2. drug interaction profesi new (prt)

7/25/2019 2. Drug Interaction Profesi New (Prt)

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Prof Lukman Hakim PhD

Department of Pharmacology and Clinical Pharmacy

Faculty of Pharmacy, Gadjah Mada University


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References for further reading

1 !oda"!im#le M$ % &oung '& (1))*+ ansten andorn-s Managing Clinically .mportant Drug.nteractions, $pplied /herapeutics, .nc, 0ancouver

!oda"!im#le et al (223+ and#oo4 of $pplied

/herapeutics, *thed, 'ippincott 5illiams % 5il4ins,Philadelphia

6 Mo7ayani $ % Raymon 'P (228+ and#oo4 of Drug.nteractions" $ Clinical and Forensic Guide, umana

Press, 9e: ;ersey8 Rodrigues $D (22+ Drug"Drug .nteractions, /aylor %

Francis, 9e: &or4

lac4:ell

=cience, 'ondon


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Web sites for more learning tools

:::ari7onacertorg (drug interactions+:::drug"interactionscom

(P8


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Bccurence of drug interactions

In VitroIn Vivo (in patients) :

Clinically eApected or uneApected

Clinically o#served or undetected

Clinical eect can #e severe or light


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In Vitro drug

interactionsDrugs Interactant esult

CeftriaAone sodium 'actated Ringers

solution

Ca"CeftriaAone precipitate

Daptomycin DeAtrose solution Daptomycin precipitate

Daptomycin 2)E saline solution'actated Ringerssolution

Compati#le

Piperacillin"ta7o#actam

$cyclovir Particle formation

$mphotericin > Flocculent

Mitomycin >lue colour

/heophylline Cefepime Cefepime degrades up to


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=um#er varia#ilitas respon pasienterhadap o#at

Pasien

!D"#

$bat$bat input %D"

$bat& $%& $'!$bat& $%& $'!

"akanan"akanan

"inuman"inuman!sap tembakau!sap tembakau

PolutanPolutan

DiurnalocturnDiurnalocturn

alal

*sia& ''*sia& ''

+ender+ender

,ehamilan,ehamilan+enetik& as+enetik& as

itmeitme

-irkadian-irkadian

$besitas$besitas

Pen.akit !D"#Pen.akit !D"#

Drug assay!ctive

compound

Ka, Vd, AUC, CL, T

Dosead/ustment


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+ea,e ++ et al. JAMA*99%2&!(*)"#%!#

/ashetti / et al. Eur J Clin Pharmacol*999%!(*2)"9%99#

0ontribution of DrugInteractions to the $verall

'urden of !Ds

Drug interactions represent 123 4 of in5

hospital !Ds

Drug interactions are an importantcontributor to number of # visits andhospital admissions


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Drug ma. interact 6ith

78 !nother drug(s) :

a8 -.nthetic drugsb8 Herbal or traditional medicines

98 ood and drinks

18 Pollutants : insecticides&herbicides& smoke of tobacco&e;haust& industries


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Pasien yang #erisi4o mengalami efe4#uru4 intera4si o#at

1 $plastic anemia $sthma

6 Cardiac arrhythmia8 Critical care?intensive care patients


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B#at"o#at yang potensial #erintera4si

1 $utoimmune disorders

Cardiovascular disease6 Gastrointestinal disease

8 .nfection


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12 fa4tor yang #er4aitan denganintera4si o#at

;umlah dan jenis o#atyang diguna4an

;alur pem#erian

!epatuhan pasien Durasi penggunaan

Dosis?4adar o#at >ioavaila#ilitas rendah

!isar /erapi =empit Masalah non"linearitas

=aat dan urutan

penggunaan o#at

Fra4si termeta#olisme


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Pharmaco4inetic Drug .nteractions H $#sorption

Alteration ActionDr1 indin1 in 34 trat

4ron may helate i,ro5lo6ain7 resltin1 indereased asor,tion

34 motility4nreased 34 motility ased y metolo,ramide

may derease e5,ro8il asor,tion

34 ,H34 alalini8ation y ome,ra8ole may dereaseasor,tion o5 etoona8ole

34 5lora

Dereased 34 aterial 5lora ased y an antiiotiadmin old derease aterial ,rodtion o5

vitamin : a1mentin1 antioa1lant e55et o5war5arin

Dr1 metaolism in wallo5 intestine

;A< in the wall o5 34 trat may e inhiited y ;Aenes" disontine mediation (AD/7 la o5 e55iay)7 delay to

relie5 o5 sym,toms (siide)7 ,rematre swith to other mediations

Doses need 5ore>ivalent e6,osre


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0.tochrome P=3> [email protected] P=3> 90@

!bsent in 7 4 0aucasians and!frican5!mericans

Primar. metabolism of : Most 9=$.Ds (incl CBQ"Most 9=$.Ds (incl CBQ" inhi#itors H CelecoAi#,inhi#itors H CelecoAi#,

RofecoAi#RofecoAi#++

=":arfarin (active form+=":arfarin (active form+

PhenytoinPhenytoin

Inhibited b. : Flucona7oleFlucona7ole


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0.tochrome P=3>0.tochrome P=3>


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0.tochrome P=3>0.tochrome P=3>907@907@

!bsent in 9>!bsent in 9>221>1>4 of !sians4 of !sians12312344

0aucasians0aucasians

Primar. metabolism ofPrimar. metabolism of:: Dia7epamDia7epam PhenytoinPhenytoin Bmepra7oleBmepra7ole/ricyclic antidepressants/ricyclic antidepressants Clopidogrel (prodrug+Clopidogrel (prodrug+

Inhibited b.Inhibited b.:: Bmepra7oleBmepra7ole .sonia7id.sonia7id !etocona7ole!etocona7ole

0.tochrome P=3>0.tochrome P=3>


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0.tochrome P=3>0.tochrome P=3>907@907@

$#sent in 262 E of $sians6< E Caucasians

Primary meta#olism of Clopidogrel (antiplatelet+

Clopidogrel meta#oli7ed #y C&PC1) to activeClopidogrel meta#oli7ed #y C&PC1) to activemeta#olite ($DP receptor J P&1+meta#olite ($DP receptor J P&1+

Clopidogrel may cause severe G. #leedingClopidogrel may cause severe G. #leeding

GuidelineGuideline H Clopidogrel is com#ined :ith PP .nhi#itors toH Clopidogrel is com#ined :ith PP .nhi#itors to

minimi7e #leedingminimi7e #leeding

.nhi#ited #y Proton"pump inhi#itors HProton"pump inhi#itors H Bmepra7oleBmepra7oleS somepra7ole TS somepra7ole T

'ansopra7ole T Pantopra7ole T Ra#epra7ole'ansopra7ole T Pantopra7ole T Ra#epra7ole


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Drug5oodDrug5ood

InteractionsInteractions%etrac.clines and milk products%etrac.clines and milk products

Warfarin and vitamin ,5containing foodsWarfarin and vitamin ,5containing foods+rapefruit /uice+rapefruit /uice

am 'rassicaceae (0ruciferous)am 'rassicaceae (0ruciferous)


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oods and Products High in Vitamin ,

$lfalfa ta#lets>roccoli>russels sproutsCa##ageCauliIo:er (ra:+Green leafy vegeta#les (spinach, collardgreens+Green tea'iver=oy#ean0egeta#le oils (canola, soy#ean+5atercress

D*+- %H!% I%#!0% WI%H


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+!P# *I% *I0#Ben7odia7epines 8 mida7olam, dia7epam, tria7olam

Cytoto6ic drugs 8cyclosporine, tacrolimus, sirolimus

yhydropyridine Calcium-channel blockers 8

amlodipine, felodipine, nifedipine, nisoldipine, nitrendipine, verapamil

"heopylline

09-estradiol

!tatins 8simvastatin, lorvastatin, atorvastatinAntidepressants 8 sertraline, buspirone, clomipramine

Antiepileptics8 carbama7epine

Antiretroviral agents8 sa:uinavir, indinavir

Antiarrhythmics 8 amiodarone

%isce8 methadone, sildenafil

3GJ " en8yme and P-1lyo,rotein inhiitor Soth ;ed J. 2009*02(#)"#0$-#09.

3GJ inreases ioavailaility 5or 5elodi,ine y 200C7 ni5edi,ine %&C and vera,amil

y #C. 4nhiition o5 P-1lyo,rotein inreases ioavailaility o5 dr1s.


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Dresser 3: et alClin Pharmacol Ther2000$(*)"2$#!

Hors a5ter Dose Hors a5ter Dose

#


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ect of grape fruit juice on talinololin rats

C#a8

2n(7#L3

AUC2'(;#in7#L3

S R S R

Control ;@ -;- >@;.

=GF? ad#ini"tered to(et!er it! a race#ic .@ #(71( 20o3 in rat"

=GF? did not c!an(e T.7 eli#ination o$ talinolol

S0a!n:Lan(('t! B Lan('t! : 'r ? +!ar# Sci; @@. Fe%.23E>/.:$'>?C

78 Parasetamol mempun.ai da.a analgetik 3=& F= 498 'rokoli menaikkan 4 da.a analgetik parasetamol

D l tik li il t b l d t l h


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Da.a analgetik salisilat sebelum dan setelahpemberian brokoli

F5kali mencit /antan '!L'0

78 -alisilat mempun.ai da.a analgetik 3A&J=498 'rokoli menaikkan 4 da.a analgetik salisilat


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Bnset dan durasi feno#ar#ital se#elum dan setelahpem#erian jus #ro4oli 3"4ali pada mencit jantan

78 'rokoli memperlama onset fenobarbital tetapitidak signiGkan (P K >&>3)

98 'rokoli mempercepat durasi fenobarbital (P>&>3)

0hlorpropamide vs #thanol


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0hlorpropamidevs #thanol

Acessive ethanol inta4e may lead to hypoglycemia $nanta#use"li4e reactionV may occur in patients ta4ingsulfonylureas

Ris4 factors H 9ot speci@c (can #e to anyone?any case+Related drugs H

.nsulin and other oral hypoglycemic agents, includingtol#utamide, cause hypoglycemia

/a4ing phenformin may develop lactic acidosis :henconsuming ethanol

Management H $void com#ination

Hansten @ Horn (*99$) ,. 99

0igarette smoking vs $ral


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g gcontraceptive

isk of $05induced adverse cardiovascularevents is increased b. smoking

Ris4 factorsH

5omen aged T 6< years old are at greater ris4=mo4ing T 1< cigs?day places :omen at greater ris4

ManagementH$void com#ination

5omen on BC are adviced not to smo4e, or useanother contraception method

Hansten @ Horn (*99$) ,. *0&

Drug5Herbal


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Drug HerbalInteractions-t ohnEs Wort

+inkgo biloba

,ava+arlic

488o and Frnst (2009) Adis data in5ormation I


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A$ter St; ?o!n" ort

"ean plasma concentration time course of indinavir8


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Pengaruh - Wort terhadap

DigoAin, FenoAfenadine, .rinotecanHmemodulasi P"glycoprotein 4adar o#at W

Cyclosporin, BC pills, Ritonavir, 0enlafaAineHindu4si C&P6$8 % modulasi Pgp 4adar o#atW

$lpra7olam, $mitriptyline, .matini#, .ndinavir,Mida7olam, Bmepra7ol, =imvastatin,

/acrolimus, 0erapamilH indu4si C&P6$8

5arfarinH indu4si C&PC)

+inkgo biloba


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+inkgo biloba(=>5A> mgM 9; sehariM 951 bulan)

#fek: antioksidan& menghambat agregasiplatelet (ginkgolide N inhibitor

P!)& men.embuhkan !lBheimer

#fek samping :

Perdarahan okular O intraserebral

Interaksi $bat :

neAt slide

#


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gdrugs

Dr'(" $$ectarama8e,ine Ial,roiaid

Hi1h dose 3 dereases anti-onvlsant e55et

As,irin7 lo,ido1rel7di,yridamole7 he,arin7tilo,idine7 war5arin.

Antioa1lation inreases

ylos,orine 3 ,rotets ell memranes 5romdama1e (ene5iial e55et)

Phenel8ine 7tranyly,romine

3 enhanes antide,ressant e55et o5;A< (serotonin re,tae) inhiitors

!ava (Pi th ti +


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!ava(Piper methysticum+

Xat a4tifH 4avapiron

fe4H penenang, sedatif

=H disorientasi, gangguan 4endali otot

Penggunaan 4ronisH gangguan 4imia darah,hipertensi paru, nafas pende4, mata merah, #erat#adan turun

.ntera4si o#atH C9= depressants, '"dopa, nem#utal,

#ar#iturat, QanaA ST efe4 aditif

488o and Frnst (2009) Adis Data

+ li


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+arlic

Drugs Indications 0linical resultsChlorpropamide Dia#etes mellitus ypoglycemia

Fluindione(co"meds H enalapril,furosemide,

pravastatin+

Chronic atrial@#rilation

Decreasedanticoagulation

5arfarin 9ot reported .ncreasedanticoagulation

DeAtromethorphanDe#risouine

ealthy su#jectsJC&PD

9o eect onelimination

$lpra7olam,Mida7olamDocetaAel

ealthy su#jectsJC&P6$8

9o eect onelimination

Ritonavir 822"22 mg#id

.0 infection =evere G. toAicity

488o and Frnst (2009) Adis Data


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Drug5Drug Interactions:

! -tep6ise !pproach

78 %ake a medication histor.

98 emember high risk patients $ny patient ta4ing medicationsY $nticonvulsants, anti#iotics, digoAin,

:arfarin, amiodarone, etc

18 0heck pocket reference

=8 0onsult pharmacistsdrug infospecialists

38 0heck up5to5date 6ebsite :::epocratescomZ

2. drug interaction profesi new (prt)

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