Clin Pharmacy ADR

8/17/2019 Clin Pharmacy ADR

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Adverse drug reactions (ADRs)


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KEY FACTS

Unintended, harmful reactions to medicines The majority of ADRs are preventable. People in every country are affected by ADRs. In some countries ADR-related costs eceed the cost of the medications. !i"ilant assessment of the ris#s $ benefits of medicines promotes patient

safety. Adverse dru" reactions are a si"nificant cause of morbidity and mortality, are

responsible for approimately % in &' hospital admissions and are a

considerable financial burden on health systems.

Predisposin" factors for adverse dru" reactions include a"e, female "ender,ethnicity, "enetic factors, co-morbidities and concomitant medication.

At least (') of ADRs are preventable, and can be due to* +ron" dia"nosis of the patients condition prescription of +ron" dru" or +ron" dosa"e of ri"ht dru" an undetected medical, "enetic or aller"ic condition that mi"ht cause a patient

reaction self-medication +ith prescription medicines not follo+in" the instructions for

ta#in" the medication reactions +ith other dru"s and certain foods use of a sub-standard medication +hose composition and in"redients do not

meet the correct scientific reuirements

use of counterfeit medicines +ith no active in"redients or the +ron" in"redients,+hich can be dan"erous or fatal.


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Examples of ADR

Amidopyrine /for inflammation0 +hite blood cell disorder

1liouinol /Iodochlorhydroyuin0 /for s#ininfections0

visual impairment

2rythromycin estolate /antibacterial0 hepatitis /liver disorder0

3ral contraceptives thromboembolism /bloodclots0

Thalidomide /mana"in" mornin" sic#ness0 phocomelia /disfi"ured

infants0

4tatins /for controllin" cholesterol0 muscle de"eneration


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Definition

The 5orld 6ealth 3r"ani7ation /5630 defines an ADR as 8a response to a dru" that is

noious and unintended and occurs at doses normally used in man for the

prophylais, dia"nosis or therapy of disease, or for modification of physiolo"ical

function /563, %9:&0.

Assessing te safet! of drugs

5hen dru"s are ne+ly introduced to the mar#et, their safety profile +ill be provisional.

5hile efficacy and evidence of safety must be demonstrated for re"ulatory authorities

to

Permit mar#etin", it is not possible to discover the complete safety profile of a ne+ dru"prior to its launch. Pre-mar#etin" clinical trials involve on avera"e &;'' patients, +ith

perhaps a hundred patients usin" the dru" for lon"er than a year. Therefore, pre-

mar#etin" trials do not have the po+er to detect important reactions that occur at

rates of % in %',''', or fe+er, dru" eposures. 3ften, only pharmacolo"ically

predictable ADRs +ith short onset times may be identified in clinical trials.

Additionally, patients +ithin trials are often carefully selected, +ithout the multiple

disease states or comple dru" histories of patients in +hom the dru" +ill eventuallybecome used.

As a result of this monitorin", the safety profile of established dru"s is often +ell #no+n,

althou"h ne+ ris#s are occasionally identified. 6o+ever, an important part of the

therapeutic mana"ement of medical conditions is the minimi7ation of these +ell-

#no+n ris#s throu"h rational prescribin" and careful monitorin" of dru" therapy.

1urrent evidence su""ests that this could be improved.


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Ra"lins#Tompson classification


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Extended Ra"lins#Tompson classification of adverse drug reactions

< Type A reactions, +hich constitute approimately =') of adverse dru" reactions, are usually aconseuence of the dru"s primary pharmacolo"ical effect /e.". bleedin" from +arfarin0 or a lo+therapeutic inde /e.". nausea from di"oin0, and they are therefore predictable. They are dose-related and usually mild, althou"h they may be serious or even fatal /e.". intracranial bleedin"from +arfarin0. 4uch reactions are usually due to inappropriate dosa"e, especially +hen dru"elimination is impaired. The term 8side effects is often applied to minor type A reactions.

< Type > /8idiosyncratic0 reactions are not predictable from the dru"s main pharmacolo"icalaction, are not dose-related and are severe, +ith a considerable mortality. The underlyin"pathophysiolo"y of type > reactions is poorly if at all understood, and often has a "enetic orimmunolo"ical basis. Type > reactions occur infreuently /%*%'''?%*%' ''' treated subjects

bein" typical0.

< type C ? continuous reactions due to lon"-term dru" use /e.". neuroleptic-related tardivedys#inesia or anal"esic nephropathy0

< type D ? delayed reactions /e.". al#ylatin" a"ents leadin" to carcino"enesis, or retinoid-associated terato"enesis0

< type E end-of-use reactions, such as adrenocortical insufficiency follo+in" +ithdra+al of

"lucocorticosteroids, or +ithdra+al syndromes follo+in" discontinuation of treatment +ithben7odia7epines or @-adrenoceptor anta"onists.


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$DE%T$F$CAT$&% &F T'E DR AT FA*T

1. A careful drug history is essential * A patients dru" history may not al+ays be conclusive

because, althou"h aller"y to a dru" implies previous eposure, the anti"en may have

occurred in foods /e.". antibiotics are often fed to livestoc# and dru" residues remain inthe flesh0, in dru" mitures or in some casual manner.

2. Provocation testing . This involves "ivin" a very small amount of the suspected dru" and

seein" +hether a reaction ensues, e.". s#in testin", +here a dru" is applied as a patch, or

is pric#ed or scratched into the s#in or injected intra-dermally. Unfortunately, pric# and

scratch testin" is less useful for assessin" the systemic reaction to dru"s than it is for the

more usual atopic anti"ens /e.". pollens0, and both false-positive and false-ne"ative

results can occur. Patch testin" is safe, and is useful for the dia"nosis of contact

sensitivity, but does not reflect systemic reactions and may itself cause aller"y.

3. Serological testing and lymphocytes testing . 4erolo"ical testin" is rarely helpful,

circulatin" antibodies to the dru" do not mean that they are necessarily the cause of the

symptoms. The demonstration of transformation occurrin" +hen the patients lymphocytes

are eposed to a dru" e vivo su""ests that the patients T-lymphocytes are sensiti7ed to

the dru". In this type of reaction, the hapten itself +ill often provo#e lymphocytetransformation, as +ell as the conju"ate.

. The best approach in patients on multiple dru" therapy is to stop all potentially causal

dru"s and reintroduce them one by one until the dru" at fault is discovered. This should

only be done if the reaction is not serious, or if the dru" is essential and no chemically

unrelated alternative is available. All dru" aller"ies should be recorded in the case notes

and the patient informed of the ris#s involved in ta#in" the dru" a"ain.


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Factors affecting suscepti+ilit! to ADRs

Age

2lderly patients may be more prone to ADRs, +ith a"e-related decline in both the metabolismand elimination of dru"s from the body. They also have multiple co-morbidities and are,

therefore, eposed to more prescribed dru"s.

1hildren differ from adults in their response to dru"s. Beonatal differences in body

composition, metabolism and other physiolo"ical parameters can increase the ris# of specific

adverse reactions. 6i"her body +ater content can increase the volume of distribution for

+ater-soluble dru"s, reduced albumin and total protein may result in hi"her concentrations of

hi"hly protein bound dru"s, +hile an immature blood?brain barrier can increase sensitivity to

dru"s such as morphine. Differences in dru" metabolism and elimination and end-or"an

responses can also increase the ris#.

3lder children and youn" adults may also be more susceptible to ADRs, a classic eample

bein" the increased ris# of etrapyramidal effects associated +ith metoclopramide. The use ofaspirin +as restricted in those under the a"e of %&, after an association +ith ReyeCs syndrome

+as found in epidemiolo"ical studies.


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Factors affecting suscepti+ilit! to ADRs ,,- (continues)

ender

5omen may be more susceptible to ADRs. In addition, there are particular adverse reactions

that appear to be more common in +omen than men. or eample, impairment ofconcentration and psychiatric adverse events associated +ith the anti-malarial meflouine are

more common in females. emales are more susceptible to dru"-induced torsade de pointes,

a ventricular arrhythmia lin#ed to ventricular fibrillation and death /thou"ht to be due to their

lon"er ETc interval0.

Co.mor+idities and concomitant medicines use

Reductions in hepatic and renal function substantially increase the ris# of ADRs. A recent

study eaminin" factors that predicted repeat admissions to hospital +ith ADRs in older

patients sho+ed that co-morbidities such as con"estive cardiac failure, diabetes, and

peripheral vascular, chronic pulmonary, rheumatolo"ical, hepatic, renal, and mali"nant

diseases +ere stron" predictors of readmissions for ADRs, +hile advancin" a"e +as not.

Reasons for this could be pharmaco#inetic and pharmacodynamic chan"es associated +ith

pulmonary, cardiovascular, renal and hepatic insufficiency, or dru" interactions because ofmultiple dru" therapy.

/F(PD0 deficiency $ Porphyrias* see pa"e ((G(: Ro"er 5al#er


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Factors affecting suscepti+ilit! to ADRs ,,- (continues)

Etnicit!

2thnicity has also been lin#ed to susceptibility to ADRs, due to inherited traits of metabolism..

or eample, 1HP&19 associated +ith poor metabolism can affect +arfarin metabolism and

increase the ris# of toicity. This occurs more freuently in +hite individuals compared toblac# individuals. Also increased ris# of an"io-edema found +ith the use of A12 inhibitors in

blac# patients. The increased propensity of +hite and blac# patients to eperience central

nervous system ADRs associated +ith meflouine compared to patients of 1hinese or

apanese ori"in, and differences in the pharmaco#inetics of rosuvastatin in Asian patients

+hich may epose them to an increased ris# of myopathy.

/armacogenetics

Pharmaco"enetics is the study of "enetic variations that influence an individualCs response to

dru"s, and eamines polymorphisms that code for dru" transporters, dru"-metaboli7in"

en7ymes and dru" receptors. Jajor "enetic variation is found in the cytochrome 1HP;'

"roup of isoen7ymes. This can result in either inadeuate responses to dru"s, or increased

ris# of ADRs. 1linically relevant "enetic variation has been seen in 1HP&D(, 1HP&19,

1HP&1%9 and 1HPKA;. A lar"e effect on the metabolism of dru"s can occur +ith 1HP&19,+hich accounts for &') of total hepatic 1HP;' content.

Anti-epileptic dru"s, such as carbama7epine and phenytoin, are #no+n causes of 4tevens?

ohnson syndrome /440 and toic epidermal necrolysis /T2B0. The reactions are more

common in 4outh 2ast Asian populations, includin" those from 1hina, Thailand, Jalaysia,

Indonesia, the Philippines and Tai+an and, to a lesser etent, India and apan.


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Immunolo"ical reactions


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Immune response to dru"s


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E0A1/*ES &F A**ER$C A%D &T'ER ADRs

RAS'ES

These are one of the most common manifestations of dru" reactions. A number of

immune and non-immune mechanisms may be involved +hich produce manydifferent types of rash ran"in" from a mild maculopapular rash to a severe

erythema multiforme major /4tevens ohnson syndrome0. 1ommonly implicated

dru"sGdru" classes include beta-lactams, sulphonamides and other antimicrobial

a"ents anti-sei7ure medications /e.". phenytoin, carbama7epine0 B4AIDs. 4ome

dru"s may "ive rise to direct tissue toicity /e.". DJP4, used as chelatin" therapy

in patients +ith heavy metal poisonin".

*Y1/'ADE%&/AT'Y

Lymph-node enlar"ement can result from ta#in" dru"s /e.". phenytoin0. The

mechanism is un#no+n, but aller"ic factors may be involved. The reaction may be

confused +ith a lymphoma, and the dru" history is important in patients +ith

lymphadenopathy of un#no+n cause.


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E0A1/*ES &F A**ER$C A%D &T'ER ADRs ,-- continues

2*&&D DYSCRAS$AS

Thrombocytopenia, anaemia /aplastic, iron deficiency, macrocytic, haemolytic0 and

a"ranulocytosis can all be caused by dru"s.Thrombocytopenia can occur +ith many dru"s, and in many but not all instances the

mechanism is direct suppression of the me"a#aryocytes rather than immune processes.

Dru"s that cause thrombocytopenia include*

< heparin

< "old salts

< cytotoic a"ents /e.". a7athioprineG(-mercaptopurine0

< uinidine

< sulphonamides

< thia7ides.

SYSTE1$C */S ERYT'E1AT&SS

4everal dru"s /includin" procainamide, isonia7id, hydrala7ine, chlorproma7ine and

anticonvulsants0 produce a syndrome that resembles systemic lupus to"ether +ith apositive antinuclear factor test. The development of this is closely related to dose, and in

the case of hydrala7ine it also depends on the rate of acetylation, +hich is "enetically

controlled. There is some evidence that the dru"s act as haptens, combinin" +ith DBA

and formin" anti"ens. 4ymptoms usually disappear +hen the dru" is stopped, but

recovery may be slo+.


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E0A1/*ES &F A**ER$C A%D &T'ER ADRs ,-- continues

3ASC*$T$S

>oth acute and chronic vasculitis can result from ta#in" dru"s, and may have an aller"ic

basis. Acute vasculitis +ith purpura and renal involvement occurs +ith penicillins,

sulphonamides and penicillamine. A more chronic form can occur +ith phenytoin.

RE%A* DYSF%CT$&%

All clinical manifestations of renal disease can be caused by dru"s, and common culprits are

non-steroidal anti-inflammatory dru"s and an"iotensin-convertin" en7yme inhibitors /+hich

cause functional and usually reversible renal failure in susceptible patients Bephrotic

syndrome results from several dru"s /e.". penicillamine, hi"h-dose captopril, "old salts0 +hichcause various immune-mediated "lomerular injuries. Interstitial nephritis can be caused by

several dru"s, includin" non-steroidal anti-inflammatory dru"s and penicillins, especially

meticillin. 1isplatin, amino"lycosides, amphotericin, radiocontrast media and vancomycin

cause direct tubular toicity. Jany dru"s cause electrolyte or acid-base disturbances via their

predictable direct or indirect effects on renal electrolyte ecretion /e.". hypo#alaemia and

hypoma"nesaemia from loop diuretics, hyper#alaemia from potassium-sparin" diuretics,

convertin" en7yme inhibitors and an"iotensin II receptor anta"onists, proimal renal tubularacidosis from carbonic anhydrase inhibitors0, and some cause unpredictable toic effects on

acid-base balance /e.". distal renal tubular acidosis from amphotericin0. 3bstructive uropathy

can be caused by uric acid crystals conseuent upon initiation of chemotherapy in patients

+ith haematolo"ical mali"nancy, and ? rarely ? poorly soluble dru"s, such as sulphonamides,

methotreate or indinavir, can cause crystalluria.


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/armacovigilance and epidemiological metods in ADR detection

Spontaneous reporting

Pharmacovi"ilance uses multiple methods, but the follo+in" +ill focus onspontaneous reportin" systems. 4pontaneous reportin" systems collect data about

suspected ADRs in a central database. 4pontaneous reportin" has a number of

advanta"es. It is relatively cheap to administer, can follo+ a product throu"hout

its life and can also accept reports to over-the-counter medication and herbal

treatments.

Signal detection

A si"nal can be described as a possible causal relationship bet+een an adverse

event and a dru", +hich +as previously un#no+n. 3ne useful analo"y for si"nal

detection in a spontaneous reportin" database is to thin# of a radio si"nal, +hich is

dis"uised by the bac#"round radio 8noise. 4tatistical approaches scan the data

accumulated throu"h spontaneous reports for 8dru"?adverse event pairs that aredisproportionately present +ithin the database as a +hole. 4uch calculations can

be run automatically by modern computer systems, providin" the opportunity to

scan lar"e databases for potential si"nals of ne+ ADRs.

Hello+ 1ard 4cheme* 4ee pa"e (9


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Causalit! assessment

3ne of the most common methods of

causality assessment in use is

unstructured clinical assessment, also

#no+n as "lobal introspection. 2pert

revie+ of clinical information is

underta#en and a jud"ment is made

about the li#elihood of the reactionbein" due to dru" eposure. The

assessment of

comple situations, often +ith missin"

information, is open to variation

bet+een different assessors and

studies have sho+n mar#eddisa"reement bet+een eperts. The

563 international monitorin" centre

uses "lobal introspection for case

assessment, assi"nin" standardi7ed

causality cate"ories to suspected

ADRs

/armacovigilance and epidemiological metods in ADR detection ,--


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/armacist4s role after te prescription

A. patient education5 Pharmacists can improve*< patientsC #no+led"e of their treatments,< monitor treatment response,< chec# and improve patientsC compliance +ith their medications / studies

have been done that sho+ :')of patients are non compliant +ith theirtreatments.0

>. 1ounselin"* 5or#in" in a multidisciplinary team, clinical pharmacists can

also provide inte"rated care from hospital to community and vice versa,assurin" a continuity of information on ris#s and benefits of dru" therapy.

1. 2ducation* 2ducation of medical and nursin" staff as to administration,observations, symptom mana"ement is an important role of the pharmacistin this phase.

D. Dru" use evaluation* 4ome countries have instituted dru" use revie+ /DUR0.

< Pharmacists play a #ey role +here they collect statistics and do researchanaly7in" dru" use, prescribin" errors, side effects, etc.

< This is a useful research and audit instrument in areas +ith lac# of scientificevidence.


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Roles of ealt professionals

$dentif!ing and assessing ADRs in clinical practice

The process of identifyin" an ADR then involves ma#in" a jud"ment about +hetheror not a particular event such as a symptom, condition or abnormal test result could

be related to a dru" used in the patient eperiencin" the event. The prior

eperiences of the patient +ith other medicines should also be ta#en into

consideration. 2very opportunity should be ta#en to uestion patients about their

eperience, to determine +hether they perceive any adverse events +hich could be

due to medicines. 5hile routinely as#in" simple uestions is important, it is of eualvalue to develop a positive attitude to+ards the patientsC perception of suspected

ADR.

/reventing ADRs

The majority of ADRs are thou"ht to be preventable hence, there is potential to

dramatically reduce the costs associated +ith ADRs and possibly also deaths. ADRs can be prevented by chec#in" previous ADR history, minimi7in" the use of

dru"s #no+n to carry a hi"h ris# of ADRs and tailorin" dru" selection to individuals

based on the factors +hich predispose them to ADRs.


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Roles of ealt professionals ,-- Continues

1onitoring terap!

Jonitorin" the effects of dru"s either by direct measurement of serum

concentration or by measurement of physiolo"ical mar#ers is another potentialmechanism to reduce the ris# of ADRs. 1lo7apine, used for the mana"ement of

treatment resistant schi7ophrenia and psychosis, is associated +ith si"nificant

ris# of a"ranulocytosis. Jandatory monitorin" of +hite blood cell counts has

effectively eliminated the ris# of fatal a"ranulocytosis. 1urrently, monitorin" is often

ne"lected, althou"h practitioners may ta#e "reater care +hen treatin" the elderly

and those +ith more co-morbidities. 5arfarin remains one of the top %' dru"sinvolved in dru" induced admissions, despite a clearly defined monitorin"

reuirement.

Explaining ris6s to patients

Bumerous studies have sho+n that patients +ant to receive

information about side effects. Patients increasin"ly access a +ide ran"e of

information sources about medicines and ADRs themselves indeed, they are

actively encoura"ed to do so. 6ence, they may uestion jud"ments about the

selection of individual products they have been prescribed or sold. In this situation,

the health professional must be able to interpret the information accessed by the

patient to ensure it is unbiased and accurate.


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4ummary

< Pharmacists are eperts on the action and uses of dru"s, includin"their chemistry, the formulation of medicines and in the +ay +hichdru"s are used to mana"e diseases.

< Physicians and nurses can no lon"er +or# +ithout the pharmacistas an inte"ral member of the healthcare team.

< Pharmacists assist the healthcare team to provide a hi"h level ofsafe competent care to the patient both in the hospital and thecommunity.


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1A42 ? %*

Jr MJ is a fairly active (9-year-old. 6e has re"ularly presented his repeat

prescription for atenolol ;' m" daily, aspirin :; m" daily and simvastatin '

m" daily to the same community pharmacy for several years. Last month

diltia7em 4R (' m" t+ice daily +as added, as he had been "ettin"

increasin" an"ina symptoms. 6e as#s for a topical product to treat nec#

pain, +hich has developed in the last fe+ days +hich he puts do+n to a

8fro7en shoulder.

EU24TI3B4*

%. 1ould this be an ADR and +hy did it develop no+N

&. Is it appropriate to chan"e to another statinN

K. 5hat actions should the pharmacist ta#eN


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1ould this be an ADR and +hy did it develop no+N

Ans+er*

Bec# pain, 8fro7en shoulder and such descriptions are typical of the muscular

pain +hich is induced by statins. The incidence of mild muscle pain +ith statins

is bet+een &) and :) in clinical trials. The onset varies from a fe+ +ee#s to

over & years after startin" treatment, the incidence is dose-related and the

severity ran"es from mild aches to severe pain, causin" reduced mobility. 3lder

people, +ho may have reduced renal function or liver function, are at "reater

ris# of statin-induced myopathy. Diltia7em can inhibit the metabolism of

simvastatin due to its actions on cytochrome P;' iso-en7yme 1HPKA,

thereby increasin" the ris# of myopathy. 4tatin-induced myopathy ran"es from

mild myopathies and myal"ias, to myositis, to rare cases of potentially life-threatenin" rhabdomyolysis, in +hich muscle cell +alls are disrupted and the

contents lea# into the systemic circulation. Juscle pain in patients ta#in" statins

should, therefore, al+ays be ta#en seriously.


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Is it appropriate to chan"e to another statinN

Ans+er*

The problem is associated +ith all dru"s in the class. Althou"h simvastatin and

atorvastatin, the most +idely prescribed, are both lipophilic and metabolised by

cytochrome P;' KA and, therefore, may be most li#ely to cause muscle pain,

there is no reliable comparative data on different statins.

5hat actions should the pharmacist ta#eN

Ans+er*1reatinine #inase /1M0 levels should have been measured beforeinitiatin" statin

therapy, but re"ardless of +hether or not this +as done, a 1 M level should be

measured no+, plus liver function tests. Jr MJCsprimary care doctor should be

contacted to inform him about the suspected ADR and the patient encoura"ed

to report the ADR via the Hello+ 1 ard 4cheme. I t may be appropriate to

discontinue or reduce the dose of the simvastatin, dependin" on the result ofthe 1 M level and the severity of the symptoms. T he problem may not resolve

immediately on discontinuation. Frape fruit juice can increase blood levels of

simvastatin and hi"h alcohol inta#e increases the ris# of myopathy, so the

pharmacist should also +arn Jr ML about avoidin" these.


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1A42 ? &*

A K9-year-old male ta#in" varenicline for smo#in" cessation reports that he

has been sufferin" from vivid dreams and has become increasin"lya""ressive to+ards his family. Last ni"h the had a major ar"ument +ith his

+ife. 6is +ife mentioned he hadnCt been the same since he started the

varenicline and he +ould li#e to #no+ if this +as a possible cause.

EU24TI3B4*

%. Is varenicline a possible cause of his vivid dreams and a""ressionN

&. Is this a reportable adverse dru" reactionN


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Is varenicline a possible cause of his vivid dreams and a""ressionN

Ans+er*

!arenicline has been associated +ith neuropsychiatric ADR s, includin"

depression, suicidal thou"hts, suicidal behaviour and a""ression. !ivid dreams

and other sleep disorders have also been reported. Prescribers have been

+arned that such reactions have been reported. Assessin" the cause of this

reaction is difficult, since smo#in" cessation itself is associated +itheacerbations of underlyin" psychiatric illness and the ris# of symptoms of

depression. As varenicline dosin" starts %?& +ee#s before stoppin" smo#in", a

#ey uestion is ho+ lon" the patient has been ta#in" the dru", and if the

symptoms appeared before the smo#in" cessation date.


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Is this a reportable adverse dru" reactionN

Ans+er*

If a health professional considers that a patientCs symptoms are a possible ADR

to a ne+er dru", then they should be reported to re"ulatory authorities /in the U

M, this +ould be throu"h the J6RACs Hello+ 1 ard 4cheme0. 3 nly a suspicion

is necessary to report a reaction, not proven causality. I n the case of

intensively monitored medicines /identified by an inverted blac# trian"le in the>B0, any reaction, no matter ho+ trivial should be reported. Patients can also

report directly to re"ulatory authorities in some countries, includin" the U M. B

europsychiatric reactions such as this are commonly reported by patients.


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1A42 ? K*

A (;-year-old man +ith heart failure is admitted to hospital +ith a potassium level of

:.% mmolGL. Already stabilised on lisinopril &' m" daily, he had recently been

started on spironolactone &; m" daily. 6e had a serum creatinine of %(' OmolGL.

EU24TI3B4*

%. 5hat is the mechanism of any possible adverse dru" reactionN

&. 6o+ should future episodes of hyper#alaemia be avoidedN


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5hat is the mechanism of any possible adverse dru" reactionN

Ans+er*

4pironolactone, an aldosterone receptor anta"onist, has a beneficial effect on

mortality and hospital admission in patients +ith heart failure. 6o+ever,

spironolactone can increase potassium serum levels due to its effect on

aldosterone. 5hen used in combination +ith A12 inhibitors, serious

hyper#alaemia can occur. Althou"h clinical trials of spironolactone sho+ed noris#, cases have been reported in the literature and other epidemiolo"ical

studies have indicated that in real-+orld clinical situations, theincidence of

hyper#alaemia is increased.


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1A42 ? *

A ;;-year-old +oman attendin" a +arfarin out-patient clinic has araised IBR. 3n

uestionin" it is discovered that she has recently started ta#in" "lucosamine for

muscle aches for the last & +ee#s.

EU24TI3B4*

%. 5hat is the li#elihood that "lucosamine +as responsible for the rise in the IBR N

&. 4hould this reaction be reported to re"ulatory authoritiesN


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5hat is the li#elihood that "lucosamine +as responsible for the rise in the IBRN

Ans+er *

Flucosamine is a popular supplement purchased for 8joint health. It is

commonly used by older patients. 4pontaneous reports of interactions bet+een

+arfarin and "lucosamine have been submitted to U M, Australian and U 4

re"ulators. Additional cases have been reported in the literature. 5hile there is

no #no+n mechanism and no formal interaction studies, the published casesand spontaneous reports are sufficient evidence to su""est a potential

interaction. Fiven the +ide use of "lucosamine, the interaction may be rare,

althou"h under-reportin" is common. Assessment of this individual case

reuires further uestionin" to eliminate other confoundin" factors such as

chan"es in diet or adherence issues.


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4hould this reaction be reported to re"ulatory authoritiesN

Ans+er*

Interactions +ith, or adverse reactions to, complementary and alternative

remedies can be reported to spontaneous reportin" schemes, such as the

Hello+ 1 ard 4cheme. 1ollation of such reports allo+s re"ulators to "ather

further information on the suspected reaction, and any susceptibilities that may

in time provide useful information to other users.

Documents

Clin Pharmacy ADR