Gout and Pseudogout

1
Gout and Pseudogout

Updated: May 13, 2014
Practice Essentials
Gout and pseudogout are the 2 most common crystal-induced arthropathies. Gout is caused by
monosodium urate monohydrate crystals pseudogout is caused by calcium pyrophosphate
crystals and is more accurately termed calcium pyrophosphate disease.
Essential update: Risk for gout appears increased in those with psoriasis and
psoriatic arthritis
!n a prospecti"e cohort study o# data #rom 2$,$%1 men and $1,0%& 'omen deri"ed respecti"ely
#rom the (ealth )ro#essionals *ollo'-up +tudy ,()*+- ,1&./02010- and 1urses2 (ealth +tudy
,1(+- ,1&&.02010-, 'ith 2,21$ incident cases o# gout during at least 12 years o# #ollo'-up,
Merola et al #ound that, compared 'ith indi"iduals 'ithout psoriasis, the ris3 #or gout 'as
increased nearly 2-#old in those 'ith psoriasis and nearly %-#old in those 'ith psoriatic arthritis.
41,
25
!n addition, the in"estigators noted a signi#icant but small increased ris3 #or gout in those 'ith a
history o# osteoarthritis, although there 'as little association bet'een the ris3 #or incident gout
and a history o# rheumatoid arthritis.
425
Signs and symptoms
+ymptoms o# gout or pseudogout include the #ollo'ing:
)odagra ,initial 6oint mani#estation in %07 o# gout cases and e"entually in"ol"ed in &07
also obser"ed in patients 'ith pseudogout and other conditions-
8rthritis in other sites 0 !n gout, the instep, an3le, 'rist, #inger 6oints, and 3nee in
pseudogout, large 6oints ,eg, the 3nee, 'rist, elbo', or an3le-
Monoarticular in"ol"ement most commonly, though polyarticular acute #lares are not
rare, and many di##erent 6oints may be in"ol"ed simultaneously or in rapid succession
!n gout, attac3s that begin abruptly and typically reach ma9imum intensity 'ithin .-12
hours in pseudogout, attac3s resembling those o# acute gout or a more insidious onset
that occurs o"er se"eral days
:ithout treatment, symptom patterns that change o"er time attac3s can become more
polyarticular, in"ol"e more pro9imal and upper-e9tremity 6oints, occur more o#ten, and
last longer
2
!n some cases, e"entual de"elopment o# chronic polyarticular arthritis that can resemble
rheumatoid arthritis
)hysical #indings may include the #ollo'ing:
!n"ol"ement o# a single ,most common- or multiple 6oints
+igns o# in#lammation 0 +'elling, 'armth, erythema ,sometimes resembling cellulitis-,
and tenderness
*e"er ,also consider in#ectious arthritis-
Migratory polyarthritis ,rare-
)osterior interosseous ner"e syndrome ,rare-
;ophi in so#t tissues ,heli9 o# the ear, #ingers, toes, prepatellar bursa, olecranon-
<ye in"ol"ement 0 ;ophi, crystal-containing con6uncti"al nodules, band 3eratopathy,
blurred "ision, anterior u"eitis ,rare-, scleritis
=omplications o# gout include the #ollo'ing:
+e"ere degenerati"e arthritis
+econdary in#ections
Urate or uric acid nephropathy
!ncreased susceptibility to in#ection
Urate nephropathy
>enal stones
1er"e or spinal cord impingement
*ractures in 6oints 'ith tophaceous gout
+ee )resentation #or more detail.
Diagnosis
+tudies that may be help#ul include the #ollo'ing:
?oint aspiration and syno"ial #luid analysis
+erum uric acid measurement ,though hyperuricemia is not diagnostic o# gout-
24-hour urinary uric acid e"aluation
3
@lood studies ,including 'hite blood cells 4:@=s, triglyceride, high-density lipoprotein,
glucose, and renal and li"er #unction tests-
)lain radiographs may sho' #indings consistent 'ith gout. <rosions 'ith o"erhanging edges are
generally considered pathognomonic #or gout ,though also #ound in other diseases-.
=haracteristics o# erosions typical o# gout include the #ollo'ing:
Maintenance o# the 6oint space
8bsence o# periarticular osteopenia
Aocation outside the 6oint capsule
+clerotic ,coo3ie-cutter, punched-out- borders
8symmetric distribution among the 6oints, 'ith a strong predilection #or distal 6oints,
especially in the lo'er e9tremities
Ultrasonographic #indings in established gout include the #ollo'ing:
8 Bdouble-contourC sign, consisting o# a hyperechoic, irregular line o# M+U crystals on
the sur#ace o# articular cartilage o"erlying an ad6acent hyperechoic bony contour
B:et clumps o# sugar,C representing tophaceous material, described as hyperechoic and
hypoechoic heterogeneous material 'ith an anechoic rim
@ony erosions ad6acent to tophaceous deposits
Dther imaging modalities that may be considered include the #ollo'ing:
=omputed tomography ,=;- 0 =omplementary to plain radiography #or recogniEing
erosions in gout
Magnetic resonance imaging ,M>!- 0 M>! 'ith gadolinium is recommended 'hen
tendon sheath in"ol"ement must be e"aluated and 'hen osteomyelitis is in the
di##erential diagnosis
+ee :or3up #or more detail.
Management
Gout is managed in the #ollo'ing 3 stages:
;reating the acute attac3
)ro"iding prophyla9is to pre"ent acute #lares
Ao'ering e9cess stores o# urate to pre"ent #lares o# gouty arthritis and to pre"ent tissue
deposition o# urate crystals
4
8cute treatment o# pro"en crystal-induced arthritis is directed at relie# o# the pain and
in#lammation. 8gents used in this setting include the #ollo'ing:
1onsteroidal anti-in#lammatory drugs ,1+8!Fs-, such as indomethacin
=orticosteroids
=olchicine ,no' less commonly used #or acute gout than it once 'as-
8drenocorticotropic hormone ,8=;(-
=ombinations o# drugs ,colchicine plus 1+8!Fs, oral corticosteroids plus colchicine,
intra-articular steroids plus colchicine or 1+8!Fs-
;herapy to control the underlying hyperuricemia generally is contraindicated until the acute
attac3 is controlled ,unless 3idneys are at ris3 because o# an unusually hea"y uric acid load-.
Aong-term management o# gout is #ocused on lo'ering uric acid le"els. 8gents used include the
#ollo'ing:
8llopurinol
*ebu9ostat
)robenecid
@ecause these agents change serum and tissue uric acid le"els, they may precipitate acute attac3s
o# gout. ;his undesired e##ect may be reduced by prophyla9is 'ith the #ollo'ing:
=olchicine or lo'-dose 1+8!Fs
Ao'-dose prednisone ,i# patients cannot ta3e colchicine or 1+8!Fs-
Dther therapeutic agents that may be considered include the #ollo'ing:
Uricase and pegloticase
Gitamin =
8na3inra
*eno#ibrate
1onpharmacologic measures that may be 'arranted are as #ollo's:
8"oidance or restricted consumption o# high-purine #oods
8"oidance o# e9cess ingestion o# alcoholic drin3s, particularly beer
8"oidance o# sodas and other be"erages or #oods s'eetened 'ith high-#ructose corn
syrup
5
Aimited use o# naturally s'eet #ruit 6uices, table sugar, and s'eetened be"erages and
desserts, as 'ell as table salt
Maintenance o# a high le"el o# hydration 'ith 'ater ,H. glasses o# liIuids daily-
8 lo'-cholesterol, lo'-#at diet, i# such a diet is other'ise appropriate #or the patient
:eight reduction in patients 'ho are obese
+ee ;reatment and Medication #or more detail.
Image library
Gout. =hronic tophaceous gout in untreated patient 'ith end-
stage renal disease.
ackground
Gout and pseudogout are the t'o most common crystal-induced arthropathies. Gout is caused by
monosodium urate monohydrate crystals pseudogout is caused by calcium pyrophosphate ,=))-
crystals and is more accurately termed calcium pyrophosphate disease ,=))F-. ,+ee
)athophysiology and <tiology.- Gout is one o# the oldest diseases in the medical literature,
43, 45
3no'n since the time o# the ancient Gree3s. )seudogout, 'hich may be clinically
indistinguishable #rom gout, 'as recogniEed as a distinct disease entity in 1&/2.
=rystal deposition can be asymptomatic, but gout and =))F can de"elop into debilitating
illnesses mar3ed by recurrent episodes o# pain and 6oint in#lammation that result #rom the
#ormation o# crystals 'ithin the 6oint space and deposition o# crystals in so#t tissue.
4%, /, $5
!#
untreated, these disorders can lead to 6oint destruction and, in the case o# uric acid crystals, renal
damage.
<le"ated serum uric acid le"els are the principal ris3 #actor #or de"eloping gout. l!n study that
compared &&3 patients 'ith asymptomatic hyperuricemia and 4,241 normouricemic patients, the
odds ratio ,D>- #or de"eloping gout 'as 32 times higher in the hyperuricemic group than in the
normouricemic group. ;he ris3 'as most stri3ing in men 'ith se"ere hyperuricemia, in 'hom
the D> #or de"eloping gout 'as /24...
4.5
8lthough gout is associated 'ith hyperuricemia, gout attac3s are triggered not by a particular
le"el o# uric acid but typically by acute changes in the le"el o# uric acid. 8ll indi"iduals 'ith
6
gout ha"e hyperuricemia ho'e"er, hyperuricemia is also #ound in patients ta3ing diuretics and
e"en in those ta3ing niacin or lo' doses o# aspirin.
Gout may be either primary or secondary ,see <tiology-. )rimary gout is related to
undere9cretion or o"erproduction o# uric acid, o#ten associated 'ith a mi9 o# dietary e9cesses or
alcohol o"eruse and metabolic syndrome. +econdary gout is related to medications or conditions
that cause hyperuricemia, such as the #ollo'ing
4&5
:
Myeloproli#erati"e diseases or their treatment
;herapeutic regimens that produce hyperuricemia
>enal #ailure
>enal tubular disorders
Aead poisoning
(yperproli#erati"e s3in disorders
<nEymatic de#ects ,eg, de#icient hypo9anthine-guanine phosphoribosyl trans#erase,
glycogen storage diseases-
Gout is de#initi"ely diagnosed on the basis o# demonstration o# urate crystals in aspirated
syno"ial #luid, in the absence o# another etiology #or arthritis. =lassic radiographic #indings are
highly suggesti"e ,see :or3up-.
8d"ances in early diagnosis and the a"ailability o# de#initi"e treatment ha"e signi#icantly
impro"ed the prognosis o# gout, as e"idenced by the declining incidence o# disabling chronic
tophaceous gout. (o'e"er, tophaceous gout may still de"elop because o# misdiagnosis, poor
management, medication intolerances, or poor patient adherence.
Ao'ering e9cess stores o# urate
;reatment o# gout is important to relie"e pain to pre"ent disease progression and to pre"ent
deposition o# urate crystals in the renal medulla or uric acid crystals in the renal collecting
system, 'hich may produce 3idney stones or urate nephropathy.
4105
,+ee ;reatment.-
Management o# pseudogout also in"ol"es treatment o# the acute attac3 and prophyla9is.
;reatment o# the acute phase o# pseudogout #ollo's the same approaches as are used in gout, and
colchicine is e##ecti"e #or prophyla9is. !n contrast 'ith gout, ho'e"er, no speci#ic therapeutic
regimen e9ists to treat the underlying cause o# =)) crystal deposition in pseudogout, e9cept in
cases associated 'ith disorders such as hemochromatosis or hyperparathyroidism. ,+ee
;reatment.-
7
Pathophysiology
Gout can be considered a disorder o# metabolism that allo's uric acid or urate to accumulate in
blood and tissues. :hen tissues become supersaturated, the urate salts precipitate, #orming
crystals. !n addition, the crystals also are less soluble under acid conditions and at lo'
temperatures, such as occur in cool, peripheral 6oints ,eg, the metatarsophalangeal 6oint o# the big
toe-.
Urate initially precipitates in the #orm o# needleli3e crystals. ;he light-retarding ,phase-shi#ting-
characteristics o# urate crystals allo' them to be recogniEed by polariEing microscopy ,see the
image belo'-.
Gout. 1eedles o# urate crystals seen on polariEing microscopy.
Many conditions and drugs ha"e been associated 'ith an increase in plasma ,and subseIuent
syno"ial- urate le"els, particularly metabolic syndrome. 8 genetic predisposition #or
hyperuricemia e9ists e9cept in rare genetic disorders, ho'e"er, the de"elopment o# gout in
hyperuricemic indi"iduals appears to be mediated by en"ironmental #actors.
411, 12, 135
;he =)) crystals that produce pseudogout comprise a combination o# inorganic pyrophosphate
and calcium. ;he inorganic pyrophosphate is produced in large part by ectonucleotide
phosphodiesterase pyrophosphatase ,<1))1-, a catalytic enEyme #ound in chondrocytes o#
cartilage, and the pyrophosphate is e9ported potently by the membrane transporter 81J(.
8 genetic predisposition e9ists #or pseudogout. (o'e"er, aging, some metabolic diseases ,eg,
hyperparathyroidism, hemochromatosis, and hypomagnesemia-, and any process that leads to
osteoarthritis also can be associated 'ith subseIuent =)) crystal deposition and pseudogout.
;he presence o# urate crystals in the so#t tissues and syno"ial tissues is a prereIuisite #or a gouty
attac3. (o'e"er, these crystals can also be #ound in syno"ial #luid or on the cartilage sur#ace in
the absence o# 6oint in#lammation.
8 gout attac3 may be triggered either by release o# crystals ,eg, #rom partial dissolution o# a
microtophus caused by changing serum urate le"els- or by precipitation o# crystals in a
supersaturated microen"ironment ,eg, release o# urate as a conseIuence o# cellular damage-. !n
either situation, it is belie"ed, na3ed urate crystals then interact 'ith intracellular and sur#ace
receptors o# local dendritic cells and macrophages, triggering a danger signal to acti"ate the
innate immune system.
4145
8
;his interaction may be enhanced by immunoglobulin G ,!gG- binding.
41%, 1/5
;riggering o# these
receptors, including ;oll-li3e receptors, #ollo'ed by intracellular signaling by the 1A>)3
in#lammasome, results in the release o# interleu3in ,!A--1K, 'hich in turn initiates a cascade o#
proin#lammatory cyto3ines, including !A-/, !A-., neutrophil chemotactic #actors, and tumor
necrosis #actor ,;1*--L.
41$, 1.5
1eutrophil phagocytosis leads to another burst o# in#lammatory
mediator production.
+ubsidence o# an acute gout attac3 results #rom multiple mechanisms, including the clearance o#
damaged neutrophils, change in the properties o# urate crystals, and the production o# anti-
in#lammatory cyto3ines such as !A-1 receptor antagonist ,!A-1>8-, !A-10, and trans#orming
gro'th #actor ,;G*--K.
41/, 1&, 20, 215
Etiology
Gout de"elops in the setting o# e9cessi"e stores o# uric acid in the #orm o# monosodium urate.
Uric acid is an end-stage by-product o# purine metabolism. (umans remo"e uric acid primarily
by renal e9cretion. :hen e9cretion is insu##icient to maintain serum urate le"els belo' the
saturation le"el o# /.. mgMdA, hyperuricemia may de"elop, and urate can crystalliEe and deposit
in so#t tissues.
8bout &07 o# patients 'ith gout de"elop e9cess urate stores because o# an inability to e9crete
su##icient amounts o# uric acid in the urine ,undere9cretion-. Most o# the remaining patients
either o"erconsume purines or produce e9cessi"e amounts o# uric acid endogenously
,o"erproduction-. 8 #e' ha"e impaired intestinal elimination o# uric acid.
!n rare cases, o"erproduction o# uric acid is the result o# a genetic disorder, such as the
#ollo'ing
4225
:
(ypo9anthine-guanine phosphoribosyltrans#erase de#iciency ,Aesch-1yhan syndrome-
Glucose-/-phosphatase de#iciency ,"on Gier3e disease-
*ructose 1-phosphate aldolase de#iciency
+uperacti"ity o# phosphoribosyl pyrophosphate synthetase ,)>))-
D"erproduction o# uric acid may also occur in disorders that cause high cell turno"er 'ith
release o# purines that are present in high concentration in cell nuclei. ;hese disorders include
myeloproli#erati"e and lymphoproli#erati"e disorders, psoriasis, and hemolytic anemias. =ell
lysis #rom chemotherapy #or malignancies, especially those o# the hematopoietic or lymphatic
systems, can raise uric acid le"els, as can e9cessi"e e9ercise and obesity.
=auses o# secondary gout due to undere9cretion o# uric acid include renal insu##iciency, lead
nephropathy ,saturnine gout-, star"ation or dehydration, certain drugs, and chronic abuse o#
ethanol ,especially beer and hard liIuor-. ;hese disorders should be identi#ied and corrected, i#
possible.
9
=ertain comorbid conditions are associated 'ith a higher incidence o# gout, including the
#ollo'ing
423, 245
:
(ypertension
Fiabetes mellitus
>enal insu##iciency
(ypertriglyceridemia
(ypercholesterolemia
Dbesity
8nemia
*oods that are rich in purines include ancho"ies, sardines, s'eetbreads, 3idney, li"er, and meat
e9tracts. =onsumption o# #ructose-rich #oods and be"erages ,eg, those s'eetened 'ith high-
#ructose corn syrup- is associated 'ith an increased ris3 o# gout in both men and 'omen.
42%, 2/5
Genetics
;he heritability o# serum urate le"els is estimated at /37.
42$5
Genome-'ide association studies
,G:8+- ha"e identi#ied se"eral candidate loci associated 'ith chronically ele"ated serum urate
concentrations and gout.
42., 2&, 30, 315
!n particular, 3 genes are noted to ha"e a strong association 'ith hyperuricemia. ;he locus 'ith
the strongest e"idence o# association is the glucose transporter & ,GLUT9) gene, commonly
re#erred to as the solute carrier 28& ,SLC2A9-, the product o# 'hich alters the renal e9cretion o#
uric acid. +ome o# the "ariants are associated 'ith a protecti"e e##ect, 'hereas others con"ey a
higher ris3 o# gout.
4325
;he urate transporter 1 ,URAT1) gene is in"ol"ed 'ith the urate-organic anion e9changer.
+e"eral mutations in this gene ha"e been associated 'ith gout.
)olymorphisms in the ABCG2 gene, 'hich is located on chromosome 4 and codes #or an
intestinal urate transporter, are strongly associated 'ith high serum uric acid concentrations and
gout. <le"ation o# uric acid le"els is greater in men than in 'omen 'ith the minor allele o#
rs2231142 in ABCG2.
42., 305
8lthough genetic #actors ha"e been strongly associated 'ith hyperuricemia, en"ironmental and
other state-o#-health #actors are responsible #or the ma6ority o# the gout burden in de"eloped
countries.
432, 335
8 study o# %14 male t'in pairs did sho' a strong concordance in hyperuricemia
among monoEygotic ,MN- t'ins ,%37- as compared 'ith diEygotic ,FN- t'ins ,247-, but it did
not sho' a signi#icant di##erence bet'een MN and FN t'ins 'ith regard to the li#etime
pre"alence o# gout.
4135
10
!auses of gout flares
!ndi"idual gout #lares are o#ten triggered by acute increases or decreases in urate le"els that may
lead to the production, e9posure, or shedding o# crystals. =hanges in urate le"els can result #rom
acute alcohol ingestion, acute o"erindulgence in #oods high in purines, rapid 'eight loss,
dehydration, or trauma.
+imilarly, #lares can be precipitated by additions o# or changes in dosage o# medications that
raise or lo'er uric acid le"els. Medications that increase uric acid le"els "ia e##ects on renal
tubular transport include loop and thiaEide diuretics, niacin, lo'-dose aspirin, and cyclosporine
8.
434, 3%, 3/5
8gents that lo'er le"els o# uric acid include radiocontrast dyes, 9anthine o9idase
inhibitors ,eg, allopurinol and #ebu9ostat-, and uricosurics ,eg, probenecid-.
Pseudogout
8lthough the pathophysiology, clinical presentation, and acute-phase treatment o# gout and
pseudogout are "ery similar, the underlying causes o# the 2 diseases are "ery di##erent. Many
cases o# pseudogout in elderly people are idiopathic, but pseudogout has also been associated
'ith trauma and 'ith many di##erent metabolic abnormalities, the most common o# 'hich are
hyperparathyroidism and hemochromatosis.
>is3 #actors #or pseudogout include use o# loop diuretics ,but not thiaEide diuretics- and proton
pump inhibitors, 'hich cause hypomagnesemia.
43/5
)seudogout attac3s ha"e been reportedly
induced by etidronate disodium therapy and angiography.
43$, 3.5
)seudogout has been recogniEed as ha"ing an underlying genetic component ho'e"er, comorbid
conditions ,such as osteoarthritis- and en"ironmental #actors are thought to play a much stronger
role.
43&5
+ome disorders that can lead to secondary pseudogout, such as hemochromatosis, do ha"e
a clear genetic cause. ;hese patients should be properly e"aluated and counseled.
Epidemiology
"nited States statistics
Gout a##ects ..3 million people in the United +tates pre"alence among adults is estimated to be
3.&7, on the basis o# data #rom the 200$-200. 1ational (ealth and 1utrition <9amination
+ur"ey ,1(81<+-.
4405
)re"alence is appro9imately 207 in patients 'ith a #amily history o# gout.
!t is estimated that more than 2 million people in the United +tates ta3e medication to decrease
serum uric acid le"els.
Gout has become increasingly common in the United +tates as the population has gro'n older
and hea"ier.
4415
*rom 1&&0 to 1&&&, the incidence rose 407.
4425
<stimates #or the number o# U+
adults 'ith sel#-reported gout in the pre"ious year rose #rom 2.1 million in 1&&% to 3 million in
11
200..
4125
!n 200., gout accounted #or 1$4,.23 emergency department ,<F- "isits in the U+, or
appro9imately 0.27 o# all <F "isits.
4435
;he #reIuency o# pseudogout "aries 'ith age. ;he annual incidence o# acute attac3s o# arthritic
pain and s'elling is about 1.3 per 1000 adults, but nearly %07 o# adults de"elop radiographic
changes typical o# =))F by age .0 years.
8ttac3s o# gout ha"e been noted to occur more #reIuently in the spring and less #reIuently in the
'inter. ;he reason #or this is un3no'n.
International statistics
Gout has a 'orld'ide distribution. ;he pre"alence "aries 'idely #rom country to country.
>egional di##erences may re#lect en"ironmental, dietary, and genetic in#luences.
4445
!n the United Jingdom #rom 2000 to 200$, the incidence o# gout 'as 2./. per 1000 person-years
O4.42 in men and 1.32 in 'omen, and increasing 'ith ad"ancing age.
44%5
!n !taly, the pre"alence
o# gout rose #rom /.$ per 1000 population in 200% to &.1 per 1000 population in 200&, increasing
'ith age and 4 times higher in men.
44/5
!n the Maori people o# 1e' Nealand, studies #rom the
1&$0s #ound that 0.37 o# men and 4.37 o# 'omen 'ere a##ected.
44$, 4.5
Se#$ and age$related demographics
Gout has a male predominance.
42/, 4&5
;he estimated pre"alence o# gout is %.&7 in men and 27 in
'omen.
4405
;his di##erence is largely a conseIuence o# age at onset estrogenic hormones ha"e a
mild uricosuric e##ect, and gout is there#ore unusual in premenopausal 'omen. *or pseudogout,
the male-to-#emale ratio is appro9imately %0:%0.
;he predominant age range o# gout is 30-/0 years. Usually, uric acid le"els are ele"ated #or 10-
20 years be#ore the onset o# gout. !n men, uric acid le"els rise at puberty, and the pea3 age o#
onset o# gout in men is in the #ourth to si9th decade o# li#e. (o'e"er, onset may occur in men in
their early 20s 'ho ha"e a genetic predisposition and li#estyle ris3 #actors.
4%05
!n 'omen, uric acid
le"els rise at menopause, and pea3 age o# onset is in the si9th to eighth decade o# li#e.
;he rate o# gout is almost % times higher in persons aged $0-$& years than in those younger than
%0 years.
4%15
;he higher pre"alence o# gout in elderly persons may also re#lect an increased
pre"alence o# metabolic syndrome, high rates o# diuretic treatment #or hypertension and chronic
heart #ailure, and the use o# lo'-dose aspirin.
4%25
<arlier onset o# gout occurs in patients 'ith renal insu##iciency or a genetic abnormality o#
purine metabolism ,eg, hypo9anthine-guanine phosphoribosyltrans#erase de#iciency or
phosphoribosylpyrophosphate synthetase superacti"ity-. =yclosporine 8 can cause an accelerated
#orm o# gout, e"en in premenopausal 'omen, that can present a#ter only a #e' years o#
hyperuricemia, particularly i# the patient is also recei"ing diuretics.
Race$related demographics
12
Gout has an increased pre"alence in some populations but is rare in others. *or e9ample, the
#reIuency o# gout is higher in populations such as the =hamorros and Maori and in the @lac3#oot
and )ima tribes. Many Maori and other )olynesian 'omen ha"e a genetic de#ect in renal urate
handling that places them at ris3 #or hyperuricemia and gout.
4%35
(o'e"er, racial di##erences may
at least in part re#lect di##erences in diet, 'hich has a large in#luence on the clinical e9pression o#
gout.
!n the United +tates, the incidence o# gout is 3.11 per 1000 person-years in 8#rican 8mericans
and 1..2 per 1000 person-years in 'hites the e9cess ris3 can be partly e9plained by a higher
#reIuency o# incident hypertension.
4%45
!n contrast, clinically recogniEed gout is e9tremely rare
among blac3s li"ing in 8#rica.
4%%5
Prognosis
Gout is associated 'ith considerable morbidity, 'ith acute episodes o#ten causing incapacitation.
(o'e"er, gout that is treated early and properly carries an e9cellent prognosis i# patient
adherence to treatment is good.
:ith early treatment, gout should be totally controlled. !# attac3s recur, success#ul uric acid
ad6ustment ,reIuiring li#elong use o# urate-lo'ering medication- usually suppresses #urther
acti"ity. Furing the #irst /-24 months o# urate-lo'ering therapy, acute attac3s o# gout o#ten occur
more #reIuently.
4%/, %$5
=hronic in6ury to intra-articular cartilage lea"es the 6oints more susceptible to subseIuent 6oint
in#ections. Fraining tophi can become secondarily in#ected. Untreated chronic tophaceous gout
can lead to se"ere 6oint destruction and, rarely, renal impairment. Feposition o# monosodium
urate crystals in the 3idney can result in in#lammation and #ibrosis, leading to reduced renal
#unction or chronic nephropathy.
4%.5
>arely, gout can produce spinal cord impingement 'hen
deposition in tissues produces a local mass.
8cute attac3s o# pseudogout usually resol"e 'ithin 10 days. )rognosis #or resolutions o# acute
attac3s is e9cellent. +ome patients e9perience progressi"e 6oint damage 'ith #unctional
limitation. =))F also can cause chronic arthritis that can resemble osteoarthritis or rheumatoid
arthritis.
(yperuricemia and gout are associated 'ith an increased o"erall li3elihood o# mortality. :hether
this is directly attributable to hyperuricemia or gout or to gout-associated diseases ,eg, insulin
resistance, type 2 diabetes mellitus, abdominal obesity, hypercholesterolemia, or hypertension-
has been much debated.
4%&, /0, /15
8lthough no e"idence has sho'n that gout or hyperuricemia causes any o# these disorders,
ele"ated urate le"els ha"e been sho'n to correlate 'ith ele"ated blood pressure in adolescents.
4/25
8mong middle-aged men, hyperuricemia is a signi#icant independent ris3 #actor #or death #rom
cardio"ascular disease.
4/35
8 meta-analysis #ound an independent association bet'een gout and
cardio"ascular mortality as 'ell as all-cause mortality.
4/15
13
!n a 2010 study, Juo et al demonstrated that gout, but not hyperuricemia, is associated 'ith
higher ris3 o# death #rom all causes and cardio"ascular diseases. 8nalysis o# 13.3 deaths among
/1,%2$ ;ai'anese sub6ects sho'ed in indi"iduals 'ith gout compared 'ith those 'ho had
normal uric acid le"els, the haEard ratio ,(>- o# all-cause mortality 'as 1.4/ and the ad6usted
(> o# cardio"ascular mortality 'as 1.&$. 8mong indi"iduals 'ith hyperuricemia, the (> o# all-
cause mortality 'as 1.0$ and the ad6usted (> o# cardio"ascular mortality 'as 1.0..
4/45
8n analysis o# nation'ide data on more than 200,000 <nglish patients indicates that indi"iduals
'ith gout are at increased ris3 #or both heart attac3 and stro3e. ;he rate ratio #or myocardial
in#arction in patients 'ith gout 'as 1..2. >ate ratios #or stro3e 'ere 1.$1 #or all stro3e, 1./. #or
ischemic stro3e, 1./& #or hemorrhagic stro3e, and 2.00 #or stro3e o# unspeci#ied type. >is3s 'ere
ele"ated in both men and 'omen and 'ere higher in the younger age groups.
4/%, //5
Patient Education
)atients 'ith se"ere hyperuricemia should a"oid #oods 'ith high purine content. Moderation in
#ood and alcohol consumption is ad"ised. <arly recognition o# acute gout attac3s is critical, in
that inter"ention 'ith medication is much more e##ecti"e earlier in the attac3.
*or patient education in#ormation, see the 8rthritis =enter, as 'ell as Gout. Dnline in#ormation
and pamphlets on gout are also a"ailable #rom the 8rthritis *oundation.
%istory
;he spontaneous onset o# e9cruciating pain, edema, and in#lammation in the metatarsal-
phalangeal 6oint o# the great toe ,podagra see the image belo'- is highly suggesti"e o# acute
crystal-induced arthritis. )odagra is the initial 6oint mani#estation in %07 o# gout cases
e"entually, it is in"ol"ed in &07 o# cases. )odagra is not synonymous 'ith gout, ho'e"er: it may
also be obser"ed in patients 'ith pseudogout, sarcoidosis, gonococcal arthritis, psoriatic arthritis,
and reacti"e arthritis.
Gout. 8cute podagra due to gout in elderly man.
Dther than the great toe, the most common sites o# gouty arthritis are the instep, an3le, 'rist,
#inger 6oints, and 3nee. !n early gout, only 1 or 2 6oints are usually in"ol"ed. =onsider the
diagnosis in any patient 'ith acute monoarticular arthritis o# any peripheral 6oint e9cept the
glenohumeral 6oint o# the shoulder.
14
;he most common sites o# pseudogout arthritis are large 6oints, such as the 3nee, 'rist, elbo', or
an3le. =ase reports ha"e documented carpal tunnel syndrome as an initial presentation o#
pseudogout. =ase reports o# calcium pyrophosphate ,=))- crystals #orming masses in the spinal
ligamentum #la"um ha"e been documented.
4/$5
;hese ha"e led to both single-le"el and multile"el
myelopathy.
8lthough crystal-induced arthritis is most commonly monoarticular, polyarticular acute #lares are
not rare, and many di##erent 6oints may be in"ol"ed simultaneously or in rapid succession.
Multiple 6oints in the same limb o#ten are in"ol"ed, as 'hen in#lammation begins in the great toe
and then progresses to in"ol"e the mid#oot and an3le.
Gout attac3s begin abruptly and typically reach ma9imum intensity 'ithin .-12 hours. 8##ected
6oints are red, hot, and e9Iuisitely tender e"en a bed sheet on the s'ollen 6oint is uncom#ortable.
;he onset o# symptoms in pseudogout can resemble acute gout or be more insidious and may
occur o"er se"eral days.
Untreated, the #irst attac3s resol"e spontaneously in less than 2 'ee3s. 8 history o# intermittent
in#lammatory arthritis, in 'hich the 6oints return to normal bet'een attac3s, is typical o#
crystalline disorders and is characteristic o# gouty arthritis early in its course.
Gout initially presents as polyarticular arthritis in 107 o# patients. <lderly 'omen, particularly
'omen 'ith renal insu##iciency 'ho are ta3ing a thiaEide diuretic, can de"elop polyarticular
arthritis as the #irst mani#estation o# gout. ;hese attac3s may occur in coe9isting (eberden and
@ouchard nodes. +uch patients may also de"elop tophi more Iuic3ly, occasionally 'ithout prior
episodes o# acute gouty arthritis.
4/., /&, $05
;he pattern o# symptoms in untreated gout changes o"er time. ;he attac3s can become more
polyarticular. More pro9imal and upper-e9tremity 6oints become in"ol"ed. 8ttac3s tend to occur
more #reIuently and last longer.
<"entually, patients may de"elop chronic polyarticular arthritis, sometimes nearly symmetrical,
that can resemble rheumatoid arthritis. !ndeed, chronic polyarticular arthritis that began as an
intermittent arthritis should prompt consideration o# a crystalline disorder in the di##erential
diagnosis.
8cute #lares o# gout can result #rom situations that lead to increased le"els o# serum uric acid,
such as the consumption o# beer or liIuor, o"erconsumption o# #oods 'ith high purine content,
trauma, dehydration, or the use o# medications that ele"ate le"els o# uric acid. 8cute #lares o#
gout also can result #rom situations that lead to decreased le"els o# serum uric acid, such as the
use o# radiocontrast dye or medications that lo'er the le"els o# uric acid, including allopurinol
and uricosurics.
)atients 'ith gout ha"e as much as 1000 times more uric acid in the body as una##ected
indi"iduals do and are almost t'ice ,1.&$ times- as li3ely to de"elop renal stones as healthy
indi"iduals are
4$15
there#ore, they may ha"e a history o# renal colic and hematuria. !ndeed, renal
stones may precede the onset o# gout in 147 o# a##ected patients. :hereas %27 o# these patients
15
may ha"e stones composed entirely o# uric acid, 207 may de"elop calcium o9alate or sometimes
calcium phosphate stones.
4$25
@ecause gout is #reIuently present in patients 'ith the metabolic syndrome ,eg, insulin resistance
or diabetes, hypertension, hypertriglyceridemia, and lo' le"els o# high-density lipoproteins- and
because the presence o# these associated disorders can lead to coronary artery disease, these
problems should be sought and treated in patients diagnosed 'ith gout.
!t is important to as3 about a history o# peptic ulcer disease, renal disease, or other conditions
that may complicate the use o# the medications used to treat gout.
*e"er, chills, and malaise do not distinguish cellulitis or septic arthritis #rom crystal-induced
arthritis, because all 3 illnesses can produce these signs and symptoms. 8 care#ul history may
unco"er ris3 #actors #or cellulitis or septic arthritis, such as possible e9posure to gonorrhea, a
recent puncture 'ound o"er the 6oint, or systemic signs o# disseminated in#ection.
Physical E#amination
)atients e9periencing an acute attac3 o# gout or pseudogout most o#ten present 'ith in"ol"ement
o# a single 6oint. (o'e"er, all 6oints must be e9amined to determine 'hether the patient2s
arthritis is monoarticular or polyarticular. !n"ol"ed 6oints ha"e all the signs o# in#lammation:
s'elling, 'armth, erythema, and tenderness.
;he erythema o"er the 6oint may resemble cellulitis the s3in may desIuamate as the attac3
subsides. ;he 6oint capsule becomes Iuic3ly s'ollen, resulting in a loss o# range o# motion o# the
in"ol"ed 6oint.
)atients may be #ebrile during an acute gout attac3, particularly i# it is polyarticular. (o'e"er, it
is important to loo3 #or sites o# in#ection that may ha"e seeded the 6oint and caused an in#ectious
arthritis resembling or coe9isting 'ith acute gouty arthritis.
Migratory polyarthritis is a rare presentation. )olyarticular gout commonly in"ol"es the small
6oints o# the #ingers and toes, as 'ell as the 3nees. 8n in#lammatory syno"ial e##usion may be
present. Uncommonly, acute gout may present as carpal tunnel syndrome.
)osterior interosseous ner"e syndrome is a rare compression neuropathy that mani#ests as
inability to e9tend the #ingers acti"ely. ;he syndrome has been reported in a patient 'ith elbo'
s'elling #rom an attac3 o# pseudogout in this case, treatment 'ith intra-articular steroids led to
resolution o# the ner"e palsy.
4$35
)atients 'ith established gout may ha"e chronic arthritis. 8##ected 6oints e"idence tenderness and
s'elling, 'ith or 'ithout redness, 'armth, or 6oint damage.
&ophi
16
8lthough gout typically causes 6oint in#lammation, it can also cause in#lammation in other
syno"ial-based structures, such as bursae and tendons. ;ophi are collections o# urate crystals in
the so#t tissues. ;hey tend to de"elop a#ter about a decade in untreated patients 'ho de"elop
chronic gouty arthritis. ;ophi may de"elop earlier in older 'omen, particularly those recei"ing
diuretics.
4/., /&, $05
;ophi are classically located along the heli9 o# the ear, but they can be #ound in multiple
locations, including the #ingers, the toes, the prepatellar bursa, and along the olecranon, 'here
they can resemble rheumatoid nodules ,see the images belo'-. >arely, a creamy discharge may
be present.
4$4, $%5
;he #inding o# an apparent rheumatoid nodule in a patient 'ith a negati"e
rheumatoid #actor assay or a history o# drainage #rom a nodule should prompt consideration o#
gout in the di##erential diagnosis.
4$/5
Gout. ;ophaceous deposits in ear.
Gout. ;ophaceous deposits on elbo'. Gout. =hronic tophaceous
gout in untreated patient 'ith end-stage renal disease.
Eye in'ol'ement
;he #ol3lore surrounding gout has also in"ol"ed the eye, and be#ore the 20th century, a myriad o#
common and unusual ocular symptoms 'ere #alsely ascribed to gout. Medical science has since
documented eye in"ol"ement as a rare but de#inite aspect o# gout. 8ll mani#estations o# gout in
the eye are secondary to deposition o# urate crystals 'ithin the ocular tissue.
4$$, $.5
;ophi ha"e been described in the eyelids.
4$&, .0, .15
=on6uncti"al nodules containing needleli3e
crystals ha"e been described 'ithin the interpalpebral areas, sometimes associated 'ith a mild
marginal 3eratitis. @and 3eratopathy 'ith re#ractile, yello' crystals in the deep corneal epithelial
cells and at the le"el o# the @o'man membrane are not uncommon.
4.25
@lurring o# "ision #rom the corneal haEe or a #oreign body sensation due to epithelial brea3do'n
may occur. Gout rarely can be associated 'ith anterior u"eitis Fu3e-<lder mentions this as a
cause o# hemorrhagic iritis in his classic Text Book of Ophthalmology. +cleritis and tendinitis
ha"e also been described. @esides the cornea, the iris, anterior chamber, lens, and sclera ha"e
17
been #ound to harbor urate crystals on postmortem e9amination, urate crystals ha"e also been
#ound in tarsal cartilage and in the tendons o# e9traocular muscles.
4$$, $.5
!omplications
=omplications o# gout include the #ollo'ing:
+e"ere degenerati"e arthritis
+econdary in#ections
Urate or uric acid nephropathy
!ncreased susceptibility to in#ection
Urate nephropathy
>enal stones
1er"e or spinal cord impingement
4.3, .45
*ractures in 6oints 'ith tophaceous gout
4.%5
Gout and Pseudogout Differential Diagnoses
8uthor: @ruce M >othschild, MF =hie# <ditor: (erbert + Fiamond, MF more...

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18
Diagnostic !onsiderations
;he cause o# ne'-onset acute monoarticular arthritis cannot be reliably determined #rom the
history and physical e9amination alone. +eptic arthritis, gout, and pseudogout can present in "ery
similar 'ays.
1e"ertheless, certain clinical presentations are so characteristic o# gout that attempts ha"e been
made to diagnose or e9clude gout 'ithout 6oint aspiration. ?anssens et al de"eloped a diagnostic
rule #or this purpose, 'hich included the #ollo'ing diagnostic criteria
4./5
:
Male se9
)re"ious arthritis attac3
Dnset 'ithin 1 day
?oint redness
*irst metatarsophalangeal 6oint in"ol"ement
(ypertension or 1 or more cardio"ascular diseases
8 serum uric acid le"el higher than %... mgMdA
!n a study o# this rule in 32. patients, the positi"e predicti"e "alue o# gout diagnosis by #amily
physicians 'as 0./4 the negati"e predicti"e "alue 'as 0..$.
4./5
1e"ertheless, the criterion standards #or the diagnosis o# gout remain the #ollo'ing:
Femonstration o# intracellular monosodium urate crystals
<9clusion o# in#ection or other crystal types in the syno"ial #luid #rom the in#lamed 6oint
)atients 'ho present 'ith acute in#lammatory arthritis need to undergo arthrocentesis to e9clude
septic arthritis, e"en i# their serum uric acid le"el is ele"ated. 1ongonococcal in#ectious arthritis
carries a 107 #atality rate and there#ore must be e9cluded.
Dther problems to be considered in the di##erential diagnosis o# gout and pseudogout include the
#ollo'ing:
8cute sarcoidosis
8myloidosis
@ursitis
=alci#ic periarthritis
=hondrocalcinosis
=ongenital #ructose intolerance
19
=on6uncti"al calcinosis
(yperparathyroidism
(ypo9anthine-guanine phosphoribosyltrans#erase de#iciency ,Aesch-1yhan syndrome-
Malignant so#t tissue tumors
Mil3-al3ali syndrome
Multicentric reticulohistiocytosis
)aronychia
)igmented "illonodular syno"itis
)hosphoribosylpyrophosphate synthetase superacti"ity
)soriatic arthropathy
>eacti"e arthritis
>enal osteodystrophy
+pondyloarthropathy
>heumatoid arthritis
;enosyno"itis
;rauma
;ype !!8 hyperlipoproteinemia
Differential Diagnoses
8rthritis as a Mani#estation o# +ystemic Fisease
=ellulitis
1ephrolithiasis
>heumatoid 8rthritis
+eptic 8rthritis
Gout and Pseudogout (orkup
20

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8pproach =onsiderations
+yno"ial *luid 8nalysis
+erum Uric 8cid
Urinary Uric 8cid
@lood +tudies
>adiography
Ultrasonography
=omputed ;omography
Magnetic >esonance !maging
(istology
+ho' 8ll
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*pproach !onsiderations
8rthrocentesis o# the a##ected 6oint is mandatory #or all patients 'ith ne'-onset acute
monoarthritis and is "ery strongly recommended #or those 'ith recurrent attac3s 'hose diagnosis
has ne"er been pro"ed by microscopic "isualiEation o# crystals. ;ophi also may be aspirated #or
crystal analysis under polariEing microscopy.
21
8 prior history o# gout or pseudogout does not rule out the possibility o# acute septic arthritis. !n
#act, the latter is more common in patients 'ith a history o# crystal-induced arthritis. +eptic
arthritis must be diagnosed and treated promptly, because irre"ersible damage can occur 'ithin
4-/ hours and the 6oint can be completely destroyed 'ithin 24-4. hours.
+end 6oint #luid #or #luid analysis, including cell count and di##erential, Gram stain, culture and
sensiti"ity, and microscopic analysis #or crystals. !# crystals are seen, their shape and appearance
under polariEed light are diagnostic.
!n gout, crystals o# monosodium urate ,M+U- appear as needle-shaped intracellular and
e9tracellular crystals. :hen e9amined 'ith a polariEing #ilter and red compensator #ilter, they are
yello' 'hen aligned parallel to the slo' a9is o# the red compensator but turn blue 'hen aligned
across the direction o# polariEation ,ie, they e9hibit negati"e bire#ringence-. 1egati"ely
bire#ringent urate crystals are seen on polariEing e9amination in .%7 o# specimens.
Microscopic analysis in pseudogout sho's calcium pyrophosphate ,=))- crystals, 'hich appear
shorter than M+U crystals and are o#ten rhomboidal. Under a polariEing #ilter, =)) crystals
change color depending upon their alignment relati"e to the direction o# the red compensator.
;hey are positi"ely bire#ringent, appearing blue 'hen aligned parallel 'ith the slo' a9is o# the
compensator and yello' 'hen perpendicular.
!n crystal arthritis, the 'hite blood cell ,:@=- count in the syno"ial #luid is usually 10,000-
$0,000MPA. (o'e"er, it may be as lo' as 1000MPA or as high as 100,000MPA.
<"en in the presence o# crystals in the 6oint #luid, blood cultures are indicated i# any sign o#
systemic to9icity is present. +eptic arthritis can occur in patients 'ith acti"e crystalline
arthropathy.
Gouty attac3s are not related to serum le"els o# uric acid. ;hus, an ele"ated serum uric acid le"el
does not pro"e the diagnosis o# acute gout, though hyperuricemia is present in &%7 o# cases, and
a normal le"el does not e9clude the diagnosis. >enal uric acid e9cretion should be measured in
high-ris3 patients, including those 'ith renal calculi, a strong #amily history o# gout, and a #irst
attac3 be#ore age 2% years.
)seudogout attac3s can be triggered by many metabolic abnormalities. ;hus, patients 'ho ha"e
an initial attac3 o# arthritis 'ith =)) crystals should ha"e a 'or3up that includes a chemistry
screen serum magnesium, calcium, and iron le"els and thyroid #unction tests.
;he :@= count in peripheral blood is usually ele"ated, 'ith a le#t shi#t during acute attac3s. ;he
erythrocyte sedimentation rate ,<+>- usually is ele"ated during acute attac3s.
!maging studies o# the a##ected 6oint or 6oints are indicated. )atients 'ith ne' onset o# acute gout
usually ha"e no radiographic abnormalities. !n established disease, radiographs may re"eal
punched-out erosions or lytic areas 'ith o"erhanging edges.
22
Magnetic resonance imaging ,M>!- is capable o# detecting crystal deposits but is not part o# any
routine e"aluation #or acute arthritis. M>! can be "ery use#ul in determining the e9tent o# the
disease and may help in the di##erential diagnosis.
)atients 'ith pseudogout usually ha"e degenerati"e 6oint changes e"ident on imaging studies. !n
addition, they may ha"e calci#ications in the so#t tissues, tendons, or bursae.
Syno'ial +luid *nalysis
:hen a patient presents 'ith acute in#lammatory monoarticular arthritis, aspiration o# the
in"ol"ed 6oint is critical to rule out an in#ectious arthritis and to attempt to con#irm a diagnosis o#
gout or pseudogout on the basis o# identi#ication o# crystals ,see the image belo'-. Minute
Iuantities o# #luid in the sha#t or hub o# the needle are su##icient #or syno"ial #luid analysis.
Gout. *luid obtained #rom tophaceous deposit in patient 'ith
gout.
Urate crystals are shaped li3e needles or toothpic3s 'ith pointed ends ,see the #irst image
belo'-. Under polariEing light microscopy, urate crystals are yello' 'hen aligned parallel to the
a9is o# the red compensator and blue 'hen aligned across the direction o# polariEation ,ie, they
e9hibit negati"e bire#ringence-. *inding negati"ely bire#ringent urate crystals ,see the second
image belo'- #irmly establishes the diagnosis o# gouty arthritis.
Gout. 1eedles o# urate crystals seen on polariEing microscopy.
Gout. +trongly negati"e bire#ringent, needle-shaped crystals
diagnostic o# gout obtained #rom acutely in#lamed 6oint.
23
)seudogout crystals ,=))- are rod-shaped 'ith blunt ends and are positi"ely bire#ringent. ;hus,
pseudogout crystals are blue 'hen aligned parallel to the slo' ray o# the compensator and yello'
'hen they are perpendicular.
=rystals must be distinguished #rom bire#ringent cartilaginous or other debris. Febris may ha"e
#uEEy borders and may be cur"ed, 'hereas crystals ha"e sharp borders and are straight. 8s
al3aliEation reduces uric acid crystal solubility and the enEyme uricase can Bdissol"eC these
crystals, reduction by addition o# sodium hydro9ide or uricase to suspected gout crystal can be
help#ul.
=orticosteroids in6ected into 6oints ha"e a crystalline structure that can mimic either M+U or
=)) crystals. ;hey can be either positi"ely or negati"ely bire#ringent.
;he sensiti"ity o# a syno"ial #luid analysis #or crystals is .47, 'ith a speci#icity o# 1007. !# gout
remains a clinical consideration a#ter negati"e analysis #indings, the procedure can be repeated in
another 6oint or 'ith a subseIuent #lare. =rystals may be absent "ery early in a #lare.
8lthough the sensiti"ity o# this test is in#erior, aspiration o# syno"ial #luid #rom pre"iously
in#lamed 6oints that are not currently in#lamed may re"eal urate crystals. +uch crystals are
generally e9tracellular.
+yno"ial #luid should also be sent #or cell count. Furing acute attac3s, the syno"ial #luid is
in#lammatory, 'ith a :@= count higher than 2000MPA ,class !! #luid- and possibly higher than
%0,000MPA, 'ith a predominance o# polymorphonuclear neutrophils, though lo' :@= counts are
occasionally #ound.
+yno"ial #luid glucose le"els are usually normal, 'hereas they may be depressed in septic
arthritis and occasionally in rheumatoid arthritis. Measurement o# syno"ial #luid protein has no
clinical "alue.
=rystalline arthritis and in#ectious arthritis can coe9ist. !ndeed, in#ectious arthritis is more
common in pre"iously damaged 6oints, 'hich may occur in patients 'ith chronic gouty arthritis.
=onseIuently, in patients 'ith acute monoarticular arthritis, send syno"ial #luid #or Gram stain
and culture and sensiti"ity.
;he pathologic specimens must be processed anhydrously. M+U is 'ater-soluble and dissol"es
in #ormalin there#ore, only the ghosts o# urate crystals may be seen i# #ormalin is used. 8bsolute
,1007- alcohol0#i9ed tissue is best #or identi#ication o# urate crystals.
Dnce a diagnosis o# gout is established by con#irmation o# crystals, repeat aspiration o# 6oints
'ith subseIuent #lares is not necessary unless in#ection is suggested or the #lare does not respond
appropriately to therapy #or acute gout.
Serum "ric *cid
24
Measurement o# serum uric acid is the most misused test in the diagnosis o# gout. ;he presence
o# hyperuricemia in the absence o# symptoms is not diagnostic o# gout. !n addition, as many as
1%7 o# patients 'ith symptoms #rom gout may ha"e normal serum uric acid le"els at the time o#
their attac3. ;hus, the diagnosis o# gout can be missed i# the 6oint is not aspirated. >emember
that situations that decrease uric acid le"els can trigger attac3s o# gout. !n such cases, the
patient2s medical records may re"eal prior ele"ations o# uric acid.
8ppro9imately 2%7 o# the population has a history o# ele"ated serum uric acid, but only a
minority o# patients 'ith hyperuricemia de"elop gout. ;hus, an abnormally high serum uric acid
le"el does not indicate or predict gout. 8s noted, gout is diagnosed by the presence o# urate
crystals in the syno"ial #luid or so#t tissues. More important, some patients 'ho present 'ith a
hot s'ollen 6oint and an ele"ated serum uric acid le"el in #act ha"e in#ectious arthritis, 'hich
may be mismanaged i# their syno"ial #luid is not e9amined.
8symptomatic hyperuricemia generally should not be treated. (o'e"er, patients 'ith le"els
higher than 11 mgMdA and o"ere9cretion o# uric acid are at increased ris3 #or renal stones and
renal impairment there#ore, renal #unction should be monitored in these indi"iduals.
4335
;he le"el o# serum uric acid does correlate 'ith the ris3 #or de"eloping gout. ;he %-year ris3 #or
de"eloping gout is appro9imately 0./7 i# the le"el is belo' $.& mgMdA, 17 i# it is .-..& mgMdA,
and 227 i# it is higher than & mgMdA.
"rinary "ric *cid
8 24-hour urinary uric acid e"aluation is generally per#ormed i# uricosuric therapy is being
considered. !# patients e9crete more than .00 mg o# uric acid in 24 hours 'hile eating a regular
diet, they are o"ere9cretors and thus o"erproducers o# uric acid. ;hese patients ,appro9imately
107 o# patients 'ith gout- reIuire allopurinol instead o# probenecid to reduce uric acid le"els.
*urthermore, patients 'ho e9crete more than 1100 mg in 24 hours should undergo close renal
#unction monitoring because o# the ris3 o# stones and urate nephropathy.
!n patients in 'hom probenecid is contraindicated ,eg, those 'ith a history o# renal stones or
renal insu##iciency-, a 24-hour urine test o# uric acid e9cretion need not be per#ormed, because
the patient clearly 'ill need allopurinol.
lood Studies
@lood studies may re"eal abnormalities associated 'ith gout or common comorbid conditions. !n
addition, abnormal results on renal #unction or li"er #unction studies may a##ect the selection o#
therapy.
Dbtaining an accurate measure o# the patient2s renal #unction be#ore deciding on therapy #or gout
is important. ;he glomerular #iltration rate can be estimated by using #ormulas such as the
Modi#ication o# Fiet in >enal Fisease ,MF>F- +tudy eIuation or the =hronic Jidney Fisease
25
<pidemiology =ollaboration ,=JF-<)!- eIuation. +erum creatinine e"aluation alone can
underestimate renal dys#unction in elderly patients or in patients 'ith lo' muscle mass.
;he :@= count may be ele"ated in patients during the acute gouty attac3, particularly i# it is
polyarticular. (ypertriglyceridemia and lo' le"els o# high-density lipoprotein ,(FA- are
associated 'ith gout. Glucose measurement is use#ul because patients 'ith gout are at increased
ris3 #or the de"elopment o# diabetes mellitus.
)seudogout attac3s can be triggered by many metabolic abnormalities. ;hus, patients 'ho ha"e
an initial attac3 o# arthritis 'ith =)) crystals should ha"e a 'or3up that includes a chemistry
screen serum magnesium, calcium, iron and iron-binding le"els and thyroid #unction tests.
Radiography
)lain radiographs may sho' #indings consistent 'ith gout, but these #indings are not diagnostic.
<arly in the disease, radiographs are o#ten normal or sho' only so#t-tissue s'elling.
>adiographic #indings characteristic o# gout, 'hich generally do not appear 'ithin the #irst year
o# disease onset, consist o# punched-out erosions or lytic areas 'ith o"erhanging edges ,see the
image belo'-. (aEiness suggesti"e o# tophi can be seen in late gout, and tophi may calci#y.
Gout. >adiograph o# erosions 'ith o"erhanging edges.
<rosions 'ith o"erhanging edges generally are considered pathognomonic #or gout but also can
be #ound in amyloidosis, multicentric reticulohistiocytosis, and type !!8 hyperlipoproteinemia.
=haracteristics o# erosions that are typical o# gout but not o# rheumatoid arthritis include the
#ollo'ing:
Maintenance o# the 6oint space
4.$, ..5
8bsence o# periarticular osteopenia
Aocation outside the 6oint capsule
8nother characteristic o# erosions typical o# gout is sclerotic borders, sometimes called coo3ie-
cutter or punched-out borders. !n addition, erosions in gout may be distributed asymmetrically
among the 6oints, 'ith strong predilection #or distal 6oints, especially in the lo'er e9tremities
,see the images belo'-.
26
Gout. )lain radiograph sho'ing typical changes o# gout in #irst
metatarsophalangeal 6oint and #ourth interphalangeal 6oint. Gout.
)lain radiograph sho'ing chronic tophaceous gouty arthritis in hands.
"ltrasonography
8t the #irst attac3, sites a##ected 'ith gout may be anechoic on ultrasonography. Aater, di##use
enhancement may be e"ident on the articular cartilage sur#ace.
4.&5
=hondrocalcinosis sho' up as a
thin, hyperechoic band 'ithin hyaline cartilage and punctuated pattern on #ibrocartilage.
Ultrasonographic #indings in established gout include the #ollo'ing
4&0, &1, &25
:
8 Bdouble-contourC sign, consisting o# a hyperechoic, irregular line o# M+U crystals on
the sur#ace o# articular cartilage o"erlying an ad6acent hyperechoic bony contour
B:et clumps o# sugar,C representing tophaceous material, described as hyperechoic and
hypoechoic heterogeneous material 'ith an anechoic rim
@ony erosions ad6acent to tophaceous deposits
Ultrasonography may demonstrate urate crystal deposition in tissues o# asymptomatic patients
'ith hyperuricemia. )ineda et al #ound double-contour signs in the #irst metatarsal-phalangeal
6oints o# 2%7 o# %0 asymptomatic patients 'ith hyperuricemia but in none o# %2 normouricemic
sub6ects.
4&35
!n a study by FeMiguel et al, ultrasonography identi#ied urate crystal deposition in 11 o# 2/
patients 'ho had asymptomatic hyperuricemia #or 2-2. years ,a"erage, /.2 years-, a##ecting the
3nee in & cases and the #irst metatarsal-phalangeal 6oint in /. ;hese results document that
asymptomatic gout may not be as innocuous as 'as once belie"ed.
4&45
!omputed &omography
27
)lain radiography and computed tomography ,=;- are complementary #or recogniEing erosions
in gout.
4&%5
Fual-energy =;, using a renal stone color-coding protocol, assesses chemical
composition, labeling urate deposits in red.
4&/5
!n a study comparing =; imaging "ersus a history o# urinary tract calculus #or identi#ication o#
nephrolithiasis in gout patients, /27 o# the patients 'ith =;-documented scans had no history o#
urolithiasis. !n 3.3 male patients 'ith primary gout, =; scanning con#irmed nephrolithiasis in
103 ,2/.&7-, 'hereas the history o# urinary tract calculus 'as positi"e in only /% ,1$7-. ;he
authors concluded that the pre"alence o# urolithiasis cannot be accurately determined on the
basis o# patients2 histories.
4&$5
Magnetic Resonance Imaging
M>! is not part o# any routine e"aluation #or acute arthritis. M>! e"idence o# edema is minimal
in gout, unless concomitant osteomyelitis is present.
4&.5
(o'e"er, M>! 'ith gadolinium is
recommended 'hen tendon sheath in"ol"ement must be e"aluated and 'hen osteomyelitis is in
the di##erential diagnosis. Aarge deposits o# crystals may be seen in bursae or ligaments. M>!
e9amination o# erosions re"eals tophi but no bone edema or syno"itis.
4&&5
;ophi usually ha"e lo' or intermediate signal intensity on ;1-'eighted spin echo images. +ignal
intensity also tends to be lo' on ;2-'eighted images. !n the absence o# in#lammation, the tophi
are sharply delineated. )resence o# in#lammation results in increased perilesional signal intensity.
;ophi and the surrounding area o# in#lammation enhance 'ith gadolinium.
41005
%istology
=hronic tophaceous gouty deposits #reIuently sho' large pale pin3 acellular areas, 'hich
represent dissol"ed urate crystals, surrounded by histiocytes and multinucleated giant cells ,see
the image belo'-.
Gout. (emato9ylin and eosin ,(Q<- stain, lo' po'er, sho'ing
abundant pale pin3 areas surrounded by histiocytes and multinucleated giant cells.
;he crystals are 'ater-soluble and thus are dissol"ed during routine tissue processing. !# there are
a large number o# crystals, ho'e"er, some may sur"i"e processing and appear as pale bro'n-
gray re#ractile material ,see the image belo'-, or they may be seen on unstained sections. ;he
urate crystals are easily seen on polariEed light.
28
Gout. (Q< stain, high po'er, sho'ing that most urate crystals
ha"e been dissol"ed but that some pale bro'n-gray crystals did sur"i"e processing.
)seudogout also demonstrates pale pin3 areas that may be surrounded by histiocytes and
multinucleated giant cells. Dn higher-po'er "ie's, ho'e"er, the crystals are purple and
rhomboid and there#ore can be distinguished #rom gout on routine histology ,see the images
belo'-.
(Q< stain, medium po'er, o# pseudogout 'ith pale pin3
#ibrocartilage in upper portion and purple crystals o# calcium pyrophosphate in lo'er portion.
)seudogout. (Q< stain, high po'er, under polariEed light to
highlight rhomboidal crystals. )seudogout. (Q< stain, high
po'er, o# calcium pyrophosphate crystals, demonstrating their
Gout and Pseudogout &reatment ,
Management
29

D"er"ie'
)resentation
FF9
:or3up
;reatment
Medication
)rint this section

8pproach =onsiderations
;reatment o# 8cute 8ttac3s
;reatment o# =hronic Gout
Fiet and 8cti"ity
=onsultations
Aong-;erm Monitoring
+ho' 8ll
Multimedia Aibrary
>e#erences
*pproach !onsiderations
Ao'ering e9cess stores o# urate to pre"ent #lares o# gouty arthritis and to pre"ent tissue
deposition o# urate crystals
!n 2012, the 8merican =ollege o# >heumatology ,8=>- published guidelines on the treatment
and prophyla9is o# acute gouty arthritis and the management o# hyperuricemia.
4101, 1025
30
8s a general rule, asymptomatic hyperuricemia should not be treated, though ultrasonographic
studies ha"e demonstrated that urate crystal deposition into so#t tissues occurs in a minority o#
patients 'ith asymptomatic hyperuricemia.
4&3, &45
)atients 'ith le"els higher than 11 mgMdA 'ho
o"ere9crete uric acid are at ris3 #or renal stones and renal impairment there#ore, renal #unction
should be monitored in these indi"iduals.
4335
Urate-lo'ering therapy appears to reduce the incidence o# 3idney damage in gout.
41035
!n a
retrospecti"e study o# 1/,1./ patients 'ith initial serum uric acid le"els abo"e $ mgMdA, Ae"y
and colleagues #ound that patients 'ith gout 'ho remained on urate-lo'ering therapy 'ere less
li3ely to de"elop 3idney damage leading to chronic 3idney disease than those 'ho 'ere
untreated.
41035
8ll patients 'ere #ollo'ed #or 3/ months #rom their #irst documented high serum
uric acid le"el.
)atients 'ho achie"ed a serum uric acid le"el belo' / mgMdA had a 3$7 impro"ement in renal
outcomes ,P R .0001-.
41035
;he haEard ratio #or 3idney damage 'as 1.0. ,&%7 con#idence
inter"al, 0.$/01.%2- in patients 'ho recei"ed urate-lo'ering therapy more than .07 o# the time
and 'as 1.2$ ,&%7 con#idence inter"al, 1.0%01.%%- in those 'ho recei"ed urate-lo'ering therapy
less than .07 o# the time.
;ophi should not be surgically remo"ed unless they are in a critical location or drain chronically.
+urgery may be indicated #or tophaceous complications, including in#ection, 6oint de#ormity,
compression ,eg, cauda eIuina or spinal cord impingement-, and intractable pain, as 'ell as #or
ulcers related to tophaceous erosions. Felayed healing is noted in %07 o# patients.
;reatment o# the acute phase o# pseudogout is identical to that o# acute gout. !n patients 'ith
idiopathic pseudogout, a deterrent regimen o# colchicine may be used. !# an underlying metabolic
problem is responsible #or pseudogout, the arthritis may be cured 'hen the underlying problem
is addressed.
&reatment of *cute *ttacks
;he temptation to treat patients 'ithout a pro"en diagnosis must be resisted. +eptic arthritis may
clinically resemble gout or pseudogout, and unrecogniEed septic arthritis can lead to loss o# li#e
or limb. Fistinguishing septic arthritis #rom crystal-induced arthritis is not possible 'ithout an
e9amination o# 6oint #luid.
8cute treatment o# pro"en crystal-induced arthritis is directed at relie# o# the pain and
in#lammation. 1onsteroidal anti-in#lammatory drugs ,1+8!Fs-, corticosteroids, colchicine, and
adrenocorticotropic hormone ,8=;(- are treatment options. ;he choice is based primarily on
'hether the patient has any concomitant health problems ,eg, renal insu##iciency or peptic ulcer
disease-. =olchicine, a classic treatment, is no' rarely indicated.
:hen comorbid conditions limit the use o# 1+8!Fs or colchicine, a pre#erred option may be an
intra-articular steroid in6ection, particularly 'hen a large, easily accessible 6oint is in"ol"ed.
+eptic arthritis must be reasonably e9cluded.
31
;herapy to control the underlying hyperuricemia generally is contraindicated until the acute
attac3 is controlled ,unless 3idneys are at ris3 because o# an unusually hea"y uric acid load-.
+tarting therapy to control hyperuricemia during an acute attac3 may intensi#y and prolong the
attac3. !# the patient has been on a consistent dosage o# probenecid or allopurinol at the time o#
the acute attac3, ho'e"er, the drug should be continued at that dosage during the attac3.
*urthermore, control o# hyperuricemia generally is not pursued #or a single attac3. !# attac3s are
recurrent or e"idence o# tophaceous or renal disease is present, therapy #or control o#
hyperuricemia is indicated.
4104, 10%, 10/5
-onsteroidal anti$inflammatory drugs
1+8!Fs are the drugs o# choice in most patients 'ith acute gout 'ho do not ha"e underlying
health problems. 8lthough indomethacin is the 1+8!F traditionally chosen #or acute gout, most
o# the other 1+8!Fs can be used as 'ell. +elect an agent 'ith a Iuic3 onset o# action. Fo not use
aspirin, because it can alter uric acid le"els and potentially prolong and intensi#y an acute attac3.
Ao'-dose aspirin alters uric acid le"els, increasing the ris3 o# gout attac3s and reIuiring close
uric acid monitoring 'hen aspirin is added to a uric acidMgout treatment regimen.
410$5
=ycloo9ygenase-2 ,=DS-2- inhibitors ha"e been used 'ith success, but patients may reIuire
higher dosages than are typically used.
410.5
8"oid 1+8!Fs in patients 'ith a history o# peptic ulcer disease or gastrointestinal ,G!- bleeding,
those 'ith renal insu##iciency or abnormal hepatic #unction, those ta3ing 'ar#arin ,a selecti"e
=DS-2 inhibitor can be used-, and those in the intensi"e care unit ,!=U- 'ho are predisposed to
gastritis. Aimit 1+8!F use in elderly patients, because o# the potential #or ad"erse central
ner"ous system ,=1+- e##ects. Use 1+8!Fs cautiously in patients 'ith diabetes and those 'ho
are recei"ing concomitant angiotensin-con"erting enEyme ,8=<- inhibitors.
;o control the acute attac3, 1+8!Fs are prescribed at #ull dosage #or 2-% days. Dnce the acute
attac3 is controlled. the dosage is reduced to appro9imately one hal# to one #ourth o# that amount.
;aper the dosage o"er appro9imately 2 'ee3s. Gout symptoms should be absent #or at least 2
days be#ore the 1+8!F is discontinued.
!olchicine
8lthough colchicine 'as once the treatment o# choice #or acute gout, it is no' less commonly
used than 1+8!Fs because o# its narro' therapeutic 'indo' and ris3 o# to9icity.
410&, 1105
;o be
e##ecti"e, colchicine therapy is ideally initiated 'ithin 3/ hours o# onset o# the acute attac3.
:hen used #or acute gout in classic hourly dosing regimens ,no longer recommended-,
colchicine causes ad"erse G! e##ects, particularly diarrhea and "omiting, in .07 o# patients.
Fosing recommendations #or colchicine in the treatment o# acute gout ha"e undergone
modi#ications as a'areness o# its to9icities has increased. 1e'er recommendations trend to'ard
lo'ered daily and cumulati"e doses.
410&, 1115
32
;he regimen currently #a"ored consists o# 1.2 mg o# colchicine, #ollo'ed by 0./ mg 1 hour later
to initiate treatment o# the early gout #lare. !n a multicenter, randomiEed, double-blind, placebo-
controlled, parallel-group study, ;er3altaub et al #ound that this regimen yielded both ma9imum
plasma concentration and early gout #lare e##icacy comparable 'ith those o# high-dose colchicine
,4.. mg total o"er / hours-, 'ith a sa#ety pro#ile indistinguishable #rom that o# placebo.
41125
Fata #rom $ separate drug-to-drug interaction ,FF!- studies suggests colchicine dose reductions
o# 33-//7 #or treatment o# acute gout and %0-$%7 #or prophyla9is 'hen colchicine is gi"en in
combination 'ith the e9tended-release calcium channel bloc3ers "erapamil and diltiaEem or 'ith
the numerous )-gp andMor =T)384 inhibitors ,eg, clarithromycin and cyclosporine- in addition,
patients should a"oid grape#ruit 6uice. Fosages o# colchicine did not ha"e to be ad6usted 'hen
the drug 'as used in combination 'ith aEithromycin.
41135
=olchicine should generally be a"oided i# the glomerular #iltration rate ,G*>- is lo'er than 10
mAMmin, and the dose should be decreased by at least hal# i# the G*> is lo'er than %0 mAMmin.
=olchicine should also be a"oided in patients 'ith hepatic dys#unction, biliary obstruction, or an
inability to tolerate diarrhea.
8 clinical response to colchicine is not pathognomonic #or gout. >esponses may also occur in
patients 'ith pseudogout, sarcoid arthropathy, psoriatic arthritis, or calci#ic tendonitis.
!n *ebruary 200., the U+ *ood and Frug 8dministration ,*F8- ruled that intra"enous ,!G-
colchicine can no longer be produced or shipped in the United +tates, because o# its to9icities.
=onseIuently, !G colchicine is no longer ad"ocated #or the treatment o# acute gout in the United
+tates.
41145
!orticosteroids
=orticosteroids can be gi"en to patients 'ith gout 'ho cannot use 1+8!Fs or colchicine.
+teroids can be gi"en orally, !G, intramuscularly ,!M-, or intra-articularly. Using parenteral
corticosteroids con#ers no ad"antage unless the patient cannot ta3e oral medications.
)rednisone can be gi"en at a dose o# appro9imately 40 mg #or 1-3 days, 'hich is then tapered
o"er appro9imately 2 'ee3s ,tapering more rapidly can result in a rebound #lare-. Monitor
closely #or corticosteroid e##ects. !# treatment continues #or more than 2 'ee3s, consider
measures to pre"ent osteoporosis.
!ntra-articular long-acting ,depot- corticosteroids are particularly use#ul in patients 'ith a
monoarticular #lare to help reduce the systemic e##ects o# oral steroids. <nsuring that the 6oint is
not in#ected be#ore in6ecting intra-articular corticosteroids is particularly important.
8n alternati"e to corticosteroid administration is to gi"e 8=;( ,40 !U subcutaneously, 'ith
repeat dosing as needed- to induce production o# corticosteroid by the patient2s o'n adrenal
glands. +uch a regimen does not depend on the patient #or proper tapering o# prednisone.
!ombination therapy
33
!# the patient does not ha"e an adeIuate response to initial therapy 'ith a single drug, 8=>
guidelines ad"ises that adding a second appropriate agent is acceptable. Using combination
therapy #rom the start is appropriate #or an acute, se"ere gout attac3, particularly i# the attac3
in"ol"es multiple large 6oints or is polyarticular. 8cceptable regimens include any o# the
#ollo'ing, in #ull or prophylactic doses as appropriate
41025
:
=olchicine plus 1+8!Fs
Dral corticosteroids plus colchicine
!ntra-articular steroids plus colchicine or 1+8!Fs
&reatment of !hronic Gout
:hen a patient e9periences a #irst attac3 o# gout, any medication regimens that may ha"e
contributed to the gout attac3 must be altered, and any predisposing medical conditions or habits
must be addressed.
411%5
)atients should be instructed to go on a diet i# obese, to stop drin3ing beer,
and to a"oid purine-rich #oods.
!n many cases, patients 'ho ha"e a #irst attac3 o# gout should undergo therapy 'ith agents that
lo'er uric acid, gi"en the high ris3 #or #urther in#lammatory attac3s and the potential #or
destructi"e tophaceous deposition in the bone, syno"ium, and 3idney, e"en 'ithout episodes o#
acute in#lammation. !# the #irst attac3 is not se"ere, ho'e"er, some rheumatologists ad"ocate
'aiting #or a second attac3 be#ore initiating such therapy not all patients e9perience a second
attac3, and some patients may reIuire con"incing that they need li#e-long therapy.
;he ris3 o# a second attac3 o# gout a#ter the #irst attac3 is /27 a#ter 1 year, $.7 a#ter 2 years,
and &37 a#ter 10 years. ;he decision to begin therapy depends partly on the baseline serum uric
acid le"els ,U& mgMdA denotes a higher ris3 #or recurrent gouty arthritis and tophi-.
8=> guidelines recommend pharmacologic urate-lo'ering therapy #or patients 'ith gout 'ho
ha"e 1 or more tophi on clinical e9amination or imaging study or ha"e #reIuent attac3s o# acute
gouty arthritis ,H2 attac3s per year-. Aess robust e"idence supports pharmacologic therapy #or
patients 'ith chronic 3idney disease o# stage 2 or 'orse or a past history o# urolithiasis.
41015
Aong-term management o# gout is #ocused on lo'ering uric acid le"els. ;he goal o# therapy is to
reduce serum uric acid le"els to belo' / mgMdA, at minimum. !n many cases, lo'ering uric acid
le"els to less than % mgMdA is necessary to impro"e the signs and symptoms o# gout. 8=>
guidelines recommend that once palpable tophi and all acute and chronic gout symptoms ha"e
resol"ed, serum uric acid le"els should be maintained belo' / mgMdA inde#initely.
41015
!n contrast, )ereE->uiE et al ha"e proposed that once dissolution o# e9isting urate crystals has
been achie"ed, less stringent control may su##ice to pre"ent #ormation o# ne' crystals.
411/5
!n their
prospecti"e cohort study o# 211 patients #rom 'hom urate-lo'ering therapy 'as 'ithdra'n
either a#ter % years i# no tophus 'as present at baseline or % years a#ter resolution o# the last
tophus, no patient 'ho maintained an a"erage serum urate le"el lo'er than $ mgMdA de"eloped a
crystal-pro"en recurrence o# gout.
34
8"oiding the use o# medications that ele"ate uric acid in patients 'ith gout is prudent. ;hus, in
patients 'ith hypertension, other agents are pre#erable to a thiaEide diuretic, pro"ided that blood
pressure can be managed easily 'ith a single drug. Ao'-dose aspirin is also uricosuric. ;he
angiotensin-receptor bloc3er ,8>@- losartan should be considered, because it is uricosuric at %0
mgMday. (o'e"er, medications that ele"ate uric acid can still be used, i# reIuired, by ma3ing
appropriate ad6ustments o# allopurinol or probenecid doses.
Urinary e9cretion amounting to less than .00 mg per 24-hour period on an unrestricted diet is
considered undere9cretion. Undere9creting patients are candidates #or uricosuric therapy 'ith
probenecid. ;he dosage is increased at monthly inter"als until the uric acid le"el is lo'ered to
target. Urinary al3aliEation ,eg, 'ith potassium citrate- and ingestion o# copious amounts o# #luid
are ad6uncti"e recommendations.
!n patients 'ith gout 'ho ha"e renal disease, 8=> guidelines recommend 9anthine o9idase
inhibitor therapy 'ith either allopurinol or #ebu9ostat as the #irst-line pharmacologic approach.
)robenecid can be used in patients 'ho ha"e contraindications to or are intolerant o# at least 1 o#
those #irst-line agents, or it may be combined 'ith a 9anthine o9idase inhibitor i# the inhibitor
does not lo'er uric acid su##iciently.
41015
)robenecid could also be used #or those patients 'ho
consider the ris3s o# 9anthine o9idase inhibitors to be too high.
;he 8=> ad"ises, ho'e"er, that monotherapy 'ith probenecid is not a #irst-line choice in
patients 'ith a creatinine clearance o# less than %0 mAMmin.
41015
!n addition, drug interactions may
occur 'ith probenecid ,see Medication-.
Prophyla#is
@ecause allopurinol, #ebu9ostat, and probenecid change serum and tissue uric acid le"els, they
may precipitate acute attac3s o# gout. ;o reduce this undesired e##ect, colchicine or lo'-dose
1+8!F treatment is pro"ided #or at least / months. !n patients 'ho cannot ta3e colchicine or
1+8!Fs, lo' doses o# prednisone can be considered. :hen used prophylactically, colchicine can
reduce such #lares by .%7.
411$5
)atients 'ith gout may be able to abort an attac3 by ta3ing a single
colchicine tablet at the #irst t'inge o# an attac3.
;he standard dosage o# colchicine #or prophyla9is is 0./ mg t'ice daily, but lo'er dosages ha"e
also been suggested. +igni#icant dosage reduction is critical #or patients 'ho are also ta3ing
calcium channel bloc3ers ,eg, "erapamil or diltiaEem- and any o# the large number o# )-gp or
=T)384 inhibitors ,eg, clarithromycin or cyclosporine-. !n patients 'ith renal insu##iciency, the
dosing #reIuency may ha"e to be decreased to once daily or e"ery other day.
8d"erse G! e##ects are uncommon 'ith this dosage, occurring in only 47 o# patients. ;his stands
in contrast to the .07 ris3 o# ad"erse G! e##ects 'ith the classic hourly colchicine regimen #or
the treatment o# acute gout.
<"en in prophylactic doses, ho'e"er, long-term use o# colchicine can lead to marro' to9icity
and to neuromyopathy, 'ith ele"ated le"els o# creatine 3inase and resulting muscle 'ea3ness.
=olchicine-induced neuromyopathy is a particular ris3 in patients 'ith renal insu##iciency.
411.5
35
!# the patient de"elops a gout #lare a#ter beginning therapy 'ith a uric acid0lo'ering agent, the
agent should not be discontinued, because discontinuance 'ill only cause another #lu9 in the uric
acid le"el, 'hich may prolong and intensi#y the attac3.
*llopurinol
8llopurinol bloc3s 9anthine o9idase and thus reduces the generation o# uric acid. 8ppro9imately
3-107 o# patients ta3ing allopurinol de"elop symptoms o# intolerance, such as dyspepsia,
headache, diarrhea, or pruritic maculopapular rash.
Aess #reIuently ,17 o# cases-, patients ta3ing allopurinol can de"elop se"ere allopurinol
hypersensiti"ity syndrome, 'hich carries a mortality o# 20-307.
411&5
*eatures o# this syndrome
include #e"er, to9ic epidermal necrolysis, bone marro' suppression, eosinophilia, leu3ocytosis,
renal #ailure, hepatic #ailure, and "asculitis. =orticosteroids are o#ten used to treat se"ere
allopurinol hypersensiti"ity syndrome.
+e"ere allopurinol hypersensiti"ity syndrome is more li3ely to occur in patients 'ith renal
insu##iciency, those 'ho are ta3ing a thiaEide diuretic, and those started on allopurinol at a
dosage o# 300 mgMday.
41205
!n addition, strong associations ha"e been #ound bet'een se"ere
allopurinol hypersensiti"ity reactions and carriage o# the (A80@V%.01 allele.
41215
8=> guidelines recommend considering screening #or (A80@V%.01 carriage, using a
polymerase chain reaction0based test, in selected high-ris3 patients be#ore starting allopurinol.
)atients at particularly high ris3 are 3no'n to include those o# (an =hinese or ;hai descent
Joreans are also at ris3, i# they ha"e stage 3 or 'orse chronic 3idney disease.
41015
!t is unclear
'hether such precautions are necessary 'ith a 100-mg starting dose o# allopurinol. 8dditionally,
a"ailability o# this test may be an issue.
+e"ere allopurinol hypersensiti"ity syndrome may present as +te"ens-?ohnson syndrome or as
drug rash 'ith eosinophilia and systemic symptoms ,F><++- syndrome. F><++ syndrome
a##ects the li"er, 3idney, and s3in. !t is a delayed-hypersensiti"ity response occurring /-. 'ee3s
a#ter initiation o# allopurinol. ;he underlying mechanism is thought to be a cell-mediated
immune reaction to allopurinol and its metabolites. 8lthough the #reIuency is only is 0.47, the
rate o# organ #ailure and death is high. ;reatment is 'ith !G N- acetylcysteine and steroids.
8llopurinol should immediately be discontinued in patients 'ho de"elop pruritus or a rash
consistent 'ith allopurinol hypersensiti"ity.
!n most patients, start allopurinol at 100 mgMday ,%0 mgMday in patients 'ith renal insu##iciency-.
+tamp et al ha"e proposed that the ris3 o# allopurinol hypersensiti"ity may be reduced by starting
allopurinol at a dose o# 1.% mg per unit o# estimated G*>.
41225
8d6ust the dosage up'ard e"ery 2-% 'ee3s according to the uric acid le"el until the goal o# a uric
acid le"el o# / mgMdA or less is achie"ed. Dnce the target uric acid le"el has been achie"ed and
maintained #or / months, discontinue colchicine prophyla9is, unless the patient has 1 or more
tophi on clinical e9am.
36
)re"iously, ad6usting the allopurinol maintenance dosage to the creatinine clearance rate 'as
recommended #or patients 'ith renal insu##iciency. (o'e"er, GWEIueE-Mellado et al #ound no
increase in the pre"alence o# ad"erse reactions to allopurinol in patients 'ho 'ere started at an
ad6usted dosage but subseIuently had their dosage raised to meet therapeutic targets.
41235
8=> guidelines ad"ise that the dosage o# allopurinol can be raised abo"e 300 mgMday, e"en in
patients 'ith renal impairment, pro"ided that the patient recei"es adeIuate education and
monitoring #or drug to9icity ,including measurement o# transaminase le"els-. ;he ma9imum
dosage o# allopurinol appro"ed by the U+ *ood and Frug 8dministration ,*F8- is .00 mgMday,
41015
but the ma9imum dosage should be lo'er in patients 'ith chronic 3idney disease.
@e'are o# drug interactions. *or e9ample, allopurinol prolongs the hal#-li#e o# aEathioprine and
/-mercaptopurine. !t enhances the bone marro' to9icity o# cyclophosphamide. )atients ta3ing
concomitant ampicillin are at an increased ris3 o# rash.
8llopurinol can be used in combination 'ith probenecid. (o'e"er, note that probenecid
increases the e9cretion o# allopurinol.
!n a retrospecti"e 24-month study o# gout patients 'ho had been prescribed allopurinol, >iedel et
al #ound that only 1.7 o# them #illed all their prescriptions throughout the entire #ollo'-up
period and thus 'ere presumably compliant 10.47 #illed only a single prescription.
41245
!n
contrast, >ees et al reported that 'hen patients recei"ing urate-lo'ering therapy 'ere gi"en a
predominantly nurse-deli"ered inter"ention that included education and indi"idualiEed li#estyle
ad"ice, &27 achie"ed target serum uric acid le"els at 1 year.
412%5
+ebu#ostat
*ebu9ostat, a nonpurine selecti"e inhibitor o# 9anthine o9idase, is a potential alternati"e to
allopurinol in patients 'ith gout.
412/, 12$5
*ebu9ostat is administered orally and is metaboliEed
mainly in the li"er. !n contrast, allopurinol and its metabolites are e9creted primarily by the
3idney. ;here#ore, #ebu9ostat can be used in patients 'ith renal impairment 'ith no dosage
ad6ustment.
412.5
!t is more e9pensi"e than allopurinol.
;he =D1*!>M+ trial demonstrated the e##icacy and sa#ety o# #ebu9ostat in lo'ering
hyperuricemia. @y / months, the primary endpointOa serum uric acid le"el o# less than /.0
mgMdAO'as achie"ed in 4%7 o# sub6ects on #ebu9ostat 40 mgMday, /$7 on #ebu9ostat .0
mgMday, and 427 on allopurinol. !n sub6ects 'ith renal impairment, the primary endpoint 'as
achie"ed in %07 o# sub6ects on #ebu9ostat 40 mgMday, $27 on #ebu9ostat .0 mgMday, and 427
on allopurinol. 8d"erse e"ent rates 'ere lo' and similar in all groups.
412&5
!n patients aged /% years or older, the primary endpoint 'as achie"ed in /27 on #ebu9ostat 40
mgMday, .27 on #ebu9ostat .0 mgMday, and 4$7 on allopurinol. ;hese #igures remained
essentially unchanged in sub6ects 'ith mild-to-moderate renal impairment.
41305
!n 8#rican-8merican sub6ects, the primary endpoint 'as reached in 4$7 on #ebu9ostat 40
mgMday, /.7 on #ebu9ostat .0 mgMday, and 437 on allopurinol. +imilar rates 'ere seen in
37
sub6ects 'ith renal impairment.
41315
8d"erse e"ent rates in both subgroups 'ere comparable 'ith
those in the o"erall trial.
;he e##icacy and sa#ety o# #ebu9ostat in 'omen 'as demonstrated in the =D1*!>M+ trial and in
2 other trials comparing #ebu9ostat and allopurinol: *8=; ,*ebu9ostat Gersus 8llopurinol
=ontrolled ;rial- and 8)<S ,8llopurinol- and )lacebo-=ontrolled, <##icacy +tudy o#
*ebu9ostat-. 8chie"ement o# a uric acid le"el belo' /.0 mgMdA rose 'ith increasing daily doses
o# #ebu9ostat doses, #rom %4.37 in patients recei"ing 40 mg to 1007 in those recei"ing 240 mg,
compared 'ith 4%.&7 'ith allopurinol. >esults 'ere similar in sub6ects 'ith renal impairment.
41325
"ricase
1onrecombinant urate-o9idase ,uricase- is used in <urope to pre"ent se"ere hyperuricemia
induced by chemotherapy in patients 'ith malignancies, as 'ell as in selected patients 'ith
treatment-re#ractory gout. +hort-term use o# such agents in patients 'ith se"ere tophaceous gout
could debul3 the total-body urate load, allo'ing maintenance 'ith probenecid or allopurinol.
!n 200&, the *F8 appro"ed recombinant uricase ,rasburicase- #or the pre"ention o# tumor lysis
syndrome. (o'e"er, it is highly immunogenic and may cause anaphyla9is.
41335
!n 2010, a polyethylene-glycol0con6ugated uricase ,pegloticase- 'as appro"ed by the *F8 #or
gout. )egloticase, 'hich enEymatically catalyEes the o9idation o# uric acid to allantoin, is an !G
biologic agent to be considered 'hen ad6ustment o# contributing medications ,eg, diuretics- and
treatment 'ith allopurinol, #ebu9ostat, and uricosuric agents are insu##icient to achie"e
appropriate reduction o# serum uric acid le"els.
41015
;he <uropean Medicines 8gency ,<M8- is no' 'eighing appro"al o# pegloticase in <urope.
8ppro"al 'as recommended by an e9pert ad"isory committee.
41345
8d"erse e##ects o# pegloticase include anaphyla9is, in#usion reactions, gout #lares, and
e9acerbation o# congesti"e heart #ailure. 8t present, substantial e9pense compromises its cost-
e##ecti"eness as an initial approach.
413%5
;he 8=> guidelines do not recommend pegloticase as a
#irst-line approach.
.ther therapeutic options
@enEbromarone is an e##ecti"e uricosuric agent a"ailable on a restricted basis only outside the
United +tates. (o'e"er, it has been 'ithdra'n because it causes #ulminant hepatoto9icity.
Gitamin =, 'ith its uricosuric e##ect, may reduce the serum concentration o# uric acid. !n one
study, %00 mgMday #or 2 months reduced uric acid by a mean o# 0.% mgMdA in patients 'ithout
gout.
413/5
(o'e"er, gout patients appear to be less responsi"e to such a lo' dose o# ascorbate.
Gitamin = treatment should be a"oided in patients 'ith nephrolithiasis, urate nephropathy, or
cystinuria.
38
!n an open-label pilot study o# 10 patients 'ith re#ractory acute gout treated 'ith the interleu3in
,!A--1 antagonist ana3inra, pain 'as substantially reduced in all patients 'ithin 2 days, 'ithout
side e##ects. =linical signs o# in#lammation had disappeared in & o# 10 patients by day 3 o#
treatment.
413$5
;he lipid-lo'ering drug #eno#ibrate, a #ibric acid deri"ati"e, lo'ers serum uric acid le"els 'hile
reducing "ery-lo'-density lipoprotein ,GAFA-, total cholesterol, and triglyceride le"els.
413.5
(o'e"er, the creatinine le"el increases, and all e##ects are negated once the drug has been
discontinued.
41335
!anakinumab
!n 2010, an .-'ee3, single-blind, double-dummy, dose-ranging study sho'ed that the selecti"e
!A-1K antibody cana3inumab yielded #ast and lasting relie# o# pain in patients 'ith acute gouty
arthritis #lares re#ractory to treatment 'ith 1+8!Fs or colchicine.
413&5
(o'e"er, in ?une 2011,
cana3inumab 'as denied appro"al by the *F8.
41405
,+ee *F8 )anel +ays 1o to =ana3inumab #or
Gout 8ttac3s.-
Diet and *cti'ity
@ecause uric acid is a brea3do'n product o# purine, high-purine #oods should be either a"oided
or consumed only in moderation. *oods "ery high in purines include organ meats such as
s'eetbreads ,eg, pancreas and thymus-, smelt, sardines, and mussels. *oods moderately high in
purines include ancho"ies, trout, haddoc3, scallops, mutton, "eal, li"er, bacon, salmon, 3idneys,
and tur3ey.
)urines are #ound in all protein #oods. 8ll sources o# purines cannot and should not be
eliminated.
D"erall, purine restriction generally reduces serum uric acid le"els by no more than 1 mgMmA,
'ith modest impact, and diets 'ith "ery lo' purine content are not palatable. Fiet modi#ications
alone are rarely able to lo'er uric acid le"els su##iciently to pre"ent accumulation o# urate, but
they may help lessen the triggers o# acute gout attac3s.
)atients 'ith gout should a"oid e9cess ingestion o# alcoholic drin3s, particularly beer, because
alcohol use ele"ates uric acid le"els and thus can precipitate attac3s o# gout. !ndeed, hea"y
drin3ers are much more li3ely to ha"e recurrent gout attac3s, e"en 'ith allopurinol therapy.
Moderate 'ine inta3e is not associated 'ith increased de"elopment o# incident gout,
435
but
e9cesses o# any #orm o# alcohol in gout patients are associated 'ith acute gout #lares.
)atients should a"oid sodas and other be"erages or #oods s'eetened 'ith high-#ructose corn
syrup. ;hey should also limit their use o# naturally s'eet #ruit 6uices, table sugar, and s'eetened
be"erages and desserts, as 'ell as table salt.
41015
)atients ta3ing colchicine should a"oid grape#ruit
and grape#ruit 6uice.
39
Maintaining a high le"el o# hydration 'ith 'ater ,at least . glasses o# liIuids per day- may be
help#ul in a"oiding attac3s o# gout. !n "ie' o# the association o# gout 'ith atherosclerosis, the
diagnosis o# gout may a##ord a particularly good opportunity #or the clinician to ad"ise a lo'-
cholesterol, lo'-#at diet i# such a diet is other'ise appropriate #or the patient. 8lthough a diet o#
this type may help uric acid le"els, such ad"ice should be gi"en primarily to help pre"ent
atherosclerosis.
:eight reduction in patients 'ho are obese can impro"e hyperuricemia. Jetosis-inducing diets
,eg, #asting- should be a"oided, ho'e"er.
@ecause acute attac3s are already su##iciently limiting o# acti"ity, additional limitations o#
acti"ity are not necessary. ;he patient should a"oid trauma to the a##ected 6oint other'ise, they
should be acti"e.
!onsultations
>heumatologists should be in"ol"ed in the care o# patients 'ith di##icult gout, as ad"ised in the
8=> guidelines. ;hey can establish the diagnosis 'ith arthrocentesis and syno"ial #luid analysis
#or crystals. ;hey also are s3illed in the management o# this disorder, and consultation may be
help#ul #or patients 'ith an acute gout attac3 that does not respond to 1+8!Fs 'ithin 2 days or
to colchicine 'ithin 1 day, as 'ell as #or patients 'ith re#ractory hyperuricemia.
>heumatology or orthopedic consultation is indicated #or any patient 'ith septic arthritis or #or
any patient in 'hom a septic arthritis cannot be ruled out.
/ong$&erm Monitoring
8#ter diagnosis and treatment o# an acute gouty arthritis episode, the patient should return #or a
#ollo'-up "isit in appro9imately 1 month to be e"aluated #or therapy to lo'er serum uric acid
le"els.
!# uric acid0lo'ering therapy is begun, patients should be seen 'ithin 2 'ee3s to ensure that no
unto'ard to9icity has de"eloped and then e"ery 1-2 months 'hile medication dosages are
ad6usted to achie"e the target uric acid le"el o# %-/ mgMdA. Dnce this le"el is achie"ed and
maintained, patients can be seen e"ery /-12 months and their serum uric acid monitored to help
assess e##icacy and adherence.
Gout and Pseudogout Medication

D"er"ie'
)resentation
40
FF9
:or3up
;reatment
Medication
)rint this section

Medication +ummary
1+8!Fs
Uricosuric 8gents
=orticosteroids
Santhine D9idase !nhibitors
>heumatologics, Dther
=orticotropic (ormones
+ho' 8ll
Multimedia Aibrary
>e#erences
Medication Summary
8cute in#lammation due to gout can be treated 'ith nonsteroidal anti-in#lammatory drugs
,1+8!Fs-, corticosteroids, or colchicine. 1+8!Fs are the most commonly used drugs in acute
gout.
D"er the long term, gout is treated by decreasing tissue stores o# uric acid 'ith the 9anthine
o9idase inhibitors allopurinol or #ebu9ostat or 'ith the uricosuric agent probenecid. @ecause
agents that lo'er uric acid can precipitate attac3s o# gout, lo'-dose colchicine is typically used
as prophyla9is ,usually #or / months- 'hen such therapy is initiated.
!# these measures, along 'ith ad6ustment o# contributing medications ,eg, diuretics-, do not result
in appropriate reduction o# serum uric acid le"els, uric acidXlo'ering treatment is escalated as
recommended in the 2012 8merican =ollege o# >heumatology ,8=>- gout guidelines.
4101, 1025
41
Dther agents lo'er uric acid le"els as a secondary e##ect. ;he angiotensin-receptor bloc3er
,8>@- losartan is moderately uricosuric at %0 mgMday. ;he lipid-lo'ering agent #eno#ibrate
reduces serum urate 1&7 and increases clearance by 3/7 at 200 mgMday.
4425

D"er"ie'
)resentation
FF9
:or3up
;reatment
Medication
)rint this section

Medication +ummary
1+8!Fs
Uricosuric 8gents
=orticosteroids
+ho' 8ll
Multimedia Aibrary
>e#erences
Medication Summary
42
gout.
4101, 1025
4425
1e9t +ection: Uricosuric 8gents
-S*IDs
!lass Summary
8s a class, 1+8!Fs are the drugs most 'idely used to treat the pain and in#lammation o# acute
gout attac3s in patients 'ho can sa#ely ta3e these medications. 8lthough 1+8!F e##ects on pain
tend to be patient-speci#ic, napro9en and indomethacin are common choices. 1e"ertheless, the
choice o# an 1+8!F is a matter more o# habit than o# science. Use o# concomitant gastric
protection 'ith misoprostol or consideration o# a cycloo9ygenase-2 ,=DS-2-0speci#ic 1+8!F
might be considered i# the patient has gastrointestinal ,G!- ris3 or is older than %1 years.
;o control the attac3 as Iuic3ly and sa#ely as possible ,recalling that it ta3es % hal#-li"es to reach
steady state-, consider using an 1+8!F 'ith a short hal#-li#e ,eg, 3etopro#en, ibupro#en, or
diclo#enac-. Use the ma9imum dosage o# 1+8!F, and taper o"er appro9imately 10-14 days,
depending on patient response.
Gie' #ull drug in#ormation
-apro#en 0*napro#1 -aprelan1 -aprosyn2

1apro9en is used #or relie# o# mild to moderate pain. !t inhibits in#lammatory reactions and pain
by decreasing acti"ity o# the enEyme cycloo9ygenase, resulting in prostaglandin synthesis.
43
3etoprofen

Jetopro#en is used #or the relie# o# mild-to-moderate pain and in#lammation. +mall doses are
initially indicated in small and elderly patients and in those 'ith renal or li"er disease. !ndi"idual
doses greater than $% mg do not increase therapeutic e##ects. 8dminister high doses 'ith caution,
and closely obser"e the patient #or response.
Diclofenac 04oltaren 5R1 !ataflam1 *rthrotec2

Ficlo#enac inhibits prostaglandin synthesis by decreasing acti"ity o# the enEyme
cycloo9ygenase, 'hich in turn decreases #ormation o# prostaglandin precursors.
Indomethacin 0Indocin2

!ndomethacin has been the 1+8!F traditionally used to treat acute in#lammation in gout, though
other 1+8!Fs are e##ecti"e in this setting as 'ell. Ai3e all 1+8!Fs, indomethacin bloc3s
cycloo9ygenase and thereby reduces the generation o# prostaglandins.
!eleco#ib 0!elebre#2

Unli3e most 1+8!Fs, 'hich inhibit both =DS-1 and =DS-2, the selecti"e =DS-2 inhibitor
celeco9ib o##ers the possibility o# relie"ing in#lammation and pain, but 'ith a lo'er ris3 o# G!
side e##ects. !t has been suggested that =DS-2 e9pression in monocytes is induced in response to
urate crystals.
+e"eral studies ha"e #ound that selecti"e =DS-2 inhibitors are comparable to other 1+8!Fs #or
treating acute gouty arthritis. (o'e"er, celeco9ib reIuires particularly high doses to pro"ide pain
relie# comparable to that pro"ided by indomethacin in acute gout.
410.5
+electi"e =DS-2 inhibitors may increase the ris3 o# cardiac disease 1 drug in this class,
ro#eco9ib, has already been remo"ed #rom the mar3et #or this reason. =eleco9ib is currently
under in"estigation #or associated ris3 o# accelerated cardiac disease. =uriously, the ris3 appears
44
to be associated 'ith ingestion o# 200 mg t'ice daily, but not 'ith ingestion o# 400 mg once
daily.

D"er"ie'
)resentation
FF9
:or3up
;reatment
Medication
)rint this section

Medication +ummary
1+8!Fs
Uricosuric 8gents
=orticosteroids
+ho' 8ll
Multimedia Aibrary
>e#erences
Medication Summary
45
gout.
4101, 1025
4425
1e9t +ection: Uricosuric 8gents
-S*IDs
!lass Summary

46
3etoprofen




urate crystals.
410.5
47
daily.
napro#en 0R#1 .&!2 $ *le'e1 E! -aprosyn1
more66*napro#1 *napro# DS1 -aprosyn1
Midol E#tended Relief1 -apro# Sodium1
-apro#en E!1 -apro#en SR1 -aprelan1
Pamprin *ll Day
=lass: 1+8!Fs

Fosing Q Uses
!nteractions
8d"erse <##ects
:arnings
)regnancy
)harmacology
!mages
)atient (andout
*ormulary
Dosing , "ses
8dult)ediatric
Dosing +orms , Strengths
Pain
%00 mg )D initially, then 2%0 mg )D I/-.hr or %00 mg )D I12hr )>1 not to e9ceed 12%0
mgMday napro9en base on day 1 subseIuent daily doses should not e9ceed 1000 mg napro9en
base
48
<9tended release: $%0-1000 mg )D IFay may temporarily increase to 1%00 mgMday i# tolerated
'ell and clinically indicated
Rheumatoid *rthritis1 .steoarthritis1 *nkylosing Spondylitis
%00-1000 mgMday )D di"ided I12hr may increase to 1%00 mgMday i# tolerated 'ell #or limited
time
<9tended release: $%0-1000 mg )D IFay may temporarily increase to 1%00 mgMday i# tolerated
'ell and clinically indicated
Dysmenorrhea
%00 mg )D initially, then 2%0 mg )D I/-.hr or %00 mg )D I12hr ,long-acting #ormula- not to
e9ceed 12%0 mgMday on #irst day subseIuent doses should not e9ceed 1000 mgMday napro9en
base
Gout1 *cute
$%0 mg )D initially, #ollo'ed by 2%0 mg I.hr until attac3 subsides
<9tended release: 1000-1%00 mg IFay, #ollo'ed by 1000 mg IFay until attac3 subsides
Migraine
$%0 mg )D initially, may gi"e additional 2%0-%00 mg i# necessary not to e9ceed 12%0 mg in 24
hr
Dosing !onsiderations
220 mg o# napro9en sodium contains 200 mg o# napro9en
Felayed-release #ormulation not recommended #or acute pain
;a3e 'ith #ood or .-12 oE o# 'ater to a"oid gastrointestinal ,G!- e##ects
Dosing Modifications
=r=l R30 mAMmin: Use not recommended
diclofenac 0R#2 $ !ataflam1 4oltaren$5R1
more66!ambia1 7ipsor1 7or'ole#
49
=lass: 1+8!Fs

Fosing Q Uses
!nteractions
8d"erse <##ects
:arnings
)regnancy
)harmacology
!mages
)atient (andout
*ormulary
Dosing , "ses
8dult)ediatric
Rheumatoid *rthritis1 .steoarthritis
Ficlo#enac potassium: %0 mg )D I.-12hr
Ficlo#enac sodium: %0 mg )D I.hr or $% mg )D I12hr
<9tended release: 100 mg )D once daily may be increased to 100 mg )D I12hr
*nkylosing Spondylitis
Ficlo#enac sodium: 2% mg )D 4 or % times daily
Ficlo#enac potassium: %0 mg )D I12hr
Dysmenorrhea
!mmediate-release ,=ata#lam-: 100 mg )D once, then %0 mg )D I.hr )>1
Mild$to$Moderate *cute Pain
50
!mmediate-release tab ,=ata#lam-: 100 mg )D once, then %0 mg )D I.hr )>1
Nipsor: 2% mg )D #our times daily )>1
Nor"ole9: 1. mg or 3% mg )D three times daily
*cute Migraine
Dral solution: %0 mg ,1 pac3et- in 30-/0 mA o# 'ater, mi9ed 'ell and drun3 immediately
1ot #or prophyla9is
Ficlo#enac potassium: =ambia, =ata#lam, Nipsor
Ficlo#enac sodium: Goltaren S>
*dministration
;abletMcapsule: ;a3e 'ith #ood or .-12 oE o# 'ater to a"oid G! ad"erse e##ects
Dral solution: Fo not use liIuids other than 'ater to reconstitute #oods decrease e##ecti"eness
May be combined 'ith misoprostol
indomethacin 0R#2 $ Indocin1 Indocin SR1
more66&i'orbe#
=lass: 1+8!Fs

Fosing Q Uses
!nteractions
8d"erse <##ects
:arnings
)regnancy
)harmacology
51
8dministration
!mages
)atient (andout
*ormulary
Dosing , "ses
8dult)ediatric
Inflammatory8Rheumatoid Disorders
!mmediate release: 2%-%0 mg )DM)> I.-12hr not to e9ceed 200 mgMday
<9tended release: $%-1%0 mgMday )D in single daily dose or di"ided I12hr not to e9ceed 1%0
mgMday
ursitis8&endinitis
!mmediate-release: $%-1%0 mgMday )DM)> di"ided I/-.hr
<9tended-release: $%-1%0 mgMday )D in single daily dose or di"ided I12hr
*cute Gouty *rthritis
%0 mg )DM)> I.hr #or 3-% days reduced once pain is under control
-ephrogenic Diabetes Insipidus
2 mgM3gMday )D di"ided I.hr
Pain
;i"orbe9: !ndicated #or mild-to-moderate acute pain
20 mg )D ;!F or 40 mg )D @!FM;!F
Geriatric
52
Monitor renal #unction ,drug is renally e9creted- decreased renal #unction more li3ely in
elderly
!ndomethacin is nonsteroidal anti-in#lammatory drug ,1+8!F- producing most central
ner"ous system ,=1+- ad"erse reactions in elderly
Ao'est dose and #reIuency recommended
*dministration
;a3e 'ith #ood or .-12 oE o# 'ater to a"oid gastrointestinal ,G!- e##ects
Drug Interactions
Interaction Checker
indomethacin and
Type a drug,

No Interactions Found
Interactions Found
Contraindicated
Serious - Use Alternative
Signifcant - Monitor Closely
Minor
Sort by :
SEVERITY

NAME
53
Contraindicated (0)
Serious - Use Alternative (5)
apixaban
indomethacin and api9aban both increase anticoagulation. (igh li3elihood serious or li#e-
threatening interaction. =ontraindicated unless bene#its out'eigh ris3s and no alternati"es
a"ailable.
ketoroac
indomethacin, 3etorolac. <ither increases to9city o# the other by pharmacodynamic
synergism. (igh li3elihood serious or li#e-threatening interaction. =ontraindicated unless
bene#its out'eigh ris3s and no alternati"es a"ailable. 1e"er use combination.
ketoroac intranasa
indomethacin, 3etorolac intranasal. <ither increases to9city o# the other by
pharmacodynamic synergism. (igh li3elihood serious or li#e-threatening interaction.
=ontraindicated unless bene#its out'eigh ris3s and no alternati"es a"ailable. 1e"er use
combination.
methotrexate
indomethacin increases le"els o# methotre9ate by decreasing renal clearance. )ossible
serious or li#e-threatening interaction. Monitor closely. Use alternati"es i# a"ailable.
=oncomitant administration o# 1+8!Fs 'ith high dose methotre9ate has been reported to
ele"ate and prolong serum methotre9ate le"els, resulting in deaths #rom se"ere
hematologic and G! to9icity. 1+8!Fs may reduce tubular secretion o# methotre9ate and
enhance to9icity. .
pemetrexed
indomethacin increases le"els o# pemetre9ed by unspeci#ied interaction mechanism.
)ossible serious or li#e-threatening interaction. Monitor closely. Use alternati"es i#
a"ailable.
Signifcant - Monitor Closely (22)
acebutoo
acebutolol and indomethacin both increase serum potassium. )otential #or interaction,
monitor.
indomethacin decreases e##ects o# acebutolol by pharmacodynamic antagonism.
+igni#icant interaction possible, monitor closely. Aong term ,U1 '3- 1+8!F use.
1+8!Fs decrease prostaglandin synthesis.
54
aceco!enac
aceclo#enac and indomethacin both increase anticoagulation. )otential #or interaction,
monitor.
aceclo#enac and indomethacin both increase serum potassium. )otential #or interaction,
monitor.
acemetacin
acemetacin and indomethacin both increase anticoagulation. )otential #or interaction,
monitor.
acemetacin and indomethacin both increase serum potassium. )otential #or interaction,
monitor.
a"rimon#
indomethacin and agrimony both increase anticoagulation. )otential #or interaction,
monitor.
abutero
indomethacin increases and albuterol decreases serum potassium. <##ect o# interaction is
not clear, use caution. )otential #or interaction, monitor.
a!a!a
indomethacin and al#al#a both increase anticoagulation. )otential #or interaction, monitor.
a!u$osin
indomethacin decreases e##ects o# al#uEosin by pharmacodynamic antagonism.
+igni#icant interaction possible, monitor closely. 1+8!Fs decrease prostaglandin
synthesis.
atepase
indomethacin and alteplase both increase anticoagulation. )otential #or interaction,
monitor. )otential #or increased ris3 o# bleeding, caution is ad"ised.
american "insen"
indomethacin and american ginseng both increase anticoagulation. )otential #or
interaction, monitor.
amioride
55
amiloride and indomethacin both increase serum potassium. )otential #or dangerous
interaction. Use 'ith caution and monitor closely.
antithrombin a!a
antithrombin al#a and indomethacin both increase anticoagulation. )otential #or
dangerous interaction. Use 'ith caution and monitor closely.
antithrombin iii
antithrombin iii and indomethacin both increase anticoagulation. )otential #or dangerous
ar!ormotero
indomethacin increases and ar#ormoterol decreases serum potassium. <##ect o# interaction
is not clear, use caution. )otential #or interaction, monitor.
ar"atroban
argatroban and indomethacin both increase anticoagulation. )otential #or dangerous
asenapine
indomethacin decreases e##ects o# asenapine by pharmacodynamic antagonism.
synthesis.
aspirin
aspirin and indomethacin both increase anticoagulation. )otential #or interaction, monitor.
aspirin and indomethacin both increase serum potassium. )otential #or interaction,
monitor.
aspirin recta
aspirin rectal and indomethacin both increase anticoagulation. )otential #or interaction,
monitor.
aspirin rectal and indomethacin both increase serum potassium. )otential #or interaction,
monitor.
aspirin%citric acid%sodium bicarbonate
56
aspirinMcitric acidMsodium bicarbonate and indomethacin both increase anticoagulation.
)otential #or interaction, monitor.
aspirinMcitric acidMsodium bicarbonate and indomethacin both increase serum potassium.
atenoo
atenolol and indomethacin both increase serum potassium. )otential #or interaction,
monitor.
indomethacin decreases e##ects o# atenolol by pharmacodynamic antagonism. +igni#icant
interaction possible, monitor closely. Aong term ,U1 '3- 1+8!F use. 1+8!Fs decrease
prostaglandin synthesis.
a$&ce't
aE#icel-t, indomethacin. Dther ,see comment-. +igni#icant interaction possible, monitor
closely. =omment: )atients ta3ing 1+8!F+ may e9perience increased bruising or
bleeding at biopsy andMor in6ection sites. =oncomitant use o# 1+8!Fs is not
recommended.
a$isartan
indomethacin, aEilsartan. <ither increases to9city o# the other by Dther ,see comment-.
+igni#icant interaction possible, monitor closely. =omment: May result in renal #unction
deterioration, particularly in elderly or "olume depleted indi"iduals.
indomethacin decreases e##ects o# aEilsartan by pharmacodynamic antagonism. )otential
#or dangerous interaction. Use 'ith caution and monitor closely. 1+8!Fs decrease
synthesis o# "asodilating renal prostaglandins, and thus a##ect #luid homeostasis and may
diminish antihypertensi"e e##ect.
bambutero
indomethacin increases and bambuterol decreases serum potassium. <##ect o# interaction
bemiparin
bemiparin and indomethacin both increase anticoagulation. )otential #or dangerous
bena$epri
57
indomethacin decreases e##ects o# benaEepril by pharmacodynamic antagonism. )otential
#or dangerous interaction. Use 'ith caution and monitor closely. )otential #or dangerous
interaction. Use 'ith caution and monitor closely. 1+8!Fs decrease synthesis o#
"asodilating renal prostaglandins, and thus a##ect #luid homeostasis and may diminish
antihypertensi"e e##ect.
benaEepril, indomethacin. <ither increases to9city o# the other by Dther ,see comment-.
bendro(umethia$ide
indomethacin increases and bendro#lumethiaEide decreases serum potassium. <##ect o#
interaction is not clear, use caution. )otential #or interaction, monitor.
betaxoo
beta9olol and indomethacin both increase serum potassium. )otential #or interaction,
monitor.
indomethacin decreases e##ects o# beta9olol by pharmacodynamic antagonism.
bisoproo
bisoprolol and indomethacin both increase serum potassium. )otential #or interaction,
monitor.
indomethacin decreases e##ects o# bisoprolol by pharmacodynamic antagonism.
bi)airudin
bi"alirudin and indomethacin both increase anticoagulation. )otential #or dangerous
budesonide
indomethacin, budesonide. <ither increases to9city o# the other by pharmacodynamic
synergism. +igni#icant interaction possible, monitor closely. !ncreased ris3 o# G!
ulceration.
bumetanide
58
indomethacin increases and bumetanide decreases serum potassium. <##ect o# interaction
indomethacin decreases e##ects o# bumetanide by pharmacodynamic antagonism.
synthesis.
candesartan
candesartan and indomethacin both increase serum potassium. )otential #or interaction,
monitor.
indomethacin decreases e##ects o# candesartan by pharmacodynamic antagonism.
)otential #or dangerous interaction. Use 'ith caution and monitor closely. 1+8!Fs
decrease synthesis o# "asodilating renal prostaglandins, and thus a##ect #luid homeostasis
and may diminish antihypertensi"e e##ect.
candesartan, indomethacin. <ither increases to9city o# the other by Dther ,see comment-.
captopri
indomethacin decreases e##ects o# captopril by pharmacodynamic antagonism. )otential
captopril, indomethacin. <ither increases to9city o# the other by Dther ,see comment-.
carbenoxoone
indomethacin increases and carbeno9olone decreases serum potassium. <##ect o#
car)edio
car"edilol and indomethacin both increase serum potassium. )otential #or interaction,
monitor.
indomethacin decreases e##ects o# car"edilol by pharmacodynamic antagonism.
59
ceecoxib
celeco9ib and indomethacin both increase anticoagulation. )otential #or interaction,
monitor.
celeco9ib and indomethacin both increase serum potassium. )otential #or interaction,
monitor.
ceiproo
celiprolol and indomethacin both increase serum potassium. )otential #or interaction,
monitor.
indomethacin decreases e##ects o# celiprolol by pharmacodynamic antagonism.
chorothia$ide
indomethacin increases and chlorothiaEide decreases serum potassium. <##ect o#
chorpropamide
indomethacin increases e##ects o# chlorpropamide by un3no'n mechanism. +igni#icant
interaction possible, monitor closely. >is3 o# hypoglycemia.
chorthaidone
indomethacin increases and chlorthalidone decreases serum potassium. <##ect o#
choine ma"nesium trisaic#ate
indomethacin and choline magnesium trisalicylate both increase anticoagulation.
indomethacin and choline magnesium trisalicylate both increase serum potassium.
cinnamon
indomethacin and cinnamon both increase anticoagulation. )otential #or interaction,
monitor.
cipro(oxacin
60
indomethacin, cipro#lo9acin. Dther ,see comment-. )otential #or dangerous interaction.
Use 'ith caution and monitor closely. =omment: Mechanism: un3no'n. !ncreased ris3 o#
=1+ stimulation and seiEures 'ith high doses o# #luoroIuinolones.
citaopram
citalopram, indomethacin. <ither increases to9city o# the other by pharmacodynamic
synergism. +igni#icant interaction possible, monitor closely. !ncreased ris3 o# upper G!
bleeding. !# possible, a"oid concurrent use.
cobetasone
indomethacin, clobetasone. <ither increases to9city o# the other by pharmacodynamic
ulceration.
comipramine
clomipramine, indomethacin. <ither increases to9city o# the other by pharmacodynamic
bleeding. =lomipramine inhib. serotonin upta3e by platelets.
copido"re
clopidogrel, indomethacin. <ither increases e##ects o# the other by pharmacodynamic
synergism. )otential #or dangerous interaction. Use 'ith caution and monitor closely.
=lopidogrel and 1+8!Fs both inhibit platelet aggregation.
cord#ceps
indomethacin and cordyceps both increase anticoagulation. )otential #or interaction,
monitor.
cortisone
indomethacin, cortisone. <ither increases to9city o# the other by pharmacodynamic
ulceration.
c#copenthia$ide
indomethacin increases and cyclopenthiaEide decreases serum potassium. <##ect o#
c#cosporine
61
indomethacin, cyclosporine. <ither increases to9city o# the other by nephroto9icity andMor
ototo9icity. )otential #or dangerous interaction. Use 'ith caution and monitor closely.
dabi"atran
dabigatran and indomethacin both increase anticoagulation. +igni#icant interaction
possible, monitor closely. =aution is ad"ised, both drugs ha"e the potential to cause
bleeding. =oncomitant use may increase ris3 o# bleeding.
dateparin
dalteparin and indomethacin both increase anticoagulation. )otential #or dangerous
de!erasirox
de#erasiro9, indomethacin. Dther ,see comment-. )otential #or interaction, monitor.
=omment: =ombination may increase G! bleeding, ulceration and irritation. Use 'ith
caution.
de(a$acort
indomethacin, de#laEacort. <ither increases to9city o# the other by pharmacodynamic
ulceration.
dexamethasone
indomethacin, de9amethasone. <ither increases to9city o# the other by pharmacodynamic
ulceration.
dico!enac
diclo#enac and indomethacin both increase anticoagulation. )otential #or interaction,
monitor.
diclo#enac and indomethacin both increase serum potassium. )otential #or interaction,
monitor.
di(unisa
di#lunisal and indomethacin both increase anticoagulation. )otential #or interaction,
monitor.
62
di#lunisal and indomethacin both increase serum potassium. )otential #or interaction,
monitor.
di"oxin
indomethacin and digo9in both increase serum potassium. )otential #or interaction,
monitor.
dobutamine
indomethacin increases and dobutamine decreases serum potassium. <##ect o# interaction
don" *uai
indomethacin and dong Iuai both increase anticoagulation. )otential #or interaction,
monitor.
dopexamine
indomethacin increases and dope9amine decreases serum potassium. <##ect o# interaction
doxa$osin
indomethacin decreases e##ects o# do9aEosin by pharmacodynamic antagonism.
synthesis.
drospirenone
drospirenone and indomethacin both increase serum potassium. )otential #or dangerous
duoxetine
dulo9etine, indomethacin. <ither increases to9city o# the other by pharmacodynamic
bleeding. ++>!s inhib. serotonin upta3e by platelets.
etrombopa"
eltrombopag increases le"els o# indomethacin by decreasing metabolism. +igni#icant
interaction possible, monitor closely. UG; inhibition signi#icance o# interaction unclear.
enaapri
63
indomethacin decreases e##ects o# enalapril by pharmacodynamic antagonism. )otential
enalapril, indomethacin. <ither increases to9city o# the other by Dther ,see comment-.
enoxaparin
eno9aparin and indomethacin both increase anticoagulation. )otential #or dangerous
ephedrine
indomethacin increases and ephedrine decreases serum potassium. <##ect o# interaction is
ephedrine +pumonar#,
indomethacin increases and ephedrine ,pulmonary- decreases serum potassium. <##ect o#
interaction is not clear, use caution. )otential #or interaction, monitor. .
epinephrine
indomethacin increases and epinephrine decreases serum potassium. <##ect o# interaction
epinephrine racemic
indomethacin increases and epinephrine racemic decreases serum potassium. <##ect o#
epoprosteno
indomethacin and epoprostenol both increase anticoagulation. )otential #or interaction,
monitor.
eprosartan
eprosartan and indomethacin both increase serum potassium. )otential #or interaction,
monitor.
indomethacin decreases e##ects o# eprosartan by pharmacodynamic antagonism. )otential
64
eprosartan, indomethacin. <ither increases to9city o# the other by Dther ,see comment-.
)otential #or interaction, monitor. =omment: May result in renal #unction deterioration,
particularly in elderly or "olume depleted indi"iduals.
escitaopram
escitalopram, indomethacin. <ither increases to9city o# the other by pharmacodynamic
esmoo
esmolol and indomethacin both increase serum potassium. )otential #or interaction,
monitor.
indomethacin decreases e##ects o# esmolol by pharmacodynamic antagonism. +igni#icant
ethacr#nic acid
indomethacin increases and ethacrynic acid decreases serum potassium. <##ect o#
etodoac
etodolac and indomethacin both increase anticoagulation. )otential #or interaction,
monitor.
etodolac and indomethacin both increase serum potassium. )otential #or interaction,
monitor.
etoricoxib
etorico9ib and indomethacin both increase anticoagulation. )otential #or interaction,
monitor.
etorico9ib and indomethacin both increase serum potassium. )otential #or interaction,
monitor.
!enbu!en
65
#enbu#en and indomethacin both increase anticoagulation. )otential #or interaction,
monitor.
#enbu#en and indomethacin both increase serum potassium. )otential #or interaction,
monitor.
!enne
indomethacin and #ennel both increase anticoagulation. )otential #or interaction, monitor.
!enopro!en
#enopro#en and indomethacin both increase anticoagulation. )otential #or interaction,
monitor.
#enopro#en and indomethacin both increase serum potassium. )otential #or interaction,
monitor.
!e)er!e-
indomethacin and #e"er#e' both increase anticoagulation. )otential #or interaction,
monitor.
(ucoxaciin
#luclo9acillin, indomethacin. <ither increases le"els o# the other by plasma protein
binding competition. +igni#icant interaction possible, monitor closely.
#luclo9acillin, indomethacin. <ither increases le"els o# the other by decreasing renal
clearance. +igni#icant interaction possible, monitor closely.
(udrocortisone
indomethacin, #ludrocortisone. <ither increases to9city o# the other by pharmacodynamic
ulceration.
(uoxetine
#luo9etine, indomethacin. <ither increases to9city o# the other by pharmacodynamic
(urbipro!en
66
#lurbipro#en and indomethacin both increase anticoagulation. )otential #or interaction,
monitor.
#lurbipro#en and indomethacin both increase serum potassium. )otential #or interaction,
monitor.
(u)oxamine
#lu"o9amine, indomethacin. <ither increases to9city o# the other by pharmacodynamic
!ondaparinux
#ondaparinu9 and indomethacin both increase anticoagulation. )otential #or dangerous
!ormotero
indomethacin increases and #ormoterol decreases serum potassium. <##ect o# interaction
!orskoin
indomethacin and #ors3olin both increase anticoagulation. )otential #or interaction,
monitor.
!osinopri
indomethacin decreases e##ects o# #osinopril by pharmacodynamic antagonism. )otential
#osinopril, indomethacin. <ither increases to9city o# the other by Dther ,see comment-.
!urosemide
indomethacin increases and #urosemide decreases serum potassium. <##ect o# interaction
"aric
indomethacin and garlic both increase anticoagulation. )otential #or interaction, monitor.
67
"emi(oxacin
gemi#lo9acin, indomethacin. Dther ,see comment-. )otential #or dangerous interaction.
Use 'ith caution and monitor closely. =omment: !ncreased ris3 o# =1+ stimulation and
seiEures 'ith high doses o# #luoroIuinolones.
"entamicin
indomethacin increases and gentamicin decreases serum potassium. <##ect o# interaction
"in"er
indomethacin and ginger both increase anticoagulation. )otential #or interaction, monitor.
"ink"o bioba
indomethacin and gin3go biloba both increase anticoagulation. )otential #or interaction,
monitor.
"imepiride
indomethacin increases e##ects o# glimepiride by un3no'n mechanism. +igni#icant
"ipi$ide
indomethacin increases e##ects o# glipiEide by un3no'n mechanism. +igni#icant
"i*uidone
indomethacin increases e##ects o# gliIuidone by un3no'n mechanism. +igni#icant
"#buride
indomethacin increases e##ects o# glyburide by un3no'n mechanism. +igni#icant
indomethacin increases le"els o# glyburide by a##ecting hepatic enEyme =T)2=&M10
metabolism. )otential #or interaction, monitor. +trong =T)2=& inhibitors may decrease
glyburide metabolism.
"reen tea
68
green tea, indomethacin. Dther ,see comment-. )otential #or interaction, monitor.
=omment: =ombination may increase ris3 o# bleeding.
heparin
heparin and indomethacin both increase anticoagulation. )otential #or dangerous
horse chestnut seed
indomethacin and horse chestnut seed both increase anticoagulation. )otential #or
h#draa$ine
indomethacin decreases e##ects o# hydralaEine by pharmacodynamic antagonism.
synthesis.
h#drochorothia$ide
indomethacin increases and hydrochlorothiaEide decreases serum potassium. <##ect o#
h#drocortisone
indomethacin, hydrocortisone. <ither increases to9city o# the other by pharmacodynamic
ulceration.
ibupro!en
ibupro#en and indomethacin both increase anticoagulation. )otential #or interaction,
monitor.
ibupro#en and indomethacin both increase serum potassium. )otential #or interaction,
monitor.
imatinib
imatinib, indomethacin. <ither increases to9city o# the other by Dther ,see comment-.
)otential #or dangerous interaction. Use 'ith caution and monitor closely. =omment:
!matinib may cause thrombocytopenia bleeding ris3 increased 'hen imatinib is
coadministered 'ith anticoagulants, 1+8!Fs, platelet inhibitors, and thrombolytic
agents.
indapamide
69
indomethacin increases and indapamide decreases serum potassium. <##ect o# interaction
irbesartan
irbesartan and indomethacin both increase serum potassium. )otential #or interaction,
monitor.
indomethacin decreases e##ects o# irbesartan by pharmacodynamic antagonism. )otential
irbesartan, indomethacin. <ither increases to9city o# the other by Dther ,see comment-.
isoprotereno
indomethacin increases and isoproterenol decreases serum potassium. <##ect o#
ketopro!en
indomethacin and 3etopro#en both increase anticoagulation. )otential #or interaction,
monitor.
indomethacin and 3etopro#en both increase serum potassium. )otential #or interaction,
monitor.
ketoroac
indomethacin and 3etorolac both increase anticoagulation. )otential #or interaction,
monitor.
indomethacin and 3etorolac both increase serum potassium. )otential #or interaction,
monitor.
ketoroac intranasa
indomethacin and 3etorolac intranasal both increase anticoagulation. )otential #or
indomethacin and 3etorolac intranasal both increase serum potassium. )otential #or
70
abetao
labetalol and indomethacin both increase serum potassium. )otential #or interaction,
monitor.
indomethacin decreases e##ects o# labetalol by pharmacodynamic antagonism. +igni#icant
acosamide
indomethacin increases le"els o# lacosamide by a##ecting hepatic enEyme =T)2=&M10
metabolism. )otential #or dangerous interaction. Use 'ith caution and monitor closely.
=onsider decreasing lacosamide dose 'hen coadministered 'ith strong =T)2=&
inhibitors.
epirudin
lepirudin and indomethacin both increase anticoagulation. )otential #or dangerous
e)abutero
indomethacin increases and le"albuterol decreases serum potassium. <##ect o# interaction
e)o(oxacin
le"o#lo9acin, indomethacin. Dther ,see comment-. )otential #or dangerous interaction.
Use 'ith caution and monitor closely. =omment: >is3 o# =1+ stimulationMseiEure.
Mechanism: Fisplacement o# G8@8 #rom receptors in brain.
e)ominacipran
le"omilnacipran, indomethacin. <ither increases to9city o# the other by
pharmacodynamic synergism. +igni#icant interaction possible, monitor closely. +1>!s
may #urther impair platelet acti"ity in patients ta3ing antiplatelet or anticoagulant drugs.
isinopri
indomethacin decreases e##ects o# lisinopril by pharmacodynamic antagonism. )otential
lisinopril, indomethacin. <ither increases to9city o# the other by Dther ,see comment-.
71
ithium
indomethacin increases le"els o# lithium by decreasing renal clearance. +igni#icant
interaction possible, monitor closely.
ornoxicam
indomethacin and lorno9icam both increase anticoagulation. )otential #or interaction,
monitor.
indomethacin and lorno9icam both increase serum potassium. )otential #or interaction,
monitor.
osartan
losartan and indomethacin both increase serum potassium. )otential #or interaction,
monitor.
indomethacin decreases e##ects o# losartan by pharmacodynamic antagonism. )otential
losartan, indomethacin. <ither increases to9city o# the other by Dther ,see comment-.
me!enamic acid
indomethacin and me#enamic acid both increase anticoagulation. )otential #or interaction,
monitor.
indomethacin and me#enamic acid both increase serum potassium. )otential #or
meatonin
melatonin increases e##ects o# indomethacin by anticoagulation. +igni#icant interaction
possible, monitor closely. Melatonin may decrease prothrombin time.
meoxicam
72
indomethacin and melo9icam both increase anticoagulation. )otential #or interaction,
monitor.
indomethacin and melo9icam both increase serum potassium. )otential #or interaction,
monitor.
mesaamine
mesalamine, indomethacin. <ither increases to9city o# the other by pharmacodynamic
synergism. +igni#icant interaction possible, monitor closely. 8dditi"e nephroto9icity.
metaprotereno
indomethacin increases and metaproterenol decreases serum potassium. <##ect o#
meth#cothia$ide
indomethacin increases and methyclothiaEide decreases serum potassium. <##ect o#
interaction is not clear, use caution. )otential #or interaction, monitor. .
meth#prednisoone
indomethacin, methylprednisolone. <ither increases to9city o# the other by
pharmacodynamic synergism. +igni#icant interaction possible, monitor closely. !ncreased
ris3 o# G! ulceration.
metoa$one
indomethacin increases and metolaEone decreases serum potassium. <##ect o# interaction
metoproo
metoprolol and indomethacin both increase serum potassium. )otential #or interaction,
monitor.
indomethacin decreases e##ects o# metoprolol by pharmacodynamic antagonism.
minacipran
milnacipran, indomethacin. <ither increases to9city o# the other by pharmacodynamic
73
mipomersen
mipomersen, indomethacin. <ither increases to9city o# the other by Dther ,see comment-.
+igni#icant interaction possible, monitor closely. =omment: @oth drugs ha"e potential to
increase hepatic enEymes monitor A*;s.
mistetoe
indomethacin increases and mistletoe decreases anticoagulation. <##ect o# interaction is
moexipri
indomethacin decreases e##ects o# moe9ipril by pharmacodynamic antagonism. )otential
moe9ipril, indomethacin. <ither increases to9city o# the other by Dther ,see comment-.
moxi(oxacin
mo9i#lo9acin, indomethacin. Dther ,see comment-. )otential #or dangerous interaction.
Use 'ith caution and monitor closely. =omment: !ncreased ris3 o# =1+ stimulation and
seiEures 'ith high doses o# #luoroIuinolones.
moxis##te
indomethacin decreases e##ects o# mo9isylyte by pharmacodynamic antagonism.
synthesis.
m#cophenoate
indomethacin 'ill increase the le"el or e##ect o# mycophenolate by acidic ,anionic- drug
competition #or renal tubular clearance. +igni#icant interaction possible, monitor closely.
nabumetone
indomethacin and nabumetone both increase anticoagulation. )otential #or interaction,
monitor.
indomethacin and nabumetone both increase serum potassium. )otential #or interaction,
monitor.
74
nadoo
nadolol and indomethacin both increase serum potassium. )otential #or interaction,
monitor.
indomethacin decreases e##ects o# nadolol by pharmacodynamic antagonism. +igni#icant
naproxen
indomethacin and napro9en both increase anticoagulation. )otential #or interaction,
monitor.
indomethacin and napro9en both increase serum potassium. )otential #or interaction,
monitor.
nebi)oo
nebi"olol and indomethacin both increase serum potassium. )otential #or interaction,
monitor.
indomethacin decreases e##ects o# nebi"olol by pharmacodynamic antagonism.
ne!a$odone
ne#aEodone, indomethacin. <ither increases to9city o# the other by pharmacodynamic
nette
indomethacin increases and nettle decreases anticoagulation. <##ect o# interaction is not
clear, use caution. )otential #or interaction, monitor.
norepinephrine
indomethacin increases and norepinephrine decreases serum potassium. <##ect o#
omesartan
olmesartan and indomethacin both increase serum potassium. )otential #or interaction,
monitor.
75
indomethacin decreases e##ects o# olmesartan by pharmacodynamic antagonism. )otential
olmesartan, indomethacin. <ither increases to9city o# the other by Dther ,see comment-.
ospemi!ene
indomethacin increases le"els o# ospemi#ene by a##ecting hepatic enEyme =T)2=&M10
metabolism. +igni#icant interaction possible, monitor closely.
indomethacin, ospemi#ene. <ither increases le"els o# the other by plasma protein binding
competition. )otential #or dangerous interaction. Use 'ith caution and monitor closely.
oxapro$in
indomethacin and o9aproEin both increase anticoagulation. )otential #or interaction,
monitor.
indomethacin and o9aproEin both increase serum potassium. )otential #or interaction,
monitor.
panax "insen"
indomethacin and pana9 ginseng both increase anticoagulation. )otential #or interaction,
monitor.
parecoxib
indomethacin and pareco9ib both increase anticoagulation. )otential #or interaction,
monitor.
indomethacin and pareco9ib both increase serum potassium. )otential #or interaction,
monitor.
paroxetine
paro9etine, indomethacin. <ither increases to9city o# the other by pharmacodynamic
pau d.arco
76
indomethacin and pau dYarco both increase anticoagulation. )otential #or interaction,
monitor.
pe"aspar"ase
pegaspargase increases e##ects o# indomethacin by pharmacodynamic synergism.
)otential #or interaction, monitor. !ncreased ris3 o# bleeding e"ents.
pe"inter!eron a!a 2b
peginter#eron al#a 2b decreases le"els o# indomethacin by a##ecting hepatic enEyme
=T)2=&M10 metabolism. )otential #or interaction, monitor. :hen patients are
administered peginter#eron alpha-2b 'ith =T)2=& substrates, the therapeutic e##ect o#
these drugs may be altered.
penbutoo
penbutolol and indomethacin both increase serum potassium. )otential #or interaction,
monitor.
indomethacin decreases e##ects o# penbutolol by pharmacodynamic antagonism.
perindopri
indomethacin decreases e##ects o# perindopril by pharmacodynamic antagonism. )otential
perindopril, indomethacin. <ither increases to9city o# the other by Dther ,see comment-.
phenindione
phenindione and indomethacin both increase anticoagulation. )otential #or dangerous
phenox#ben$amine
indomethacin decreases e##ects o# pheno9ybenEamine by pharmacodynamic antagonism.
synthesis.
77
phentoamine
indomethacin decreases e##ects o# phentolamine by pharmacodynamic antagonism.
synthesis.
ph#toestro"ens
indomethacin and phytoestrogens both increase anticoagulation. )otential #or interaction,
monitor.
pindoo
pindolol and indomethacin both increase serum potassium. )otential #or interaction,
monitor.
indomethacin decreases e##ects o# pindolol by pharmacodynamic antagonism. +igni#icant
pirbutero
indomethacin increases and pirbuterol decreases serum potassium. <##ect o# interaction is
piroxicam
indomethacin and piro9icam both increase anticoagulation. )otential #or interaction,
monitor.
indomethacin and piro9icam both increase serum potassium. )otential #or interaction,
monitor.
pi)meciinam
pi"mecillinam, indomethacin. <ither increases le"els o# the other by plasma protein
binding competition. +igni#icant interaction possible, monitor closely.
pi"mecillinam, indomethacin. <ither increases le"els o# the other by decreasing renal
potassium acid phosphate
indomethacin and potassium acid phosphate both increase serum potassium. )otential #or
potassium choride
78
indomethacin and potassium chloride both increase serum potassium. )otential #or
potassium citrate
indomethacin and potassium citrate both increase serum potassium. )otential #or
praatrexate
indomethacin increases le"els o# pralatre9ate by decreasing renal clearance. +igni#icant
interaction possible, monitor closely. 1+8!Fs may delay pralatre9ate clearance,
increasing drug e9posure. 8d6ust the pralatre9ate dose as needed.
pra$osin
indomethacin decreases e##ects o# praEosin by pharmacodynamic antagonism. +igni#icant
interaction possible, monitor closely. 1+8!Fs decrease prostaglandin synthesis.
prednisoone
indomethacin, prednisolone. <ither increases to9city o# the other by pharmacodynamic
ulceration.
prednisone
indomethacin, prednisone. <ither increases to9city o# the other by pharmacodynamic
ulceration.
probenecid
indomethacin 'ill increase the le"el or e##ect o# probenecid by acidic ,anionic- drug
competition #or renal tubular clearance. +igni#icant interaction possible, monitor closely.
propranoo
propranolol and indomethacin both increase serum potassium. )otential #or interaction,
monitor.
indomethacin decreases e##ects o# propranolol by pharmacodynamic antagonism.
protamine
79
protamine and indomethacin both increase anticoagulation. )otential #or dangerous
*uinapri
indomethacin decreases e##ects o# Iuinapril by pharmacodynamic antagonism. )otential
Iuinapril, indomethacin. <ither increases to9city o# the other by Dther ,see comment-.
ramipri
indomethacin decreases e##ects o# ramipril by pharmacodynamic antagonism. )otential
ramipril, indomethacin. <ither increases to9city o# the other by Dther ,see comment-.
reishi
indomethacin and reishi both increase anticoagulation. )otential #or interaction, monitor.
retepase
indomethacin and reteplase both increase anticoagulation. )otential #or interaction,
ri)aroxaban
ri"aro9aban, indomethacin. Dther ,see comment-. )otential #or interaction, monitor.
=omment: 1+8!Fs are 3no'n to increase bleeding. @leeding ris3 may be increased
'hen 1+8!Fs are used concomitantly 'ith ri"aro9aban. Monitor #or signsMsymptoms o#
blood loss.
ri)asti"mine
ri"astigmine increases to9city o# indomethacin by pharmacodynamic synergism. )otential
#or interaction, monitor. Monitor patients #or symptoms o# acti"e or occult
gastrointestinal bleeding.
80
saic#ates +non'asa,
indomethacin and salicylates ,non-asa- both increase anticoagulation. )otential #or
indomethacin and salicylates ,non-asa- both increase serum potassium. )otential #or
sametero
indomethacin increases and salmeterol decreases serum potassium. <##ect o# interaction is
sasaate
indomethacin and salsalate both increase anticoagulation. )otential #or interaction,
monitor.
indomethacin and salsalate both increase serum potassium. )otential #or interaction,
monitor.
sertraine
sertraline, indomethacin. <ither increases to9city o# the other by pharmacodynamic
siberian "insen"
indomethacin and siberian ginseng both increase anticoagulation. )otential #or
siodosin
indomethacin decreases e##ects o# silodosin by pharmacodynamic antagonism. +igni#icant
sodium picosu!ate%ma"nesium oxide%anh#drous citric acid
indomethacin, sodium picosul#ateMmagnesium o9ideManhydrous citric acid. <ither
increases to9city o# the other by Dther ,see comment-. +igni#icant interaction possible,
monitor closely. =omment: May be associated 'ith #luid and electrolyte imbalances.
sodium su!ate%potassium su!ate%ma"nesium su!ate
indomethacin, sodium sul#ateMpotassium sul#ateMmagnesium sul#ate. Dther ,see
comment-. )otential #or interaction, monitor. =omment: =aution 'hen bo'el preps are
81
used 'ith drugs that cause +!8F( or 1+8!Fs increased ris3 #or 'ater retention or
electrolyte imbalance.
sodium su!ate%potassium su!ate%ma"nesium su!ate%po#eth#ene "#co
indomethacin, sodium sul#ateMpotassium sul#ateMmagnesium sul#ateMpolyethylene glycol.
Dther ,see comment-. )otential #or interaction, monitor. =omment: =aution 'hen bo'el
preps are used 'ith drugs that cause +!8F( or 1+8!Fs increased ris3 #or 'ater
retention or electrolyte imbalance.
sotao
sotalol and indomethacin both increase serum potassium. )otential #or interaction,
monitor.
indomethacin decreases e##ects o# sotalol by pharmacodynamic antagonism. +igni#icant
spironoactone
spironolactone and indomethacin both increase serum potassium. )otential #or dangerous
succin#choine
indomethacin and succinylcholine both increase serum potassium. )otential #or
su!asaa$ine
indomethacin and sul#asalaEine both increase anticoagulation. )otential #or interaction,
monitor.
indomethacin and sul#asalaEine both increase serum potassium. )otential #or interaction,
monitor.
suindac
indomethacin and sulindac both increase anticoagulation. )otential #or interaction,
monitor.
indomethacin and sulindac both increase serum potassium. )otential #or interaction,
monitor.
temisartan
82
telmisartan and indomethacin both increase serum potassium. )otential #or interaction,
monitor.
indomethacin decreases e##ects o# telmisartan by pharmacodynamic antagonism. )otential
telmisartan, indomethacin. <ither increases to9city o# the other by Dther ,see comment-.
temociin
temocillin, indomethacin. <ither increases le"els o# the other by plasma protein binding
competition. +igni#icant interaction possible, monitor closely.
temocillin, indomethacin. <ither increases le"els o# the other by decreasing renal
tenectepase
indomethacin and tenecteplase both increase anticoagulation. )otential #or interaction,
tera$osin
indomethacin decreases e##ects o# teraEosin by pharmacodynamic antagonism. +igni#icant
terbutaine
indomethacin increases and terbutaline decreases serum potassium. <##ect o# interaction
tica"reor
ticagrelor, indomethacin. <ither increases e##ects o# the other by anticoagulation.
+igni#icant interaction possible, monitor closely. !ncreased ris3 o# bleeding 'ith use o#
ticagrelor and chronic 1+8!F use. .
ticarciin
ticarcillin, indomethacin. <ither increases le"els o# the other by plasma protein binding
competition. +igni#icant interaction possible, monitor closely.
83
ticarcillin, indomethacin. <ither increases le"els o# the other by decreasing renal
timoo
timolol and indomethacin both increase serum potassium. )otential #or interaction,
monitor.
indomethacin decreases e##ects o# timolol by pharmacodynamic antagonism. +igni#icant
tin$aparin
tinEaparin and indomethacin both increase anticoagulation. )otential #or dangerous
toa$amide
indomethacin increases e##ects o# tolaEamide by un3no'n mechanism. +igni#icant
tobutamide
indomethacin increases e##ects o# tolbutamide by un3no'n mechanism. +igni#icant
to!enamic acid
indomethacin and tol#enamic acid both increase anticoagulation. )otential #or interaction,
monitor.
indomethacin and tol#enamic acid both increase serum potassium. )otential #or
tometin
indomethacin and tolmetin both increase anticoagulation. )otential #or interaction,
monitor.
indomethacin and tolmetin both increase serum potassium. )otential #or interaction,
monitor.
to)aptan
84
indomethacin and tol"aptan both increase serum potassium. )otential #or interaction,
monitor.
torsemide
indomethacin increases and torsemide decreases serum potassium. <##ect o# interaction is
trandoapri
indomethacin decreases e##ects o# trandolapril by pharmacodynamic antagonism.
)otential #or dangerous interaction. Use 'ith caution and monitor closely. 1+8!Fs
decrease synthesis o# "asodilating renal prostaglandins, and thus a##ect #luid homeostasis
and may diminish antihypertenis"e e##ect.
trandolapril, indomethacin. <ither increases to9city o# the other by Dther ,see comment-.
tra$odone
traEodone, indomethacin. <ither increases to9city o# the other by pharmacodynamic
triamcinoone
indomethacin, triamcinolone. <ither increases to9city o# the other by pharmacodynamic
ulceration.
triamterene
triamterene and indomethacin both increase serum potassium. )otential #or dangerous
)asartan
"alsartan and indomethacin both increase serum potassium. )otential #or interaction,
monitor.
indomethacin decreases e##ects o# "alsartan by pharmacodynamic antagonism. )otential
85
"alsartan, indomethacin. <ither increases to9city o# the other by Dther ,see comment-.
)ena!axine
"enla#a9ine, indomethacin. <ither increases to9city o# the other by pharmacodynamic
)itamin k1 +ph#tonadione,
indomethacin increases and "itamin 31 ,phytonadione- decreases anticoagulation. <##ect
o# interaction is not clear, use caution. )otential #or interaction, monitor.
)orapaxar
indomethacin, "orapa9ar. <ither increases e##ects o# the other by pharmacodynamic
synergism. +igni#icant interaction possible, monitor closely. 8dditi"e antiplatelet e##ect
may occur.
)ortioxetine
indomethacin, "ortio9etine. <ither increases e##ects o# the other by anticoagulation.
+igni#icant interaction possible, monitor closely.
-ar!arin
'ar#arin and indomethacin both increase anticoagulation. )otential #or dangerous
$otepine
indomethacin decreases e##ects o# Eotepine by pharmacodynamic antagonism. +igni#icant
Minor (!")
aceco!enac
aceclo#enac 'ill increase the le"el or e##ect o# indomethacin by acidic ,anionic- drug
competition #or renal tubular clearance. Minor or non-signi#icant interaction.
acemetacin
acemetacin 'ill increase the le"el or e##ect o# indomethacin by acidic ,anionic- drug
86
ac#co)ir
indomethacin 'ill increase the le"el or e##ect o# acyclo"ir by acidic ,anionic- drug
aendronate
indomethacin, alendronate. <ither increases to9city o# the other by pharmacodynamic
synergism. Minor or non-signi#icant interaction. !ncreased ris3 o# G! ulceration.
amikacin
indomethacin increases le"els o# ami3acin by decreasing renal clearance. Minor or non-
signi#icant interaction. !nteraction mainly occurs in preterm in#ants.
aminohippurate sodium
indomethacin 'ill increase the le"el or e##ect o# aminohippurate sodium by acidic
,anionic- drug competition #or renal tubular clearance. Minor or non-signi#icant
interaction.
anamu
indomethacin and anamu both increase anticoagulation. Minor or non-signi#icant
interaction.
aspirin
aspirin 'ill increase the le"el or e##ect o# indomethacin by acidic ,anionic- drug
aspirin recta
aspirin rectal 'ill increase the le"el or e##ect o# indomethacin by acidic ,anionic- drug
aspirin%citric acid%sodium bicarbonate
aspirinMcitric acidMsodium bicarbonate 'ill increase the le"el or e##ect o# indomethacin by
acidic ,anionic- drug competition #or renal tubular clearance. Minor or non-signi#icant
interaction.
basaa$ide
indomethacin 'ill increase the le"el or e##ect o# balsalaEide by acidic ,anionic- drug
87
bendro(umethia$ide
bendro#lumethiaEide 'ill increase the le"el or e##ect o# indomethacin by acidic ,anionic-
drug competition #or renal tubular clearance. Minor or non-signi#icant interaction.
ce!adroxi
ce#adro9il 'ill increase the le"el or e##ect o# indomethacin by acidic ,anionic- drug
ce!amandoe
ce#amandole 'ill increase the le"el or e##ect o# indomethacin by acidic ,anionic- drug
ce!pirome
ce#pirome 'ill increase the le"el or e##ect o# indomethacin by acidic ,anionic- drug
ce!tibuten
ce#tibuten 'ill increase the le"el or e##ect o# indomethacin by acidic ,anionic- drug
ce!ti$oxime
ce#tiEo9ime 'ill increase the le"el or e##ect o# indomethacin by acidic ,anionic- drug
ceecoxib
celeco9ib 'ill increase the le"el or e##ect o# indomethacin by acidic ,anionic- drug
cephaexin
cephale9in 'ill increase the le"el or e##ect o# indomethacin by acidic ,anionic- drug
chorothia$ide
chlorothiaEide 'ill increase the le"el or e##ect o# indomethacin by acidic ,anionic- drug
chorpropamide
88
indomethacin 'ill increase the le"el or e##ect o# chlorpropamide by acidic ,anionic- drug
chorthaidone
chlorthalidone 'ill increase the le"el or e##ect o# indomethacin by acidic ,anionic- drug
choine ma"nesium trisaic#ate
indomethacin 'ill increase the le"el or e##ect o# choline magnesium trisalicylate by acidic
,anionic- drug competition #or renal tubular clearance. Minor or non-signi#icant
interaction.
chromium
indomethacin increases le"els o# chromium by unspeci#ied interaction mechanism. Minor
or non-signi#icant interaction.
creatine
creatine, indomethacin. Mechanism: pharmacodynamic synergism. Minor or non-
signi#icant interaction. ,;heoretical interaction- =ombination may ha"e additi"e
nephroto9ic e##ects.
c#copenthia$ide
cyclopenthiaEide 'ill increase the le"el or e##ect o# indomethacin by acidic ,anionic- drug
danshen
indomethacin and danshen both increase anticoagulation. Minor or non-signi#icant
interaction.
de)i.s ca-
indomethacin and de"ilYs cla' both increase anticoagulation. Minor or non-signi#icant
interaction.
dico!enac
diclo#enac 'ill increase the le"el or e##ect o# indomethacin by acidic ,anionic- drug
dico!enac topica
89
diclo#enac topical, indomethacin. <ither increases e##ects o# the other by
pharmacodynamic synergism. Minor or non-signi#icant interaction. 8lthough lo', there is
systemic e9posure to diclo#enac topical theoretically, concomitant administration 'ith
systemic 1+8!F+ or aspirin may result in increased 1+8!F ad"erse e##ects.
di(unisa
di#lunisal 'ill increase the le"el or e##ect o# indomethacin by acidic ,anionic- drug
di"oxin
indomethacin increases le"els o# digo9in by decreasing renal clearance. Minor or non-
signi#icant interaction.
eperenone
indomethacin decreases e##ects o# eplerenone by pharmacodynamic antagonism. Minor or
non-signi#icant interaction. 1+8!Fs decrease prostaglandin synthesis.
etodoac
etodolac 'ill increase the le"el or e##ect o# indomethacin by acidic ,anionic- drug
etoricoxib
etorico9ib 'ill increase the le"el or e##ect o# indomethacin by acidic ,anionic- drug
!enbu!en
#enbu#en 'ill increase the le"el or e##ect o# indomethacin by acidic ,anionic- drug
!enopro!en
#enopro#en 'ill increase the le"el or e##ect o# indomethacin by acidic ,anionic- drug
!e)er!e-
indomethacin decreases e##ects o# #e"er#e' by pharmacodynamic antagonism. Minor or
non-signi#icant interaction.
(urbipro!en
90
#lurbipro#en 'ill increase the le"el or e##ect o# indomethacin by acidic ,anionic- drug
!urosemide
indomethacin decreases e##ects o# #urosemide by pharmacodynamic antagonism. Minor
or non-signi#icant interaction. 1+8!Fs decrease prostaglandin synthesis.
"ancico)ir
indomethacin 'ill increase the le"el or e##ect o# ganciclo"ir by acidic ,anionic- drug
"entamicin
indomethacin increases le"els o# gentamicin by decreasing renal clearance. Minor or non-
haoperido
indomethacin increases to9city o# haloperidol by un3no'n mechanism. Minor or non-
signi#icant interaction.
h#drochorothia$ide
hydrochlorothiaEide 'ill increase the le"el or e##ect o# indomethacin by acidic ,anionic-
ibupro!en
ibupro#en 'ill increase the le"el or e##ect o# indomethacin by acidic ,anionic- drug
imidapri
indomethacin decreases e##ects o# imidapril by pharmacodynamic antagonism. Minor or
non-signi#icant interaction. 1+8!Fs decrease prostaglandin synthesis.
indapamide
indapamide 'ill increase the le"el or e##ect o# indomethacin by acidic ,anionic- drug
kanam#cin
indomethacin increases le"els o# 3anamycin by decreasing renal clearance. Minor or non-
91
ketopro!en
indomethacin 'ill increase the le"el or e##ect o# 3etopro#en by acidic ,anionic- drug
ketoroac
indomethacin 'ill increase the le"el or e##ect o# 3etorolac by acidic ,anionic- drug
ketoroac intranasa
indomethacin 'ill increase the le"el or e##ect o# 3etorolac intranasal by acidic ,anionic-
ornoxicam
indomethacin 'ill increase the le"el or e##ect o# lorno9icam by acidic ,anionic- drug
me!enamic acid
indomethacin 'ill increase the le"el or e##ect o# me#enamic acid by acidic ,anionic- drug
meoxicam
indomethacin 'ill increase the le"el or e##ect o# melo9icam by acidic ,anionic- drug
mesaamine
indomethacin 'ill increase the le"el or e##ect o# mesalamine by acidic ,anionic- drug
meth#cothia$ide
methyclothiaEide 'ill increase the le"el or e##ect o# indomethacin by acidic ,anionic-
metoa$one
metolaEone 'ill increase the le"el or e##ect o# indomethacin by acidic ,anionic- drug
nabumetone
92
indomethacin 'ill increase the le"el or e##ect o# nabumetone by acidic ,anionic- drug
naproxen
indomethacin 'ill increase the le"el or e##ect o# napro9en by acidic ,anionic- drug
neom#cin po
indomethacin increases le"els o# neomycin po by decreasing renal clearance. Minor or
non-signi#icant interaction. !nteraction mainly occurs in preterm in#ants.
netimicin
indomethacin increases le"els o# netilmicin by decreasing renal clearance. Minor or non-
noni /uice
indomethacin and noni 6uice both increase serum potassium. Minor or non-signi#icant
interaction.
nor(oxacin
nor#lo9acin, indomethacin. Dther ,see comment-. Minor or non-signi#icant interaction.
=omment: >is3 o# =1+ stimulationMseiEure. Mechanism: Fisplacement o# G8@8 #rom
receptors in brain.
o(oxacin
o#lo9acin, indomethacin. Dther ,see comment-. Minor or non-signi#icant interaction.
=omment: >is3 o# =1+ stimulationMseiEure. Mechanism: Fisplacement o# G8@8 #rom
receptors in brain.
oxapro$in
indomethacin 'ill increase the le"el or e##ect o# o9aproEin by acidic ,anionic- drug
parecoxib
indomethacin 'ill increase the le"el or e##ect o# pareco9ib by acidic ,anionic- drug
paromom#cin
93
indomethacin increases le"els o# paromomycin by decreasing renal clearance. Minor or
piroxicam
indomethacin 'ill increase the le"el or e##ect o# piro9icam by acidic ,anionic- drug
rose hips
rose hips 'ill increase the le"el or e##ect o# indomethacin by acidic ,anionic- drug
saic#ates +non'asa,
indomethacin 'ill increase the le"el or e##ect o# salicylates ,non-asa- by acidic ,anionic-
sasaate
indomethacin 'ill increase the le"el or e##ect o# salsalate by acidic ,anionic- drug
streptom#cin
indomethacin increases le"els o# streptomycin by decreasing renal clearance. Minor or
su!adia$ine
indomethacin increases le"els o# sul#adiaEine by unspeci#ied interaction mechanism.
Minor or non-signi#icant interaction.
su!amethoxa$oe
indomethacin increases le"els o# sul#ametho9aEole by unspeci#ied interaction
mechanism. Minor or non-signi#icant interaction.
su!asaa$ine
indomethacin 'ill increase the le"el or e##ect o# sul#asalaEine by acidic ,anionic- drug
su&soxa$oe
indomethacin increases le"els o# sul#iso9aEole by unspeci#ied interaction mechanism.
Minor or non-signi#icant interaction.
94
suindac
indomethacin 'ill increase the le"el or e##ect o# sulindac by acidic ,anionic- drug
tiudronate
indomethacin increases le"els o# tiludronate by enhancing G! absorption. 8pplies only to
oral #orm o# both agents. Minor or non-signi#icant interaction.
tobram#cin
indomethacin increases le"els o# tobramycin by decreasing renal clearance. Minor or
to!enamic acid
indomethacin 'ill increase the le"el or e##ect o# tol#enamic acid by acidic ,anionic- drug
tometin
indomethacin 'ill increase the le"el or e##ect o# tolmetin by acidic ,anionic- drug
triamterene
triamterene, indomethacin. Dther ,see comment-. Minor or non-signi#icant interaction.
=omment: >is3 o# acute renal #ailure. Mechanism: 1+8!Fs decrease prostaglandin
synthesis, 'hich normally protect against nephroto9icity.
indomethacin increases to9city o# triamterene by pharmacodynamic antagonism. Minor
or non-signi#icant interaction. 1+8!Fs decrease prostaglandin synthesis, increasing the
ris3 o# nephroto9icity.
)a"ancico)ir
indomethacin 'ill increase the le"el or e##ect o# "alganciclo"ir by acidic ,anionic- drug
)ancom#cin
indomethacin increases le"els o# "ancomycin by decreasing renal clearance. Minor or
non-signi#icant interaction. !nteraction mainly occurs in neonates.
-io- bark
95
indomethacin 'ill increase the le"el or e##ect o# 'illo' bar3 by acidic ,anionic- drug
$oedronic acid
*d'erse Effects
9:;<
;ransient renal insu##iciency ,407-
?aundice ,Z1%7-
<le"ated li"er #unction test "alues ,Z1%7-
(eadache ,127-
:$:;<
FiEEiness ,3-&7-
Fyspepsia ,3-&7-
<pigastric pain ,3-&7-
!ndigestion ,3-&7-
1ausea ,3-&7-
+ymptomatic upper G! ulcers, gross bleedingMper#oration ,47 o# patients treated #or 1 year 17
o# patients treated #or 3-/ months-.
8bnormal painMcrampsMdistress ,R37-
=onstipation ,1-37-
Fepression ,1-37-
Fiarrhea ,1-37-
*atigue ,1-37-
+omnolence ,1-37-
;innitus ,1-37-
96
Gertigo ,1-37-
=:<
8cute interstitial nephritis 'ith hematuriaMproteinuria
8cute respiratory distress
8granulocytosis
8ngioedema
8plastic anemia
8sthma
@one marro' depression
=ongesti"e heart #ailure ,=(*-
(emolytic anemia
Aeu3openia
Macular and morbilli#orm eruptions
)ulmonary edema
;hrombocytopenia
;hrombocytopenic purpura
Ulcerati"e stomatitis
Urticaria
celeco#ib 0R#2 $ !elebre#
=lass: 1+8!Fs

Fosing Q Uses
!nteractions
97
8d"erse <##ects
:arnings
)regnancy
)harmacology
!mages
)atient (andout
*ormulary
Dosing , "ses
8dult)ediatric
*cute Pain , Primary Dysmenorrhea
400 mg )D initially, then 200 mg )>1 on #irst day 200 mg I12hr )>1 on subseIuent days
*nkylosing Spondylitis
200 mg )D once daily or di"ided I12hr i# no e##ect a#ter / 'ee3s, may increase to 400 mgMday
i# no adeIuate resonse obser"ed a#ter / 'ee3s o# ta3ing 400 mgMday consider discontinuing
therapy
.steoarthritis
200 mg )D once daily or di"ided I12hr
Rheumatoid *rthritis
100-200 mg )D I12hr
+amilial *denomatous Polyposis 0.ff$label2
400 mg )D I12hr, ta3en 'ith #ood
Usual medical care should be continued during celeco9ib therapy
98
(epatic impairment
Moderate ,=hild-)ugh class @-: Fecrease dose by %07
+e"ere ,=hild-)ugh class =-: 1ot recommended
>enal impairment
>elati"e contraindication to use

D"er"ie'
)resentation
FF9
:or3up
;reatment
Medication
)rint this section

Medication +ummary
1+8!Fs
Uricosuric 8gents
=orticosteroids
+ho' 8ll
Multimedia Aibrary
99
>e#erences
Medication Summary
gout.
4101, 1025
4425
1e9t +ection: =orticosteroids
-S*IDs
!lass Summary

100
3etoprofen




urate crystals.
101
410.5
daily.
)re"ious
1e9t +ection: =orticosteroids
"ricosuric *gents
!lass Summary
Uricosuric agents lo'er uric acid le"els by inhibiting renal tubular reabsorption o# uric acid,
thereby increasing net renal e9cretion o# uric acid. ;hese agents increase the ris3 o# renal stones,
'ith about a &-107 ris3 #or probenecid. ;hey should not be started during an attac3 o# acute
gouty arthritis. ;he goal o# therapy is to lo'er serum uric acid to appro9imately %-/ mgMdA
'ithout causing renal stones.
!olchicine 0!olcrys2

=olchicine inhibits microtubules and may thereby inhibit phagocytosis, neutrophil mobility, and
chemota9is. !t also may inhibit generation o# prostaglandins. ;he traditional approach o# gi"ing
colchicine until "omiting or diarrhea appears is not appropriate these are signs o# to9icity.
!nstead, 1.2 mg is gi"en orally, #ollo'ed by 0./ mg a#ter 1 hour. Fose reduction is reIuired #or
coingestion o# interacting drugs ,eg, )-gp or =T)384 inhibitors-.
Probenecid

)robenecid lo'ers tissue stores o# uric acid by increasing net renal e9cretion o# uric acid through
inhibition o# tubular reabsorption. +ome authorities recommend al3aliEing the urine 'hen
starting probenecid to reduce the ris3 #or renal stone #ormation. )robenecid is indicated #or long-
term management o# hyperuricemia associated 'ith gout.
102
colchicine 0R#2 $ !olcrys
=lass: Uricosuric 8gents

Fosing Q Uses
!nteractions
8d"erse <##ects
:arnings
)regnancy
)harmacology
8dministration
!mages
)atient (andout
*ormulary
Dosing , "ses
8dult)ediatric
Gout
;reatment o# acute gout #lares: 1.2 mg )D at #irst sign o# #lare, then 0./ mg 1 hr later not to
e9ceed 1.. mg in 1-hr period
)rophyla9is: 0./ mg )D once daily or I12hr not to e9ceed 1.2 mgMday a#ter gout #lare, 'ait 12
hr to continue prophyla9is
+amilial Mediterranean +e'er
1.2-2.4 mgMday )D in single daily dose or di"ided I12hr increased in 0.3 mgMday increments as
necessary to control disease decreased in 0.3 mgMday increments i# intolerable side e##ects
de"elop not to e9ceed 2.4 mgMday
103
ehcet Syndrome 0.rphan2
Drphan sponsor
8> +cienti#ic, !nc, 1100 Drthodo9 +treet, )hiladelphia, )8 1&124
Post$S&EMI Pericarditis 0.ff$label2
;reatment o# pericarditis a#ter +;-ele"ation myocardial in#arction ,+;<M!-
0./ mg )D I12hr
>enal impairment ,gout-
Mild ,=r=l %0-.0 mAMmin- and moderate ,=r=l 30-%0 mAMmin-: Fosage ad6ustment not
necessary monitor patients #or ad"erse e##ects
+e"ere ,=r=l R30 mAMmin-: Fosage ad6ustment not necessary do not repeat more
#reIuently than e"ery 2 'ee3s
(emodialysis: 0./ mg once do not repeat more #reIuently than e"ery 2 'ee3s
>enal impairment ,#amilial Mediterranean #e"er-
Mild ,=r=l %0-.0 mAMmin- and moderate ,=r=l 30-%0 mAMmin-: Monitor patients #or
ad"erse e##ects dosage ad6ustment may be reIuired
+e"ere ,=r=l R30 mAMmin-: 0.3 mgMday initially dosage increases should be done 'ith
adeIuate monitoring #or ad"erse e##ects
(emodialysis: 0.3 mg )D once dosage increases should be done 'ith adeIuate
monitoring #or ad"erse e##ects
(epatic impairment ,gout-
Mild to moderate: Fosage ad6ustment not necessary monitor patients #or ad"erse e##ects
+e"ere: Fosage ad6ustment not necessary do not repeat more #reIuently than e"ery 2
'ee3s consider alternati"e therapy i# repeated courses are reIuired
(epatic impairment ,#amilial Mediterranean #e"er-
Mild to moderate: Monitor patients #or ad"erse e##ects
+e"ere: =onsider dosage reduction do not repeat more #reIuently than e"ery 2 'ee3s
+trong =T)384 inhibitors
104
;reatment o# acute gout #lares: 0./ mg, then 0.3 mg 1 hour later to be repeated no earlier
than 3 days later
)rophyla9is o# acute gout #lares: !# the original colchicine regimen 'as 0./ mg @!F,
decrease dose to 0.3 mg IFay i# the original colchicine regimen 'as 0./ mg IFay,
decrease dose to 0.3 mg once e"ery other day
*amilial Mediterranean #e"er ,*M*-: 1ot to e9ceed 0./ mgMday 0./ mg can be gi"en as
0.3 mg I12hr
Moderate =T)384 inhibitors
Gout: 1.2 mg )D once to be repeated no earlier than 3 days later
*M*: 1ot to e9ceed 1.2 mgMday 0./ mg can be gi"en as 0./ mg I12hr
)-gp inhibitors
Gout: 0./ mg )D once to be repeated no earlier than 3 days later
*M*: 1ot to e9ceed 0./ mgMday 0./ mg can be gi"en as 0.3 mg I12hr
*dministration
Fosing regimens must be indi"idualiEed to indication
8dministered )D, 'ithout regard to meals
probenecid 0R#2 $ enemid
=lass: Uricosuric 8gents

Fosing Q Uses
!nteractions
8d"erse <##ects
:arnings
)regnancy
)harmacology
!mages
)atient (andout
105
*ormulary
Dosing , "ses
8dult)ediatric
Gout
2%0 mg )D t'ice daily #or 1 'ee3 increase to %00 mg )D t'ice daily to 2 gMday ma9imum 'ith
dosage increases o# %00 mg I4'ee3s
!# gout attac3s do not occur #or 4 months and uric acid le"els are 'ithin normal may reduce dose
by %00 mg I/monts
Prolong Penicillin Serum /e'els
%00 mg )D #our times daily
Pel'ic Inflammatory Disease
1 g )D 'ith 2 g ce#o9itin !M as single dose
Gonorrhea
1 g )D 'ith 2 g ce#o9itin !M as single dose
Renal Impairment
=r=lR30 mAMmin: 8"oid use

D"er"ie'
)resentation
FF9
:or3up
;reatment
106
Medication
)rint this section

Medication +ummary
1+8!Fs
Uricosuric 8gents
=orticosteroids
+ho' 8ll
Multimedia Aibrary
>e#erences
Medication Summary
gout.
4101, 1025
4425
1e9t +ection: >heumatologics, Dther
107
-S*IDs
!lass Summary

3etoprofen


108


urate crystals.
410.5
daily.
)re"ious
"ricosuric *gents
!lass Summary
Uricosuric agents lo'er uric acid le"els by inhibiting renal tubular reabsorption o# uric acid,
thereby increasing net renal e9cretion o# uric acid. ;hese agents increase the ris3 o# renal stones,
'ith about a &-107 ris3 #or probenecid. ;hey should not be started during an attac3 o# acute
gouty arthritis. ;he goal o# therapy is to lo'er serum uric acid to appro9imately %-/ mgMdA
'ithout causing renal stones.
109
!olchicine 0!olcrys2

=olchicine inhibits microtubules and may thereby inhibit phagocytosis, neutrophil mobility, and
chemota9is. !t also may inhibit generation o# prostaglandins. ;he traditional approach o# gi"ing
colchicine until "omiting or diarrhea appears is not appropriate these are signs o# to9icity.
!nstead, 1.2 mg is gi"en orally, #ollo'ed by 0./ mg a#ter 1 hour. Fose reduction is reIuired #or
coingestion o# interacting drugs ,eg, )-gp or =T)384 inhibitors-.
Probenecid

)robenecid lo'ers tissue stores o# uric acid by increasing net renal e9cretion o# uric acid through
inhibition o# tubular reabsorption. +ome authorities recommend al3aliEing the urine 'hen
starting probenecid to reduce the ris3 #or renal stone #ormation. )robenecid is indicated #or long-
term management o# hyperuricemia associated 'ith gout.
)re"ious
!orticosteroids
!lass Summary
=orticosteroids are potent and e##ecti"e anti-in#lammatory drugs that can be used to treat acute
gout in patients 'ho cannot tolerate 1+8!Fs or colchicine. ;hey can be gi"en orally,
intramuscularly ,!M-, intra"enously ,!G-, or intra-articularly. 8drenocorticotropic hormone
,8=;(- also acts in gout, in part by inducing adrenal steroids. 1o intrinsic ad"antage to treating
'ith !G corticosteroids e9ists unless the patient cannot ta3e oral medications.
;he short-burst corticosteroid regimen used to treat an acute #lare o# gout is generally 'ell
tolerated. 1e"ertheless, patients may e9perience the ad"erse e##ects seen 'ith long-term steroid
use.
!n patients 'ith only 1 or 2 in"ol"ed 6oints, intra-articular corticosteroids are a sa#e and e##ecti"e
treatment option, once in#ection has been e9cluded. :ater-soluble steroids ,eg, de9amethasone-
are teleologically inappropriate #or use as a depot steroid treatment.
Prednisone
110

Dral prednisone can be gi"en to abort an attac3 o# gout. @y re"ersing increased capillary
permeability and suppressing polymorphonuclear leu3ocyte ,)M1- acti"ity, this agent may
decrease in#lammation. +teroid dose pac3s that clearly label the dose to be ta3en each day can be
con"enient #or some patients.
&riamcinolone 0*ristocort2

!ntra-articular use is considered by some as the treatment o# choice #or pseudogout and #or acute
gouty attac3s in patients 'ho cannot be gi"en 1+8!Fs, colchicine, or high-dose systemic
corticosteroids.
!orticotropin 0%P *cthar Gel1 *cthar Gel2

=orticotropin stimulates endogenous production o# corticosteroids and directly and rapidly acts
on peripheral leu3ocyte acti"ation. !t decreases in#lammation by suppressing migration o# )M1s
and re"ersing increased capillary permeability.
)re"ious
5anthine .#idase Inhibitors
!lass Summary
!nhibition o# 9anthine o9idase, the enEyme that synthesiEes uric acid #rom hypo9anthine, reduces
the synthesis o# uric acid 'ithout disrupting the biosynthesis o# "ital purines. ;his results in the
reduction o# the tissue stores o# uric acid. ;he goal o# therapy is to lo'er the serum uric acid
le"el to appro9imately %-/ mgMdA. ;hese agents should not be started during an attac3 o# acute
gouty arthritis 'ithout adeIuate control o# the gouty in#lammation.
*llopurinol 07yloprim1 *loprim2

111
8llopurinol reduces production o# uric acid, thereby allo'ing the body to dispose o# e9cess uric
acid stores. !t is the most e##ecti"e therapy #or lo'ering serum uric acid. Most patients achie"e
the target uric acid le"el o# % mgMdA at a dosage o# 300-400 mgMday. 8 lo'er dosage is used i#
renal insu##iciency is present.
+ebu#ostat 0"loric2

*ebu9ostat is a potential alternati"e to allopurinol.
412/, 12$5
Ai3e allopurinol, #ebu9ostat is a
9anthine o9idase inhibitor that pre"ents uric acid production and lo'ers ele"ated serum uric acid
le"els. Unli3e allopurinol, it is a thiaEolecarbo9ylic acid deri"ati"e, not a purine base analogue.
*ebu9ostat physically bloc3s the channel to the molybdenum-pterin acti"e site o# 9anthine
o9idase and is metaboliEed by li"er o9idation and glucuronidation.
4425
=ommon ad"erse e"ents include upper respiratory tract in#ections, arthralgias, diarrhea,
headache, and li"er #unction abnormalities. 8trio"entricular bloc3 or atrial #ibrillation and
cholecystitis also ha"e been reported.
41415
8s 'ith other uricosuric agents, initiation o# #ebu9ostat
may precipitate gouty attac3s.
442, 1415
allopurinol 0R#2 $ 7yloprim1 *loprim
=lass: Santhine D9idase !nhibitors
8ntigout 8gents

Fosing Q Uses
!nteractions
8d"erse <##ects
:arnings
)regnancy
)harmacology
8dministration
!mages
)atient (andout
112
*ormulary
Dosing , "ses
8dult)ediatric
Gout
Mild: 100 mgMday )D initially increased 'ee3ly to 200-300 mgMday
Moderate to se"ere: 100 mgMday )D initially increased 'ee3ly to 400-/00 mgMday
*ntineoplastic$Induced %yperuricemia
)D: /00-.00 mg di"ided I.-12hr, starting 1-2 days be#ore chemotherapy
!G: 200-400 mgMm[Mday not to e9ceed /00 mgMm[Mday
Minimum )D dosage: 100-200 mgMday
Ma9imum )D dosage: .00 mgMday
>enal impairment
=r=l 10-20 mAMmin: 200 mgMday
=r=l 3-10 mAMmin: 100 mgMday
=r=l R3 mAMmin: 100 mgMday at e9tended inter"als
febu#ostat 0R#2 $ "loric
=lass: Santhine D9idase !nhibitors
8ntigout 8gents

Fosing Q Uses
113
!nteractions
8d"erse <##ects
:arnings
)regnancy
)harmacology
!mages
)atient (andout
*ormulary
Dosing , "ses
8dult)ediatric
!hronic Gout
40 mgMday )D initially maintenance: 40-.0 mgMday increased i# serum uric acid is U/ mgMmA
a#ter 2 'ee3s
>enal impairment
Mild to moderate ,=r=l 30-.& mAMmin-: Fosage ad6ustment not necessary
+e"ere ,=r=l R30 mAMmin-: Fata not a"ailable use 'ith caution
(epatic impairment
Mild to moderate ,=hild-)ugh class 8 or @-: Fosage ad6ustment not necessary
+e"ere ,=hild-)ugh class =-: Fata not a"ailable use 'ith caution

Gout and Pseudogout

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Gout and Pseudogout

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Gout and Pseudogout

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