elimination

The systemic clearance of golimumab was estimated to be 6.9 ± 2.0 ml/day/kg, terminal half-life value was estimated to

be approximately 12 ± 3 days in healthy subjects and similar values were observed in patients with RA, PsA, AS, or UC.

When 50 mg golimumab was administered subcutaneously to patients with RA, PsA or AS every 4 weeks, serum concentrations

reached steady state by week 12. With concomitant use of MTX, treatment with 50 mg golimumab subcutaneous every 4

weeks resulted in a mean (± standard deviation) steady-state trough serum concentration of approximately 0.6 ± 0.4

g/ml

in RA patients with active RA despite MTX therapy, and approximately 0.5 ± 0.4

g/ml in patients with active PsA and

approximately 0.8 ± 0.4

g/ml in patients with AS. Steady-state trough mean serum golimumab concentrations in patients

with nr-Axial SpA were similar to those observed in patients with AS following subcutaneous administration of 50 mg

golimumab every 4 weeks.

Patients with RA, PsA or AS who did not receive concomitant MTX had approximately 30% lower steady-state trough

concentrations of golimumab than those who received golimumab with MTX. In a limited number of RA patients treated

with subcutaneous golimumab over a 6-month period, concomitant use of MTX reduced the apparent clearance of

golimumab by approximately 36%. However, population pharmacokinetic analysis indicated that concomitant use of

NSAIDs, oral corticosteroids or sulfasalazine did not influence the apparent clearance of golimumab.

Following induction doses of 200 mg and 100 mg golimumab at weeks 0 and 2, respectively, and maintenance doses

of 50 mg or 100 mg golimumab subcutaneously every 4 weeks thereafter to patients with UC, serum golimumab

concentrations reached steady state approximately 14 weeks after the start of therapy. Treatment with 50 mg or 100 mg

golimumab subcutaneous every 4 weeks during maintenance resulted in a mean steady-state trough serum concentration

of approximately 0.9 ± 0.5

g/ml and 1.8 ± 1.1

g/ml, respectively.

In UC patients treated with 50 mg or 100 mg golimumab subcutaneously every 4 weeks, concomitant use of immunomodulators

did not have a substantial effect on steady-state trough levels of golimumab.

Patients who developed anti-golimumab antibodies generally had low trough steady-state serum concentrations of

golimumab (see section 5.1).

Linearity

Golimumab exhibited approximately dose-proportional pharmacokinetics in patients with RA over the dose range of 0.1

to 10.0 mg/kg following a single intravenous dose. Following a single SC dose in healthy subjects, approximately dose-

proportional pharmacokinetics were also observed over a dose range of 50 mg to 400 mg.

Effect of weight on pharmacokinetics

There was a trend toward higher apparent clearance of golimumab with increasing weight (see section 4.2).

Paediatric population

The pharmacokinetics of golimumab were determined in 173 children with pJIA with an age range from 2 to 17 years of

age. In the pJIA study, children who received golimumab 30 mg/m

(maximum 50 mg) subcutaneously every 4 weeks, had

median steady-state trough golimumab concentrations which were similar across different age groups, and which were

also similar to or slightly higher than those seen in adult RA patients who received 50 mg golimumab every 4 weeks.

Population pharmacokinetic/pharmacodynamic modeling and simulation in children with pJIA confirmed the relationship

between golimumab serum exposures and clinical efficacy and supports that the dosing regimen of golimumab 50 mg every

4 weeks in children with pJIA of at least 40 kg achieves similar exposures to those shown to be efficacious in adults.

5.3

Preclinical safety data

Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated

dose toxicity, toxicity to reproduction and development.

No mutagenicity studies, animal fertility studies nor long-term carcinogenic studies have been conducted with golimumab.

In a fertility and general reproductive function study in mice, using an analogous antibody that selectively inhibits the

functional activity of mouse TNF-

, the number of pregnant mice was reduced. It is not known whether this finding

was due to effects on the males and/or the females. In a developmental toxicity study conducted in mice following

administration of the same analogous antibody, and in cynomolgus monkeys using golimumab, there was no indication

of maternal toxicity, embryotoxicity or teratogenicity.

6.

PHARMACEUTICAL PARTICULARS

6.1

List of excipients

Sorbitol

L-histidine

Polysorbate 80

Water for injections.

6.2

Incompatibilities

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

6.3

Shelf life

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

6.4

Special precautions for storage

Store in a refrigerator (2°C-8°C).

Do not freeze.

Keep the auto-injector pen / pre-filled syringe in the outer carton in order to protect it from light.

6.5

Nature and contents of container

0.5/1 ml solution in a pre-filled syringe (1.0 ml Type 1 glass) with a fixed needle (stainless steel) and a needle cover (rubber

containing latex) in a auto-injector pen / pre-filled syringe.

Simponi should not be used if the solution is discoloured, cloudy or contains visible foreign particles.

6.6

Special precautions for disposal and other handling

Simponi is supplied in a single-use auto-injector pen called SmartJect / pre-filled syringe. Each Simponi pack is provided

with instructions for use that fully describe the use of the pen/syringe. After removing auto-injector pen / pre-filled syringe

from the refrigerator, auto-injector pen / pre-filled syringe should be allowed to reach room temperature by waiting for

30 minutes, before injecting Simponi. The pen/syringe should not be shaken.

The solution is clear to slightly opalescent, colourless to light yellow and may contain a few small translucent or white

particles of protein. This appearance is not unusual for solutions containing protein. Simponi should not be used if the

solution is discoloured, cloudy or contains visible foreign particles.

Comprehensive instructions for the preparation and administration of Simponi in auto-injector pen / pre-filled syringe

are given in the package leaflet.

Any unused product or waste material should be disposed of in accordance with local requirements.

Manufacturer: Janssen Biologics, Einsteinweg 101, Leiden, The Netherlands

Registration Holder: J-C Health Care Ltd., Kibbutz Shefayim 6099000, Israel

The content of this leaflet was approved by the Ministry of Health in 01.2017 and updated according to the guidelines

of the Ministry of Health on 30.04.2018

Simponi Pen/Syringe PL+PHY SH 08/18

J-C 2018

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