Bpac Polypharmacy Poem 2006 Pf

nzbpacbetter edicin m e

POLYPHARMACY

bpacnz Development Team: RachaelClarke

SoniaRoss

DrTrevorWalker

DavidWoods

Acknowledgement:

bpacnzwouldliketothankProfessorJohnCampbell,AssociateProfessorNgaireKerseandDrNeilWhittakerfortheirhelpandguidance

onthedevelopmentofthisresource.

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Allinformationisintendedforusebycompetenthealthcareprofessionalsandshouldbeutilisedinconjunctionwithpertinentclinical

data.

www.bpac.org.nz

Soonyouwillreceiveamultimeds self-administered patient questionnairetoidentifypeopleathigherriskof

drugrelatedproblems,amedicinesgridtoprovideavisualrepresentationofmedicationuseandaSIMPLEschema

formedicinesreview.

http://www.bpac.org.nz/

“But know also, man has an inborn

craving for medicine ...the desire to

take medicine is one feature which

distinguishes man the animal, from

his fellow creatures. It is really one

of the most serious difficulties with

which we have to contend.”

WilliamOsler1894

Contents

Background,GoalandObjectives.......................................................................................................................2

Polypharmacy-weighingupthebenefitsandharms.............................................................................................3

Elderlypeopleareatincreasedriskofdrugrelatedproblems...............................................................................4

Drugsassociatedwithincreasedriskofadversedrugreactionsinelderlypeople...................................................6

Commondruginteractionsinelderlypeople........................................................................................................7

Recognisingadversedrugreactions...................................................................................................................8

Riskfactorsfordrugrelatedproblemsinelderlypeople.................................................................................... 10

AreallygoodrecipeforDRP............................................................................................................................ 11

Drugrelatedharm;termsanddefinitions........................................................................................................... 12

Hospitaladmissionsforadversedrugreactions................................................................................................. 14

CARMcomment.............................................................................................................................................. 16

References,Bibliography................................................................................................................................. 17

bpacnzPolypharmacyIPage1

POLYPHARMACY

Goal

Thegoalofthiscampaignistodecreasedrugrelatedproblemsinelderlypeoplebyreducingprescribing

factorsassociatedwithincreasedrisk.

Background

Drugrelatedproblemscausesignificantpreventablemorbidityandmortality.Theireconomiccostis

estimatedtorankfourthinthedevelopedworld,behindcardiovasculardisease,canceranddiabetes.

Drugrelatedproblems includeadversedrugevents,adversedrugreactionsanddrug interactions.

Polypharmacyhasvariousdefinitionsandconnotationsintheliteraturerangingfromtheuseof4,5,

6ormoredrugsincombinationtothemoresimplisticadditionofjustoneinappropriatedrugtoan

existingdrugregimen.Theadditionofanydrugisonetoomanyifitprovidesnobenefitandcauses

potentialharm.Ourdefinitionofpolypharmacyforthepurposeofthiscampaignis:“theadditionofone

ormoredrugstoanexistingregimenwhichprovidesnoadditionaltherapeuticbenefitand/orcauses

drugrelatedharm”.Elderlypeopleonmultiplemedicationsareatparticularlyhighriskofdrugrelated

problems.

Objectives

To raise awareness of the increased risk of drug related problems associated with

polypharmacyand toprovide tools, includingmedicines review, to identify andmanage

highriskpatients.

Identifyandraiseawarenessofmajorcategoriesofadversedrugreactionsandhighrisk

drugcombinationsinNewZealand.

Reducetheinappropriateuseofhighriskdrugsanddrugcombinationsespeciallyinelderly

people.

Reducethe“prescribingcascade”phenomenon.

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Page2 IbpacnzPolypharmacy

“Don’t treat risk factors. Don’t even treat disease. Treat patients, and treat them as individuals”

ProfessorJohnCampbell,2005

POLYPHARMACY

Polypharmacy

Potentialbenefits Riskofharm

Synergisticcombinationsallowlowerdosesandthereforeless

adverseeffectsthanindividualdrugs.

e.g.treatmentofhypertension

Synergisticadverseeffectsincreaseriskofharm.

e.g.mayincreaseriskoffallsduetoposturalhypotension

Supplementaldrugmaydecreaseadverseeffectofinitialdrug.

e.g.anticholinergicaddedfordruginducedextrapyramidaleffects

Increasedcomplexityoftheregimencanleadtoconfusion,error

andpooradherence.

e.g.multipletablets,multipledoses,increasedriskofsideeffects

Additionaldrugmayimproveoutcomes.

e.g.additionofspironolactonetoACEinhibitorforheartfailure

Increasedopportunitiesfordruginteractions.

e.g.increasedriskofhyperkalaemia

Multipledrugsmaybeneededformultipleconditions.

e.g.diabetesplusosteoarthritis

Moredrugs=moreopportunityforadverseeffects.Difficultto

predictinteractionswithinacomplexregimen.

e.g.ACEinhibitorplusNSAIDincreasestheriskofrenalfailure

Polypharmacy - weighing up the benefits and harms

“First do no harm”

Hippocrates,460-355BC

Theuseofmultipledrugsisacceptedbestpracticeforcommon

chronicconditionssuchashypertensionanddiabetes.Conscientious

clinicians,whoadheretoevidence-basedguidelines,willoftenfind

themselvesprescribingsixormoredrugsforpeoplewithseveral

chronic conditions. However, trials investigate populations and

clinicianstreatindividuals.

Manypeopleon fiveormoredrugswill be takinganunfamiliaroreven

uniquecombination (Bjerrum,1998). Thepotential benefits and risksof

harmofsuchregimenswillnothavebeensubjecttoresearchandareoften

difficulttopredict.

The difficulty is balancing the potential benefits of these drugs,

as described in the guidelines, with the risk of harm from the

highnumberofdrugsused.Cliniciansneedtoconsidercarefully

numbers needed to treat, numbers needed to harm, long term

prognosisandthewishesofindividualpatients.


Riskofevent

Figure 1. Risk of harm increases with number of drugs taken

The risk of an adverse drug event has been

estimated at 13% for two drugs, 58% for five

drugsand82%forsevenormore(Fulton&Allen,

2005).

0 %

20 %

40 %

60 %

80 %

100 %

0 %

20 %

40 %

60 %

80 %

100 %

2drugs 5drugs 7+drugs

Elderly people are at particular risk of drug related problems

becauseofcomplexdrugregimensinvolvingmultipledrugsandthe

physiologicalchangeswhichaccompanyaging.Upto30percent

ofhospitaladmissionsintheelderlymaybeassociatedwithdrug

relatedproblems(Hanlon,1997).

Large clinical trials often exclude elderly people and those with

co-morbidities. Thismeans that subjects of trials are often very

differentfromtheelderlypatientswithmultipleco-morbiditiesseen

inpractice.AUKstudyfoundstrokepatientsinprimarycarewere

on average 12 years older than patients in the research which

formedthebasisofnationalguidelinesforbloodpressurelowering

for patientswith stroke (Mant, 2006). Theguidelines, therefore,

cannotbeapplieduncriticallytothepatientsofthesepractices.

Elderly people are at increased risk of drug related problems

Prescribersneedtoconsiderthespecialneedsofelderlypatients

whenfollowingclinicalguidelines.Iftheydonot,theyarelikelyto

exposetheirpatientstoincreasedriskofdrugrelatedproblems.

Changes which accompany aging make people particularly susceptible to drug related problems.

Physiological changes associated with aging affect a person’s

handling and response to drugs. Changes in the excretion and

metabolism of drugs lead to increased drug concentrations,

changesinreceptorsensitivitycauseexaggerationorbluntingof

drugeffects,anddeclineincognitivefunctionmakesadherenceto

acomplexdrugregimendifficult.


Some examples of age related changes to drug effects include:

increasedposturalswaywithbenzodiazepines

increasedsensitivitytoCNSdrugs,e.g.benzodiazepines,opioids,antipsychoticsandantiparkinsondrugs

posturalinstabilitypre-disposingtodruginducedhypotensionanddrugrelatedfalls

increasedanalgesiceffectofmorphine

reducedpeakdiureticresponsetofrusemide

increasedanticoagulanteffectofwarfarin,and

impairedthermoregulatorymechanismspredisposingtodruginducedhypothermia

MangoniandJackson,2003

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Age related changes which increase the risk of drug related problems


Receptor sensitivities changeRenal function declines

Cognitive function declinesGastro-protection reduced

Liver metabolism slowsCirculatory instability

Increasing age

Some drugs associated with adverse drug reactions in the elderly

Drugordrugclass Comments

AlldrugsStartlow,goslow.Manydrugs,e.g.oxybutynin,antipsychotics,TCAs,

antihypertensivesneedmuchlowerdosesinelderlypeople.

benzodiazepines

Thosewithalonghalf-life,suchasdiazepam,nitrazepamcauseexcessiveand

prolongedsedation.Temazepamisabetterchoiceifnecessarybutallarebest

avoided.

cimetidine Moredruginteractionsandagreaterpotentialforconfusionthanranitidine.

dextropropoxyphene Cancauseconfusionandexcessivesedationintheelderly.

digoxinUselowdosesinitially.Extravigilancerequiredforthosewhoneedtobeonhigher

doses.

indomethacin ThisNSAIDhasahighincidenceofCNSeffectsandgastrotoxicity.

nefopam(Acupan) CNSeffectsandmarkedanticholinergicactions;avoid.

NSAIDsUselowestdosenecessaryfortheshortestperiod.Avoidlong-termuseoffulldose,

longerhalf-lifedrugssuchasnaproxenandpiroxicam.

tricyclicantidepressants(TCAs)Doxepinandamitriptylineareverysedatingandhavestronganticholinergicactions.

Notpreferredasfirstchoicefordepressionintheelderly.

thioridazine(Aldazine) GreaterpotentialforCNSandextrapyramidaleffects.

Drugs associated with increased risk of adverse drug reactions in elderly people

Because of age related changes in drug handling described on

page5certaindrugsareassociatedwithincreasedriskofadverse

drugreactionswhengiventoelderlypeople.

If the potential benefits of these drugs for an individual patient

appear to outweigh the risks of harm they should be used with

caution;otherwisetheyshouldbeavoided.


Common Drug Interactions

Drugcombination Riskofharm Prevention

warfarin/NSAIDs

increasedriskofbleeding

reviewneedforNSAIDconsider

paracetamolasanalternative

warfarin/amiodaronemonitorINRandadjustwarfarindose

accordingly

warfarin/sulfadrugs

usealternativeantibioticwarfarin/macrolides

warfarin/norfloxacin

warfarin/phenytoin

increasedorpossibledecreasedeffectsof

warfarin

phenytoinconcentrationpossiblyincreased

monitorphenytoinlevelandINR

ACEinhibitors/K+supplements elevatedpotassiumlevelsmonitorpotassiumlevels

discontinueK+supplementifnotneeded

ACEinhibitors/spironolactoneelevatedpotassiumlevels

renalfailuremonitorpotassiumlevelsandrenalfunction

ACEinhibitors/NSAIDs renalfailure

re-evaluateneedforNSAID

monitorrenalfunction

avoidhypovolaemia

digoxin/amiodarone digoxintoxicity

decreasedoseofdigoxinby50%when

addingamiodaroneandcheckdigoxin

levelsweeklyuntilstable

digoxin/verapamildigoxintoxicity

bradycardia,heartblock

checkECG

re-evaluateneedforthesedrugs

theophylline/norfloxacinandciprofloxacin theophyllinetoxicityre-evaluateneedforthesedrugs

monitortheophyllinelevels

anticholinergiccombinationse.g.TCA,

sedatingantihistamine,antipsychotic,

oxybutynin,orphenadrine,benztropine,etc

sedation,confusion,blurredvision,fallsreducenumbers,strengthordosesof

thesedrugs

drugsactingontheCNS

combinationsofantiepileptics,

antipsychotics,analgesics,

antidepressants,etc

sedation,confusion,fallsreducenumbers,strengthordosesof

thesedrugs

“The ingenuity of man has ever been fond of exerting itself to varied forms and combinations of medicines.” WilliamWithering,1785

Common drug interactions in elderly people

It is impossible to remember all possible drug interactions; see

howlongthelistisinappendixoneoftheBNF!Anumberofdrug

combinationsarefrequentlyusedbuthavethepotentialtocause

significant harm if notmanaged appropriately.Not every elderly

adult who takes these medications together will experience an

adversereaction.


Recognising adverse drug reactions

Common presentations of adverse drug reactions in the elderly

Symptom Possiblecausativeoraggravatingdrugs

Confusion

benzodiazepines,phenothiazines(e.g.chlorpromazine,promethazine,methotrimeprazine),anticholinergic

drugs,TCAs,opioids,antiparkinsondrugs,anticonvulsants,corticosteroids,NSAIDs,cimetidine,ranitidine

orsuddenbenzodiazepinewithdrawal

Unsteadinessandfallscombinationsofdrugswithsedatingproperties(e.g.TCAs,anticonvulsants,phenothiazines,sedatinganti-

histamine,antipsychotic,benztropine,opioids)anticholinergics

Constipationcalciumchannelblockers(especiallydiltiazemandverapamil),phenothiazines,tricyclics,anticholinergic

drugs

Depression longtermbenzodiazepineuse,highdosesofTCAs(especiallyamitriptylineanddoxepin)

Dyspepsia NSAIDs

Electrolytedisturbancesloopandthiazidediuretics(hypokalaemia,hyponatraemia),potassiumsparingdiuretics(hyperkalaemia),

antidepressants(SSRIs,venlafaxine-hyponatraemia,syndromeofinappropriateantidiuretichormone)

Heartfailure,

hypertensionNSAIDs

Hypotensionandfalls combinationsofdrugsactingonthecirculation

Hypothermia phenothiazines,risperidone,benzodiazepines,alcohol,opioids

Insomnia theophyllineanddecongestants

Parkinsoniansymptoms metoclopramide,methotrimeprazine,prochlorperazine

Urinaryretention anticholinergicdrugs.Manydrugs,includingOTCdecongestants,cancauseoraggravateurinaryproblems

Stressincontinence alpha-blockers(e.g.doxazosin),calciumchannelblockers

Adversedrugreactionsareoftenunrecognisedandthereforenot

managed.Evenworseanewdrugmaybeprescribed to treata

symptomwhichhasnotbeenrecognisedasbeingcausedbyan

existingmedication.

This leads to a prescribing cascade where the additional drug

prescribed increases the risk of more adverse reactions raising

therisksoffurtherprescribingtotreatthesenewsymptoms.

People with communication difficulties such as those with

Alzheimer’s disease, dysphasia or intellectual disabilities are at

particularriskofhavingunrecognisedadversedrugreactions.


Examples of the prescribing cascade:

Ankleoedemaduetoacalciumchannelblockerleadstoprescribingofadiuretic.

This type of oedema does not respond to a diuretic.

Prescribedorover-the-counterNSAIDdrugcausesanincreaseinbloodpressureandtheaddition

ofanantihypertensivedrug.

NSAIDs cause a small rise in BP and may tip the balance into the hypertensive category. Review the

need for the NSAID in these patients.

Apatientonamitriptyline50mgnocteforpain.Afteradoseincreasefrom25–50mgthepatient

complainsof incontinenceandoxybutynin isprescribed.The incontinenceworsensandthedose

ofoxybutynin is increased.Thepatientalsocomplainsofconstipationandastimulant laxative is

prescribed.

Amitriptyline has anticholinergic actions and can cause urinary retention leading to overflow

incontinence which was not recognised. Oxybutynin also has anticholinergic actions but is used for

urge incontinence. The situation worsens, the person gets constipated and a laxative is prescribed.

“I do not want two diseases – one nature-made, one doctor-made”NapoleonBonaparte,1820


Useofnarrowtherapeuticindexdrugs,suchasdigoxin,warfarin,lithium,anticonvulsantsincreasesthe

riskofdrugtoxicityanddruginteractions.

Useofmultipledrugsincreasesrisksofunpredictedinteractions.

Useofdrugscommonlyassociatedwithdrugrelatedproblemsrequiringhospitaladmissions,suchas

warfarin,NSAIDs,ACEinhibitorsandopioidanalgesics.

Useofdrugsthathavesynergisticadverseeffects,suchashypotensionorsedation.

Useofdrugsfrommultipleprescribers.

Recentcommencementofnewmedicine.

Recentdischargefromhospital.

Unsuperviseduseofover-the-counterorcomplementarymedicines.

When a patient cannot communicate effectively, for example because of Alzheimer’s disease or

intellectualhandicap.

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Risk factors for drug related problems in elderly people


Rx: Gli anziani cadono

Buona Salute!

A really good recipe for DRP

Ingredients

6ormoredrugs

12ormoredailydoses

2ormorechronicconditions

2ormoreprescribers

1ormoreofthefollowing:

highriskdrugs

highriskdrugcombinations

highriskdrug-conditioncombinations

Optional

Variousherbaloralternativeremedies

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Anyoneoftheseingredientsorseveralcombinedcan,iflefttosimmer,

produceasurprisingconcoctionthatmakeselderlypeoplegoweakat

thekneesandmakestheirheadsspin.

To increase the risk of an unfortunate outcome you can leave the

mixture tostand,without regularchecking,or throw inanadditional

ingredientwithout first assessing the effects of the ones already in

thepot.

Unlikekitchenrecipesyoucanremoveingredientswhichdon’tappear

tobeworking.

Simplifying the recipe, assessing the need for the ingredients, and

monitoring their effectsare thesecrets toachieving thebenefitsof

drugtherapywhilstavoidingunfortunateoutcomes.

“Elderly people all overNewZealandare falling for thisdeceptively easy recipe. Its

basicingredientsarecommonineverydaypracticeasprescriberstrytobalancethe

possiblebenefitsofdrugtherapywiththepotentialforunfortunateoutcomes.”


Drug related harm; terms and definitions

Adverse drug event (ADE)

Examples:

Severe bronchospasm following use of metoprolol in an

asthmatic patient with a history of beta-blocker induced

bronchospasm.Thisisamedicationerrorasthehistorywas

not recognised. The metoprolol unmasked and aggravated

thebronchospasmratherthancausingitdirectly.

Metoprolol stopped suddenly resulting in tachycardia and

hypertension.This is alsoamedicationerror resulting from

abrupt discontinuation of the metoprolol and associated

rebound effects. The dose should have been gradually

reduced.

1.

2.

Severebradycardiaresultingfromtheadministrationofthree

timestheintendeddoseofmetoprolol(47.5mgTIDinstead

ofdaily).Anothermedicationerrorwhichcouldbeduetoan

incorrectprescriptionorincorrectreadingorinterpretationof

theprescription.

NBthetermadversedrugeventdoesnotincludesituationswhen

adrugisnotusedwhenthepatientcouldpotentiallybenefitfrom

it.Forexample,failuretouseabeta-blockerinapatientwithstable

wellcontrolledCOPDandheartfailureorpostmyocardialinfarction.

Thisisan“untreatedindication”.

3.

An injury resulting from the use of a drug

Anadversedrugeventisabroadertermwhichincludesadversedrugreactionsplusharmfromtheuseofthedrugincluding

prescribing,administration,overdoses,dosereductionsanddiscontinuationsoftherapy(medicationerrors).


An event or circumstance involving a patient’s drug treatment (or lack of drug treatment) that actually or potentially

interferes with the achievement of an optimal outcome. AdaptedfromHeplerandStrand,1990.

DRPsinclude:

Untreatedindications

Drugusewithoutaclearindication

Sub-therapeuticdosage

Excessivedosage

Adversedrugreaction

Druginteraction

Drugwithdrawalreaction

Medicationerror

Non-adherencetodrugtreatment

Therapeuticfailure

(AdaptedfromHanlonetal,2004)

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DRPs cause significant morbidity and mortality in the general

population.Someauthorshaveestimatedthattheeconomiccost

ofDRPrankaroundfourthbehind,cardiovasculardisease,cancer

and diabetes in the developed world (Johnson and Bootman,

1995).

Arecentsystematicreviewreportedthatamedian7.1%(range

5.7–16.2) of hospital admissions result from drug related

problems,ofwhich59%wereconsideredpreventable(Winterstein

etal,2002).

Drug related problem (DRP) nowsometimesreferredtoasMedicinesrelatedproblem

Adversedrugreactionsfallintooneoftwomaincategories:

Type A reactions arepredictable,dose-relatedreactionswhere

theintensityoftheeffectincreaseswithdoseorreducedclearance

ofthedrugfromthebody,i.e.increasedbloodconcentrations.For

example,theanticholinergiceffects(constipation,blurredvision)of

amitriptylinewilltendtoworsenifthedoseisincreasedfrom25

mgto50mgdaily.Inadditionthepatientwilltendtobecomemore

drowsyandsedated.

Type B reactions are not related to dose and are largely

unpredictable (idiosyncratic). These represent many potentially

serious adverse reactions such as blood dyscrasias and

ADRs

ADEs

DRPs

A response to a drug which is noxious and unintended and which occurs at doses normally used in man for prophylaxis, diagnosis or therapy of a disease or for the modification of physiological function.

Inotherwords,harmdirectlycausedbythedrugatnormaldoses.Forexample,depressioncausedbyabeta-blocker.

hepatotoxicity.

Forsomeadversedrugreactionsthereappearstobeathreshold

drugdoseorconcentrationatwhichatypeBreactionbecomes

more likely. For example, it is difficult to predict who will get

confusionduetocimetidineorranitidine,buttheelderlyseemtobe

moresusceptibleespeciallyifthedoseisnotreducedaccordingto

thedeclineinrenalfunction.Similarly,theriskoftherareallopurinol

hypersensitivitysyndromeisincreasedifthedoseisnotadjusted

inrenalimpairment.


Adverse drug reaction (ADR)

Hospital admissions foradverse drug reactions

3000

2500

2000

1500

1000

500

050-54 55-59 60-64 65-69 70-74 75-79 80-84 85-89 90+

NumberofADRhospitaladmissions

Admissionsper50,000population

We identified hospital admissions in 2005 for adverse drug

reactions in people over 50 years of age by extracting ICD-10

codesandpatientdemographicdatafromtheHospitalSeparation

Diagnosis Database. International literature suggests that these

dataarelikelytounderestimatetheactualnumberofadmissions

foradversedrugreactionsbecauseofincompletecoding.

Overtheyear,therewere15,254admissionsfor17,806adverse

drugreactions.Therewere146differentadversedrugreactions

recorded.Adversedrugreactionsincreasewithage(graphbelow).

Fiftysixpercentwere female.Only8%ofoverall admissions for

adverse drug reactions were for Māori people although Māori

represent approximately 15%of the population.However, in the

youngerage-bands50-59,Māorirepresentedagreaterproportion

ofadmissionsprobablyduetobeingonmoredrugsatayounger

agecausedbyearlieronsetofchronicdisease.

Hospital admissions for adverse drug reactions increase with age


Age

A

dmis

sion

s

Anticoagulantswerethemostfrequentlyimplicateddrugsfollowedbydiuretics,opioids,nonsteroidalanti-inflammatorydrugsandbeta

blockers.

Number of admissions for ADR by drug group

Maindruggroup Admissions Sub-group Admissions

Cardiovascular

(43.3%)7711

anticoagulants 1779

diuretics 1552

beta-blockers 1023

ACEinhibitors 810

antiarrhythmics 703

vasodilators 577

calciumchannelblockers 434

antihypertensive 288

aspirin 230

α-adrenoceptorblocker 155

lipid-lowering 153

other 7

Nervous system

(17.4%)3107

opioids 1289

antidepressants 424

antipsychotics 362

anaesthetic 180

benzodiazepines 159

antiepileptics 143

analgesics 121

other 429

Anti-inflammatory

(11.6%)2074

NSAIDs 1124

corticosteroids 950

Anti-infectives

(10.3%)1826

penicillin 698

cephalosporin 192

other 936

Oncology agents

(6.4%)1139

anti-neoplasm 978

immunosuppressant 152

other 9

Alimentary tract

(4.5%)805

insulin&oralhypoglycaemics 440

other 365

Other

(6.4%)1144

musculo-skeletal 178

hormonepreparations 106

respiratory 81

topical 38

sensorysystem 25

vaccine 13

other 703

TOTAL 17806


Hyponatraemia is an adverse reaction that can be serious and

is reported most often in the elderly with fluoxetine, paroxetine

andbendrofluazideindividuallyorincombination.Inaseriesof11

patientsaged65yearsandolderwithhyponatraemiaattributedto

bendrofluazide,fourweretakingothermedicinesalsolikelytocause

hyponatraemia, these were frusemide, fluoxetine and paroxetine,

and in one case both frusemide and fluoxetine. Presenting

symptomsweresometimesvagueandincludedlethargy,confusion

andnausea.Oneyoungerpatientdevelopedconvulsions.Sixofthe

eleven patients required hospital admission and in one case the

conditionwaslife-threatening.Onepatientwasalsotakingquinine

anddevelopedatrialfibrillation,probablyanadverseeffectofquinine

mademorelikelybecauseoftheelectrolytedisturbance.Thepatient

takingbendrofluazide,frusemideandfluoxetinealsotookenalapril

androfecoxiband,aswellashyponatraemia,developedacuterenal

failureduetothecombinationofdiuretics,ACEinhibitorandanon

steroidalanti-inflammatoryagent(bpacnz,ACEInhibitors).

Interactions with simvastatinarealsocommonlyreported.Myalgia

occursfrequentlywithsimvastatinbuthighdosesorco-prescription

offibratesormedicinesthatinhibitsimvastatinmetabolismcanlead

to myopathy, including on rare occasions, rhabdomyolysis which

isoftenfatal.Reportshavebeenreceivedofsuchreactionswhen

otherpotent inhibitorsofhepaticCYP3A4 isoenzymeshavebeen

prescribedsuchasazoleantifungals,erythromycinandciclosporin.

Ofnote is thatdiltiazem,aweak inhibitorofCYP3A4,appearsto

haveprecipitatedrhabdomyolysiswhengivenwithhighdoses(80

mg daily) of simvastatin or at lower doses where there were a

numberofco-morbidities.Theseinteractionsalsoaffectatorvastatin

(Savage,2006).

Interactions with warfarin continue to be commonly reported.

Thereareanumberofrecentreportsofroxithromycin increasing

theeffectofwarfarin.Thisislikelytobetoalesserdegreethanwith

erythromycinbuttheproductinformationforroxithromycinindicates

that the effect may be clinically significant in patients receiving

polytherapy or in the elderly (Medsafe, 2006). The interaction

betweenmiconazoleandwarfariniswell-recognisedbutreportsto

CARM,someserious,indicatethatitisnotalwaysrecognisedthat

miconazoleoralgelwillalsointeract.

ReportstoCARMofhypotension in the elderlydemonstrate in

particular that the addition of psychoactive medicines that lower

bloodpressuretoanantihypertensiveregimemaymeanthatsome

antihypertensive medicines need to be discontinued or the dose

lowered if the psychoactive medication is considered necessary.

A combination of trifluoperazine, atenolol and amlodipine in one

patient led to ataxia, hypotension and syncope. A patient with

bradycardia and heart block probably due to the combination of

diltiazemandmetoprolol,wasalsotakingdonepezilandthismay

have contributed to the dizziness and hypotension the patient

alsoexperienced.Apatienttakingnortriptyline,timolol,nifedipine,

captopril and hydrochlorothiazide developed hypotension and

syncope and recovered when nortriptyline and nifedipine were

withdrawn.

Where the prescription of potentially interacting medicines is

unavoidable, careful follow up for indicators that an unwanted

outcomeisdevelopingisessential.

CARMCentreforAdverseReactionsMonitoring

TheCentreforAdverseReactionsMonitoring(CARM)hasidentifiedsomecommonlyreportedadversedrugreactions

inthelast10yearsoccurringinpatientsaged65yearsandolderandoftenresultingfrominteractingmedicines.


Commonly reported adverse drug reactions

http://carm.otago.ac.nz/

http://carm.otago.ac.nz/

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http://www.bpac.org.nz/default.asp?action=article&id=27&category=247

http://www.nzma.org.nz/journal/115-1167/271/

http://www.dh.gov.uk/assetRoot/04/06/72/47/04067247.pdf

http://www.nps.org.au/site.php?content=/html/news.php&news=/resources/NPS_News/news34

http://www.nps.org.au/site.php?content=/html/news.php&news=/resources/NPS_News/news34

http://www.npc.co.uk/MeReC_Bulletins/2000Volumes/pdfs/vol11n10.pdf

http://www.medicines-partnership.org/medication-review/room-for-review

http://www.medicines-partnership.org/medication-review/room-for-review

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