Anti- inflammatory, Analgesic and Antipyretic
lbuprofen is a member 0f the propionic acid group 0f nonsteroidal anti-inflammatory drugs (NSAIOs). is a propionic acid derivative with analgesic. anti-inflammatory and anti·pyretic activity. The drug’s therapeutic effects are thought to result its inhibitory effect on the enzyme cydooxygenase.
which results in a marked reduction in synthesis.
Brufen Is lndicated for the treatment of :
– Rheumatoid arthritis, including juvenile arthritis Of stills disease, ankylosing spondylitis, Osteoarthritis
– Other non rheumatOld (seronegative) arthropathies and acute gouty arthritis. It Is also indicated for the treatment of non-articular rheumatic oondiIions and periarticular conditions such as frozen
shoulder (capsulrtlS), bursitis. lendiriIis, tenosynovitis and low – back pain.
– In the treatment 0f soft-tissue injuries such as sprains and strains ,for relief of mild to moderate pain such as primary ctysmenotrhea. dental and post-operative pain postepisiotomy pain ,post partum pain and for the symptomatic relief of headache including migraine headache
DOSAGE AND ADMINISTRATION :
brufen Tablets 200 mg / 400 mg/ 600 mg /Sachets 600 mg :
– The recommended dose is 1200 10 1800 fTJ9′ day in divided doses.
– Some patients can be maintained on 600 10 1200 mg/day.
– In severe and acute cases it could be advantageous to increase the dosage until the acute phase is over
– Daily dose should not exceed 2400 mg in divided doses brufen retard 800 mg :
– The recommeoded daily dosage 0f slow release ibuprofen is two tablets as asingle dose, preferably in the early evening, welt before retiring to bed The tablets should be swallowed whole with plenty 01 fluid. In severe Or acute conditions. the total daily dose may be incteased t0 three tablets in divided doses
No special dose modifications are necessary unless renal or hapatic function is impaired in which case dosage should be assessed individually. Caution should be taken with dosage in this group
– Daily dose of ibuprofen is 20 mg/ kg body weight in divided doses.
– this can be achieved by using the syrup as follows:
Age Dose Frequency
1-2 years 2.5 ml 50 mg 3-4 times aday
3-7 years 5 ml 100 mg 3-4 times aday
8-12 years 10 ml 200 mg 3-4 times aday
NB: Bfufen ibuprofen is not recommended for children weight less than 7 kg ibuprofen 800, slow release ibuprofen and Ibuprofen granules are not suitable for children under the age 01 12 years. In JUVenile rheumatoid arthritis. up to 40 mg/kg body weight per day in divided doses may be laken.
– Cardiovascular Risk:
NSAIDs may cause an increased risk of serious cardiovascular thrombotic events myocardiel infarction, and stroke, which can be fatal this risk may increase with duration of use
Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greeter riak. NSAlDs contraindicated for the trMtment of peri-operatlve Pain In the setting coroMIY.-tery bypass graft (CABG) surgery
Gastrointestinal Risk :
NSAIDs cause an increased risk of serious gastrointestinal adverse events Inctuding inflammation, bleeding, ulceration,and perforetion of the stomach or Intestines, which can be fatel these events, can occur at eny time during use and without warning symptoms. Elderly petients are at risk for serious gastrointestinal events.
WARNING & PRECAUTIONS :
General Precautions :
Undesirable effects may be minimized by Using the lowest effective dose 101 the shortost duration necessary In control symptoms (see DOSAGE AND ADMINtSTAATIONj. As with othor NSADIS. Bfulen may mask the signs of Illtection. Geriatric Use: Elderly patients have an 1OCf8ased frequency of adverse reactions to NSAIDs. especiaIty gastrointestinal bleeding and perforatiOn, with may be fatal.
gastrointestinal bleeding, ulceration and perforation lbuproIcn should be given with cere to patients with a hiseory of peptic ulceration and other gastrointestinal disease since their conditions
may be exacerbated Gastrointestinal bleeding, tAcefalion or pertorabon has been reported with aM NSAIOs 81 any Inne
dunng treatment These adverse ewnls can be fatal and may occur with or without wamlll9
symptoms or a history of serious gastrointostlll8i events.
Tho risk 01 gastrolOlesllnal bleeding, ulceralion Of perforatIOn is higher with lflCI’oaslng lbuprofen doses In ceueote with a history of ueees. particularly if compIicaled with hemorThage Of porlora, aroe the elderly These patients shou6d commence tJeatment on the lowest dose available
Combinabon therapy WIth protective agents (e,g. tTlISOpf’OSIOI Of proton pump IMbIofsl shoukt be
~ fOf eeee pab8ntS, as ‘III’d as f)8bents requinng ooncorTMIltnt low do8e aspirin, Of for
other drugs “tliy 10 1flO8aSe gastrOlflteSllnlll ~ (see OAUG lNTERACTlONS).
The concomitant admin~1nttion of lbuprofen and o~ NSAlo., InctudIng
cyclooJlygenase-2 (Co.l·2) M6ective Inhfbftors, Mould be avoided due to the Increased risk
of ulCOf”ation or bleeding (see OAUG INTERACTIONS).
Patients with a history 01 gaSlroinlestioal disease, partIcuIarty when elderly. ShOuld report any
unusual abdominal symptoms (especially gastroinlestinaJ bleeding) in the initial stages cA
CM.IUon shoI.Ild be o.-clMd In p«ients receiving c:onc:ombnt IMdIcation whk:h could
IncreeMthertskofulcer’M6onorb\lMcMng,.uc:h. oraI~ •.• ~
&UCh _ w.f1.rtn, .-.ctiw ~ N-UptaiD InhIltIeors or ••••••••• drugs; MICh ••
spirin (see OAUG IHTEFIACnONS).
“gaslfointestinal bleeding or uIcefation (ICCU(S In patients receiving ibI..IproMn. the 1rHImItnI
should be withdfawn.
Respiratory Di.ardera: Cartion is requwed it ibuprofen is actnini$Iered 10 patients suffering
from. Of with a previous history 01. bronchial asthma since ItMJprolen has been reported to cause
bronchospasm in sudl patients.
Cerd6K. ReneI ••• HIIpItic 1rnpetr’mIInt: caution IS required in patients with renal, hepatic or
..catdiacirnpain\’lenMceIhe •.•• otNSAX>smayresultlnde4eriOratlOnofreoallunctJon. The
dose should be kepi as iow as pos.sitM and renal function ihouId be monitcwed in these patients.
c.rdIo’lllacul •.• nd c..broYUCUIer Effecta: ItJuprden shoukS be gwen with care 10
patients with 8 history of hear! failure or hypertensol since edema ha$ been reported in
Epidemiological data suggest that use ollboproleo, particularty at a high ecse (2400 mg daily)
and in long-term treatment, may be 8SSOCI81ed with a small increased risk 01 anerial th!’omootlc
events, suc:h as myocardial infarctIOn or stroke. EpdemioIogicaI studies do not suggest thallow
do$e ibuproten (8.g <-1200 mg daiy) IS as.scdated with an increased risk 01 aneriallhrombotic
events, partiaJlarty~ infarction.
Palients with unc::ontrnIed h)’pefI8I’ISO’t, c:ongestiYe hean laiU8, established ischemic !lean
disease, per1)heral 8I1eriat cisease andIor cerebrovascular <hease ShoukI only be treated with
ibuprofen after careful CCInIidefation. Similar consideration should be made before initiating
longer-term treatment of patients with risK factors for cardiovascular disease (e.g. hypertenSion,
hypet1ipidemia. diabetes rMIIitus and smoking).
Def’matok)g~ E~: Serious sIun reactIonS, some 01 them lataI, including edokatiYe
dermatiIis. ~ syndmrne and tmcic epidennaI neaoIySi$. have been repof1ed Yf!WY
rarely in association with the U&8 01 NSAIOs. Patients appear to be at twghest risk of Ihese
reactions elllty In the course 01 thetap)’. In the ma,onty 01 cases, the onset oIlhe reaction occurs
within the ftrSl month of trealmenlibuproferl should be disc:onInJed at Ihe first appearance of
sKin rash. mucosal lesions or any other signs of hypersensitivity.
R ••.•• I Effect.: Caution ShOuld be used when initiating treatment with lbuprofen in patients with
As with other NSAIOs, Iong-Mnn aaninlstratJOn of ibupnHn has ~ 10 renal piiiiiiIary
necrosis ard oIher reMI pdIoIogic changes. Renal k:»ddty has Mo oeen seen in patients in
wtIom renal pr~ haYe a compensatOry role ,n themallllenanc&oIrenalperlusion.1n
!heM palieota. ~ 01 a nonsI8I’oidaI anti-innammatory drug may CKlse Cl
~t reduCtion in prostaglandin formation am, secondarily. in renal blood How. wtrich
may precipitate ovef1 renal eecceceosetoo. Patl8fllS et greatest nak oIlt1is reacOOn are thoso
with Impaired renal function, heart failure, Wvet dyslunctlOn, those taking diuretics 800 ACE
inhibilors and Ihe eIdefty. DiIcontinuatioo 0( nonslOrOidal anCi-tnlfammalory drug therapy is usually
foIowed by reoovery to IM prwe.atrnenl stale
Heme~ E •••• : lJuprofen, like 0Iher NSAIOs, QI’Ilf’IINbt JAtelot aggregatIOn and has
beetl Shown 10 prolong tIIeectng !me In normal SUbfect$.
AMptk lleningltia: AIeptic meninglbs has been observed on rare occasions irI patients on
ibuprolen therapy. AIIhoogh it Is probably more likely 10 occur In patienls WIth syslemic tupus
erythematosus and related ecooecweuesoe diseases. it has been repotted In pallef’lts who do
not nave an underlying c:lvonic oeeese ..
care should be ~ In petients treated vWIh any of the IoIowIng drugs as ,”,er actiOns have been
reported in some petiera:
Antl-hYJMl1*’l ••••• : ~ Md diuretics: NSAtOs may reduce the el1ect 01 anti-
h~siYes, such as ACE Inhibitors. 8et~ Md diuretics. DIuretics un.so
mcr.. •• tM rl” of fMIPhrotoa.aty of NSAlDs.
UtttIum: NSAIOs may eeeeese eliminatlOl’l oIlitNum.
Methotrexate: NSAIDs IMY InhIbtlIhe ttmut. ~ 01 metttotAlllittlll and reecce
Increased ris6( 0( ~I bIeedng ‘Irith NSAIOs.
Amlnoglyco •••• : NSAlDs may decrease Ihe 811Cfetion of aminogfycoSides.
A.I~rin: As with other products containing NSAIOs. ooncomitant adminIstration of ibuprofen and
aspirin Is not generaIy recommended because oIlhe potential of increased actvt:.rse effects.
EKP9″imental data suggest ths1 ibuprofen may inhibit ee eHec1 of tow dose aspirin on platelel
aggregation when 1hey •• doeecI cortCOmItanIty However,!he limitations of these data and the
uncettaintJeSregardingextnlpOlatlOnof eXVNOdatalO!hedinlCajSltuahon~that no firm
eceececos can be made kif AIQUI. ibuprofen use. IInd no dinicaJy relevant efIect IS CXJnSKIefed
to be likefy for occasionIIIlbuproeen use (see CLtHtCAL PHARUACOLOGY).
Cflfdiec Glycoaklee: NSAtOs may 8118Cefbate caf<iac la~ufe, reduce glomerulaf hltfatlOl’l rate
and increase plasma cardiac: gIyooside levels.
Cho6eatyr.mlne: The concomitant edmInt.treUon of ibuP'”ofen and cholestyramine IMY
reduCetM MtsOfption ~……..,.In the g •• trointestlnal tract. However, the cHnk:at
algnftk:Mce Is uMnown.
Cyctoaporine: lnaeaed,. of neplYCUdDty IMth NSAJOs,.
Corttcosterokta: lnCreaaed risk 01 gasUcnesOOal ulcefabOn Of bleeding WIth NSAtDs
Cox-2lnhlbltora and otMr NSAlOa: Concomitant use with othef NSAIOs. Including
cycloolilY98nase·2 seIsdive inhibitors, snoutd be It’t/oIded due to !he pot8fltiallOf additive ettecte.
Herbal Extracts: GInkgO bIoba may potentiateltl8 nsk of bleeding with NSAIOs
Mlfepriatone: A decr-.In the efficacy of the medldnal P'”oduct can theoretically occur
due to the .,,~ prnperties of HSlJOs. Umtted evidence suggests that:
co.dI ••• i •• ,wtlOh of ~ on the dIIy ot proswgt.ndln MtrmnistrMlon does not adversely
In~ the.nects 01 ~ at the prosteglMdln on cervicIIl ripening Of uterine
contrKtilty.net doe. not reduce the ctinical.tflc.acy of med~ twmination of
Qulnolone anttblotlcs: Animal data Indicate that NSAtOs CM increase the fiSk 01 convulsions
asaociated with quinolone antibiolics. Patients taking NSAIOs and quinoiones may have an
increased risk of developing convulsions.
Sulfonytu,….: NSAIOt rNlY pot-.u.ce the.n.cts of suHonytree medieetlons.
There hllve been ,….. NpOrtI of hypoglycemla in patients on sulfonylurN medications
Tecrotimus: Possib6It Inc:reaged nsk of neptwokIxlCrty ‘Nhen NSAIOs aregwen with tacrolimus.
Zldovudine: Increased risk of hematologlcal toKlaty Ymen NSAlOs are given WIth ZIdovucine.
There is evidence of an increased risk 01 hemarttlroses and hematoma in HtV(+) hemophiliacs
receiving ooncurrentlreatment with zidovudine and Ibuprol8fl.
CYP2C9 Inhibitors: Concomitant adlNnlstraHon of ibuP'”ofen with CYP2C9 Inhibitors may
Incr ••• tM uposure to IbuprofM (CYP2Ci substrste). In • study with voriconazoltl..-Kt
ftuconazoitt (CYP2Ct Inhlbltcn), *rI ~ S(+)-ibupfofen exposure by approlllmately
10 to 100% has been shown. Reduction of the Ibuproten dose shoukI be conllkMred when
potent CYP2C9Inhibiton •• admInlatered concomitantty, particularly when high-doM
IbuptotwIls~'” etther YOric:onazoIe Of tkK:onazoWt
PREGNANCY AND LACTATION
Pregn.ncy: In~ of ptOSt.sg*’dln synthesis may ad .••••• y affect the pregnancy
andIor ettibryoo’1eta1 ~ [)eta fn)m ~icalstudMts suggest an k1Cf8H8d
risk of miscarriage and of c:erdiac matfol’lMtk)n and gastroschisis IIfter Ihe UM of a
prostaglandin swn”‘-‘- inhbtof In ~y pNgnancy. In .”imals, the administration of a
prosUgIendin s~ 6nNbItar ha been at.o.n to…,.,n in InctMMd pr. and post·
ImpfMtation 10 •••• and ~ 1etNItty.In.:kHtion, incnlsMd ~ ot various
malformations, Indudlng urdlovaacular, have been reported In anlmats given a
prostaglandin syntn.!s Inhtbltor during the organogenetic period.
During the first and MConcI tri~ of ~y, ibuptOlen shoukt not be given unless
deerty MCMNry. “1:M.Iprof.-. Is uMd by a womM1 attampting to conoeIve. or durtng the
tnt Of MCOnd ~ of PNIIIMnCY, the do •••.• oukt be up as low and duretion 01
trwtnw’It. 1Ihort. poeaMM.
Duling the third trtmeAsr of pregnancy. all proatagt.ndln ayntheets Inhibitota may expoee
Ihe fistus to Ihe folloWIng:
CerdIopul~ toalctty (wlttl P'”emature CIoaure 01 Ihe ductus srterlosus and
Rer\III dyafunction, which may ~ to…,.. taillwe wtth oIIgotIydtamnloe;,
At the end of ~nency, prolll-Ulandln aynthesla Inhibitors may expose the mother and
the neoNIte to the foltowlng:
· PouIbIe prolongation of bleld6ng Hme
inhibition of utIrine contractions, whk:tI rNy ~ In ctet.yed or prok)nged iabof’.
ConMqUefrtty, ~ is conlr •• ndk:8ted during the third tri •••••• of pregnancy.
Labor and Delivery: Admjnislration oIlbuprofen is no! recommended during tabor and delivery
The onset of tabor may be delayed and the duration increased with a greater bleeding tendency in
boIh mother and child.
Nu~ng Mothers: In ee limited studieS so far available, ibuprofen appears in the breast m~k in
very low concentrations. lbuprofen is not recommended for use in nursing mothers.
Female Fertility: The vu at Ibuprofen may I~r femate fertility and la not recornn.nded
In women attempting 10 conceive. In womM1 who have difficulties conceiving or who are
undtrgotng investigation of 1nfertNfty, withdr_aI ot lbuprofen Mould be conaidet’ed.
EFFECTS ON A8tUTY TO DRIVE AND TO USE MACHINES:
FOI~ tNetment with Ibuprot.n, IN ~ Hme of prients rNy be affected. This
ahouId be ~ Into .ccount where ~sed vigil.nce ‘a required, e.g. when driving a car
or operating 1MChinery.
The pattern of acMne events reported for ibuprofen is similar to that for other N5A10s.
Immune system disorders: Hypersensitivity reactions have been reported following treatment
with ibuprOfen. These may consist of (a) non-specific aHergic reaction ar.:! anaphylaxis, (b)
respiratory tract reactivity comprising asthma, aggravated asthma. bronchospasm or dyspnea. or
(c) assorted skin diSOfderS, including rashes of vances ~s, pruritus, urticaria, purpura,
angioedema and, very rarely, bullous dermatoses (indudIng Slevens-Johnson syndrome. toxic
epidefmaI necnJIysis and erythema muttiforme).
GMtrolntestin.t disorders: T~ rnost.oommoo/y observed adverse 8¥&nt9 ••
gastrointestinal in nalure. Nausea, vomiting, diarmea. Hatulence, conslipation, dyspepsia,
abdommal pain, rrielena, hematemesis, ulceralNe stomalibs, gastrOinlesllna! hemorrtlage and
exacerbation of a:MiIis and Crohn’s disease (see CONTRAINOICATIQNS) have been reported
IoIowing ibuproten actninistralion. less trequently. gastritis, duodena! Ulcer and gastric utcer have
G •• lr6intestlnel perfor8tton h •• been rsrely reported with ibuprofen use..
Panaeatitis has also been reported very rarely.
GentnI dlllOlcter. and edm!nlatrtltion slCe conditions: Edema and latigue have been reported
in association with ibuprofen treatment.
Other advefse events reported less commonly and for which causality has not necessarity been
established are include below. These -v ••• events •• Hsted k1 order of decrvaslng
frequency within MCh sys.., otgIIn c ••••.
Stood Md lymphMk: system di.orders: leukopenia, thrombocytopenia. apestc eoene,
neutropenia, agranulocy1osis, and hemoIytic anemia
Psychiatric clIlOf’ders: Insomnia, anxiety. depre5SlOn and oonfusiona/ state
Nervous system disorders: Headache, diumess. paresthesia, somoolenoe and ccec neufltrs
eye disorders;: Visual impairment and toxc optIC neuropathy
Ear Md t.byrlnlh disorders: Hearing rmpaired. vertigo, and tinnitus
HepatobIUary disorders: Hepatrtis, taundice. hepalic fonctIOn abnormal and hepatic failure
Skin and ~s tissue dtIIOnMn: PhotoseosibvJty reacllon
Renal and urinary disorders: TOKic: nephropathy in various lorms, IOduding Interstrtial
nephritIS, nephrotic syndrome and renerrauoro.
TOdcity: Signs and symploms 01 tOKiciCy generally not been observed at doses below 100
~g in children or cdIlts,
However. supportive care may be needed In some cases,
Children have been observed 10 manifest signs and symploms of toxicity after ingestion 01400
mgJkg or greater.
Symptoms: Most patients Yhll’lave ingested significant amounts 01 ibuprolen will ma.-fest
symptoms within 4 to 6 hours.
The ~ frequeotly reported symptomS of OYeI’dose indude nausea, vomiting, abdominal paIn.
lelhargy and drowsiness.
Cenlral nervous system (CNS) e’tects include headache, tinnitus, dizzrness convulslcn and loss
01 consciousness ,Nystagmus. metabolic acidosis. hypothermia, renal enects. gastrointestinal
bleeding. coma, apnea, and depression of the CNS and respiratory system have also been rarely
reported. cardiovascular toxicrty, rnck.Iding hypolension, bradycardia and tachycardia, has been
rejX)tled.ln cases of significant overdose, renal faiture and liver damage are possible Large
overdoses are generally well toterated when no other drugs are being laken.
Treatment: There is no specific antidote fOf ibuprofen cvereose. Gaslric emptying followed by
suppor’Iive meesees is recommended if the quantJty ingested exceeds 400 mgf kg within the
previous hour. For the most current Jf11ormaliorr, contact the loCal poison control canter
Pharmacodynamic Properties: jbuproten IS a proplOllfc acid derivative with analgtlSIC, anu-
inflammatory and anti-pyretic activity. The drug’S therapeutic enects are thought to result from ItS
inhibitory eHee! on the enzyme cydooKygenase, which results in a mar1l.ed reduction in
EKj)QIimeolaI-data suggest that ibuprofen mlIty inhibit the etfect of low doge aspirin on platelet
aggregation when they are dosed concomitantty. In one study, when a single dose Of ibuprofen
400 mg was taken within a hours before or within 30 minutes after immediate release aspirin
dosing (al mg), a decreased enect of acetylsalicytic acid on the formation of thrombQ)tane 01
platelet aggregation occurred. However, the ~mitaUons of these data and the uncertamiJes
regarding elctrapotation of eK vivo data 10 the cliOlCaI situa\Jon tmpty that no firm ecoececos can
be made f()f regular ibuprofen use. and no dinlcaly r.yant eflect is considered to be likety for
occasional ibuprolen use.
Pharmacokinetk: Properties: lbuprOfen is rapidly absorbed from the gastrointestina! tract
peak serum ooncentrations occurring one to two hours after administration. The elimina\JOtl hall-
life is approlCimately two hours.
lbuprofen is metabolized in the liver to two inactive metabOlites and the kidney excretes these,
together with unchanged ibuprofen, either as such or as conjugates. Excretion by the kidney IS
bolh rapid and complete.
tbuprofen is 6Ktensiyely bound to ptasma proteins.
Store at a lemperature not exceeding 3Q”C in a cool, dry place in a well-dosed ccoreoer
-ProfeCI from lighl.
– Keep out of the reach of children
_ Bruten 200 mg Sugsr coated tstJkt.: PVC stJ’1). 2 strips eoo a stnps of to tablets inSIde
carton box Wlth insert, 500 PVC Strips inside a big carton boll V.;m insert
Brufen 400″‘il sugar coated tllblet.: PVC smo. 2 strips and 3 strips 0110 tablets inside
carton box with Insert, 250 PVC Strips inside a btg carton box with insert
Bruten 600 mg Film coated tsbIets: PVC strip, 2 strips and 3 stops of 10 labIets ms~
carton 00x with insen
– Brulen 8OO”‘iI sustained,….., tablets: PVDC strip and 2 stnps of 10 tablets, inSIde
carton box witn insert
– Srufen 600 mg granu'” In uchet form: 10 & 20 sachets each sachet contains 6OOr’r19
ibuprofeninside carton box with inserI
Brufen syrup 100 mg Ibuprofen I Slnl: bottle 01110 mI and bottles of 150 mI inside
Revised Noyember 20 11 CCDS 03280 71 1
KaNr. ~ •• Chemlc:allndustriell Company
Abbot! laboratories- USA