PRANDASE ® 50

:בכרה

Acarbose 50 mg or 100 mg :הליכמ הילבט לכ

:םיליעפ יתלב םירמוח

Microcrystallinecellulose,highlydispersedsilicondioxide,

magnesium stearate,maize starch .

.זאדיזוקולג אפלא םיזנאה יבכעמ:תיטיופרת הצובק

:תיאופר תוליעפ

םילוחב)ןילוסניאבהיולתהניאשתרכוס( II גוסמתרכוסבלופיטל

ידי-לעםינזואמםניאשםילוחבוא,דבלבהנוזתידי-לעםינזואמםניאש

.תרכוסב לופיטל הפה ךרד ןתמב תורחא תופורתו הנוזת

ידי-לע,החורארחאלםדבזוקולגהתומרבהיילעהתאןיטקמזאדנרפ

זוקולגהתגיפסבהטאהו,יעמבתומימחפהלשלוכיעהךילהתבוכיע

.םדה םרזל

?רישכתב שמתשהל ןיא יתמ

.הקינמ וא ןוירהב ךניה רשאכ הפורתב ישמתשת לא

.הפורתה יביכרממ דחאל תושיגר העודי םא שמתשהל ןיא

תינורכתובייכתהואתינורכתקלדמת/לבוסךניהםאשמתשהלןיא

תלחמוא) ulcerativecolitis (תיביכסיטילוק:אמגודל,יעמהלש

רימחהלםילוכירשאםיבצממת/לבוסךניהםאשמתשהלןיא.ןהורק

תפערסהלשהמרה:אמגודל,יעמבםיזגלשתורבטצהמהאצותכ

יתעשפמעקב,) Roemheld’ssyndrome (יעמהתוחפנתהמהאצותכ

שמתשהלןיא.יעמבםיביכ,יעמתומיסח,רומחיתפערסעקב,רומח

.תוילכה ידוקפתב הרומח הערפהמ ת/לבוס ךניה םא

תורומחתוערפהמת/לבוסךניהםארישכתבשמתשהלןיא

.דבכה דוקפתב

?ךלש םוי םויה ייח לע הפורתה עיפשת ךיא

תרכוסבלופיטלתורחאתופורתםעבולישבוזהפורתבשומישה

תוריהזבייחמןכלעו,)הימקילגופיה(םדברכוסתתלםורגללולע

תבייחמהתוליעפלכבותונכוסמתונוכמתלעפהב,בכרבהגיהנב

םיקחשממואםיינפואלעהביכרמםריהזהלשיםידלילרשאב.תונרע

.המודכו שיבכה תברקב

:תורהזא

ךורעלשי,וזהפורתבלופיטלםינושארהםישדוחה6-12ךלהמב

בולישבוזהפורתבשומיש.דבכימיזנארוטינלתויתפוקתםדתוקידב

םדברכוסתתלםורגללולעתרכוסבלופיטלתורחאתופורתםע

רכוסתתלשםיפירחםינימסתםיחתפתמשהרקמב.)הימקילגופיה(

דימךורצלשי,דערוא/והעזה,ריהמקפוד:ןוגכ,)הימקילגופיה(םדב

ריהמלופיטךרוצל)הנקרכוס(יתיברכוסאלו)םיבנערכוס(זוקולג

םאתומהטירפתלדמציהלשיוזהפורתבלופיטהתפוקתב.וזהעפותב

םיליכמהתונוזמוא)הנקרכוס(יתיברכוסלשהכירצ.תרכוסילוחל

ןטבבהפירחתוחונ-יאלםורגלהלולעזאדנרפבלופיטהןמזבהזרכוס

הפורתהתוליעיותוחיטב.)"יאוולתועפות"ףיעסי/האר(לושלשלו

.וחכוה אל18ליג דע םירגבתמבו םידליב שומישב

ךכ-לעעידוהלךילע,יהשלכהפורתלואוהשלכןוזמלה/שיגרךניהםא

.הפורתה תליטנ ינפל אפורל

:תויתפורת-ןיב תובוגת

לופיטהתעהזתרמגםאוא,תופסונתופורתת/לטונךניהםא

יפסותואפורםשרמאללתורכמנהתופורתללוכ,תורחאתופורתב

תוליעי-יאואםינוכיסעונמלידכלפטמהאפורלחוודלךילע,הנוזת

תוצובקהמתופורתיבגלדחוימב,תויתפורת-ןיבתובוגתמםיעבונה

תופורת,ןילוסניא,ןימרופטמ:ןוגכ(תרכוסבלופיטלתופורת:תואבה

תופורתוםחפירצומ,)בלבלופיטל(ןיסקוגיד,)האירואלינופלוסהתצובקמ

,ןימריטסלוכ,לוכיעבםיעייסמהםייטמיזנאםירישכת,יעמהמםיזגתוגפוס

.הפה ךרד ןיצימואנ

:יאוול תועפות

תולולעהבשומישהןמזב,הפורתהלשהיוצרהתוליעפלףסונב

.יאוול תועפות עיפוהל

.לוכיעה תכרעמב םיזג תורבטצה:דואמ תוחיכש יאוול תועפות

.ןטב יבאכ ,לושלש:תוחיכש יאוול תועפות

הנוזתהתרמשנשהדימבוהגרדהבהלועןתינהןונימהרשאכ,רישכתל

.ךל המאתוהש

הכיפההיילע,לוכיעתויעב,האקה,הליחב:תוחיכשאליאוולתועפות

.דבכ ימיזנאב

.תבהצ ,)םיילגרב רקיעב( םילזונ תורבטצה:תורידנ יאוול תועפות

,)הינפוטיצובמורט(םדהתויסטרפסמבהדירי:תופסוניאוולתועפות

,האלמ/תיקלחםייעמתמיסח,)תדפרס,החירפ,םדוא(תויגרלאתובוגת

תקלד,) pneumatosiscystoides intestinalis (יעמהןפודבםיזגתורבטצה

.דבכל קזנ ,גירח ידבכ דוקפת ,תוידבכ תוערפה ,)סיטיטפה( דבכה

:תדחוימ תוסחייתה תובייחמה תועפות

ךניאםארבגתהלתולולעלוכיעהתכרעמלתורושקהיאוולהתועפות

ןניאולאיאוולתועפותשהדימב.ךלהמאתוהשהנוזתלת/תייצמ

,)ךלהמאתוהשהנוזתהלעהרימשתורמל(תומצעתמףאואתופלוח

לעמתוכשמנהיאוולתועפותואתורומחיאוולתועפות.אפורלי/הנפ

.אפורל י/הנפ - )לושלש לש הרקמב דחוימב( םיימויל

וא,הזןולעבוניוצאלשיאוולתועפותה/שיגרמךניהובשהרקמלכב

.דימ אפורה םע ץעייתהל ךילע ,תיללכה ךתשגרהב יוניש לח םא

:ןונימ

.דבלב אפורה תוארוה יפל ןונימ

.תצלמומה הנמה לע רובעל ןיא

.לפטמה אפורה ידי-לע עבקיי לופיטה ךשמ

:אפורמ תרחא הארוה רדעהב לבוקמ ןונימ

-100זאדנרפלשהילבטיצחוא50זאדנרפלשתחאהילבט

.םויב םימעפ3

תועפותתיחפהלתעייסמןונימבתיתגרדההיילעםימיוסמםילוחב

דעתחאלשןונימבליחתהלשיולאםירקמב.םייעמבתורושקהיאוול

)100זאדנרפםיאצחינשדעהילבטיצחוא(50זאדנרפתוילבטיתש

םדברכוסהתומרלםאתהבהגרדהבןונימהתאהלעיאפורה.הממיב

)100זאדנרפלשתחאהילבטוא(50זאדנרפתוילבט2לשןונימלדע

.םויב םימעפ3

לשתוילבטיתשלדעןונימהתאתולעהלןתינםירידנםירקמב

.םויב םימעפ3-100זאדנרפ

יאוולתועפותתוחתפתמךלהמאתוהשהנוזתהלעהרימשףאלעםא

תוסחייתהתובייחמהתועפות"ףיעסי/האר(םייעמלתורושקהתודירטמ

.ודירוהל ןתינ ךרוצ שי םאו ,ןונימה תא תולעהל ןיא ,)"תדחוימ

אפורהידי-לעעבקנשיפכםיבוצקםינמזבוזהפורתבשמתשהלשי

דחיבהנמלוטילשי,בוצקןמזבוזהפורתלוטילתחכשםא.לפטמה

!דחיב תונמ יתש לוטיל ןיא ןפוא םושב ךא ,האבה החוראה םע

תורבטצהואןטבבאכ,םילושלשונכתיי,הלופכהנמתועטבתלטנםא

תומימחפםיליכמההייתשוןוזממענמיהלשי.לוכיעהתכרעמבםיזג

.תואבה תועשה4-6ךשמל

לופיטהתפוקתבתרכוסילוחלתמאתומההנוזתלעדיפקהלשי

.וז הפורתב

:שומישה ןפוא

הסיגנהםעוא,החוראהינפלדימהפורתהתאעולבלואסועללשי

.החוראהמ הנושארה

.שומישל ךומסב קר רטסילבהמ הילבטה תא איצוהל שי

?לופיטה תחלצהל עייסל י/לכות דציכ

.אפורה ידי-לע ץלמוהש לופיטה תא םילשהל ךילע

אללהפורתבלופיטהקיספהלןיא,ךתואירבבצמברופישלחםאםג

.אפור םע תוצעייתה

!הלערה י/ענמ

גשיהלץוחמרוגסםוקמברומשלשיתרחאהפורתלכווזהפורת

.הלערה י/ענמת ךכ ידי-לעו תוקונית וא/ו םידלי לש םדי

דימי/הנפ,הפורתהןמדליעלבתועטבםאוארתיתנמתלטנםא

.ךתיא הפורתה תזירא י/אבהו ,םילוח-תיב לש ןוימ רדחל

!אפורמ תשרופמ הארוה אללהאקהל םורגל ןיא

.קיזהלהלולעאיהת/רחאהלוחב,ךתלחמבלופיטלהמשרנוזהפורת

.ךירכמ וא ךינכש ,ךיבורקל וז הפורת י/ןתית לא

ךניהשםעפלכבהנמהותיוותהתאקודבלשי!ךשוחבתופורתלוטילןיא

.םהל ה/קוקז ךניה םא םייפקשמ ביכרהל שי .הפורת ת/לטונ

-מ הכומנה הרוטרפמטב ןסחאל שי:הנסחא

הפוקתלתורמשנתופורת,םיצלמומההנסחאה/הזיראהיאנתיפלםג

הרקמלכב!רישכתהלשהגופתהךיראתלבלםישלאנ.דבלבתלבגומ

.הפורתה תא ךל קפיסש חקורב ץעוויהל ךילע ,קפס לש

.הזירא התואב תונוש תופורת ןסחאל ןיא

:הפורתה םושיר 'סמ

125 30 30521 00:100זאדנרפ,125 29 30520 00:50זאדנרפ

.הינמרג ,ןזוקרוול ,.ג.א המרפ רייאב:ןרצי

,מ"עב לארשי רייאב:םושירה לעב

1986- ו"משתה )םירישכת( םיחקורה תונקת יפל ןכרצל ןולע

אפור םשרמב תבייח וז הפורת

הפורתב י/שמתשת םרטב ופוס דע ןולעה תא ןויעב י/ארק

תואירבה דרשמ ידי-לע עבקנ הז ןולע טמרופ

2012יאמב ודי-לע רשואו קדבנ ונכותו

100זאדנרפ ,50זאדנרפ

תוילבט

PRAN TAB PL SH 160712

Uncommonsideeffects:nausea,vomiting,digestivedisorders,

reversible elevation in liver enzymes.

Raresideeffects:accumulationoffluid (particularlyinthelegs),

jaundice.

Additionalsideeffects:reductioninthenumberofplatelets

(thrombocytopenia),allergicreactions(redness,rash,urticaria),

partial/completeintestinalobstruction,accumulationofgasesin

theintestinalwall (pneumatosiscystoidesintestinalis),hepatitis,

liver disorders,abnormal liver function,liver damage.

Effects that require special attention:

Digestivetractrelatedsideeffectsmayincreaseifyoudonotcomply

withthedietprescribedforyou.Intheeventthatthesesideeffects

donotpassoriftheyworsen(despitecomplyingwithaprescribed

diet),refertothedoctor.Severesideeffectsorsideeffectsthatpersist

formorethantwodays(especiallyinthecaseofdiarrhea)-referto

the doctor.

Intheeventthatyouexperiencesideeffectsnotmentionedinthis

leaflet,orifthereisachangeinyourgeneralhealth,consultyour

doctor immediately.

DOSAGE:

Dosage is according to doctor’s instructions only.

Do not exceed the recommended dosage.

Duration oftreatment will be determined by the attending doctor.

Recommended dosage unless otherwise prescribed by the doctor:

One Prandase50tabletoronehalfatabletofPrandase100-

3 times a day.

Insomepatientsagradualincreaseinthedosagehelpsreduce

intestinalsideeffects.Insuchcasesyoushouldstartwithadosage

ofonetotwo Prandase50tablets(oronehalfatablettotwohalves

of Prandase100)per24-hourday.Thedoctor,inaccordancewith

yourbloodsugarlevels,willincreasethedosagegraduallyupto2

Prandase 50tablets(or onePrandase 100tablet)3 times a day.

Inrarecasesthedosagecanberaiseduptotwo Prandase100tablet-

3 times a day.

Ifinspiteofkeepingthedietdesignedforyoubothersomeintestinal

sideeffectsdevelop(seesection“Effectsthatrequirespecialattention”),

the dosage should not be raised,and ifnecessary it can be lowered.

Thismedicineistobeusedatspecifiedtimesasdeterminedbythe

attendingdoctor.Ifyouhaveforgottentotakethismedicineatthe

specifiedtime,takeadosewithyournextmeal,butnevertaketwo

doses together!

Ifyoutookadoubledosebymistakeyoumayexperiencediarrhea,

abdominalpainoraccumulationofgasesinthedigestivetract.Avoid

food and drinks containing carbohydrates for the next 4-6 hours.

Besuretocomplywithadiabetes-compatibledietduringtreatment

with this medicine.

DIRECTIONS FOR USE:

Cheworswallowthemedicineimmediatelybeforethemealorwith

the first mouthful ofthe meal.

Take the tablet out ofthe blister just before use.

HOWCANYOUCONTRIBUTETOTHESUCCESSOFTHE

TREATMENT?

Completethefullcourseoftreatmentrecommendedbythedoctor.

Evenifthereisanimprovementinyourhealth,donotstoptreatment

with the medicine without consulting the doctor.

AVOID POISONING!

Thismedicine,andallothermedicines,mustbestoredinasafeplace

out ofthe reach ofchildren and/or infants,to avoid poisoning.

Ifyouhavetakenanoverdose,orifachildhasaccidentallyswallowed

themedicine,proceedimmediatelytoahospitalemergencyroomand

bring the package ofthe medicine with you.

Donotinducevomitingunlessexplicitlyinstructedtodosobya

doctor!Thismedicinehasbeenprescribedforthetreatmentofyour

ailment;inanotherpatientitmaycauseharm. Donotgivethis

medicine to your relatives,neighbors or acquaintances.

Donottakemedicinesinthedark!Checkthelabelandthedose

each timeyou take your medicine.Wear glasses ifyou need them.

STORAGE:

Store at a temperature below 25oC.

Evenifkeptintheiroriginalcontainerandstoredasrecommended,

medicinesmaybekeptforalimitedperiodonly.Pleasenotetheexpiry

dateofthemedicine!Incaseofdoubt,consultthepharmacistwho

dispensed the medicine to you.

Do not store different medications in the same package.

LICENSE NUMBERS:

Prandase 50:125 29 30520 00, Prandase 100:125 30 30521 00

MANUFACTURER:

Bayer Pharma AG,Leverkusen,Germany.

REGISTRATION HOLDER:

COMPOSITION:

Each tablet contains: Acarbose 50 mg or 100 mg

Inactiveingredients:Microcrystallinecellulose,highlydispersed

silicon dioxide,magnesium stearate,maize starch.

THERAPEUTIC GROUP:Alpha-glucosidase inhibitors.

THERAPEUTIC ACTIVITY:

ForthetreatmentoftypeIIdiabetes(non-insulindependentdiabetes)

inpatientswhosediabetesisnotcontrolledbydietaloneorbydiet

and other oral hypoglycemic medications.

Prandasereducestheincreaseinbloodglucoselevelsafterameal

byhinderingcarbohydratedigestionintheintestinesandslowingthe

absorption ofglucose into the bloodstream.

WHEN SHOULD THE PREPARATION NOT BE USED?

Do not use this medicine ifyou are pregnant or breastfeeding.

Donotusethismedicineifthereisaknownsensitivitytoanyof

its ingredients.

Donotusethismedicineifyousufferfromchronicinflammationor

chroniculcerationoftheintestines,forexample: ulcerative colitis

orCrohn’sdisease.Donotusethismedicineifyousufferfrom

conditionsthatmaybecomeworseasaresultofaccumulation

ofgasesintheintestine,forexample:elevationofthediaphragm

duetointestinalbloating(Roemheld’ssyndrome),severeinguinal

hernia,severediaphragmatichernia,intestinalobstructions,

intestinalulcers.Donotusethismedicineifyousufferfroma

severe kidney function disorder.

Donotusethismedicineifyousufferfromsevereliverfunction

disorders.

HOW WILL THIS MEDICINE AFFECT YOUR DAILY LIFE?

Useofthismedicineincombinationwithothermedicinesforthe

treatmentofdiabetesmaycauselowbloodsugarlevel(hypoglycemia);

therefore,cautionshouldbeexercisedwhenengaginginactivities

suchasdrivingacar,operatingdangerousmachineryoranyother

activityrequiringalertness.Childrenshouldbecautionedagainst

riding bicycles or playing near the road,and the like.

WARNINGS:

Duringthefirst6-12monthsoftreatmentwiththismedicineperiodic

bloodtestsshouldbeperformedtomonitorliverenzymes.Useof

thismedicineincombinationwithothermedicinesfortreatmentof

diabetesmaycausehypoglycemia.Ifyoudevelopacutesymptoms

ofhypoglycemia,e.g.:rapidpulse,sweatingand/ortrembling,take

glucose(grapesugar)immediately,andnottablesugar(canesugar),

forquicktreatmentofthiseffect.Duringtreatmentwiththismedicine

adherestrictlytoamenuappropriatefordiabetespatients.During

treatmentwith Prandaseconsumptionoftablesugar(canesugar)or

foodscontainingthissugarmayleadtoacuteabdominaldiscomfort

anddiarrhea (seesection“Sideeffects”).Thesafetyandefficacyof

useofthismedicineinchildrenandadolescentsuptotheageof18

have not been established.

Ifyouaresensitivetoanytypeoffoodormedicine,informyourdoctor

before commencing treatment with this medicine.

DRUG INTERACTIONS:

Ifyouaretakingotherdrugsconcomitantly,orifyouhavejustfinished

treatmentwithothermedicines,includingnon-prescriptionmedicines

andfoodsupplements,informtheattendingdoctor,inordertoprevent

hazardsorlackofefficacyarisingfromdruginteractions.Thisis

especiallyimportantformedicinesbelongingtothefollowinggroups:

medicinesforthetreatmentofdiabetes (e.g.:metformin,insulin,

sulfonylureas),digoxin(for treating the heart),carbon products and

intestinalgasadsorbents,enzymepreparationsthataidindigestion,

cholestyramine,oral neomycin.

SIDE EFFECTS:

Inadditiontothedesiredeffectofthemedicine,adversereactions

may occur during the course oftaking this medicine.

Very common side effects:flatulence.

Common side effects:diarrhea,abdominal pain.

Thesesideeffectsusuallydisappearwithinashorttimefollowingthe

periodofadaptationtothemedicine,whentheadministereddosageis

Prandase®50,Prandase®100

Tablets PATIENT PACKAGE INSERT IN ACCORDANCE WITH

THE PHARMACISTS’ REGULATIONS(PREPARATIONS)- 1986

The dispensing ofthis medicine requires a doctor’s prescription

Read this package insert carefully in its entirety

before using this medicine

The format ofthis leaflet was determined by the Ministry ofHealth

and its content was checked and approved by it in May 2012

Theformatofthis leafletwas determinedby theMinistry ofHealthandits

content was checkedandapprovedby itonMarch2012

1. NAMEOFTHEMEDICINALPRODUCT

PRANDASE50

PRANDASE100

2. QUALITATIVEAND QUANTITATIVECOMPOSITION

Prandase 50mg:1tablet contains 50mgacarbose.

Prandase 100mg:1 tablet contains 100mgacarbose

Forafulllist of excipients seesection 6.1 «Pharmaceutical particulars–Listof

excipients»

3. PHARMACEUTICAL FORM

Tablets fororal administration.

Tablets 50mg: Whiteto yellow-tinged round, convextablets of 7mmdiameterand

10mmradius of curvature. On oneside the tablet codeis “G”and “50”and on the

otherside “Bayer cross”.

Tablets 100mg: Whiteto yellow-tinged round, convextablets of 9mmdiameterand

15mmradius of curvature. On oneside the tablet codeis “G”,”score”and “100”and

on the other sidethe “Bayer cross”.

4. CLINICALPARTICULARS

4.1 Indications

Prandaseisrecommendedforthetreatmentofnon-insulindependent diabetes mellitus

(NIDDM)inpatientsinadequatelycontrolledondietalone,orondietandoralhypo-

glycaemicagents.

4.2 Dosage and administration

Dosage

Thedosagemustbeadjustedbythedoctortosuiteachpatient,becauseefficacyand

tolerabilityvaryfrom oneindividual to another. Treatment should begin with:

3x1 tablet 50 mgPrandase/day

or3x½ tablet 100 mgPrandase/day

(corresponds to 150 mgacarbose/day).

Insomepatients,agradualincreaseinthedosageofPrandasehashelpedtoreduce

gastrointestinal sideeffects, startingwith:

1xto 2x1 tablet 50 mgPrandase/day

(corresponds to 50 to 100 mgacarbose/day).

Thedosecanbegraduallyincreased,dependingonthebloodglucoselevel,andalso

as treatment progresses if it is nottherapeuticallyeffectiveenough, up to:

3x1 tablet 100 mgPrandase/day

(corresponds to 300 mgacarbose/day).

Theaveragedoseis150to300mgacarbose/day,dependingontherequirementsof

the individual patient.

A furtherincreasein dosageto:

3x2 tablets 100mgPrandase/day

(correspondsto 600 mgacarbose/day).

mayoccasionallybenecessary(seealso Section 4.8 "Undesirable effects").

Ifdistressingcomplaintsdevelopinspiteofstrictadherencetothediet,thedose

should not be increased further, and if necessaryshould besomewhatreduced.

Typeand duration ofadministration

Prandasetabletsareeffectiveonlyifswallowedwholewithalittleliquiddirectly

beforethe meal or if chewed with thefirst few mouthfuls of themeal.

It is notenvisaged that therewillbeanytime restriction on theuse ofPrandase.

Specialmonitoring advice

see"Special Warnings andPrecautions forUse”

Additional informationonspecialpopulations

Childrenand adolescents:

see“Special Warnings andPrecautions forUse”

Geriaticpatients

No alteration of dosageor dosingfrequencyis recommended with regard to the ageof

the patients.

Patients withHepaticimpairment:

No doseadjustment isrequired in patients with preexistingimpaired hepaticfunction.

Patients withrenal impairment:

seecontraindications.

Durationofuse:Itisnotenvisagedthattherewillbeanytimerestrictionintheuseof

Prandasetablets.

4.3 Contraindications

Hypersensitivityto acarboseand/orto inactiveconstituents.

Inflammatoryboweldisease,coloniculceration,partialintestinalobstructionorin

patients predisposed to intestinal obstruction

Chronicintestinaldisordersassociatedwithdistinctdisturbancesofdigestionand

absorption

Stateswhichmaydeteriorateasaresultofincreasedgasformationintheintestine

(e.g.Roemheld’ssyndrome,majorhernias,intestinalobstructionsandintestinal

ulcers).

Prandaseiscontraindicatedinpatientswithsevererenalimpairment(creatinine

clearance<25ml/min).

Pregnancyand breast-feeding

4.4 SpecialWarningsandPrecautionsfor Use

Asymptomaticliverenzymeelevationsmayoccurinindividualcases.Thereforeliver

enzymemonitoringshouldbeconsideredduringthefirst6to12monthsoftreatment.

InevaluablecasesthesechangeswerereversibleondiscontinuationofPrandase

therapy.

SafetyandefficacyofPrandaseinpatientsunder18yearsofagehavenotbeen

established.

4.5 Interactionwith other medicinalproductsand other formsof

interaction:

Sucrose(canesugar)andfoodscontainingsucroseoftencauseabdominaldiscomfort

orevendiarrhoeaduringtreatmentwithPrandaseasaresultofincreasedcarbohydrate

fermentation in the colon.

Prandasehas an antihyperglycaemiceffect, butdoes notitself inducehypoglycaeemia.

IfPrandaseisprescribedinadditiontodrugscontainingsulphonylureasormetformin,

orinadditiontoinsulin,afallofthebloodglucosevaluesintothehypoglycaemic

rangemaynecessitateasuitabledecreaseinthesulphonylurea,metforminorinsulin

dose.

In individual cases hypoglycaemicshock mayoccur.

Ifacutehypoglycaemiadevelopsitshouldbeborneinmindthatsucrose(canesugar)

isbrokendownintofructoseandglucosemoreslowlyduringtreatmentwithacarbose

tablets;forthisreasonsucroseisunsuitableforarapidalleviationofhypoglycaemia

and glucoseshould beinserted instead.

Inindividualcasesacarbosemayaffectdigoxinbioavailability,whichmayrequire

doseadjustment ofdigoxin.

Becausetheymaypossiblyinfluencetheactionofacarbose,simultaneous

administrationofcholestyramine,intestinaladsorbentsanddigestiveenzymeproducts

should beavoided.

TheconcomitantadministrationofPrandaseandoralneomycinmayleadtoenhanced

reductionsofpostprandialbloodglucoseandtoanincreaseinthefrequencyand

severityofgastro-intestinalside-effects.Ifthesymptomsaresevere,atemporarydose

reduction ofPrandasemaybeconsidered.

No interaction was observed with dimeticone/simeticone.

4.6 Pregnancyand Lactation

Pregnancy

Prandasetabletsshouldnotbeadministeredduringpregnancy,asnoinformationis

available on itsuse in pregnant women.

Lactation

Afteradministrationofradiolabelledacarbosetolactatingratsasmallquantityofthe

radioactivitywasfoundinthemilk.Thereareasyetnocorrespondingfindingsin

humans.However, as drug-induced effects of acarbosein milk havenot been excluded

inbabies,inprincipleitisadvisablenottoprescribePrandasetabletsduringthe

breastfeedingperiod.

4.7 Effectson abilityto drive oruse machines

No data on impaired abilityto driveand operate machineryareavailable forPrandase.

4.8 Undesirableeffects

ThefrequenciesofADRsreportedwithPrandase basedonplacebo-controlledstudies

withPrandase sortedbyCIOMSIIIcategoriesoffrequency(placebo-controlled

studiesinclinicaltrialdatabase:Prandase N=8,595;placeboN=7,278;status:10

Feb 2006)aresummarized in thetablebelow.

Withineachfrequencygrouping,undesirableeffectsarepresentedinorderof

decreasingseriousness.Frequenciesaredefinedasverycommon(≥1/10),common

(≥1/100to<1/10),uncommon(≥1/1,000to<1/100)andrare(≥1/10,000to

<1/1,000).

TheADRsidentifiedonlyduringpostmarketingsurveillance(status:31Dec2005),

and for which afrequencycould notbeestimated, arelisted under “not known”.

SystemOrgan

Class

(MedDRA) Very

Common

Common

Uncommo

n

Rare

Notknown

Blood and

Lymphatic

System

Dsorders Thrombo-

cytopenia

Immune

System

Disorders Allergic

reaction

(rash,

erythema,

exanthema,

urticaria)

Vascular

Disorders Oedema

Gastrointestina

lDisorders Flatulence

Diarrhea

Gastrointestina

land

abdominal

pains Nausea

Vomiting

Dyspepsia Subileus/

Ileus

Pneumatosis

cystoidis

intestinalis

Hepatobiliary

Disorders increasein

liver

enzymes Jaundice Hepatitis

The MedDRA preferred termis used to describe a certain reaction and its synonyms and

related conditions.ADR term representation is based on MedDRA version 11.1.

Inadditioneventsreportedasliverdisorder,hepaticfunctionabnormal,andliver

injuryhavebeenreceived especiallyfrom Japan.

Individualcasesoffulminanthepatitiswithfataloutcomehavebeenreportedin

Japan. Therelationship to Prandaseis unclear.

Iftheprescribeddiabeticdietisnotobservedtheintestinalsideeffectsmaybe

intensified.

Ifstronglydistressingsymptomsdevelopinspiteofadherencetothediabeticdiet

prescribed,thedoctormustbeconsultedandthedosetemporarilyorpermanently

reduced.

Inpatientsreceivingtherecommendeddailydoseof150to300mgAcarbose/day,

rarelyclinicallyrelevantabnormalliverfunctiontests(threetimesaboveupperlimit

ofnormalrange)wereobserved.Abnormalvaluesmaybetransientunderongoing

Acarbosetherapy(seeSpecialWarnings and Precautions for Use).

4.9 Overdosage

WhenPrandasetabletsaretakenwithdrinksand/ormealscontainingcarbohydrates

(disaccharides,oligosaccharidesorpolysaccharides),overdosagecanleadto

meteorism, flatulenceand diarrhoea.

IntheeventofPrandasetabletsbeingtakeninanoverdoseindependentlyoffood,

excessiveintestinal symptoms need not be anticipated.

Incaseofoverdosagethepatientshouldnotbegivendrinksormealscontaining

carbohydrates(disaccharides,oligosaccharidesorpolysaccharides)forthenext4to6

hours.

5.PHARMACOLOGICALPROPERTIES

5.1 Pharmacodynamic properties

ATC Code: A10BF01

Theactiveingredientofthetabletsisacarbose,apseudotetrasaccharideofmicrobial

origin.Acarbosetabletscanbeusedforthetreatmentofinsulin-dependent(IDDM)

and non-insulin-dependent (NIDDM) diabetes.

Inallspeciestestedacarboseexertsitsactivityintheintestinaltract.Theactionof

acarboseisbasedoninhibitionoftheintestinalenzymes( 

-glucosidases)involvedin

the degradation ofdisaccharides, oligosaccharides, and polysaccharides.

This leads to adose-dependent delayin thedigestion ofthesecarbohydrates.

Mostimportantly,glucosederivedfromcarbohydratesisreleasedandtakenupinto

thebloodmoreslowly.Inthiswayacarbosepostponesandreducesthepostprandial

riseinbloodglucose.Asaresultofthebalancingeffectontheuptakeofglucosefrom

theintestine,thebloodglucosefluctuationsoverthedayarereducedandthemean

blood glucosevalues decrease.

Acarboselowers abnormallyhigh concentrations of glycosylated haemoglobin.

Inaprospective,randomized,placebo-controlled,double-blindstudy(treatment

3-5years,average3,3years)with1.429subjectswithconfirmedimpairedglucose

tolerance*therelativeriskofdevelopingtype2diabeteswasreducedby25%.In

thesepatientstheincidenceofallcardiovasculareventsdecreasedsignificantlyby

49%,while theincidenceof MIwas significantlyreduced by91%.

Theseeffectswereconfirmedbyameta-analysisof 7placebo controlled trials (total of

2180patients,1248acarbose,932placebo)ofacarboseinthetreatmentoftype2

diabetes.Inthesepatientstheriskofanycardiovasculareventwasreducedby24%,

while therisk of myocardial infarction was decreased by64%.

Both changeswerestatisticallysignificant.

5.2 Pharmacokinetic properties

Absorptionand Bioavailability

Thepharmacokineticsofacarbosewasinvestigatedafteroraladministrationofthe

labeled substance(200 mg) to healthyvolunteers.

Absorption:

Sinceonaverage35%ofthetotalradioactivity(sumoftheinhibitorysubstanceand

anydegradationproducts)wasexcretedbythekidneyswithin96h,itcanbeassumed

that the degreeof absorption is as least in this range.

Thecourseofthetotalradioactivityconcentrationinplasmawentthroughtwopeaks.

Thefirstpeak,withanaverageacarbose-equivalentconcentrationof52.2

15.7µg/l

after1.1

0.3h,isinagreementwithcorrespondingdatafortheconcentrationcourse

oftheinhibitorsubstance(49.5

26.9µg/lafter2.1

1.6h).Thesecondpeakison

average586.3

282.7µg/landisreachedafter20.7

5.2h.Incontrasttothetotal

radioactivity,themaximumplasmaconcentrationsoftheinhibitorysubstanceare

lowerbyafactorof10-20.Thesecond,higherpeakafterabout14-24hisbelievedto

beduetoabsorptionofbacterialdegradationproductsfromdeeperpartsofthe

intestine.

Thebioavailabilityis1–2%only.Thisextremelylowsystemicallyavailable

percentageofinhibitorysubstanceisdesirable,becauseacarboseactsonlylocallyin

the intestine. Thus, this low Bioavailabilityhas no relevanceforthe therapeuticeffect.

Distribution:

Arelativevolumeofdistributionof0.32l/kgbodyweighthasbeencalculatedin

healthyvolunteersfromtheconcentrationcourseintheplasma(intravenousdosing,

0.4 mg/kgb.w.)

MetabolismandElimination

Theplasmaeliminationhalf-livesoftheinhibitorysubstanceare3.7

2.7hforthe

distribution phaseand 9.6

4.4 h forthe elimination phase.

Theproportionofinhibitorysubstanceexcretedintheurinewas1.7%ofthe

administered dose. 51%of theactivitywas eliminated within 96 h in thefaeces.

Preclinicalsafetydata

Acutetoxicity:

Acutetoxicitystudiesafteroralandintravenousadministrationofacarbosehavebeen

conductedinmice,ratsanddogs.Theresultsoftheacutetoxicitystudiesare

summarized in thetablebelow.

Species Sex Routeof

Administration LD

50 SIU/kg (3) Confidence

limits

forp<0.05

Mouse m (1) per os > 1000000

Mouse M i.v. > 500000

Rat M per os > 1000000

Rat M i.v. 478000 (421000-546000)

Rat f (2) i.v. 359000 (286000-423000)

Dog m and fper os > 650000

Dog m and fi.v. > 250000

(1) Male

(2) Female

(3) 65000 SIU correspond to about 1gof theproduct

(SIU =saccharaseinhibitoryunits)

Onthebasisoftheseresultsacarbosemaybedescribedasnon-toxicaftersingleoral

doses;evenafterdosesof10g/kganLD

50 couldnotbedetermined.Moreover,no

symptomsofintoxicationwereobservedinanyofthetestspeciesinthedoserange

under investigation.

Thesubstanceis also practicallynon-toxic after i.v. administration.

Subchronic toxicity:

Tolerabilitystudieshavebeenconductedinratsandindogsoverperiodsof3months.

Inratsacarbosehasbeeninvestigatedindosesof50-450mg/kgp.o.All

haematologicalandclinicochemicalparametersremainedunchangedcomparedtoa

controlgroupreceivingnoacarbose.Subsequenthisto-pathologicalinvestigations

similarlyyielded no evidenceof damageat anydose.

Dosesof50-450mg/kgp.o.havealsobeeninvestigatedindogs.Comparedtoa

controlgroupwhichreceivednoacarbose,changesduetothetestsubstancewere

demonstratedinthedevelopmentoftheanimals'bodyweight,α-amylaseactivityin

theserum,andthebloodureaconcentration.Inalldosegroupsthebodyweight

developmentwasinfluencedinthatwhenconstantquantityof350gfeed/dayhad

beengiventhemeangroupvaluesfelldistinctlyduringthefirst4weeksofthestudy.

Whenthequantityoffeedprovidedhadbeenincreasedto500g/dayinthe5 th weekof

thestudy,theanimalsremainedatthesameweightlevel.Theseweightchanges

inducedbyacarboseinquantitiesexceedingthetherapeuticdoseshouldberegarded

asanexpressionofincreasedpharmacodynamicactivityofthetestsubstancedueto

anisocaloricfeedimbalance(lossofcarbohydrates);theydonotrepresentanactual

toxiceffect.Theslightincreasesintheureaconcentrationshouldalsoberegardedas

anindirectresultofthetreatment,i.e.ofacatabolicmetabolicsituationdeveloping

withthelossinweight.Thediminishedα-amylaseactivitycanalsobeinterpretedasa

sign of increased pharmacodynamiceffect.

Chronictoxicity:

Chronicstudieshavebeenconductedinrats,dogs,andhamsters,withtreatment

durationsofrespectively24months,12months,and80weeks.Inadditiontothe

questionofdamagecausedbychronicadministration,thestudiesinratsandhamsters

werealso intended to address possiblecarcinogenic effects.

Carcinogenicity:

A numberofstudies areavailable on carcinogenicity.

Sprague-Dawleyratsreceivedupto4500ppmacarboseinfeedoveraperiodof

24-26months.Administrationofacarboseinthefeedcausedconsiderable

malnutritionintheanimals.Underthesestudyconditions,tumoursoftherenal

parenchyma(adenoma,hypernephroidcarcinoma)werefounddose-dependently

comparedtothecontrols,whiletheoveralltumourrate(inparticulartheratefor

hormonedependent tumours) decreased.

Topreventmalnutrition,insubsequentstudiestheanimalsreceivedglucose

substitution.Atadoseof4500ppmacarboseplusglucosesubstitution,thebody

weightwas10%lowerthaninthecontrolgroup.Anincreasedincidenceofrenal

tumours was notobserved.

Whenthestudywasrepeatedwithoutglucosesubstitutionovera26-monthperiod,an

increaseinbenigntumoursofLeydigcellsofthetesteswasalsoobserved.Inall

groupsreceivingglucosesubstitutiontheglucosevalueswere(sometimes

pathologically)elevated(alimentarydiabetesonadministrationoflargequantitiesof

glucose).

Onadministrationofacarboseviaastomachtubethebodyweightswerewithinthe

controlrange,andwiththisstudydesignelevatedpharmacodynamicactivitywas

avoided. Thetumour rate was normal.

Wistarratsreceived0–4500ppmacarbosefor30monthsinfeedorviaastomach

tube.Administrationofacarboseinthefeeddidnotleadtoanypronouncedweight

loss.From500ppmacarbosethecaecumwasenlarged.Theoveralltumourrate

decreased, and therewas no evidenceof an increased incidenceof tumours.

Hamstersreceived0-4000ppmacarboseinfeedover80weeks,withandwithout

glucosesubstitution.Increasedbloodglucoseconcentrationswereseeninanimalsof

the highest-dosegroup.Tumour incidences werenot elevated.

Reproduction toxicology:

Investigationsforteratogenic effects wereconducted in rats and in rabbits, usingdoses

of0,30,120,and480mg/kgp.o.inbothspecies.Intheratsthetreatmentwas

administeredfromthe6thtothe15 th dayofgestation,andintherabbitsfromthe6th

to the18thdayof gestation.

Therewasnoevidenceofteratogeniceffectsduetoacarboseineitherspeciesinthe

rangeof doses under test.

Noimpairmentoffertilitywasobservedinmaleorfemaleratsuptoadoseof

540mg/kg/day.

Administrationofupto540mg/kg/dayduringfoetaldevelopmentandlactationinrats

hadnoeffectonthebirthprocessortheyoung.Nodataareavailableontheuseof

acarboseduringpregnancyand lactation in humans.

Mutagenicity:

Accordingtoanumberofmutagenicitystudies,thereisnoevidenceofanygenotoxic

action ofacarbose.

6.PHARMACEUTICALPARTICULARS

6.1 List of excipients

Microcrystallinecellulose,highlydispersedsilicondioxide,magnesiumstearate,

maizestarch

6.2 Incompatibilities

None

6.3 Shelf-life

3 years

6.4 Specialprecautionsfor storage

Thetabletsshouldbestoredinthemanufacturer’soriginalcontainerinadryplaceat

temperatures below25

C.

6.5 Nature and contentsof container

Blisterpacks in cardboard outercontaining:

Prandase50:30 tablets,

Prandase100:30 tablets.

6.6 Instructionsfor use / handling

Atstorageconditionsupto25°Candbelow60%relativehumiditytheunpacked

tabletscanbestoredforuptotwoweeks.Athighertemperaturesand/orhigher

relativehumidity,discolorationcanoccurintabletsthatarenotinthepack.The

tabletsshouldthereforeonlyberemovedfromthefoilorbottleimmediatelypriorto

use.

MANUFACTURER

BayerScheringPharmaAG,Leverkusen,Germany

REGISTRATION HOLDER

Bayer Israel Ltd36 Hacharash St., Hod Hasharon 45244