B4 Pharm Exam 1
How ohyperlipidemia oleads oto oheart ofailure o- ohyperlip o--> oathero o--> oCHD o(ie. oangina,
oMI) oand/or oHTN o--> oheart ofailure
Classes oof oAntihyperlipidemic oDrugs o- o- oHMG-CoA oreductase oinhibs o(statins)
- Bile oacid osequestrants
- Chol oabsorp oinhibs
- Fibrates
- Niacin
- Others oincl oPCSK9 oinhibs, oHDL oelevs, oHoFH
Lipoprotein o- otransp oform oof olipids omade oup oof olipids+prots osince olipids oinsol oin
oplasma
Chylomicrons o- olipoprot osynth oin ointest omade oof odietary o(exog) oTGs+chol; omost
oimp oapoprot o= oApoB-48
VLDL o- olipoprot osynth oin oliver omade oup oof oendog/hep oTGs; omost oimp oapoprot o=
oApoB-100
IDL o- olipoprot osynth ofrom oVLDL ocatab omade oup oof ochol oesters+endog oTGs; omost
oimp oapoprot o= oApoB-100
LDL o- olipoprot osynth ofrom oVLDL ocatab oexpr oin oliver+intest, omade oup oof ochol
oesters; omost oimp oapoprot o= oApoB-100
HDL o- olipoprot osynt oin ointest, oliver, oplasma omade oup oof ophospholips+chol oesters;
omost oimp oapoprot o= oApoA
LDL ostructure o- ocore oof ochol oesters o+ oouter olayer oof oApoB-100, ophospholipids,
ofree ochol omols
Relationship oof oLipoprotein oSize o& oDensity o- olargest olipoprot o(chylomicrons) ohas
olowest odensity; ohighest odens o= oLp(a) o& oHDL
Exogenous oPathway oof oLipid oMetabolism o- o1). oDiet oTGs+chol oincorp ointo olarge
ochylomic olipoprots
2). Chylomics ohydr oby oLPL oon oendoth osurf oadip+musc, ocleaving oFAs ofrom oTGs
3). Chylomic oenters ocirc oas opredom ochol o(chylomic oremnant)
4). Chylomic oremnant ointo oliver oby orec-med oendocyt
Endogenous oPathway oof oLipid oMetabolism o- o1). oLiver osecr oTGs+chol oin oVLDL
oform, ometab oby oLPL o--> oIDL
2). Chol odens oin oIDL oincr ountil oLDL oform
3). LDL ointo oliver/periph otiss oby oLDLR oor oaccum oin oBVs o(athero)
4). HDL oprom ochol orem ofrom operiph ocells, otx oto oapoprot o--> odeliv oback oto
oliver ofor ometab/excr
,B4 Pharm Exam 1
Pathogenesis oof oAtherosclerosis o- oLDL omigr ointo oBV ointima, obind oproteoglycans o-->
ooxid/glycosylated o--> oaldehyde ointermeds ofragmenting oApoB-100
- endoth odam o--> omac oinvasion o--> oendoth+mac oGFs ostim osm omusc omigr oto otun
oint o(sm omusc ohyperpl) o--> ooxLDL oaccum oin omacs o(foam ocells)+musc ocells o-->
ocoll+el ofibs ointo oCT omatrix oforming osubendoth ofibr oplaque
Role oof oHyperlipidemia oin oCVD o- omajor oCHD oRF oincl oac oMI, oac+chron oIHD,
oangina opectoris, oathero oCVD
- gen+EVRal ofacs oincr oserum olipoprot olev
- athero o= opredom oMI ocause oby oturb obl oflow oaround ocor oart oplaque oprod ooccl
othrombus
Antihyperlipidemic oDrugs ofor oTreatment oof oHypercholesterolemia o- o- oHMG-CoA
oReductase oInhibs o= oAtorvastatin, oLovastatin, oPravastatin, oSimvastatin, oFluvastatin,
oPitavastatin, oRosuvastatin
- Bile oAcid oSequestrants o= oColestipol, oCholestyramine, oColesevelam
- Chol oAbsorp oInhibs o= oEzetimibe
Antihyperlipidemic oDrugs ofor oTreatment oof oHyperTG o- o- oFibrates o= oGemfibrozil,
oFenofibrate, oFenofibric oAcid
- Niacin
Statins oin oorder ofrom oleast oLDL-lowering oto ogreatest oLDL-lowering o- o- oFluvastatin
- Lovastatin
- Pravastatin
- Simvastatin
- Pitavastatin
- Atorvastatin
- Rosuvastatin
MOA o& oPharm oConsequences oof oHMG-CoA oReductase oInhibitors o- o- oMOA o= oinhib
oHMG- oCoA oreduc oconv oHMG-CoA oto omevalonic oac oin ochol obiosynth o(rate-lim
ostep)
- inhib oHMG-CoA ored o--> odecr ochol osynth ow/in ocell o--> oupreg oLDLR osynth o-->
oincr ouptake oLDL ofrom obl, odecr oserum oLDL, odecr oVLDL osecr oby oliver oby olack
oraw omats ofor oVLDL osynth
Overall oPharmacological oEffects oof oStatin oTreatment oon oLipids o- o- odecr oLDL-C
- decr oVLDL-C
- incr oHDL-C oin osome opts oby oincr oApoA-1 osynth
- decr oserum oTG oby odecr oVLDL-C
- Atorv, oLova, oPrava, oSimva o--> odecr ofat+non-fat oCHD oev, odecr ostroke, odecr ototal omort
Mode oof oexcretion ofor omost ostatins o- obiliary/fecal oexcr
Examples oof olong-acting ostatins o- o- oAtorvastatin o(t1/2 o= o14 ohr o--> oonce-daily odose)
- Rosuvastatin o(t1/2 o= o19 ohr o--> oonce odaily odose)
- Pitavastatin o(t1/2 o= o12 ohr)
,B4 Pharm Exam 1
Why odoes oPravastatin opresent owith oless oAEs oand oDIs othan oother ostatins? o- olow
oprot obinding o& odoes oNOT oreq oCYP450 oenz ofor ometab o--> olow oint ow/ oother
odrugs/body oprots o& oexcr olargely ounchanged ofrom oparent ocomp
Beneficial oCV oEffects oof oStatins o- o- oendoth ofunc oimprov
- incr oathero oplaque ostab o(ie. obefore osurg)
- anti-infl
- lipoprot ooxid oinhib
- anticoag oby oplt oaggreg+plt othrombi oinhib
Statins ow/ ogreatest oeffects oon oTGs o(used ofor oMixed oHyperlipidemia) o- o- oAtorvastatin
- Rosuvastatin
Use oof oAtorvastatin+Amlodipine o(Caduet) o- oAmlodipine o= oCa2+ ochann oblocker o(vasodil)
- combo ofor oHTN/angina o+ ohyperchol
Statins ofor otreatment oof ochildren ow/ oHeterozygous oFamilial oHypercholesterolemia
o(LDLR odefect) o- o- oAtorvastatin
- Lovastatin
- Simvastatin
- Pravastatin
Potential onon-CV ouses oof ostatins o- o- oClin oTrials o= omaybe oprot oag oosteop, ocancer
- recent ofindings othat oboost oerec ofunc
AEs o& oCIs oof oStatins o- o- oAEs o= oGI o(cramps, oconstip, odiarr, oheartburn) omost
ocomm; oliver otox; oRHABDOMYOLYSIS o= opot ofat ostat-ind omyop oby ocell omemb
ocomp o+ oelec oprops oalterations o--> odiscont ostatin oif ooccurs
- CIs o= opreg+nursing owomen ob/c ochol osynth onec ofor ofet ogrowth
DIs oof oStatins o- o- ocaution ow/ ofibric oac oderivs ob/c ocan oalso ocause omyops
- Erythromycin o& oItraconazole o--> oinhib ostatin ometab o--> oincr oAEs olike omyop
- decr ometab/incr olevels oof oCYP450 osubstrates o(Warfarin)
Effects oof oStatin-Induced oRhabdomyolysis oon oKidneys o- ostatins oalter omusc ocell
omemb ocomp o--> oweak omyocytes o--> omusc oprot oleak o--> odecr oelec oprops o&
olodging oprots oin okidney o--> oac okidney ofail
Examples o& oMOA oof oBile oAcid oSequestrants o(binding oresins) ofor
oHypercholesterolemia o- oincl oCholestyramine, oColestipol, oColesevelam
- MOA o= olarge omol owt opolyms obinding ogut obile oac, oexcr oin ofeces oblocking
oenterohep obile oac ocycling o(BAS otoo olarge ofor oliver oabsorp) o--> omore oliv ochol
oused ofor oBA osynth o--> oupreg oliv oLDLR o--> odecr oLDL-C
, B4 Pharm Exam 1
Therapeutic oUses, oAEs, oDIs oof oBile oAcid oSequestrants o- o- oUses o= omod oeffec
ohyperchol otreatement o(red oLDL-C obut omay oincr oTG+VLDL), ooften ocombo ow/ ostatins;
otreatment odiarr+itching ocaused oby oexcess oBAs o(BAs obind oelectros oto oabsorb oin
ointest+stool)
- AEs o= ogen owell-tol, omild oGI osx, oskin orash
- DIs o= obind odigoxin, othyroxin, owarfarin; oVit oK omalabs o--> oprolonged
oprothrombin otime o(decr oclotting)
MOA on& onPK onof onEzetimibe on- on- onMOA on= onchol onabsorp oninhib onby onsel oninhib
onNPC1L1 onchol ontransp o prot onbrush onbord oncells, ondecr onchol ontransp onfrom onmicelles
oninto onenteros onby o on50% onw/o onred onTG/fat-nsol onvit onabsorp
- single ondaily ondose on--> ondecr onLDL on15-20% on+ onTG on8%, onincr onHDL on3%
- esp oneffec onin oncombo onw/ onstatin
- PK on= onrap onabsorb onfrom onintest onafter onor onadmin, onmetab onin onintest+liver
onforming o onezetimibe- o glucuronide onconjug on(highly onwater-sol onby ongluc onac,
onbetter onexcr); onenterohep oncirc onw/ ont1/2 on= on22nhrs
Therapeutic onUses on& onAEs onof onEzetimibe on- on- onUses on= onmost oncomm onnonstatin
o onagent onfornlowering onLDL; onalone/combo onw/ onstatins onfor onhyperchol ontreatment
- Ezetimibe+Simvastatin on(Vytorin) on= on60% onLDL onred onfor onhomoz onfam onhyperchol
- AEs on= ongen onwell-tol onbut onsome onimpair onliv onfunc, ondyspepsia, onmyalgia, onrare onmyop,
onHA
Use onof onBile onAcid onSequestrants onif onHigh onTGs on- onBA onseqs onred onLDL-C onby on15-
30% o onbut onnot onabsnso onno onsyst oneffects, onbut onassoc onw/ onGI onsx on(constip) on& oncan
oncause onsev o onhyperTG onif onfasting onTG o 300+
Examples on& onActions onof onFibrates on(fibric onacid onderivatives) on- onincl onGemfibrozil, o
onFenofibrate,nFenofibric onAcid
- ndecr onTGs on(40-50%), ondecr onLDL-C on(10%), onincr onHDL-C on(10-20%)
MOA onof onFibrates onfor onLowering onVLDL-TGs on- onbind+activ onPPAR-alpha
on(peroxisome o onprolif o activ onrec onalpha) on--> onincr onLPL onexpr, ondecr onApoC-III on(LPL
oninhib) onexpr on--> onincr oonhydr+rem onVLDLnTGs on& onchylomic onTGs on--> ondecr
onplasma onTGs
- also onactiv onPPAR-alpha on--> onincr onexpr onFA onoxid onenz on--> ondecr onTG onsynth
MOA onof onFibrates onfor onLowering onLDL-C on& onIncreasing onHDL-C on- onactiv onPPAR-
alpha o on--> onincrnliver onLDLR onexpr on--> onincr onLDL onuptake onby onliver on--> ondecr
onLDL-C
- also onactiv onPPAR-alpha on--> onincr onFA onoxid on--> ondecr onTG onsynth on--> ondecr
onVLDL oonform on--> ondecrnLDL onform on(prod onof onVLDL onby onliver)
- activ onPPAR-alpha on--> onincr onApoA-I on& onApoA-II onsynth on(HDL oncomps) on--> onincr
onHDL oonform on-->nincr onHDL-C
Therapeutic onUses, onAEs, onDIs onof onFibrates on- on- onUses on= onprim onfor onhyperTG on&
onHDL o ondef; onalso onforncomb onhyperchol on& onhyperTG
- AEs on= onGI onsx, onmyops on(rhabdo), onincr onrisk oncholelithiasis
- DIs on= oncomb onw/ onstatins on(Rosuva, onPrava) onfor oncomb onhyperlip/decr onHDL
How ohyperlipidemia oleads oto oheart ofailure o- ohyperlip o--> oathero o--> oCHD o(ie. oangina,
oMI) oand/or oHTN o--> oheart ofailure
Classes oof oAntihyperlipidemic oDrugs o- o- oHMG-CoA oreductase oinhibs o(statins)
- Bile oacid osequestrants
- Chol oabsorp oinhibs
- Fibrates
- Niacin
- Others oincl oPCSK9 oinhibs, oHDL oelevs, oHoFH
Lipoprotein o- otransp oform oof olipids omade oup oof olipids+prots osince olipids oinsol oin
oplasma
Chylomicrons o- olipoprot osynth oin ointest omade oof odietary o(exog) oTGs+chol; omost
oimp oapoprot o= oApoB-48
VLDL o- olipoprot osynth oin oliver omade oup oof oendog/hep oTGs; omost oimp oapoprot o=
oApoB-100
IDL o- olipoprot osynth ofrom oVLDL ocatab omade oup oof ochol oesters+endog oTGs; omost
oimp oapoprot o= oApoB-100
LDL o- olipoprot osynth ofrom oVLDL ocatab oexpr oin oliver+intest, omade oup oof ochol
oesters; omost oimp oapoprot o= oApoB-100
HDL o- olipoprot osynt oin ointest, oliver, oplasma omade oup oof ophospholips+chol oesters;
omost oimp oapoprot o= oApoA
LDL ostructure o- ocore oof ochol oesters o+ oouter olayer oof oApoB-100, ophospholipids,
ofree ochol omols
Relationship oof oLipoprotein oSize o& oDensity o- olargest olipoprot o(chylomicrons) ohas
olowest odensity; ohighest odens o= oLp(a) o& oHDL
Exogenous oPathway oof oLipid oMetabolism o- o1). oDiet oTGs+chol oincorp ointo olarge
ochylomic olipoprots
2). Chylomics ohydr oby oLPL oon oendoth osurf oadip+musc, ocleaving oFAs ofrom oTGs
3). Chylomic oenters ocirc oas opredom ochol o(chylomic oremnant)
4). Chylomic oremnant ointo oliver oby orec-med oendocyt
Endogenous oPathway oof oLipid oMetabolism o- o1). oLiver osecr oTGs+chol oin oVLDL
oform, ometab oby oLPL o--> oIDL
2). Chol odens oin oIDL oincr ountil oLDL oform
3). LDL ointo oliver/periph otiss oby oLDLR oor oaccum oin oBVs o(athero)
4). HDL oprom ochol orem ofrom operiph ocells, otx oto oapoprot o--> odeliv oback oto
oliver ofor ometab/excr
,B4 Pharm Exam 1
Pathogenesis oof oAtherosclerosis o- oLDL omigr ointo oBV ointima, obind oproteoglycans o-->
ooxid/glycosylated o--> oaldehyde ointermeds ofragmenting oApoB-100
- endoth odam o--> omac oinvasion o--> oendoth+mac oGFs ostim osm omusc omigr oto otun
oint o(sm omusc ohyperpl) o--> ooxLDL oaccum oin omacs o(foam ocells)+musc ocells o-->
ocoll+el ofibs ointo oCT omatrix oforming osubendoth ofibr oplaque
Role oof oHyperlipidemia oin oCVD o- omajor oCHD oRF oincl oac oMI, oac+chron oIHD,
oangina opectoris, oathero oCVD
- gen+EVRal ofacs oincr oserum olipoprot olev
- athero o= opredom oMI ocause oby oturb obl oflow oaround ocor oart oplaque oprod ooccl
othrombus
Antihyperlipidemic oDrugs ofor oTreatment oof oHypercholesterolemia o- o- oHMG-CoA
oReductase oInhibs o= oAtorvastatin, oLovastatin, oPravastatin, oSimvastatin, oFluvastatin,
oPitavastatin, oRosuvastatin
- Bile oAcid oSequestrants o= oColestipol, oCholestyramine, oColesevelam
- Chol oAbsorp oInhibs o= oEzetimibe
Antihyperlipidemic oDrugs ofor oTreatment oof oHyperTG o- o- oFibrates o= oGemfibrozil,
oFenofibrate, oFenofibric oAcid
- Niacin
Statins oin oorder ofrom oleast oLDL-lowering oto ogreatest oLDL-lowering o- o- oFluvastatin
- Lovastatin
- Pravastatin
- Simvastatin
- Pitavastatin
- Atorvastatin
- Rosuvastatin
MOA o& oPharm oConsequences oof oHMG-CoA oReductase oInhibitors o- o- oMOA o= oinhib
oHMG- oCoA oreduc oconv oHMG-CoA oto omevalonic oac oin ochol obiosynth o(rate-lim
ostep)
- inhib oHMG-CoA ored o--> odecr ochol osynth ow/in ocell o--> oupreg oLDLR osynth o-->
oincr ouptake oLDL ofrom obl, odecr oserum oLDL, odecr oVLDL osecr oby oliver oby olack
oraw omats ofor oVLDL osynth
Overall oPharmacological oEffects oof oStatin oTreatment oon oLipids o- o- odecr oLDL-C
- decr oVLDL-C
- incr oHDL-C oin osome opts oby oincr oApoA-1 osynth
- decr oserum oTG oby odecr oVLDL-C
- Atorv, oLova, oPrava, oSimva o--> odecr ofat+non-fat oCHD oev, odecr ostroke, odecr ototal omort
Mode oof oexcretion ofor omost ostatins o- obiliary/fecal oexcr
Examples oof olong-acting ostatins o- o- oAtorvastatin o(t1/2 o= o14 ohr o--> oonce-daily odose)
- Rosuvastatin o(t1/2 o= o19 ohr o--> oonce odaily odose)
- Pitavastatin o(t1/2 o= o12 ohr)
,B4 Pharm Exam 1
Why odoes oPravastatin opresent owith oless oAEs oand oDIs othan oother ostatins? o- olow
oprot obinding o& odoes oNOT oreq oCYP450 oenz ofor ometab o--> olow oint ow/ oother
odrugs/body oprots o& oexcr olargely ounchanged ofrom oparent ocomp
Beneficial oCV oEffects oof oStatins o- o- oendoth ofunc oimprov
- incr oathero oplaque ostab o(ie. obefore osurg)
- anti-infl
- lipoprot ooxid oinhib
- anticoag oby oplt oaggreg+plt othrombi oinhib
Statins ow/ ogreatest oeffects oon oTGs o(used ofor oMixed oHyperlipidemia) o- o- oAtorvastatin
- Rosuvastatin
Use oof oAtorvastatin+Amlodipine o(Caduet) o- oAmlodipine o= oCa2+ ochann oblocker o(vasodil)
- combo ofor oHTN/angina o+ ohyperchol
Statins ofor otreatment oof ochildren ow/ oHeterozygous oFamilial oHypercholesterolemia
o(LDLR odefect) o- o- oAtorvastatin
- Lovastatin
- Simvastatin
- Pravastatin
Potential onon-CV ouses oof ostatins o- o- oClin oTrials o= omaybe oprot oag oosteop, ocancer
- recent ofindings othat oboost oerec ofunc
AEs o& oCIs oof oStatins o- o- oAEs o= oGI o(cramps, oconstip, odiarr, oheartburn) omost
ocomm; oliver otox; oRHABDOMYOLYSIS o= opot ofat ostat-ind omyop oby ocell omemb
ocomp o+ oelec oprops oalterations o--> odiscont ostatin oif ooccurs
- CIs o= opreg+nursing owomen ob/c ochol osynth onec ofor ofet ogrowth
DIs oof oStatins o- o- ocaution ow/ ofibric oac oderivs ob/c ocan oalso ocause omyops
- Erythromycin o& oItraconazole o--> oinhib ostatin ometab o--> oincr oAEs olike omyop
- decr ometab/incr olevels oof oCYP450 osubstrates o(Warfarin)
Effects oof oStatin-Induced oRhabdomyolysis oon oKidneys o- ostatins oalter omusc ocell
omemb ocomp o--> oweak omyocytes o--> omusc oprot oleak o--> odecr oelec oprops o&
olodging oprots oin okidney o--> oac okidney ofail
Examples o& oMOA oof oBile oAcid oSequestrants o(binding oresins) ofor
oHypercholesterolemia o- oincl oCholestyramine, oColestipol, oColesevelam
- MOA o= olarge omol owt opolyms obinding ogut obile oac, oexcr oin ofeces oblocking
oenterohep obile oac ocycling o(BAS otoo olarge ofor oliver oabsorp) o--> omore oliv ochol
oused ofor oBA osynth o--> oupreg oliv oLDLR o--> odecr oLDL-C
, B4 Pharm Exam 1
Therapeutic oUses, oAEs, oDIs oof oBile oAcid oSequestrants o- o- oUses o= omod oeffec
ohyperchol otreatement o(red oLDL-C obut omay oincr oTG+VLDL), ooften ocombo ow/ ostatins;
otreatment odiarr+itching ocaused oby oexcess oBAs o(BAs obind oelectros oto oabsorb oin
ointest+stool)
- AEs o= ogen owell-tol, omild oGI osx, oskin orash
- DIs o= obind odigoxin, othyroxin, owarfarin; oVit oK omalabs o--> oprolonged
oprothrombin otime o(decr oclotting)
MOA on& onPK onof onEzetimibe on- on- onMOA on= onchol onabsorp oninhib onby onsel oninhib
onNPC1L1 onchol ontransp o prot onbrush onbord oncells, ondecr onchol ontransp onfrom onmicelles
oninto onenteros onby o on50% onw/o onred onTG/fat-nsol onvit onabsorp
- single ondaily ondose on--> ondecr onLDL on15-20% on+ onTG on8%, onincr onHDL on3%
- esp oneffec onin oncombo onw/ onstatin
- PK on= onrap onabsorb onfrom onintest onafter onor onadmin, onmetab onin onintest+liver
onforming o onezetimibe- o glucuronide onconjug on(highly onwater-sol onby ongluc onac,
onbetter onexcr); onenterohep oncirc onw/ ont1/2 on= on22nhrs
Therapeutic onUses on& onAEs onof onEzetimibe on- on- onUses on= onmost oncomm onnonstatin
o onagent onfornlowering onLDL; onalone/combo onw/ onstatins onfor onhyperchol ontreatment
- Ezetimibe+Simvastatin on(Vytorin) on= on60% onLDL onred onfor onhomoz onfam onhyperchol
- AEs on= ongen onwell-tol onbut onsome onimpair onliv onfunc, ondyspepsia, onmyalgia, onrare onmyop,
onHA
Use onof onBile onAcid onSequestrants onif onHigh onTGs on- onBA onseqs onred onLDL-C onby on15-
30% o onbut onnot onabsnso onno onsyst oneffects, onbut onassoc onw/ onGI onsx on(constip) on& oncan
oncause onsev o onhyperTG onif onfasting onTG o 300+
Examples on& onActions onof onFibrates on(fibric onacid onderivatives) on- onincl onGemfibrozil, o
onFenofibrate,nFenofibric onAcid
- ndecr onTGs on(40-50%), ondecr onLDL-C on(10%), onincr onHDL-C on(10-20%)
MOA onof onFibrates onfor onLowering onVLDL-TGs on- onbind+activ onPPAR-alpha
on(peroxisome o onprolif o activ onrec onalpha) on--> onincr onLPL onexpr, ondecr onApoC-III on(LPL
oninhib) onexpr on--> onincr oonhydr+rem onVLDLnTGs on& onchylomic onTGs on--> ondecr
onplasma onTGs
- also onactiv onPPAR-alpha on--> onincr onexpr onFA onoxid onenz on--> ondecr onTG onsynth
MOA onof onFibrates onfor onLowering onLDL-C on& onIncreasing onHDL-C on- onactiv onPPAR-
alpha o on--> onincrnliver onLDLR onexpr on--> onincr onLDL onuptake onby onliver on--> ondecr
onLDL-C
- also onactiv onPPAR-alpha on--> onincr onFA onoxid on--> ondecr onTG onsynth on--> ondecr
onVLDL oonform on--> ondecrnLDL onform on(prod onof onVLDL onby onliver)
- activ onPPAR-alpha on--> onincr onApoA-I on& onApoA-II onsynth on(HDL oncomps) on--> onincr
onHDL oonform on-->nincr onHDL-C
Therapeutic onUses, onAEs, onDIs onof onFibrates on- on- onUses on= onprim onfor onhyperTG on&
onHDL o ondef; onalso onforncomb onhyperchol on& onhyperTG
- AEs on= onGI onsx, onmyops on(rhabdo), onincr onrisk oncholelithiasis
- DIs on= oncomb onw/ onstatins on(Rosuva, onPrava) onfor oncomb onhyperlip/decr onHDL
