SlideShare a Scribd company logo

C 02

•
•
S
sorinciuciuc

Cours spécialisés pour les médecins de famille et spécialistes - sous les auspices de Collège des Médecins Roumain sur : Nutrition et les suppléments, Les vitamines BIO et les suppléments minéraux thérapeutiques, Cardiologie et diabétologie, Nutrition infantile, Articles de cosmétologie

Health & Medicine
1 of 235
Download to read offline
1 SWOTAnalysis on HipolipemiantMarket bySorinCiuciuc forTerapiaS.A.
2 MedicalSWOTAnalysis ProductsontheMarket: •Zocor(Simvastatinum)–MSD •Vasilip(Simvastatinum)–KRKA •Sortis(Atorvastatinum)–Pfizer •Lipanthyl(Fenofibratum)–LaboratoiresFournier •Regadrin(Bezafibratum)–BerlinChemie
3 ClassMajorMolecules OnRomanianMarket MechanismofActionTherapeutic Indications StatinesAtorvastatinum Fluvastatinum Lovastatinum Pravastatinum Simvastatinum HMGCo-AreductaseinhibitingHyper-lipoproteinemias TypeIIa,IIb FibratesBezafibratum Ciprofibratum Fenofibratum Gemfibrozilum TGsynthesisinhibition, EnhanceVLDLcatabolism Hyper-lipoproteinemias TypeIIb,III,IV,V BiliaryAcids blockers NoneBindingbiliaryacids,thus blockingintestinal reabsorbtion Hyper-lipoproteinemias TypeIIa,IIb Nicotinic Acidand Derivates AcipimoxumHyper-lipoproteinemias TypeII,III OthersMoleculesunknownVariousNonspecific MedicalProperties
4 Zocor&Vasilip(Simvastatinum) MedicalSWOTAnalysis -30 -20 -10 0 10 20 % TOTAL-CLDL-CHDL-CTG* EficientaZocor(studiupe6sapt.) Lower Dose Comparativ Simvastatin 5mgqpm Simvastatin 10mgqpm -40 -30 -20 -10 0 10 % TOTAL-CLDL-CHDL-CTG* EficientaZocor(studiu6sapt.) Placebo Simvastatin 20mgqpm-50 -40 -30 -20 -10 0 10 % TOTAL-CLDL-CHDL-CTG* EficientaZocor(studiu18-24sapt.) Simvastatin 40mgqpm Simvastatin 80mgqpm Strengths: •lowersTotal-Chol,LDL-Chol andTGevenatsmallerdoses •highestefficiencyat20mgdose •increasedHDL-Cholmaintained athigherdoses
Zocor&Vasilip(Simvastatinum) MedicalSWOTAnalysis Weaknesses: •althoughisequallyefficientonTotal- CholandLDL-Cholloweringas fenofibrate,itisnotefficientonTG loweringintypeIIaHLP •furthermore,intypeIIbHLPtheenhance ofHDL-Cholfractionissmallerandthe effectuponTGlevelisreversed, comparedwithfenofibrate •limitedtherapeuticspectrumtotypeIIa andIIbHLP
6 Zocor&Vasilip(Simvastatinum) MedicalSWOTAnalysis Opportunities: •newlaunchedgroupofhipolipemiantagents,likeEzetimibes,whichmaybe recommendedinacombinedtherapywithHMGCo-Areductaseinhibitors -25 -20 -15 -10 -5 0 5 % Total- C LDL- C Apo B TGbHDL- C ZetiaefficiencywhencombinedwiyhHMG Co-AreductaseInhibitors On-goingHMG-CoA reductaseinhibitor +Placebod On-goingHMG-CoA reductaseinhibitor +ZETIAd
7 Zocor&Vasilip(Simvastatinum) MedicalSWOTAnalysis Threats: •costoftreatment/dayishigh •newtypesofmoleculeswhichmightbeavailablesoon(Ezetimides) -20 -15 -10 -5 0 5 % Total- C LDL-CApoBTGaHDL-C ZetiaefficiencyinLipidMetabolismmanagement Placebo Ezetimibe
8 Sortis(Atorvastatinum) MedicalSWOTAnalysis -40 -30 -20 -10 0 10 % LDL-CTGNon- HDL- C/HDL- C StudiuAtorvastatina/Lovastatina Study1 Atorvastatin 10mg Lovastatin20 mg -40 -35 -30 -25 -20 -15 -10 -5 0 5 10 % ApoBNon- HDL- C/HDL- C StudiuAtorvastatina/Pravastatina Atorvastatin 10mg Pravastatin 20mg Strengths: •accordingtothesestudies, Atorvastatinumismoreefficientthan Pravastatinum,Lovastatinumand Simvastatinum -40 -30 -20 -10 0 10 % LDL-CTGNon- HDL- C/HDL- C StudiuAtorvastatina/Simvastatina Atorvastatin10mg Simvastatin10mg
9 Sortis(Atorvastatinum) MedicalSWOTAnalysis Weaknesses: •sharpusage spectrum,although lateststudies conductedbythe producertendto broadenthe therapeutic spectrum Pharmacologic Action FenofibrateAtorvastatine TGlowering+++/- HDL-cholesterol enhance +++/- Totalcholesterol lowering +/-++ LDL-cholesterol lowering +/-++ Therapeutic Indications Hyper- lipoproteinemias TypeIIb,III,IV,V Hyper- lipoproteinemias TypeIIa,IIb
10 Sortis(Atorvastatinum) MedicalSWOTAnalysis Opportunities: •lateststudiesconductedbytheproducertendtobroadenthetherapeutic spectrumtowardstypesIIIandIVHLP •newlaunchedgroupofhipolipemiantagents,likeEzetimibes,which mayberecommendedinacombinedtherapywithHMGCo-Areductase inhibitors -25 -20 -15 -10 -5 0 5 % Total- C LDL- C Apo B TGbHDL- C ZetiaefficiencywhencombinedwiyhHMGCo-A reductaseInhibitors On-goingHMG-CoA reductaseinhibitor +Placebod On-goingHMG-CoA reductaseinhibitor +ZETIAd
11 Sortis(Atorvastatinum) MedicalSWOTAnalysis Threats: •costoftreatment/dayishigh •newtypesofmoleculeswhichmightbeavailablesoon(Ezetimides) -20 -15 -10 -5 0 5 % Total- C LDL-CApoBTGaHDL-C ZetiaefficiencyinLipidMetabolismmanagement Placebo Ezetimibe
12 Lipanthyl(Fenofibratum) MedicalSWOTAnalysis EfectulFenofibratului asupraHDL-C -5 0 5 10 15 20 25 02468 PacienticuTG=350-499mg/dl (%)mediudevariatie delavaloareade baza Strengths: •lowerstheTotal-Chol •lowersLDL-Choland VLDL-Cholfractions •lowersTGlevel •hypo-lipidemiant agentwiththebroadest therapeuticalspectrum, indicatedintypesIIb, III,IVandVHLP •thelongclinicalusage insurethesafetyand clinicalefficiencyand providednewideasof pharmacological improvements 0 5 10 15 20 25 30 02468 PacienticuTG=500-1500mg/dl Placebo Fenofibrat
13 Lipanthyl(Fenofibratum) MedicalSWOTAnalysis Weaknesses: •themedicaldebatebetweenstatinesandfibratesinterventioninlipid metabolismmanagementisinfulldevelopment,withoutproclaiminga “winner”
14 Lipanthyl(Fenofibratum) MedicalSWOTAnalysis Opportunities: •fenofibratehasahigherefficiency thansimvastatinum,especiallyin loweringTGandLDL-Cholfraction andenhancingHDL-Chol,coronary protectivefraction •fenofibratehasahigherefficiency thanbezafibratuminmanagingall thecomponentsalteredin dyslipidemias 26% 38,70% 41,50% 54,10% 27,50% 39,10% 15% 27,80% 0% 10% 20% 30% 40% 50% 60% Reducerea colesteroluluiseric total ReducereaVLDL- colesterol ReducereaTGtotaleCrestereaHDL- colesterol StudiucomparativBezafibrat-Fenofibrat Bezafibrat(400mg)Fenofibrat(200mg)
15 Lipanthyl(Fenofibratum) MedicalSWOTAnalysis Threats: •themedicaldebatebetweenstatines andfibratesinterventioninlipid metabolismmanagementisinfull development •fenofibrateistheleaderoffibratesin thisdebate •enteringinthisdebatewithoutworld- widesupportmaynotbeusefulforthe imageoftheproduct(“Statindrugsgivento patientswithtype2diabeteswithknowncoronary diseasehavebeenshowntoreducecoronary events,eveninthosewithmildlipidabnormalities. Fenofibrateappearstoreducetherateof angiographicprogressionofatherosclerosisbut hasnotbeenshowntoreducecoronaryevents.” -Conclusion5ofDAISStudy) -25 -20 -15 -10 -5 0 5 % Total- C LDL- C Apo B TGbHDL- C ZetiaefficiencywhencombinedwiyhHMG Co-AreductaseInhibitors On-goingHMG-CoA reductaseinhibitor +Placebod On-goingHMG-CoA reductaseinhibitor +ZETIAd •newgroupofhipolipemiantagents, likeEzetimibes,whichmaybe administeredalongwithHMGCo-A reductaseinhibitors
16 Regadrin(Bezafibratum) MedicalSWOTAnalysis Strenghts:
17 Regadrin(Bezafibratum) MedicalSWOTAnalysis Weaknesses: •bezafibratumhasalowerefficiencythanfenofibratuminmanaging allthecomponentsalteredindyslipidemias 26% 38,70% 41,50% 54,10% 27,50% 39,10% 15% 27,80% 0% 10% 20% 30% 40% 50% 60% Reducerea colesteroluluiseric total ReducereaVLDL- colesterol ReducereaTGtotaleCrestereaHDL- colesterol StudiucomparativBezafibrat-Fenofibrat Bezafibrat(400mg)Fenofibrat(200mg)
18 Regadrin(Bezafibratum) MedicalSWOTAnalysis Opportunities:
19 Regadrin(Bezafibratum) MedicalSWOTAnalysis Threats: •themedicaldebatebetweenstatines andfibratesinterventioninlipid metabolismmanagementisinfull development •fenofibrateistheleaderoffibratesin thisdebate •enteringinthisdebatewithoutworld- widesupportmaynotbeusefulforthe imageoftheproduct(“Statindrugsgivento patientswithtype2diabeteswithknowncoronary diseasehavebeenshowntoreducecoronary events,eveninthosewithmildlipidabnormalities. Fenofibrateappearstoreducetherateof angiographicprogressionofatherosclerosisbut hasnotbeenshowntoreducecoronaryevents.” -Conclusion5ofDAISStudy) •newgroupofhipolipemiantagents, likeEzetimibes,whichmaybe administeredalongwithHMGCo-A reductaseinhibitors -25 -20 -15 -10 -5 0 5 % Total- C LDL- C Apo B TGbHDL- C ZetiaefficiencywhencombinedwiyhHMG Co-AreductaseInhibitors On-goingHMG-CoA reductaseinhibitor +Placebod On-goingHMG-CoA reductaseinhibitor +ZETIAd
20 MarketingSWOTAnalysis ProductsontheMarket: •Zocor(Simvastatinum)–MSD •Vasilip(Simvastatinum)–KRKA •Sortis(Atorvastatinum)–Pfizer •Lipanthyl(Fenofibratum)–LaboratoiresFournier •Regadrin(Bezafibratum)–BerlinChemie
21 Zocor(Simvastatinum) MarketingSWOTAnalysis 0 100 200 300 400 500 600 700 800 '000 1998_units2000_units2002_units HipolipemiantMarketEvolution-Units SIMVASTATINUM Totalgeneral Strengths: •Simvastatinumistheleading moleculeinthehipolipemiant marketanditsgrowthinsuredthe totalgrowthofthemarketinthepast 5years 0 1000 2000 3000 4000 5000 6000 7000 8000 '000 1998_usd2000_usd2002_usd HipolipemiantmarketEvolution-Value SIMVASTATINUM Totalgeneral
22 Zocor(Simvastatinum) MarketingSWOTAnalysis 0 50 100 150 200 250 '000 1998_units2000_units2002_units SimvastatinumEvolution-Units Zocor SIMVASTATINUM Weaknesses: •newgenericSimvastatinum enteredmanageto“steal”app. 15%fromZocorbusiness 0 500 1000 1500 2000 2500 3000 3500 4000 '000 1998_usd2000_usd2002_usd SimvastatinumEvolution-Value Zocor SIMVASTATINUM
23 Zocor&Vasilip(Simvastatinum) MarketingSWOTAnalysis Opportunities: •newlaunchedgroupofhipolipemiantagents,likeEzetimibes,whichmaybe recommendedinacombinedtherapywithHMGCo-Areductaseinhibitors -25 -20 -15 -10 -5 0 5 % Total- C LDL- C Apo B TGbHDL- C ZetiaefficiencywhencombinedwiyhHMG Co-AreductaseInhibitors On-goingHMG-CoA reductaseinhibitor +Placebod On-goingHMG-CoA reductaseinhibitor +ZETIAd
24 Zocor&Vasilip(Simvastatinum) MarketingSWOTAnalysis Threats: •costoftreatment/dayishigh •newtypesofmoleculeswhichmightbeavailablesoon(Ezetimides) -20 -15 -10 -5 0 5 % Total- C LDL-CApoBTGaHDL-C ZetiaefficiencyinLipidMetabolismmanagement Placebo Ezetimibe
25 Vasilip(Simvastatinum) MarketingSWOTAnalysis 0 500 1000 1500 2000 2500 3000 3500 4000 '000 2001_usd2002_usd SimvastatinumEvolution-Value Zocor SIMVASTATINUM Strengths: •Simvastatinumistheleading moleculeinthehipolipemiant marketanditsgrowthinsured thetotalgrowthofthemarketin thepast5years •Newgenericsinvastatinum manageto“steal”app.15%in valueandunitsinthefirstyear onthemarket 0 50 100 150 200 250 '000 2001_units2002_units SimvastatinumEvolution-Units Zocor SIMVASTATINUM
26 Vasilip(Simvastatinum) MarketingSWOTAnalysis Weaknesses:
27 Vasilip(Simvastatinum) MarketingSWOTAnalysis Opportunities: •newlaunchedgroupofhipolipemiantagents,likeEzetimibes,whichmaybe recommendedinacombinedtherapywithHMGCo-Areductaseinhibitors -25 -20 -15 -10 -5 0 5 % Total- C LDL- C Apo B TGbHDL- C ZetiaefficiencywhencombinedwiyhHMG Co-AreductaseInhibitors On-goingHMG-CoA reductaseinhibitor +Placebod On-goingHMG-CoA reductaseinhibitor +ZETIAd
28 Vasilip(Simvastatinum) MarketingSWOTAnalysis Threats: •newtypesofmoleculeswhichmightbeavailablesoon(Ezetimides) -20 -15 -10 -5 0 5 % Total- C LDL-CApoBTGaHDL-C ZetiaefficiencyinLipidMetabolismmanagement Placebo Ezetimibe
29 Sortis(Atorvastatinum) MarketingSWOTAnalysis 0 100 200 300 400 500 600 700 800 '000 1998_units2000_units2002_units HipolipemiantMarketEvolution-Units Sortis Totalgeneral Strengths: •althoughinunitsSortisgrowth barelyreachapp.10%,itsgrowth invalueisover20% 0 1000 2000 3000 4000 5000 6000 7000 8000 '000 1998_usd2000_usd2002_usd HipolipemiantmarketEvolution-Value Sortis Totalgeneral
30 Sortis(Atorvastatinum) MarketingSWOTAnalysis Weaknesses:
31 Opportunities: •newlaunchedgroupofhipolipemiantagents,likeEzetimibes,whichmaybe recommendedinacombinedtherapywithHMGCo-Areductaseinhibitors -25 -20 -15 -10 -5 0 5 % Total- C LDL- C Apo B TGbHDL- C ZetiaefficiencywhencombinedwiyhHMG Co-AreductaseInhibitors On-goingHMG-CoA reductaseinhibitor +Placebod On-goingHMG-CoA reductaseinhibitor +ZETIAd Sortis(Atorvastatinum) MarketingSWOTAnalysis
32 Threats: •costoftreatment/dayishigh •newtypesofmoleculeswhichmightbeavailablesoon(Ezetimides) -20 -15 -10 -5 0 5 % Total- C LDL-CApoBTGaHDL-C ZetiaefficiencyinLipidMetabolismmanagement Placebo Ezetimibe Sortis(Atorvastatinum) MarketingSWOTAnalysis
33 Lipanthyl(Fenofibratum) MarketingSWOTAnalysis FenofibratvsMarketEvolution-Units 0 100 200 300 400 500 600 700 800 900 1998_units1999_units2000_units2001_units2002_units FENOFIBRATUM Totalgeneral Strengths: •followsthetrendofthemarket
34 Lipanthyl(Fenofibratum) MarketingSWOTAnalysis Weaknesses: •valuewise,fenofibrateslostthemarket“explosion”generatedbystatines FenofibratvsMarketEvolution-Value 0 1000 2000 3000 4000 5000 6000 7000 8000 1998_usd1999_usd2000_usd2001_usd2002_usd FENOFIBRATUM Totalgeneral
35 Lipanthyl(Fenofibratum) MarketingSWOTAnalysis Opportunities:
36 Lipanthyl(Fenofibratum) MarketingSWOTAnalysis Threats: •themedicaldebatebetweenstatinesandfibratesinterventioninlipid metabolismmanagementisinfulldevelopment •fenofibrateistheleaderoffibratesinthisdebate •enteringinthisdebatewithoutworld-widesupportmaynotbeusefulforthe imageoftheproduct “Statindrugsgiventopatientswithtype2diabetes withknowncoronarydiseasehavebeenshownto reducecoronaryevents,eveninthosewithmildlipid abnormalities.Fenofibrateappearstoreducetherate ofangiographicprogressionofatherosclerosisbuthas notbeenshowntoreducecoronaryevents.” -Conclusion5ofDAISStudy
37 Regadrin(Bezafibratum) MarketingSWOTAnalysis Strengths:
38 Regadrin(Bezafibratum) MarketingSWOTAnalysis Weaknesses:
39 Regadrin(Bezafibratum) MarketingSWOTAnalysis Opportunities:
40 Regadrin(Bezafibratum) MarketingSWOTAnalysis Threats:
41 EfectulFenofibratului asupraHDL-C -5 0 5 10 15 20 25 02468 PacienticuTG=350-499mg/dl (%)mediudevariatie delavaloareade baza Strengths: •lowerstheTotal-Chol •lowersLDL-Choland VLDL-Cholfractions •lowersTGlevel •hypo-lipidemiant agentwiththebroadest therapeuticalspectrum, indicatedintypesIIb, III,IVandVHLP •thelongclinicalusage insurethesafetyand clinicalefficiencyand providednewideasof pharmacological improvements 0 5 10 15 20 25 30 02468 PacienticuTG=500-1500mg/dl Placebo Fenofibrat LipofibSR(Fenofibratum) MedicalSWOTAnalysis
42 LipofibSR(Fenofibratum) MedicalSWOTAnalysis Weaknesses: •newlaunchedgroupofhipolipemiantagents,likeEzetimibes,whichmaybe recommendedinacombinedtherapywithHMGCo-Areductaseinhibitors -25 -20 -15 -10 -5 0 5 % Total- C LDL- C Apo B TGbHDL- C ZetiaefficiencywhencombinedwiyhHMG Co-AreductaseInhibitors On-goingHMG-CoA reductaseinhibitor +Placebod On-goingHMG-CoA reductaseinhibitor +ZETIAd
43 LipofibSR(Fenofibratum) MedicalSWOTAnalysis Opportunities: •fenofibratehasahigherefficiency thansimvastatinum,especiallyin loweringTGandLDL-Cholfraction andenhancingHDL-Chol,coronary protectivefraction •fenofibratehasahigherefficiency thanbezafibratuminmanagingall thecomponentsalteredin dyslipidemias 26% 38,70% 41,50% 54,10% 27,50% 39,10% 15% 27,80% 0% 10% 20% 30% 40% 50% 60% Reducerea colesteroluluiseric total ReducereaVLDL- colesterol ReducereaTGtotaleCrestereaHDL- colesterol StudiucomparativBezafibrat-Fenofibrat Bezafibrat(400mg)Fenofibrat(200mg)
44 LipofibSR(Fenofibratum) MedicalSWOTAnalysis Threats: •themedicaldebatebetweenstatines andfibratesinterventioninlipid metabolismmanagementisinfull development •fenofibrateistheleaderoffibratesin thisdebate •enteringinthisdebatewithoutworld- widesupportmaynotbeusefulforthe imageoftheproduct(“Statindrugsgivento patientswithtype2diabeteswithknowncoronary diseasehavebeenshowntoreducecoronary events,eveninthosewithmildlipidabnormalities. Fenofibrateappearstoreducetherateof angiographicprogressionofatherosclerosisbut hasnotbeenshowntoreducecoronaryevents.” -Conclusion5ofDAISStudy) •newgroupofhipolipemiantagents, likeEzetimibes,whichmaybe administeredalongwithHMGCo-A reductaseinhibitors -25 -20 -15 -10 -5 0 5 % Total- C LDL- C Apo B TGbHDL- C ZetiaefficiencywhencombinedwiyhHMG Co-AreductaseInhibitors On-goingHMG-CoA reductaseinhibitor +Placebod On-goingHMG-CoA reductaseinhibitor +ZETIAd
45 LipofibSR(Fenofibratum) MarketingSWOTAnalysis FenofibratvsMarketEvolution-Units 0 100 200 300 400 500 600 700 800 900 1998_units1999_units2000_units2001_units2002_units FENOFIBRATUM Totalgeneral Strengths: •followsthemarketgrowingtrend
46 LipofibSR(Fenofibratum) MarketingSWOTAnalysis Weaknesses: •intermsofvalue,fenofibrateshavelostthepacewiththe“market explosion”causedbystatines FenofibratvsMarketEvolution-Value 0 1000 2000 3000 4000 5000 6000 7000 8000 1998_usd1999_usd2000_usd2001_usd2002_usd FENOFIBRATUM Totalgeneral
47 LipofibSR(Fenofibratum) MarketingSWOTAnalysis Opportunities:
48 LipofibSR(Fenofibratum) MarketingSWOTAnalysis Threats: •themedicaldebatebetweenstatinesandfibratesinterventioninlipid metabolismmanagementisinfulldevelopment •fenofibrateistheleaderoffibratesinthisdebate •enteringinthisdebatewithoutworld-widesupportmaynotbeusefulforthe imageoftheproduct “Statindrugsgiventopatientswithtype2diabetes withknowncoronarydiseasehavebeenshownto reducecoronaryevents,eveninthosewithmildlipid abnormalities.Fenofibrateappearstoreducetherate ofangiographicprogressionofatherosclerosisbuthas notbeenshowntoreducecoronaryevents.” -Conclusion5ofDAISStudy
LipofibSR250mg (fenofibratmicronizat) LipofibSR250mg Capsulecueliberareprelungită
Proprietăţigenerale •LipofibSR250mgesteunagentregulatorallipidemiei, pebazădefenofibratmicronizat. •LipofibSR250mgprezintăonouăformularefarmaceutică, cueliberareprelungită. •LipofibSR250mgbeneficiazădepeste30anideexperienţăclinică, validatăprintr-omultitudinedestudiiclinice. LipofibSR250mg Capsulecueliberareprelungită
Efectefarmacologice LipofibSR250mgdetermină: •scădereacolesteroluluiplasmatictotal; •scădereafracţiilordeLDL-colesterolşiVLDL-colesterol; •scădereaniveluluiplasmaticdetrigliceride; •creştereaniveluluiplasmaticalfracţiei“protective”deHDL-colesterol. LipofibSR250mg Capsulecueliberareprelungită
Farmacocinetică •AbsorbţiaLipofibSR250mgdintractuldigestiveste deaproximativ85%,atingândunpeakplasmaticdupă6-8ore. •Distribuţiaplasmaticăstabilăesteatinsăla5ziledelaprima administrare,fărăevidenţiereafenomenelordeacumularela administrareaprelungită. •Metabolizareafenofibratuluiesterealizatădecătreesteraze laacidfenofibric-metabolitulactiv. •ExcreţiaLipofibSR250mgestepredominantrenală(65%). •T½deaproximativ20oreoferăposibilitateaadministrăriiodatăpezi. LipofibSR250mg Capsulecueliberareprelungită
Formafarmaceuticăcueliberareprelungită… •Menţinestabilăconcentraţiaterapeuticăeficientă. •Reducenumăruldeadministrărişidozazilnicătotală, diminuândefecteletoxice. •Amelioareazărezultateleobţinute,maialesîntratamentul bolilorcronice. •Scadecosturiletotalealetratamentului. LipofibSR250mg Capsulecueliberareprelungită
…îmbunătăţeştecomplianţapacientului! •Scădereadramaticăa complianţeipacientuluila administrareaamaimultde3 dozezilniceestebinecunoscută. •Reducereanumarului administrărilorasiguratăde formelefarmaceuticecueliberare prelungităreprezintăceamai eficientăsoluţieînterapiade lungădurată. LipofibSR250mg Capsulecueliberareprelungită 83 75 59 0 10 20 30 40 50 60 70 80 90 complianta% 1admin/zi 2admin/zi 3admin/zi •Îmbunătăţireaprogresivăacomplianţei(dela60%la3administrari pezila85%pentru1doză/zi)areoimportanţăsporită,maialesîn cazulbolilorcronice“silenţioase”clinic(cardiopatii,diabetzaharat).
Dozareeficientasisigura LipofibSR250mg asigura: atingereasi mentinerea dozeioptimeinca dinprimelezilede tratament, fara efecte adverse! LipofibSR250mg Capsulecueliberareprelungită 0 50 100 150 200 250 300 350 Z1 Z2 Z3 Z4 Z5 ziletratament mgsubstantaactiva/zi intervaloptimterapeutic dozaminima terapeutica adaptatdupaEthypharm DrugDeliverySolutions,1999
Mecanismdeacţiune LipofibSR250mgacţioneazaastfel: •inhibăsintezatrigliceridelor,scazândnivelullorplasmatic; consecutiv,scadeeliberareaVLDL-colesterolîncirculaţie. •stimuleazăcatabolismullipoproteinelorbogateîntrigliceride (VLDL-colesterol). •reducenivelulplasmaticdeaciduric,princreştereaexcreţieiurinare. LipofibSR250mg Capsulecueliberareprelungită
CaracteristicileunicealeLipofibSR250mg… •Agentregulatorallipidemiei,pebazădefenofibratmicronizat, cuurmătoareleefectelefarmacologice: -scădereacolesteroluluiplasmatictotal; -scădereafracţiilordeLDL-colesterolşiVLDL-colesterol; -scădereaniveluluiplasmaticdetrigliceride; -creştereaniveluluiplasmaticalfracţieideHDL-colesterol. •Onouăformularefarmaceutică,cueliberareprelungită,ceasigură complianţamaximă. •Dozade250mgasiguraunplusdesigurantainatingereasimentinerea dozeieficienteterapeutic,faraexacerbareaefecteloradverse. •Peste30anideexperienţăclinică,validatăprinmultiplestudii. …conduclareconsiderareaterapeuticăafenofibratului. LipofibSR250mg Capsulecueliberareprelungită
Indicaţiiterapeutice LipofibSR250mgesteunagenthipolipemiantadministrabiladulţilor, cuurmătoareleindicaţiiterapeutice: •hipertrigliceridemiesimplă(tipIV); •hipertrigliceridemiecombinată(tipIIb,III); •hipercolesterolemie(tipIIa)-atuncicândregimuldietetic nuestesuficient,iarcolesterolemiarămâneridicată,chiarîncondiţiile dieteiadecvateşi/saudupăînlăturareafactorilorderisc. Respectarearegimuluidieteticesteabsolutnecesarăîntimpultratamentului.Acestmedicament, înasocierecudieta,constituieuntratamentsimptomaticpetermenlung,acăruieficacitatetrebuie evaluatăînmodregulat. LipofibSR250mg Capsulecueliberareprelungită
Hiperlipoproteinemii-strategiidecontrol NikkilaEA,1983 BrownWV,1986 KeatingGM,OrmrodD,2002 GuayDP,2002 LipofibSR250mg Capsulecueliberareprelungită
Hiperlipoproteinemii-opţiuniterapeutice Clasa Moleculelemai importanteMecanismdeacţiuneIndicaţiiterapeutice StatineAtorvastatinum Fluvastatinum Lovastatinum Pravastatinum Simvastatinum InhibitorideHMGCo-A reductaza Hiperlipoproteinemii TipIIa,IIb FibraţiBezafibratum Ciprofibratum Fenofibratum Gemfibrozilum InhibăsintezaTG, creştecatabolismul VLDL Hiperlipoproteinemii TipIIb,III,IV,V Chelanţide acizibiliari NuecazulLeagăaciziibiliari, împiedicândreabsorbţia Hiperlipoproteinemii TipIIa,IIb Acidnicotinic şiderivaţi AcipimoxumHiperlipoproteinemii TipII,III LipofibSR250mg Capsulecueliberareprelungită
Acţiuneafenofibratuluiînhiperlipoproteinemii KeatingGM,OrmrodD,2002 BrissonD,etal.,2002 leRouxCW,MurphyE,SeedM,2002 GuayDP,2002 SasakiJ,YamamotoK,AgetaM,2002 LipofibSR250mg Capsulecueliberareprelungită
Dateleclinicedemonstreazăeficienţafenofibratuluiîn… …încetinireaprogresieiaterosclerozeicoronarelapacienţiicudiabet zaharattipII,princreştereafracţieiHDL-colesterol; Theeffectoffenofibrateontheprogressionofcoronaryheartdiseaseinpatientswithtype2diabetes-thediabetes aterosclerosisinterventiontrial–randomizedtrial(DAIS).Lancet,2001 …tratamentulhipercolesterolemiei; ThirdreportoftheNationalCholesterolEducationProgram-NCEP).Expertpanelon:detection,evaluationandtreatmentof highbloodcholesterolinadults …managementulpetermenlungaldislipidemiilormetabolice; Micronisedfenofibrate:anupdatedreviewofitsclinicalefficacyinthemanagementofdyslipidaemia,2002 …tratamentulpacientilordislipidemici; EffectsofmicronizedfenofibrateversusatorvastatininthetreatmentofdyslipidaemicpatientswithlowplasmaHDL- cholesterollevels,2002; ComparisonoftheeffectsofatorvastatinorfenofibrateonnonlipidbiochemicalriskfactorsandtheLDLparticlesizein subjectswithcombinedhyperlipidemia,2002; Efficacyofatorvastatincomparedwithfenofibrateinpacientswithcombinedhyperlipemia.XIIthIntSymposium AtherosclerosisISA,2000; LipofibSR250mg Capsulecueliberareprelungită
EficienţafenofibratuluiîndislipidemiiletipIVşiV GoldbergAC,1989 SasakiJ,YamamotoK,AgetaM.,2002 LipofibSR250mg Capsulecueliberareprelungită
Eficienţafenofibratuluiîntrigliceridemii -41% -17% 18% 15% -25% 0% -50% -40% -30% -20% -10% 0% 10% 20% modificari%postterapeutic TGHDL-colAcuric pacienticuHLPtipIIasiIIb Fenofibrat Simvastatina DespresJP,DelavalD,2002 SebestjenM,KeberI,2002 SteinmetzAetal.,1996 FarnierM,TurpinG,2000 LipofibSR250mg Capsulecueliberareprelungită Fenofibratul înregistrează scorurimaibune peTGsiHDL-col, comparativcu simvastatinaîn HLPtipIIaşiIIb.
Eficienţafenofibratuluifaţădesimvastatină -28%-28% -34% -36% 0%0% -37% 0% -40% -35% -30% -25% -20% -15% -10% -5% 0% modificari%postterapeutic Col-totalLDL-colHDL-colTG pacienticuHLPtipIIa Fenofibrat Simvastatina FermierM,etal.,1994 LipofibSR250mg Capsulecueliberareprelungită Fenofibratulare eficacitatesimilara simvastatineiasupra Col-totalsiafractiei LDL-collapacienţii cuHLPtipIIa.
Eficienţafenofibratuluifaţădesimvastatină -23%-22%-25% -30% 29% 17% -52% 18% -60% -50% -40% -30% -20% -10% 0% 10% 20% 30% modificari%postterapeutic Col-totalLDL-colHDL-colTG pacienticuHLPtipIIb Fenofibrat Simvastatina FermierM,etal.,1994 LipofibSR250mg Capsulecueliberareprelungită Fenofibratul estesuperiorin HLPtipIIb,atatprin scadereafractieiLDL-col siaTG,citsiprin crestereafractiei protectiveHDL-col.
Eficienţafenofibratuluifaţădeatorvastatină DespresJP,DelavalD.,2002 SebestjenM,KeberI.,2002 GuayDP.,2002 FarnierM,TurpinG,2000 LipofibSR250mg Capsulecueliberareprelungită
-26% -39%-42% -54% -28% -39% 15% 28% -1 -1 0 0 0 0 0 0 0 0 Reducerea colesterolului serictotal Reducerea VLDL- colesterol Reducerea TGtotale Cresterea HDL- colesterol Bezafibrat (400mg) Fenofibrat (200mg) modificari%postterapeutic FeussnerG,KurthB, LohrmannJ,1997 LipofibSR250mg Capsulecueliberareprelungită Eficienţafenofibratuluifaţădebezafibrat Fenofibratul estesuperior bezafibratului reducândeficient atatCol-totalsiTG, citsifractiaVLDL. Crestereafractiei protectiveHDL-col estemaipronuntata.
StudiuclinicpentruLipofibSR250mg •Scopul:determinareaeficienţeiterapeuticeaLipofibSR250mgîn dislipidemiilesindromuluimetabolic,încolaborarecuCentruldeDiabet, NutritieşiBoliMetabolicedinClujNapoca. •Sponsor:TerapiaS.A.ClujNapoca. •Coordonatorstudiu:Prof.Univ.Dr.NicolaeHancu,şefulCentrului deDiabet,NuţritieşiBoliMetaboliceClujNapoca. •Investigatori:Dr.GabrielaRoman,Dr.CorneliaBala,Dr.I.A.Veresiu, Dr.LiviaDuma. •Laborator:Dr.MarianaCoca. LipofibSR250mg Capsulecueliberareprelungită
StudiuincursalCentruluiClinicdeDiabet, NutritiesiBoliMetaboliceClujNapoca LipofibSR250mg Capsulecueliberareprelungită Rezultatelepartialealestudiuluiclinic Beneficiileterapieicu LipofibSR250mg, dupa6saptamani: •Coltotalcu14,1% •LDL-colcu18,4% •HDL-colcu16,2% •TGcu38,2% 244.9 210.8 141.2 115.1 3641.9 554.3 342 0 100 200 300 400 500 600 modificarilepostterapeutice ColtotalLDL-colHDL-colTG I-aVizita aII-aVizita N=51,p<0,005
ModdeprezentareLipofibSR250mg •cutieoriginalăcu3blisterex10capsulecueliberareprelungită LipofibSR250mg Capsulecueliberareprelungită
LIPOFIBSRLIPOFIBSR 2004September,Malta2004September,Malta PM:SORINCIUCIUCPM:SORINCIUCIUC
1.MarketEvolution-i HipolipemiantMarketgrewwith140%USDand136%UN,basedon: •Fenofibratum(154%USDand120%UN) •Simvastatine(142%USDand182%UN) •Atorvastatine(136%USDand134%UN) FenofibratesMarket: •LipofibSR220%UNand242%USD2004F •Lipanthyl200mg107%UNand125%USD2004F •Lipivim-6%UNand–1%USD2004F •NewarrivalforLipanthylSupra
1.MarketEvolution-ii SalesUn&Val2003-2004 0 10000 20000 30000 40000 50000 60000 70000 80000 IanFebMarAprMaiIunIulAugSepOctNovDec Un2003 USD2003 Un2004 USD2004 Liniară (USD2003) Liniară (USD2004) LipofibSRisamongtheBestPerformanceBrands with209%growthinUSDJulyvs.January2004
2.ObjectivesandTarget ObjectiveLipofib2004 0 10000 20000 30000 40000 50000 60000 70000 80000 AugSepOctNovDec Continuetheascendingtrend towards75000USD/monthin December2004 bytargeting: •Diabetologists •Cardiologists •Internalmedicine •GP’s
4.MessagesandStrategies •LipofibSRmaintainthestabile efficienttherapeutical concentration. •LipofibSRhastheadvantage ofitswideindicationsforthe wholespectrumof hiperlipoproteinemias •ChoosingLipofibSRreduce thenumberofadministrations andthetotaldailydose, loweringthesideeffects. •Longtermadministrationof LipofibSRlowersthetotal costsofthetreatment. •Maintainthediabetologists prescriptionthrough presentationstowardsthe DiabetesCenters •Renewthemessagetoward cardiologistsLipofibSRhasthe advantageofitswide indicationsforthewhole spectrumof hiperlipoproteinemias •Maketheswitchtowardthe GP’susingtheMedicalLetters obtainedthroughtheIndividual Studies
5.MarketingSupport •Productpresentations •Dedicatedleaf-letfortheclinical efficiency •Promotetheclinicalresultsobtainedat theDiabetesInstituteBucharest •PromotionthroughMedicalCongresses Cardiology–Sept2004 Diabetes–Nov2004
Noiposibilitatiterapeutice inHiperlipoproteinemii LipofibSR250mg Capsulecueliberareprelungită
Hiperlipoproteinemii-strategiidecontrol NikkilaEA,1983 BrownWV,1986 GuayDP,2002 LipofibSR250mg Capsulecueliberareprelungită
Hiperlipoproteinemii-opţiuniterapeutice Clasa Moleculelemai importanteMecanismdeacţiuneIndicaţiiterapeutice StatineAtorvastatinum Fluvastatinum Lovastatinum Pravastatinum Simvastatinum InhibitorideHMGCo-A reductaza Hiperlipoproteinemii TipIIa,IIb FibraţiBezafibratum Ciprofibratum Fenofibratum Gemfibrozilum InhibăsintezaTG,creşte catabolismulVLDL Hiperlipoproteinemii TipIIb,III,IV,V Chelanţide acizibiliari NuecazulLeagăaciziibiliari, împiedicândreabsorbţia Hiperlipoproteinemii TipIIa,IIb Acidnicotinic şiderivaţi AcipimoxumHiperlipoproteinemii TipII,III LipofibSR250mg Capsulecueliberareprelungită MelenovschiV,2002 leRouxCW,2002 GuayDP,2002
Protocoaleterapeuticeinhiperlipoproteinemii LipofibSR250mg Capsulecueliberareprelungită LDL-CHDL-CTG FIBRAŢI Gemfibrozil2X600mg Clofibrat2X1000mg Fenofibrat200mg  5–20%  10–20%  20–50% STATINE Lovastatin20-80mg Pravastatin20-40mg Simvastatin20-80mg Fluvastatin20-80mg Atorvastatin10-80mg Cerivastatin0.4-0.8mg  18–55%  5–15%  7–30% Recomandari infunctiede profilullipidical pacientului sieficienta terapeuticaa fiecareiclase deagenti hipolipemianti ExpertPanelonDetection,Evaluationand TreatmentofHighBloodCholesterolin Adults,JAMA2001;285:2486-2497
Alegereaagentuluihipolipemiant LipofibSR250mg Capsulecueliberareprelungită infuncţiedeprofilullipidicalpacientului •PROFILAXIAPRIMARĂ DacăHDL-colestescăzutşiTGsuntcrescute: Primaalegere-FIBRAT DacăLDL-colestecrescutşiCol-totalestenormal: Primaalegere-STATINA •PROFILAXIASECUNDARĂ DacăLDL-colestecrescut: Primaalegere-STATINA DacăLDL-colestenormal,HDL-colscăzutşiTGsuntcrescute: Primaalegere-FIBRAT ExpertPanelonDetection,Evaluationand TreatmentofHighBloodCholesterolin Adults,JAMA2001
GhidulADAinhiperlipoproteinemiadiabetica LipofibSR250mg Capsulecueliberareprelungită PentrucreştereaHDL-colşi/sauscădereaTG: primaalegere-FENOFIBRAT PentruscădereaLDL-col: adouaalegere-FENOFIBRAT Pentruhiperlipidemiacombinată: adouaalegere–STATINA+FENOFIBRAT AmericanDiabetesAssociation Guidelines/DiabetesCare,January2001 (Volume24,Supplement1)
Avantajeleterapeutice oferitedeFenofibrat LipofibSR250mg Capsulecueliberareprelungită
Mecanismdeacţiune(I) LipofibSR250mg Capsulecueliberareprelungită Prezenta PPAR’s inperetiicelulari vasculari Celula musculara neteda Celula endoteliala vasculara Macrofag PPARalfaPPARalfa PPARgama PPARalfa PPARgama Descoperirea PPAR-alfa elucideaza mecanismul deactiune alfenofibratului. *PPAR=PeroxizomeProliferator-ActivatedFactor
Mecanismdeacţiune(II) LipofibSR250mg Capsulecueliberareprelungită Activarea PPAR-alfa cresteefluxul decolesterol dinmacrofage Efluxulde colesterol Expresia geneiABC-1 PPAR-alfa activat Fenofibrat MACROFAG
Mecanismdeacţiune(III) LipofibSR250mg Capsulecueliberareprelungită Activarea PPAR-alfa inhiba numeroase mecanisme aleaterosclerozei. FenofibratActiuniasupra Metabolismului Lipoproteinelor PPAR alfaStimuleaza producerea ApoA-I, ApoA-II,LPL Stimuleaza ß-oxidarea mitocondriala Inhibasinteza ApoC-III Actiuniasupra inflamatiei vasculare InhibasintezaIL-6 siactivitateaCOX-2 Stimuleazaapoptoza magrofaguluiactivat Inhibarea aterosclerozei
Fenofibratulactioneaza: Metabolic:*StimuleazaproducereaApoA-I,ApoA-II,LPL *Stimuleazaß-oxidareamitocondriala *InhibasintezaApoC-III Vascular:*InhibasintezaIL-6siactivitateaCOX-2 *Stimuleazaapoptozamagrofaguluiactivat *Scadeinflamatiavasculara Antitrombotic:*Scadefibrinogenul *Scademoleculeledeadeziune Reduceprogresiaaterosclerozei Mecanismdeacţiune-concluzii LipofibSR250mg Capsulecueliberareprelungită
Acţiuneafenofibratuluiînhiperlipoproteinemii BrissonD,etal.,2002 leRouxCW,MurphyE,SeedM,2002 GuayDP,2002 SasakiJ,YamamotoK,AgetaM,2002 LipofibSR250mg Capsulecueliberareprelungită >>
EficienţafenofibratuluiîndislipidemiiletipIVşiV LipofibSR250mg Capsulecueliberareprelungită An18-week,multicenterUS trialoffenofibrateintypeIVandVhyperlipoproteinemias, triglyceridelevels(TGs)-patientswithelevatedbaselinelevels(350mg/dL to499mg/dL)andwithveryelevatedbaseline(500mg/dLto1500mg/dL). Source:GoldbergACetal.ClinTher.1989. SasakiJ,YamamotoK,AgetaM,2002 Fenofibratul reduceeficient trigliceridemiainca dinprimeledoua saptamanide tratament, atatlapacientiicu nivelecrescutedeTG, catsilaceicu niveleextremde crescutedeTG
Eficienţafenofibratuluiintrigliceridemii -23%-22%-25% -30% 29% 17% -52% 18% -60% -50% -40% -30% -20% -10% 0% 10% 20% 30% modificari%postterapeutic Col-totalLDL-colHDL-colTG pacienticuHLPtipIIb Fenofibrat Simvastatina LipofibSR250mg Capsulecueliberareprelungită Fenofibratul estesuperiorin HLPtipIIb, atatprinscaderea fractieiLDL-colsia TG,citsiprin crestereafractiei protectiveHDL-col. ClinicalReviewofFenofibrate asTherapyforDyslipidemia AllPatients(N=9,503) TypeII-bSubgroup(n=2,165) Source:KirchgasslerKUetal.ClinDrugInvest.1998 DrugBenefitTrends11(11sC):12-24,1999.©1999 CliggottPublishing,DivisionofSCPCommunications
Eficienţafenofibratuluifaţădeatorvastatină SebestjenM,KeberI.,2002 GuayDP.,2002 FarnierM,TurpinG,2000 LipofibSR250mg Capsulecueliberareprelungită
-26% -39%-42% -54% -28% -39% 15% 28% -1 -1 0 0 0 0 0 0 0 0 Reducerea colesterolului serictotal Reducerea VLDL- colesterol Reducerea TGtotale Cresterea HDL- colesterol Bezafibrat (400mg) Fenofibrat (200mg) modificari%postterapeutic “ComparativeeffectsofBezafibrate andFenofibrateinpatientswithtypeIII Hyperlipoproteinemia”, FeussnerG,KurthB,LohrmannJ.,EurJMedRes1997Apr 21;2(4):165-8FeussnerG,KurthB,LohrmannJ,1997 LipofibSR250mg Capsulecueliberareprelungită Eficienţafenofibratuluifaţădebezafibrat Fenofibratul estesuperior bezafibratului reducândeficient atatCol-totalsiTG, citsifractiaVLDL. Crestereafractiei protectiveHDL-col estemaipronuntata.
LipofibSR250mg fenofibratmicrogranuleincapsulate LipofibSR250mg Capsulecueliberareprelungită
Proprietăţigenerale •LipofibSR250mgesteunagentregulatorallipidemiei, pebazădefenofibrat,subformademicrogranuleincapsulate. •LipofibSR250mgprezintăonouăformularefarmaceutică, cueliberareprelungită. •LipofibSR250mgbeneficiazădepeste30anideexperienţăclinică, validatăprintr-omultitudinedestudiiclinice. LipofibSR250mg Capsulecueliberareprelungită
Efectefarmacologice LipofibSR250mgdetermină: •scădereacolesteroluluiplasmatictotal; •scădereafracţiilordeLDL-colesterolşiVLDL-colesterol; •scădereaniveluluiplasmaticdetrigliceride; •creştereaniveluluiplasmaticalfracţiei“protective”deHDL-colesterol. LipofibSR250mg Capsulecueliberareprelungită
Farmacocinetică •AbsorbţiaLipofibSR250mgdintractuldigestiveste deaproximativ85%,atingândunpeakplasmaticdupă6-8ore. •Distribuţiaplasmaticăstabilăesteatinsăla5ziledelaprima administrare,fărăevidenţiereafenomenelordeacumularela administrareaprelungită. •Metabolizareafenofibratuluiesterealizatădecătreesteraze laacidfenofibric-metabolitulactiv. •ExcreţiaLipofibSR250mgestepredominantrenală(65%). •T½deaproximativ20oreoferăposibilitateaadministrăriiodatăpezi. LipofibSR250mg Capsulecueliberareprelungită
Formafarmaceuticăcueliberareprelungită… •Menţinestabilăconcentraţiaterapeuticăeficientă. •Reducenumăruldeadministrărişidozazilnicătotală, diminuândefecteletoxice. •Amelioareazărezultateleobţinute,maialesîntratamentul bolilorcronice. •Scadecosturiletotalealetratamentului. LipofibSR250mg Capsulecueliberareprelungită
…îmbunătăţeştecomplianţapacientului! •Scădereadramaticăa complianţeipacientuluila administrareaamaimult de3dozezilniceestebine cunoscută. •Reducereanumarului administrărilorreprezintă ceamaieficientăsoluţie înterapiadelungădurată. LipofibSR250mg Capsulecueliberareprelungită 83 75 59 0 10 20 30 40 50 60 70 80 90 complianta% 1admin/zi 2admin/zi 3admin/zi •Îmbunătăţireaprogresivăacomplianţeiareoimportanţăsporită, maialesîncazulbolilorcronice“silenţioase”clinic (cardiopatii,diabetzaharat).
Indicaţiiterapeutice LipofibSR250mgesteunagenthipolipemiantadministrabiladulţilor, cuurmătoareleindicaţiiterapeutice: •hipertrigliceridemiesimplă(tipIV); •hipertrigliceridemiecombinată(tipIIb,III); •hipercolesterolemie(tipIIa)-atuncicândregimuldietetic nuestesuficient,iarcolesterolemiarămâneridicată,chiarîncondiţiile dieteiadecvateşi/saudupăînlăturareafactorilorderisc. Respectarearegimuluidieteticesteabsolutnecesarăîntimpultratamentului.Acestmedicament, înasocierecudieta,constituieuntratamentsimptomaticpetermenlung,acăruieficacitatetrebuie evaluatăînmodregulat. LipofibSR250mg Capsulecueliberareprelungită
Recomandari Atentionariterapeutice: •Reevaluareaprofiluluilipidicdupã3-6lunidetratament. •Monitorizareaniveluluitransaminazelorsericedin3în3luni,înprimul andetratament. •Urmãrireatimpuluidetromboplastinãpartialactivat(APTT)labolnavii trataticoncomitentcuanticoagulanteorale. Contraindicatii: •Absolute:hipersensibilitatelafenofibratsaulaoricaredintre componentiiprodusului,insuficientãhepaticã,insuficientãrenalã,copii. •Relative:tratamentconcomitentcuinhibitoriaiHMGCoAreductazei saucualtifibrati. LipofibSR250mg Capsulecueliberareprelungită
StudiuclinicpentruLipofibSR250mg •Scopul:determinareaeficienţeiterapeuticeaLipofibSR250mgîn dislipidemiilesindromuluimetabolic,încolaborarecuCentruldeDiabet, NutritieşiBoliMetabolicedinClujNapoca. •Sponsor:TerapiaS.A.ClujNapoca. •Coordonatorstudiu:Prof.Univ.Dr.NicolaeHancu,şefulCentrului deDiabet,NuţritieşiBoliMetaboliceClujNapoca. •Investigatori:Dr.GabrielaRoman,Dr.CorneliaBala,Dr.I.A.Veresiu, Dr.LiviaDuma. •Laborator:Dr.MarianaCoca. LipofibSR250mg Capsulecueliberareprelungită
DescriereastudiuluicliniccuLipofibSR250mg Studiusimplu,deschis,“intentiontotreat” Medicaţiadestudiu:LipofibSR250mg,cuadministrareunică,dimineaţa Duratastudiului:24săptămâni Înrolare:Martie–Aprilie2003Terminare:Octombrie2003 Include:80persoanecusindrommetabolic,dincare50cuDZtipII EvaluareaeficienţeiLipofibSR250mgprin: •modificareaprocentualăavaloriiCol-total,LDL-col,HDL-col,TG, •%persoanelorcareauatinsobiectivelelipidice(ATPIII,ADA2003) •modificareaRCV LipofibSR250mg Capsulecueliberareprelungită
StudiuincursalCentruluiClinicdeDiabet, NutritiesiBoliMetaboliceClujNapoca LipofibSR250mg Capsulecueliberareprelungită Rezultatelepartialealestudiuluiclinic Beneficiileterapieicu LipofibSR250mg, dupa6saptamani: •Coltotalcu14,1% •LDL-colcu18,4% •HDL-colcu16,2% •TGcu38,2% 244.9 210.8 141.2 115.1 3641.9 554.3 342 -600 -500 -400 -300 -200 -100 0 100 modificarilepostterapeutice(mg/dL) ColtotalLDL-colHDL-colTG I-aVizita aII-aVizita N=51,p<0,005 -14,1% -18,4% +16,2% -38,2%
ConcluziilestudiuluicliniccuLipofibSR250mg •Eficienţăfoartebunăpemodificareaparametrilorlipidici •Procentsemnificativdepersoanecareauatinsobiectiveleterapeutice pentruTGşiHDL-colesterol •ImbunatatireaRCV •Siguranţăşitolerabilitatefoartebună •Fărăreacţiiadverse LipofibSR250mg Capsulecueliberareprelungită
ModdeprezentareLipofibSR250mg •cutieoriginalăcu3blisterex10capsulecueliberareprelungită LipofibSR250mg Capsulecueliberareprelungită
CaracteristicileunicealeLipofibSR250mg… •Agentregulatorallipidemiei,pebazădefenofibratsubformade capsulecumicrogranule,cuurmătoareleefectelefarmacologice: -scădereacolesteroluluiplasmatictotal; -scădereafracţiilordeLDL-colesterolşiVLDL-colesterol; -scădereaniveluluiplasmaticdetrigliceride; -creştereaniveluluiplasmaticalfracţieideHDL-colesterol. •Onouăformularefarmaceutică,cueliberareprelungită,ceasigură complianţamaximă. •Dozade250mgasiguraunplusdesigurantainatingereasimentinerea dozeieficienteterapeutic,faraexacerbareaefecteloradverse. •Peste30anideexperienţăclinică,validatăprinmultiplestudii. …conduclareconsiderareaterapeuticăafenofibratului. LipofibSR250mg Capsulecueliberareprelungită
1 PENTOXIPENTOXI RETARDRETARD Comprimatefilmatecueliberareprelungită,400mg
PENTOXIRETARD PENTOXIRETARD Substanţaactivă:pentoxifilina Clasaterapeutică:Vasodilatatorarterialperiferic musculotrop Formafarmaceutică:comprimatefilmatecueliberare prelungităcu400mgpentoxifilină
3 PENTOXIRETARD Mecanismdeacţiune VasodilatatorHemoreologicAntiinflamator FARMACOLOGIECLINICĂ:MECANISMDEACŢIUNE
4 PENTOXIRETARD MECANISMDEACŢIUNE–vasodilatator măreştecirculaţialanivelulmembrelorsial creierului,fărăsămodificeTA (Stroescu–Bazelefarmacologiei)
5 PENTOXIRETARD MECANISMDEACŢIUNE–hemoreologic Creşte fluxulsangvin înţesuturile ischemice Creşte oxigenarea tisulară Scade vâscozitatea sangvină
6 PENTOXIRETARD MECANISMDEACTIUNE–hemoreologic directinfluenţatededozade PENTOXIRETARDadministrată, eficienţafiindsemnificativ crescutăladozeleterapeutice (800-1200mg/zi). Vâscozitateasangvină Flexibilitateaeritrocitară Oxigenareatisulară
7 PENTOXIRETARD MECANISMDEACŢIUNE–antiinflamator inhibăTNF-alfa,IL1,IL6şialtecitokine proinflamatorii inhibăcascadacomplementului
8 PENTOXIRETARD PENTOXIFILINACU ELIBERAREIMEDIATĂ T1/2=0,4-0,6ore Concentraţiaplasmatică rămâneconstantă1,6-3,2ore Existăofluctuaţie permanentăasubstanţei activelanivelsangvin Riscmaimaredeefecte secundaregastrointestinale PENTOXIFILINARETARD T1/2=2–4ore Concentraţiaplasmatică rămâneconstantă12-16ore Elibereazăpermanent substanţaactivăşiasigurăo absorbţieconstantă Creştereatolerabilităţii gastrointestinale
9 PENTOXIRETARD INDICAŢIITERAPEUTICE: Tratamentulsimptomaticalclaudicaţieiintermitentedin arteriopatiacronicăobliterantăamembrelorinferioare (stadiulIIFontaine); Tratamentulsimptomaticadjuvantaldeficitului patologiccognitivsineurosenzorialcronical vârstnicului(cuexcepţiaboliiAlzheimerşiaaltor demenţe); Tratamentulsimptomaticaltulburărilorvasomotorii periferice
10 PENTOXIRETARD CLAUDICAŢIAINTERMITENTĂ Seestimeazăcăpeste10milioanedeadulţidinSUAsuntafectaţi deboliperifericevasculare,deşinumărulrealestemultmaimare, căcimulţibolnaviceprezintăsimptomedebolivasculareperiferice nuseprezintălamedic,considerându-lemanifestărinormaleale îmbătrânirii. FDA(FoodandDrugAdministration)recomandă Pentoxifilinadeprimăintenţieîntratamentul simptomaticalclaudicaţieiintermitente. Pânădecurând,Pentoxifilinaafostsingurulmedicamentaprobat deFDAîntratamentulsimptomaticalclaudicaţieiintermitente.
PENTOXIRETARD REACŢIIADVERSE Gastrointestinal:greaţă,vărsături,pirozisşi diaree Rareori:tahicardie,hTA,bufeuri,cefalee, vertij,insomnie,agitaţie Foarterar:reacţiicutanate(erupţie cutanată,urticarie,prurit)şicazuriizolate dereacţiianafilactoidecuşoc,edem Quinkeşibronhospasm Izolat:s-ausemnalatcâtevacazuride hemoragieşidescădereavalorilor protrombineilapacienţiicurischemoragic trataţicuanticoagulantesauantiagregante plachetareşipentoxifilină
12 PENTOXIRETARD INTERACŢIUNIMEDICAMENTOASE Anticoagulanteorale:asociereacreşteriscul hemoragic;estenecesarămonitorizareaclinică, avalorilorprotrombineişiaINR-ului Antiagreganteplachetare:asociereacreşte risculhemoragic;estenecesarămonitorizarea clinicăşiatimpuluidesângerare Teofilinaşiaminofilina:asociereacreşte concentraţiaplasmaticăateofilineicuriscde supradozaj;estenecesarămonitorizareaclinică şiaconcentraţiilorplasmaticealeteofilinei Medicamenteantihipertensive:pentoxifilinale potenţeazăefectul;estenecesară monitorizareaTA
PENTOXIRETARD DOZĂŞIMODDEADMINISTRARE Dozainiţială:400mgx3/zi Dozadeîntreţinere:400mgx2/zi Efecteletratamentuluiaparla2-4săptămânidelainiţierea tratamentuluişiserecomandăminim8săptămâni PREZENTARE
Alerid,10mg diclorhidratdecetirizina Alerid
Afectiunileatopice Alerid •astmulalergic, •rinitaalergică, •dermatitaatopică, •alergiilealimentare •RaportulcomunalOMSşiIAACIstipulează: *prevalentaastmuluişiamanifestariloratopiceesteîncreştere *peste15-20%dinpopulaţiatotalăestealergică *astmulesteîntâlnitla10–15%dintrecopii;incidenţatotalăa atopiiloratinge40%. •Principaliifactoriimplicaţiîndezvoltareaalergiilorsuntlegaţideistoricul familialşideprezenţaalergenului *IAACI-AsociaţiaInternaţionaladeAlergieşiImunologieClinică increşterecu20–30% înultimii20ani, maialesla copiiidevârstăscolară.
Proprietatigenerale Alerid •Aleridesteunantihistaminicsistemicselectivanti-H1degeneraţiaaII-a, cuadministrareoralăînprizăunică/24ore; •Aleridestedeprimăintenţieîntratamentulşiprevenirearecurenţelor riniteloratopice(atâtsezoniere,câtşicronice,trenante),dermatitelor atopice,urticarieişialtoratopiisistemice. •Aleridarecelmairapiddebutalactiuniifarmacologice,50%dintre pacientiraspunzindinprimele20minutedelaadministrareaorala; 95%dinpacientiraspundinprimaoradelaadministrare.
Farmacocinetica Alerid •Alerid(cetirizina)seabsoarberapid,avandTmaxlaaproximativ1ora; T1/2=8,3ore. •PenetrarealanivelulreceptorilorH1cerebraliesteneglijabila. •Eliminareaestepredominantrenala(70%),dincare50%nemodificata biochimic. •Nuafostobservatefectuldeacumulare,farmacocineticafiindliniara ladozecuprinseintre5si60mg(depanala6oridozazilnica recomandata).
Mecanismdeactiune Alerid Alerid(cetirizina)estemetabolitulnaturalalhidroxizinei,cuactiune antihistaminicaselectivapereceptoriiH1. Efecteleprincipalesuntmediateprininhibareaselectivaareceptorilor perifericiH1. Studiileefectuateatatinvivo,citsiinvitroaudemonstratca cetirizinanuareafinitatipentrualtireceptori, cuexceptiareceptorilorH1..
SelectivitateapereceptoriiH1 Alerid Antihistaminice degeneratiaI Antihistaminice degeneratiaII Selectivitatea pentru receptoriiH1 NuprezintaMaxima Efecte adverse •Somnolentasi/sau iritabilitate •Alterareaperformantelor psihomotorii •Retentieurinara •Glaucom •Crestereingreutate •Efectesedativereduse asupraSNC •Eficientamultcrescutain ameliorarea simptomatologieiatopicela nivelulmucoaseirespiratorii siadermului
Indicatiiterapeutice Alerid Rinitealergicesezoniere: Simptomeletratateeficient:stranut,rinoree,pruritnazal,pruritocular, catarlacrimo-nazalsieritemuloculo-palpebral. Rinitealergicecronice: Simptometratateeficient:stranut,rinoree,pruritnazal,pruritocularsi catarlacrimonazal. Urticariecronicaidiopatica: Reducesemnificativaparitia,severitateasidurataepisoadeloratopice. Areunputernicefectantipruriginos.
coincidecupeak-ulriniteloralergice! SigurantaAlerid10mg… Alerid Relatia incidentei riniteloralergice infunctiede virstadedebut asimptomelor, conformIAACI 6789101112131415 varstainani
0 5 10 15 20 25 30 timp(ore) Aleridasigura ceamairapida ratadereducere asuprafetei dermiceafectate sicelmai pronuntatefect antihistaminic pe24ore. eficientaasuprareactivitatiidermice Studiileclinicedemonstreaza Alerid AdaptatdupaGrantetal. IntArch.AllergyImmunol 1999;118:339-340 Cetirizina Placebo Loratadina Fexofenadina
Cetirizina Terfenadina Loratadina Astemizol Placebo 0 20 40 60 80 100 CetirizinaTerfenadinaLoratadinaAstemizolPlacebo DayJHetal.AnnAllergy AsthmaImmunol1997, 79:163-72 Procentulde pacientisatisfacuti detratamentulcu cetirizina sidispusisareia tratamentulla nevoieestenet superioraltor antihistaminice. tolerabilitatesicompliantamaxima Studiileclinicedemonstreaza Alerid 83% 68% 40% 65% 38%
Loratadina 10mgn=67 Cetirizina 10mgn=67 010203040 Rapiditateainstalarii Alerid DayJHetal.JAllergyClin Immunol1998,101:638- 45 DayJHetal.AnnAllergy AsthmaImmunol1997, 79:163-72 95%dintre pacientiau raspunsantihistaminic maximinprimaora delaadministrareade cetirizina, comparativcu loratadina, alcareiraspunsmaxim estela3ore. efectuluiantihistaminic… 1ora 3ore
Procentul pacientilor careinregistreaza rezolutiatotalaa simptomatologiei alergiceconsecutiv administrarii cetirizineieste maxim. Cetirizina Loratadina Placebo 0% 10% 20% 30% 40% 50% 60% 70% Cetirizinan=23Loratadinan=22Placebon=22 asimptomatologieialergice! …asiguraameliorareaeficienta Alerid AdaptatdupaMeltzeretal. –JallergyclinImmunol 1996,97:617-26 65% 31% 22%
Cetirizina Placebo 0% 5% 10% 15% 20% 25% 30% Cetirizinan=23Placebon=22 imbunatatireacalitatiivietii! Studiileclinicedemonstreaza Alerid VanderbiltUniversity, AsthmaSinusAllergy Program,2611West EndAve,#120,Nashville, TN37203USA Scorul complexuluituturor simptomeloralergice severecare influenteaza calitateavietii pacientiloreste maximpentru cetirizina. 28,9% 12,7%
58.8 43.6 27.8 38.1 33.2 47.1 020406080 IgEprafde casa IgEpolen IgEtotal PlaceboCetirizina 34.7 35 33.5 51.5 58.8 43.6 33.2 47.1 020406080 IgEpardepisica IgEprafdecasa IgEpolen IgEtotal NormalCrescut risculuirelativpentruastm StudiulETAC-evaluarea Alerid Prevalenta astmului lacopiii tratati cuplacebo (*1) comparativ cucei tratati cucetirizina (*2) (*1)(*2) *R.R. 1,4 1,5 0,5 1,7 0,91,3 *R.R. 0,6 *R.R.–risculrelativ
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 prevalenteiastmuluisubtratament StudiulETAC-evaluarea Alerid 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 Cetirizina(n=56)Cetirizina(n=36) Placebo(n=34)Placebo(n=68) (*1)(*2) timpul(inluni) Prevalenta astmului lacopiii cualergie lapolen(*1) silacei cualergie laprafuldecasa (*2) aflatisub tratament
Efecteleadverse Alerid •somnolenta,cuoincidentade14%; •fatigabilitatesiuscaciuneamucoaseibucale7%; •ameteli,cuincidentade3%; •cefalee,cuincidentade2%; •greata,varsaturi,dureriabdominale,diaree,cuincidentasub2%.
Administrare Alerid •seadministreazaindozaunica,1tabletaa10mgAlerid (diclorhidratdecetirizina)pe24ore; •serecomandaadministrareadela12ani;dozajuleste acelasilacopiisilaadulti; •serecomandaajustareadozajuluilajumatate incazulpacientilorcuinsuficientarenalasihepatica;
Prezentare Alerid •Cutieoriginalacu1blisterx10tabletefimate-10mgsubstantaactiva.
Sinteza Alerid Aleridasigura: •actiunerapida, raspunsantihistaminic inprimaora •efectantihistaminic eficace •actiunededurata (1admin./24ore) •siguranta tratamentului simptomeloralergice cetirizinaloratadinafexofenadina Raspunsantihistaminic rapid 1ora3ore2ore Dozaunicaofera sigurantapentru24ore √√√ Spectrularg√√ -numai 180mg Efecteadversereduse√√√ Utilizabilincure terapeuticeindelungate √√√
TeofilinaSR ActionPlan Sept-Dec2004 bySorinCiuciuc forTERAPIA
1.Evolutiedepiata-i Piataxantinelorafostrelativct. dpdvalUN •Crestereautilizariiteofilineiin defavoareaaminofilinei+140%UN •Dpdvvaloriccrestereaestede 270%inultimii6ani XantinesUN 0 500000 1000000 1500000 2000000 2500000 3000000 3500000 4000000 4500000 1998 units 1999 units 2000 units 2001 units 2002 units 2003 units AMINOPHYLLINUM Total THEOPHYLLINUM Total Totalgeneral XantinesUSD 0 500000 1000000 1500000 2000000 2500000 AMINOPHYLLINUM Total THEOPHYLLINUM Total Totalgeneral
1.Evolutiedepiata-iiTheophylineUN 0 50000 100000 150000 200000 250000 300000 350000 400000 GLAXOSMITHKLINE 0300MG GLAXOSMITHKLINE 0100MG GLAXOSMITHKLINE 0200MG KRKA0350MG KRKA0200MG TheophylineUSD 0 100000 200000 300000 400000 500000 600000 700000 GLAXOSMITHKLINE 0300MG GLAXOSMITHKLINE 0100MG GLAXOSMITHKLINE 0200MG KRKA0350MG KRKA0200MG Piatateofilinei: •Teo200mgGlaxo–cresterect 2004Fvs.2000:433%USD •Teo100mgGlaxo–cresterect 2004Fvs.2000:457% •TeoKRKA–reculdupa2003 spectaculos 0 0.5 1 1.5 2 UNgrowthUSDgrowth Growth2004vs.2003 GLAXOSMITHKLINE 0300MG GLAXOSMITHKLINE 0100MG GLAXOSMITHKLINE 0200MG KRKA0350MG KRKA0200MG
2.Obiective ObiectivTeofilinaSR2004 0 2000 4000 6000 8000 10000 12000 IanFebMarAprMaiIunIulAugSepOctNovDec 100mgtarget 200mgtarget TeofilinaForecast2004 50mgUN17000 0.59USD/cutUSD10000 100mgUN13900 0.72USD/cutUSD10000 200mgUN56600 1.06USD/cutUSD60000 300mgUN12600 1.59USD/cutUSD20000 TotalUN100100 TotalUSD100000
2.Obiective 020000400006000080000100000120000 50mg 100mg 200mg 300mg TotalUN ForecastTeofilina2004 Forecast200417000100001390010000566006000012600200001E+01E+0 50m g 0.59 USD/ 100 mg 0.72 USD/ 200 mg 1.06 USD/ 300 mg 1.59 USD/ Total UN Total USD
3.Target •Mediciinternisti •Medicicardiologi •Medicidemedicinagenerala
4.Mesaje Teofilinaareacţiunebronhodilatatoareprinrelaxarea musculaturiinetedebronşice. Teofilinaestestimulantcentral,psihostimulant;determină convulsiiladozemari Teofilinaproducevasodilataţiecoronariană,stimularecardiacă cucreştereanecesaruluideoxigenalmiocardului
5.Strategii Promovarecatremediciiinternisticatratamentcontinuual astmuluibronsicpersistentşiaaltorbronhopneumopatii croniceobstructive Promovarecatrecardiologi:amintireaprodusului–teofilinacu eliberareprelungita,administrabilain2prize/zi,in concentratiede100mgsi200mg Promovarecatremediciidefamiliecatratamentcontinuual astmuluibronsicpersistent
6.Alocarevizite Inconcordantacuprogramulstabilitinfunctiede: •Echipeledepromovare •Portofoliuldeproduse
7.SuportMarketing •Prezentarea produsului •Pliantdedicat indicatiilor respiratorii •Promovareina doualiniela Congresulde Cardiologie,sept 2004
TeofilinăSR …pentruexpirprelungit!
pentruTerapiaBronhodilatatoare TEOFILINĂSR100mg TEOFILINĂSR200mg capsulecueliberareprelungităceconţinteofilină anhidră Indicaţii Tratamentulsimptomaticcontinuu alastmuluibronşicpersistentşi aaltorbronhopneumopatiicroniceobstructive
Farmacodinamică Teofilinaareacţiunebronhodilatatoareprinrelaxarea musculaturiinetedebronşice. Teofilinaexercităurmătoareleacţiuni: -relaxeazămusculaturanetedăacăilorurinare,biliareşi asfincteruluiesofagianinferior; -estestimulantcentral,psihostimulantşidetermină convulsiiladozemari; -producevasodilataţiecoronariană,stimularecardiacă cucreştereanecesaruluideoxigenalmiocardului. -areacţiunediuretică.
Farmacocinetică Capsulelecueliberareprelungităconţinmicrogranule dincareteofilinaesteeliberatăgradat,asigurându-se oconcentraţieplasmaticăconstantălaadministrarea îndouăprizezilnice Teofilinaestemetabolizatăînprincipaldecătreficat (90%dindozaabsorbită)şiesteeliminatăpecale renală
DozajşiAdministrare(I) Dozeleseindividualizeazăînfuncţiederăspunsul terapeuticşidereacţiileadverse. Începereatratamentuluisefacecuodozămoderată careseajusteazăgradat(aprox.2mg teofilina/kgcorp/zi)pânălaobţinereaefectului terapeutic. Concentraţiaplasmaticăechilibratăşieficientă terapeuticesteatinsădupă3ziledetratament. Concentraţiaplasmaticăeficaceesteîntre 8-15µgteofilină/ml.
DozajşiAdministrare(II) Copii30luni-8ani(13–25kg): •Dozainiţială:10-14mgteofilină/kgcorp/zi; •Dozauzualăeficace:13-20mgteofilină/kgcorp/zi; •Dozazilnicăseadministreazăîndouăprize.
DozajşiAdministrare(III) Copii9-16ani(peste25kg): •Dozainiţială:10-12mgteofilină/kgcorp/zi; •Dozauzualăeficace:10-16mg/kgcorp/zi; •Dozazilnicăseadministreazăîndouăprize. Adulţi: •Dozainiţială:5-8mgteofilină/kgcorp/zi; •Dozauzualăeficace:7-12mgteofilină/kgcorp/zi,fără adepăşi800mgteofilinăzilnic; •Dozazilnicăseadministreazăîndouăprize.
Contraindicaţii Hipersensibilitatelateofilinăsaulaoricaredintre excipienţiiprodusului. Porfirieacutăintermitentă. Asociereacumedicamentececonţintroleandomicinăşi enoxacină. Copiisub30luni.
AtenţionărişiPrecauţii Serecomandăutilizareacuprudenţăşimonitorizarea concentraţiilorplasmaticedeteofilinăînurmătoarele cazuri: insuficienţăcardiacăacută(scădereadozelordatorită risculuidesupradozaj);insuficienţăcoronariană; obezitate(ajustareadozelorînfuncţiedegreutatea ideală);hipertiroidie;insuficienţăhepatică(scăderea dozelordatoritărisculuidesupradozaj);antecedente deepilepsie;administrareaconcomitentăde cimetidină,allopurinol,fluconazol,ciprofloxacină, norfloxacină,pefloxacină,fluvoxamină,mexiletină, ticlopidină,pentoxifilină,tiabendazol,tacrin,inductori enzimatici(carbamazepină,fenobarbital,fenitoină, primidonă,rifabutină,rifampicină,ritonavir).Nuse recomandăasociereacueritromicinăsauviloxazină.
InteracţiuniMedicamentoase(I) Asociericontraindicate: •Enoxacină,troleandomicină:riscdesupradozajal teofilinei(scădereasemnificativăacatabolizării teofilinei).
InteracţiuniMedicamentoase(II) Asocierinerecomandate: •Eritromicină:riscdesupradozaj(scădereaeliminării hepatice),înspeciallacopii.Serecomandăutilizarea altormacrolide(cuexcepţiatroleandromicinei); teofilinapoatefifolosităconcomitentsuboatentă supraveghereclinică •Viloxazină:creştereaconcentraţiilorplasmaticede teofilinăcuriscdesupradozaj(scădereacatabolizării teofilinei).
InteracţiuniMedicamentoase(III) Asociericenecesităprudenţă: -Cimetidină(doze≥800mg/zi),fluconazol,ciprofloxacină, norfloxacină,pefloxacină,fluvoxamină,mexiletină,ticlopidină, ritonavir,tacrin,pentoxifilină:creştereaconcentraţieiplasmatice deteofilinăcuriscdesupradozaj. -Tiabendazol:creştereaconcentraţieiplasmaticedeteofilinăcurisc desupradozaj,datoratăscăderiimetabolizăriihepaticea teofilinei. -Allopurinol:creştereaconcentraţieiplasmaticedeteofilinăîncazul administrăriiunordozemarideallopurinol(600mg/zi). -Carbamazepină,fenobarbital,fenitoin,primidonă,rifabutină, rifampicină,ritonavir(inductorienzimatici):scăderea concentraţieiplasmaticedeteofilină.Serecomandă supraveghereclinicăatentă,eventualmonitorizarea concentraţiilorplasmaticedeteofilină;dacăestecazul,se recomandăadaptareadozelorîntimpulasocieriişidupă întrerupeaacesteia.
SarcinăşiAlăptare Utilizareateofilineinuesterecomandatăîntimpul sarciniidecâtdacăestenecesar.Tratamentulcu teofilinalasfârşitulsarciniinecesitămonitorizarea nou-născutuluipentrucâtevazile. Teofilinaseexcretăînlaptelematernşipoatedetermina hiperexcitabilitatelanou-născuţi.Înconsecinţă,nu serecomandăalăptareaîntimpultratamentuluicu teofilină.
ReacţiiAdverse Celemaifrecventereacţiiadversesunt: -greaţă,vărsături,dureriepigastrice; -cefalee,staredeexcitabilitate,insomnie; -tahicardie. Acestereacţiipotfiprimelesemnedesupradozaj.
Supradozaj(I) •Simptomatologie Lacopii:agitaţie,logoree,staredeconfuzie,vărsături repetate,hipertermie,tahicardie,fibrilaţie ventriculară,convulsii,hipotensiunearterială, tulburărirespiratorii,hiperventilaţieapoideprimare respiratorie. Laadulţi:semnelesupradozajuluivariazădelaun individlaaltul;principalelesemneobservatesunt: greaţă,vărsături,dureriepigastrice;tahicardie; cefalee,insomnie,excitabilitate,dezorientare,delir; convulsii,hipertermieşistopcardiac.
Supradozaj(II) •Tratament:lavajgastric,administraredecărbune activat,măsurideterapieintensivă.Teofilinaeste dializabilă.
bySorinCiuciucforConvaTechbySorinCiuciucforConvaTech11 ConvaTecConvaTec RomaniaRomania
bySorinCiuciucforConvaTechbySorinCiuciucforConvaTech22 GoalGoal EnvironmentEnvironmentNeedsNeeds StructureStructureFunctionsFunctions HumanResourcesHumanResources MyofferMyoffer
bySorinCiuciucforConvaTech3 EnvironmentEnvironment COUNTRYCOUNTRY PHARMAPHARMA MARKETMARKET 2001200120022002200320032004F2004F GDPgrowthGDPgrowth5.75.74.94.94.54.55.05.0 USD/ROL(av)USD/ROL(av)29.06129.06133.05533.05533.00033.00035.00035.000 Euro/ROL(av)Euro/ROL(av)26.02826.02831.23431.23437.05137.05141.38741.387 0 100.000 200.000 300.000 400.000 500.000 600.000 700.000 19992000200120022003F UNITS(000,s) USD(000,s)
bySorinCiuciucforConvaTech4 NeedsNeeds MARKETINGMARKETINGMarketingresearchMarketingresearch MarketingplanningMarketingplanning IntegratescienceandmarketingIntegratescienceandmarketing SALESSALESBusinessrelationshipBusinessrelationship SalesteameffectivenessSalesteameffectiveness TerritorymanagementTerritorymanagement HUMANRESOURCESHUMANRESOURCESSelectandrecruitSelectandrecruit Training,coaching,motivateTraining,coaching,motivate EvaluateanddevelopmentEvaluateanddevelopment
bySorinCiuciucforConvaTech5 MARKETINGMARKETING ANDAFFAIRSANDAFFAIRS *Marketingresearch,*Marketingresearch, marketingplanmarketingplan *Establishtheannualbudget*Establishtheannualbudget *Directionandsupportforkey*Directionandsupportforkey medicalmeetingstooptimizemedicalmeetingstooptimize theintegrationofScienceandtheintegrationofScienceand MarketingMarketing MarketMarket managementmanagement ProductProduct portfolioportfolio PeopleandPRPeopleandPR SALESANDSALESAND DISTRIBUTIONDISTRIBUTION *Develop,cultivateand*Develop,cultivateand maintainbusinessrelationshipsmaintainbusinessrelationships *Hire,trainandcoachthesale*Hire,trainandcoachthesale team;ensureteamteam;ensureteam effectivenesseffectiveness *Driveoverallsaleswithinthe*Driveoverallsaleswithinthe territorybydevelopingandterritorybydevelopingand implementaneffectiveterritoryimplementaneffectiveterritory coverplancoverplan SalesSales TerritoryTerritory coveragecoverage DistributionDistribution StructureStructureFunctionsFunctionsGoalGoal
bySorinCiuciucforConvaTech6 MarketingandAffairsMarketingandAffairs MARKETSEGMENTSMARKETSEGMENTS Surgeons,Gastrology,Urology,Surgeons,Gastrology,Urology, Diabetes,Cardiologists,DermatologistsDiabetes,Cardiologists,Dermatologists FamilyDoctors,PharmacistsFamilyDoctors,Pharmacists PharmaceuticalwarehousesanddistributorsPharmaceuticalwarehousesanddistributors OPPORTUNITIESOPPORTUNITIES Ostomymarket“unexplored”andundevelopedOstomymarket“unexplored”andundeveloped Dermatologicalproductsmarketunder“10%rule”:Dermatologicalproductsmarketunder“10%rule”: -16mioUSD*-Dmarket**-16mioUSD*-Dmarket** -app.10%woundhealingagents-app.10%woundhealingagents -app.10%MSownedbythemostimportantplayers-app.10%MSownedbythemostimportantplayers NoproductservicesprovidedNoproductservicesprovided *CEGEDIMData**ATCclassification*CEGEDIMData**ATCclassification MarketmanagementMarketmanagement
bySorinCiuciucforConvaTech7 MarketingandAffairsMarketingandAffairs LAUNCHINGSTRATEGIESLAUNCHINGSTRATEGIES MedicalofficialsMedicalofficials Medicalk.o.l.Medicalk.o.l. PharmaceuticaldistributorsPharmaceuticaldistributors SalesRepresentativeteamSalesRepresentativeteam MedicalRepresentativeteamMedicalRepresentativeteam SUCCESSMETRICS1SUCCESSMETRICS1stst YEARYEAR -Attractk.o.l.inourbusinessAttractk.o.l.inourbusiness -SalesteamestablishmentwithinitsterritorySalesteamestablishmentwithinitsterritory -MedicalteamefficiencyMedicalteamefficiency -LeaderofopinioninostomyandwoundcarethroughLeaderofopinioninostomyandwoundcarethrough ourproductserviceourproductservice MarketmanagementMarketmanagement
bySorinCiuciucforConvaTech8 MarketingandAffairsMarketingandAffairs MARKETMARKET DefineanddeveloptheoverallmarketingplanDefineanddeveloptheoverallmarketingplan (objectives,strategies,shorttermandmediumplans)(objectives,strategies,shorttermandmediumplans) andensuresuccessfulimplementation.andensuresuccessfulimplementation. Marketanalysis(collection,presentationandMarketanalysis(collection,presentationand interpretationofmarketandcompetitorinformation)interpretationofmarketandcompetitorinformation) andactionsplanning(i.e.:activitiesnecessaryforandactionsplanning(i.e.:activitiesnecessaryfor productlaunch)productlaunch) DeterminenewclientsandmarketpotentialDeterminenewclientsandmarketpotential Supportforfieldactivities(productexpertisetoSupportforfieldactivities(productexpertiseto healthcarepersonnel,preparationanddistributionofhealthcarepersonnel,preparationanddistributionof POSmaterialstoensurecorrectimage)POSmaterialstoensurecorrectimage) PositioningonthemarketandacquisitionofMSPositioningonthemarketandacquisitionofMS MarketmanagementMarketmanagement
bySorinCiuciucforConvaTech9 MarketingandAffairsMarketingandAffairs ProductportfolioProductportfolio PRODUCTPORTFOLIOPRODUCTPORTFOLIO OstomyOstomy SkincareSkincare WoundcareWoundcare Product-relatedservicesProduct-relatedservices
bySorinCiuciucforConvaTech10 MarketingandAffairsMarketingandAffairs ProductportfolioProductportfolio PRODUCTPORTFOLIOPRODUCTPORTFOLIO OstomyOstomy OSTOMYSYSTEMOPTIONCHARTSOSTOMYSYSTEMOPTIONCHARTS SUR-FITSUR-FITNatura®Two-PiecePouchesNatura®Two-PiecePouches SUR-FITSUR-FIT®AutoLock®Two-PiecePouches®AutoLock®Two-PiecePouches SUR-FITSUR-FITNatura®Two-PieceWafersNatura®Two-PieceWafers SUR-FITSUR-FIT®AutoLock®Two-PieceWafers®AutoLock®Two-PieceWafers ActiveLife®One-PieceOptionsActiveLife®One-PieceOptions OSTOMYSYSTEMPACKCONVERSIONCHARTSOSTOMYSYSTEMPACKCONVERSIONCHARTS SUR-FITSUR-FITNatura®Two-PieceOptionsNatura®Two-PieceOptions ActiveLife®One-PieceOptionsActiveLife®One-PieceOptions OSTOMYCAREPRODUCTSOSTOMYCAREPRODUCTS SUR-FITSUR-FITNatura®Two-PieceProductsNatura®Two-PieceProducts
bySorinCiuciucforConvaTech11 MarketingandAffairsMarketingandAffairs ProductportfolioProductportfolio PRODUCTPORTFOLIOPRODUCTPORTFOLIO SkincareSkincare PATIENTBATHINGPATIENTBATHING PERINEAL/SKINCLEANSERSPERINEAL/SKINCLEANSERS SKINPROTECTANTS/MOISTUREBARRIERSSKINPROTECTANTS/MOISTUREBARRIERS ANTIFUNGALSANTIFUNGALS SKINPROTECTANTS/MOISTURIZERSSKINPROTECTANTS/MOISTURIZERS DISPENSERSDISPENSERS
bySorinCiuciucforConvaTech12 MarketingandAffairsMarketingandAffairs ProductportfolioProductportfolio PRODUCTPORTFOLIOPRODUCTPORTFOLIO WoundcareWoundcare WOUNDCLEANSINGWOUNDCLEANSING WOUNDHYDRATIONWOUNDHYDRATION MOISTURERETENTIVEDRESSINGSMOISTURERETENTIVEDRESSINGS EXUDATEMANAGEMENTEXUDATEMANAGEMENT ADVANCEDWOUNDCAREPRODUCTSADVANCEDWOUNDCAREPRODUCTS COMPRESSIONCOMPRESSION TUBULARBANDAGEAPPLICATORSTUBULARBANDAGEAPPLICATORS SPECIALTYBANDAGINGSPECIALTYBANDAGING
bySorinCiuciucforConvaTech13 MarketingandAffairsMarketingandAffairs PeopleandPRPeopleandPR PEOPLEPEOPLE ProductandMarkettrainingforpromotionalteamtoProductandMarkettrainingforpromotionalteamto ensurethehighstandardofpromotionalactivity,ensurethehighstandardofpromotionalactivity, brandpresentationandcompanyimage.brandpresentationandcompanyimage. PRPR LeadthemarketingcommunicationsprogramtoLeadthemarketingcommunicationsprogramto supportthebusinessobjectivesandmarketingplan.supportthebusinessobjectivesandmarketingplan. Initiate,maintainanddeveloprelationshipwithkeyInitiate,maintainanddeveloprelationshipwithkey customersandauthorities.customersandauthorities. Companyandproductimage-building.Companyandproductimage-building.
bySorinCiuciucforConvaTech14 SalesandDistributionSalesandDistribution SalesSales OBJECTIVESOBJECTIVES LeadtheostomyproductsmarketLeadtheostomyproductsmarket SignificantpresenceinwoundhealingagentsSignificantpresenceinwoundhealingagents ImplementproductsrelatedservicesforprofessionalsImplementproductsrelatedservicesforprofessionals RISKSRISKS -UnexploredandundevelopedmarketUnexploredandundevelopedmarket -MarketsolvabilityMarketsolvability Risksmanagement:Risksmanagement: -MedicalRepresentativesteamMedicalRepresentativesteam -SalesRepresentativesteamSalesRepresentativesteam REWARDSREWARDS -MarketleaderinostomyproductsMarketleaderinostomyproducts -SignificantpresenceinwoundcareproductsSignificantpresenceinwoundcareproducts
bySorinCiuciucforConvaTech15 SalesandDistributionSalesandDistribution SalesSales REACHABLEREACHABLE OstomyleadershipOstomyleadership Woundcareproducts-30%MS(500,000USD)Woundcareproducts-30%MS(500,000USD) STRONGPOINTSSTRONGPOINTS SaleteamSaleteam MedicalteamMedicalteam Product-relatedservicesProduct-relatedservices
bySorinCiuciucforConvaTech16 SalesandDistributionSalesandDistribution SalesSales QualityQuality productsproducts Medicalk.o.l.Medicalk.o.l. back-upback-up ValueValue formoneyformoney Customer’sCustomer’s satisfactionsatisfaction SalesSales teamteam MedicalMedical teamteam Product-relatedProduct-related servicesservices ObjectivesObjectives achievedachieved roadroad toto successsuccess
bySorinCiuciucforConvaTech17 SalesandDistributionSalesandDistribution SalesSales SALESSALES EstablishanddeveloptheRomanianbranchEstablishanddeveloptheRomanianbranch BusinessplanandbudgetsBusinessplanandbudgets Strategies,shortandmidtermplansforsalesandStrategies,shortandmidtermplansforsalesand distributiondistribution ManageanddevelopcommercialpolicyManageanddevelopcommercialpolicy RelationshipwithkeycustomersandauthoritiesRelationshipwithkeycustomersandauthorities ProvideproductexpertisetohealthcarepersonnelProvideproductexpertisetohealthcarepersonnel
bySorinCiuciucforConvaTech19 SalesandDistributionSalesandDistribution DistributionDistribution DISTRIBUTIONDISTRIBUTION DistributionchannelmanagementDistributionchannelmanagement DevelopmentandimplementationofchannelDevelopmentandimplementationofchannel strategiesstrategies Development,co-ordinationandcontrolofactivitiesDevelopment,co-ordinationandcontrolofactivities acrossalltradechannelstoensureefficientacrossalltradechannelstoensureefficient achievementofmarketingandsalesobjectivesachievementofmarketingandsalesobjectives ManageanddevelopcommercialpolicyManageanddevelopcommercialpolicy Developstrade-marketingstrategiesthatassureDevelopstrade-marketingstrategiesthatassure profitablebusinessgrowthprofitablebusinessgrowth DeterminenewclientandmarketpotentialDeterminenewclientandmarketpotential
bySorinCiuciucforConvaTech20 SalesandDistributionSalesandDistribution DistributionDistribution MAJORDISTRIBUTORSMAJORDISTRIBUTORS DistributorDistributorEstimatedmarketshareEstimatedmarketshare MediplusMediplus13.18%13.18%++++++ ReladRelad10.42%10.42%++ EuropharmEuropharm9.90%9.90%-- FarmexpertFarmexpert9.90%9.90%++++ MonteroMontero7.75%7.75%---- FildasFildas7.08%7.08%++ FarmeximFarmexim7.05%7.05%++++ TerapiaTerapia5.34%5.34%++++ DitaDita3.86%3.86%---- PharmaFarmPharmaFarm3.62%3.62%++
bySorinCiuciucforConvaTech21 HumanResourcesHumanResources People’smanagementPeople’smanagement SELECTSELECT RECRUITRECRUIT TRAININGTRAINING COACHINGCOACHING MOTIVATEMOTIVATE EVALUATEEVALUATE DEVELOPMENTDEVELOPMENT
bySorinCiuciucforConvaTech22 MyofferMyoffer People’smanagementPeople’smanagement 7yearsexperienceinbusinessdevelopment7yearsexperienceinbusinessdevelopment Privateinitiative,multinationalworkingenvironmentPrivateinitiative,multinationalworkingenvironment andRomanian-basedpharmaceuticalbusinessandRomanian-basedpharmaceuticalbusiness StructureandfunctionsoftheMedicalRelationshipStructureandfunctionsoftheMedicalRelationship DepartmentforSaltoHealthcareCenter(1997-1998)DepartmentforSaltoHealthcareCenter(1997-1998) Training,coachingandperformanceevaluationoftheTraining,coachingandperformanceevaluationofthe MedicalRepsteam(2002-2003)MedicalRepsteam(2002-2003) DevelopmentofFarmaDivisionofInterbrandsM&DDevelopmentofFarmaDivisionofInterbrandsM&D actinginWesternRomaniaunderNestleRomaniaactinginWesternRomaniaunderNestleRomania supervision(2000-2002)supervision(2000-2002) InitiateandmanagenumerousprojectstocreateandInitiateandmanagenumerousprojectstocreateand enhancetheCompanyimageandbrandsforNestleenhancetheCompanyimageandbrandsforNestle RomaniaandTerapiaS.A(2000-2003).RomaniaandTerapiaS.A(2000-2003).
bySorinCiuciucforConvaTech23 MyofferMyoffer People’smanagementPeople’smanagement BUSINESSDEVELOPMENTBUSINESSDEVELOPMENT *MedicalRelationshipDeptofSaltoMedicalHealthcareCenter*MedicalRelationshipDeptofSaltoMedicalHealthcareCenter (1997-1998)(1997-1998) *DevelopFarmaDivisionofInterbrandsM&DactinginWestern*DevelopFarmaDivisionofInterbrandsM&DactinginWestern RomaniaunderNestleRomaniasupervision(2000-2003)RomaniaunderNestleRomaniasupervision(2000-2003) *Cardio-Vascular,Diabetes/NutritionandCNSportfolio*Cardio-Vascular,Diabetes/NutritionandCNSportfolio development,inclosedrelationwithotherdepartments:research,development,inclosedrelationwithotherdepartments:research, registration,qualitycontrol,production,salesandsupplyforTerapiaregistration,qualitycontrol,production,salesandsupplyforTerapia SA(2003)SA(2003) SALESANDDISTRIBUTIONSALESANDDISTRIBUTION *CoachandmanagetheMedicalRepresentativeteamandsupervise*CoachandmanagetheMedicalRepresentativeteamandsupervise theachievementsoftheSalesteamforNestleRomaniatheachievementsoftheSalesteamforNestleRomania (2000-2003)(2000-2003) *Training,coachingandperformanceevaluationoftheMedical*Training,coachingandperformanceevaluationoftheMedical RepsteamforTerapia(2003)RepsteamforTerapia(2003)
bySorinCiuciucforConvaTech24 MyofferMyoffer People’smanagementPeople’smanagement MARKETING…MARKETING… *InfantNutritionCornerforNestleRomania(2002)*InfantNutritionCornerforNestleRomania(2002) *DevelopmentofCardio-vascularandCNSportfolio:marketing*DevelopmentofCardio-vascularandCNSportfolio:marketing researchandpotential,brandmarketingplanning,longtermresearchandpotential,brandmarketingplanning,longterm communicationstrategies,salesanalysisandforecastingforTerapiacommunicationstrategies,salesanalysisandforecastingforTerapia SA(2003).SA(2003). *Productlifecyclemanagement;marketing,trainingfortheM.R.*Productlifecyclemanagement;marketing,trainingfortheM.R. team,develop,organizeandevaluateclinicalstudies,coursesandteam,develop,organizeandevaluateclinicalstudies,coursesand seminars(2003)seminars(2003) ……ANDMEDICALANDMEDICAL *Clinicalstudies,courses,seminarsforTerapiaSA(2003).*Clinicalstudies,courses,seminarsforTerapiaSA(2003). *CoursesonFoodAllergyandInfantNutrition,Mother’sSchools,*CoursesonFoodAllergyandInfantNutrition,Mother’sSchools, SeminarsonAtopicDiseases,CongressesandClinicalValidationSeminarsonAtopicDiseases,CongressesandClinicalValidation TrialsforNestleRomania(2000-2003)TrialsforNestleRomania(2000-2003) *DirectMailingtowardmedicalprofessionalsforNestleRomania*DirectMailingtowardmedicalprofessionalsforNestleRomania (2001-2003)(2001-2003)
bySorinCiuciucforConvaTech25 MyofferMyoffer People’smanagementPeople’smanagement PEOPLE’SMANAGEMENTPEOPLE’SMANAGEMENT SALESANDPROMOTIONALSALESANDPROMOTIONAL FarmaDivisiondevelopmentforInterbrandsM&DactinginWesternFarmaDivisiondevelopmentforInterbrandsM&DactinginWestern RomaniaunderNestleRomaniasupervision(2000-2003)RomaniaunderNestleRomaniasupervision(2000-2003) CoachandmanagetheMedicalRepresentativeteamandsuperviseCoachandmanagetheMedicalRepresentativeteamandsupervise theachievementsoftheSalesteamforNestleRomania(2000-2003)theachievementsoftheSalesteamforNestleRomania(2000-2003) Training,coachingandperformanceevaluationoftheMedicalRepsTraining,coachingandperformanceevaluationoftheMedicalReps teamforTerapia(2003)teamforTerapia(2003)
ProduseleKingslac pentrunutritieinfantila
ProduseleKingslac pentrunutritiainfantila suntgrupatein: •Formuledelapte pentrusugarisicopii •Cerealepentrusugari sicopii Kingslacrecunoastein laptelematerncelmaibun alimentpentrunou-nascut
Kingslac1 Formuladelanastere *Raportzer/cazeina =60/40 *Lactozaglucidmajoritar *Farasucroza *CuTaurinasiL-Carnitina Compozitieconformacureglementarile ESPGHAN DirectiveleEuropene AcademiaAmericanadePediatrie
Kingslac2 Formuladecontinuare *Aportcrescutde CasiFe *Lactozaglucidmajoritar *Farasucroza *CuAc.linoleicsi Ac.α-linolenic Compozitieconformacureglementarile ESPGHAN DirectiveleEuropene AcademiaAmericanadePediatrie
Kingslac3 Formuladecrestere *CuPREBIOTICE LC-PUFA *Lactozaglucidmajoritar *Farasucroza *CuTaurinasiL-Carnitina Compozitieconformacureglementarile ESPGHAN DirectiveleEuropene AcademiaAmericanadePediatrie
Compozitieconformacureglementarile ESPGHAN DirectiveleEuropene AcademiaAmericanadePediatrie Kingslaccerealepentrusugari *usordigerabile *usordeacceptat *suplimentatecu12vitaminesiFe
Importanaprobioticelorîncreşterea şidezvoltareasănătoasăacopilului
FERROSAN–Compania Dezvoltareaproduselorprobiotice(începândcu1980), agameidevitamineMulti-tabs(încădin1960)– adaptateperfectdiferitelorcategoriidevârstăşi/sau necesităireprezintădireciaprincipalăde dezvoltare Cercetărilerecenteaucaintădezvoltareadeproduse avândîncomponenăacizigraşiomega-3,datorită importaneilordeosebiteîndezvoltareaşi meninereabuneistăridesănătateasistemului nervos Ferrosan–companieinternaională,cubazele operaionaleînDanemarca,prezentăpepiaa suplimentelordevitamineşiminerale 1920–IDOZAN–primulpreparat, antianemic,careastatlabazaînfiinării companieiFerrosanA/S În1930afostlansatprimulcomplexde vitaminaAşiD
FERROSAN–Produsedezvoltateînurmacercetărilorştiinifice Probioticeleîncepafistudiateintenscu1980. LGG®(lactobacillusrhamnosus)sedovedeştea aveacertăeficienăclinică,maialesîn: Meninereaechilibruluimicrofloreiintestinale tulburatdeantibioterapie Înmanagementulsindroamelordiareice, reducândperioadadeconvalescenă Cercetărilefarmacologiceşicliniceconduc ladezvoltareaunuinouprodus Bifiform®,pentrucare studiileevideniază: Capacitateatulpinilordea rezistapasajuluigastric Aderenaputernică lamucoasaintestinală Capacitateacrescută deaformacolonii
Bifiform®–deelecieînsindroamelediareiceşiantibioterapie Bifiform®KIDSesteocombinaieunicăadouă componenteprobiotice:LactobacillusrhamnosusGG (LGG®)şiBifidobacteriumanimalissusp.lactis(Bb12), suplimentatecuvitamineleB1şiB6 Bifiform®KIDSesteindicatcasoluiedeprimă intenieînrefacereaşimeninereaechilibrului fiziologicalmicrofloreiintestinaleşiîn disbacteriozeleintestinale determinatede: diareeacutăşicronică balonărigastro-intestinale intoleranălalactoză stress discomfortabdominal alergiialimentareşinealimentare constipaie(tulburăridetranzitintestinal) stildeviaădezordonatd.p.d.v.alimentar
Bifiform®–administrarefacilă,complianămaximă Bifiform®KIDSasigurăcomplianămaximă: 1/zicomprimatmasticabilcuaromădezmeurăşi portocale Formularespecialadaptatăpentrucopiicuvârsta cuprinsăîntre1şi10ani. Pentrueficienămaximă,serecomandă administrarea: Imediatodatăcuîncepereaantibioterapiei, plusminim5zileconsecutivedupă întrerupereatratamentuluicuantibiotice Delaprimelesimptomediareice, continuându-seminimosăptămânădupă dispariiasimptomatologiei
Bifiform®–eficienădemonstratăprinstudiicliniceriguroase
Multi-tabs®Immuno–rezultatalcercetărilordedatărecentă Combinaiesinergicădeprobiotice (LGG®)cuvitamineşimineralecare întăreştesistemulimunitar Ocombinaieunică,eficientăîn modularearăspunsului imun: Probiotice Vitamineşiminerale LGG®(lactobacillus rhamnosus)aderălamucoasa intestinalăşiformeazăcolonii Suplimentareadecvatăcu vitamineşiminerale Tehnologieunicădeformulare farmaceutică,încomprimate dublustratificate,ambalate înatmosferăprotejată
Multi-tabs®Immuno–suplimentareadecvatăcuvitamineşiminerale Fier Zinc Mangan Crom Seleniu Iod Suplimentareaadecvatăcu vitamineşimineralespecial adaptatăsituaiilordestress imunitar: VitaminaA VitaminaD VitaminaE VitamineleB1,B2,B6,B12 Niacină Acidpantotenic Acidfolic VitaminaC Biotină VitaminaK
Multi-tabs®ImmunoKIDS2în1–eficienăclinicădemonstrată Studiileclinice(*)audemonstrat: Scădereaincideneiinfeciiloracuterespiratorii superioarecu17% Reducerearecomandărilordeantibioterapiecu19% Diminuareaabsenteismuluişcolarmedicalcu18% (*)Studiuclinicpetermenlungasupraa571copiiurmăriiambulator Hatakkaetal.BMJ,2001
Multi-tabs®ImmunoPlus2în1–formularedestinatăadulilorşi copiilor peste12ani Multi-tabs®ImmunoPlus2în1ajutălaîntărirea sistemuluiimunitar,princombinaiaunică,sinergică deLGG®cuvitamineşiminerale 30decomprimatefilmate,ambalateînatmosferă protejatădeazot Administrarecucomplianămaximă: 1comprimat/zi EficienamaximăaMulti-tabs®Immunose constatădupăadministrareauneicurede minim30zile. Serecomandăutilizareapreventivă: -atuncicândurmeazăsituaiiprevizibilede stressimunitar(schimbărialemediului, colectivităii,etc.) -încazulunuiistoriccunoscutdeinfecii recurente.
Multi-tabs®Omega3KIDS–sursădeacizigraşieseniali Aciziigraşipolinesaturaiesenialireprezintăunelementindispensabilîn dezvoltareasistemuluinervoscentralşiaaparatuluivizual Sursanaturalădeacizigraşi polinesaturaiesenialiOmega3 (aciddocosahexaenoic–DHA) esteuleiuldepeşte DHAintrăîncomponena structuralăamembranei celulare DHAconferăfuncionalitate membraneicelulare
Multi-tabs®Omega3KIDS–esenial…compliant! Administrareaconcomitentăa2capsulemasticabile deMulti-tabs®Omega3KIDSşiaunui comprimatdeMulti-tabs®KIDSasigurăîntregul necesardevitamine,mineraleşiconstitueni esenialipentruodezvoltaresănătoasă,inclusiv dinpunctdevederealcapacităiimentale. Multi-tabs®Omega3KIDSseprezintăsubformă decapsulemasticabilecuaromădecoacăzenegre şicireşe,fărăgustdepeşte Administrare:2capsule/zi DatorităimportaneideosebiteaDHAîndezvoltarea creieruluişiaaparatuluivizual,dovedităprinstudii clinice,serecomandăadministrareaàlalonga suplimentelorcuunconinutridicatînacizigraşi polinesaturai
Multi-tabs®Omega3KIDS–pentrucopiiistei DeceaunevoiecopiideMulti-tabs® Omega3KIDS Peşteleesteunalimentdebază, necesarîndietazilnicăacopiilor Multi-tabs® Omega3KIDSconine acizigraşiesenialidinuleidepeşte DeceeimportantconsumuldeacizigraşiOmega3lacopii Multi-tabs®Omega3KIDSjoacăunrolimportantîndezvoltarea armonioasăasistemuluinervos,crescândputereade concentrareşicapacitateadeînvăareacopiilor –deaceeaesterecomandatînperioadadedezvoltareşicreştere
Multi-tabs®Omega3KIDS–pentrucopiiistei CuceestediferitMulti-tabs®Omega3 KIDSdealteproduse Multi-tabs®Omega3KIDSseprezintă subformădecapsulemasticabilecu aromădecoacăzenegreşicireşe, fărăgustdepeşte,specialadaptate pentrunevoilecopiilorpeste2ani
GamaMulti-tabs®KIDS–asigură100%dinDZR(*)devitamineşi minerale (*)DZR–dozazilnicărecomandată GamaMulti-tabs®KIDS comprimatemasticabilecuarome diferiteceasigură100%dinDZR(*) devitamineşiminerale, specialadaptate copiilorcuvârtaîntre1şi10ani Aromelediferite colaşilime zmeurăşicăpşuni portocaleşicăpşuni tutti-frutti Administrareaunuisingur comprimat/ziasigură complianamaximă
Multi-tabs®KIDS+Calciu Acelaşiaportdevitamineşiminerale dinMulti-tabs®KIDS,plusCalciu Coninutdeminerale“armonizat” pentrucreştereaabsorbieideCalciu
GamaMulti-tabs®Pronatal–dingrijăpentrumamăşicopil GamaMulti-tabs®Pronatalasigurăaportulspecial adaptatpentrusarcinăşialăptaredevitamineşiminerale esenialepentruobunădezvoltareşicreştereafătului Multi-tabs®PronatalOmega3estesingurul produscareasigurăaportuldeacizigraşi polinesaturai,esenialiîndezvoltarea sistemuluinervosşiaaparatuluivizual Multi-tabs®PronatalMultivitamin +acidfolicasigurăînprimulrând aportulde: Acidfolic–indispensabilîncreştereaşi dezvoltareafătului Fier–esenialpentruformareasângelui
GamaMulti-tabs®Pronatal–dingrijăpentrumamăşicopil ATENIE!Însarcină,aportuldevitaminaAtrebuiestrictmonitorizat.Înexces, aceastaesteteratogenă.Deaceea,înMulti-tabs®PronatalMultivitamin+acid folicdozadevitaminaAestede50%dinDZR(*) Multi-tabs®PronatalMultivitamin +acidfolicasigurăaportuladaptatde vitamineşiminerale Multi-tabs®PronatalOmega3
GamaMulti-tabs®Pronatal–dingrijăpentrumamăşicopil GamaMulti-tabs®Pronatal: 2capsule/zide Multi-tabs®PronatalcuOmega3 asigurăaportulspecialadaptat pentrusarcinăşialăptaredeacizi graşipolinesaturaieseniali 1comprimat/zide Multi-tabs®Pronatal Multivitamin+acidfolic asigurăaportulspecialadaptat pentrusarcinăşialăptarede vitamineşimineraleeseniale
Multi-tabs®Baby–vitaminaD3 Multi-tabs®Babyesteunprodusspecial destinatnou-născuilorşisugarilorpentru prevenirearahitismuluişitratamentul hipovitaminozeiD Colecalciferolulesteformaceamaiuşor absorbabilăşiutilizabilăformădevitaminaD Pentrufacilitateaînutilizareşidozareaexactăa dozeizilnicedevitaminăD,sticluaesteprevăzută cuopipetăspecială Nuconinecoloranisauconservani!!! AcoperăîntregnecesaruldevitaminăDal sugaruluieutrofic
EchipaFERROSAN EsteladispoziiaDumneavoastrăpentrudetalii Vămulumeştepentruateniaacordată!
OOcompaniecompaniededicatdedicatăă frumusefrumusețțiiii––lalafemininfeminin!!
UnproiectinvestiționalinovatorUnproiectinvestiționalinovator Background ExperiențaunuiproducătorisraelianExperiențaunuiproducătorisraelian–liderîn producțiadecosmetice,cupeste2.000decolaboratori încosmetologieșiînfrumusețare RezultatelecercetărilordeultimăorăaleunuiRezultatelecercetărilordeultimăorăaleunui laboratorolandezlaboratorolandez–rolulcelulelorstemvegetaleîn refacereatenului ImplicareainvestiționalăaunuiconcernImplicareainvestiționalăaunuiconcern spaniolspaniol–exportatorînpeste40dețăridinEuropa, Asia,AmericadeNordșiAmericaLatină ExperiențaînproiectepilotdinRomâniaExperiențaînproiectepilotdinRomânia LaDuchesseLaDuchesse––primacompaniededicatăprimacompaniededicată dezvoltăriiunuinouconceptdeprezentareșidezvoltăriiunuinouconceptdeprezentareși promovareaproduselorcosmeticedepromovareaproduselorcosmeticedecalitate!calitate!
DezvoltarearegionalăDezvoltarearegională Place Potential People Purpose Partners Product Positioning Price Promotion Performance Profit ClujNapocaClujNapoca–HQșiprimulorașîncarese implementeazăacestproiect TransilvaniaTransilvania BucureștiBucurești ExtindereacătreUEExtindereacătreUE
OpiațăalcăreipotențialdeOpiațăalcăreipotențialde creștererămâneridicat!creștererămâneridicat! Place Potential People Purpose Partners Product Positioning Price Promotion Performance Profit ClujNapoca:ClujNapoca: peste7.000defemeicuvârstapeste30deanicu educațiesuperioarășivenituripropriipestemedie peste100desaloaneșicabineteceoferăserviciide cosmetică Transilvania:Transilvania: peste50.000defemeipeste30deani–cueducație superioarășivenituripestemedie aprox.1.000defurnizorideserviciiîndomeniul cosmetic România:România: opiațăîncreșteredela655MEURîn2006la 848MEURîn2009și,înciudadificultățiloreconimice- peste1.000MEURîn2011! ExtindereacătreUE:ExtindereacătreUE:cudublu-focus: țărilelatine–Franța,Italia,Spania tradițiagermanică:Austria,Germania,Elveția
Entuziasmșiprofesionism!Entuziasmșiprofesionism! Place Potential People Purpose Partners Product Positioning Price Promotion Performance Profit SpecialiștiinterniSpecialiștiinterni experiențăînvânzări specalizațiînmarketing profesioniștiîncosmetică ColaboratoriprofesioniștiColaboratoriprofesioniști agențiidemedia logistică saloaneșicabinetedecosmeticășiînfrumusețare AplecațicătredezvoltarecontinuăAplecațicătredezvoltarecontinuă
VremconştientizareaVremconştientizarea consumatorilor!consumatorilor! Place Potential People Purpose Partners Product Positioning Price Promotion Performance Profit Oofetăunică,inovativăcătreconsumatorulOofetăunică,inovativăcătreconsumatorul defrumusețe:defrumusețe: Creștereagraduluideeducațieînceeacepriveșteîngrijirea tenului–printr-oexpuneretransparentășiîntr-ocontinuă dezvoltareîncolaborarecufurnizorii deserviciiîndomeniulcosmetic primiipași:primiipași: deschidereashowroom-uluidin cadrulgaleriilorcomercialeCora primulsimpoziondedicat profesioniștilorîncosmetică primelesaloaneșicabinete incluseînprogram
ExpertizăinternaționalășiExpertizăinternaționalăși concentrarelocalăconcentrarelocală Place Potential People Purpose Partners Product Positioning Price Promotion Performance Profit PermitețiPermiteți--nesăfimpartenerulnesăfimpartenerul Dumneavoastră!Dumneavoastră!
JustlikeMagic!JustlikeMagic! Place Potential People Purpose Partners Product Positioning Price Promotion Performance Profit http://stirileprotv.ro/stiri/stiinta /am-putea-fi-prima-generatie- de-oameni-vesnic-tineri- elixirul-tineretii-gasit-si-testat- cu-succes.html SingureleSingureleproduseprodusececeoferăoferă îngrijireatenuluipebazăîngrijireatenuluipebazădede celulecelulestemstemvevegetalegetale!! Produsedermocosmetice pebazădecelulestem vegetaleobținuteprintehnologia PhytoCellTecPhytoCellTecTMTM,conceputăspecial pentrudiminuarearidurilor,diminuarearidurilor, creștereafermitățiipieliișicreștereafermitățiipieliiși întârziereaaparițieiprimelorsemneîntârziereaaparițieiprimelorsemne aletreceriitimpuluialetreceriitimpului. Intensificămetabolismulcelular,cu rezultatevizibilerapidșiefectederezultatevizibilerapidșiefectede duratădurată.
Ușurințăînutilizare,eficiențăUșurințăînutilizare,eficiență testată,doveditășireproductibilă!testată,doveditășireproductibilă! Place Potential People Purpose Partners Product Positioning Price Promotion Performance Profit UnmixdeUnmixdeproduseproduse dermocosmeticedermocosmeticeșișicosmeticecosmetice cueficiențătestată, dovedită,organizate înprogramedistincte personalizatepe tipologiatenului OOabordaretransparentășiabordaretransparentăși profesionistăaeficienței!profesionistăaeficienței! urmărităîndeaproape–fieînconfortul domiciliului,fieîmpreunăcucometicianata!
FrumusețeanutrebuiesăfieFrumusețeanutrebuiesăfie neapăratcostisitoare!neapăratcostisitoare! Place Potential People Purpose Partners Product Positioning Price Promotion Performance Profit AAvemopermanentăgrijăînpăstrareavemopermanentăgrijăînpăstrarea produselorlaîndemânaconsumatoarelorproduselorlaîndemânaconsumatoarelor– inclusivdinpunctdevederealprețului! TTehnologiileînglobateînproduseehnologiileînglobateînprodusepermit utilizareaunorcantitățirelativmici,păstrându-șieficiența ProgrameledezvoltateProgrameledezvoltatepermit utilizareaproduselorînlimitedecosturi maimultdecâtrezonabile
ÎntotdeaunalângăconsumatorÎntotdeaunalângăconsumator Place Potential People Purpose Partners Product Positioning Price Promotion Performance Profit PromovareadirectăcătrePromovareadirectăcătre clienteleshowroomclienteleshowroom--uluiului testaregratuită sesiunidemake-upgratuit catalogullazialproduselor personalulcalificatîn cosmetică concursuri,promoţii, tombolecupremiisubstanţiale PromovareaprinmediaPromovareaprinmedia KissFM ProFM concursuri advertoriale
PerformanţăPerformanţă––înpasvioi!înpasvioi! Place Potential People Purpose Partners Product Positioning Price Promotion Performance Profit Pentruocompanieceactiveazăîncepânddin10decembrie 2011aiputeacredecăperformanţaedeparte...şitotuşi! AvemcelmaiinovatorshowroomdindomeniuAvemcelmaiinovatorshowroomdindomeniu AmorganizatprimulseminarpetemaîngrijiriiAmorganizatprimulseminarpetemaîngrijirii tenuluitenului–într-oambianţăplăcutăşicuoparticipareextrem demare! AvemcâtevasutedeclientemulţumitedeAvemcâtevasutedeclientemulţumitede primulcontactcuproduseleprimulcontactcuprodusele AAvemprimelesaloaneşicabinetedornicesăvemprimelesaloaneşicabinetedornicesă lucrezecuproduselenoastrelucrezecuproduselenoastre ...Şiplanurideextindererapidă!...Şiplanurideextindererapidă!
ProfitulProfitul––îldatorămcomunităţii!îldatorămcomunităţii! Place Potential People Purpose Partners Product Positioning Price Promotion Performance Profit DorimsăneimplicămînproiectelecomunităţiiînDorimsăneimplicămînproiectelecomunităţiiîn careoperăm!careoperăm! VremînprimulrândsădevenimunpartenerVremînprimulrândsădevenimunpartener activpentrusuportulfemeilorînsocietateactivpentrusuportulfemeilorînsocietate VremsăcontribuimlasoluţionareaunoradintreVremsăcontribuimlasoluţionareaunoradintre problemesocialestringenteproblemesocialestringente DeaceeaamfionoraţisădezvoltămunDeaceeaamfionoraţisădezvoltămun parteneriatactivcuparteneriatactivcu
C 02
C 02

Recommended

Nutrigenomics of the two hits: non-resolving metabolic and pro-inflammatory s...
Nutrigenomics of the two hits: non-resolving metabolic and pro-inflammatory s...Nutrigenomics of the two hits: non-resolving metabolic and pro-inflammatory s...
Nutrigenomics of the two hits: non-resolving metabolic and pro-inflammatory s...Norwich Research Park
 
Bio transformation of Warfarin
Bio transformation of WarfarinBio transformation of Warfarin
Bio transformation of WarfarinAlagar Suresh
 
TYROSINE KINASE INHIBITORS
TYROSINE KINASE INHIBITORSTYROSINE KINASE INHIBITORS
TYROSINE KINASE INHIBITORSyerroju vijay
 
Anticoagulants Nursing esther
Anticoagulants Nursing estherAnticoagulants Nursing esther
Anticoagulants Nursing estherEsther Mary Mathew
 
Paracetamol poisoning
Paracetamol poisoningParacetamol poisoning
Paracetamol poisoningSaurabh pathak
 
Ado
AdoAdo
AdoRohayu Asnawi
 
Anticoagulant-medicinal chemistry
Anticoagulant-medicinal chemistryAnticoagulant-medicinal chemistry
Anticoagulant-medicinal chemistryGaneshprabu10
 
AN OVERVIEW OF DRUGS ACTING ON BLOOD FORMING.pptx
AN OVERVIEW OF DRUGS ACTING ON BLOOD FORMING.pptxAN OVERVIEW OF DRUGS ACTING ON BLOOD FORMING.pptx
AN OVERVIEW OF DRUGS ACTING ON BLOOD FORMING.pptxBakut John Maiganga
 

Recommended

Nutrigenomics of the two hits: non-resolving metabolic and pro-inflammatory s...
Nutrigenomics of the two hits: non-resolving metabolic and pro-inflammatory s...Nutrigenomics of the two hits: non-resolving metabolic and pro-inflammatory s...
Nutrigenomics of the two hits: non-resolving metabolic and pro-inflammatory s...Norwich Research Park
 
Bio transformation of Warfarin
Bio transformation of WarfarinBio transformation of Warfarin
Bio transformation of WarfarinAlagar Suresh
 
TYROSINE KINASE INHIBITORS
TYROSINE KINASE INHIBITORSTYROSINE KINASE INHIBITORS
TYROSINE KINASE INHIBITORSyerroju vijay
 
Anticoagulants Nursing esther
Anticoagulants Nursing estherAnticoagulants Nursing esther
Anticoagulants Nursing estherEsther Mary Mathew
 
Paracetamol poisoning
Paracetamol poisoningParacetamol poisoning
Paracetamol poisoningSaurabh pathak
 
Ado
AdoAdo
AdoRohayu Asnawi
 
Anticoagulant-medicinal chemistry
Anticoagulant-medicinal chemistryAnticoagulant-medicinal chemistry
Anticoagulant-medicinal chemistryGaneshprabu10
 
AN OVERVIEW OF DRUGS ACTING ON BLOOD FORMING.pptx
AN OVERVIEW OF DRUGS ACTING ON BLOOD FORMING.pptxAN OVERVIEW OF DRUGS ACTING ON BLOOD FORMING.pptx
AN OVERVIEW OF DRUGS ACTING ON BLOOD FORMING.pptxBakut John Maiganga
 
D 07
D 07D 07
D 07sorinciuciuc
 
D 02
D 02D 02
D 02sorinciuciuc
 
D 04
D 04D 04
D 04sorinciuciuc
 
C 04
C 04C 04
C 04sorinciuciuc
 
D 08
D 08D 08
D 08sorinciuciuc
 
D 01
D 01D 01
D 01sorinciuciuc
 
C 03
C 03C 03
C 03sorinciuciuc
 
C 05
C 05C 05
C 05sorinciuciuc
 
B 06
B 06B 06
B 06sorinciuciuc
 
B 02
B 02B 02
B 02sorinciuciuc
 
B 04
B 04B 04
B 04sorinciuciuc
 
B 01
B 01B 01
B 01sorinciuciuc
 
A 03
A 03A 03
A 03sorinciuciuc
 
A 02
A 02A 02
A 02sorinciuciuc
 
C 01
C 01C 01
C 01sorinciuciuc
 
A 01
A 01A 01
A 01sorinciuciuc
 
E 09
E 09E 09
E 09sorinciuciuc
 
B 03
B 03B 03
B 03sorinciuciuc
 
B 05
B 05B 05
B 05sorinciuciuc
 
EN-CV - Dr Sorin Ciuciuc
EN-CV - Dr Sorin CiuciucEN-CV - Dr Sorin Ciuciuc
EN-CV - Dr Sorin Ciuciucsorinciuciuc
 
Russian Call Girls Chickpet - 7001305949 Booking and charges genuine rate for...
Russian Call Girls Chickpet - 7001305949 Booking and charges genuine rate for...Russian Call Girls Chickpet - 7001305949 Booking and charges genuine rate for...
Russian Call Girls Chickpet - 7001305949 Booking and charges genuine rate for...narwatsonia7
 
sauth delhi call girls in Bhajanpura 🔝 9953056974 🔝 escort Service
sauth delhi call girls in Bhajanpura 🔝 9953056974 🔝 escort Servicesauth delhi call girls in Bhajanpura 🔝 9953056974 🔝 escort Service
sauth delhi call girls in Bhajanpura 🔝 9953056974 🔝 escort Service9953056974 Low Rate Call Girls In Saket, Delhi NCR
 

More Related Content

More from sorinciuciuc

EN-CV - Dr Sorin Ciuciuc
EN-CV - Dr Sorin CiuciucEN-CV - Dr Sorin Ciuciuc
EN-CV - Dr Sorin Ciuciucsorinciuciuc
 

More from sorinciuciuc (20)

D 07
D 07D 07
D 07
 
D 02
D 02D 02
D 02
 
D 04
D 04D 04
D 04
 
C 04
C 04C 04
C 04
 
D 08
D 08D 08
D 08
 
D 01
D 01D 01
D 01
 
C 03
C 03C 03
C 03
 
C 05
C 05C 05
C 05
 
B 06
B 06B 06
B 06
 
B 02
B 02B 02
B 02
 
B 04
B 04B 04
B 04
 
B 01
B 01B 01
B 01
 
A 03
A 03A 03
A 03
 
A 02
A 02A 02
A 02
 
C 01
C 01C 01
C 01
 
A 01
A 01A 01
A 01
 
E 09
E 09E 09
E 09
 
B 03
B 03B 03
B 03
 
B 05
B 05B 05
B 05
 
EN-CV - Dr Sorin Ciuciuc
EN-CV - Dr Sorin CiuciucEN-CV - Dr Sorin Ciuciuc
EN-CV - Dr Sorin Ciuciuc
 

Recently uploaded

Russian Call Girls Chickpet - 7001305949 Booking and charges genuine rate for...
Russian Call Girls Chickpet - 7001305949 Booking and charges genuine rate for...Russian Call Girls Chickpet - 7001305949 Booking and charges genuine rate for...
Russian Call Girls Chickpet - 7001305949 Booking and charges genuine rate for...narwatsonia7
 
Bangalore Call Girls Majestic 📞 9907093804 High Profile Service 100% Safe
Bangalore Call Girls Majestic 📞 9907093804 High Profile Service 100% SafeBangalore Call Girls Majestic 📞 9907093804 High Profile Service 100% Safe
Bangalore Call Girls Majestic 📞 9907093804 High Profile Service 100% Safenarwatsonia7
 
Call Girls Hsr Layout Just Call 7001305949 Top Class Call Girl Service Available
Call Girls Hsr Layout Just Call 7001305949 Top Class Call Girl Service AvailableCall Girls Hsr Layout Just Call 7001305949 Top Class Call Girl Service Available
Call Girls Hsr Layout Just Call 7001305949 Top Class Call Girl Service Availablenarwatsonia7
 
College Call Girls Vyasarpadi Whatsapp 7001305949 Independent Escort Service
College Call Girls Vyasarpadi Whatsapp 7001305949 Independent Escort ServiceCollege Call Girls Vyasarpadi Whatsapp 7001305949 Independent Escort Service
College Call Girls Vyasarpadi Whatsapp 7001305949 Independent Escort ServiceNehru place Escorts
 
Call Girls Whitefield Just Call 7001305949 Top Class Call Girl Service Available
Call Girls Whitefield Just Call 7001305949 Top Class Call Girl Service AvailableCall Girls Whitefield Just Call 7001305949 Top Class Call Girl Service Available
Call Girls Whitefield Just Call 7001305949 Top Class Call Girl Service Availablenarwatsonia7
 
Hi,Fi Call Girl In Mysore Road - 7001305949 | 24x7 Service Available Near Me
Hi,Fi Call Girl In Mysore Road - 7001305949 | 24x7 Service Available Near MeHi,Fi Call Girl In Mysore Road - 7001305949 | 24x7 Service Available Near Me
Hi,Fi Call Girl In Mysore Road - 7001305949 | 24x7 Service Available Near Menarwatsonia7
 
Call Girls Service Jaipur Grishma WhatsApp ❤8445551418 VIP Call Girls Jaipur
Call Girls Service Jaipur Grishma WhatsApp ❤8445551418 VIP Call Girls JaipurCall Girls Service Jaipur Grishma WhatsApp ❤8445551418 VIP Call Girls Jaipur
Call Girls Service Jaipur Grishma WhatsApp ❤8445551418 VIP Call Girls Jaipurparulsinha
 
Kesar Bagh Call Girl Price 9548273370 , Lucknow Call Girls Service
Kesar Bagh Call Girl Price 9548273370 , Lucknow Call Girls ServiceKesar Bagh Call Girl Price 9548273370 , Lucknow Call Girls Service
Kesar Bagh Call Girl Price 9548273370 , Lucknow Call Girls Servicemakika9823
 
Call Girls In Andheri East Call 9920874524 Book Hot And Sexy Girls
Call Girls In Andheri East Call 9920874524 Book Hot And Sexy GirlsCall Girls In Andheri East Call 9920874524 Book Hot And Sexy Girls
Call Girls In Andheri East Call 9920874524 Book Hot And Sexy Girlsnehamumbai
 
Asthma Review - GINA guidelines summary 2024
Asthma Review - GINA guidelines summary 2024Asthma Review - GINA guidelines summary 2024
Asthma Review - GINA guidelines summary 2024Gabriel Guevara MD
 
Aspirin presentation slides by Dr. Rewas Ali
Aspirin presentation slides by Dr. Rewas AliAspirin presentation slides by Dr. Rewas Ali
Aspirin presentation slides by Dr. Rewas AliRewAs ALI
 
Call Girl Indore Vrinda 9907093804 Independent Escort Service Indore
Call Girl Indore Vrinda 9907093804 Independent Escort Service IndoreCall Girl Indore Vrinda 9907093804 Independent Escort Service Indore
Call Girl Indore Vrinda 9907093804 Independent Escort Service IndoreRiya Pathan
 
College Call Girls Pune Mira 9907093804 Short 1500 Night 6000 Best call girls...
College Call Girls Pune Mira 9907093804 Short 1500 Night 6000 Best call girls...College Call Girls Pune Mira 9907093804 Short 1500 Night 6000 Best call girls...
College Call Girls Pune Mira 9907093804 Short 1500 Night 6000 Best call girls...Miss joya
 
Low Rate Call Girls Pune Esha 9907093804 Short 1500 Night 6000 Best call girl...
Low Rate Call Girls Pune Esha 9907093804 Short 1500 Night 6000 Best call girl...Low Rate Call Girls Pune Esha 9907093804 Short 1500 Night 6000 Best call girl...
Low Rate Call Girls Pune Esha 9907093804 Short 1500 Night 6000 Best call girl...Miss joya
 
Call Girls Electronic City Just Call 7001305949 Top Class Call Girl Service A...
Call Girls Electronic City Just Call 7001305949 Top Class Call Girl Service A...Call Girls Electronic City Just Call 7001305949 Top Class Call Girl Service A...
Call Girls Electronic City Just Call 7001305949 Top Class Call Girl Service A...narwatsonia7
 
Call Girls Kanakapura Road Just Call 7001305949 Top Class Call Girl Service A...
Call Girls Kanakapura Road Just Call 7001305949 Top Class Call Girl Service A...Call Girls Kanakapura Road Just Call 7001305949 Top Class Call Girl Service A...
Call Girls Kanakapura Road Just Call 7001305949 Top Class Call Girl Service A...narwatsonia7
 
Call Girls Service Chennai Jiya 7001305949 Independent Escort Service Chennai
Call Girls Service Chennai Jiya 7001305949 Independent Escort Service ChennaiCall Girls Service Chennai Jiya 7001305949 Independent Escort Service Chennai
Call Girls Service Chennai Jiya 7001305949 Independent Escort Service ChennaiNehru place Escorts
 
Vip Call Girls Anna Salai Chennai 👉 8250192130 ❣️💯 Top Class Girls Available
Vip Call Girls Anna Salai Chennai 👉 8250192130 ❣️💯 Top Class Girls AvailableVip Call Girls Anna Salai Chennai 👉 8250192130 ❣️💯 Top Class Girls Available
Vip Call Girls Anna Salai Chennai 👉 8250192130 ❣️💯 Top Class Girls AvailableNehru place Escorts
 
Low Rate Call Girls Mumbai Suman 9910780858 Independent Escort Service Mumbai
Low Rate Call Girls Mumbai Suman 9910780858 Independent Escort Service MumbaiLow Rate Call Girls Mumbai Suman 9910780858 Independent Escort Service Mumbai
Low Rate Call Girls Mumbai Suman 9910780858 Independent Escort Service Mumbaisonalikaur4
 

Recently uploaded (20)

Russian Call Girls Chickpet - 7001305949 Booking and charges genuine rate for...
Russian Call Girls Chickpet - 7001305949 Booking and charges genuine rate for...Russian Call Girls Chickpet - 7001305949 Booking and charges genuine rate for...
Russian Call Girls Chickpet - 7001305949 Booking and charges genuine rate for...
 
sauth delhi call girls in Bhajanpura 🔝 9953056974 🔝 escort Service
sauth delhi call girls in Bhajanpura 🔝 9953056974 🔝 escort Servicesauth delhi call girls in Bhajanpura 🔝 9953056974 🔝 escort Service
sauth delhi call girls in Bhajanpura 🔝 9953056974 🔝 escort Service
 
Bangalore Call Girls Majestic 📞 9907093804 High Profile Service 100% Safe
Bangalore Call Girls Majestic 📞 9907093804 High Profile Service 100% SafeBangalore Call Girls Majestic 📞 9907093804 High Profile Service 100% Safe
Bangalore Call Girls Majestic 📞 9907093804 High Profile Service 100% Safe
 
Call Girls Hsr Layout Just Call 7001305949 Top Class Call Girl Service Available
Call Girls Hsr Layout Just Call 7001305949 Top Class Call Girl Service AvailableCall Girls Hsr Layout Just Call 7001305949 Top Class Call Girl Service Available
Call Girls Hsr Layout Just Call 7001305949 Top Class Call Girl Service Available
 
College Call Girls Vyasarpadi Whatsapp 7001305949 Independent Escort Service
College Call Girls Vyasarpadi Whatsapp 7001305949 Independent Escort ServiceCollege Call Girls Vyasarpadi Whatsapp 7001305949 Independent Escort Service
College Call Girls Vyasarpadi Whatsapp 7001305949 Independent Escort Service
 
Call Girls Whitefield Just Call 7001305949 Top Class Call Girl Service Available
Call Girls Whitefield Just Call 7001305949 Top Class Call Girl Service AvailableCall Girls Whitefield Just Call 7001305949 Top Class Call Girl Service Available
Call Girls Whitefield Just Call 7001305949 Top Class Call Girl Service Available
 
Hi,Fi Call Girl In Mysore Road - 7001305949 | 24x7 Service Available Near Me
Hi,Fi Call Girl In Mysore Road - 7001305949 | 24x7 Service Available Near MeHi,Fi Call Girl In Mysore Road - 7001305949 | 24x7 Service Available Near Me
Hi,Fi Call Girl In Mysore Road - 7001305949 | 24x7 Service Available Near Me
 
Call Girls Service Jaipur Grishma WhatsApp ❤8445551418 VIP Call Girls Jaipur
Call Girls Service Jaipur Grishma WhatsApp ❤8445551418 VIP Call Girls JaipurCall Girls Service Jaipur Grishma WhatsApp ❤8445551418 VIP Call Girls Jaipur
Call Girls Service Jaipur Grishma WhatsApp ❤8445551418 VIP Call Girls Jaipur
 
Kesar Bagh Call Girl Price 9548273370 , Lucknow Call Girls Service
Kesar Bagh Call Girl Price 9548273370 , Lucknow Call Girls ServiceKesar Bagh Call Girl Price 9548273370 , Lucknow Call Girls Service
Kesar Bagh Call Girl Price 9548273370 , Lucknow Call Girls Service
 
Call Girls In Andheri East Call 9920874524 Book Hot And Sexy Girls
Call Girls In Andheri East Call 9920874524 Book Hot And Sexy GirlsCall Girls In Andheri East Call 9920874524 Book Hot And Sexy Girls
Call Girls In Andheri East Call 9920874524 Book Hot And Sexy Girls
 
Asthma Review - GINA guidelines summary 2024
Asthma Review - GINA guidelines summary 2024Asthma Review - GINA guidelines summary 2024
Asthma Review - GINA guidelines summary 2024
 
Aspirin presentation slides by Dr. Rewas Ali
Aspirin presentation slides by Dr. Rewas AliAspirin presentation slides by Dr. Rewas Ali
Aspirin presentation slides by Dr. Rewas Ali
 
Call Girl Indore Vrinda 9907093804 Independent Escort Service Indore
Call Girl Indore Vrinda 9907093804 Independent Escort Service IndoreCall Girl Indore Vrinda 9907093804 Independent Escort Service Indore
Call Girl Indore Vrinda 9907093804 Independent Escort Service Indore
 
College Call Girls Pune Mira 9907093804 Short 1500 Night 6000 Best call girls...
College Call Girls Pune Mira 9907093804 Short 1500 Night 6000 Best call girls...College Call Girls Pune Mira 9907093804 Short 1500 Night 6000 Best call girls...
College Call Girls Pune Mira 9907093804 Short 1500 Night 6000 Best call girls...
 
Low Rate Call Girls Pune Esha 9907093804 Short 1500 Night 6000 Best call girl...
Low Rate Call Girls Pune Esha 9907093804 Short 1500 Night 6000 Best call girl...Low Rate Call Girls Pune Esha 9907093804 Short 1500 Night 6000 Best call girl...
Low Rate Call Girls Pune Esha 9907093804 Short 1500 Night 6000 Best call girl...
 
Call Girls Electronic City Just Call 7001305949 Top Class Call Girl Service A...
Call Girls Electronic City Just Call 7001305949 Top Class Call Girl Service A...Call Girls Electronic City Just Call 7001305949 Top Class Call Girl Service A...
Call Girls Electronic City Just Call 7001305949 Top Class Call Girl Service A...
 
Call Girls Kanakapura Road Just Call 7001305949 Top Class Call Girl Service A...
Call Girls Kanakapura Road Just Call 7001305949 Top Class Call Girl Service A...Call Girls Kanakapura Road Just Call 7001305949 Top Class Call Girl Service A...
Call Girls Kanakapura Road Just Call 7001305949 Top Class Call Girl Service A...
 
Call Girls Service Chennai Jiya 7001305949 Independent Escort Service Chennai
Call Girls Service Chennai Jiya 7001305949 Independent Escort Service ChennaiCall Girls Service Chennai Jiya 7001305949 Independent Escort Service Chennai
Call Girls Service Chennai Jiya 7001305949 Independent Escort Service Chennai
 
Vip Call Girls Anna Salai Chennai 👉 8250192130 ❣️💯 Top Class Girls Available
Vip Call Girls Anna Salai Chennai 👉 8250192130 ❣️💯 Top Class Girls AvailableVip Call Girls Anna Salai Chennai 👉 8250192130 ❣️💯 Top Class Girls Available
Vip Call Girls Anna Salai Chennai 👉 8250192130 ❣️💯 Top Class Girls Available
 
Low Rate Call Girls Mumbai Suman 9910780858 Independent Escort Service Mumbai
Low Rate Call Girls Mumbai Suman 9910780858 Independent Escort Service MumbaiLow Rate Call Girls Mumbai Suman 9910780858 Independent Escort Service Mumbai
Low Rate Call Girls Mumbai Suman 9910780858 Independent Escort Service Mumbai
 

C 02