PROGRAF 1 MG

Israel - English - Ministry of Health

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Active ingredient:
TACROLIMUS
Available from:
ABIC MARKETING LTD, ISRAEL
ATC code:
L04AA05
Pharmaceutical form:
CAPSULES
Composition:
TACROLIMUS 1 MG
Administration route:
PER OS
Prescription type:
Required
Manufactured by:
ASTELLAS IRELAND CO. LTD, IRELAND
Therapeutic group:
TACROLIMUS
Therapeutic area:
TACROLIMUS
Therapeutic indications:
Prophylaxis of transplant rejection in liver kidney or heart allograft recipients.Treatment of allograft rejection resistant to treatment with other immunosuppressive medicinal products.
Authorization number:
107 69 29158 00
Authorization date:
2012-10-31

Documents in other languages

Patient Information leaflet Patient Information leaflet - Arabic

20-01-2021

Patient Information leaflet Patient Information leaflet - Hebrew

12-01-2020

1986 - ו״משתה )םירישכת( םיחקורה תונקת יפל ןכרצל ןולע דבלב אפור םשרמ יפ לע תקוושמ הפורתה תוסומכ

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ףרגורפ ג״מ 5

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ףרגורפ ג״מ 1

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ףרגורפ ג״מ 0.5

®

ףרגורפ תוסומכ

תוסומכ

תוסומכ בכרה :הליכמ הסומכ לכ ג״מ 5 סומילורקט ג״מ 1 סומילורקט ג״מ 0.5 סומילורקט

Tacrolimus 5 mg

Tacrolimus 1 mg

Tacrolimus 0.5 mg

ףיעס האר םיינגרלאו םיליעפ יתלב םיביכרמ לע עדימל ףיעסו ״הפורתה לש םיביכרמהמ קלח לע בושח עדימ״ 2 .״ףסונ עדימ״ - 6 .הפורתב שמתשת םרטב ופוס דע ןולעה תא ןויעב ארק תולאש ךל שי םא .הפורתה לע יתיצמת עדימ ליכמ הז ןולע .חקורה לא וא אפורה לא הנפ ,תופסונ .םירחאל התוא ריבעת לא .ךרובע לופיטל המשרנ וז הפורת .המוד יאופרה םבצמ יכ ךל הארנ םא וליפא םהל קיזהל הלולע איה ?הפורתה תדעוימ המל .1 .בל וא הילכ ,דבכ לש הלתשה רחאל לתש לש הייחד תעינמ תכרעמ תא תואכדמה תורחא תופורתל דימעה לתש לש הייחדב לופיט .)immunosuppressive drugs( ןוסיחה .ןוסיחה תכרעמ תא תואכדמה תופורת תצובקל תכייתשמ ףרגורפ הפורתה הסנת ךפוג לש ןוסיחה תכרעמ )בלו הילכ ,דבכ ןוגכ( רביאה תלתשה רחאל לש תינוסיחה הבוגתה תוסיוול תשמשמ ףרגורפ .שדחה רביאה תא תוחדל .לתשומה רביאה תא לבקל ךלש ףוגל תרשפאמו ךלש ףוגה .ןוסיחה תכרעמ יאכדמ :תיטיופרת הצובק הפורתב שומישה ינפל .2 לש ורושיאבו ותעידיב אלא רחא סומילורקט רישכתב ףילחהל ןיא .לפוטמ התא הב תולתשהה תאפרממ אפורה :םא הפורתב שמתשהל ןיא םיפסונה םיביכרמהמ דחא לכל וא סומילורקטל )יגרלא( שיגר התא .)״ףסונ עדימ״ – 6 ףיעס האר( הפורתה הליכמ רשא תצובקל תכייתשמה איהשלכ תיטויביטנא הפורתל )יגרלא( שיגר התא ,ןיצימורתירלק ,ןיצימורתירא :ןוגכ( םידילורקמה גוסמ תוקיטויביטנאה .)ןיצימסו'ג הפורתב שומישל תועגונה תודחוימ תורהזא הפורתה התוא תא לבקמ דימת התאש אדוותש בושח ,ךביל תמושתל תיבב הפורתה תא לבקמ התאש םעפ לכב תולתשהה החמומ ךל םשרש ךרדב לבקמ התאש וזמ הנוש תיארנ תלביקש הפורתה םא .תחקרמה תלביקש אדוול חקורל דימ הנפ אנא ,ונתשה שומישה תויחנהש וא ללכ הליכמה הפורת לש ןונימ יוניש וא הפלחה לכ .הנוכנה הפורתה תא ורושיאבו ותעידיב עצבתהל םיבייח )הפורתב ליעפה רמוחה( סומילורקט ומש תא קודב אנא .לפוטמ התא הב תולתשהה תאפרממ אפורה לש תלביקש הפורתה לומ םשרמב אפורה םשרש רישכתה לש ירחסמה .םיהז םהש אדוו חקורהמ :אפורל רפס ףרגורפב לופיטה ינפל לע ינוסיח יוכידל קוקז התא דוע לכ ,םוי ידמ ףרגורפ תחקל ךירצ התא רידס רשק לע רומשל ךילע .ךלש לתשומה רביאה לש הייחד עונמל תנמ .ךלש אפורה םע עוציבל ךתוא הנפי ךלש אפורהו ןכתיי ףרגורפ תוסומכ לטונ התאש ןמזב הייאר תוקידב ,בלה דוקפת ,ןתש ,םד תוקידב ללוכ( תוקידב רפסמ ךלש אפורל רוזעי אוהו ליגר ךילה והז .תעל תעמ )תויגולוריונ תוקידבו .ךרובע ףרגורפ לש רתויב םיאתמה ןונימה והמ טילחהל St. John׳s( םוקירפיה ןוגכ ,יחמצ רוקממ הפורת לכ תליטנמ ענמיהל שי רחאמ ,יחמצ רוקממ רחא רצומ לכ וא ,)wort [

hypericum perforatum

ףרגורפ לש תשרדנה הנמה לעו לופיטה תוליעי לע עיפשהל לולע הזו תליטנ ינפל ךלש אפורל תונפל ךילע קפס לש הרקמב .לבקל ךירצ התאש .יחמצ רוקממ הפורת וא רצומ לכ דבכה לע עיפשהל הלולעה הלחמ ךל שיש וא דבכב תויעב ךל שי םא ףרגורפ לש ןונימה לע עיפשהל לולע הזו רחאמ ךלש אפורל רפס ,ךלש .לבקמ התאש ,םירחא םינימסתב הוולמ וניאש וא הוולמה קזח ןטב באכ שח התא םא .האקה וא הליחב ,םוח ,תורומרמצ ןוגכ ,ךלש אפורל ךכ לע רפס ,דחא םוימ רתוי ךשמל לושלשמ לבוס התא םא .לבקמ התאש ףרגורפה ןונימ תא םיאתהל ךרוצ היהיו ןכתייש ןוויכ עטקמ תכראה״ ארקנה ךלש בלה לש תילמשחה הכלוהב יוניש שי םא

.״QT ףרגורפב לופיטה ןמזב UV תנירקלו שמשה רואל ךתפישח תא לבגה םע שמשה ינפמ הנגה םרקב שומישו םיאתמ ןגמ דוגיב תשיבל ידי-לע םיריאממ םייונישל ירשפאה ןוכיסה איה ךכל הביסה .הובג הנגה םדקמ .ןוסיחה תכרעמ תא אכדמש לופיטל הוולנה רועב אפורה .שארמ ךלש אפורה תא עדי ,םהשלכ םינוסיח לבקל ךירצ התא םא .רתויב הבוטה לופיטה ךרד לע ךל ץילמי ךלש תכרעמב יוקיל לש רבגומ ןוכיס לע חווד ףרגורפב ולפוטש םילפוטמב )lymphoproliferative disorders( םיאת לש רתי רוצייב אטבתמה הפמילה .הלא תוערפה יבגל אפורה םע ץעייתה .)״יאוול תועפות״ – 4 ףיעס האר( :מ לבוס התא לופיטה ךלהמב םא ידיימ ןפואב אפורל חווד ישוק ,םיעבצ לש הייארב םייוניש ,תשטשוטמ הייאר ןוגכ הייארב תויעב .לבגומ היהנ ךלש הייארה הדש םא וא םיטרפ תוארל תויתפורת ןיב תובוגת תופורת ללוכ תורחא תופורת ,הנורחאל תחקל םא וא ,חקול התא םא .חקורל וא אפורל ךכ לע רפס ,הנוזת יפסותו םשרמ אלל .ןירופסולקיצ םע דחי ףרגורפ לוטיל ןיא ,לטונ התאש תורחא תופורתמ תעפשומ תויהל הלולע םדב ףרגורפה תמר רבד ,ףרגורפמ תועפשומ תויהל תולולע םדב תורחא תופורת לש תומרו ךילע ,דחוימב .ףרגורפ לש ןונימב הדירי וא היילע ,הקספה בייחל לולע הז םירמוח םע תופורת הנורחאל תחקל וא חקול התא םא ךלש אפורל רפסל :ןוגכ םיליעפ תצובקמ תוקיטויביטנא דחוימב ,תוקיטויביטנאו תוירטפ דגנ תופורת ,לוזאנוקולפ ,לוזנוקוטק ןוגכ םימוהיזב לופיטל תושמשמה ,םידילורקמה ,ןיצימורתירא ,לוזאנוקובאסיא ,לוזמירטולק ,לוזנוקירוו ,לוזנוקארטיא .ןיציפמאפירו ןיצימסו'ג ,ןיצימורתירלק -ולגמוטיצ( CMV ףיגנ ידי-לע תמרגנה הלחמ תעינמל שמשמה ,ריבומרטל .)human cytomegalovirus ,ישונא סוריו הפורתה ,)ריבאניווקאסו ריבאניפלנ ,ריבאנוטיר ןוגכ( HIV זאטורפ יבכעמ םוהיזב לופיטל םישמשמה ,תובלושמ תוילבטו טאטסיסיבוק הריבגמה .)ישונאה ינוסיחה לשכה ףיגנ( HIV /ריבסאטיבמוא בולישהו ריברפצוב ,ריברפלט ןוגכ( HCV זאטורפ יבכעמ לופיטל םישמשמה ,)ריבובאסאד אלל וא םע ריבאנוטיר/ריברפאטיראפ .)C סיטיטפה( C דבכ תקלד םוהיזב .)םימייוסמ ןטרס יגוסב לופיטל םישמשמה( ביניטאמיאו ביניטולינ תכרעמ יוכידל תשמשמה )mycophenolic acid( תילונפוקימ הצמוח .לתש תייחד עונמל תנמ לע ןוסיחה ,לוזרפמוא ןוגכ( )acid reflux( יטשו רזחהלו הביק ביכב לופיטל תופורת .)ןידיטמיס וא לוזרפוסנל .)דימארפולקותמ ןוגכ( תואקהבו תוליחבב לופיטל תופורת לופיטל םישמשמה דיסקורדיה-םוינימולא-םויזנגמ םיליכמה הצמוח ידגונ .תברצב תעינמל תולולג ןוגכ( לוידארטסאליניתא םיליכמה םיילאנומרוה םילופיט

.לוזאנאד וא )ןויריה ,ןיפידרקינ ,ןיפידפינ ןוגכ בל תויעבב וא םד ץחל רתיב לופיטל תופורת .לימאפארוו םזאיטליד בצקב תוערפהב לופיטל תושמשמה )ןוראדוימא( תוימתירא-יטנא תופורת .)הימתירא( בלה לורטסלוכ לש תוהובג תומרב לופיטל תושמשמה םיניטטס תוארקנה תופורת .םידירצילגירטו .לטיברבונפ וא ןיאוטינפ )תויטפליפא יטנא( םיסוכרפה תודגונ תופורתה .ןולוזינדרפליתמו ןולוזינדרפ תוידיאורטסוקיטרוקה תופורתה .ןודוזאפנ ןואכידה תדגונ הפורתה St. John׳s wort [

hypericum

( םוקירפיה םיליכמה יחמצ רוקממ םירישכת

Schisandra sphenanthera

לש תויצמת וא )[

perforatum

וא B ןיצירטופמא ,ןפורפוביא תחקל ךירצ וא חקול התא םא אפורל רפס תויעב רימחהל תולולע הלא תופורת .)ריבולקיצא ןוגכ( םיפיגנ דגנ תופורת .ףרגורפ םע דחי תוחקלנ ןה רשאכ םיבצעה תכרעמב וא תוילכב ירמשמ םינתשמ וא ןגלשא יפסות חקול התא םא ךלש אפורל רפס ,ףסונב םיבאכ יככשמ ,)ןוטקלונוריפס וא ,ןירטמאירט ,דירולימא ןוגכ( ןגלשא ,)ןפורפוביא ןוגכ [NSAIDs[ םידיאורטס אל תקלד ידגונ גוסמ( םימיוסמ התאש ןמזב ,הפה ךרד תונתינה תרכוסב לופיטל תופורת וא ,השירק ידגונ .ףרגורפ לטונ .שארמ ךלש אפורה תא עדי ,םהשלכ םינוסיח לבקל ךירצ התא םא ןוזמו הפורתב שומיש ינפל תחא העש תוחפל וא הקיר הביק לע ללכ ךרדב הפורתה תא לוטיל שי ץימו תוילוכשא תכירצמ ענמיהל שי .החוראה ירחא תועש 2-3 וא החוראה .ףרגורפב לופיטה תפוקתב תוילוכשא הקנהו ןויריה יצעוויה ,ןויריה תננכתמ וא ,ןויריהב תאש תבשוח ,הקינמ וא ןויריהב תא םא .וז הפורת תליטנ ינפל חקורב וא אפורב .ףרגורפ תלטונ תא הב הפוקתב קינהל ןיא ןכל .םא בלחב תשרפומ ףרגורפ תונוכמב שומישו הגיהנ

וא תרוחרחס שיגרמ התא םא תונוכמב וא םילכב שמתשהל וא גוהנל ןיא ולא תועפות .ףרגורפ תליטנ רחאל רוריבב האור אל התא םא וא ,תוינונשי .לוהוכלא תכירצ םע בולישב החקלנ ףרגורפ רשאכ רתוי ההובג תורידתב ופצנ הפורתה לש םיביכרמהמ קלח לע בושח עדימ תוליבס-יא ךל שיש ךלש אפורה ידי-לע ךל רמאנ םא .זוטקל תוליכמ ףרגורפ תוסומכ

.וז הפורת תליטנ ינפל ךלש אפורל הנפ ,םימיוסמ םירכוסל ןיטיצל ליכמ ג״מ 1-ו ג״מ 0.5 ףרגורפ תוסומכ לע ספדומה בותיכה לש וידה תנמ-לע אפורל עידוהל ךילע היוסל וא םינטובל שיגר התא םא .היוס רוקממ .וז הפורת לוטיל ךילע םא עובקל .ןרתנ תלוטנ תבשחנ ךכיפלו הסומכב ןרתנ ג״מ 23-מ תוחפ הליכמ וז הפורת ?הפורתב שמתשת דציכ .3 .אפורה תוארוהל םאתהב דימת רישכתב שמתשהל שי לופיטה ןפואו ןונימל עגונב חוטב ךניא םא חקורה וא אפורה םע קודבל ךילע .רישכתב לבקמ התאש םעפ לכב סומילורקט רישכת ותוא תא לבקמ התאש אדוול ךילע תולתשהה תאפרממ החמומה אפורה םא אלא ,תחקרמה תיבב הפורתה תא .רחא סומילורקט רישכתל תונשל םיכסה לפוטמ התא הב .דבלב אפורה ידי-לע ועבקיי לופיטה ןפואו ןונימה :אוה ללכ ךרדב לבוקמה ןונימה הפורתה הארמב יונישב תנחבהו הדימב .םויב םיימעפ וז הפורת לוטיל שי לע ירשפאה םדקהב חקורל וא אפורל חוודל ךילע ,שומישה תוארוהב וא .הנוכנה הפורתה תא לטונ התאש אדוול תנמ אפורה ידי-לע עבקיי ךלש לתשומה רביאה תייחד תעינמל יתלחתהה ןונימה הלתשהה רחאל דימ יתלחתהה ןונימה .ךפוג לקשמל םאתהב בושיח יפל ךלש תולתכ ,םויל ףוג לקשמ ג״קל ג״מ 0.075-0.30 לש חווטב ללכ ךרדב היהי .לתשומה רביאב םירישכת וליא לעו יללכה ךתואירב בצמ לע ססובמ ךל םיאתמה ןונימה םד תוקידב עצבל שי .לטונ התא ןוסיחה תכרעמ יאכדמ גוסמ םיפסונ םעפמ ומיאתהלו ןוכנה ןונימה תעיבק םשל אפורה תייחנה יפל תויתרגיש אפורה .ךבצמ תובצייתה רחאל ףרגורפה ןונימ תדרוה לוקשי אפורה .םעפל .ןתליטנ תורידתו קייודמה תוסומכה רפסמ יבגל ךתוא החני .תצלמומה הנמה לע רובעל ןיא שומישה ןפוא ףרגורפ לוטיל שי .ברעבו רקובב ללכ ךרדב ,םויב םיימעפ ףרגורפ לוטיל שי תועש 2-3 וא החוראה ינפל תחא העש תוחפל וא ,הקיר הביק לע ללכ ךרדב לוטיל שי .םימ סוכ םע ןתומלשב תוסומכה תא עולבל שי .החוראה ירחא תכירצמ ענמיהל שי .)רטסילב( תישגמהמ ןתאצוה רחאל דימ תוסומכה תא תיקש תא עולבל ןיא .ףרגורפב שומישה ןמזב תוילוכשא ץימו תוילוכשא .םוינימולאה תפיטע ךותבש תוחלה חפוס רתי תנמ תועטב תלטנ םא תונפל שי ,הפורתה ןמ דלי עלב תועטב םא וא רתי תנמ תועטב תלטנ םא .הפורתה תזירא תא איבהלו םילוח תיב לש ןוימ רדחל וא אפורל דימ הפורתה תא לוטיל תחכש םא .החכשנש הנמה לע תוצפל תנמ לע הלופכ הנמ לוטיל ןיא ךשמהו האבה הנמה דעומל דע הכח ,ףרגורפ תסומכ לוטיל תחכש םא .תוסומכה תליטנב ליגרכ .אפורה ידי-לע ץלמוהש יפכ לופיטב דימתהל שי הפורתה תליטנ תא קיספמ התא םא .לתשומה רביאה תייחדל ןוכיסה תא לידגהל הלולע ףרגורפב לופיטה תקספה .ךכ תושעל ךל הרוה ךלש אפורה םא אלא ךלש לופיטה תא קיספת לא לטונ התאש םעפ לכב הנמהו תיוותה קודב !ךשוחב תופורת לוטיל ןיא .םהל קוקז התא םא םייפקשמ בכרה .הפורת וא אפורב ץעוויה ,הפורתב שומישל עגונב תופסונ תולאש ךל שי םא .חקורב יאוול תועפות .4 קלחב יאוול תועפותל םורגל לולע ףרגורפב שומישה ,הפורת לכב ומכ אלו ןכתיי .יאוולה תועפות תמישר ארקמל להבית לא .םישמתשמהמ .ןהמ תחא ףאמ לובסת רביאה תייחד תא עונמל תנמ לע ךפוג לש הנגהה ןונגנמ תא התיחפמ ףרגורפ .ליגרה ובצמב ומכ םימוהיזב םחליהל לכוי אל ךפוג ,ךכמ האצותכ .לתשומה תולחמב ליגרהמ רתוי תולחל לולע התא ,ףרגורפ לטונ התא רשאכ ,ןכל .ןתשה יכרדו תואירה ,םייעמה ,הביקה ,הפה ,רועה לש םימוהיז ןוגכ ,תוימוהיז .ןלהל תוטרופמה ולא ללוכ ,שחרתהל תולולע תורומח יאוול תועפות תחא ךל שיש דשוח התא םא וא ךל שי םא ידיימ ןפואב אפורל הנפ :תואבה תורומחה יאוולה תועפותמ :)יליפט וא יפיגנ ,יתיירטפ ,יקדייח םוהיז( םייטסינוטרופוא םימוהיז .ןורג באכו םוח ,ךשוממ לושלש תכרעמ יוכידמ האצותכ לופיט תובקעב וחווד םיריאממו םיריפש םילודיג .ןוסיחה thrombotic( תויסט רסוחו השירק לש )הרופרופ( תנמגרא

תורובח ,םוחב ןייפואמה בצמ ,)thrombocytopenic purpura [TTP[ תופייע אלל וא םע ,תונטק תומודא תודוקנכ עיפוהל תויושעש תוירוע-תת ,)תבהצ( םייניעה וא רועה לש הבהצה ,לובלב ,תרבסומ יתלב תינוציק .)ןתש תריצע וא טועימ( הפירח תוילכ תקיפס יא לש םינימסת םע ,pure red cell aplasia( םימודאה םדה יאת לש היזלפא לש םירקמ וחווד הדירי( תיטילומה הימנא ,)םימודאה םדה יאת תריפסב דואמ הרומח הדירי םוחו )תופייעב הוולמה גירח סרה תובקעב םימודאה םדה יאת רפסמב הוולמ ,םוהיזב םחלנ רשא גוסהמ םינבלה םדה יאתב הדירי( ינפורטיונ ןכתיי .תועיפומ הלא יאוול תועפות תורידת וזיאב קוידב עודי אל .)םוחב :ב שוחתו ןכתיי ךבצמ תרמוחב תולתכ וא ,םינימסתב ללכ שוחת אלו באכ ,תרוחרחס ,המישנ רצוק ,רועה לש גירח ןורוויח ,תושידא ,תופייע .םיילגרה תופכבו םיידיב רוק תשוחתו הזחב באכ ,שאר םינבלה םדה יאת רפסמב הרומח הדירי( סיזוטיצולונרגא לש םירקמ ללכ םינימסת ךל ויהי אלו ןכתיי .)םימוהיזו םוח ,הפב םיביכב הוולמה .ןורג באכו תורומרמצ ,ימואתפ םוחב שוחתש וא תימואתפ החירפ :םיאבה םינימסתה םע תויטקליפנאו תויגרלא תובוגת ,םינפה ,לוסרקה ,םיילגרה תופכ ,םיידיה לש תוחיפנ ,)תדפרס( תדרגמ התאו )המישנ וא העילב יישקל םורגל הלולעש( ןורגה וא הפה ,םייתפשה .ןופליע ףס לע שיגרהל יושע Posterior Reversible( הכיפה תירוחא היתפולפצנא תנומסת

,ישפנה בצמב יוניש ,שאר באכ :)Encephalopathy Syndrome [PRES[ .הייאר תוערפהו םיסוכרפ תורידתב םייוניש :

Torsades de Pointes

גוסמ בלה בצקב תוערפה תקועת( הזחב באכ ןוגכ םינימסת אלל וא םע עיפוהל םייושעש בלה בצק )בל תוקיפד לש השוחת( תויצטיפלפ ,הליחב וא וגיטרו ,ןופליע ,)הזח .המישנב ישוקו הוולמ וניאש וא הוולמה קזח ןטב באכ :לוכיעה תכרעמב תובקנתה

.האקה וא הליחב ,םוח ,תורומרמצ ןוגכ ,םיפסונ םינימסתב אל םיבאכ :)Stevens-Johnson syndrome( ןוסנו׳ג-סנביטס תנומסת ,רועב תויחופלש םע השק ילוח ,םינפב תוחיפנ ,רועב םיבחרנ םירבסומ לש תוטשפתה ,ןושלב תוחיפנ ,תדפרס ,ןימה ירבאבו םייניעב ,הפב .רועה לש הרישנ ,רועב הלוגס וא המודא החירפ רועב תויחופלשו )היזורא( םוסרכ :Toxic epidermal necrolysis תנומסת לש םילודג םיקלחב קתניהל לולעש חופנו םודא רוע ,תויריר תומקרב וא .ףוגה בצמ ,)Haemolytic uraemic syndrome( תימארוא תיטילומה תנומסת תוילכ תקיפס יא( ןתש תריצע וא טועימ :םיאבה םינימסתב ןייפואמה תורובח ,)תבהצ( םייניעה וא רועה לש הבהצה ,תינוציק תופייע ,)הפירח .םוהיז לש םינמיסו םומיד וא תוגירח .ךלש לתשומה רביאה לש יוקל דוקפת :ףרגורפ תלבק רחאל שחרתהל תולולע ןלהל תוטרופמה יאוולה תועפות 10 ךותמ 1-מ רתוי לע עיפשהל תולולע( דואמ תוחיכש יאוול תועפות :)םילפוטמ םדב ןגלשאה תמרב היילע ,תרכוס ,םדב רכוסה תמרב היילע הניש יישק שאר באכ ,דער םדה ץחלב היילע הליחב ,לושלש הילכב תויעב :)םילפוטמ 10 ךותמ 1 דע לע עיפשהל תולולע( תוחיכש יאוול תועפות סמוע ,םדב ןרתנה וא ןדיסה ,ןגלשאה ,טאפסופה ,םויזנגמה תמרב הדירי היילע ,ןובאיתב הדירי ,םדב םינמוש וא ןתש תצמוח תמרב היילע ,םילזונ םדב םיחלמב םירחא םייוניש ,םדה תויצמוחב ,םיטויס ,חורה בצמב םייוניש ,ןואכיד ,תואצמתה יאו לובלב ,הדרח ינימסת

תוישפנ תוערפה ,תויזה )באכב םיוולמ םיתיעל( לומינ תשוחתו ץוצקע ,הרכהב תוערפה ,םיסוכרפ תוערפה ,הביתכה תלוכיב העיגפ ,תרוחרחס ,םיילגרה תופכבו םיידיב םיבצעה תכרעמב םייניעב תויעב ,רואל תרבגומ תושיגר ,הייאר שוטשט םיינזואב םילוצלצ ריהמ בל קפוד ,בלב םדה ילכב םדה תמירזב הדירי םדה ץחלב הדירי ,םדה ילכ לש האלמ וא תיקלח המיסח ,םומיד ,תואירה ביבס םילזונ תורבטצה ,תואירה תמקרב םייוניש ,המישנ רצוק תעפש ייומד םינימסת ,לועיש ,עולה לש תקלד תוקלד ,הביקב םימומיד ,לושלשל וא ןטב באכל םימרוגה םיביכ וא תוקלד ,לוכיע יישק ,ןטב יבאכ ,תואקה ,ןטבב םילזונ תורבטצה ,הפב םיביכ וא הביקב תויעב ,הכר האוצ ,תונחיפנ ,םיזג ,תוריצע תויעב עקר לע רועה לש הבהצה ,דבכה דוקפתבו דבכה ימיזנאב םייוניש דבכ תקלדו ,דבכה תמקרל קזנ ,דבכב תרבגומ העיז ,הנקא ,רעיש תרישנ ,החירפ ,דרג םירירש תויוצווכתה ,םיילגרה תופכבו בגב ,םייפגב ,םיקרפמב םיבאכ ןתש ןתמ תעב באכ וא יוקיל ,ןתש רוצייב הדירי ,תיתיילכ הקיפס יא היילע ,תוחונ רסוחו באכ ,ףוגב םילזונ תורבטצה ,םוח ,תיללכ השלוח שוביש לש השוחת ,לקשמב היילע ,םדב זאטפסופ ןילקלא םיזנאה תמרב ףוגה תרוטרפמטב 100 ךותמ 1 דע לע עיפשהל תולולע( תוחיכש ןניאש יאוול תועפות :)םילפוטמ םדה יאת תוריפס לכב הדירי ,םדה תשירקב םייוניש טאפסופה תמרב היילע ,םדב רכוס וא ןובלח תומרב הדירי ,תושבייתה םדב רובידב םייוקיל ,תיחומ הערפה ,קותיש ,יחומ ץבש ,חומב םומיד ,תמדרת ןורכיז תויעב ,הפשבו םייניעה תושדעב יוקיל לשב הייאר שוטשט העימש יוקיל הלדגה ,בלה רירשב הערפה ,בלה דוקפתב הדירי ,בל םוד ,רידס אל קפוד םיגירח בל קפודו בצק ,גירח .ג.ק.א ,קזח קפוד ,בלה רירש לש )קוש( םלה ,םייפגה לש דירווב םד שירק המתסא ,המישנה יכרדב תוערפה ,המישנ יישק הביקה ןכות לש רזחה ,םדב זאלימע םיזנאה תמרב היילע ,םייעמ תמיסח הביקה תונקורתהב בוכיע ,)סקולפיר( ןורגל שמשל הפישחב הבירצ תשגרה ,רועב תקלד םיקרפמב תוערפה גירח יתסו םומידו תסו יבאכ ,ןתש תתל תלוכי רסוח תרבגומ תושיגר ,תעפש תיומד הלחמ ,םימיוסמ םירביא לש דוקפתב לשכ היילע ,הליגר אל השגרה וא תונבצע ,הזחב ץחל לש השוחת ,רוקלו םוחל לקשמב הדירי ,םדב זאנגורדיהד טאטקל םיזנאה תמרב :)םילפוטמ 1,000 ךותמ 1 דע לע עיפשהל תולולע( תורידנ יאוול תועפות םד ישירקמ האצותכ רועב םילק םימומיד םירירשה לש תרבגומ תושקונ ןורוויע תושריח בלה ביבס םילזונ תורבטצה ףירח המישנ רצוק בלבלב הטסיצ תורצוויה דבכב םדה תמירזב תויעב רתי רועיש ביכ ,תויתעונתב הדירי ,הזחב תוחיתמ לש השוחת ,לופיל הייטנ ,ןואמיצ 10,000 ךותמ 1 דע לע עיפשהל תולולע( דואמ תורידנ יאוול תועפות :)םילפוטמ םירירש תשלוח בל וקא תקידבב תוניקת אל תואצות הרמה רוניצ לש תורציה ,דבכ תקיפס יא ןתשב םדב הוולמ ןתש ןתמב באכ ןמושה תמקרב היילע תוחיכשה תא ךירעהל ןתינ אל( העודי הניא ןתוחיכשש יאוול תועפות :)םייקה עדימהמ )תיטפוא היתפוריונ( הייארה בצעב הגירח רשאכ וא ,הרימחמ יאוולה תועפותמ תחא םא ,יאוול תעפות העיפוה םא .אפורה םע ץעייתהל ךילע ,ןולעב הניוצ אלש יאוול תעפותמ לבוס התא יאוול תועפות לע חוויד רושיקה לע הציחל תועצמאב תואירבה דרשמל יאוול תועפות לע חוודל ןתינ רתא לש תיבה ףדב אצמנש ״יתפורת לופיט בקע יאוול תועפות לע חוויד״ לע חווידל ןווקמה ספוטל הנפמה )www.health.gov.il( תואירבה דרשמ :רושיקל הסינכ ידי-לע וא ,יאוול תועפות

https://sideeffects.health.gov.il

?הפורתה תא ןסחאל ךיא .5 ץוחמ רוגס םוקמב רומשל שי תרחא הפורת לכו וז הפורת !הלערה ענמ .הלערה ענמת ךכ ידי-לעו תוקונית וא/ו םידלי לש םתייאר חווטו םדי גשיהל .אפורהמ תשרופמ הארוה אלל האקהל םורגת לא יבג לע עיפומה )exp. Date( הגופתה ךיראת ירחא הפורתב שמתשהל ןיא .שדוח ותוא לש ןורחאה םויל סחייתמ הגופתה ךיראת .הזיראה .)רטסילב( תישגמהמ ןתאצוה רחאל דימ תוסומכה תא לוטיל שי ןגהל תנמ לע תירוקמה הזיראב רומשל שי .25ºC-ל תחתמ ןסחאל שי .תוחלמ ,םישדוח 12 ךות תוסומכב שמתשהל שי םוינימולאה תפיטע תחיתפ רחאל .הזיראה יבג לע ןיוצמה הגופתה ךיראת רחאל אל ךא .עולבל ןיא .תוחל חפוס םע תיקש הנשי םוינימולא תפיטע לכב ףסונ עדימ .6 :םג הליכמ הפורתה ליעפה ביכרמה לע ףסונ ג״מ 0.5 תוסומכ ףרגורפ :הסומכה ןכות בכרה

Lactose monohydrate, magnesium stearate, hydroxypropyl

methylcellulose, croscarmellose sodium

:הסומכה תפטעמ בכרה

Titanium dioxide )E 171(, ferric oxide yellow )E 172(, gelatin,

shellac glaze, lecithin )soya(, simeticone, ferric oxide red )E 172(,

hydroxypropyl cellulose

ג״מ 1 תוסומכ ףרגורפ :הסומכה ןכות בכרה

Lactose monohydrate, hydroxypropyl methylcellulose,

croscarmellose sodium, magnesium stearate

:הסומכה תפטעמ בכרה

Titanium dioxide )E 171(, gelatin, shellac glaze, lecithin )soya(,

simeticone, ferric oxide red )E 172(, hydroxypropyl cellulose

ג״מ 5 תוסומכ ףרגורפ :הסומכה ןכות בכרה

Lactose monohydrate, hydroxypropyl methylcellulose,

croscarmellose sodium, magnesium stearate

:הסומכה תפטעמ בכרה

Titanium dioxide )E 171(, ferric oxide red )E 172(, gelatin, shellac,

propylene glycol

הזיראה ןכות המו הפורתה תיארנ דציכ ג״מ 0.5 תוסומכ ףרגורפ ״[f[ 607״-ו ״0.5 mg״ םע םודא וידב תועבטומ ריהב בוהצ עבצב תוסומכ .הנבל הקבא תוליכמו ג״מ 1 תוסומכ ףרגורפ ״[f[ 617״-ו ״1 mg״ םע םודא וידב תועבטומ ןבל עבצב תומוטא תוסומכ .הנבל הקבא תוליכמו ג״מ 5 תוסומכ ףרגורפ ״[f[ 657״-ו ״5 mg״ םע ןבל וידב תועבטומ רפרפא םודא עבצב תומוטא תוסומכ

.הנבל הקבא תוליכמו ךותב ,)רטסילב( תוישגמב תוזורא ,תוסומכ 100 וא 50 הליכמ הזיראה .תוחל חפוס תללוכה םוינימולא תפיטע .םיקוושמ הזיראה ילדג לכ אלו ןכתיי :ותבותכו םושירה לעב םש )עבט תצובקמ( מ״עב קוויש קיבא .הינתנ ,8077 .ד.ת :ותבותכו ןרציה םש .דנלריא ,ןילגרוליק ,מ״עב ינפמוק דנלריא סאלטסא ידי-לע רשואו קדבנ ונכותו תואירבה דרשמ ידי-לע עבקנ הז ןולע טמרופ דרשמ תוארוהל םאתהב ןכדועו 2015 טסוגוא ךיראתב תואירבה דרשמ .2019 רבמבונ ךיראתב תואירבה :תואירבה דרשמב יתכלממה תופורתה סקנפב הפורתה םושיר ירפסמ

122.07.30215

:ג״מ 0.5 ףרגורפ

107.69.29158

:ג״מ 1 ףרגורפ

107.70.29159

:ג״מ 5 ףרגורפ ,תאז ףא לע .רכז ןושלב חסונ הז ןולע ,האירקה תלקהלו תוטשפה םשל .םינימה ינש ינבל תדעוימ הפורתה

PROG CAPS PL SH 300420

1986 ـ ) تارضحتسم ( ةلديصلا ةمظنأ بجومب كلهتسملل ةرشن طقف بيبط ةفصو بجومب داودلا ق

وسي تلاوسبك فارچورپ غلم 5 فارچورپ غلم 1 فارچورپ غلم 0.5 فارچورپ تلاوسبك

تلاوسبك

تلاوسبك بيكرتلا :ىلع ةلوسبك لك يوتحت غلم 5 سوميلوركات غلم 1 سوميلوركات غلم 0.5 سوميلوركات

Tacrolimus 5 mg

Tacrolimus 1 mg

Tacrolimus 0.5 mg

نع ةماه تامولعم" 2 ةرقفلا رظنأ ةيساسحلا تادلومو ةلاعفلا ريغ تابكرملا نع تامولعمل ."ةيفاضإ تامولعم" ـ 6 ةرقفلاو "ءاودلا تابكرم ضعب تامولعم ىلع ةرشنلا هذه

وتحت .ءاودلل كلامعتسإ لبق اهتياهن ىتح نعمتب ةرشنلا أرقإ .يلديصلا وأ بيبطلا عجار ،ةيفاضإ ةلئسأ كيدل ترفوت اذإ .ءاودلا نع ةزجوم نأ كل ادب ولو ىتح مهرضي دق وهف .نيرخلآل هيطعت لا .كضرم جلاعل ءاودلا اذه فصو .كتلاحل ةهباشم ةيبطلا مهتلاح ؟ءاودلا صصخم ضرغ يلأ )1 .بلق وأ ةيلك ،دبك ةعارز ةيلمع دعب عورزم وضع ضفر عنمل immunosuppressive( يعانملا زاهجلل ةطبثم ىرخأ ةيودلأ مواقم عورزم وضع ضفر جلاع

.)drugs

،دبك لثم( وضعلا ةعارز دعب .يعانملا زاهجلل ةطبثملا ةيودلأا ةليصفل فارچورپ ءاودلا يمتني فارچورپ لمعتسي .ديدجلا وضعلا ضفر لواحيس كمسج يف ةعانملا زاهج نإف )بلقو ةيلك .عورزملا وضعلا لبقت كمسجل حيتيو كمسجل يعانملا لعفلا در طبضل .ةعانملا زاهج تاطبثم :ةيجلاعلا ةليصفلا ءاودلا لامعتسإ لبق )2 نم بيبطلا ةقفاومبو ةفرعمب

ّ

لاإ رخآ سوميلوركات رضحتسمب لادبتسلإا زوجي لا .تنأ اهيف جلاعتت يتلا ءاضعلأا عرز ةدايع :اذإ ءاودلا لامعتسإ زوجي لا اهيوتحي يتلا ةيفاضلإا تابكرملا نم دحاو لكل وأ سوميلوركات ـل )يجريلأ(

اساسح تنك .)"ةيفاضإ تامولعم" ـ 6 ةرقفلا رظنأ( ءاودلا عون نم ةيويحلا تاداضملا ةعومجمل يمتني يويح داضم يلأ )يجريلأ(

اساسح تنك .)نيسيماسوج ،نيسيمورتيرلاك ،نيسيمورتيريإ :لثم( تاديلوركاملا ءاودلا لامعتسإب قلعتت ةصاخ تاريذحت يئاصخأ كل هفصو يذلا ءاودلا سفن

ً

امئاد ىقلتت كنأب دكأتت نأ مهملا نم ،كهابتنإ تفلن ءاودلا نأ كل ادب اذإ .ةيلديصلا يف ءاودلا اهيف ىقلتت ةرم لك يف كلذو ءاضعلأا عرز ،لامعتسلإا تاداشرإ تفلتخإ اذإ وأ ةداع هاقلتت يذلا ءاودلا نع

ً

افلتخم هتيقلت يذلا رييغت وأ ليدبت لك .حيحصلا ءاودلا تيقلت دق كنأب دكأتلل

ً

لااح يلديصلا عجار ءاجرلا نأ بجي )ءاودلاب ةلاعفلا ةداملا( سوميلوركات ىلع يوتحي يذلا يئاودلا رادقملاب ءاجرلا .تنأ اهيف جلاعتت يتلا ءاضعلأا عرز ةدايع نم بيبطلا ةقفاومو ةفرعمب ا

ّ

متي لباقم ةيبطلا ةفصولا يف بيبطلا هفصو

ي

ذلا رضحتسملل يراجتلا مسلإا صحفإ .ناقباطتم امهن

أ

نم دكأتو يلديصلا نم هتيقلت يذلا ءاودلا :بيبطلل كحإ فارچورپ ـب جلاعلا لبق عنم لجأ نم كلذو يعانم طيبثتل ةجاحب تنأ املاطل ،

ايموي فارچورپ لوانت كيلع بجوتي .كبيبط عم مظتنم لاصتإ ىلع ظافحلا كيلع .كيدل عورزملا وضعلا ضفر صوحف ةدع ءارجإ ىلإ فارچورپ تلاوسبكل كلوانت ةرتف للاخ كبيبط كهجوي نأ زئاجلا نم نم )باصعلأل صوحفو رصبلا صوحف ،بلقلا فئاظو ،لوبلا ،مدلا صوحف كلذ يف امب( ةيئاودلا ةعرجلا يه ام ررقي نأ ىلع كبيبط دعاسيسو يدايتعإ ءارجإ كلذ ربتعي .رخلآ نيح .كل ةبسنلاب فارچورپ نم لثملأا St. John׳s wort( موكيريپيه لثم ،يتابن ردصم نم ءاود يأ لوانت نع عانتملإا بجي ىلع رثؤي دق كلذ نلأ ،يتابن ردصم نم رخآ جتنم يأ وأ ،)[

hypericum perforatum

يف .اهلوانت كيلع بجوتي يذلا فارچورپ نم ةبولطملا ةيئاودلا ةعرجلا ىلعو جلاعلا ةعاجن .يتابن ردصم نم ءاود وأ جتنم يأ لامعتسإ لبق كبيبط ىلإ هجوتلا كيلع كشلا ةلاح نلأ كبيبطل كحإ ،كدبك ىلع رثؤي دق يذلا ضرم كيدل وأ دبكلا يف لكاشم كيدل تدجو اذإ .فارچورپ نم هاقلتت يذلا يئاودلا رادقملا ىلع رثؤي دق كلذ ،ةريرعشق لثم ،ىرخأ ضارعأب قفارتي لا وأ قفارتي يذلا نطبلا يف ديدش ملأب ترعش اذإ .ؤيقت وأ نايثغ ،ةنوخس نوكي نأ زئاجلا نم هنلأ ،كلذ نع كبيبطل كحإ ،دحاو موي نم رثكلأ لاهسإ نم يناعت تنك اذإ .فارچورپ نم هاقلتت يذلا يئاودلا رادقملا ةمءلامل ةجاح كلانه ."QT عطقم ةلاطإ" ىمسملا بلقلل يئابرهكلا ليصوتلا يف ريغت كيدل دجو اذإ فارچورپ ـب جلاعلا ةرتف للاخ UV ةعشلأو سمشلا ءوضل كضرعت نم دحت نأ بجي ةياقو لماع وذ سمشلا نم ةياقو ميرك لامعتسإو ةبسانم ةيقاو سبلام ءادترإ ةطساوب قفارت يتلا دلجلا يف ةيناطرس تاريغت ثودحل ةلمتحملا ةروطخلا وه كلذ ببس .عفترم .يعانملا زاهجلل طبثملا جلاعلا جلاعلا ةقيرط صوصخب كبيبط كيصوي .

اقبسم كبيبط غلب ،تاحاقل يأ يقلت كيلع بجوت اذإ .لضفلأا ايلاخلل طرفم جاتنإب ىلجتي يذلا يوافميللا زاهجلا يف للخل ةدئاز ةروطخ نع غلب ىدل )"ةيبناجلا ضارعلأا" ـ 4 ةرقفلا رظنأ( )lymphoproliferative disorders( .تابارطضلإا هذه صوصخب بيبطلا رشتسإ .فارچورپ ـب اوجلوع نيجلاعتم :نم جلاعلا للاخ تيناع اذإ يروف لكشب بيبطلا غلب وأ ءايشلأا ةيؤر يف ةبوعص ،ناوللأا ةيؤر يف تاريغت ،ةيؤرلا شوشت لثم ةيؤرلا يف لكاشم

ادودحم كتيؤر لاجم حبصأ ةيودلأا نيب تلاخادتلا ةفصو نودب ةيودأ كلذ يف امب ىرخأ ةيودأ ،

ً

ارخؤم تلمعتسا اذإ وأ ،لمعتست تنك اذإ .كلذ نع يلديصلا وأ بيبطلل كحإ ،ةيئاذغ تافاضإو ةيبط .نيروپسولكيس عم ةيوس فارچورپ لوانت زوجي لا يف ىرخلأا ةيودلأا بسنو ،تنأ اهلوانتت ىرخأ ةيودأ نم مدلا يف فارچورپ ةبسن رثأتت دق نم يئاودلا رادقملا ضفخ وأ عفر ،فقوتلا رملأا اذه مزلي دق ،فارچورپ نم رثأتت دق مدلا يوتحت ةيودأ

ارخؤم تلمعتسإ وأ لمعتست تنك اذإ كبيبط غلابإ كيلع صخلأاب .فارچورپ :لثم ةلاعف داوم ىلع ،تاديلوركاملا ةعومجم نم ةيويح تاداضم ةصاخ ،ةيويح تاداضمو تايرطفلل ةداضم ةيودأ ،لوزانوكيروڤ ،لوزانوكارتيإ ،لوزانوكولف ،لوزانوكوتيك لثم تاثولتلا جلاعل ةلمعتسملا .نيسيپمافيرو نيسيماسوج ،نيسيمورتيرلاك ،نيسيمورتيريإ ،لوزانوكوڤاسيإ ،لوزاميرتولك ايلاخلل مخضملا سوريڤ( CMV سوريڤ نع مجان ضرم عنمل لمعتسملا ،ريڤومريتيل .)human cytomegalovirus ،يرشبلا تاتسيسيبوك ززعي يذلا ءاودلا ،)ريڤانيوكاسو ريڤانيفلن ،ريڤانوتير لثم( HIV زايتورپ تاطبثم

.)يرشبلا يعانملا زوعلا سوريڤ( HIV ثولت جلاعل ةلمعتسملا ،ةبكرم صارقأو /ريڤيرپاتيراپ/ريڤساتيبموأ جيزملاو ريڤيرپيسوب ،ريڤيرپلايت لثم( HCV زايتورپ تاطبثم

hepatitis

( C دبكلا باهتلإ ثولت جلاعل ةلمعتسملا ،)ريڤوباساد نودب وأ عم ريڤانوتير

.)ةنيعم ناطرس عاونأ جلاعل نلامعتسملا( بينيتاميإو بينيتولين عنمل ةعانملا زاهج طيبثل لمعتسي يذلا )mycophenolic acid( كيلونيفوكيم ضمح .عورزملا وضعلا ضفر لوزارپوسنلا ،لوزارپيموأ لثم( )acid reflux( يئيرملا دادترلإاو ةيدعملا ةحرقلا جلاعل ةيودأ .)نيديتيميس وأ .)ديمارپولكوتيم لثم( تاؤيقتلاو نايثغلا جلاعل ةيودأ جلاعل نلامعتسملا موينموللأا ـ مويزينغملا ديسكورديه ىلع ةيواحلا ةضومحلا تاداضم .ناقرحلا .لوزاناد وأ )لمحلا عنم صارقأ لثم( لويدارتسإ لينيثيإ ىلع يوتحت يتلا ةينومروه تاجلاع .ليماپاريڤ ،مزايتليد ،نيپيدراكين ،نيپيديفين لثم بلقلا لكاشم وأ مدلا طغض عافترإ جلاعل ةيودأ .)ةيمظن لا( بلقلا مظن يف تابارطضإ جلاعل ةلمعتسملا )نورادويمأ( ةيمظنلالا تاداضم .ةيثلاثلا موحشلاو لورتسيلوكلا بسن عافترإ جلاعل ةلمعتسملا تانيتاتس ةامسملا ةيودأ .لاتيبرابونيف وأ نيئوتينيف )عرصلا تاداضم( تاجلاتخلإل ةداضم ةيودأ .نولوزينديرپ ليثيمو نولوزينديرپ ةيديئوريتسوكيتروكلا ةيودلأا .نودوزافين بائتكلإل داضملا ءاودلا St. John׳s wort( موكيريپيه ىلع يوتحت يتلا يتابن ردصم نم تارضحتسم

Schisandra sphenanthera

ـلا تاصلاخ وأ )[

hypericum

perforatum

ةيودأ وأ B نيسيريتوفمأ ،نفورپوبيإ لوانت كيلع بجوتي وأ لوانتت تنك اذإ بيبطلل كحإ زاهجلا يف وأ ىلكلا يف لكاشم مقافت دق ةيودلأا هذه .)ريڤولكيسأ لثم( تاسوريڤلل ةداضم .فارچورپ عم ةيوس لمعتست امدنع يبصعلا ةظفاح ةيلوب تاردم وأ مويساتوپلا تافاضإ لمعتست تنك اذإ كبيبطل كحإ ،كلذل ةفاضلإاب عون نم( ةنيعم ملاآ تانكسم ،)نوتكلاونوريپس وأ نيريتمايرت ،ديروليمأ لثم( مويساتوپلل ةيودأ و

،رثختلا تاداضم ،)نفورپوبيإ لثم [NSAIDs] ةيديئوريتسلالا باهتللإا تاداضم .فارچورپ لوانت ةرتف للاخ ،مفلا قيرط نع ةاطعملا يركسلا جلاعل

اقبسم كبيبط غلب ،تاحاقل ةيأ يقلت كيلع بجوت اذإ ماعطلاو ءاودلا لامعتسإ ماعطلا ةبجو لبق ةدحاو ةعاس لقلأا ىلع وأ ةيواخ ةدعم ىلع ماع لكشب ءاودلا لوانت بجي پيرچلا ريصعو تورف پيرچلا كلاهتسإ نع عانتملإا بجي .ماعطلا ةبجو دعب تاعاس 2-3 وأ .فارچورپ ـب جلاعلا ةرتف للاخ تورف عاضرلإاو لمحلا يريشتسإ ،لمحلل نيططخت وأ ،لماح كنأب نيدقتعت ،ةعاضرلا وأ لمحلا ةرتف يف تنك اذإ .ءاودلا اذه لامعتسإ لبق يلديصلا وأ بيبطلا .فارچورپ اهيف نيلوانتت يتلا ةرتفلا للاخ عاضرلإا زوجي لا اذل .ملأا بيلح يف فارچورپ حرط

تانكاملا لامعتسإو ةقايسلا تنك اذإ وأ ،مونلل ليم وأ راودب ترعش اذإ تانكاملا وأ تادعملا لامعتسإ وأ ةقايسلا زوجي لا لوانت مت امدنع ربكأ ةريتوب ضارعلأا هذه تظحول .فارچورپ لوانت دعب حضاو لكشب ىرت لا .لوحكلا كلاهتسإ عم فارچورپ ءاودلا تابكرم ضعب نع ةماه تامولعم لمحت مدع كيدل نأب كبيبط لبق نم كل ليق اذإ .زوتكل ىلع فارچورپ تلاوسبك يوتحت .ءاودلا اذه لوانت لبق كبيبطل هجوت ،ةنيعم تايركسل هردصم نيتيسيل ىلع يوتحي غلم 1 -و غلم 0.5 فارچورپ تلاوسبك ىلع عوبطملا ةباتكلا ربح اميف هرودب ررقي يذلا بيبطلا غلابإ كيلع ايوصلل وأ ينادوسلا لوفلل

اساسح تنك اذإ .ايوصلا .ءاودلا اذه لوانت كيلع ناك اذإ .مويدوصلا نم

لاخ ربتعي اذل ةلوسبكلا يف مويدوص غلم 23 نم لقأ ىلع ءاودلا اذه يوتحي ؟ءاودلا لامعتسإ ةيفيك )3 .بيبطلا تاميلعت بسح رضحتسملا لامعتسإ

امئاد بجي ةقيرطو يئاودلا رادقملا صوصخب

اقثاو نكت مل اذإ يلديصلا وأ بيبطلا نم حاضيتسلإا كيلع .رضحتسملاب جلاعلا ،ةيلديصلا يف ءاودلا ىقلتت ةرم لك يف هتاذ سوميلوركات رضحتسملا ىقلتت كنأ نم دكأتلا كيلع رييغتلا ىلع تنأ اهيف جلاعتت يتلا ءاضعلأا عرز ةدايع نم يئاصخلأا بيبطلا قفاو اذإ لاإ .رخآ سوميلوركات رضحتسمل .طقف بيبطلا لبق نم ناددحي جلاعلا ةقيرطو يئاودلا رادقملا :ةداع وه يدايتعلإا يئاودلا رادقملا تاميلعت يف وأ ءاودلا رهظم يف ريغت تظحلا اذإ .مويلا يف نيترم ءاودلا اذه لوانت بجي .حيحصلا ءاودلا لوانتت كنأ نم دكأتلل نكمي ام عرسأب يلديصلا وأ بيبطلا غيلبت كيلع ،لامعتسلإا هباسحب كبيبط لبق نم ددحي كيدل عورزملا وضعلا ضفر عنمل يئادتبلإا يئاودلا رادقملا هردق لاجمب نوكي نأ بجي عرزلا دعب ةرشابم يئادتبلإا يئاودلا رادقملا .كمسج نزو قفو .عورزملا وضعلاب قلعتم رمأك ،مويلل مسج نزو غلكل غلم 0.075-0.30 ةيفاضإ تارضحتسم ةيأ ىلعو ماعلا يحصلا كعضو ىلع كل بسانملا يئاودلا رادقملا دمتعي تاهيجوت بسحب ةينيتور مد صوحف ءارجإ بجي .تنأ اهلوانتت ةعانملا زاهج تاطبثم عون نم ضفخ بيبطلا سردي .رخلآ نيح نم هتمءلامو حيحصلا يئاودلا رادقملا ديدحت لجأ نم بيبطلا قيقدلا ددعلا صوصخب بيبطلا كهجوي .كتلاح رارقتسإ دعب فارچورپ نم يئاودلا رادقملا .اهلوانت ةريتوو تلاوسبكلل .هب ىصوملا يئاودلا رادقملا زواجت زوجي لا لامعتسلإا ةقيرط ىلع ةداع فارچورپ لوانت بجي .ءاسمو

احابص ةداع ،مويلا يف نيترم فارچورپ لوانت بجي .ماعطلا ةبجو دعب تاعاس 2-3 وأ ماعطلا ةبجو لبق ةدحاو ةعاس لقلأا ىلع وأ ،ةيواخ ةدعم اهجارخإ دعب

اروف تلاوسبكلا لوانت بجي .ءاملا نم سأك عم لماكلا اهلكشب تلاوسبكلا علب بجي ءانثأ تورف پيرچلا ريصعو تورف پيرچلا كلاهتسإ نع عانتملإا بجي .)رتسيلب( ةحيوللا نم .موينموللأا فلاغ نمض دوجوملا ةبوطرلل صاملا سيكلا علب زوجي لا .فارچورپ لامعتسإ

ً

اطرفم

ً

ايئاود

ً

ارادقم أطخلاب تلوانت اذإ

لااح هجوتلا بجي ،ءاودلا نم أطخلاب لفط علب اذإ وأ

اطرفم

ايئاود

ارادقم أطخلاب تلوانت اذإ .ءاودلا ةبلع كعم رضحأو ىفشتسملا يف ئراوطلا ةفرغ ىلإ وأ بيبطلا ىلإ ءاودلا لوانت تيسن اذإ .يسنملا يئاودلا رادقملا نع ضيوعتلل

افعاضم

ايئاود

ارادقم لوانت زوجي لا لصاوو ةيلاتلا ةيئاودلا ةعرجلا دعوم نيحي ىتح رظتنإف ،فارچورپ ةلوسبك لوانت تيسن اذإ .تلاوسبكلا لوانتب داتعملاك .بيبطلا ةيصوت بسح جلاعلا ىلع ةبظاوملا بجي ءاودلا لوانت نع تفقوت اذإ فقوتت لا .عورزملا وضعلا ضفرل ةروطخلا نم ديزي دق فارچورپ ـب جلاعلا نع فقوتلا نإ .كلذ لعفب بيبطلا كاصوأ اذإ لاإ كب صاخلا جلاعلا نع يئاودلا رادقملا نم دكأتلاو ءاودلا عباط صيخشت بجي !ةمتعلا يف ةيودأ لوانت زوجي لا .كلذ رملأا مزل اذإ ةيبطلا تاراظنلا عض .ءاود اهيف لوانتت ةرم لك يف .يلديصلا وأ بيبطلا رشتسإ ،ءاودلا اذه لامعتسإ لوح ةيفاضإ ةلئسأ كيدل ترفوت اذإ ةيبناجلا ضارعلأا )4 .نيلمعتسملا ضعب دنع ةيبناج

ً

اضارعأ ببسي دق فارچورپ لامعتسإ نإ ،ءاود لكب امك .اهنم

ً

ايأ يناعت لاأ زئاجلا نم .ةيبناجلا ضارعلأا ةمئاق نم شهدنت لا نوكي لا ،كلذل ةجيتن .عورزملا وضعلا ضفر عنمل كمسجل ةيعافدلا ةيللآا فارچورپ فعضي .ةيداعلا ةلاحلا يف امك تاثولتلا ةبراحم كمسج ناكمإب ،دلجلا تاثولت لثم ،ةيثولت ضارمأب داتعملا نم رثكأ ضرمت دق ،فارچورپ لوانتت امدنع ،اذل .ةيلوبلا كلاسملاو نيتئرلا ،ءاعملأا ،ةدعملا ،مفلا .يلي اميف ةلصفملا كلت كلذ يف امب ،ةريطخ ةيبناج ضارعأ ثدحت دق ضارعلأا نم ةدحاو كيدل نأب كشت تنك وأ كيدل ناك ناك اذإ لاحلا يف بيبطلل هجوت :ةيلاتلا ةريطخلا ةيبناجلا ةنوخس ،لصاوتم لاهسإ :)يليفط وأ ،يسوريڤ ،يرطف ،يموثرج ثولت( ةيزاهتنإ تاثولت .ةرجنحلا يف ملأو .يعانملا زاهجلا طيبثت ةجيتن جلاع ءارج ةثيبخو ةديمح ماروأ نع غل

ب دقل عبتي

PATIENT LEAFLET IN ACCORDANCE WITH THE

PHARMACISTS’ REGULATIONS )PREPARATIONS( – 1986

The medicine is dispensed with a doctor’s prescription only

Prograf

®

capsules

Prograf

®

0.5 mg

Prograf

®

1 mg

Prograf

®

5 mg

capsules

capsules

capsules

Composition

Each capsule contains:

Tacrolimus 0.5 mg

Tacrolimus 1 mg

Tacrolimus 5 mg

For information regarding inactive ingredients and allergens, see

section 2 - “Important information about some ingredients of the

medicine” and section 6 - “Additional information”.

Read the entire leaflet carefully before using the medicine. This

leaflet contains concise information about the medicine. If you have

additional questions, refer to the doctor or the pharmacist.

This medicine has been prescribed for your treatment. Do not pass it

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

condition is similar.

1. What is the medicine intended for?

Prophylaxis of transplant rejection in liver, kidney or heart allograft

recipients.

Treatment of allograft rejection resistant to treatment with other

immunosuppressive drugs.

Prograf belongs to a group of medicines that suppress the immune

system. Following organ transplant )such as liver, kidney and heart(

your body’s immune system will try to reject the new organ. Prograf is

used for modulation of your body’s immune reaction and allows your

body to accept the transplanted organ.

Therapeutic class: immunosuppressive agents.

2. Before using the medicine

Do not replace with another tacrolimus preparation, unless the

doctor from the transplant clinic you are treated in approves that.

Do not use this medicine if:

You are sensitive )allergic( to tacrolimus or to any of the other

ingredients this medicine contains )see section 6 – “Additional

information”(.

You are sensitive )allergic( to any antibiotic of the macrolide group

)e.g. erythromycin, clarithromycin, josamycin(.

Special warnings regarding the use of the medicine

FOR YOUR ATTENTION, it is important to ascertain that you

always receive the same medicine prescribed by your transplant

specialist each time you get the medicine at the pharmacy. In the

event you find out that the medicine you received looks different

from the one you usually receive, or the directions for use have

been changed, immediately refer to the pharmacist in order to

confirm that you have been supplied with the correct medicine.

Any replacement or change in dosing of a medicine containing

tacrolimus )the active ingredient in the medicine( must be

performed under the knowledge and approval of the physician

from the transplant clinic you are being treated in. Please check

the commercial name of the medicine written by the physician in

the prescription vis-à-vis the medicine you have received from

the pharmacist and verify that the names are identical.

Inform your doctor before using Prograf:

You need to take Prograf every day, so long as you need

immunosuppression in order to prevent your transplanted organ from

being rejected. You should keep in touch with your doctor regularly.

During treatment with Prograf capsules, your doctor may order

several tests )including blood, urine, heart function, visual and

neurological tests( from time to time. This is a normal procedure

and it will help your doctor to decide what is the most suitable dosage

of Prograf for you.

Avoid taking any herbal remedies, e.g., St. John’s wort [

hypericum

perforatum

], or any other herbal products, as this may affect the

effectiveness and the dose of Prograf that you need to receive. If in

doubt, please consult your doctor prior to taking any herbal products

or remedies.

If you have liver problems or any disease that may affect your liver,

inform your doctor as this may affect the dosage of Prograf you are

receiving.

If you feel strong abdominal pain accompanied or not by other

symptoms, such as chills, fever, nausea or vomiting.

If you have diarrhea for more than one day, please tell your doctor,

because it might be necessary to adjust the dose of Prograf that you

are receiving.

If there is a change in the electrical conduction of your heart called

“QT prolongation”.

Limit your exposure to sunlight and UV light while taking Prograf

by wearing appropriate protective clothing and using a sunscreen

with a high sun protection factor. The reason is the potential risk of

malignant skin changes with immunosuppressive therapy.

If you need to receive any vaccinations, inform your doctor

beforehand. Your doctor will recommend to you the best method of

treatment.

Patients treated with Prograf have been reported to have an

increased risk of lymphoproliferative disorders )see section 4 - “Side

effects”(. Consult the doctor regarding these disorders.

Report to the doctor immediately if during the treatment you are

suffering from:

Visual disturbances, such as blurry vision, changes in color vision,

difficulty seeing details or if your field of view becomes limited.

Drug-drug interactions

If you are taking or have recently taken other medicines

including non-prescription medicines and food supplements,

tell the doctor or the pharmacist.

Prograf should not be taken together with cyclosporin.

Prograf blood levels can be affected by other medicines you take, and

blood levels of other medicines can be affected by taking Prograf.

This may require stopping treatment, or increasing or decreasing the

Prograf dose. In particular, you should tell your doctor if you are taking

or have recently taken medicines with active ingredients such as:

Antifungals and antibiotics, especially macrolide antibiotics,

which are used for treatment of infections, such as ketoconazole,

fluconazole, itraconazole, voriconazole, clotrimazole, isavuconazole,

erythromycin, clarithromycin, josamycin and rifampicin.

Letermovir, which is used to prevent an illness caused by the human

cytomegalovirus )CMV(.

HIV-protease inhibitors )e.g. ritonavir, nelfinavir and saquinavir(,

the enhancer cobicistat and combined tablets, which are used for

treatment of HIV infection )human immunodeficiency virus(.

HCV protease inhibitors )e.g. telaprevir, boceprevir and the

combination ombitasvir/paritaprevir/ritonavir with or without

dasabuvir(, which are used for treatment of hepatitis C infection.

Nilotinib and imatinib )used for treatment of certain cancer types(.

Mycophenolic acid which is used for immunosuppression for

prevention of graft rejection.

Medicines to treat gastric ulcer and acid reflux )e.g., omeprazole,

lansoprazole or cimetidine(.

Medicines to treat nausea and vomiting )e.g. metoclopramide(.

Antacids that contain magnesium-aluminum-hydroxide for treatment

of heartburn.

Hormonal treatments that contain ethinylestradiol )e.g. contraceptive

tablets( or danazol.

Antihypertensives and medicines for heart problems, e.g. nifedipine,

nicardipine, diltiazem, verapamil.

Anti-arrhythmics )e.g. amiodarone( which are used for treatment of

heartbeat disturbances )arrhythmia(.

Medicines called statins which are used for treatment of high levels

of cholesterol and triglycerides.

The anti-epileptics phenytoin or phenobarbital.

The corticosteroids prednisolone and methylprednisolone.

The antidepressant nefazodone.

Herbal medicines that contain Hypericum )St. John’s wort [

hypericum

perforatum

]( or

Schisandra sphenanthera

extracts.

Inform the doctor if you are taking or should take ibuprofen,

amphotericin B or antiviral medicines )e.g. acyclovir(. These medicines

may worsen kidney or nervous system problems when taken together

with Prograf.

In addition, tell your doctor if you are taking potassium supplements

or potassium-sparing diuretics )e.g. amiloride, triamterene or

spironolactone(, certain analgesics )non-steroidal anti-inflammatory

drugs [NSAIDs], e.g. ibuprofen(, anticoagulants or oral antidiabetics,

while taking Prograf.

If you need to receive any vaccinations, inform your doctor beforehand.

Use of the medicine and food

You should generally take the medicine on an empty stomach or at

least 1 hour before or 2-3 hours after a meal. Grapefruit and grapefruit

juice should be avoided while taking Prograf.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, thinking you might be pregnant

or are planning to become pregnant, consult a doctor or a pharmacist

before taking this medicine.

Prograf is excreted into breastmilk. Therefore, you should not

breastfeed while taking Prograf.

Driving and operating machinery

Do not drive, use tools or operate machinery if you are feeling dizziness

or sleepiness, or if you cannot see clearly after taking Prograf. These

effects are more frequently observed if Prograf is taken in conjunction

with alcohol use.

Important information about some ingredients of the medicine

Prograf capsules contain lactose. If you have been told by your doctor

that you have an intolerance to certain sugars, speak to your doctor

before taking this medicine.

The printing ink used on Prograf 0.5 mg and 1 mg capsules contains

soya lecithin. If you are sensitive to peanuts or soya, inform the doctor

in order to determine if you should take this medicine.

This medicine contains less than 23 mg of sodium in a capsule, and

is therefore considered sodium-free.

3. How should you use the medicine?

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

Check with the doctor or pharmacist if you are uncertain about the

dosage and how to use the preparation.

You should make sure that you are receiving the same tacrolimus

preparation every time you get the medicine at the pharmacy, unless

the specialist from the transplant clinic you are treated in has agreed

to change to another tacrolimus preparation.

The dosage and treatment regimen will be determined only by the

doctor.

The generally accepted dosage is:

This medicine should be taken twice a day. If you notice any change

in the appearance of this medicine or in the instructions of use, inform

your doctor or pharmacist as soon as possible to make sure that you

are taking the right medicine.

The starting dose to prevent the rejection of your transplanted organ

will be determined by your doctor and calculated according to your

body weight. Initial doses just after transplantation will generally be in

the range of 0.075-0.30 mg per kg body weight per day, depending

on the transplanted organ.

The appropriate dosage for you depends on your general condition

and on which other immunosuppressive medications you are taking.

Regular blood tests as ordered by your doctor will be required to

determine the correct dose and to adjust it from time to time. Your

doctor will consider reducing your Prograf dosage once your condition

has stabilized. Your doctor will tell you exactly how many capsules to

take and how often.

Do not exceed the recommended dose.

Method of use

Prograf should be taken orally twice daily, usually in the morning and

evening. Prograf should generally be taken on an empty stomach or at

least 1 hour before or 2-3 hours after a meal. The capsules should be

swallowed whole with a glass of water. Take the capsules immediately

following removal from the blister. Avoid grapefruit and grapefruit juice

while taking Prograf. Do not swallow the desiccant contained in the

aluminum wrapping.

If you accidentally took an overdose

If you accidentally took an overdose of this medicine or if a child

accidentally swallowed this medicine, refer to your doctor or a hospital

emergency room immediately and bring the package of the medicine

with you.

If you have forgotten to take the medicine

Do not take a double dose in order to compensate for the dose that

you forgot to take.

If you have forgotten to take a Prograf capsule, wait until it is time for

the next dose and continue to take the capsules as usual.

Follow the treatment as recommended by the doctor.

If you stop taking the medicine

Stopping treatment with Prograf may increase the risk of rejection

of your transplanted organ. Do not stop your treatment unless your

doctor tells you to do so.

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

every time you take the medicine. Wear glasses if you need them.

If you have any other questions regarding use of the medicine,

consult the doctor or the pharmacist.

4. Side effects

As with any medicine, using Prograf may cause side effects in

some users. Do not be alarmed when reading the list of side

effects. You may not experience any of them.

Prograf reduces your body’s own defense mechanism to prevent the

rejection of your transplanted organ. Consequently, your body will

not be as good as usual at fighting infections. Therefore, when taking

Prograf you may catch more infections than usual, such as infections

of the skin, mouth, stomach, intestines, lungs and urinary tract.

Severe side effects may occur, including the ones listed below.

Refer to the doctor immediately if you experience or suspect you

may be experiencing any of the following severe side effects:

Opportunistic infections )bacterial, fungal, viral or parasite(:

prolonged diarrhea, fever and sore throat.

Incidents of benign and malignant tumors resulting from

immunosuppressive therapy have been reported.

Purpura of reduction in platelets and thrombocytes )thrombotic

thrombocytopenic purpura [TTP]( - a condition manifested by fever

and bruises under the skin that may appear as small red dots, with

or without extreme and unexplained tiredness, confusion, yellowing

of the skin or eyes )jaundice(, with symptoms of acute renal failure

)low or no urine output(.

Cases of pure red blood cell aplasia )a sharp decline in red blood

cell counts(, hemolytic anemia )a decline in red blood cell counts

as a result of abnormal breakdown of these cells accompanied by

tiredness( and febrile neutropenia )a decline in the type of white

blood cells that fight infection, accompanied by fever(. It is not known

exactly how often these side effects occur. You may not experience

any symptoms at all, or depending on the severity of your condition,

you may experience: fatigue, apathy, abnormal paleness of the skin,

shortness of breath, dizziness, headaches, chest pains and cold

sensation in the hands and feet.

Cases of agranulocytosis )a sharp decline in white blood cell counts,

accompanied by mouth sores, fever and infections(. You may not

have any symptoms at all, or you may have a sudden fever, chills

and sore throat.

Allergic and anaphylactic reactions, manifested by the following

symptoms: a sudden itchy rash )hives(, swelling of the hands, feet,

ankles, face, lips, mouth or throat )which may cause difficulty in

swallowing or breathing( and you may feel on the verge of fainting.

Posterior Reversible Encephalopathy Syndrome )PRES(: headaches,

altered mental status, seizures, and visual disturbances.

Torsades de Pointes

-type heart rate disturbances: a change in heart

rate that may or may not be accompanied by symptoms such as

chest pains )angina(, fainting, vertigo or nausea, palpitations and

difficulty breathing.

Gastrointestinal perforation: strong abdominal pains, which may or

may not be accompanied by other symptoms, such as chills, fever,

nausea or vomiting.

Stevens-Johnson syndrome: widespread and unexplained skin pain,

facial swelling, serious illness with blistering of skin, mouth, eyes and

genitals, hives, tongue swelling, red or purple skin rash that spreads

through the skin, skin shedding.

Toxic epidermal necrolysis syndrome: erosion and blisters on the

skin or mucosal tissues, red and swollen skin that may detach in

large parts of the body.

Hemolytic uremic syndrome, manifested by the following symptoms:

low or no urine output )acute renal failure(, extreme tiredness,

yellowing of the skin or eyes )jaundice(, abnormal bruising or

bleeding and signs of infection.

Impaired function of your transplanted organ.

The following side effects may also occur after taking Prograf:

Very common side effects )may affect more than 1 in 10 patients(:

Increased blood sugar, diabetes mellitus, increased potassium in

the blood

Sleeping difficulties

Tremor, headache

Rise in blood pressure

Diarrhea, nausea

Kidney problems

Common side effects )may affect up to 1 in 10 patients(:

Reduced magnesium, phosphate, potassium, calcium or sodium

in the blood, fluid overload, increased level of uric acid or lipids in

the blood, decreased appetite, increased acidity of the blood, other

changes in blood salts

Anxiety symptoms, confusion and disorientation, depression, mood

changes, nightmares, hallucinations, mental disorders

Convulsions, disturbances in consciousness, tingling and numbness

)sometimes painful( in the hands and feet, dizziness, impaired writing

ability, nervous system disorders

Blurred vision, increased sensitivity to light, eye disorders

Tinnitus )ringing sound in your ears(

Reduced blood flow in blood vessels in the heart, rapid heartbeat

Bleeding, partial or complete blocking of blood vessels, reduced

blood pressure

Shortness of breath, changes in lung tissue, collection of fluids

around the lungs, inflammation of the pharynx, cough, flu-like

symptoms

Inflammations or ulcers causing abdominal pain or diarrhea, bleeding

in the stomach, inflammations or ulcers in the mouth, collection

of fluids in the abdomen, vomiting, abdominal pains, indigestion,

constipation, flatulence, bloating, loose stools, stomach problems

Changes in liver enzymes and function, yellowing of the skin due to

liver problems, liver tissue damage and inflammation of the liver

Itching, rash, hair loss, acne, increased sweating

Pain in joints, limbs, back and feet, muscle cramps

Renal failure, reduced production of urine, impaired or painful

urination

General weakness, fever, collection of fluids in your body, pain and

discomfort, increase in the levels of the enzyme alkaline phosphatase

in your blood, weight gain, sensation of changes in body temperature

Uncommon side effects )may affect up to 1 in 100 patients(:

Changes in blood clotting, reduction in all blood cell counts

Dehydration, reduced protein or sugar levels in the blood, increased

phosphate levels in the blood

Coma, bleeding in the brain, stroke, paralysis, brain disorder, speech

and language impairments, memory problems

Blurry vision due to impairment of the eye lens

Impaired hearing

Irregular heartbeat, cardiac arrest, reduced heart performance,

impaired heart muscle, enlargement of the heart muscle )hypertrophic

cardiomyopathy(, stronger heartbeat, abnormal ECG, abnormal

heart rate and pulse

Blood clot in a vein of a limb, shock

Breathing difficulties, respiratory tract disorders, asthma

Obstruction of the gut, increase in the levels of the enzyme amylase

in your blood, reflux of stomach content into the throat, delayed

emptying of the stomach

Dermatitis, burning sensation in sunlight

Joint disorders

Inability to urinate, painful menstruation and abnormal menstrual

bleeding

Failure of some organs, flu-like illness, increased sensitivity to heat

and cold, sensation of pressure in your chest, agitation or abnormal

feeling, increase in the levels of the enzyme lactate dehydrogenase

in your blood, weight loss

Rare side effects )may affect up to 1 in 1,000 patients(:

Small bleedings in your skin due to blood clots

Increased muscle stiffness

Blindness

Deafness

Collection of fluids around the heart

Acute shortness of breath

Cyst formation in your pancreas

Problems with blood flow in the liver

Excessive hairiness

Thirst, tendency to fall, feeling of tightness in your chest, decreased

mobility, ulcer

Very rare side effects )may affect up to 1 in 10,000 patients(:

Muscle weakness

Abnormal results in echocardiogram

Liver failure, narrowing of the bile vessel

Painful urination with blood in the urine

Increase in fat tissue

Side effects with unknown incidence )incidence cannot be

estimated from existing data(:

Abnormality in the optical nerve )optical neuropathy(

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

if you suffer from a side effect not mentioned in this leaflet,

consult your doctor.

Reporting side effects

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

the link “report side effects due to medicinal treatment” found on the

Ministry of Health website homepage )www.health.gov.il(, which will

direct you to the online form for reporting side effects, or by clicking

on the following link:

https://sideeffects.health.gov.il

5. How to store the medicine?

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

in a closed place out of the reach and sight of children and/or infants to

avoid poisoning. Do not induce vomiting without an explicit instruction

from 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.

Take the capsules immediately following removal from the blister.

Store below 25°C. Keep in original package to protect from

moisture.

After opening the aluminum wrapping the capsules should

be used within 12 months, but no later than the expiry date

indicated on the package.

In each aluminum wrapping there is a desiccant )moisture absorber(.

Do not swallow.

6. Additional information

In addition to the active ingredient, the medicine also contains:

Prograf capsules 0.5 mg

Capsule content composition:

Lactose monohydrate, magnesium stearate, hydroxypropyl

methylcellulose, croscarmellose sodium

Capsule shell composition:

Titanium dioxide )E 171(, ferric oxide yellow )E 172(, gelatin,

shellac glaze, lecithin )soya(, simeticone, ferric oxide red )E 172(,

hydroxypropyl cellulose

Prograf capsules 1 mg

Capsule content composition:

Lactose monohydrate, hydroxypropyl methylcellulose, croscarmellose

sodium, magnesium stearate

Capsule shell composition:

Titanium dioxide )E 171(, gelatin, shellac glaze, lecithin )soya(,

simeticone, ferric oxide red )E 172(, hydroxypropyl cellulose

Prograf capsules 5 mg

Capsule content composition:

Lactose monohydrate, hydroxypropyl methylcellulose, croscarmellose

sodium, magnesium stearate

Capsule shell composition:

Titanium dioxide )E 171(, ferric oxide red )E 172(, gelatin, shellac,

propylene glycol

What does the medicine look like and what are the contents

of the package

Prograf capsules 0.5 mg

Light yellow capsules imprinted in red with “0.5 mg” and “[f] 607”,

containing white powder.

Prograf capsules 1 mg

Opaque white capsules imprinted in red with “1 mg” and “[f] 617”,

containing white powder.

Prograf capsules 5 mg

Opaque greyish-red capsules imprinted in white with “5 mg” and

“[f] 657”, containing white powder.

The package contains 50 or 100 capsules, packed in trays )blisters(,

in an aluminum wrapping that contains a desiccant.

Not all package sizes may be marketed.

License holder and the address:

Abic Marketing Ltd. )a Teva subsidiary(

P.O. Box 8077, Netanya.

Name and address of the manufacturer:

Astellas Ireland Co. Ltd., Killorglin, Ireland.

The format of this leaflet was determined by the Ministry of

Health and its content was checked and approved by the Ministry

of Health in: August 2015, and was updated in accordance with

the Ministry of Health instructions in: November 2019.

Registration numbers of the medicine in the National Drug

Registry of the Ministry of Health:

Prograf 0.5 mg:

122.07.30215

Prograf 1 mg:

107.69.29158

Prograf 5 mg:

107.70.29159

PROG CAPS PL SH 300420

PROG CAPS PL SH 300420

thrombotic ( ةيرثختلا ةيومدلا تاحيفصلا صقن )

Purpura

( ةيرفرف

دلجلا تحت تامدك ،ةنوخسب زيمتت ةلاح ،)thrombocytopenic purpura [TTP] ديدش قاهرإب قفارتت لا وأ قفارتت ،ةريغص ءارمح طاقن لكش ىلع رهظت نأ اهنأش نم يتلا داح يولك روصقل ضارعأ عم ،)ناقري( نينيعلا وأ دلجلا رارفصإ ،كابترإ ،ببسلا لوهجم .)لوبلا فقوت وأ ضافخنإ( ضافخنإ

pure red cell aplasia( ءارمحلا مدلا ايلاخ جسنت مدعل تلااح نع غلب مدلا ايلاخ ددع يف ضافخنإ( يللاحنإ مد رقف ،)ءارمحلا مدلا ايلاخ دادعت يف

ادج ريطخ مدلا ايلاخ يف ضافخنإ( تلادعلا صقن ىمحو )قاهرإب قفارتي ذاش فلت ءارج ءارمحلا رهظت طبضلاب ةريتو يأب فرعي لا .)ةنوخسب قفارتي ،ثولتلا براحي يذلا عونلا نم ءاضيبلا نم كتلاح ةدشب قلعتم رمأك وأ ،ضارعأب

ادبأ رعشت لاأ زئاجلا نم .ةيبناجلا ضارعلأا هذه ملأ ،عادص ،راود ،سفنت قيض ،دلجلل ذاش بوحش ،ثارتكإ مدع ،قاهرإ :ـب رعشت نأ زئاجلا .نيمدقلاو نيديلا يف ةدوربب روعشو ردصلا يف قفارتي

ذلا ءاضيبلا مدلا ايلاخ ددع يف ريطخ ضافخنإ( ةببحملا تايركلا صقنل تلااح رعشت نأ وأ

ادبأ ضارعأ كيدل نوكت لاأ زئاجلا نم .)تاثولتو ةنوخس ،مفلا يف تاحرقتب .ةرجنحلا يف ملأو ةريرعشق ،ةئجافم ةنوخسب خافتنإ

ىرش( ئجافمو كاح حفط :ةيلاتلا ضارعلأاب لثمتت ةيقأتو ةيسسحت لعف دودر ببسي ن

هنأش نم يذلا( ةرجنحلا وأ مفلا ،نيتفشلا ،هجولا ،لحاكلا ،نيمدقلا ،نيديلا يف .ءامغلإا ىلع كشوت كنأب رعشت دق تنأو )سفنتلا وأ علبلا يف تابوعص Posterior Reversible Encephalopathy( سوكعلا يفلخلا يغامدلا للاتعلإا ةمزلاتم .ةيؤرلا شوشتو ،تاجلاتخإ ،ةيسفنلا ةلاحلا يف ريغت ،عادص :)Syndrome [PRES[ مظن ةريتو يف تاريغت :

Torsades de Pointes

عون نم بلقلا مظن يف تابارطضإ ،ءامغإ ،)ةيردص ةحبذ( ردصلا يف ملأ لثم ضارعأ نودب وأ عم رهظت نأ نكمي يتلا بلقلا .سفنتلا يف تابوعصو )بلقلا تابرضب روعشلا( ناقفخ ،نايثغ و

وغيتريڤ ،ةيفاضإ ضارعأب قفارتي لا وأ قفارتي يذلا نطبلا يف ديدش ملأ :يمضهلا زاهجلا يف باقثنإ .ؤيقت وأ نايثغ ،ةنوخس ،ةريرعشق لثم ةرسفم ريغ ملاآ )Stevens-Johnson syndrome(: نوسنوج – سنيڤيتس ةمزلاتم يف ،دلجلا يف تلاصيوح عم ديدش ضرم ،هجولا يف خافتنإ ،دلجلا نم ةعساش قطانم يف وأ رمحأ حفط راشتنإ ،ناسللا يف خافتنإ ،ىرش ،ةيلسانتلا ءاضعلأا يفو نينيعلا يف ،مفلا .دلجلا طقاست ،دلجلا ىلع يجسفنب دلجلا يف تلاصيوحو )

erosion

( لكآت :Toxic epidermal necrolysis ةمزلاتم .مسجلا نم ةريبك ءازجأ يف لصفني دق يذلا خفتنمو رمحأ دلج ،ةيطاخملا ةجسنلأا يف وأ زيمتت ةلاح ،)Haemolytic uraemic syndrome( ةيميرويلا مدلا للاحنإ ةمزلاتم دلجلا رارفصإ ،ديدش قاهرإ ،)داح يولك روصق( لوبلا فقوت وأ ضافخنإ :ةيلاتلا ضارعلأاب .ثولتل تاملاعو فزن وأ ةذاش تامدك ،)ناقري( نينيعلاو .كيدل عورزملا وضعلل يفيظولا ءادلأا يف للخ :فارچورپ لوانت دعب ثدحت دق هاندأ ةلصفملا ةيبناجلا ضارعلأا :)نيجلاعتم 10 نيب نم 1 نم رثكأ ىلع رثؤت دق(

ً

ادج ةعئاش ةيبناج ضارعأ مدلا يف مويساتوپلا ةبسن عافترإ ،يركسلا ،مدلا يف ركسلا ةبسن عافترإ مونلا يف تابوعص عادص ،فاجترإ مدلا طغض عافترإ نايثغ ،لاهسإ ةيلكلا يف لكاشم :)نيج

َ

لاعم 10 نيب نم 1 ىتح ىلع رثؤت دق( ةعئاش ةيبناج ضارعأ ضئاف ،مدلا يف مويدوصلا وأ مويسلاكلا ،مويساتوپلا ،تافسوفلا ،مويزنغملا ةبسن ضافخنإ ،ماعطلل ةيهشلا ضافخنإو ،مدلا يف موحشلا وأ لوبلا ضمح ةبسن عافترإ ،لئاوسلا نم مدلا حلامأ يف ىرخأ تارييغت ،مدلا ةضومح يف عافترإ تابارطضإ ،نايذه ،سيباوك ،ةيسفنلا ةلاحلا يف تاريغت ،بائتكإ ،ناهوتو كابترإ ،قلق ضارعأ ةيسفن نيديلا يف )ملأب

انايحأ قفارتت( ليمنتلاب روعشلاو زخو ،كاردلإا يف تابارطضإ ،تاجلاتخإ يبصعلا زاهجلا يف تابارطضإ ،ةباتكلا ىلع ةردقلا ررضت ،راود ،نيمدقلاو نينيعلا يف لكاشم ،ءوضلل ةدئاز ةيساسح ،ةيؤرلا يف شوشت نينذلأا يف نينط

ةعيرس بلق تاضبن ،بلقلا يف ةيومدلا ةيعولأا يف مدلا نايرج صقن مدلا طغض ضافخنإ ،ةيومدلا ةيعولأل مات و

يئزج دادسنإ ،فزن ،لاعس ،موعلبلا باهتلإ ،نيتئرلا لوح لئاوس مكارت ،نيتئرلا جيسن يف تاريغت ،سفنت قيض ازنإولفنلإل ةهباشم ضارعأ تاحرقت وأ تاباهتلإ ،ةدعملا يف ةفزنأ ،لاهسلإ وأ نطبلا يف ملالآ ةببسملا تاحرقت وأ تاباهتلإ ،ةخفن ،تازاغ ،كاسمإ ،مضه رسع ،نطبلا يف ملاآ ،تاؤيقت ،نطبلا يف لئاوس مكارت ،مفلا يف ةدعملا يف لكاشم ،ن

يل زارب ،دبكلا يف لكاشم ةيفلخ ىلع دلجلا رارفصإ ،دبكلا ةفيظو يفو دبكلا تاميزنإ يف تاريغت دبكلا باهتلإو ،دبكلا جيسن يف ررض دئاز قرعت ،بابش بح ،رعش طقاست ،حفط ،ةكح ةيلضع تاصلقت ،نيمدقلاو رهظلا يف ،فارطلأا يف ،لصافملا يف ملاآ لوبتلا دنع ملأ وأ للخ ،لوبلا جاتنإ يف ضافخنإ ،يولك روصق زاتفسوف ميزنلإا ةبسن عافترإ ،حايترإ مدعو ملأ ،مسجلا يف لئاوس مكارت ،ةنوخس ،ماع فعض مسجلا ةرارح ةجرد يف للاتخإب روعشلا ،نزولا يف ةدايز ،مدلا يف يولقلا )جلاعتم 100 نيب نم 1 ىتح ىلع رثؤت دق( ةعئاش ريغ ةيبناج ضارعأ مدلا ايلاخ دادعت ةفاك يف ضافخنإ ،مدلا رثخت يف تاريغت مدلا يف تافسوفلا ةبسن عافترإ ،مدلا يف ركسلا وأ نيتورپلا بسن يف ضافخنإ ،فافجت ،ةغللاو قطنلا يف للخ ،غامدلا يف بارطضإ ،للش ،ةيغامد ةتكس ،غامدلا يف فزن ،تاب

س ةركاذلا يف لكاشم نينيعلا يتسدع يف للخ ببسب ةيؤرلا شوشت عمسلا يف للخ مخضت ،بلقلا ةلضع

يف بارطضإ

،بلقلا ةفيظو يف ضافخنإ

،ةيبلق ةتكس ،مظتنم ريغ ضبن ناذاش بلق ضبنو مظن ،بلقلل يئابرهكلا طيطختلا يف ذوذش ،يوق ضبن ،بلقلا ةلضع

shock

( ةمدص ،فارطلأا ىدحلإ ديرو يف ةيومد ةرثخ وبر ،ةيسفنتلا قرطلا يف تابارطضإ ،سفنتلا يف تابوعص ةرجنحلا ىلإ ةدعملا ىوتحم دادترإ ،مدلا يف زلايملأا ميزنإ ةبسن عافترإ ،ءاعملأا دادسنإ ةدعملا غارفإ يف ريخأت ،)Reflux( سمشلل ضرعتلا دنع ةقرحب روعشلا ،دلجلا يف باهتلإ لصافملا يف تابارطضإ ذاش يثمط فزنو ثمطلا ملاآ ،لوبتلا ىلع ةردقلا مدع ةرارحلل ةطرفم ةيساسح

،ازنإولفنلإاب هيبش ضرم

،ةنيعم ءاضعلأ

يفيظولا ءادلأا

يف لشف ميزنلإا ةبسن

يف عافترإ

،يدايتعإ ريغ

روعش وأ ةيبصع ، ر د ص ل ا

يف طغضب روعشلا

،ةدوربلاو

نزولا ضافخنإ ،مدلا يف زانيجورديهيد تاتكلا )جلاعتم 1,000 نيب نم 1 ىتح ىلع رثؤت دق( ةردان ةيبناج ضارعأ ةيومد تارثخ ةجيتن دلجلا يف ةفيفط ةفزنأ تلاضعلل دئاز بلصت ىمع ممص

بلقلا لوح لئاوس مكارت داح سفنت قيض سايركنبلا يف ةسيك لكشت دبكلا يف مدلا نايرج يف لكاشم رعشلل طرفم ومن ةحرق ،ةكرحلا يف صقن ،ردصلا يف قيضب روعش ،طوقسلل ليم ،شطع )جلاعتم 10,000 نيب نم 1 ىتح ىلع رثؤت دق(

ً

ادج ةردان ةيبناج ضارعأ تلاضعلا فعض

بلقلا ىدص ط يطخت صحف جئاتن ةملاس مدع ةيوارفصلا ةانقلا قيضت ،دبكلا روصق لوبلا يف مدب قفارتي لوبتلا دنع ملأ يمحشلا جيسنلا ةدايز :)ةرفوتملا تامولعملا نم عويشلا مييقت نكمي لا( فورعم ريغ اهعويش ةيبناج ضارعأ )يرصب يبصع للاتعإ( ةيؤرلا بصع يف ذوذش ضرع نم يناعت امدنع وأ ،ةيبناجلا ضارعلأا ىدحإ تمقافت اذإ ،يبناج ضرع رهظ اذإ .بيبطلا ةراشتسإ كيلع ،ةرشنلا هذه يف ركذي مل يبناج ةيبناج ضارعأ نع غيلبتلا نع غيلبت" طبارلا ىلع طغضلا ةطساوب ةحصلا ةرازول ةيبناج ضارعأ نع غيلبتلا ناكملإاب ةحصلا ةرازو عقومل ةيسيئرلا ةحفصلا ىلع دوجوملا "يئاود جلاع بقع ةيبناج ضارعأ ،ةيبناج ضارعأ نع غيلبتلل رشابملا جذومنلا ىلإ كهجوي يذلا )www.health.gov.il( :طبارلا حفصت قيرط نع وأ

https://sideeffects.health.gov.il

؟ءاودلا نيزخت ةيفيك )5 يديأ لوانتم نع

اديعب قلغم ناكم يف رخآ ءاود لكو ءاودلا اذه ظفح بجي ! ممستلا بنجت نودب ؤيقتلا ببست لا . ممستلاب مهتباصإ يدافتل كلذو ،عضرلا وأ/و لافطلأا ةيؤر لاجمو . بيبطلا نم ةحيرص تاميلعت رهظ ىلع رهظي يذلا )exp. Date( ةيحلاصلا خيرات ءاضقنإ دعب ءاودلا لامعتسإ زوجي لا .رهشلا سفن نم ريخلأا مويلا ىلإ ةيحلاصلا خيرات ريشي .ةبلعلا .)رتسيلب( ةحيوللا نم اهجارخإ دعب ةرشابم تلاوسبكلا لوانت بجي ةيامحلل ةيلصلأا ةبلعلا يف ءاودلا ظفح بجي .ةيوئم ةجرد 25 نود نيزختلا بجي .ةبوطرلا نم امب نكل ،

ً

ارهش 12 نوضغ يف تلاوسبكلا لامعتسإ بجي موينموللأا فلاغ حتف دعب .ةبلعلا رهظ ىلع نودملا ةيحلاصلا ءاضقنإ خيرات زواجتي لا .هعلب زوجي لا . ةبوطرلل صام ىلع يوتحي سيك موينمولأ فلاغ لك لخاد دجوي ةيفاضإ تامولعم )6

:

ً

اضيأ لاعفلا بكرملل ةفاضلإاب ءاودلا يوتحي غلم 0.5 تلاوسبك فارچورپ :ةلوسبكلا ىوتحم بيكرت

Lactose monohydrate, magnesium stearate, hydroxypropyl

methylcellulose, croscarmellose sodium

:ةلوسبكلا فلاغ بيكرت

Titanium dioxide )E 171(, ferric oxide yellow )E 172(, gelatin,

shellac glaze, lecithin )soya(, simeticone, ferric oxide red )E 172(,

hydroxypropyl cellulose

غلم 1 تلاوسبك فارچورپ :ةلوسبكلا ىوتحم بيكرت

Lactose monohydrate, hydroxypropyl methylcellulose,

croscarmellose sodium, magnesium stearate

:ةلوسبكلا فلاغ بيكرت

Titanium dioxide )E 171(, gelatin, shellac glaze, lecithin )soya(,

simeticone, ferric oxide red )E 172(, hydroxypropyl cellulose

غلم 5 تلاوسبك فارچورپ :ةلوسبكلا ىوتحم بيكرت

Lactose monohydrate, hydroxypropyl methylcellulose,

croscarmellose sodium, magnesium stearate

:ةلوسبكلا فلاغ بيكرت

Titanium dioxide )E 171(, ferric oxide red )E 172(, gelatin, shellac,

propylene glycol

ةبلعلا ىوتحم وه امو ءاودلا ودبي فيك غلم 0.5 تلاوسبك فارچورپ يوحتو »[f] 607« ـو »0.5 mg« رمحأ ربحب اهيلع عب

حتاف رفصأ نولب تلاوسبك .ضيبأ قوحسم غلم 1 تلاوسبك فارچورپ يوحتو »[f] 617« ـو »1 mg« رمحأ ربحب اهيلع عب

ط ضيبأ نولب ةفافش ريغ تلاوسبك .ضيبأ قوحسم غلم 5 تلاوسبك فارچورپ »[f[ 657« ـو »5 mg« ضيبأ ربحب اهيلع عب

ط يدامرلل لئام رمحأ نولب ةفافش ريغ تلاوسبك .ضيبأ قوحسم يوحتو موينموللأا فلاغ لخاد ،)رتسيلب( تاحيول نمض ةأبعم ،ةلوسبك 100 وأ 50 ىلع ةبلعلا يوتحت .ةبوطرلل صام يوحي يذلا .بلعلا ماجحأ ةفاك ق

وست لاأ زئاجلا نم :هناونعو زايتملإا بحاص )عڤيت ةعومجم نم( .ض.م قيوستلل كيبأ .ايناتن ،8077 .ب.ص هناونعو جتنملا مسإ .ادنلريإ ،نيلچروليك ،.ض.م يناپموك ادنلريإ سلاتسإ 2015 بآ خيراتب صخ

ُ

رو صح

ُ

ف اهاوتحمو ةرشنلا هذه ةغيص ةحصلا ةرازو ترقأ .2019 يناثلا نيرشت خيراتب ةحصلا ةرازو تاميلعت بجومب اهثيدحت متو :ةحصلا ةرازو يف يموكحلا ةيودلأا لجس يف ءاودلا لجس ماقرأ

122.07.30215

:غلم 0.5 فارچورپ

107.69.29158

:غلم 1 فارچورپ

107.70.29159

:غلم 5 فارچورپ ،كلذ نم مغرلا ىلع .ركذملا ةغيصب ةرشنلا هذه ةغايص تمت ،ةءارقلا نيوهتو ةلوهس لجأ نم .نيسنجلا لاكل صصخم ءاودلا نإف ةمتت

Prograf Capsules MF 11/2019 Notification

SUMMARY OF PRODUCT CHARACTERISTICS

Prograf

®

0.5 mg

Prograf

®

1 mg

Prograf

®

5 mg

IMPORTANT!

In order to ensure the continuity of different products of tacrolimus in individual patients it should be

emphasized that if patients are changed from one tacrolimus product to another it should be done only

with specific counselling and tight monitoring from their transplantation specialist.

1.

NAME OF THE MEDICINAL PRODUCT

Prograf 0.5 mg

Prograf 1 mg

Prograf 5 mg

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION

Prograf 0.5 mg capsules

Each capsule contains 0.5 mg of tacrolimus.

Excipient with known effect: 62.85 mg of lactose monohydrate.

Each capsule contains less than 1 mmol sodium (23 mg).

The printing ink used to mark the capsule contains trace amounts of soya lecithin (0.48% of total

printing ink composition).

Prograf 1 mg capsules

Each capsule contains 1 mg of tacrolimus.

Excipient with known effect: 61.35 mg of lactose monohydrate.

Each capsule contains less than 1 mmol sodium (23 mg).

The printing ink used to mark the capsule contains trace amounts of soya lecithin (0.48% of total

printing ink composition).

Prograf 5 mg capsules

Each capsule contains 5 mg of tacrolimus.

Excipient with known effect: 123.60 mg of lactose monohydrate.

Each capsule contains less than 1 mmol sodium (23 mg).

For the full list of excipients, see section 6.1.

3.

PHARMACEUTICAL FORM

Prograf 0.5 mg capsules

Capsule, hard

Light yellow hard gelatin capsules imprinted in red with "0.5 mg" and "[f] 607", containing white

powder.

Prograf 1 mg capsules

Capsule, hard

Opaque white hard gelatin capsules imprinted in red with ”1 mg” and “[f] 617”, containing white

powder.

Prograf Capsules MF 11/2019 Notification

Prograf 5 mg capsules

Capsule, hard

Opaque greyish red hard gelatin capsules imprinted in white with "5 mg" and "[f] 657", containing

white powder.

4.

CLINICAL PARTICULARS

4.1

Therapeutic indications

Prophylaxis of transplant rejection in liver, kidney or heart allograft recipients.

Treatment of allograft rejection resistant to treatment with other immunosuppressive

medicinal

products.

4.2

Posology and method of administration

Prograf therapy requires careful monitoring by adequately qualified and equipped personnel. The

medicinal product should only be prescribed, and changes in immunosuppressive therapy initiated, by

physicians experienced in immunosuppressive therapy and the management of transplant patients.

Inadvertent, unintentional or unsupervised switching of immediate- or prolonged-release formulations

of tacrolimus is unsafe. This can lead to graft rejection or increased incidence of side effects, including

under- or over immunosuppression, due to clinically relevant differences in systemic exposure to

tacrolimus.

Patients

should

maintained

single

formulation

tacrolimus

with

corresponding daily dosing regimen; alterations in formulation or regimen should only take place

under the close supervision of a transplant specialist (see sections 4.4 and 4.8). Following conversion

to any alternative formulation, therapeutic drug monitoring must be performed and dose adjustments

made to ensure that systemic exposure to tacrolimus is maintained.

General considerations

The recommended initial dosages presented below are intended to act solely as a guideline. Prograf

dosing should primarily be based on clinical assessments of rejection and tolerability in each patient

individually aided by blood level monitoring (see below for recommended target whole blood trough

concentrations). If clinical signs of rejection are apparent, alteration of the immunosuppressive

regimen should be considered.

Prograf can be administered intravenously or orally. In general, dosing may commence orally; if

necessary, by administering the capsule contents suspended in water, via nasogastric tubing.

Prograf is routinely administered in conjunction with other immunosuppressive agents in the initial

post-operative period. The Prograf dose may vary depending upon the immunosuppressive regimen

chosen.

Posology

Dosage recommandations – Liver transplantation

Prophylaxis of transplant rejection - adults

Oral Prograf therapy should commence at 0.10 - 0.20 mg/kg/day administered as two divided doses

(e.g. morning and evening). Administration should commence approximately 12 hours after the

completion of surgery.

If the dose cannot be administered orally as a result of the clinical condition of the patient, intravenous

therapy of 0.01 - 0.05 mg/kg/day should be initiated as a continuous 24-hour infusion.

Prophylaxis of transplant rejection - children

An initial oral dose of 0.30 mg/kg/day should be administered in two divided doses (e.g. morning and

evening). If the clinical condition of the patient prevents oral dosing, an initial intravenous dose of

0.05 mg/kg/day should be administered as a continuous 24-hour infusion.

Prograf Capsules MF 11/2019 Notification

Dose adjustment during post-transplant period in adults and children

Prograf doses are usually reduced in the post-transplant period. It is possible in some cases to

withdraw concomitant immunosuppressive therapy, leading to Prograf monotherapy. Post-transplant

improvement in the condition of the patient may alter the pharmacokinetics of tacrolimus and may

necessitate further dose adjustments.

Rejection therapy – adults and children

Increased Prograf doses, supplemental corticosteroid therapy, and introduction of short courses of

mono-/polyclonal antibodies have all been used to manage rejection episodes. If signs of toxicity are

noted (e.g. pronounced adverse reactions - see section 4.8) the dose of Prograf may need to be

reduced.

For conversion to Prograf, treatment should begin with the initial oral dose recommended for primary

immunosuppression.

For information on conversion from ciclosporin to Prograf, see below under “Dose adjustments in

specific patient populations”.

Dosage recommendations - Kidney transplantation

Prophylaxis of transplant rejection – adults

Oral Prograf therapy should commence at 0.20 - 0.30 mg/kg/day administered as two divided doses

(e.g. morning and evening). Administration should commence within 24 hours after the completion of

surgery.

If the dose cannot be administered orally as a result of the clinical condition of the patient, intravenous

therapy of 0.05 - 0.10 mg/kg/day should be initiated as a continuous 24-hour infusion.

Prophylaxis of transplant rejection – children

An initial oral dose of 0.30

mg/kg/day should be administered in two divided doses (e.g. morning and

evening). If the clinical condition of the patient prevents oral dosing, an initial intravenous dose of

0.075

0.100 mg/kg/day should be administered as a continuous 24-hour infusion.

Dose adjustment during post-transplant period in adults and children

Prograf doses are usually reduced in the post-transplant period. It is possible in some cases to

withdraw concomitant immunosuppressive therapy, leading to Prograf-based dual-therapy. Post-

transplant improvement in the condition of the patient may alter the pharmacokinetics of tacrolimus

and may necessitate further dose adjustments.

Rejection therapy – adults and children

Increased Prograf doses, supplemental corticosteroid therapy, and introduction of short courses of

mono-/polyclonal antibodies have all been used to manage rejection episodes. If signs of toxicity are

noted (e.g. pronounced adverse reactions - see section 4.8) the dose of Prograf may need to be

reduced.

For conversion to Prograf, treatment should begin with the initial oral dose recommended for primary

immunosuppression.

For information on conversion from ciclosporin to Prograf, see below under “Dose adjustments in

specific patient populations”.

Dosage recommendations - Heart transplantation

Prophylaxis of transplant rejection – adults

Prograf can be used with antibody induction (allowing for delayed start of Prograf therapy) or

alternatively in clinically stable patients without antibody induction.

Prograf Capsules MF 11/2019 Notification

Following antibody induction, oral Prograf therapy should commence at a dose of 0.075 mg/kg/day

administered as two divided doses (e.g. morning and evening). Administration should commence

within 5 days after the completion of surgery as soon as the patient's clinical condition is stabilised. If

the dose cannot be administered orally as a result of the clinical condition of the patient, intravenous

therapy of 0.01 to 0.02 mg/kg/day should be initiated as a continuous 24-hour infusion.

An alternative strategy was published where oral tacrolimus was administered within 12 hours post

transplantation.

This

approach

reserved

patients

without

organ

dysfunction

(e.g.

renal

dysfunction). In that case, an initial oral tacrolimus dose of 2 to 4 mg per day was used in combination

with mycophenolate mofetil and corticosteroids or in combination with sirolimus and corticosteroids.

Prophylaxis of transplant rejection – children

Prograf has been used with or without antibody induction in paediatric heart transplantation.

In patients without antibody induction, if Prograf therapy is initiated intravenously, the recommended

starting dose is 0.03 - 0.05 mg/kg/day as a continuous 24-hour infusion targeted to achieve tacrolimus

whole blood concentrations of 15 - 25 ng/ml.

Patients should be converted to oral therapy as soon as

clinically practicable. The first dose of oral therapy should be 0.30 mg/kg/day starting 8 to 12 hours

after discontinuing intravenous therapy.

Following antibody induction, if Prograf therapy is initiated orally, the recommended starting dose is

0.10 - 0.30 mg/kg/day administered as two divided doses (e.g. morning and evening).

Dose adjustment during post-transplant period in adults and children

Prograf doses are usually reduced in the post-transplant period. Post-transplant improvement in the

condition of the patient may alter the pharmacokinetics of tacrolimus and may necessitate further dose

adjustments.

Rejection therapy – adults and children

Increased Prograf doses, supplemental corticosteroid therapy, and introduction of short courses of

mono-/polyclonal antibodies have all been used to manage rejection episodes.

In adult patients converted to Prograf, an initial oral dose of 0.15 mg/kg/day should be administered in

two divided doses (e.g. morning and evening).

In paediatric patients converted to Prograf, an initial oral dose of 0.20 - 0.30 mg/kg/day should be

administered in two divided doses (e.g. morning and evening).

For information on conversion from ciclosporin to Prograf, see below under “Dose adjustments in

specific patient populations”.

Dosage recommendations - Rejection therapy, other allografts

The dose recommendations for lung, pancreas and intestinal transplantation are based on limited

prospective clinical trial data. In lung-transplanted patients Prograf has been used at an initial oral dose

of 0.10 - 0.15 mg/kg/day, in pancreas-transplanted patients at an initial oral dose of 0.2 mg/kg/day and

in intestinal transplantation at an initial oral dose of 0.3 mg/kg/day.

Dosage adjustments in specific patient populations

Patients with liver impairment

Dose reduction may be necessary in patients with severe liver impairment in order to maintain the

blood trough levels within the recommended target range.

Patients with kidney impairment

As the pharmacokinetics of tacrolimus are unaffected by renal function, no dose adjustment should be

required. However, owing to the nephrotoxic potential of tacrolimus careful monitoring of renal

Prograf Capsules MF 11/2019 Notification

function is recommended (including serial serum creatinine concentrations, calculation of creatinine

clearance and monitoring of urine output).

Paediatric population

In general, paediatric patients require doses 1½ - 2 times higher than the adult doses to achieve similar

blood levels.

Older people

There is no evidence currently available to indicate that dosing should be adjusted in older people

Conversion from ciclosporin

Care should be taken when converting patients from ciclosporin-based to Prograf based therapy (see

sections

4.5).

Prograf

therapy

should

initiated

after

considering

ciclosporin

blood

concentrations and the clinical condition of the patient. Dosing should be delayed in the presence of

elevated ciclosporin blood levels. In practice, Prograf therapy has been initiated 12 - 24 hours after

discontinuation of ciclosporin. Monitoring of ciclosporin blood levels should be continued following

conversion as the clearance of ciclosporin might be affected.

Target whole blood trough concentration recommendations

Dosing should primarily be based on clinical assessments of rejection and tolerability in each

individual patient.

optimise

dosing,

several

immunoassays

available

determining

tacrolimus

concentrations

whole

blood

including

semi-automated

microparticle

enzyme

immunoassay

(MEIA). Comparisons of concentrations from the published literature to individual values in clinical

practice should be assessed with care and knowledge of the assay methods employed. In current

clinical practice, whole blood levels are monitored using immunoassay methods.

Blood trough levels of tacrolimus should be monitored during the post-transplantation period. When

dosed orally, blood trough levels should be drawn approximately 12 hours post-dosing, just prior to

the next dose. The frequency of blood level monitoring should be based on clinical needs. As Prograf

is a medicinal product with low clearance, adjustments to the dosage regimen may take several days

before changes in blood levels are apparent. Blood trough levels should be monitored approximately

twice weekly during the early post-transplant period and then periodically during maintenance

therapy. Blood trough levels of tacrolimus should also be monitored following dose adjustment,

changes in the immunosuppressive regimen, or following co-administration of substances which may

alter tacrolimus whole blood concentrations (see section 4.5).

Clinical study analysis suggests that the majority of patients can be successfully managed if tacrolimus

blood trough levels are maintained below 20 ng/ml. It is necessary to consider the clinical condition of

the patient when interpreting whole blood levels.

In clinical practice, whole blood trough levels have generally been in the range 5 - 20 ng/ml in liver

transplant recipients and 10 - 20 ng/ml in kidney and heart transplant patients in the early post-

transplant period. Subsequently, during maintenance therapy, blood concentrations have generally

been in the range of 5 - 15 ng/ml in liver, kidney and heart transplant recipients.

Method of administration

It is recommended that the oral daily dose be administered in two divided doses (e.g. morning and

evening). Capsules should be taken immediately following removal from the blister. Patients should

be advised not to swallow the desiccant.

The capsules should be swallowed with fluid (preferably water).

Capsules should generally be administered on an empty stomach or at least 1 hour before or

2 to 3 hours after a meal, to achieve maximal absorption (see section 5.2).

Prograf Capsules MF 11/2019 Notification

Duration of dosing

To suppress graft rejection, immunosuppression must be maintained; consequently, no limit to the

duration of oral therapy can be given.

4.3

Contraindications

Hypersensitivity to tacrolimus or other macrolides.

Hypersensitivity to any of the excipients listed in section 6.1.

4.4

Special warnings and precautions for use

Medication errors, including inadvertent, unintentional or unsupervised substitution of immediate- or

prolonged-release tacrolimus formulations, have been observed. This has led to serious adverse events,

including graft rejection, or other side effects which could be a consequence of either under- or over-

exposure to tacrolimus. Patients should be maintained on a single formulation of tacrolimus with the

corresponding daily dosing regimen; alterations in formulation or regimen should only take place

under the close supervision of a transplant specialist (see sections 4.2 and 4.8).

During the initial post-transplant period, monitoring of the following parameters should be undertaken

on a routine basis: blood pressure, ECG, neurological and visual status, fasting blood glucose levels,

electrolytes

(particularly

potassium),

liver

renal

function

tests,

haematology

parameters,

coagulation

values,

plasma

protein

determinations.

clinically

relevant

changes

seen,

adjustments of the immunosuppressive regimen should be considered.

Substances with potential for interaction

When substances with a potential for interaction (see section 4.5) - particularly strong inhibitors of

CYP3A4

(such

telaprevir,

boceprevir,

ritonavir,

ketoconazole,

voriconazole,

itraconazole,

telithromycin or clarithromycin) or inducers of CYP3A4 (such as rifampicin, rifabutin) – are being

combined with tacrolimus, tacrolimus blood levels should be monitored to adjust the tacrolimus dose

as appropriate in order to maintain similar tacrolimus exposure.

Herbal preparations containing St. John’s wort (Hypericum perforatum) or other herbal preparations

should be avoided when taking Prograf due to the risk of interactions that lead to either a decrease in

blood concentrations of tacrolimus and reduced clinical effect of tacrolimus, or an increase in blood

concentrations of tacrolimus and risk of tacrolimus toxicity (see section 4.5).

The combined administration of ciclosporin and tacrolimus should be avoided and care should be

taken when administering tacrolimus to patients who have previously received ciclosporin (see

sections 4.2 and 4.5).

High potassium intake or potassium-sparing diuretics should be avoided (see section 4.5).

Certain combinations of tacrolimus with drugs known to have nephrotoxic or neurotoxic effects may

increase the risk of these effects (see section 4.5).

Vaccination

Immunosuppressants may affect the response to vaccination and vaccination during treatment with

tacrolimus may be less effective. The use of live attenuated vaccines should be avoided.

Gastrointestinal disorders

Gastrointestinal perforation has been reported in patients treated with tacrolimus. As gastrointestinal

perforation is a medically important event that may lead to a life-threatening or serious condition,

adequate treatments should be considered immediately after suspected symptoms or signs occur.

Since

levels

tacrolimus

blood

significantly

change

during

diarrhoea

episodes,

extra

monitoring of tacrolimus concentrations is recommended during episodes of diarrhoea.

Prograf Capsules MF 11/2019 Notification

Cardiac disorders

Ventricular hypertrophy or hypertrophy of the septum, reported as cardiomyopathies, have been

observed on rare occasions. Most cases have been reversible, occurring primarily in children with

tacrolimus blood trough concentrations much higher than the recommended maximum levels. Other

factors observed to increase the risk of these clinical conditions included pre-existing heart disease,

corticosteroid

usage,

hypertension,

renal

hepatic

dysfunction,

infections,

fluid

overload,

oedema. Accordingly, high-risk patients, particularly young children and those receiving substantial

immunosuppression should be monitored, using such procedures as echocardiography or ECG pre-

and post-transplant (e.g. initially at three months and then at 9-12 months).

If abnormalities develop, dose reduction of Prograf therapy, or change of treatment to another

immunosuppressive agent should be considered. Tacrolimus may prolong the QT interval and may

cause

Torsades

de

Pointes

Caution

should

exercised

patients

with

risk

factors

prolongation, including patients with a personal or family history of QT prolongation, congestive heart

failure, bradyarrhythmias and electrolyte abnormalities. Caution should also be exercised in patients

diagnosed or suspected to have Congenital Long QT Syndrome or acquired QT prolongation or

patients

concomitant

medications

known

prolong

interval,

induce

electrolyte

abnormalities or known to increase tacrolimus exposure (see section 4.5).

Lymphoproliferative disorders and malignancies

Patients treated with Prograf have been reported to develop Epstein-Barr virus (EBV)-associated

lymphoproliferative disorders (see section 4.8). Patients switched to Prograf therapy should not

receive

anti-lymphocyte

treatment

concomitantly.

Very

young

(< 2 years),

EBV-VCA-negative

children have been reported to have an increased risk of developing lymphoproliferative disorders.

Therefore, in this patient group, EBV-VCA serology should be ascertained before starting treatment

with Prograf. During treatment, careful monitoring with EBV-PCR is recommended. Positive EBV-

PCR may persist for months and is per se not indicative of lymphoproliferative disease or lymphoma.

As with other immunosuppressive agents, owing to the potential risk of malignant skin changes,

exposure to sunlight and UV light should be limited by wearing protective clothing and using a

sunscreen with a high protection factor.

As with other potent immunosuppressive compounds, the risk of secondary cancer is unknown (see

section 4.8).

Posterior reversible encephalopathy syndrome (PRES)

Patients treated with tacrolimus have been reported to develop posterior reversible encephalopathy

syndrome (PRES). If patients taking tacrolimus present with symptoms indicating PRES such as

headache, altered mental status, seizures, and visual disturbances, a radiological procedure (e.g. MRI)

should

performed.

PRES

diagnosed,

adequate

blood

pressure

control

immediate

discontinuation of systemic tacrolimus is advised. Most patients completely recover after appropriate

measures are taken.

Eye disorders

Eye disorders, sometimes progressing to loss of vision, have been reported in patients treated with

tacrolimus. Some cases have reported resolution on switching to alternative immunosuppression.

Patients should be advised to report changes in visual acuity, changes in colour vision, blurred vision,

or visual field defect, and in such cases, prompt evaluation is recommended with referral to an

ophthalmologist as appropriate.

Infections including opportunistic infections

Patients treated with immunosuppressants, including Prograf are at increased risk for infections

including opportunistic infections (bacterial, fungal, viral and protozoal) such as BK virus associated

nephropathy and JC virus associated progressive multifocal leukoencephalopathy (PML). Patients are

also at an increased risk of infections with viral hepatitis (for example, hepatitis B and C reactivation

and de novo infection, as well as hepatitis E, which may become chronic).These infections are often

Prograf Capsules MF 11/2019 Notification

related to a high total immunosuppressive burden and may lead to serious or fatal conditions that

physicians

should

consider

differential

diagnosis

immunosuppressed

patients

with

deteriorating hepatic or renal function or neurological symptoms.

Prevention and management should be in accordance with appropriate clinical guidance.

Pure Red Cell Aplasia

Cases of pure red cell aplasia (PRCA) have been reported in patients treated with tacrolimus. All

patients reported risk factors for PRCA such as parvovirus B19 infection, underlying disease or

concomitant medications associated with PRCA.

Excipients

As Prograf capsules contain lactose, special care should be taken in patients with rare hereditary

problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.

The printing ink used to mark Prograf capsules 0.5 mg and 1 mg contains soya lecithin. In patients

who are hypersensitive to peanut or soya, the risk and severity of hypersensitivity should be weighed

against the benefit of using Prograf.

This medicine contains less than 1 mmol sodium (23 mg) per capsule, that is to say essentially

‘sodium-free’.

4.5

Interaction with other medicinal products and other forms of interaction

Metabolic interactions

Systemically available tacrolimus is metabolised by hepatic CYP3A4. There is also evidence of

gastrointestinal metabolism by CYP3A4 in the intestinal wall. Concomitant use of medicinal products

or herbal remedies known to inhibit or induce CYP3A4 may affect the metabolism of tacrolimus and

thereby increase or decrease tacrolimus blood levels.

It is therefore strongly recommended to closely monitor tacrolimus blood levels, as well as, QT

prolongation (with ECG), renal function and other side effects, whenever substances which have the

potential to alter CYP3A4 metabolism are used concomitantly and to interrupt or adjust the tacrolimus

dose as appropriate in order to maintain similar tacrolimus exposure (see sections 4.2 and 4.4).

Inhibitors of metabolism

Clinically the following substances have been shown to increase tacrolimus blood levels:

Strong interactions have been observed with antifungal agents such as ketoconazole, fluconazole,

itraconazole, voriconazole and isavuconazole, the macrolide antibiotic erythromycin, HIV protease

inhibitors (e.g. ritonavir, nelfinavir, saquinavir), HCV protease inhibitors (e.g. telaprevir, boceprevir,

and the combination of ombitasvir and paritaprevir with ritonavir, when used with and without

dasabuvir), or the CMV antiviral letermovir, the pharmacokinetic enhancer cobicistat, and the tyrosine

kinase inhibitors nilotinib and imatinib. Concomitant use of these substances may require decreased

tacrolimus doses in nearly all patients.

Weaker interactions have been observed with clotrimazole, clarithromycin, josamycin, nifedipine,

nicardipine, diltiazem, verapamil, amiodarone, danazol, ethinylestradiol, omeprazole, nefazodone and

(Chinese) herbal remedies containing extracts of

Schisandra sphenanthera

In vitro

the following substances have been shown to be potential inhibitors of tacrolimus metabolism:

bromocriptine,

cortisone,

dapsone,

ergotamine,

gestodene,

lidocaine,

mephenytoin,

miconazole,

midazolam, nilvadipine, norethisterone, quinidine, tamoxifen, troleandomycin.

Grapefruit juice has been reported to increase the blood level of tacrolimus and should therefore be

avoided.

Lansoprazole and ciclosporin may potentially inhibit CYP3A4-mediated metabolism of tacrolimus and

thereby increase tacrolimus whole blood concentrations.

Prograf Capsules MF 11/2019 Notification

Other interactions potentially leading to increased tacrolimus blood levels

Tacrolimus is extensively bound to plasma proteins. Possible interactions with other medicinal

products known to have high affinity for plasma proteins should be considered (e.g., NSAIDs, oral

anticoagulants, or oral antidiabetics).

Other potential interactions that may increase systemic exposure of tacrolimus include the prokinetic agent

metoclopramide, cimetidine and magnesium-aluminium-hydroxide.

Inducers of metabolism

Clinically the following substances have been shown to decrease tacrolimus blood levels:

Strong interactions have been observed with rifampicin, phenytoin or St. John’s Wort

(Hypericum

perforatum)

which may require increased tacrolimus doses in almost all patients. Clinically significant

interactions have also been observed with phenobarbital. Maintenance doses of corticosteroids have

been shown to reduce tacrolimus blood levels.

High dose prednisolone or methylprednisolone administered for the treatment of acute rejection have

the potential to increase or decrease tacrolimus blood levels.

Carbamazepine, metamizole and isoniazid have the potential to decrease tacrolimus concentrations.

Effect of tacrolimus on the metabolism of other medicinal products

Tacrolimus is a known CYP3A4 inhibitor; thus concomitant use of tacrolimus with medicinal products

known to be metabolised by CYP3A4 may affect the metabolism of such medicinal products.

The half-life of ciclosporin is prolonged when tacrolimus is given concomitantly. In addition,

synergistic/additive nephrotoxic effects can occur. For these reasons, the combined administration of

ciclosporin

tacrolimus

recommended

care

should

taken

when

administering

tacrolimus to patients who have previously received ciclosporin (see sections 4.2 and 4.4).

Tacrolimus has been shown to increase the blood level of phenytoin.

As tacrolimus may reduce the clearance of steroid-based contraceptives leading to increased hormone

exposure, particular care should be exercised when deciding upon contraceptive measures.

Limited knowledge of interactions between tacrolimus and statins is available. Available data suggests

that the pharmacokinetics of statins are largely unaltered by the co-administration of tacrolimus.

Animal data have shown that tacrolimus could potentially decrease the clearance and increase the half-

life of pentobarbital and phenazone.

Mycophenolic

acid.

Caution

should

exercised

when

switching

combination

therapy

from

ciclosporin, which interferes with enterohepatic recirculation of mycophenolic acid, to tacrolimus,

which is devoid of this effect, as this might result in changes of mycophenolic acid exposure. Drugs

which interfere with mycophenolic acid's enterohepatic cycle have potential to reduce the plasma level

and efficacy of mycophenolic acid. Therapeutic drug monitoring of mycophenolic acid may be

appropriate when switching from ciclosporin to tacrolimus or vice versa.

Other interactions which have led to clinically detrimental effects

Concurrent use of tacrolimus with medicinal products known to have nephrotoxic or neurotoxic

effects

increase

these

effects

(e.g.,

aminoglycosides,

gyrase

inhibitors,

vancomycin,

sulfamethoxazole + trimethoprim, NSAIDs, ganciclovir or aciclovir).

Enhanced nephrotoxicity has been observed following the administration of amphotericin B and

ibuprofen in conjunction with tacrolimus.

tacrolimus

treatment

associated

with

hyperkalaemia,

increase

pre-existing

hyperkalaemia, high potassium intake, or potassium-sparing diuretics (e.g., amiloride, triamterene, or

spironolactone) should be avoided (see section 4.4).

Prograf Capsules MF 11/2019 Notification

Immunosuppressants may affect the response to vaccination and vaccination during treatment with

tacrolimus may be less effective. The use of live attenuated vaccines should be avoided (see section

4.4).

4.6

Fertility, pregnancy and lactation

Pregnancy

Human data show that tacrolimus is able to cross the placenta. Limited data from organ transplant

recipients show no evidence of an increased risk of adverse effects on the course and outcome of

pregnancy under tacrolimus treatment compared with other immunosuppressive medicinal products.

However,

cases

spontaneous

abortion

have

been

reported.

date,

other

relevant

epidemiological data are available. Due to the need of treatment, tacrolimus can be considered in

pregnant women when there is no safer alternative and when the perceived benefit justifies the

potential risk to the foetus. In case of

in utero

exposure, monitoring of the newborn for the potential

adverse effects of tacrolimus is recommended (in particular the effects on the kidneys). There is a risk

for premature delivery (<37 week) as well as for hyperkalaemia in the newborn, which, however,

normalizes spontaneously.

In rats and rabbits, tacrolimus caused embryofoetal toxicity at doses which demonstrated maternal

toxicity (see section 5.3).

Breast-feeding

Human data demonstrate that tacrolimus is excreted into breast milk. As detrimental effects on the

newborn cannot be excluded, women should not breast-feed whilst receiving Prograf.

Fertility

A negative effect of tacrolimus on male fertility in the form of reduced sperm counts and motility was

observed in rats (see section 5.3).

4.7

Effects on ability to drive and use machines

Tacrolimus may cause visual and neurological disturbances. This effect may be enhanced if Prograf is

administered in association with alcohol.

4.8

Undesirable effects

The adverse drug reaction profile associated with immunosuppressive agents is often difficult to

establish owing to the underlying disease and the concurrent use of multiple medications.

Many of the adverse drug reactions stated below are reversible and/or respond to dose reduction. Oral

administration appears to be associated with a lower incidence of adverse drug reactions compared

with intravenous use. Adverse drug reactions are listed below in descending order by frequency of

occurrence: very common (

1/10); common (

1/100, <1/10); uncommon (

1/1,000, <1/100); rare

1/10,000, <1/1,000); very rare (<1/10,000); not known (cannot be estimated from the available

data).

Infections and infestations

As is well known for other potent immunosuppressive agents, patients receiving tacrolimus are

frequently at increased risk for infections (viral, bacterial, fungal, protozoal). The course of pre-

existing infections may be aggravated. Both generalised and localised infections can occur.

Cases of BK virus associated nephropathy, as well as cases of JC virus associated progressive

multifocal leukoencephalopathy (PML), have been reported in patients treated with

immunosuppressants, including Prograf.

Prograf Capsules MF 11/2019 Notification

Neoplasms benign, malignant and unspecified (incl. cysts and polyps)

Patients receiving immunosuppressive therapy are at increased risk of developing malignancies.

Benign as well as malignant neoplasms including EBV-associated lymphoproliferative disorders and

skin malignancies have been reported in association with tacrolimus treatment.

Blood and lymphatic system disorders

common:

anaemia, leukopenia, thrombocytopenia, leukocytosis, red blood cell analyses

abnormal

uncommon:

coagulopathies, coagulation and bleeding analyses abnormal, pancytopenia,

neutropenia

rare:

thrombotic thrombocytopenic purpura, hypoprothrombinaemia, thrombotic

microangiopathy

not known:

pure red cell aplasia, agranulocytosis, haemolytic anaemia

Immune system disorders

Allergic and anaphylactoid reactions have been observed in patients receiving tacrolimus (see section

4.4).

Endocrine disorders

rare:

hirsutism

Metabolism and nutrition disorders

very common:

hyperglycaemic conditions, diabetes mellitus, hyperkalaemia

common:

hypomagnesaemia, hypophosphataemia, hypokalaemia, hypocalcaemia,

hyponatraemia, fluid overload, hyperuricaemia, appetite decreased, metabolic

acidoses, hyperlipidaemia, hypercholesterolaemia, hypertriglyceridaemia, other

electrolyte abnormalities

uncommon:

dehydration, hypoproteinaemia, hyperphosphataemia, hypoglycaemia

Psychiatric disorders

very common:

insomnia

common:

anxiety symptoms, confusion and disorientation, depression, depressed mood, mood

disorders and disturbances, nightmare, hallucination, mental disorders

uncommon:

psychotic disorder

Nervous system disorders

very common:

tremor, headache

common:

seizures, disturbances in consciousness, paraesthesias and dysaesthesias, peripheral

neuropathies, dizziness, writing impaired, nervous system disorders

uncommon:

coma, central nervous system haemorrhages and cerebrovascular accidents, paralysis

and paresis, encephalopathy, speech and language abnormalities, amnesia

rare:

hypertonia

very rare:

myasthenia

Eye disorders

common:

vision blurred, photophobia, eye disorders

uncommon:

cataract

rare:

blindness

not known:

optic neuropathy

Ear and labyrinth disorders

common:

tinnitus

uncommon:

hypoacusis

Prograf Capsules MF 11/2019 Notification

rare:

deafness neurosensory

very rare:

hearing impaired

Cardiac disorders

common:

ischaemic coronary artery disorders, tachycardia

uncommon:

ventricular

arrhythmias

cardiac

arrest,

heart

failures,

cardiomyopathies,

ventricular hypertrophy, supraventricular arrhythmias, palpitations

rare:

pericardial effusion

very rare:

Torsades de Pointes

Vascular disorders

very common: hypertension

common:

haemorrhage, thrombembolic and ischaemic events, peripheral vascular disorders,

vascular hypotensive disorders

uncommon:

infarction, venous thrombosis deep limb, shock

Respiratory, thoracic and mediastinal disorders

common:

dyspnoea, parenchymal lung disorders, pleural effusion, pharyngitis, cough, nasal

congestion and inflammations

uncommon:

respiratory failures, respiratory tract disorders, asthma

rare:

acute respiratory distress syndrome

Gastrointestinal disorders

very common:

diarrhoea, nausea

common:

gastrointestinal inflammatory conditions, gastrointestinal ulceration and perforation,

gastrointestinal

haemorrhages,

stomatitis

ulceration,

ascites,

vomiting,

gastrointestinal and abdominal pains, dyspeptic signs and symptoms, constipation,

flatulence, bloating and distension, loose stools, gastrointestinal signs and symptoms

uncommon:

ileus

paralytic,

acute

chronic

pancreatitis,

gastrooesophageal

reflux

disease,

impaired gastric emptying

rare:

subileus, pancreatic pseudocyst

Hepatobiliary disorders

common:

cholestasis and jaundice, hepatocellular damage and hepatitis, cholangitis

rare:

hepatitic artery thrombosis, venoocclusive liver disease

very rare:

hepatic failure, bile duct stenosis

Skin and subcutaneous tissue disorders

common:

pruritus, rash, alopecias, acne, sweating increased

uncommon:

dermatitis, photosensitivity

rare:

toxic epidermal necrolysis (Lyell’s syndrome)

very rare:

Stevens Johnson syndrome

Musculoskeletal and connective tissue disorders

common:

arthralgia, muscle spasms, pain in extremity, back pain

uncommon:

joint disorders

rare:

mobility decreased

Renal and urinary disorders

very common:

renal impairment

common:

renal failure, renal failure acute, oliguria, renal tubular necrosis, nephropathy toxic,

urinary abnormalities, bladder and urethral symptoms

uncommon:

anuria, haemolytic uraemic syndrome

very rare:

nephropathy, cystitis haemorrhagic

Prograf Capsules MF 11/2019 Notification

Reproductive system and breast disorders

uncommon:

dysmenorrhoea and uterine bleeding

General disorders and administration site conditions

common:

asthenic conditions, febrile disorders, oedema, pain and discomfort, body temperature

perception disturbed

uncommon:

multi-organ failure, influenza like illness, temperature intolerance, chest pressure

sensation, feeling jittery, feeling abnormal

rare:

thirst, fall, chest tightness, ulcer

very rare:

fat tissue increased

not known:

febrile neutropenia

Investigations

common:

hepatic enzymes and function abnormalities, blood alkaline phosphatase increased,

weight increased

uncommon:

amylase increased, ECG investigations abnormal, heart rate and pulse investigations

abnormal, weight decreased, blood lactate dehydrogenase increased

very rare:

echocardiogram abnormal, electrocardiogram QT prolonged

Injury, poisoning and procedural complications

common:

primary graft dysfunction

Medication errors, including inadvertent, unintentional or unsupervised substitution of immediate- or

prolonged-release tacrolimus formulations, have been observed. A number of associated cases of

transplant rejection have been reported (frequency cannot be estimated from available data).

Description of selected adverse reactions

Pain in extremity has been described in a number of published case reports as part of Calcineurin-

Inhibitor Induced Pain Syndrome (CIPS). This typically presents as a bilateral and symmetrical,

severe, ascending pain in the lower extremities and may be associated with supra-therapeutic levels of

tacrolimus. The syndrome may respond to tacrolimus dose reduction. In some cases, it was necessary

to switch to alternative immunosuppression.

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:

https://sideeffects.health.gov.il

4.9

Overdose

Experience with overdosage is limited. Several cases of accidental overdosage have been reported;

symptoms have included tremor, headache, nausea and vomiting, infections, urticaria, lethargy,

increased blood urea nitrogen and elevated serum creatinine concentrations, and increase in alanine

aminotransferase levels.

No specific antidote to Prograf therapy is available. If overdosage occurs, general supportive measures

and symptomatic treatment should be conducted.

Based on its high molecular weight, poor aqueous solubility, and extensive erythrocyte and plasma

protein binding, it is anticipated that tacrolimus will not be dialysable. In isolated patients with very

high

plasma

levels,

haemofiltration

-diafiltration

have

been

effective

reducing

toxic

concentrations. In cases of oral intoxication, gastric lavage and/or the use of adsorbents (such as

activated charcoal) may be helpful, if used shortly after intake.

Prograf Capsules MF 11/2019 Notification

5.

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties

Pharmacotherapeutic group: Immunosuppressants, calcineurin inhibitors, ATC code: L04AD02.

Mechanism of action and pharmacodynamic effects

At the molecular level, the effects of tacrolimus appear to be mediated by binding to a cytosolic

protein (FKBP12) which is responsible for the intracellular accumulation of the compound. The

FKBP12-tacrolimus complex specifically and competitively binds to and inhibits calcineurin, leading

calcium-dependent

inhibition

T-cell

signal

transduction

pathways,

thereby

preventing

transcription of a discrete set of lymphokine genes.

Tacrolimus is a highly potent immunosuppressive agent and has proven activity in both

in vitro

in

vivo

experiments.

In particular, tacrolimus inhibits the formation of cytotoxic lymphocytes, which are mainly responsible

graft

rejection.

Tacrolimus

suppresses

T-cell

activation

T-helper-cell

dependent

B-cell

proliferation, as well as the formation of lymphokines (such as interleukins-2, -3, and γ-interferon) and

the expression of the interleukin-2 receptor.

Results from published data in other primary organ transplantation

Prograf has evolved into an accepted treatment as primary immunosuppressive medicinal product

following pancreas, lung and intestinal transplantation. In prospective published studies tacrolimus

investigated

primary

immunosuppressant

approximately 175

patients

following

lung,

475 patients following pancreas and 630 patients following intestinal transplantation. Overall, the

safety profile of tacrolimus in these published studies appeared to be similar to what was reported in

large

studies,

where

tacrolimus

used

primary

treatment

liver,

kidney

heart

transplantation. Efficacy results of the largest studies in each indication are summarised below.

Lung transplantation

interim

analysis

recent

multicentre

study

discussed

patients

underwent

1:1 randomisation

either

tacrolimus

ciclosporin.

Tacrolimus

started

continuous

intravenous infusion at a dose of 0.01 to 0.03 mg/kg/day and oral tacrolimus was administered at a

dose of 0.05 to 0.3 mg/kg/day. A lower incidence of acute rejection episodes for tacrolimus- versus

ciclosporin-treated patients (11.5% versus 22.6%) and a lower incidence of chronic rejection, the

bronchiolitis obliterans syndrome (2.86% versus 8.57%), was reported within the first year after

transplantation. The 1-year patient survival rate was 80.8% in the tacrolimus and 83% in the

ciclosporin group (Treede et al., 3

ICI San Diego, US, 2004;Abstract 22).

Another randomised study included 66 patients on tacrolimus versus 67 patients on ciclosporin.

Tacrolimus was started as continuous intravenous infusion at a dose of 0.025 mg/kg/day and oral

tacrolimus was administered at a dose of 0.15 mg/kg/day with subsequent dose adjustments to target

trough levels of 10 to 20 ng/ml. The 1-year patient survival was 83% in the tacrolimus and 71% in the

ciclosporin group, the 2-year survival rates were 76% and 66%, respectively. Acute rejection episodes

per 100 patient-days were numerically fewer in the tacrolimus (0.85 episodes) than in the ciclosporin

group (1.09 episodes). Obliterative bronchiolitis developed in 21.7% of patients in the tacrolimus

group compared with 38.0% of patients in the ciclosporin group (p = 0.025). Significantly more

ciclosporin-treated patients (n = 13) required a switch to tacrolimus than tacrolimus-treated patients to

ciclosporin (n = 2) (p = 0.02) (Keenan et al., Ann Thoracic Surg 1995;60:580).

In an additional two-centre study, 26 patients were randomised to the tacrolimus versus 24 patients to

the ciclosporin group. Tacrolimus was started as continuous intravenous infusion at a dose of

0.05 mg/kg/day

oral

tacrolimus

administered

dose

0.1 to

mg/kg/day

with

subsequent dose adjustments to target trough levels of 12 to 15 ng/ml. The 1-year survival rates were

73.1% in the tacrolimus versus 79.2% in the ciclosporin group. Freedom from acute rejection was

higher

tacrolimus

group

months

(57.7%

versus

45.8%)

1 year

after

lung

transplantation (50% versus 33.3%) (Treede et al., J Heart Lung Transplant 2001;20:511).

Prograf Capsules MF 11/2019 Notification

three

studies

demonstrated

similar

survival

rates.

incidences

acute

rejection

were

numerically lower with tacrolimus in all three studies and one of the studies reported a significantly

lower incidence of bronchiolitis obliterans syndrome with tacrolimus.

Pancreas transplantation

A multicentre study included 205 patients undergoing simultaneous pancreas-kidney transplantation

who were randomised to tacrolimus (n=103) or to ciclosporin (n=102). The initial oral per protocol

dose of tacrolimus was 0.2 mg/kg/day with subsequent dose adjustments to target trough levels of 8 to

15 ng/ml by Day 5 and 5 to 10 ng/mL after Month 6. Pancreas survival at 1 year was significantly

superior with tacrolimus: 91.3% versus 74.5% with ciclosporin (p < 0.0005), whereas renal graft

survival was similar in both groups. In total 34 patients switched treatment from ciclosporin to

tacrolimus,

whereas

only

tacrolimus

patients

required

alternative

therapy

(Bechstein

al.,

Transplantation 2004;77:1221).

Intestinal transplantation

Published clinical experience from a single centre on the use of tacrolimus for primary treatment

following intestinal transplantation showed that the actuarial survival rate of 155 patients (65 intestine

alone, 75 liver and intestine, and 25 multivisceral) receiving tacrolimus and prednisone was 75% at

1 year, 54% at 5 years, and 42% at 10 years. In the early years the initial oral dose of tacrolimus was

0.3 mg/kg/day. Results continuously improved with increasing experience over the course of 11 years.

A variety of innovations, such as techniques for early detection of Epstein-Barr (EBV) and CMV

infections, bone marrow augmentation, the adjunct use of the interleukin-2 antagonist daclizumab,

lower initial tacrolimus doses with target trough levels of 10 to 15 ng/ml, and most recently allograft

irradiation were considered to have contributed to improved results in this indication over time (Abu-

Elmagd et al., Ann Surg 2001;234:404).

5.2

Pharmacokinetic properties

Absorption

In man tacrolimus has been shown to be able to be absorbed throughout the gastrointestinal tract.

Following oral administration of Prograf capsules peak concentrations (C

) of tacrolimus in blood

are achieved in approximately 1 - 3 hours. In some patients, tacrolimus appears to be continuously

absorbed

over

prolonged

period

yielding

relatively

flat

absorption

profile.

mean

oral

bioavailability of tacrolimus is in the range of 20% - 25%.

After oral administration (0.30 mg/kg/day) to liver transplant patients, steady-state concentrations of

Prograf were achieved within 3 days in the majority of patients.

In healthy subjects, Prograf 0.5 mg, Prograf 1 mg and Prograf 5 mg Capsules, hard have been shown

to be bioequivalent, when administered as equivalent dose.

The rate and extent of absorption of tacrolimus is greatest under fasted conditions. The presence of

food decreases both the rate and extent of absorption of tacrolimus, the effect being most pronounced

after a high-fat meal. The effect of a high-carbohydrate meal is less pronounced.

In stable liver transplant patients, the oral bioavailability of Prograf was reduced when it was

administered after a meal of moderate fat (34% of calories) content. Decreases in AUC (27%) and

(50%), and an increase in t

(173%) in whole blood were evident.

In a study of stable renal transplant patients who were administered Prograf immediately after a

standard continental breakfast the effect on oral bioavailability was less pronounced. Decreases in

AUC (2 to 12%) and C

(15 to 38%), and an increase in t

(38 to 80%) in whole blood were

evident.

Bile flow does not influence the absorption of Prograf.

A strong correlation exists between AUC and whole blood trough levels at steady-state. Monitoring of

whole blood trough levels therefore provides a good estimate of systemic exposure.

Prograf Capsules MF 11/2019 Notification

Distribution and elimination

In man, the disposition of tacrolimus after intravenous infusion may be described as biphasic.

In the systemic circulation, tacrolimus binds strongly to erythrocytes resulting in an approximate

20:1 distribution ratio of whole blood/plasma concentrations. In plasma, tacrolimus is highly bound

(> 98.8%) to plasma proteins, mainly to serum albumin and α-1-acid glycoprotein.

Tacrolimus is extensively distributed in the body. The steady-state volume of distribution based on

plasma concentrations is approximately 1300 l (healthy subjects). Corresponding data based on whole

blood averaged 47.6 l.

Tacrolimus is a low-clearance substance. In healthy subjects, the average total body clearance (TBC)

estimated from whole blood concentrations was 2.25 l/h. In adult liver, kidney and heart transplant

patients, values of 4.1 l/h, 6.7 l/h and 3.9 l/h, respectively, have been observed. Paediatric liver

transplant recipients have a TBC approximately twice that of adult liver transplant patients. Factors

such as low haematocrit and protein levels, which result in an increase in the unbound fraction of

tacrolimus, or corticosteroid-induced increased metabolism are considered to be responsible for the

higher clearance rates observed following transplantation.

The half-life of tacrolimus is long and variable. In healthy subjects, the mean half-life in whole blood

is approximately 43 hours. In adult and paediatric liver transplant patients, it averaged 11.7 hours and

12.4 hours, respectively, compared with 15.6 hours in adult kidney transplant recipients. Increased

clearance rates contribute to the shorter half-life observed in transplant recipients.

Metabolism and biotransformation

Tacrolimus is widely metabolised in the liver, primarily by the cytochrome P450-3A4. Tacrolimus is

also considerably metabolised in the intestinal wall. There are several metabolites identified. Only one

of these has been shown

in vitro

to have immunosuppressive activity similar to that of tacrolimus. The

other metabolites have only weak or no immunosuppressive activity. In systemic circulation only one

of the inactive metabolites is present at low concentrations. Therefore, metabolites do not contribute to

pharmacological activity of tacrolimus.

Excretion

Following intravenous and oral administration of

C-labelled tacrolimus, most of the radioactivity

was eliminated in the faeces. Approximately 2% of the radioactivity was eliminated in the urine. Less

than 1% of unchanged tacrolimus was detected in the urine and faeces, indicating that tacrolimus is

almost completely metabolised prior to elimination: bile being the principal route of elimination.

5.3

Preclinical safety data

The kidneys and the pancreas were the primary organs affected in toxicity studies performed in rats

and baboons. In rats, tacrolimus caused toxic effects to the nervous system and the eyes. Reversible

cardiotoxic effects were observed in rabbits following intravenous administration of tacrolimus.

When tacrolimus is administered intravenously as rapid infusion/bolus injection at a dose of 0.1 to 1.0

mg/kg, QTc prolongation has been observed in some animal species. Peak blood concentrations

achieved with these doses were above 150 ng/mL which is more than 6-fold higher than mean peak

concentrations observed with Prograf in clinical transplantation.

Embryofoetal toxicity was observed in rats and rabbits and was limited to doses that caused significant

toxicity in maternal animals. In rats, female reproductive function including birth was impaired at

toxic dosages and the offspring showed reduced birth weights, viability and growth.

A negative effect of tacrolimus on male fertility in the form of reduced sperm counts and motility was

observed in rats.

Prograf Capsules MF 11/2019 Notification

6.

PHARMACEUTICAL PARTICULARS

6.1

List of excipients

Prograf 0.5 mg capsules

Capsule content:

Lactose monohydrate

Magnesium stearate

hydroxypropyl methylcellulose

Croscarmellose sodium

Capsule shell:

Titanium dioxide (E 171)

Ferric oxide yellow (E 172)

Gelatin

Printing ink of capsule shell: Shellac glaze, lecithin (soya), simeticone, ferric oxide red (E 172),

hydroxypropyl cellulose.

Prograf 1 mg capsules

Capsule content:

Lactose monohydrate

hydroxypropyl methylcellulose

Croscarmellose sodium

Magnesium stearate

Capsule shell:

Titanium dioxide (E 171)

Gelatin

Printing ink of capsule shell: Shellac glaze, lecithin (soya), simeticone, ferric oxide red (E 172),

hydroxypropyl cellulose.

Prograf 5 mg capsules

Capsule content:

Lactose monohydrate

hydroxypropyl methylcellulose

Croscarmellose sodium

Magnesium stearate

Capsule shell:

Titanium dioxide (E 171)

Ferric oxide red (E 172)

Gelatin

Printing ink of capsule shell: Shellac, titanium dioxide (E 171), propylene glycol.

6.2

Incompatibilities

Tacrolimus is not compatible with PVC. Tubing, syringes and other equipment used to prepare or

administer a suspension of Prograf capsule contents should not contain PVC.

6.3

Shelf life

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

After opening the aluminium wrapper: 12 months.

Prograf Capsules MF 11/2019 Notification

6.4

Special precautions for storage

Store below 25

Store in the original package in order to protect from moisture.

Capsules should be taken immediately following removal from the blister.

6.5

Nature and contents of container

PVC/PVDC/Aluminium blisters. Ten capsules per blister. Five or ten blisters with a desiccant, in an

aluminium wrapper.

Prograf 0.5 mg capsules

Ten capsules per strip. Five or ten blister strips with one desiccant in one aluminium wrapper.

Pack sizes: 50 and 100 capsules in blisters.

Prograf 1 mg capsules

Ten capsules per strip. Five or ten blister strips with one desiccant in one aluminium wrapper.

Pack sizes: 50 and 100 capsules in blisters.

Prograf 5 mg capsules

Ten capsules per strip. Five blister strips with one desiccant in one aluminium wrapper.

Pack sizes: 50 and 100 capsules in blisters.

Not all pack sizes may be marketed.

6.6

Special precautions for disposal and other handling

No special requirements.

7.

LICENCE HOLDER AND MANUFACTURER

Licence Holder:

Abic Marketing Ltd. (Teva group),

P.O.Box 8077, Netanya

Manufacturer:

Astellas Ireland Co. Ltd.,

Killorglin, Ireland

8.

REGISTRATION NUMBERS

Prograf 0.5 mg capsules

122.07.30215

Prograf 1 mg capsules

107.69.29158

Prograf 5 mg capsules

107.70.29159

The format of this leaflet was determined by the Ministry of Health and its content was checked and

approved by the Ministry of Health in August 2015 and updated according to Ministry of Health

instructions in November 2019

:ךיראת לירפא

2019

ה/דבכנ ת/חקור ,ה/אפור

העידומ עבט תרבח לע

ולעב םיאבה םינוכדעה

ן

ןכרצל

ו

ןולעב :רישכתה לש אפורל

Prograf 0.5 mg/ 1 mg/ 5 mg capsules

ףרגורפ

0.5

/ג"מ

1

/ג"מ

5

תוסומכ ג"מ

Contains: Tacrolimus 0.5 mg/ 1 mg/ 5 mg

ןכרצל ןולעב םינוכדע

ו

אפורל ןולעב

------------------------------------------------------------------------------------------------------------

:םושירה תדועתב הרשואש יפכ היוותה

Prophylaxis of transplant rejection in liver kidney or heart allograft recipients.

Treatment of allograft rejection resistant to treatment with other immunosuppressive medicinal

products.

ל ןולעהש עידוהל וננוצרב אפור

ןכרצל ןולעהו כדוע ונ תופסות( דבלב םיירקיעה םינוכדעה םילולכ ןלהלש טוריפב , תונמוסמ םודאב

:)קוחמ טסקטכ עדימ תורסהו

:אפורל ןולעב םינוכדע

4.4

Special warnings and precautions for use

[...]

Eye disorders

disorders,

sometimes progressing to

loss of vision,

have

been

reported in

patients treated

with

tacrolimus. Some cases have reported resolution on switching to alternative immunosuppression. Patients

should be advised to report changes in visual acuity, changes in colour vision, blurred vision, or visual field

defect, and in such cases, prompt evaluation is recommended with referral to an ophthalmologist as

appropriate.

Infections including opportunistic infections

Patients treated with immunosuppressants, including Prograf are at increased risk for infections including

opportunistic infections (bacterial, fungal, viral and protozoal) such as BK virus associated nephropathy and

JC virus associated progressive multifocal leukoencephalopathy (PML). Patients are also at an increased risk

of infections with viral hepatitis (for example, hepatitis B and C reactivation and de novo infection, as well

hepatitis

which

become

chronic).These

infections

often

related

high

total

immunosuppressive burden and may lead to serious or fatal conditions that physicians should consider in the

differential

diagnosis

immunosuppressed

patients

with

deteriorating

hepatic

renal

function

neurological symptoms.

Prevention and management should be in accordance with appropriate clinical guidance.

Excipients

This medicine contains less than 1 mmol sodium (23 mg) per capsule, that is to say essentially ‘sodium-free’.

[...]

4.5

Interaction with other medicinal products and other forms of interaction

[...]

Inhibitors of metabolism

Clinically the following substances have been shown to increase tacrolimus blood levels:

Strong

interactions

have

been

observed

with

antifungal

agents

such

ketoconazole,

fluconazole,

itraconazole, voriconazole and isavuconazole, the macrolide antibiotic erythromycin, HIV protease inhibitors

(e.g. ritonavir, nelfinavir, saquinavir) or HCV protease inhibitors (e.g. telaprevir, boceprevir

and the

combination of ombitasvir and paritaprevir with ritonavir, when used with and without dasabuvir), the

pharmacokinetic enhancer cobicistat, and the tyrosine kinase inhibitors nilotinib and imatinib. Concomitant

use of these substances may require decreased tacrolimus doses in nearly all patients.

[...]

Mycophenolic acid. Caution should be exercised when switching combination therapy from ciclosporin,

which interferes with enterohepatic recirculation of mycophenolic acid, to tacrolimus, which is devoid of this

effect,

this

might

result

changes

mycophenolic

acid

exposure.

Drugs

which

interfere

with

mycophenolic

acid's

enterohepatic

cycle

have

potential

reduce

plasma

level

efficacy

mycophenolic acid. Therapeutic drug monitoring of mycophenolic acid may be appropriate when switching

from ciclosporin to tacrolimus or vice versa.

4.8

Undesirable effects

[...]

Blood and lymphatic system disorders

[...]

rare:

thrombotic thrombocytopenic purpura, hypoprothrombinaemia, thrombotic microangiopathy

[...]

Eye disorders

common:

vision blurred, photophobia, eye disorders

uncommon:

cataract

rare:

blindness

not known:

optic neuropathy

Description of selected adverse reactions

Pain in extremity has been described in a number of published case reports as part of Calcineurin-Inhibitor

Induced Pain Syndrome (CIPS). This typically presents as a bilateral and symmetrical, severe, ascending

pain in the lower extremities and may be associated with supra-therapeutic levels of tacrolimus. The

syndrome may respond to tacrolimus dose reduction. In some cases, it was necessary to switch to alternative

immunosuppression.

[...]

:ןכרצל ןולעב םינוכדע

2

הפורתב שומישה ינפל .

:םא הפורתב שמתשהל ןיא

רשאכ הפורתב ישמתשת לא תא

הקינמ

לכל וא סומילורקטל )יגרלא( שיגר התא מ דחא

יביכרמ

ףיעס האר( הפורתה הליכמ רשא םיפסונה

עדימ" .)"ףסונ

תכייתשמה איהשלכ תיטויביטנא הפורתל )יגרלא( שיגר התא

תצובק גוסמ תוקיטויביטנאה םידילורקמה

:ןוגכ( .)ןיצימסו'ג ,ןיצימורתירלק ,ןיצימורתירא

ןירופסולקיצ םע דחיב וז הפורתב שמתשהל ןיא

תועגונה תודחוימ תורהזא

ל

הפורתב שומיש

]...[

ךלהמב םא ידיימ ןפואב אפורל חווד :מ לבוס התא לופיטה

םייוניש ,תשטשוטמ הייאר ןוגכ הייארב תויעב לש הייארב

עבצ םי ךלש הייארה הדש םא וא םיטרפ תוארל ישוק , היהנ

.לבגומ

]...[

תויתפורת ןיב תובוגת

ו תוירטפ דגנ תופורת קיטויביטנא תו דחוימב ,

קיטויביטנא תו

םידילורקמה תצובקמ

שמשמה

םימוהיזב לופיטל ת ןוגכ נוקולפ ,לוזנוקוטק

רטיא ,לוז

לוזמירטולק ,לוזנוקירוו ,לוזנוק

לוזאנוקובאסיא

,ןיצימורתירלק ,ןיצימורתירא ו'ג

ןיצימ

.ןיציפמאפירו

זאטורפ יבכעמ

נוטיר ןוגכ(

ריב ריבאניווקאסו ריבאניפלנ ,

פורתה

תוילבטו טאטסיסיבוק הריבגמה תובלושמ

םוהיזב לופיטל םישמשמה

ישונאה ינוסיחה לשכה ףיגנ

זאטורפ יבכעמ

ריברפצוב ,ריברפלט ןוגכ( אלל וא םע ריבאנוטיר/ריברפאטיראפ/ריבסאטיבמוא בולישהו ריבובאסאד דבכ תקלד םוהיזב לופיטל םישמשמה ,)

סיטיטפה(

.)םימייוסמ ןטרס יגוסב לופיטל םישמשמה( ביניטאמיאו ביניטולינ

( תילונפוקימ הצמוח

mycophenolic acid

.לתש תייחד עונמל תנמ לע ןוסיחה תכרעמ יוכידל תשמשמה )

הפורתה לש םיביכרמהמ קלח לע בושח עדימ

מ תוחפ הליכמ וז הפורת

ןרתנ ג"מ הסומכב

.ןרתנ תלוטנ תבשחנ ךכיפלו

3

?הפורתב שמתשת דציכ .

]...[

.החכשנש הנמה לע תוצפל תנמ לע הלופכ הנמ לוטיל ןיא

לוטיל תחכש םא הכח ,ףרגורפ תסומכ האבה הנמה דעומל דע

ליגרכ ךשמה תוסומכה תליטנב

לוטיל תחכש םא דחיב תונמ יתש לוטיל ןיא ןפוא םושב ךא ;תרכזנשכ דימ הנמה תא לוטיל שי ,בוצקה ןמזב וז הפורת

מ תוחפ ורתונ םא

האבה הנמה דעומל דע תועש

האבה הנמב ליגרכ ךשמהו החכשנש הנמה לע גלד

4

יאוול תועפות .

]...[

ל דע לע עיפשהל תולולע( תוחיכש יאוול תועפות

-

1

ךותמ

10

:)םילפוטמ

בגב וא םייפגב ,םיקרפמב םיבאכ

םיילגרה תופכבו םירירש תוצווכתה ,

]...[

תוחיכש ןניאש יאוול תועפות ל דע לע עיפשהל תולולע(

-

1

ךותמ

0

10

:)םילפוטמ

הייאר שוטשט יוקיל לשב

םייניעה תושדעב

]...[

:)םייקה עדימהמ תוחיכשה תא ךירעהל ןתינ אל( העודי הניא ןתוחיכשש יאוול תועפות

)תיטפוא היתפוריונ( הייארה בצעב הגירח

]...[

ולעה אפורל םינ

ו

חלשנ ןכרצל

ו

תואירבה דרשמ לש טנרטניאה רתאבש תופורתה רגאמב םוסרפל

http://www.health.gov.il

לבקל ןתינו ,

ם

ספדומ םי

.עבט תרבחל הינפ י"ע

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