2026枸橼酸西地那非干混悬剂参比制剂说明书

2026/3/311:25Revatio10mg/mlPowderforOralSuspension-SummaryofProductCharacteristics(SmPC)-printfriendly-(emc)

Revatio10mg/mlPowderforOralSuspension

SummaryofProductCharacteristicsUpdated09-Feb-2026|Viatris(formerlyMylanorUpjohn)

1.Nameofthemedicinalproduct

Revatio10mg/mlpowderfororalsuspension

2.Qualitativeandquantitativecomposition

Afterreconstitution,eachmloftheoralsuspensioncontains10mgofsildenafil(ascitrate)

Onebottleofreconstitutedoralsuspension(112ml)contains1.12gofsildenafil(ascitrate)

Excipient(s)withknowneffect

Eachmlofreconstitutedoralsuspensioncontains250mgsorbitol.

Eachmlofreconstitutedoralsuspensioncontains1mgsodiumbenzoate.

Forthefulllistofexcipients,seesection6.1.

3.Pharmaceuticalform

Powderfororalsuspension.

Whitetooff-whitepowder.

4.Clinicalparticulars

4.1Therapeuticindications

Adults

TreatmentofadultpatientswithpulmonaryarterialhypertensionclassifiedasWHOfunctionalclassIIandIII,toimproveexercisecapacity.Efficacyhasbeenshowninprimarypulmonaryhypertensionandpulmonaryhypertensionassociatedwithconnectivetissuedisease.

Paediatricpopulation

Treatmentofpaediatricpatientsaged1yearto17yearsoldwithpulmonaryarterialhypertension.Efficacyintermsofimprovementofexercisecapacityorpulmonaryhaemodynamicshasbeenshowninprimarypulmonaryhypertensionandpulmonaryhypertensionassociatedwithcongenitalheart

disease(seesection5.1).

4.2Posologyandmethodofadministration

Treatmentshouldonlybeinitiatedandmonitoredbyaphysicianexperiencedinthetreatmentofpulmonaryarterialhypertension.IncaseofclinicaldeteriorationinspiteofRevatiotreatment,alternativetherapiesshouldbeconsidered.

Posology

Adults

Therecommendeddoseis20mgthreetimesaday(TID).PhysiciansshouldadvisepatientswhoforgettotakeRevatiototakeadoseassoonaspossibleandthencontinuewiththenormaldose.Patientsshouldnottakeadoubledosetocompensateforthemisseddose.

Paediatricpopulation(1yearto17years)

Forpaediatricpatientsaged1yearto17yearsold,therecommendeddoseinpatients≤20kgis10mg(1mlofreconstitutedsuspension)threetimesadayandforpatients>20kgis20mg(2mlofreconstitutedsuspension)threetimesaday.HigherthanrecommendeddosesshouldnotbeusedinpaediatricpatientswithPAH(seealsosections4.4and5.1).

Patientsusingothermedicinalproducts

Ingeneral,anydoseadjustmentshouldbeadministeredonlyafteracarefulbenefit-riskassessment.Adownwarddoseadjustmentto20mgtwicedailyshouldbeconsideredwhensildenafilisco_administeredtopatientsalreadyreceivingCYP3A4inhibitorslikeerythromycinorsaquinavir.Adownwarddoseadjustmentto20mgoncedailyisrecommendedincaseofco_administrationwithmorepotentCYP3A4inhibitorsclarithromycin,telithromycin

andnefazodone.FortheuseofsildenafilwiththemostpotentCYP3A4inhibitors,seesection4.3.Doseadjustmentsforsildenafilmayberequiredwhenco-administeredwithCYP3A4inducers(seesection4.5).

Specialpopulations

Elderly(≥65years)

Doseadjustmentsarenotrequiredinelderlypatients.Clinicalefficacyasmeasuredby6-minutewalkdistancecouldbelessinelderlypatients.

Renalimpairment

Initialdoseadjustmentsarenotrequiredinpatientswithrenalimpairment,includingsevererenalimpairment(creatinineclearance<30ml/min).Adownwarddoseadjustmentto20mgtwicedailyshouldbeconsideredafteracarefulbenefit-riskassessmentonlyiftherapyisnotwell-tolerated.

Hepaticimpairment

Initialdoseadjustmentsarenotrequiredinpatientswithhepaticimpairment(Child-PughclassAandB).Adownwarddoseadjustmentto20mgtwicedailyshouldbeconsideredafteracarefulbenefit_riskassessmentonlyiftherapyisnotwell-tolerated.

Revatioiscontraindicatedinpatientswithseverehepaticimpairment(Child-PughclassC),(seesection4.3).

Paediatricpopulation(childrenlessthan1yearandneonates)

Outsideitsauthorisedindications,sildenafilshouldnotbeusedinneonateswithpersistentpulmonaryhypertensionofthenewbornasrisksoutweighthebenefits(seesection5.1).ThesafetyandefficacyofRevatioinotherconditionsinchildrenbelow1yearofagehasnotbeenestablished.Nodataareavailable.

Discontinuationoftreatment

LimiteddatasuggestthattheabruptdiscontinuationofRevatioisnotassociatedwithreboundworseningofpulmonaryarterialhypertension.Howevertoavoidthepossibleoccurrenceofsuddenclinicaldeteriorationduringwithdrawal,agradualdosereductionshouldbeconsidered.Intensified

monitoringisrecommendedduringthediscontinuationperiod.

Methodofadministration

.uk/emc/product/2850/smpc/print

1/14

.uk/emc/product/2850/smpc/print

2/14

2026/3/311:25Revatio10mg/mlPowderforOralSuspension-SummaryofProductCharacteristics(SmPC)-printfriendly-(emc)

etodofadiistratio

Revatiopowderfororalsuspensionisfororaluseonly.Thereconstitutedoralsuspension(awhite,grapeflavouredoralsuspension)shouldbetakenapproximately6to8hoursapartwithorwithoutfood.

Beforewithdrawingtherequireddose,shakethebottlevigorouslyforaminimumof10seconds.

Forinstructionsonreconstitutionofthemedicinalproductbeforeadministration,seesection6.6.

4.3Contraindications

Hypersensitivitytotheactivesubstanceortoanyoftheexcipientslistedinsection6.1.

Co-administrationwithnitricoxidedonors(suchasamylnitrite)ornitratesinanyformduetothehypotensiveeffectsofnitrates(seesection5.1).

Theco-administrationofPDE5inhibitors,includingsildenafil,withguanylatecyclasestimulators,suchasriociguat,iscontraindicatedasitmaypotentiallyleadtosymptomatichypotension(seesection4.5).

CombinationwiththemostpotentoftheCYP3A4inhibitors(eg,ketoconazole,itraconazole,ritonavir)(seesection4.5).

Patientswhohavelossofvisioninoneeyebecauseofnon-arteriticanteriorischaemicopticneuropathy(NAION),regardlessofwhetherthisepisodewasinconnectionornotwithpreviousPDE5inhibitorexposure(seesection4.4).

Thesafetyofsildenafilhasnotbeenstudiedinthefollowingsub-groupsofpatientsanditsuseisthereforecontraindicated:

Severehepaticimpairment,

Recenthistoryofstrokeormyocardialinfarction,

Severehypotension(bloodpressure<90/50mmHg)atinitiation.

4.4Specialwarningsandprecautionsforuse

TheefficacyofRevatiohasnotbeenestablishedinpatientswithseverepulmonaryarterialhypertension(functionalclassIV).Iftheclinicalsituationdeteriorates,therapiesthatarerecommendedattheseverestageofthedisease(eg,epoprostenol)shouldbeconsidered(seesection4.2).The

benefit-riskbalanceofsildenafilhasnotbeenestablishedinpatientsassessedtobeatWHOfunctionalclassIpulmonaryarterialhypertension.

Studieswithsildenafilhavebeenperformedinformsofpulmonaryarterialhypertensionrelatedtoprimary(idiopathic),connectivetissuediseaseassociatedorcongenitalheartdiseaseassociatedformsofPAH(seesection5.1).TheuseofsildenafilinotherformsofPAHisnotrecommended.

Inthelongtermpaediatricextensionstudy,anincreaseindeathswasobservedinpatientsadministereddoseshigherthantherecommendeddose.Therefore,doseshigherthantherecommendeddosesshouldnotbeusedinpaediatricpatientswithPAH(seealsosections4.2and5.1).

Retinitispigmentosa

Thesafetyofsildenafilhasnotbeenstudiedinpatientswithknownhereditarydegenerativeretinaldisorderssuchasretinitispigmentosa(aminorityofthesepatientshavegeneticdisordersofretinalphosphodiesterases)andthereforeitsuseisnotrecommended.

Vasodilatoryaction

Whenprescribingsildenafil,physiciansshouldcarefullyconsiderwhetherpatientswithcertainunderlyingconditionscouldbeadverselyaffectedbysildenafil'smildtomoderatevasodilatoryeffects,forexamplepatientswithhypotension,patientswithfluiddepletion,severeleftventricularoutflowobstructionorautonomicdysfunction(seesection4.4).

Cardiovascularriskfactors

Inpost-marketingexperiencewithsildenafilformaleerectiledysfunction,seriouscardiovascularevents,includingmyocardialinfarction,unstable

angina,suddencardiacdeath,ventriculararrhythmia,cerebrovascularhaemorrhage,transientischaemicattack,hypertensionandhypotensionhavebeenreportedintemporalassociationwiththeuseofsildenafil.Most,butnotall,ofthesepatientshadpre-existingcardiovascularriskfactors.Manyeventswerereportedtooccurduringorshortlyaftersexualintercourseandafewwerereportedtooccurshortlyaftertheuseofsildenafilwithout

sexualactivity.Itisnotpossibletodeterminewhethertheseeventsarerelateddirectlytothesefactorsortootherfactors.

Priapism

Sildenafilshouldbeusedwithcautioninpatientswithanatomicaldeformationofthepenis(suchasangulation,cavernosalfibrosisorPeyronie's

disease),orinpatientswhohaveconditionswhichmaypredisposethemtopriapism(suchassicklecellanaemia,multiplemyelomaorleukaemia).

Prolongederectionsandpriapismhavebeenreportedwithsildenafilinpost-marketingexperience.Intheeventofanerectionthatpersistslongerthan

4hours,thepatientshouldseekimmediatemedicalassistance.Ifpriapismisnottreatedimmediately,peniletissuedamageandpermanentlossofpotencycouldresult(seesection4.8).

Vaso-occlusivecrisesinpatientswithsicklecellanaemia

Sildenafilshouldnotbeusedinpatientswithpulmonaryhypertensionsecondarytosicklecellanaemia.Inaclinicalstudyeventsofvaso-occlusivecrisesrequiringhospitalisationwerereportedmorecommonlybypatientsreceivingRevatiothanthosereceivingplaceboleadingtotheprematureterminationofthisstudy.

Visualevents

CasesofvisualdefectshavebeenreportedspontaneouslyinconnectionwiththeintakeofsildenafilandotherPDE5inhibitors.Casesofnon_arteriticanteriorischaemicopticneuropathy,ararecondition,havebeenreportedspontaneouslyandinanobservationalstudyinconnectionwiththeintakeofsildenafilandotherPDE5inhibitors(seesection4.8).Intheeventofanysuddenvisualdefect,thetreatmentshouldbestoppedimmediatelyand

alternativetreatmentshouldbeconsidered(seesection4.3).

Alpha-blockers

Cautionisadvisedwhensildenafilisadministeredtopatientstakinganalpha-blockerastheco_administrationmayleadtosymptomatichypotensioninsusceptibleindividuals(seesection4.5).Inordertominimisethepotentialfordevelopingposturalhypotension,patientsshouldbehaemodynamicallystableonalpha-blockertherapypriortoinitiatingsildenafiltreatment.Physiciansshouldadvisepatientswhattodointheeventofposturalhypotensivesymptoms.

Bleedingdisorders

Studieswithhumanplateletsindicatethatsildenafilpotentiatestheantiaggregatoryeffectofsodiumnitroprussideinvitro.Thereisnosafetyinformationontheadministrationofsildenafiltopatientswithbleedingdisordersoractivepepticulceration.Thereforesildenafilshouldbeadministeredtothese

patientsonlyaftercarefulbenefit-riskassessment.

VitaminKantagonists

Inpulmonaryarterialhypertensionpatients,theremaybeapotentialforincreasedriskofbleedingwhensildenafilisinitiatedinpatientsalreadyusingaVitaminKantagonist,particularlyinpatientswithpulmonaryarterialhypertensionsecondarytoconnectivetissuedisease.

2026/3/311:25Revatio10mg/mlPowderforOralSuspension-SummaryofProductCharacteristics(SmPC)-printfriendly-(emc)

Singledosesofantacid(magnesiumhydroxide/aluminiumhydroxide)didnotaffectthebioavailabilityofsildenafil

.uk/emc/product/2850/smpc/print

3/14

Veno-occlusivedisease

Nodataareavailablewithsildenafilinpatientswithpulmonaryhypertensionassociatedwithpulmonaryveno-occlusivedisease.However,casesoflifethreateningpulmonaryoedemahavebeenreportedwithvasodilators(mainlyprostacyclin)whenusedinthosepatients.Consequently,shouldsignsofpulmonaryoedemaoccurwhensildenafilisadministeredinpatientswithpulmonaryhypertension,thepossibilityofassociatedveno-occlusivediseaseshouldbeconsidered.

Excipientinformation

Revatio10mg/mlpowderfororalsuspensioncontainssorbitol,whichisasourceoffructose.Patientswithrarehereditaryfructoseintolerance(HFI)shouldnottakethismedicinalproduct.

Revatio10mg/mlpowderfororalsuspensioncontains1mgsodiumbenzoatepermlofreconstitutedoralsuspension.Benzoatesmayincrease

unconjugatedbilirubinlevelsbydisplacingbilirubinfromalbumin,whichmayincreaseneonataljaundice.Neonatalhyperbilirubinaemiamayleadtokernicterus(non-conjugatedbilirubindepositsinthebraintissue)andencephalopathy.

Revatio10mg/mlpowderfororalsuspensioncontainslessthan1mmolsodium(23mg)permlofreconstitutedoralsuspension.Patientsonlowsodiumdietscanbeinformedthatthismedicinalproductisessentially'sodium-free'.

Useofsildenafilwithbosentan

Theefficacyofsildenafilinpatientsalreadyonbosentantherapyhasnotbeenconclusivelydemonstrated(seesections4.5and5.1).

ConcomitantusewithotherPDE5inhibitors

Thesafetyandefficacyofsildenafilwhenco-administeredwithotherPDE5inhibitorproducts,includingViagra,hasnotbeenstudiedinPAHpatientsandsuchconcomitantuseisnotrecommended(seesection4.5).

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Effectsofothermedicinalproductsonsildenafil

Invitrostudies

SildenafilmetabolismisprincipallymediatedbythecytochromeP450(CYP)isoforms3A4(majorroute)and2C9(minorroute).Therefore,inhibitorsoftheseisoenzymesmayreducesildenafilclearanceandinducersoftheseisoenzymesmayincreasesildenafilclearance.Fordoserecommendations,seesections4.2and4.3.

Invivostudies

Co-administrationoforalsildenafilandintravenousepoprostenolhasbeenevaluated(seesections4.8and5.1).

Theefficacyandsafetyofsildenafilco-administeredwithothertreatmentsforpulmonaryarterialhypertension(eg,ambrisentan,iloprost)hasnotbeenstudiedincontrolledclinicaltrials.Therefore,cautionisrecommendedincaseofco-administration.

Thesafetyandefficacyofsildenafilwhenco-administeredwithotherPDE5inhibitorshasnotbeenstudiedinpulmonaryarterialhypertensionpatients(seesection4.4).

Populationpharmacokineticanalysisofpulmonaryarterialhypertensionclinicaltrialdataindicatedareductioninsildenafilclearanceand/oranincreaseoforalbioavailabilitywhenco-administeredwithCYP3A4substratesandthecombinationofCYP3A4substratesandbeta-blockers.Thesewerethe

onlyfactorswithastatisticallysignificantimpactonsildenafilpharmacokineticsinpatientswithpulmonaryarterialhypertension.Theexposureto

sildenafilinpatientsonCYP3A4substratesandCYP3A4substratesplusbeta-blockerswas43%and66%higher,respectively,comparedtopatientsnotreceivingtheseclassesofmedicines.Sildenafilexposurewas5_foldhigheratadoseof80mgthreetimesadaycomparedtotheexposureatadoseof20mgthreetimesaday.ThisconcentrationrangecoverstheincreaseinsildenafilexposureobservedinspecificallydesigneddruginteractionstudieswithCYP3A4inhibitors(exceptwiththemostpotentoftheCYP3A4inhibitorseg,ketoconazole,itraconazole,ritonavir).

CYP3A4inducersseemedtohaveasubstantialimpactonthepharmacokineticsofsildenafilinpulmonaryarterialhypertensionpatients,whichwasconfirmedinthein-vivointeractionstudywithCYP3A4inducerbosentan.

Co-administrationofbosentan(amoderateinducerofCYP3A4,CYP2C9andpossiblyofCYP2C19)125mgtwicedailywithsildenafil80mgthree

timesaday(atsteadystate)concomitantlyadministeredduring6daysinhealthyvolunteersresultedina63%decreaseofsildenafilAUC.ApopulationpharmacokineticanalysisofsildenafildatafromadultPAHpatientsinclinicaltrialsincludinga12weekstudytoassesstheefficacyandsafetyoforal

sildenafil20mgthreetimesadaywhenaddedtoastabledoseofbosentan(62.5mg–125mgtwiceaday)indicatedadecreaseinsildenafilexposurewithbosentanco-administration,similartothatobservedinhealthyvolunteers(seesections4.4and5.1).

EfficacyofsildenafilshouldbecloselymonitoredinpatientsusingconcomitantpotentCYP3A4inducers,suchascarbamazepine,phenytoin,phenobarbital,StJohn'swortandrifampicine.

Co-administrationoftheHIVproteaseinhibitorritonavir,whichisahighlypotentP450inhibitor,atsteadystate(500mgtwicedaily)withsildenafil(100mgsingledose)resultedina300%(4_fold)increaseinsildenafilCmaxanda1,000%(11_fold)increaseinsildenafilplasmaAUC.At24hours,the

plasmalevelsofsildenafilwerestillapproximately200ng/ml,comparedtoapproximately5ng/mlwhensildenafilwasadministeredalone.Thisis

consistentwithritonavir'smarkedeffectsonabroadrangeofP450substrates.Basedonthesepharmacokineticresultsco-administrationofsildenafilwithritonaviriscontraindicatedinpulmonaryarterialhypertensionpatients(seesection4.3).

Co-administrationoftheHIVproteaseinhibitorsaquinavir,aCYP3A4inhibitor,atsteadystate(1200mgthreetimesaday)withsildenafil(100mgsingledose)resultedina140%increaseinsildenafilCmaxanda210%increaseinsildenafilAUC.Sildenafilhadnoeffectonsaquinavir

pharmacokinetics.Fordoserecommendations,seesection4.2.

Whenasingle100mgdoseofsildenafilwasadministeredwitherythromycin,amoderateCYP3A4inhibitor,atsteadystate(500mgtwicedailyfor5

days),therewasa182%increaseinsildenafilsystemicexposure(AUC).Fordoserecommendations,seesection4.2.Inhealthymalevolunteers,

therewasnoevidenceofaneffectofazithromycin(500mgdailyfor3days)ontheAUC,Cmax,Tmax,eliminationrateconstant,orsubsequenthalf-lifeofsildenafiloritsprincipalcirculatingmetabolite.Nodoseadjustmentisrequired.Cimetidine(800mg),acytochromeP450inhibitorandanon-specificCYP3A4inhibitor,causeda56%increaseinplasmasildenafilconcentrationswhenco_administeredwithsildenafil(50mg)tohealthyvolunteers.Nodoseadjustmentisrequired.

ThemostpotentoftheCYP3A4inhibitorssuchasketoconazoleanditraconazolewouldbeexpectedtohaveeffectssimilartoritonavir(seesection4.3).CYP3A4inhibitorslikeclarithromycin,telithromycinandnefazodoneareexpectedtohaveaneffectinbetweenthatofritonavirandCYP3A4

inhibitorslikesaquinavirorerythromycin,aseven-foldincreaseinexposureisassumed.ThereforedoseadjustmentsarerecommendedwhenusingCYP3A4inhibitors(seesection4.2).

Thepopulationpharmacokineticanalysisinpulmonaryarterialhypertensionpatientssuggestedthatco-administrationofbeta-blockersincombinationwithCYP3A4substratesmightresultinanadditionalincreaseinsildenafilexposurecomparedwithadministrationofCYP3A4substratesalone.

GrapefruitjuiceisaweakinhibitorofCYP3A4gutwallmetabolismandmaygiverisetomodestincreasesinplasmalevelsofsildenafil.Nodoseadjustmentisrequiredbuttheconcomitantuseofsildenafilandgrapefruitjuiceisnotrecommended.

.uk/emc/product/2850/smpc/print

4/14

2026/3/311:25Revatio10mg/mlPowderforOralSuspension-SummaryofProductCharacteristics(SmPC)-printfriendly-(emc)

Singledosesofantacid(magnesiumhydroxide/aluminiumhydroxide)didnotaffectthebioavailabilityofsildenafil.

Co-administrationoforalcontraceptives(ethinyloestradiol30μgandlevonorgestrel150μg)didnotaffectthepharmacokineticsofsildenafil.

Nicorandilisahybridofpotassiumchannelactivatorandnitrate.Duetothenitratecomponentithasthepotentialtohaveseriousinteractionwithsildenafil(seesection4.3).

Effectsofsildenafilonothermedicinalproducts

Invitrostudies

SildenafilisaweakinhibitorofthecytochromeP450isoforms1A2,2C9,2C19,2D6,2E1and3A4(IC50>150μM).

Therearenodataontheinteractionofsildenafilandnon-specificphosphodiesteraseinhibitorssuchastheophyllineordipyridamole.

Invivostudies

Nosignificantinteractionswereshownwhensildenafil(50mg)wasco-administeredwithtolbutamide(250mg)orwarfarin(40mg),bothofwhicharemetabolisedbyCYP2C9.

Sildenafilhadnosignificanteffectonatorvastatinexposure(AUCincreased11%),suggestingthatsildenafildoesnothaveaclinicallyrelevanteffectonCYP3A4.

Nointeractionswereobservedbetweensildenafil(100mgsingledose)andacenocoumarol.

Sildenafil(50mg)didnotpotentiatetheincreaseinbleedingtimecausedbyacetylsalicylicacid(150mg).

Sildenafil(50mg)didnotpotentiatethehypotensiveeffectsofalcoholinhealthyvolunteerswithmeanmaximumbloodalcohollevelsof80mg/dl.

Inastudyofhealthyvolunteerssildenafilatsteadystate(80mgthreetimesaday)resultedina50%increaseinbosentanAUC(125mgtwicedaily).ApopulationpharmacokineticanalysisofdatafromastudyofadultPAHpatientsonbackgroundbosentantherapy(62.5mg-125mgtwiceaday)

indicatedanincrease(20%(95%CI:9.8-30.8))ofbosentanAUCwithco-administrationofsteady_statesildenafil(20mgthreetimesaday)ofasmallermagnitudethanseeninhealthyvolunteerswhenco-administeredwith80mgsildenafilthreetimesaday(seesections4.4and5.1).

Inaspecificinteractionstudy,wheresildenafil(100mg)wasco-administeredwithamlodipineinhypertensivepatients,therewasanadditional

reductiononsupinesystolicbloodpressureof8mmHg.Thecorrespondingadditionalreductioninsupinediastolicbloodpressurewas7mmHg.Theseadditionalbloodpressurereductionswereofasimilarmagnitudetothoseseenwhensildenafilwasadministeredalonetohealthyvolunteers.

Inthreespecificdrug-druginteractionstudies,thealpha-blockerdoxazosin(4mgand8mg)andsildenafil(25mg,50mg,or100mg)were

administeredsimultaneouslytopatientswithbenignprostatichyperplasia(BPH)stabilizedondoxazosintherapy.Inthesestudypopulations,meanadditionalreductionsofsupinesystolicanddiastolicbloodpressureof7/7mmHg,9/5mmHg,and8/4mmHg,respectively,andmeanadditional

reductionsofstandingbloodpressureof6/6mmHg,11/4mmHg,and4/5mmHg,respectivelywereobserved.Whensildenafilanddoxazosinwereadministeredsimultaneouslytopatientsstabilizedondoxazosintherapy,therewereinfrequentreportsofpatientswhoexperiencedsymptomaticposturalhypotension.Thesereportsincludeddizzinessandlightheadedness,butnotsyncope.Concomitantadministrationofsildenafiltopatientstakingalpha_blockertherapymayleadtosymptomatichypotensioninsusceptibleindividuals(seesection4.4).

Sildenafil(100mgsingledose)didnotaffectthesteadystatepharmacokineticsoftheHIVproteaseinhibitorsaquinavir,whichisaCYP3A4substrate/inhibitor.

Consistentwithitsknowneffectsonthenitricoxide/cGMPpathway(seesection5.1),sildenafilwasshowntopotentiatethehypotensiveeffectsofnitrates,anditsco-administrationwithnitricoxidedonorsornitratesinanyformisthereforecontraindicated(seesection4.3).

Riociguat:PreclinicalstudiesshowedadditivesystemicbloodpressureloweringeffectwhenPDE5inhibitorswerecombinedwithriociguat.Inclinicalstudies,riociguathasbeenshowntoaugmentthehypotensiveeffectsofPDE5inhibitors.Therewasnoevidenceoffavourableclinicaleffectofthecombinationinthepopulationstudied.ConcomitantuseofriociguatwithPDE5inhibitors,includingsildenafil,iscontraindicated(seesection4.3).

Sildenafilhadnoclinicallysignificantimpactontheplasmalevelsoforalcontraceptives(ethinyloestradiol30μgandlevonorgestrel150μg).

Additionofasingledoseofsildenafiltosacubitril/valsartanatsteadystateinpatientswithhypertensionwasassociatedwithasignificantlygreater

bloodpressurereductioncomparedtoadministrationofsacubitril/valsartanalone.Therefore,cautionshouldbeexercisedwhensildenafilisinitiatedinpatientstreatedwithsacubitril/valsartan.

Paediatricpopulation

Interactionstudieshaveonlybeenperformedinadults.

4.6Fertility,pregnancyandlactation

Womenofchildbearingpotentialandcontraceptioninmalesandfemales

DuetolackofdataoneffectsofRevatioinpregnantwomen,Revatioisnotrecommendedforwomenofchildbearingpotentialunlessalsousingappropriatecontraceptivemeasures.

Pregnancy

Therearenodatafromtheuseofsildenafilinpregnantwomen.Animalstudiesdonotindicatedirectorindirectharmfuleffectswithrespecttopregnancyandembryonal/foetaldevelopment.Studiesinanimalshaveshowntoxicitywithrespecttopostnataldevelopment(seesection5.3).

Duetolackofdata,Revatioshouldnotbeusedinpregnantwomenunlessstrictlynecessary.

Breast-feeding

Therearenoadequateandwellcontrolledstudiesinlactatingwomen.DatafromonelactatingwomanindicatethatsildenafilanditsactivemetaboliteN-desmethylsildenafilareexcretedintobreastmilkatverylowlevels.Noclinicaldataareavailableregardingadverseeventsinbreast-fedinfants,butamountsingestedwouldnotbeexpectedtocauseanyadverseeffects.Prescribersshouldcarefullyassessthemother'sclinicalneedforsildenafilandanypotentialadverseeffectsonthebreast_fedchild.

Fertility

Non-clinicaldatarevealednospecialhazardforhumansbasedonconventionalstudiesoffertility(seesection5.3).

4.7Effectsonabilitytodriveandusemachines

Revatiohasm