Transcription of Section5 - nes.scot.nhs.uk
1 29 Section 5 Factorsaffecti ng wa rfar inObjectivesOn co mplet ionofth is se ct ionyo u sh ould beableto: analys e thewid e ran geof factorsthatcanaff ect warfarintherapy summaris e th e mainfactors th at pharmacists an d pharmacytechniciansshoul d be particularly awareof(eg,druginteractions,di et, lifestyle) predi ct dr uganddiseasein te ra ct io nswi or s can af fe ct an indi vid ual s responseto warfarin , including: dr ug int eract io ns (i nc ludi ng he rbal remedies) diseasesta tes age preg nan cy diet alcoh ol con cord Dru g interactionsAlmostany dru g ca n inte rac t wi th warfar in.
2 Interactionsinv olvi ng warfarin can bedivid ed int o two mai n groups: ph armacokinet ic ph rma cokineticeff ectsA ph armacokinet ic inte rac ti on is one that will alter the pla sma co ncent rationofwarfarinand res ult in a ch ang e in the IN R. Thesetypes of interactionsare mainlydue to an ef fect on the me tab oli sm of warfarin , but somedrugsalso affectth eabso rp ti on of warf ari n, while ot her s can causedi splacement from proteinbin dingsites .Pha rma codynamic effe ct sA ph armacodynamic ef fe ct is one th at increasesth e ris k of bleedingwithoutalt eringth e plasmaco ncen trati on of warf ari n (eg , when paroxetine is taken with warfarin ).
3 Th e mech anismof th is inte rac ti on is not fully unders tood. Any drug th at affectspla telet agg regat ion (e g, clop idogrel) wil l also increasethe risk of bleedingwithoutchan gi ng the INR .O C TO B E R 2 0 0 8 Read an y st an dar d cli nicalpharm ac y tex tb ook for moredetai ls ab out the mec han ismof drug inter ac ti ons wit hwarf ar signif ica nt drug int eract ionsTh e use of an inte ra cti ng drug wi th warfari n is very di fficultto av oid in pati entswith multi ple di se as e sta te s and conseq uent eractions maylea d to a lo ss of anti coa gu latio n (the reby in creasin g the ris k of thrombosis)
4 Or th eymay ca us e ove r-an tic oagu lati on (th ereby lead ing to a risk of haemorrhage).Whe n a pati en t is stabi lis ed on warf ar in th e INR mu st be closelymoni tore d du rin gthe intro duc tio n, di sc ontin uati on or do sage ad ju stm en ts of any in te ra cti ngmedi ca tio n (eg , ami odaro ne ).Th e BC SH gu ide li nes on ora l ant icoagulantsstate that: if a drug chan ge lasts les s thanfive days eith er no change,minor dose reductionor om iton e co mpl ete do se of warfarin .
5 If kn own potentiatingdruggiven if the dru g chan ge last s moreth an fi ve da ys chec k the IN R one weekaftercommen ci ngthe new dru g an d ad jus t th e warfarindo se on the basisof the actic e poi ntFind out wh at arrangementsare in place locallyfor add itionalINR blo odchec ks wh en intera cting drugs are co-prescribedfor a patientalread y onwa rf arin. How do you ensurethat these addi tionalINR checkshave beencar ri ed out?It is impo rt ant to unde rst an d th e mechanism of any drug/ drug int eractio n wi thwarf ar in and to kno w what advi ce to giv e to the pat ient abouttheir wa rfar in wh enot her me dic ati on is alter ed in an y rfa rin is me taboli se d by se ve ral P450iso-enzymesin the liver.
6 Any dru g thataf fe cts th e cyto chromeP4 50 P2C 9 enzymesys tem (wh ich is th e primar y sit e of themeta bo lis m of the S-i so me r of warfa rin , th e more potentform of warfarin ) ha s th epo ten tia l to hav e a marke d eff ec t on ant ico agu lation,eit her by increa sing ordec rea si ng the IN R. Bot h ami od aro ne and fluconazoleaffectthi s en zyme sys temand ca n po ten tia te the an tic oag ula nt effectof ere are othe r me di ci ne s wh ic h, if co-prescribed with warfarin , requireadd it io na lco uns elli ng advi ce suc h as.
7 Any me dic ine wit h the pot ent ial to causegast rointestinalul cerationan dsub se que nt ga st roi nte st in al ble ed in g (eg, alen dronicacid or NSAIDs) an y med ic ine th at inhi bit s plate le t functiontend s to in creaseth e ris k of bleed ing(e g, NSAID s, as pi ri n and clo pi dro grel). Th is effecton plateletfunctionis no tref lec te d in the IN R and wi ll not be det ected by ents and pha rma ci sts sh ou ld be parti cu larly alert to the potential for in terac ti onbet we en warf ari n and ove r-th e-c ount er produ ct s (eg, cimeti dine, mi conazole an dora l or to pi cal NS AIDs ).
8 In addi ti on, phar mac is ts sho uld also be awareof the potentialinteractions be twe enherb al medi ci nes an d warfa rin .30S E C T I O N 5O C TO B E R 2 0 0 8 Pharmacists sh ou ld also beawareof the po ten tialinteractions betw een herbalmedicinesan d war mostfr equ ent andsignificant in terac tionsinvolv e the hepat ic inhibitionor in ductionof war is list is not exh au to cu rren t pu blishedrefer en ces an d text for moredetai led inform at ion .FA C TO R S A F F E C T I N G WA R FA R I NTh e co-ad min istr ati on of warf ari n and NSAIDsis cited by the Nati on al PatientSafety Age ncy (NPSA)as th e dr ug interaction most commonlyass ociat ed wit hclinicallysigni ficantadv ers e re ac po ssib le, NSAIDssh ou ld be av oidedby pati en ts takin g wa rfar in, particularlybyth ose at great er ri sk from drug inte racti on s such as the elderlyor patientswithsevereliv er di sease.
9 If an NSAIDis requi red to tre at a pati ent wh o is takin g warfarin it sh ou ld preferablybe giv en at lo w dos ag es and introduced slowly,wit h close mo nitori ng of the INRand the pat ien t fo r sig ns of ble edin g complicat ions. Somecen tres also advisethe useof a pro to n pumpinhi bi descr ibe s somedr ug s whic h are knownto interact wit h warfarin , asdescr ibed in th eBr itishna tionalform ular LE 3 Sel ectedexample s of druginteractionswith warfarinDrugswh ich enhancetheDrugswhichreducetheant icoagulantef fectanticoagulanteffectAl lop uri no lCarbamazepineAm iod aron eOestrogensAs pi rinPhenytoin*Azo le anti fun ga ls (flu conazole, itraconazole,Primidoneke tcon azol e, mico nazole)
10 Ci me tid in eProges to gen sCi pro fl oxaci nRifam ycin sEn ta capo neVitam in K pres en t in someenteralfeedsFi bra tesFl uv as tatinMe tron id azol eOme prazo leSi mv astati nTa moxi fenTe stosteroneTe tra cycl inesTh yr oxin eTra madolSSRI s* The metabol is m of coumarinsis acceleratedby phenytoin (thereis a possibility of a reducedantico agul an t effect,but enhancementhas also been reported).Eryth rom yci n an d other macrolidesinteractwith warfarinunpredictablyand only ac tic e po intHav e a loo k at appendix 1 (Inter actio ns)
