BONAPENYA 5 Milligram Film Coated Tablet

Ireland - English - HPRA (Health Products Regulatory Authority)

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Active ingredient:
RISEDRONATE SODIUM
Available from:
Pharmathen S.A.
ATC code:
M05BA07
INN (International Name):
RISEDRONATE SODIUM
Dosage:
5 Milligram
Pharmaceutical form:
Film Coated Tablet
Prescription type:
Product subject to prescription which may be renewed (B)
Therapeutic area:
Bisphosphonates
Authorization status:
Authorised
Authorization number:
PA1368/008/001
Authorization date:
2010-11-26

Package leaflet: Information for the user

Bonapenya 5 mg film-coated tablets

Risedronate sodium

Read all of this leaflet carefully before you start

taking this medicine because it contains

important information for you.

- Keep this leaflet.You may need to read it again.

- If you have any further questions, ask your doctor or

pharmacist.

-This medicine has been prescribed for you only. Do

not pass it on to others. It may harm them, even if their

signs of illness are the same as yours.

- If you get any side effects talk to your doctor or

pharmacist or nurse.This includes any possible side

effects not listed in this leaflet. See section 4.

What is in this leaflet:

1.What Bonapenya is and what it is used for

2.What you need to know before you take Bonapenya

3. How to take Bonapenya

4. Possible side effects

5. How to store Bonapenya

6. Contents of the pack and other information

1.What Bonapenya is and what it is used for

What Bonapenya is

Bonapenya belongs to a group of non-hormonal

medicines called bisphosphonates which are used to

treat bone diseases. It works directly on your bones to

make them stronger and therefore less likely to break.

Bone is a living tissue. Old bone is constantly removed

from your skeleton and replaced with new bone.

Postmenopausal osteoporosis is a condition occurring

in women after the menopause where the bones

become weaker, more fragile and more likely to break

after a fall or strain.

Osteoporosis is more likely to occur in women who

have reached the menopause early and also in patients

treated long-term with steroids.

The spine, hip and wrist are the most likely bones to

break, although this can happen to any bone in your

body. Osteoporosis –related fractures can also cause

back pain, height loss and a curved back. Many

patients with osteoporosis have no symptoms and you

may not even have known that you had it.

What Bonapenya is used for

The treatment of osteoporosis

inpostmenopausal women

The prevention of osteoporosis

inwomen with an increased risk of osteoporosis

(including low bone mass, early menopause or a family

history of osteoporosis).

inpostmenopausal womenwho have been onhigh

doses of steroid drugs for a long time. It maintains or

increases bone mass.

2.What you need to know before you take

Bonapenya

Do not take Bonapenya

- if you are allergic to risedronate sodium or any of the

other ingredients of this medicine (listed in section 6) .

- if your doctor has told you that you have a condition

called hypocalcaemia (a low blood calcium level).

- if you may be pregnant, are pregnant or are planning

to become pregnant.

- if you are breast-feeding.

- if you have severe kidney problems.

Warnings and precautions

If you are unable to stay in an upright position (sitting

or standing) for at least 30 minutes.

If you have abnormal bone and mineral metabolism

(for example lack of vitamin D, parathyroid hormone

abnormalities, both leading to a low blood calcium

level).

If you have had problems in the past with your

oesophagus (the tube that connects your mouth with

your stomach). For instance you may have had pain or

difficulty in swallowing food or you have previously

been told that you have Barrett's oesophagus (a

condition associated with changes in the cells that line

the lower oesophagus).

If you have been told by your doctor that you have an

intolerance to some sugars (such as lactose).

If you have had or have pain, swelling or numbness of

the jaw or a“heavy jaw feeling”or loosening of a tooth.

If you are under dental treatment or will undergo

dental surgery, tell your dentist that you are being

treated with Bonapenya.

Your doctor will advise you on what to do when taking

Bonapenya if you have any of the above.

Children and adolescents

Risedronate sodium is not recommended for use in

children below 18 due to insufficient data on safety and

Other medicines and Bonapenya

Medicines containing one of the following lessen the

effect of Bonapenya if taken at the same time:

calcium

magnesium

aluminium (for example some indigestion mixtures)

iron

Take these medicines at least 30 minutes after taking

Bonapenya.

Tell your doctor or pharmacist if you are taking, have

recently taken or might take any other medicines.

Taking Bonapenya with food and drink

It is very important that you do NOT take your

Bonapenya tablet with food or drinks (other than

plain water) so that it can work properly. In particular

do not take this medicine at the same time as dairy

products (such as milk) as they contain calcium (see

section 2,“Other medicines and Bonapenya”).

Take food and drinks (other than plain water) at least 30

minutes after your Bonapenya tablet.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be

pregnant or are planning to have a baby, ask your

doctor or pharmacist for advice before taking this

medicine.

Do NOT take Bonapenya if you may be pregnant, are

pregnant or are planning to become pregnant (see

section 2“Do not take Bonapenya”). ]”).The potential

risk associated with the use of risedronate sodium

(active substance in Bonapenya) in pregnant women is

unknown.

Do NOT take Bonapenya if you are breast-feeding (see

section 2“Do not take Bonapenya”).

Driving and using machines

Bonapenya is not known to affect your ability to drive

and use machines.

Bonapenya contains lactose

If you have been told by your doctor that you have an

intolorance to some sugars, contact your doctor before

taking this medicinal product (see section 2,“Warnings

and precautions”).

3. How to take Bonapenya

Dosage

Always take this medicine exactly as your doctor has

told you. Check with your doctor or pharmacist if you

are not sure.

Usual dose

Take one Bonapenya (5 mg risedronate sodium) once a

day.

When to take your Bonapenya tablet:

IT IS BEST to take your tablet at least 30 minutes before

the first food, drink (other than plain water) or other

medicine of the day.

If in particular instance you are unable to take your

Bonapenya tablet at this time, you may take it on an

empty stomach, at the same time every day, in one of

the following ways:

EITHER:

Between meals: at least 2 hours after your last food,

drink (other than plain water) or other medicine. Do

not eat or drink (other than plain water) for 2 hours

after taking the tablet.

In the evening: at least 2 hours after your last food,

drink (other than plain water) or other medicine of the

day. Bonapenya should be taken at least 30 minutes

before going to bed.

How to take your Bonapenya tablet:

Take the tablet whilst you are in anupright position

(you may sit or stand) to avoid heartburn.

Swallowit with at least one glass (120 ml)of plain

water.

Swallow it whole. Do not suck or chew the tablet.

Donot lie down for 30 minutes aftertaking the

tablet.

Your doctor will tell you if you need calcium and

vitamin supplements, if you are not taking enough

from your diet.

If you take more Bonapenya than you should

If you or somebody else has accidentally taken more

Bonapenya tablets than prescribed, drink one fullglass

of milkandseek medical attention.

If you forget to take Bonapenya

If you have forgotten to take your table t at your regular

time, you can take it at the next possible time accord-

ing to the instruction above (i.e. before breakfast,

between meals, or in the evening).

Do not take two tablets in one day to make up for the

tablet you missed.

If you stop taking Bonapenya

If you stop treatment you may begin to lose bone mass.

Please talk to your doctor before you consider stopping

treatment.

4.Possible side effects

Like all medicines, this medicine can cause side effects,

although not everybody gets them.

Stop taking Bonapenya and contact a doctor

immediatelyif you experience any of the following:

Symptoms of a severe allergic reaction such as;

Swelling of the face, tongue or throat

Difficulties in swallowing

Hives and difficulties in breathing

Severe skin reactions that can include blistering of

the skin.

Tell your doctor promptlyif you experience the

following side effects:

Eye inflammation, usually with pain, redness and light

sensitivity.

Bone necrosis of the jaw (osteonecrosis) associated

with delayed healing and infection, often following

tooth extraction (see section 2,“Warnings and precau-

tions”).

Symptoms from oesophagus such as pain when you

swallow, difficulties in swallowing, chest pain or

new/worsened heartburn.

However in clinical studies the other side effects that

were observed were usually mild and did not cause the

patient to stop taking their tablets.

Common side effects(affects 1 to 10 users in 100):

Indigestion, feeling sick, stomach ache, stomach

cramps or discomfort, constipation, feelings of fullness,

bloating, diarrhoea.

Pain in your bones, muscles or joints. Headache.

Uncommon side effects(affects 1 to 10 users in 1,000):

Inflammation or ulcer of the oesophagus (the tube that

connects your mouth with your stomach) causing

difficulty and pain in swallowing (see also section 2,

“Warnings and precautions”), inflammation of the

stomach and duodenum (bowel draining the stomach).

Inflammation of the coloured part of the eye (iris) (red

painful eyes with a possible change in vision).

Rare side effects(affects 1 to 10 users in 10,000):

Inflammation of the tongue (red swollen, possibly

painful), narrowing of the oesophagus

(the tube that connects your mouth with your

stomach).

Abnormal liver tests have been reported.These can

only be diagnosed from a blood test.

Unusual fracture of the thigh bone particularly in

patients on long-term treatment for osteoporosis may

occur rarely. Contact your doctor if you experience

pain, weakness or discomfort in your thigh, hip or groin

as this may be an early indication of a possible fracture

of the thigh bone.

During post-marketing experience, the following have

been reported (unknown frequency);

Allergic reactions of the skin such as urticaria (hives),

skin rash, swelling of the face, lips, tongue and/or neck,

difficulty in swallowing or breathing. Servere skin

reactions including vesiculation (blistering) under the

skin; inflammation of small blood vessels, characterised

by palpable red spots on the skin (leukocytoclastic

vasculitis); a serious illness called Stevens Johnson

syndrome (SJS) with blistering of the skin, mouth, eyes

and other moist body surfaces (genitals); a severe

illness called toxic epidermal necrolysis (TEN) which

causes a red rash over many parts of the body and/or

loss of the outer layer of skin.

Hair loss. Allergic reactions (hypersensitivity). Serious

liver disorders, mainly if you are treated with other

medicinal products known to cause liver problems.

Inflammation of the eye which causes pain and

redness.

Rarely, at the beginning of treatment, a patient’s blood

calcium and phosphate levels may fall.

These changes are usually small and cause no symp-

toms.

Reporting of side effects

If you get any side effects, talk to your doctor or

pharmacist or nurse.This includes any possible side

effects not listed in this leaflet.You can also report side

effects directly via the national reporting system listed

in AppendixV. By reporting side effects you can help

provide more information on the safety of this

medicine.

5. How to store Bonapenya

Keep this medicine out of the sight and reach of

children.

This medicinal product does not require any special

Do not use this medicine after the expiry date which is

stated on the carton.The expiry date refers to the last

day of that month.

Do not throw away any medicines via wastewater or

household waste. Ask your pharmacist how to throw

away medicines you no longer use.These measures will

help to protect the environment.

6. Contents of the pack and other information

What Bonapenya contains

-The active substance is Risedronate sodium. Each

tablet contains 5 mg risedronate sodium, equivalent to

4.64 mg risedronic acid.

-The other ingredients are:

Tablet core: Starch, pregelatinised (maize); Cellulose,

microcrystalline; Crospovidone; Magnesium stearate.

Film coating: Hypromellose, Lactose monohydrate,

Titanium dioxide (E171), Macrogol 4000.

What Bonapenya looks like and contents of the

pack

Bonapenya are white round biconvex film-coated

tablets with diameter of 6.1 mm and 2.6 mm in

thickness. It is supplied in blister packs containing: 14,

28, 84, 98 tablets

Not all packsizes may be marketed.

Marketing Authorisation Holder

Pharmathen S.A.

6, Dervenakion str.

153 51 Pallini, Attiki

Greece

Manufacturer

Batch releaser

Pharmathen S.A.

6, Dervenakion str.

153 51 Pallini, Attiki

Greece

This medicinal product is authorised in the Member

States of the EEA under the following names:

DK: Karadronat 5mg Filmovertrukne tabletter

DE: Karadronat 5 mg Filmtabletten

EE: Ossinat, 5 mg õhukese polümeerikattega tabletid

IE: Bonapenya 5 mg Film-coated tablets

IS: Risedronate sodium Portfarma 5 mg filmuhúðaðar

töflur

LT: Risedronate sodium Portfarma 5 mg plėvele

dengtos tabletės

LV: Risedronate sodium Portfarma 5 mg apvalkotās

tabletes

This leaflet was last revised in {MM/YYYY}.

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Bonapenya5mgfilm-coatedtablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachfilm-coatedtabletcontains5mgrisedronatesodium(equivalentto4.64mgrisedronicacid).

Excipient:0.57mglactoseineachtablet

Forafulllistofexcipientsseesection6.1.

3PHARMACEUTICALFORM

Film-coatedtablet.

Whiteroundbiconvexfilm-coatedtabletwithdiameterof6.1mmand2.6mminthickness.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Treatmentofpostmenopausalosteoporosis,toreducetheriskofvertebralfractures.Treatmentofestablished

postmenopausalosteoporosis,toreducetheriskofhipfractures.Preventionofosteoporosisinpostmenopausalwomen

withincreasedriskofosteoporosis(seesection5.1).Tomaintainorincreasebonemassinpostmenopausalwomen

undergoinglong-term(morethan3months),systemiccorticosteroidtreatmentatdoses 7.5mg/dayprednisoneor

equivalent.

4.2Posologyandmethodofadministration

Posology

Therecommendeddailydoseinadultsisone5mgtabletorally.

Methodofadministration

TheabsorptionofRisedronateisaffectedbyfood,thustoensureadequateabsorptionpatientsshouldtakeRisedronate:

Beforebreakfast:Atleast30minutesbeforethefirstfood,othermedicinalproductordrink(otherthanplain

water)oftheday.

Intheparticularinstancethatbeforebreakfastdosingisnotpractical,Risedronatecanbetaken

betweenmealsorintheeveningatthesametimeeveryday,withstrictadherencetothefollowinginstructions,to

ensureRisedronateistakenonanemptystomach:

Betweenmeals:Risedronateshouldbetakenatleast2hoursbeforeandatleast2hoursafteranyfood,medicinal

productordrink(otherthanplainwater).

Intheevening:Risedronateshouldbetakenatleast2hoursafterthelastfood,medicinalproductordrink(other

thanplainwater)oftheday.Risedronateshouldbetakenatleast30minutesbeforegoingtobed.

Ifanoccasionaldoseismissed,Risedronatecanbetakenbeforebreakfast,betweenmeals,orin

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Thetabletsmustbeswallowedwholeandnotsuckedorchewed.Toaiddeliveryofthetablettothestomach

Risedronateistobetakenwhileinanupright(standingorsitting)positionwithaglassofplainwater(120ml).

Patientsshouldnotliedownfor30minutesaftertakingthetablet(seesection4.4).

SupplementalcalciumandvitaminDshouldbeconsideredifthedietaryintakeisinadequate.

Elderly:

Nodosageadjustmentisnecessarysincebioavailability,distributionandeliminationweresimilarinelderly(>60years

ofage)comparedtoyoungersubjects.

Renalimpairment:

Nodosageadjustmentisrequiredforthosepatientswithmildtomoderaterenalimpairment.Theuseofrisedronate

sodiumiscontraindicatedinpatientswithsevererenalimpairment(creatinineclearancelowerthan30ml/min)(see

sections4.3and5.2).

Paediatricpopulation:

Risedronatesodiumisnotrecommendedforuseinchildrenbelow18yearsofageduetoinsufficientdataonitssafety

andefficacy(alsoseesection5.1).

Theoptimaldurationofbisphosphonatetreatmentforosteoporosishasnotbeenestablished.Theneedforcontinued

treatmentshouldbere-evaluatedperiodicallybasedonthebenefitsandpotentialrisksofBonapenya5mgonan

individualpatientbasis,particularlyafter5ormoreyearsofuse.

4.3Contraindications

Hypersensitivitytorisedronatesodiumortoanyoftheexcipientslistedinsection6.1.

Hypocalcaemia(seesection4.4).

Pregnancyandlactation.

Severerenalimpairment(creatinineclearance<30ml/min).

4.4Specialwarningsandprecautionsforuse

Foods,drinks(otherthanplainwater)andmedicinalproductscontainingpolyvalentcations(suchascalcium,

magnesium,ironandaluminium)interferewiththeabsorptionofbisphosphonatesandshouldnotbetakenatthesame

timeasRisedronate(seesection4.5)Inordertoachievetheintendedefficacy,strictadherencetodosing

recommendationsisnecessary(seesection4.2).

Efficacyofbisphosphonatesinthetreatmentofpostmenopausalosteoporosisisrelatedtothepresenceoflowbone

mineraldensity(BMDT-scoreathiporlumbarspine -2.5SD)and/orprevalentfracture.

Highageorclinicalriskfactorsforfracturealonearenotreasonstoinitiatetreatmentofosteoporosiswitha

bisphosphonate.TheevidencetosupportefficacyofbisphosphonatesincludingRisedronateinveryelderlywomen

(>80years)islimited(seesection5.1).

Bisphosphonateshavebeenassociatedwithoesophagitis,gastritis,oesophagealulcerationsandgastroduodenal

ulcerations.Thuscautionshouldbeused:

Inpatientswhohaveahistoryofoesophagealdisorderswhichdelayoesophagealtransitoremptyinge.g.stricture

orachalasia.

Inpatientswhoareunabletostayintheuprightpositionforatleast30minutesaftertakingthetable.

Ifrisedronateisgiventopatientswithactiveorrecentoesophagealoruppergastrointestinalproblems(including

knownBarrett'soesophagus).

Prescribersshouldemphasisetopatientstheimportanceofpayingattentiontothedosinginstructionsandbealertto

anysignsorsymptomsofpossibleoesophagealreaction.Thepatientsshouldbeinstructedtoseektimelymedical

attentioniftheydevelopsymptomsofoesophagealirritationsuchasdysphagia,painonswallowing,retrosternalpain

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HypocalcaemiashouldbetreatedbeforestartingRisedronatetherapy.Otherdisturbancesofboneandmineral

metabolism(e.g.parathyroiddysfunction,hypovitaminosisD)shouldbetreatedatthetimeofstartingRisedronate

therapy.

Osteonecrosisofthejaw,generallyassociatedwithtoothextractionand/orlocalinfection(includingosteomyelitis)has

beenreportedinpatientswithcancerreceivingtreatmentregimensincludingprimarilyintravenouslyadministered

bisphophonates.Manyofthesepatientswerealsoreceivingchemotherapyandcorticosteroids.Osteonecrosisofthejaw

hasalsobeenreportedinpatientswithosteoporosisreceivingoralbisphosphonates.

Adentalexaminationwithappropriatepreventivedentistryshouldbeconsideredpriortotreatmentwith

bisphosphonatesinpatientswithconcomitantriskfactors(e.g.cancer,chemotherapy,radiotherapy,corticosteroids,

poororalhygiene).

Whileontreatment,thesepatientsshouldavoidinvasivedentalproceduresifpossible.Forpatientswhodevelop

osteonecrosisofthejawwhileonbisphosphonatetherapy,dentalsurgerymayexacerbatethecondition.Forpatients

requiringdentalprocedures,therearenodataavailabletosuggestwhetherdiscontinuationofbisphosphonatetreatment

reducestheriskofosteonecrosisofthejaw.

Clinicaljudgmentofthetreatingphysicianshouldguidethemanagementplanofeachpatientbasedonindividual

benefit/riskassessment.

Thismedicinecontainslactose.Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapplactase

deficiencyorglucose-galactosemalabsorptionshouldnottakethismedicine.

Atypicalfracturesofthefemur

Atypicalsubtrochantericanddiaphysealfemoralfractureshavebeenreportedwithbisphosphonatetherapy,primarily

inpatientsreceivinglong-termtreatmentforosteoporosis.Thesetransverseorshortoblique,fracturescanoccur

anywherealongthefemurfromjustbelowthelessertrochantertojustabovethesupracondylarflare.Thesefractures

occurafterminimalornotraumaandsomepatientsexperiencethighorgroinpain,oftenassociatedwithimaging

featuresofstressfractures,weekstomonthsbeforepresentingwithacompletedfemoralfracture.Fracturesareoften

bilateral;thereforethecontralateralfemurshouldbeexaminedinbisphosphonate-treatedpatientswhohavesustaineda

femoralshaftfracture.Poorhealingofthesefractureshasalsobeenreported.Discontinuationofbisphosphonate

therapyinpatientssuspectedtohaveanatypicalfemurfractureshouldbeconsideredpendingevaluationofthepatient,

basedonanindividualbenefitriskassessment.

Duringbisphosphonatetreatmentpatientsshouldbeadvisedtoreportanythigh,hiporgroinpainandanypatient

presentingwithsuchsymptomsshouldbeevaluatedforanincompletefemurfracture.

Osteonecrosisoftheexternalauditorycanal

Osteonecrosisoftheexternalauditorycanalhasbeenreportedwithbisphosphonates,mainlyinassociationwithlong-

termtherapy.Possibleriskfactorsforosteonecrosisoftheexternalauditorycanalincludesteroiduseand

chemotherapyand/orlocalriskfactorssuchasinfectionortrauma.Thepossibilityofosteonecrosisoftheexternal

auditorycanalshouldbeconsideredinpatientsreceivingbisphosphonateswhopresentwithearsymptomsincluding

chronicearinfections.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Noformalinteractionstudieshavebeenperformed,howevernoclinicallyrelevantinteractionswithothermedicinal

productswerefoundduringclinicaltrials.

Concomitantingestionofmedicinalproductscontainingpolyvalentcations(suchascalcium,magnesium,ironand

aluminium)interferewiththeabsorptionofRisedronate(seesection4.4).

Risedronateisnotsystemicallymetabolised,doesnotinducecytochromeP450enzymes,andhaslowproteinbinding.

IntheRisedronatePhaseIIIosteoporosisstudies,acetylsalicylicacidorNSAIDusewasreportedby33%and45%of

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IfconsideredappropriateRisedronatemaybeusedconcomitantlywithoestrogensupplementation.

4.6Fertility,pregnancyandlactation

Therearenoadequatedatafromtheuseofrisedronatesodiuminpregnantwomen.Studiesinanimalshaveshown

reproductivetoxicity(seesection5.3).Thepotentialriskforhumansisunknown.Studiesinanimalindicatethata

smallamountofrisedronatesodiumpassintobreastmilk.

Risedronatesodiummustnotbeusedduringpregnancyorbybreast-feedingwomen.

4.7Effectsonabilitytodriveandusemachines

Noeffectsonabilitytodriveandusemachineshavebeenobserved.

4.8Undesirableeffects

RisedronatesodiumhasbeenstudiedinphaseIIIclinicaltrialsinvolvingmorethan15,000patients.

Themajorityofundesirableeffectsobservedinclinicaltrialsweremildtomoderateinseverityandusuallydidnot

requirecessationoftherapy.

AdverseexperiencesreportedinphaseIIIclinicaltrialsinpostmenopausalwomenwithosteoporosistreatedforupto

36monthswithrisedronate5mg/day(n=5020)orplacebo(n=5048)andconsideredpossiblyorprobablyrelatedto

risedronatearelistedbelowusingthefollowingconvention(incidencesversusplaceboareshowninbrackets):

Verycommon(1/10);common(1/100;<1/10);uncommon(1/1,000;<1/100);rare(1/10,000;<1/1,000);veryrare

(<1/10,000).

Nervoussystemdisorders:

Common:headache(1.8%vs.1.4%)

Eyedisorders:

Uncommon:iritis*

Gastrointestinaldisorders:

Common:constipation(5.0%vs.4.8%),dyspepsia(4.5%vs.4.1%),nausea(4.3%vs.4.0%),abdominalpain(3.5%vs.

3.3%),diarrhoea(3.0%vs.2.7%)

Uncommon:gastritis(0.9%vs.0.7%),oesophagitis(0.9%vs.0.9%),dysphagia(0.4%vs.0.2%),duodenitis(0.2%vs.

0.1%),oesophagealulcer(0.2%vs.0.2%)

Rare:glossitis(<0.1%vs.0.1%),oesophagealstricture(<0.1%vs.0.0%)

Musculoskeletalandconnectivetissuesdisorders:

Common:musculoskeletalpain(2.1%vs.1.9%)

Investigations:

Rare:abnormalliverfunctiontests*

*NorelevantincidencesfromPhaseIIIosteoporosisstudies;frequencybasedonadverseevent/laboratory/rechallenge

findingsinearlierclinicaltrials.

InaphaseIIIPaget’sDiseaseclinicaltrialcomparingrisedronatevs.etidronate(61patientsineachgroup),the

followingadditionaladverseexperiencesconsideredpossiblyorprobablydrugrelatedbyinvestigatorshavebeen

reported(incidencegreaterinrisedronatethaninetidronate):arthralgia(9.8%vs.8.2%);amblyopia,apnoea,bronchitis,

colitis,corneallesion,crampsleg,dizziness,dryeye,flusyndrome,hypocalcaemia,myasthenia,neoplasm,nocturia,

oedemaperipheral,painbone,painchest,rash,sinusitis,tinnitus,andweightdecrease(allat1.6%vs.0.0%).

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beenobservedinsomepatients.

Duringpost-marketingexperiencethefollowingreactionshavebeenreported(Rare):

Atypicalsubtrochantericanddiaphysealfemoralfractures(biphosphonateclassadversereaction)

Veryrare:osteonecrosisoftheexternalauditorycanal(bisphosphonateclassadversereaction)

Thefollowingadditionaladversereactionshavebeenreportedduringpost-marketinguse(frequencyunknown):

Eyedisorders:

iritis,uveitis

Muskuloskeletalandconnectivetissuesdisorders:

osteonecrosisofthejaw

Skinandsubcutaneoustissuedisorders:

hypersensitivityandskinreactions,includingangioedema,generalisedrash,urticaria,bullousskinreactionsand

leukocytoclasticvasculitis,somesevereincludingisolatedreportsofStevensJohnsonsyndromeandtoxicepidermal

necrolysis.

Hairloss.

Immunesystemdisorders:

anaphylactic reaction

Hepatobiliarydisorders:

serioushepaticdisorders.Inmostofthereportedcasesthepatientswerealsotreatedwithotherproductsknownto

causehepaticdisorders.

Reportingofsuspectedadversereactions

Reportingsuspectedadversereactionsafterauthorisationofthemedicinalproductisimportant.Itallowscontinued

monitoringofthebenefit/riskbalanceofthemedicinalproduct.Healthcareprofessionalsareaskedtoreportany

suspectedadversereactionsviaHPRAPharmacovigilance,EarlsfortTerrace,IRL-Dublin2;Tel:+35316764971;

Fax:+35316762517.Website: www.hpra.ie ;E-mail: medsafety@hpra.ie .

4.9Overdose

Nospecificinformationisavailableonthetreatmentofoverdosewithrisedronatesodium.

Decreasesinserumcalciumfollowingsubstantialoverdosemaybeexpected.Signsandsymptomsofhypocalcaemia

mayalsooccurinsomeofthesepatients

Milkorantacidscontainingmagnesium,calciumoraluminiumshouldbegiventobindrisedronateandreduce

absorptionofrisedronatesodium.Incasesofsubstantialoverdose,gastriclavagemaybeconsideredtoremove

unabsorbedrisedronatesodium.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmaco-therapeuticgroup:Bisphosphonates

ATCCode:M05BA07

Risedronatesodiumisapyridinylbisphosphonatethatbindstobonehydroxyapatiteandinhibitsosteoclast-mediated

boneresorption.Theboneturnoverisreducedwhiletheosteoblastactivityandbonemineralisationispreserved.In

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dependentlyincreasedbonemassandbiomechanicalskeletalstrength.Theactivityofrisedronatesodiumwas

confirmedbymeasuringbiochemicalmarkersforboneturnoverduringpharmacodynamicandclinicalstudies.

Decreasesinbiochemicalmarkersofboneturnoverwereobservedwithin1monthandreachedamaximumin3-6

months.

TreatmentandPreventionofPostmenopausalOsteoporosis:

Anumberofriskfactorsareassociatedwithpostmenopausalosteoporosisincludinglowbonemass,lowbonemineral

density,earlymenopause,ahistoryofsmokingandafamilyhistoryofosteoporosis.Theclinicalconsequenceof

osteoporosisisfractures.Theriskoffracturesisincreasedwiththenumberofriskfactors.

Theclinicalprogrammestudiedtheeffectofrisedronatesodiumontheriskofhipandvertebralfracturesandcontained

earlyandlatepostmenopausalwomenwithandwithoutfracture.Dailydosesof2.5mgand5mgwerestudiedandall

groups,includingthecontrolgroups,receivedcalciumandvitaminD(ifbaselinelevelswerelow).Theabsoluteand

relativeriskofnewvertebralandhipfractureswereestimatedbyuseofatime-to-firsteventanalysis.

Twoplacebo-controlledtrials(n=3,661)enrolledpostmenopausalwomenunder85yearswithvertebralfracturesat

baseline.Risedronatesodium5mgdailygivenfor3yearsreducedtheriskofnewvertebralfracturesrelativetothe

controlgroup.Inwomenwithrespectivelyatleast2oratleast1vertebralfractures,therelativeriskreductionwas

49%and41%respectively(incidenceofnewvertebralfractureswithrisedronatesodium18.1%and11.3%,with

placebo29.0%and16.3%,respectively).Theeffectoftreatmentwasseenasearlyastheendofthefirstyearof

treatment.Benefitswerealsodemonstratedinwomenwithmultiplefracturesatbaseline.Risedronatesodium5mg

dailyalsoreducedtheyearlyheightlosscomparedtothecontrolgroup.

Twofurtherplacebocontrolledtrialsenrolledpostmenopausalwomenabove70yearswithorwithoutvertebral

fracturesatbaseline.Women70-79yearswereenrolledwithfemoralneckBMDT-score<-3SD(manufacturer’s

range,i.e.-2.5SDusingNHANESIII)andatleastoneadditionalriskfactor.Women 80yearscouldbeenrolled

onthebasisofatleastonenon-skeletalriskfactorforhipfractureorlowbonemineraldensityatthefemoralneck.

Statisticalsignificanceoftheefficacyofrisedronatesodiumversusplaceboisonlyreachedwhenthetwotreatment

groups2.5mgand5mgarepooled.Thefollowingresultsareonlybasedona-posteriorianalysisofsubgroups

definedbyclinicalpractiseandcurrentdefinitionsofosteoporosis:

-InthesubgroupofpatientswithfemoralneckBMDT-score<-2.5SD(NHANESIII)andatleastonevertebral

fractureatbaseline,risedronatesodiumgivenfor3yearsreducedtheriskofhipfracturesby46%relativetothecontrol

group(incidenceofhipfracturesincombinedrisedronatesodium2.5and5mggroups3.8%,placebo7.4%).

-Datasuggestthatamorelimitedprotectionthanthismaybeobservedintheveryelderly(>80years).Thismaybe

duetotheincreasingimportanceofnon-skeletalfactorsforhipfracturewithincreasingage.Inthesetrials,data

analysedasasecondaryendpointindicatedadecreaseintheriskofnewvertebralfracturesinpatientswithlowfemoral

neckBMDwithoutvertebralfractureandinpatientswithlowfemoralneckBMDwithorwithoutvertebralfracture.

-Risedronatesodium5mgdailygivenfor3yearsincreasedbonemineraldensity(BMD)relativetocontrolatthe

lumbarspine,femoralneck,trochanterandwristandpreventedbonelossatthemid-shaftradius.

-Inaone-yearfollow-upofftherapyafterthreeyearstreatmentwithrisedronatesodium5mgdailytherewasrapid

reversibilityofthesuppressingeffectofrisedronatesodiumonboneturnoverrate.

-Inpostmenopausalwomentakingoestrogen,risedronatesodium5mgdailyincreasedbonemineraldensity(BMD)at

thefemoralneckandmid-shaftradiusonly,comparedtooestrogenalone.

-Bonebiopsysamplesfrompostmenopausalwomentreatedwithrisedronatesodium5mgdailyfor2to3years,

showedanexpectedmoderatedecreaseinboneturnover.Boneformedduringrisedronatesodiumtreatmentwasof

normallamellarstructureandbonemineralisation.Thesedatatogetherwiththedecreasedincidenceofosteoporosis

relatedfracturesatvertebralsitesinwomenwithosteoporosisappearto

indicatenodetrimentaleffectonbonequality.

-Endoscopicfindingsfromanumberofpatientswithanumberofmoderatetoseveregastrointestinalcomplaintsin

bothrisedronatesodiumandcontrolpatientsindicatednoevidenceoftreatmentrelatedgastric,duodenalor

oesophagealulcersineithergroup,althoughduodenitiswasuncommonlyobservedintherisedronatesodiumgroup.

-Inatrialcomparingbefore-breakfastdosinganddosingatothertimesofthedayinwomenwithpostmenopausal

osteoporosis,lumbarspineBMDgainswerestatisticallyhigherwithbefore-breakfastdosing.

Inosteoepenicpostmenopausalwomen,risedronatesodiumhasshownsuperioritytoplaceboinincreasinglumbar

spineBMDat12and24months.

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mg/dayprednisoneorequivalent)withintheprevious3monthsorpatientswhohadbeentakingcorticosteroidsfor

morethan6months.Resultsofthesestudiesdemonstratethat:

Risedronatesodium5mgdailygivenforoneyearmaintainsorincreasesbonemineraldensity(BMD)relativeto

controlatthelumbarspine,femoralneck,andtrochanter.

Risedronatesodium5mgdailyreducedtheincidenceofvertebralfractures,monitoredforsafety,relativetocontrol

at1yearinpooledstudies.

Histologicalexaminationofbonebiopsiesfrompatientstakingcorticosteroidsandrisedronatesodium5mgdaily

didnotshowsignsofdisturbedmineralisationprocess.

Paediatricpopulation:

Thesafetyandefficacyofrisedronatesodiumhasbeeninvestigatedina3yearstudy(arandomized,double-blind,

placebocontrolled,multicenter,parallelgroupstudyofone-yeardurationfollowedby2yearsofopen-labeltreatment)

inpaediatricpatientsaged4tolessthan16yearswithmildtomoderateosteogenesisimperfecta.Inthisstudy,patients

weighing10-30kgreceivedrisedronate2.5mgdailyandpatientsweighingmorethan30kgreceivedrisedronate5mg

daily.

Aftercompletionofitsone-yearrandomized,double-blind,placebocontrolledphase,astatisticallysignificantincrease

inlumbarspineBMDintherisedronategroupversusplacebogroupwasdemonstrated;howeveranincreasednumber

ofpatientswithatleast1newmorphometric(identifiedbyx-ray)vertebralfracturewasfoundintherisedronategroup

comparedtoplacebo.Duringtheoneyeardoubleblindperiod,thepercentageofpatientswhoreportedclinical

fractureswas30.9%intherisedronategroupand49.0%intheplacebogroup.

Intheopenlabelperiodwhenallpatientsreceivedrisedronate(month12tomonth36),clinicalfractureswerereported

by65.3%ofpatientsinitiallyrandomizedtotheplacebogroupandby52.9%ofpatientsinitiallyrandomizedtothe

risedronategroup.Overall,resultsareinsufficienttosupporttheuseofrisedronatesodiuminpaediatricpatientswith

mildtomoderateosteogenesisimperfecta.

5.2Pharmacokineticproperties

Absorption:Absorptionafteranoraldoseisrelativelyrapid(tmax~1hour)andisindependentofdoseovertherange

studied(2.5to30mg).Meanoralbioavailabilityofthetabletis0.63%andisdecreasedwhenrisedronatesodiumis

administeredwithfood.Bioavailabilitywassimilarinmenandwomen.

Distribution:Themeansteadystatevolumeofdistributionis6.3l/kginhumans.Plasmaproteinbindingisabout24%.

Metabolism:Thereisnoevidenceofsystemicmetabolismofrisedronatesodium.

Elimination:Approximatelyhalfoftheabsorbeddoseisexcretedinurinewithin24hours,and85%ofanintravenous

doseisrecoveredintheurineafter28days.Meanrenalclearanceis105ml/minandmeantotalclearanceis122

ml/min,withthedifferenceprobablyattributedtoclearanceduetoadsorptiontobone.Therenalclearanceisnot

concentrationdependent,andthereisalinearrelationshipbetweenrenalclearanceandcreatinineclearance.

Unabsorbedrisedronatesodiumiseliminatedunchangedinfaeces.Afteroraladministrationtheconcentration-time

profileshowsthreeeliminationphaseswithaterminalhalf-lifeof480hours.

Specialpopulations:

Elderly:nodosageadjustmentisnecessary.

Acetylsalicylicacid/NSAIDusers:AmongregularacetylsalicylicacidorNSAIDusers(3ormoredaysperweek)the

incidenceofuppergastrointestinaladverseeventsinRisedronatetreatedpatientswassimilartothatincontrolpatients.

5.3Preclinicalsafetydata

Intoxicologicalstudiesinratanddogdosedependentlivertoxiceffectsofrisedronatesodiumwereseen,primarilyas

enzymeincreaseswithhistologicalchangesinrat.Theclinicalrelevanceoftheseobservationsisunknown.Testicular

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incidencesofupperairwayirritationwerefrequentlynotedinrodents.Similareffectshavebeenseenwithother

bisphosphonates.Lowerrespiratorytracteffectswerealsoseeninlongertermstudiesinrodents,althoughtheclinical

significanceofthesefindingsisunclear.Inreproductiontoxicitystudiesatexposuresclosetoclinicalexposure

ossificationchangeswereseeninsternumand/orskulloffoetusesfromtreatedratsandhypocalcemiaandmortalityin

pregnantfemalesallowedtodeliver.Therewasnoevidenceofteratogenesisat3.2mg/kg/dayinratand10mg/kg/dayin

rabbit,althoughdataareonlyavailableonasmallnumberofrabbits.Maternaltoxicitypreventedtestingofhigher

doses.Studiesongenotoxicityandcarcinogenesisdidnotshowanyparticularrisksforhumans.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Tabletcore:

Starch,pregelatinised(maize)

Cellulose,microcrystalline

Crospovidone

Magnesiumstearate

Filmcoating:

Hypromellose

Lactosemonohydrate

Titaniumdioxide(E171)

Macrogol4000

6.2Incompatibilities

Notapplicable.

6.3Shelflife

5years

6.4Specialprecautionsforstorage

Thismedicinalproductdoesnotrequireanyspecialstorageconditions.

6.5Natureandcontentsofcontainer

Natureofcontainer:OpaquePVC/PE/PVDC/Aluminiumblisterinacartonbox.

Packsizes:14,28,84,98tablets

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalandotherhandling

Nospecialrequirements

7MARKETINGAUTHORISATIONHOLDER

PharmathenS.A.

6Devernakionstr.,

15351Pallini,Attiki

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8MARKETINGAUTHORISATIONNUMBER

PA1368/008/001

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:26 th

November2010

Dateoflastrenewal:11 th

June2014

10DATEOFREVISIONOFTHETEXT

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Date Printed 07/04/2016 CRN 2170668 page number: 9

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